Finding Einstein's Brain 9780813580418

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Finding Einstein’s Brain

(Photo courtesy of Brown Brothers.)

Finding Einstein’s Brain Frederick E. Lepore, MD

rutgers university press n e w b r u n s w i c k , c a m d e n , a n d n e wa r k , n e w j e r s e y, a n d l o n d o n

Library of Congress Cataloging-­in-­Publication Data Names: Lepore, Frederick E., 1949–­author. Title: Finding Einstein’s brain / by Frederick E. Lepore, MD. Description: New Brunswick, New Jersey : Rutgers University Press, [2018] | Includes bibliographical references and index. Identifiers: LCCN 2017047395 | ISBN 9780813580395 (cloth : alk. paper) | ISBN 9780813580418 (web pdf ) Subjects: LCSH: Einstein, Albert, 1879–1955. | Einstein, Albert, 1879–1955—­Knowledge. | Harvey, Thomas Stoltz. | Brain. | Brain—­Dissection. Classification: LCC QC16.E5 L378 2018 | DDC 612.8/2—­dc23 LC rec­ord available at https://­lccn.loc.gov/2017047395 A British Cataloging-­in-­Publication rec­ord for this book is available from the British Library. Copyright © 2018 by Frederick E. Lepore All rights reserved No part of this book may be reproduced or utilized in any form or by any means, electronic or mechanical, or by any information storage and retrieval system, without written permission from the publisher. Please contact Rutgers University Press, 106 Somerset Street, New Brunswick, NJ 08901. The only exception to this prohibition is “fair use” as defined by U.S. copyright law. The paper used in this publication meets the requirements of the American National Standard for Information Sciences—­Permanence of Paper for Printed Library Materials, ANSI Z39​.­48​-­1992. www​.­rutgersuniversitypress​.­org Manufactured in the United States of Amer­i­ca

To Dean Falk, who had an idea. To Lynn Lepore, who listened with conspiratorial intelligence. To Ardean Everett Lepore, who loved words (and had the Scrabble scores to prove it). To Michael J. Lepore, MD, who taught me to be curious in between seeing patients.

Contents

Preface ix 1 A Neurologist Walks in Prince­ton

1

2 April 18, 1955

21

3 What the Neuropathologist Knew . . . ​ and ­Didn’t Know

39

4 The Lost De­cades (1955–1985), the Cider Box, and the Microscope

57

5 The Exceptional Brain(s) of Albert Einstein

77

6 How Does a Genius Think?

117

7 The Pursuit of Genius

179

8 Where Do We Go from ­Here? (And Where Have We Been?)

207

Notes

263

Index

301

vii

Preface It is usually found that only the ­little stuffy men [in scientific work] object to what is called “popularization,” by which they mean writing with a clarity understandable to one not familiar with the tricks and codes of the cult. We have not known a single ­great scientist who could not discourse freely and interestingly with a child. —­s teinbeck, The Log from the Sea of Cortez

Simply put, this is a biography of the brain of an extraordinary scientist. We ­will learn ­whether 1,230 grams of inert ce­re­bral tissue, studied for over six de­cades, has taught us anything about Albert Einstein as he lived and worked, the brains of other h ­ umans, or the nature of genius. To embark upon our study, we rediscovered Thomas Harvey’s photo­graphs of Einstein’s intact brain that w ­ ere taken in the spring of 1955 and then languished for many years in the basement of a home in Titusville, New Jersey.1 Thereupon, we explored the intersection of twenty-­first ­century neuroscience and Einstein’s ­grand achievements, illuminated by his vivid accounts of his pro­cesses of scientific thinking better known as gedankenexperiments. The eminently successful writer of ­legal fiction John Grisham advises would-be authors to avoid the “gimmick” of prologues (or in my case, a preface).2 Nevertheless, I’ll take my chances with a few prefatory paragraphs (both pro and con) as to why the intrepid reader should plunge into the next eighty-­seven thousand–­plus words. Dead for over sixty years, Einstein still speaks to us about the majesty and the mystery of the Very Big and the Very Small. I ­will ix

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reassert that this is not a true biography of the man, but you ­will get a sense of him . . . ​and his science (and this w ­ ill be time well spent). As I wrote about him, it gradually dawned on me that Einstein was an im­mensely likeable guy who “could discourse freely and interestingly with a child.” Much of t­ oday’s consuming interest in the neuroscience of consciousness is to be found in the relationship of Einstein’s brain to his mind writ large. My occupational biases as a clinical neurologist aside, I w ­ ill try to fairly assess if we are any closer to resolving ­whether the mind and the brain are separate (dualism) or one and the same (materialism). Can we ­really conjecture a mind apart from a brain without becoming “quite giddy,” like Alice when she saw the grin that remained a­ fter the Cheshire Cat “had vanished quite slowly”?3 Interwoven with the ­grand topics of theoretical physics and neuro­ science is a frisson of academic politics. When presented with set ­after set of brain slices that Thomas Harvey, an academic “outsider,” had mounted on microscope slides, what did the “best and the brightest” neuroscientists do (or not do) with Einstein’s brain for over fifty years? And why (at the time of this writing) is the brain lost again? My par­tic­u­lar perspective on Einstein’s brain w ­ ill be instructive, but it is not for every­one. For ­those who are ­going to have a prob­ lem with Finding Einstein’s Brain, get in line. Neuroscientists ­will find it way too clinical and antithetical to reductionist systems neuroscience. Neurologists ­will complain that they d ­ on’t treat patients with a diagnosis of “genius”—­it’s not a disease. Neuropsychologists ­will grumble about a neurologist (aka, a “brain guy”) writing about the mind. Neurophi­los­o­phers ­will shake their heads over my imprecise language—­“Did he mean property or substance dualism?” Physicists w ­ ill gape open-­mouthed at the presumption of a guy who treats migraines writing about general relativity without resorting to math. (Actually, I included Einstein’s field equation of

Preface xi

gravitation in chapter 6 to placate them. I fear they w ­ ill see through my ruse.) Neuroanatomists ­will grouse, “Cortical surface anatomy! How quaint! Korbinian Brodmann and 1909 are asking for their study back.”4 Neuroradiologists and cognitive neuroscientists ­will disallow any conclusions based on nonliving brain tissue and chant in unison, “Where’s Einstein’s functional magnetic resonance imaging?” Sorry, that par­tic­u­lar signature technology of neuroscience ­didn’t arrive ­until thirty-­six years ­after Einstein’s death. Iw ­ on’t belabor the cavils of psychiatrists, neurophysiologists, historians of science, phrenologists, iridologists (Einstein’s ophthalmologist purloined his eyes at autopsy, so ­there are no irises to study), Thomas Harvey critics (How do we know that it’s ­really Einstein’s brain?), neuroge­ne­ticists, et cetera. As I said, the line forms to the right. I can only implore the reader to please heed the words of an old Arab proverb: “The dogs bark, but the caravan moves on”—­and to turn the page.5 Dean Falk’s gyrus-­by-­g yrus and sulcus-­by-­sulcus analy­sis of Einstein’s brain incontrovertibly established its singular anatomy. Anatomy aside, do Thomas Harvey’s ce­re­bral “postcards” from 1955 have anything to tell the modern reader about the mind of a genius? I believe that brain anatomy, as studied at least from the time of Paul Broca (and his examination of the brain of the aphasic Leborgne in 1861), has illuminated (and not obscured) the workings of the mind (see chapter 8). Nearly a ­century ­later, the birth of Einstein’s brain as an object of scientific study began sadly with his death on April 18, 1955. We s­ hall see if Harvey’s brash and spontaneous brain dissection can speak informatively across the de­cades to modern neuroscience.

Finding Einstein’s Brain

chapter 1

A Neurologist Walks in Prince­ton

More than sixty years ­after his death, the streets of Prince­ton, New Jersey, have not yielded the last traces of Albert Einstein’s life and times. With a brief period as an undergraduate excepted, I have lived in Prince­ton for close to a quarter c­ entury and have walked or jogged daily through its tree-­lined streets and campus quadrangles alone or with my wife, d ­ aughters, or a succession of golden retrievers. Most of the time, distractions—­thoughts of a difficult clinical prob­ lem at the hospital that day or my dog tugging me in hot pursuit of an indigenous black squirrel—­abound, but traces of Einstein emerge from the landscape if you give them a chance. Even with its doorpost numbers painted over, Einstein’s white clapboard h ­ ouse at 112 Mercer Street is readily identified (Figure 1.1). The cash-­strapped Einstein purchased it in 1935 with proceeds from the sale of an impor­tant manuscript on relativity theory a­ fter the Nazis blocked his Berlin bank accounts.1 This was Einstein’s last home, and although well maintained it is not consistently lived in. From his front porch, Einstein would walk southwesterly for less than a mile—he never obtained a driver’s license—to his ground-­ floor office in Fuld Hall at the Institute for Advanced Study. His walk back home, sometimes deep in conversation with colleague Kurt Gödel, traversed the magnificent greensward sloping up from 1

2

Finding Einstein’s Brain

Figure 1.1. Within walking distance from the Institute for Advanced Study, Einstein lived at 112 Mercer Street in Prince­ton from 1935 to 1955. (Photo by Frederick E. Lepore, 2011.)

Fuld Hall (Figure 1.2) and evokes appreciative contemplation as I retrace his steps on an autumn after­noon. Einstein feared postmortem “canonization” of the artifacts of his life, and you ­will search in vain for plaques identifying the buildings where he lived or worked. The ­human impulse to remember the ­great is not to be denied in­def­initely (or in this case for more than fifty years ­after Einstein’s death), and in 2005 the Borough of Prince­ ton did visibly acknowledge its most famous resident by placing Robert Berks’s leonine bust of Einstein on a pedestal (Figure 1.3) in EMC Square. And so on my way to mail a letter, I w ­ ill not infrequently look up and engage the sightless bronze eyes of the sage who “saw” the curvature of space-­time. Neighborhood rambles aside, how did I become involved in the pursuit to understand a ­little more about our epoch’s (arguably) greatest intellect? Growing up, I was fascinated by my ­father’s



A Neurologist Walks in Prince­ton 3

Figure 1.2. Fuld Hall at the Institute for Advanced Study in Prince­ton, New Jersey, opened in 1939. Einstein would walk out the front door and up the ­gently sloping front lawn on his way home. (Photo by Frederick E. Lepore, 2011.)

stories of his military ser­vice as a doctor on Tinian, from which the B-29 bomber Enola Gay took off to drop the first atomic bomb on Hiroshima, Japan, on August  6, 1945. This introduced me to the ominous implications of Einstein’s iconic formula E = mc 2. As a college sophomore, I learned more about the atom and relativity from physics professor Eric Rogers, who worked in the 1920s as an assistant to Lord Rutherford (the discoverer of the proton) at the Cavendish Laboratory at the University of Cambridge. My interest in the Very Small (quantum mechanics), the Very Large (the universe), and Einstein remained in my intellectual portmanteau as I went through medical training and eventually became a neurologist specializing in vision disorders (neuro-­ophthalmology). Although neurologists know a lot about brains, our stock-­in-­trade is damaged brains, not the brains of geniuses. (An in-­between case

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Finding Einstein’s Brain

Figure 1.3. Einstein posed for sculptor Robert Berks for two days in 1953, and in 2005 Berks donated this rough cast-­bronze bust to the Borough of Prince­ton. Fittingly for the scientist whose theory of general relativity was proven correct by the total solar eclipse of 1919, this photo­graph was taken on August 21, 2017, as a total eclipse traversed Amer­ic­ a from coast to coast. (Photo by Frederick E. Lepore, 2017.)

would be a patient of normal intellect who wants to be a genius and requests, with more hope than judgment, cognitive enhancement drugs, such as methylphenidate and modafinil.) Two events in 1999 greatly increased my curiosity about Albert Einstein. First, Sandra Witelson, PhD, a professor of neuroscience at McMaster University, published an article with five photo­graphs



A Neurologist Walks in Prince­ton 5

of Einstein’s brain in the venerable medical journal the Lancet.2 The paper described Einstein’s exceptional brain with enlarged inferior parietal lobules and concluded that “anatomical features of parietal cortex may be related to visuospatial intelligence.” The study was hailed as “elegant” and “consistent with the themes of modern cognitive neuroscience” by Steven Pinker in the New York Times.3 Second, Einstein nosed out Franklin D. Roo­se­velt and Gandhi as Time magazine’s Person of the C ­ entury and was characterized as “the embodiment of pure intellect” and “the genius among geniuses who discovered, merely by thinking about it, that the universe was not as it seemed.”4 Time’s reiteration of Einstein’s profound and pre-­eminent legacy, in concert with Witelson’s startling observations, occupied my thoughts during the winter of 1999–2000 and led me to submit a proposal to write a scholarly article for the Dana Foundation. Published in March 2001, my article “Dissecting Genius: Einstein’s Brain and the Search for the Neural Basis of Intellect” questioned the premise that somehow Einstein was a “parietal lobe genius” but more importantly explored why “the intense interest in Einstein’s brain is emblematic of our abiding curiosity about intellect in general and genius in par­tic­u­lar.”5 Not being a neuroanatomist, I lacked the expertise to authoritatively agree or disagree with the four (surprisingly few!) anatomical studies of Einstein’s brain that existed in 1999. I set out to learn every­thing I could for my writing proj­ect, and on May 15, 2000, I went to the autopsy room of the Medical Center at Prince­ton (MCP), which has no affiliation with Prince­ton University, to speak with my former Robert Wood Johnson Medical School colleague and the chief of pathology, Dr. Elliot Krauss, MD, and to photo­ graph Einstein’s brain. Or rather, the 180 or so gauze-­wrapped sections floating in what suspiciously resembled two large cookie jars filled with formalin! My first surprise (in a long succession of surprises and revelations) was that Einstein’s brain had ceased to be two intact hemi­spheres sometime in the spring or summer of 1955 (and we are not exactly sure when the braincutting took place). As

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Finding Einstein’s Brain

Figure 1.4. Taken in May 2000, to my knowledge this is among the last published color photo­graphs of most of the remaining gauze-­ wrapped, celloidin-­embedded blocks of Einstein’s brain. Etched in the upper-­left surface of the jar is “GSMUP” for Gradu­ate School (of ) Medicine University (of ) Pennsylvania where Thomas Harvey returned in the spring of 1955 to dissect Einstein’s brain. (Photo by Frederick E. Lepore, 2000.)

I clicked off one thirty-­five-­millimeter Kodacolor shot ­after another, I was awestruck, obsessed, fascinated, and worried about the correct f-­stop on the lens (and aghast at the prospect of screwing up the photos). Somewhere between the exhilaration of scientific curiosity in overdrive and the fear of a botched photo op, I became intrigued by the prospect of a story exploring “What­ever became of Einstein’s brain?” Was this photo session a once-­in-­a-­lifetime opportunity? I ­didn’t think so at the time, but astonishingly, it was. Th ­ ose pictures (Figure 1.4), which made the cover of the journal Cerebrum and have been extensively reprinted, w ­ ere the last published color photo­graphs taken of Einstein’s brain—­a brain that inexplicably continues to be hidden from public view and scientific scrutiny to the pres­ent day.



A Neurologist Walks in Prince­ton 7

The shock of my first encounter with the gauze-­shrouded jigsaw puzzle that was Einstein’s brain was not cushioned by Michael Paterniti’s article “Driving Mr. Albert: A Trip across Amer­i­ca with Einstein’s Brain,” which had appeared in Harper’s Magazine in October 1997. Paterniti wrote that the brain “was chopped into nearly two hundred pieces.” His count was prob­ably off by 10 ­percent, but in his defense t­ here is still no published inventory of the contents of the two glass jars t­oday. More importantly, the article introduced eighty-­four-­year-­old Thomas S. Harvey, MD, the pathologist who had performed Einstein’s autopsy.6 I realized that to learn more about Einstein’s brain, I would have to find Dr. Harvey, who con­ve­niently lived in the neighboring town of Titusville, New Jersey. Unfortunately for me, the journalistic style of Paterniti’s Harper’s article and subsequent book of the same title offset the value of his information.7 Both describe a road trip across Amer­ i­c a, during which Paterniti drove Dr. Harvey from New Jersey to California with the goal of showing the brain to Einstein’s ­adopted grand­daughter, Evelyn. The Harvey ­family was deeply troubled by Paterniti’s eccentric characterization of Dr. Harvey, which included the account of a meeting with William S. Burroughs, who probed, “Tell me about your addictions, Doctor.” As a result, from that time forward, Dr. Harvey’s sons exhibited justifiable wariness (to my mind, at least) t­ oward inquiries about their f­ ather, and this would greatly complicate scholarly access to Dr. Harvey’s Einstein archives ­after his death in 2007. I met Dr. Harvey on June 4, 2000. Over the course of several hours, the Yale-­educated pathologist with a slight midwestern drawl went over his forty-­five-­year-­long quest “to see the difference between your brain and a genius’s.”8 On his sunny deck in Titusville, Harvey reminisced about convalescing from tuberculosis as a fourth-­year medical student, opened his slotted boxes overflowing with microscope slides of Einstein’s brain, and underscored the need to follow up on Witelson’s study of Einstein’s anomalous parietal lobes from the year before. Early in 1955 Harvey had committed to the proposition that the brain’s microscopic structure, termed

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Finding Einstein’s Brain

“neurohistology” (and not gross anatomy), was the royal road to Einstein’s genius. (“I had never r­ eally related this to gross morphology of the brain,” he said.) He voiced his disappointment “over the lack of reports from experts” and the fact that we had only “one ­ ere never to meet face-­to-­face again, but I brain” to study.9 We w ­will always remember the spirit of scientific inquiry defining his professional life and expressed even in his ninth de­cade at his retreat in rural New Jersey. Only l­ater would I come to realize the ­great personal cost incurred by his pursuit of Einstein’s genius. With the 2001 publication of “Dissecting Genius” showcasing color photo­graphs of Einstein’s brain for the first time, I had made the case for the intense interest surrounding the brain without any consideration for a research agenda, and Einstein’s brain seemingly returned to its half-­century-­long scholarly slumber.10 That slumber was not to be long-­lived. Dr. Harvey, knowing of my interest (as a card-­carrying—­OK, it’s a visual acuity testing card; we d ­ on’t have membership cards—­ neuro-­ophthalmologist) in the brain’s visual system, suggested further study of Einstein’s occipital lobes (one of the brain’s visual centers). Again, I should mention that I take care of living patients rather than postmortem specimens, so I sought the advice of two academic neuropathologists. They in turn referred me to the Armed Forces Institute of Pathology (AFIP), the high church of pathologic anatomy. In biomedical ­matters, seeking the advice of appropriate specialists is de rigueur; however, this conventional stratagem was consigned to failure when Dr. Harvey and his colleague Dr. Krauss requested specific research proposals for the Einstein brain specimens. The AFIP was willing to accept the specimens only if no strings w ­ ere attached and would not consent to any specified research program as a condition for donation. Unbeknownst to the denizens of the AFIP in 2001, Harvey could remember all too well the 1955 conference convened by Dr. Webb Haymaker, head of neuro­ pathology at the AFIP. Lieutenant Col­o­nel Haymaker imperiously demanded that the small-­town pathologist from Prince­ton hand over Einstein’s brain to the Big Boys of academic neuropathology.



A Neurologist Walks in Prince­ton 9

Harvey did not relinquish the brain but was left with a very bad impression. Accordingly, he was not about to let history try to repeat itself, and the AFIP came away empty-­handed again in 2001. The ghosts of the 1950s would continue to influence the scholarly pursuit of the brain, and Harvey’s on-­again, off-­again relationship with the academic establishment w ­ ill be an ongoing leitmotif as we trace the errant course of Einstein’s brain. However, the AFIP was not through with Harvey. On November 7, 2001, Adrianne Noe, PhD, director of the National Museum of Health and Medicine (NMHM) of the AFIP, wrote to me inquiring about my willingness to discuss the NMHM as a “repository for the brain of Albert Einstein” with Drs. Harvey and Krauss. My efforts as a “good broker” and her entreaties of access to cutting-­ edge “nondestructive imaging modalities” notwithstanding, Harvey stuck to his guns, and the brain remained at the MCP. Although Dr. Noe’s relationship with AFIP was to radically change, her curatorial interest in Einstein’s brain never flagged, and biding her time, she is to rejoin the hunt nine years ­later. For the six years following 2001, the world seemingly forgot about Einstein’s brain. As if memorializing this transient global amnesia (note: not the kind that I diagnose in the clinic), in 2001 Carolyn Abraham’s terrific account of “the bizarre odyssey of Einstein’s Brain”—­Possessing Genius—­drew to a close with the “damp and unglorious wedges” of the brain displayed on Dr. Krauss’s desk, “still in the dubious ser­vice of science.”11 Occupied with the day-­to-­day management of the Department of Pathology of the MCP, Dr. Krauss has authored no published Einstein research to the pres­ent day. One paper, a description of abnormal astrocytes in a piece of Einstein’s cortex that Drs. Harvey and Krauss loaned out, emerged from Argentina in 2006. This microscopic finding was “of unknown significance.”12 ­A fter arranging to receive brain tissue blocks, slides, and photo­graphs from Harvey in 1995, Sandra Witelson wrote Harvey in December  2005 requesting to “borrow some of your original Nissl slides” to evaluate the cell density in Einstein’s inferior parietal lobes.13 ­W hether she ever received the additional slides

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Finding Einstein’s Brain

or not, only one subsequent abstract on Einstein’s cytoarchitecture came forth. The brain’s obscurity persisted at the time of Dr.  Harvey’s death on April  5, 2007. He died of complications from a stroke in the same hospital where he had performed Einstein’s autopsy almost fifty-­seven years earlier. On December 22, 2007, I received an e-­mail from Dean Falk, PhD, chair of the Department of Anthropology at Florida State University. She had read “Dissecting Genius” and wished “to access the photo­graphs that w ­ ere taken of Einstein’s gross brain in 1955. . . . ​ Can you point me in the right direction?” Although Witelson had reproduced five such photo­graphs in her 1999 Lancet article,14 I was certain more photo­graphs must exist. I just ­didn’t know where to find them. Undeterred, Falk and I approached two likely sources—­Elliot Krauss and Sandra Witelson. Krauss had tissue blocks but no photo­ graphs of the intact brain, and Witelson did not respond to Dean Falk’s collegial entreaties. Professor Falk soldiered on and reanalyzed the five grainy photos reproduced in the Lancet. Her paper “New Information about Albert Einstein’s Brain” appeared online in Frontiers in Evolutionary Neuroscience in 2009.15 This publication reawakened scientific interest in Einstein’s brain and was cited as one of the top one hundred science stories in 2009 (number ninety-­ three: “Re-­analyzing One of the Greatest Brains in History”) by Discover magazine.16 It also intensified the pressure to find the missing photo­graphs of Einstein’s brain . . . ​and that’s when I remembered Cleora Wheatley. ­A fter leaving Prince­ton and its environs for his native Midwest in the 1970s, Harvey, thrice-­divorced, returned in 1995 and lived the remainder of his life with his former business associate and Prince­ ton Hospital nurse, Cleora Wheatley. I met them both when I interviewed Harvey on June 4, 2000. Then, as now, Cleora was fiercely in­de­pen­dent, and a­ fter Harvey’s death in 2007 she continued (well into her nineties) to live alone in her modest ranch ­house among the trees and hills of Titusville. Would Harvey have entrusted his



A Neurologist Walks in Prince­ton 11

Einstein archives (including photo­graphs) to her safekeeping? Harvey was an inveterate photographer who used a thirty-­five-­millimeter Exakta camera for his specimens, and he had enlisted the aid of a photographer, Howard Schroeder, for his Einstein proj­ect. In and of itself, Harvey’s photographic proficiency and tendency to keep his specimens close at hand (“brain fragments . . . ​kept in a cider box, u ­ nder a beer cooler, in Harvey’s office”) did not clearly point to a par­tic­u­lar storage location for his Einstein brain photos.17 As I came to learn, Harvey was capricious in his distribution of Einstein materials, and dif­fer­ent researchers received dif­fer­ent sets of specimens. No investigator received a “complete” set of tissue blocks, slides, and photo­graphs. Even worse, ­t here is no address book or cata­log of the destinations of all the Einstein materials Harvey created. As many as twenty-­four hundred microscope slides may have been cut, stained, and mounted by Harvey and University of Pennsylvania technician Marta Keller,18 but the whereabouts of well over two-­thirds are still unknown. To pursue a comprehensive neuroanatomical study of a genius, Dean Falk had impressed upon me the need to obtain more photo­ graphs of Einstein’s undissected brain in general and his frontal lobes in par­tic­u ­lar. ­A fter ­going down too many blind alleys and with nothing to lose, I phoned Cleora on May 1, 2009. A ­ fter expressing my sympathy for the loss of Dr.  Harvey two years earlier, I inquired ­whether he had kept any Einstein-­related materials at her ­house. She offhandedly replied that a number of boxes (eventually, eight ­were archived) ­were sitting in her cellar! As luck would have it, Dr. Harvey’s m ­ iddle son, Arthur, was visiting her that day. I acquainted them with Dean’s recent study and the crying need to obtain additional photo­graphs to better delineate Einstein’s cortical anatomy. Arthur informed me that his eldest ­brother, Thomas, who was serving as executor to Dr. Harvey’s estate, must grant access to the Einstein materials. When I called Thomas’s home in North Carolina, his wife, Nancy, tactfully informed me that he was not answering phone calls

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Finding Einstein’s Brain

regarding Einstein in the wake of the Harvey ­family’s wounded feelings over the “comic tone” of Paterniti’s book, Driving Mr. Albert. I spent a ­great deal of time persuading her that I did not subscribe to the Michael Paterniti “school” of journalism and that I was seeking to further the research that Dr. Harvey had begun in 1955. As a result, Thomas spoke with his ­brother Arthur, and I learned that the Harveys had written the MCP with the intent of giving the boxes to Dr. Krauss. This was not welcome news, and the prospects for open scholarly access dimmed considerably. With Krauss as the sole custodian of the single-­largest cache of Einstein brain tissue (“about half the brain” was returned to Prince­ton, according to Harvey),19 no peer-­ reviewed research publications ­under his se­nior authorship ­were forthcoming (and none would appear as of 2017). Dr. Krauss would infrequently “loan” brain tissue to other investigators and he had intoned a lugubrious philosophical sentiment—­“It’s kind of anticlimactic, i­ sn’t it?”—­when showing the brain to journalist Carolyn Abraham. She trenchantly and regretfully observed that “a single, smalltown pathologist is left to decide the fate of history’s most celebrated brain.”20 I wrote to Arthur on May 17, 2009, and pointed out that with the exception of Dean Falk’s research based on limited photo­graphs, Einstein research had been in the doldrums for a de­cade. The newly discovered archives in Cleora’s basement w ­ ere “too impor­tant to be entrusted to the judgment of a single curator.” Steering clear of the notion of solo curatorship, I asked Arthur and his extended f­ amily to consider academic institutions, such as the Smithsonian Institution; the American Museum of Natu­ral History; the AFIP; Prince­ ton University; and somewhat self-­servingly, my own medical school, Robert Wood Johnson, at which I could assem­ble a multidisciplinary team to study Einstein’s brain. (Dear Reader, if my plan strikes you as a trifle ad hoc and improvised, ­don’t worry, it most as­suredly was.) In my defense, ­there are no Institutes for the Study of the Gross and Microscopic Neuroanatomy of Supergeniuses. The study of profound geniuses is a very infrequently traveled detour



A Neurologist Walks in Prince­ton 13

from mainstream neuroscience, which embraces a reductionist paradigm and increasingly focuses on so-­called “­simple” ner­vous systems, such as Caenorhabiditis elegans, a roundworm endowed with 302 (count ’em, 302) neurons. The scientists who study the physical trappings of empyreal reaches of intellect are few and far between, and they remain separate from their parent institutions u ­ nder the guise of one-­or two-­person subspecialty “shops.” Katrin Amunts and Karl Zilles in Germany; Sandra Witelson in Canada; and my collaborator, Dean Falk, are all investigators par excellence in this esoteric field of scientific inquiry. As the Harvey ­family considered the list of potential recipient institutions, which by now had expanded to include Yale, Harvard (McLean Hospital), and the Institute for Advanced Study, I remained hopeful that the pitfall of a single curator for the newly found Einstein materials could be avoided by the intercession of a renowned scholarly institution. My hopes w ­ ere soon to be dashed! A few days before I began my attempt to redirect the disposition of Dr. Harvey’s archives, David LaBerge, PhD, e-­mailed Dean Falk with an intriguing proposal for collaborative research. LaBerge, professor of cognitive sciences emeritus at the University of California, Irvine, had read Dean’s recent article on Einstein’s brain and was particularly interested in her detailed descriptions of the parietal lobes. He hypothesized that the thickness of the cortex was a crucial f­ actor for “holding over time of an image (or a perception).” He had studied the apical dendrites (elongated cell pro­cesses) of layer five (­there are six layers in the neocortex) of cortical pyramidal neurons and found layer five apical dendrite length to be highly correlated with cortical thickness. Moreover, the dendrite length increased across the mammalian phyla from mouse to ­human.21 As an informal illustration of his hypothesis, he wrote that cats (with longer layer five apical dendrites) “can hold their attention to a mouse hole from the outside longer than a mouse [with shorter dendrites] can hold its attention to the hole from the inside; this helps cats catch mice.”22 The logical upshot of this hypothesis would be “to mea­sure the thickness of the parietal region in Einstein’s brain,

14

Finding Einstein’s Brain

and compare it with similar mea­sure­ments of control brains.” Up to this point, Dean and I had focused on finding old photo­graphs of Einstein’s intact and partially dissected brain with the purpose of rigorously analyzing the gyri (ridges) and sulci (crevices) of its surface anatomy. LaBerge was taking a radically dif­fer­ent approach by proposing to study the microscopic connections (axons and dendrites) between Einstein’s neurons. Reader, you might well be thinking that the study of the microscopic anatomy of biologic materials has been fairly routine since the advent of Leeuwenhoek’s microscopes in the seventeenth c­ entury, but this has been only partly true in the instance of Einstein’s brain. Although Marian Diamond had performed cell counts of Einstein’s neurons and glial cells nearly a quarter ­century earlier, amazingly, no one had mea­ sured the connections (or in this case apical dendrites), as LaBerge boldly proposed. Extrapolating from the anatomy of apical dendrites, LaBerge was collaborating with a biophysicist, Ray Kasevich, to formulate an electric cir­cuit model showing how the apical dendrite’s increased length might fine-­tune the resonating frequency of the pyramidal neurons embedded in the recurrent corticothalamic cir­cuits. This would lead to “clearer” ­mental images “relatively ­free of distracting noise (and therefore more sustainable over time).”23 With Dr. Harvey’s archives in philanthropic limbo and unobtainable, the only game in town for LaBerge was to access Elliot Krauss’s repository of Einstein brain tissue. As Dr. LaBerge was to discover, Krauss alternately blew hot and cold on the prospects of collaborative research. LaBerge e-­mailed that a­ fter a “very pleasant 7-­minute conversation,”24 Krauss agreed to send a copy of Harvey’s “road map”—­pencil sketches of Einstein’s brain with the locations of the 240 tissue blocks numbered and demarcated (Figure 1.5). Dr. Harvey had numbered the microscope slides to correspond with their cortical sites of origin, making the road map an invaluable key for neurohistologic research. True to his word, Krauss e-­mailed the road map to LaBerge on July 22, 2009. Unfortunately, this was to be the zenith of a proposed collaboration with Dr. Krauss.

Figure 1.5. Five (of nine) diagrams of the orientation of the 240 blocks sectioned from Einstein’s ce­re­bral hemi­spheres. Sketched by Harvey in 1955, ­these served as “road maps” for the locations of each numbered brain block from which microscope slides ­were sectioned. Although the brain stem and the cerebellum ­were preserved, they w ­ ere not incorporated in the schema of numbered brain sections. (Harvey Collection, National Museum of Health and Medicine.)

16

Finding Einstein’s Brain

Repeated entreaties for a loan of the numbered slides cut from cortical areas of interest went unheeded. Two obstacles became readily apparent. First, Krauss was increasingly reluctant to send out tissue ­because he could not directly observe what the “researchers are ­doing,” and he feared that samples would “not be returned.” Second, although he assured LaBerge that “a slide had been taken from each slice” of brain, he did not vouchsafe for a complete set of microscope slides at the MCP. It would turn out that his slide set was incomplete (with fewer than ninety slides), and when I informed him of the seven additional slide sets in the boxes in Cleora’s cellar, in a last-­d itch effort to complete his set he vainly importuned Arthur Harvey for more slides. The frustrating confusion over Krauss’s slide set reflects Dr. Harvey’s haphazard allocation of Einstein materials. More fundamentally, it shows that Krauss was preoccupied with the daily ­running of a busy hospital pathology ser­vice and that investigating the neuroanatomy of genius was simply not a priority for him. Dean Falk had successfully interested the distinguished neuroanatomists Karl Zilles and Katrin Amunts in our fledgling proj­ect. No strangers to the anatomy of genius, they had demonstrated the distinctive cytoarchitecture of Broca’s (language) area in the brain of Emil Krebs, who fluently spoke more than sixty languages.25 With this international research team taking form, we invited Dr. Krauss to join us. He never responded and on December 2, 2009, he confirmed that he would not allow Einstein’s slides to leave the MCP. From that day forward, the largest extant collection of Einstein brain tissue ceased to be available (if it ever truly was) for open scholarly study. We ­were back at square one with no photos, no slides, and no brain tissue. By October  2009 the Harvey ­family had narrowed the field down to Robert Wood Johnson Medical School (RWJMS), Yale, Prince­ton, the Smithsonian Institution, or the AFIP as the ­future home of their f­ ather’s archives. On May 17, 2010, I had the unenviable privilege of informing my boss, Dean Peter Amenta of RWJMS, that our medical school was runner-up in the pursuit of



A Neurologist Walks in Prince­ton 17

the collection of Thomas S. Harvey, père. As spelled out in the letter of Thomas J. Harvey, son and executor, the Einstein materials ­were ­going to “the National Museum of Health and Medicine, which is part of the Armed Forces Institute of Pathology in Washington, D.C.” Fifty-­five years a­ fter the failed strong-­arm tactics of Dr. Webb Haymaker of the AFIP and nine years ­after Adrianne Noe’s futile bid on behalf of the AFIP and the NMHM for the Einstein materials, the AFIP had at last won out . . . ​or had it? In its heyday the AFIP was the mecca of diagnosis, teaching, and research in pathology. As a University of ­Virginia neurology resident, I dutifully made the pilgrimage from Charlottesville to Washington, DC, and spent a week learning the rudiments of neuropathology from AFIP pathologists while studying the magisterial green and tan AFIP brain tumor monographs. The AFIP’s mission of research was world-­renowned, and its tissue repository contained fifty-­five million glass slides, thirty-­one million paraffin blocks, and more than five hundred thousand wet tissue samples.26 By 2005 federal bud­get priorities ­were changing, and the disestablishment of the once mighty AFIP began in earnest. The decline was irrevocable, and on September 15, 2011, the AFIP closed its doors ­after 150 years. In the past the AFIP had been inextricably interlinked with the Army Medical Museum, which was the forerunner of the NMHM. From the perspective of the NMHM, the formidable research operations of the AFIP ­were slowly receding from sight in the opening years of the twenty-­first c­ entury, and in 2011 they vanished altogether. When Adrianne Noe drove to Titusville in June 2010 to pick up the boxes of Einstein materials and deliver them to the NMHM, the Harvey ­family was unaware of the imminent demise of the AFIP-­NMHM partnership. Without this partner­ ship, ­f uture collaborative research on Einstein’s brain would be imperiled. The NMHM, if not the soon-­to-­be-­defunct AFIP, was the clear winner of the Einstein sweepstakes. And our primary object was to gain access to the NMHM’s prize acquisition. H ­ ere, we ran headon into Dr. Noe’s curatorial prerogative, which, for the time being,

18

Finding Einstein’s Brain

prevailed over research initiatives. For example, although Einstein’s brain was arguably the NMHM’s most impor­tant holding (with the bullet that killed Lincoln r­ unning a close second), the museum did not publicly acknowledge the Harvey bequest u ­ ntil more than two years a­ fter the fact. (This tactic beggared credulity, and I l­ ater told Adrianne that this would be as if Thomas Hoving had kept the imminent blockbuster King Tut exhibit at the Metropolitan Museum of Art ­under his hat in 1976 . . . ​of course, he ­didn’t, and eight million attended!) The Harvey f­amily supported our efforts and wrote, “We believe that it should be pos­si­ble for Dr. Lepore and his partners to carry out their study with the National Museum of Health and Medicine as the custodian of the material.”27 Nevertheless, multiple requests to examine the cartons from Cleora Wheatley’s cellar elicited vague and evasive responses from Dr. Noe and the NMHM that appeared to be stalling for time. Admittedly, the NMHM was being relocated to a new building at Fort Detrick in Silver Spring, Mary­land, and some delay was inevitable. However, over a year had elapsed since the boxes had left Titusville, and no publications, exhibits, or public announcements regarding the Einstein acquisitions had issued forth from the NMHM. On July 29, 2011, bursting with impatience, I wrote Adrianne Noe again, requesting a full day to examine the Einstein materials and remonstrating that “the Einstein materials are too impor­tant to be withheld from the scientific community any longer.” Eventually (very eventually!), Dr. Noe graciously acceded to my request, and the NMHM threw its doors open for Dean Falk and me on September 12, 2011. We learned that the NMHM is very dif­ fer­ent from most museums and is administered by the Department of Defense. It is part of Fort Detrick, the current host of the U.S. Biological Defense Program, and as we drove past sentries, we ­were informed that no photo­graphs of the grounds ­were permitted. Undeterred, in the eight fleeting hours granted to us, we pored over 567 microscope slides, documents that included Einstein’s Last ­Will and Testament, and dozens of hitherto unknown and unpublished photo­graphs of Einstein’s ­whole and partly dissected brain that



A Neurologist Walks in Prince­ton 19

Dr. Harvey had taken in the spring of 1955. For more than a half ­century, the rec­ords surrounding Einstein’s autopsy had been out of bounds to scholarly inquiry and questions ­were rampant. Did Einstein’s w ­ ill forbid the study of his brain? No. Did the collection contain more than the five photo­graphs of the brain published by Witelson in 1999? Yes, many more. W ­ ere t­ here any microscope slides stained to show the myelinated “wiring” (composed of axons and dendrites) of brain cells? Yes. Did the executor of Einstein’s estate or religious authorities criticize Dr. Harvey? Yes. And on and on. Over the course of eight hours, we found answers to questions persisting since 1955 and set the course for ­future investigations into the neural under­pinnings of Einstein’s genius. The intellectual exhilaration experienced on that day in Silver Spring was scientific exploration at its most invigorating. As a clinical scientist, my closest experience to the pure discovery of the newfound Einstein archives was on a field expedition to the Mariana Islands in the remote Western Pacific. ­There, I examined dozens of patients and wrote the first comprehensive description of the neuro-­ophthalmological findings in Lytico-­Bodig, an invariably fatal (and now, thankfully, vanishing) neurological disease of the indigenous Chamorran ­people.28 The myriad notes and digital photo­graphs we took that sunny September day would provide the foundation for our discovery of Albert Einstein’s astonishing brain anatomy. Months of work lay ahead of us. Before we can proceed any further ­toward an account of our findings and the frontiers of neuroscience, however, we must go back in time to April 18, 1955, and turn our attention to a seventy-­ six-­year-­old physicist with an inoperably ruptured abdominal aortic aneurysm and to an audacious college-­town pathologist waiting in the wings.

chapter 2

April 18, 1955

By the lights of medical prognostication, Albert Einstein should have died five years earlier than April 18, 1955. Einstein had experienced bouts of abdominal pain with occasional vomiting for many years, and in December  1948 Dr.  Rudolph Nissen at Brooklyn Jewish Hospital performed an exploratory laparotomy and found a “grapefruit-­sized” abdominal aortic aneurysm. Midcentury vascular surgery had not yet developed open or endovascular grafts for the repair of aortic aneurysms, and the surgeon wrapped the weakened blood vessel with polyethylene cellophane.1 Einstein was discharged on January 13, 1949. Einstein was living on borrowed time. A large untreated abdominal aortic aneurysm was typically associated with a median survival of nine months.2 The cellophane-­induced foreign-­body reaction and fibrosis may well have strengthened the walls of Einstein’s weakened abdominal aorta and delayed its rupture u ­ ntil April 13, 1955, when he collapsed while experiencing right upper-­quadrant abdominal pain. Called in for consultation, Dr. Frank Glenn, chief of surgery at New York Hospital-­Cornell Medical Center, went to Prince­ton and proposed a highly risky resection of the aneurysm. Einstein declined, replying, “It is tasteless to prolong life artificially. I have done my share, it is time to go. I w ­ ill do it elegantly.”3 Einstein was admitted to Prince­ton Hospital on April 15. The day before he died, he was jotting down calculations (twelve pages of 21

22

Finding Einstein’s Brain

Figure 2.1. Thomas Stoltz Harvey, MD, chief of pathology at Prince­ton Hospital, as photographed (but never published) for Life magazine by Ralph Morse in the hospital’s pathology laboratory on the day that Einstein died. (Ralph Morse, “Einstein’s Pathologist,” in Life, April 18, 1955.)

“tightly written equations” ­were found next to his deathbed).4 At 1:15 a.m. on April 18, the night nurse, Alberta Rozsel, heard a few German words (incomprehensible to her), two agonal breaths . . . ​ and then he was gone.5 Enter Thomas Stolz Harvey, MD (Figure 2.1). The forty-­t wo-­ year-­old chief of pathology at Prince­ton Hospital was notified of Einstein’s death at dawn. That morning the Yale-­and University



April 18, 1955 23

of Pennsylvania-­trained pathologist performed the autopsy in the presence of Einstein’s executor and fellow émigré, Otto Nathan. Only Harvey’s ­later recollections rec­ord the events of that day; the Prince­ton Hospital autopsy report has been missing for de­cades. Further procedural irregularities on that April morning included the removal of Einstein’s eyes by his ophthalmologist, Dr. Henry Abrams, possibly during the interval when Dr. Harvey left the morgue to speak to the reporters gathered at the front steps of Prince­ton Hospital.6 When I spoke with Harvey (over fifty-­five years ­later) about the postmortem examination, he recalled his findings of an abdominal aortic aneurysm and an “abdomen full of blood.”7 He had found a hemorrhage into the tissues surrounding the gallbladder, mimicking a gallbladder attack but actually occurring in the more ominous setting of an abdominal aortic aneurysm (the Einstein sign).8 Harvey also recollected that the inner wall of the aorta was “just riddled with [cholesterol] plaques,”9 reflecting Einstein’s (and his generation’s) blissful ignorance of the perils of a cholesterol-­rich diet. If the cellophane-­induced fibrosis of the aorta from the surgery in 1949 was found, its presence goes unrecorded. On the morning of April 18, Harvey announced to the gathered journalists that “a big blister on the aorta which broke fi­nally like a worn out inner tube” was the cause of death.10 ­A fter systematically examining Einstein’s viscera earlier that morning, Harvey opened the cranium with a saw, incised the dura (sometimes inadvertently slicing into the cortex, as we would find in 2011), severed the twelve pairs of cranial nerves, cut the intracranial portions of the carotid and vertebral arteries, and adroitly lifted the gelatinous brain up from the cranial vault, its abode for seventy-­six years. A tissue fixative, formalin, was injected through the carotid arteries to infuse the brain and ensure maximal preservation. A “less impor­tant” brain would have warranted the more routine preservation technique of immersion in formalin without arterial infusion. Einstein’s brain was both perfused and immersed in a

24

Finding Einstein’s Brain

formalin bath, where strings held it suspended in the liquid to prevent flattening before the formalin-­induced hardening could set in. The preservation of the brain tissue was performed with room temperature fixative—­the standard in midcentury neuropathology. Even though Watson and Crick had discovered that DNA was the ge­ne­tic code of life in 1953,11 preservation techniques for DNA ­were not in routine use in 1955. Thomas Harvey could not know that at the ambient temperature of the Prince­ton Hospital morgue, the inexorable laws of thermodynamics and enzymology irrevocably denatured Albert Einstein’s strands of DNA into fragments (snippets), barring the way for any f­ uture attempts to reassemble his genome in its entirety.12 The front page of the next morning’s New York Times ran the headline “Dr. Albert Einstein Dies in Sleep at 76.” Above the fold, the article’s sixth paragraph noted that “the body was cremated without ceremony . . . ​­after the removal, for scientific study, of vital organs, among them the brain that had worked out the theory of relativity and made pos­si­ble the development of nuclear fission.”13 This was very unexpected (and possibly unwelcome) news for Einstein’s eldest son, Hans Albert, and stepdaughter, Margot. (At this point Einstein had been predeceased by his two wives, and his youn­gest son, Eduard, was institutionalized.) Hans Albert (as recounted by Harvey) was “very upset” that not all his ­father’s organs had been cremated. The small-­town pathologist ­gently reminded him that he had signed the permit for autopsy and, with inspired boldness, that this was an unpre­ce­dented and vanishingly rare opportunity to study the brain of a genius. Harvey also assured him this would be a scholarly, scientific study not to be sensationalized in popu­lar publications, such as Time.14 Hans Albert, himself a professor specializing in hydraulic engineering at the University of California, Berkeley, saw the scientific merit of Harvey’s compelling proposal to retain the brain for anatomical study. ­W hether Einstein’s executor, Otto Nathan, thought other­wise is not known. With permission granted by Einstein’s eldest (and only mentally competent) son, Nathan had no choice but to comply.15



April 18, 1955 25

The confusion regarding the propriety of preserving his brain for study arises in no small part from the lack of directives that Einstein provided. The assertion that “in accordance with his wishes, he was cremated in Trenton on the after­noon he died, before most of the world had heard the news” lacks any documentation of t­ hose so-­called “wishes.”16 If such wishes ­were expressed to Hans Albert, Otto Nathan, or Einstein’s secretary and ­house­keeper, Helen Dukas, they w ­ ere left unrecorded. Nathan averred that no “specific oral instructions that his body was to be used for scientific research” ­were given but that Einstein had remarked “from time to time on the usefulness of the ­human body ­after death.”17 Neither does Einstein’s Last ­Will and Testament of March 18, 1950, provide any guidance as to the disposition of his mortal remains.18 Witnessed by his ­great friend and colleague Kurt Gödel, the document disposed of $75,000  in five legacies, bestowed manuscripts and royalties to Hebrew University, and bequeathed his violin to his grand­son . . . ​ but no mention is made of cremation, funeral rites, interment, or final arrangements for his body. It remains an unanswered question as to ­whether Einstein would have been aggrieved, intrigued, or uncertain over the utility of studying his brain anatomy. ­There is modest evidence that Einstein was interested in the functions of his own brain. In the 1940s he wrote a detailed description of his thought pro­cesses (“visual and some of muscular type”) when solicited by his colleague, the mathematician Jacques Hadamard, who was writing a book about mathematical creativity and the mathematician’s mind.19 In 1945 Einstein consented to have Dr. Gustav Bucky, his friend and patent coholder, perform a plain skull x-­ray (anterior-­posterior and lateral views) for unknown reasons. (The films subsequently fetched $38,750 at auction in 2010.) Could this have been nascent neuroanatomical research? In 1951 Einstein (along with John Von Neumann and Norbert Wiener) underwent electroencephalography (EEG) at Mas­sa­chu­setts General Hospital to assess changes in his brain waves while relaxing or thinking about prob­lems of relativity.20 In his Autobiographical Notes, Einstein declares that “the essential in

26

Finding Einstein’s Brain

the being of a man of my type lies precisely in what he thinks and how he thinks.”21 Based on t­ hese glimpses of Einstein’s interest in his own cognition, I believe he would have endorsed the spirit of scientific inquiry that led Harvey and his successors to begin studying his brain on April 18, 1955. Permission secured, Harvey confronted the audacious task of studying the brain of the man who was arguably the greatest genius of our epoch. First and foremost, the brain required a few days to harden enough to permit ­handling outside its formalin bath. From that point, “mea­sure­ments and external observations w ­ ill be made before it is dissected, photographed in color and analyzed.”22 No color photo­graphs of Einstein’s brain in 1955 have ever surfaced, and this would not be the last time the Prince­ton pathologist’s intentions failed to materialize. Of greater significance was Harvey’s decision to dissect the brain. As we would learn over a half ­century ­later, it is exceedingly difficult to assess the complex three-­ dimensional surface of the brain by examining two-­dimensional photo­graphs. Once the brain was cut apart, the opportunity for a truly detailed examination of the external cortex was lost. When queried as to ­whether “the brain could be reassembled ­after its dissection in small segments for minute studies,” Dr. Harvey replied in the negative.23 Harvey would section the dissected blocks of brain tissue into microscope slides and study the fine anatomy (histology) of neurons, their connections (axons and dendrites), and their supporting cells (glia), but he irrevocably gave up the chance to examine Einstein’s intact gross cortical anatomy. This trade-­off was the keystone of Harvey’s overarching philosophy as he took his first faltering steps to approach the “prob­lem” of Einstein’s brain. Forty-­ five years ­later, he confided to me that he “had never ­really related this [Einstein’s genius] to gross morphology of the brain.”24 For the rec­ord, Harvey believed that microscopic neuroanatomy would be the most informative approach. On April 20 Harvey was quoted as saying that “the study [of Einstein’s brain] ­will be made by a team of outstanding medical men,” and among them would be Dr. Harry M. Zimmerman, chief of



April 18, 1955 27

the laboratory division at Montefiore Hospital and Harvey’s mentor at Yale.25 Two days l­ater Harvey declined to name the other physicians who would work with him and now said Dr. Zimmerman “might” be among the group. Harvey also announced that a conference would be held on April 25 “to work out plans for the study of Dr.  Albert Einstein’s brain.”26 The Prince­ton Hospital Board of Trustees balked at handing the public relations gold mine that was Einstein’s brain over to a hospital in the Bronx and thwarted Harvey’s scholarly intentions. Months would pass before Zimmerman would see not the intact brain but a slide set—­a bittersweet experience for the neuropathologist who in 1953 had personally convinced Einstein to lend his name to the fledgling medical school that Zimmerman had founded! Harvey’s conference of outstanding medical men was further derailed when Otto Nathan, livid at the “utterly distasteful notoriety” now surrounding the brain, demanded the cancellation of the conference and suspended further “analy­sis or study of any kind” of the brain.27 Harvey drove from Prince­ton to Nathan’s Greenwich Village apartment and met with the incensed executor. The substance of the conversation is not known, but somehow he placated and regained Nathan’s confidence—­for a time. Throughout the journey of Einstein’s brain, Harvey had a knack for changing his course as circumstances dictated. At the close of April 1955, we find Harvey, a general pathologist with neither academic credentials nor specialized expertise in neuropathology, forced to improvise an approach to the World’s Most Impor­tant Brain without benefit of the sagacious Harry Zimmerman or a team of neuropathologic luminaries. How was Thomas Harvey to proceed? In medicine (no less than many other fields), exceptional mentors may inordinately influence the training pro­cess. In Harvey’s case his “intellectual bloodline” descended from several teachers who profoundly s­ haped clinical neuroscience in the twentieth ­century. ­A fter contracting tuberculosis in 1937 Harvey ultimately graduated from the Yale School of Medicine in 1941. From 1934 to 1939 as a Yale undergraduate and medical student he was within the orbit of Harvey Cushing

28

Finding Einstein’s Brain

(arguably, the most famous neurosurgeon in the world), and Cushing encouraged him to enter the emerging field of neurosurgery.28 (Rickman Godlee had surgically removed a brain tumor for the first time in 1884—­only a half ­century earlier.) Harvey Cushing trained the men (and one ­woman, Louise Eisenhardt) who would define neurosurgery throughout the world in the twentieth ­century. One of his most gifted trainees off and on from 1919 to 1928 was Percival Bailey, who hailed from L ­ ittle Egypt (southernmost Illinois).29 Bailey and Gerhardt von Bonin wrote The Isocortex of Man in 1951, and Thomas Harvey’s dog-­eared and heavi­ly annotated copy of this tome served as both bible and atlas as he embarked on his study of Einstein’s brain. In the book’s first pages, Bailey and von Bonin declare that “the architecture of the ce­re­bral cortex is the main topic of this study.”30 They disagreed with the prevailing neuroanatomical maps of K. Brodmann31 (1909) and A. W. Campbell32 (1905) (Figure 2.2 and Figure 2.3), which parcellated the ­human ce­re­bral cortex into forty-­t hree and fourteen areas, respectively. They inveighed against such black-­and-­white maps giving “a false impression of areal bound­aries” and under­lying a “shaky foundation” for clinical work.33 They departed from the methods of Brodmann and Campbell by cutting not forty-­t hree or fourteen but twenty-­one sections of cortex perpendicularly oriented to the brain’s surface. The formalin-­perfused ce­re­bral tissue was embedded in celloidin (hardened nitrocellulose) and stained with thionine (a cell body stain). Harvey, an apt pupil, used some of Bailey’s methods but then struck out on his own to cut Einstein’s hemi­spheres into 240 blocks. Emulating Bailey, Harvey also employed a cell body stain to visualize neurons, but he preferred Nissl stain, which demarcated each cell body’s rough endoplasmic reticulum, a site of protein synthesis. Not content with delineating neuronal cell bodies alone, the Prince­ton pathologist used a Weigert stain to trace the course and extent of myelinated axons, which connect each neuron with many ­others. In neuroanatomical parlance the gross appearance of the brain’s countless cell bodies (neurons and glia) is termed gray ­matter and that of the myelinated axons is described as white

Figure 2.2. Brodmann’s classical map of lateral (top) and medial (bottom) ­human cortex designated forty-­three histologically distinct areas. (­There are gaps in his numbering system, which goes to fifty-­two.) This map was based on a de­cade of meticulous study of the microscopic anatomy of Nissl (cell body) stained slides of the ­human brain. (Korbinian Brodmann, Localisation of the Cerebral Cortex: The Principles of Comparative Localisation in the Cerebral Cortex Based on Cyto-architectonics. New York: Springer, 2006.)

Figure 2.3. A. W. Campbell’s 1905 map of lateral (top) and medial (bottom) surfaces of the left hemi­sphere of a forty-­one-­year-­old man delineated fourteen areas. Campbell stained both cell bodies and myelinated nerve fibers to differentiate cortical regions. Unlike Brodmann, who focused on purely histologic localization, Campbell’s map additionally sought to point to exact areas of cortex with known function. (A. W. Campbell, Histological Studies on the Localization of Ce­re­bral Function. Cambridge: Cambridge University Press, 1905.)



April 18, 1955 31

­matter (although to my eye they appear pinkish tan and light beige, respectively). Harvey’s decision to stain both Einstein’s gray m ­ atter and white ­matter appears inevitable from our perspective of twenty-­ first c­ entury neuroscience, but in 1955 it was prescient (and sixty years ­later, we are just beginning to explore the significance of Einstein’s white ­matter). Truth be told, neurology was a relatively young science in 1955. The building block (and seminal concept) of central ner­vous system anatomy, the neuron, awaited scientific recognition u ­ ntil the awarding of the 1906 Nobel Prize in Physiology or Medicine—­a scant forty-­nine years before Harvey began to cut Einstein’s brain. Even at that Nobel Prize ceremony, the recipients, Santiago Ramón y Cajal34 ­ hether the neuand Camillo Golgi,35 wrangled from the dais over w ron was an individual unit or part of a single, all-­encompassing neural network—­a syncytium. Sanford Palay and Edward De Robertis’s electron microscopy in 1954 would once and for all reveal the neuron’s anatomical discontinuity at the synapse and validate the neuron doctrine of the neuron as a single unit. However, before Harvey could begin to use his Nissl and Weigert stains on the eighty-­five or eighty-­six billion or so neurons that constituted Einstein’s brain, it needed to be cut into blocks and microscopic sections. And to accomplish this, he would have to cross the Delaware River and enlist the assistance of an old friend, Marta Keller. Thomas Harvey’s well-­laid plans to become a pediatrician w ­ ere derailed when he contracted tuberculosis in 1939, requiring a prolonged convalescence in a sanatorium, and again during World War II, when he worked in the U.S. Chemical Warfare Ser­vice at Edgewood Arsenal in Mary­land.36 ­A fter the war Harvey deci­ded to pursue a c­ areer in pathology, a field in which he received additional training at Yale. A ­ fter a rotating internship from 1947–1948 at the legendary and now defunct Philadelphia General Hospital, Harvey was offered a position as an assistant to Fritz Heinrich Lewy (becoming Frederick Henry Lewey in 1940) at the University of Pennsylvania. His boss had attained neuropathologic renown as a

32

Finding Einstein’s Brain

twenty-­seven-­year-­old with the discovery of the neuronal inclusion (Lewy body) that became the hallmark of Parkinson’s disease.37 Lewy, the son of a Jewish physician, fled Germany in 1933, and fourteen years l­ater one of the German technicians who had followed him to his laboratory at the University of Pennsylvania was Marta Keller. Keller was a master of embedding blocks of brain in celloidin, and she was one of only eleven technicians in the United States qualified to section the blocks with the twelve-­inch blade of the Sartorius microtome, “the state-­of-­t he-­a rt brain slicer of the mid-1950’s.”38 Marta Keller’s expertise with neurohistologic specimens was invaluable to Harvey, who in the spring of 1955 was trying to reconcile the disparity of Einstein’s towering intellect with the 1,230-­gram average-­sized brain removed in the autopsy room of Prince­ton Hospital. For the next eight months, Harvey would drive from Prince­ ton to Philadelphia once or twice monthly and upon arriving look through a microscope at the slides prepared by Keller. The brain was cut into 240 blocks at Penn, and during his visits Harvey would direct Keller to the next portions of the brain to be embedded in celloidin, sectioned on the microtome, and stained. The brain was gradually transformed from two recognizably intact hemi­spheres into 240 gauze-­wrapped chunks of ce­re­bral tissue floating in two glass jars of formalin. When the brain was not being sectioned, it was stored in a locked basement closet of the Anatomy/Chemistry Building of Penn’s Gradu­ate School of Medicine.39 It is likely that Harvey carved out the 240 blocks, and Keller sliced the fine sections from each embedded block. Dr. Harvey told me they made twelve sets of slides, with about two hundred slides per set.40 Each slide was correlated with a numbered brain block, and the original anatomical location of each block was shown on Harvey’s meticulously drawn road map (Figure 1.5). One part of Einstein’s brain was not deemed essential for microscopic examination—­the cerebellum. This “­little brain” orchestrates the coordination of voluntary movements but was not thought by Harvey and his contemporaries to



April 18, 1955 33

play a significant role in intellect. This may be why no histologic images of the cerebellum ­were found among the 350 digital neuroanatomical images selected out of 567 microscope slides in the National Museum of Health and Medicine Harvey Collection.41 At some point in late 1955 or early 1956, Thomas Harvey had thousands (twenty-­four hundred, actually) of microscope slides; 240 brain blocks; and dozens, if not hundreds, of photo­graphs of Einstein’s brain. Now, he needed to draw deeply on his own expertise and find the best and the brightest of mid-­t wentieth-­century neuroscientists to decipher Einstein’s neuroanatomy. Before we begin to track the on-­again, off-­again—­and at times errant—­route of Dr. Harvey and Einstein’s brain, I should draw the reader’s attention to my business-­as-­usual choice of the possessive verb—­“had”—­when describing Harvey and his relationship to Einstein’s brain—­whole, cut up, and other­wise. It begs the question: Who owned Einstein’s brain? Let me unequivocally declare from the outset that I’m not a jurist—­not even close! Regarding “owner­ship” of the brain, I believe the answer depends on the historical time frame. The biomedical ethos of 1955 was very dif­fer­ent from our con­temporary approach to patient-­centered issues, which are dominated by informed consent and privacy regulations (i.e., the Health Insurance Portability and Accountability Act [HIPAA]). Harvey’s actions on April 18, 1955, reflected the prevailing belief that a h ­ uman organ procured at autopsy was a scientific “specimen or object” and that working on ­human material enabled the physician to “acquire property rights.”42 In the void left by the absence of written directives for the disposal of Einstein’s mortal remains, Harvey was able to obtain permission for scientific study from Einstein’s closest (and competent) living relative (his son, Hans Albert) and Einstein’s executor, Otto Nathan. This was likely a verbal or handshake agreement; if ­there was a signed consent form, it has never surfaced (and for that ­matter, informed consent in 1955 would not encompass genome sequencing, which is commonplace in the study of biological specimens

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Finding Einstein’s Brain

t­oday). A scholarly scientific study was proposed with absolute avoidance of the popu­lar press (“not Time,” in Harvey’s words), crass commercialism, and monetary gain. From that point on, Einstein’s brain was in Harvey’s personal possession as a scientific specimen to study in­def­initely. He kept it on shelves in the cellar of his Prince­ ton home or in a cider box u ­ nder his desk when he moved to the Midwest. With the pos­si­ble exception of its sojourn (and sectioning) at the University of Pennsylvania in 1955, Harvey and Einstein’s brain ­were inseparable u ­ ntil he gave the two jars of brain blocks to Dr. Elliot Krauss at the Medical Center of Prince­ton in the 1990s. Harvey’s contemporaries ­were divided on the legitimacy of his retention of the brain. Although Einstein was by no means an observant Jew, a rabbi exhorted Harvey to relinquish the brain and proceed with a proper funeral.43 On the other hand, Otto Nathan criticized Harvey for not producing the promised research publications on Einstein’s brain, with the implication that he should retain the brain and get on with its study.44 On a related note of ­human organ owner­ship, then, as now, “no case law has fully clarified ­whether you own or have the right to control your tissues. When t­ hey’re part of your body, t­ hey’re clearly yours. Once t­ hey’re excised, your rights get murky.”45 The foregoing statement refers to the disposition of what is arguably humankind’s most famous tissue—­HeLa cells—­which w ­ ere removed from the cancerous cervix of Henrietta Lacks without her (or her f­ amily’s) knowledge or consent only four years before Einstein’s autopsy. ­These w ­ ere the first h ­ uman cells to grow well u ­ nder laboratory conditions, and as far as we can tell they are immortal! In the 1950s, like Thomas Harvey, the physicians at Johns Hopkins who biopsied Henrietta Lacks’s tumor and sent the tissue for cell culture did not seek permission regarding the disposition of biological specimens. The fate of HeLa cells over the next half ­century is emblematic of the shift in medical (and societal) mores. Henrietta Lacks’s ­family did not learn that she was the source of HeLa cells ­until 1973. Eventually, they learned of the im­mense biomedical research utility and



April 18, 1955 35

commercial value of the cells. The HeLa genome in its entirety was published in 2013 without the ­family’s knowledge. Rebecca Skloot raised the hue and cry in the New York Times: “The publication of the HeLa genome without consent i­ sn’t an example of a few researchers making a ­mistake. The ­whole system allowed it. Every­ one involved followed standard practices. They presented their research at conferences and in a peer-­reviewed journal. No one raised questions about consent.”46 Seemingly in response to t­ hese criticisms, in August 2013 the National Institutes of Health (NIH) and the Lacks ­family reached an agreement in which a committee that included Lacks’s f­amily members would grant access g­ oing forward to the HeLa genomic sequence data.47 How did Einstein’s brain escape a similar fate of supervision and research regulation? Most importantly, the pres­ent climate of health information confidentiality confronts the dilemma that the genome can increasingly be used to determine our biological fate. For instance, if your health insurer could access your whole-­ genome sequencing data and determine that you have an increased likelihood of developing Alzheimer disease, it might classify you as a bad risk and increase your premium or refuse long-­term insurance. In the case of HeLa cells, the presently available DNA sequence “can reveal certain heritable aspects of Lacks’ germline DNA, and can thus be used to draw inferences, admittedly of uncertain significance, about her descendants.”48 The Lacks ­family’s all-­too-­legitimate concerns do not carry over to Einstein’s DNA sequence, which was irretrievably denatured by the standard room-­temperature preservation techniques in the 1950s. We are unable to reassemble Einstein’s DNA snippets into a complete genome that would reveal the potential biological strengths and weaknesses of his descendants. Unlike the Lacks’s large multigenerational extended ­family, Einstein’s lone sibling, two wives, three c­ hildren, and grandchildren are all dead, and no great-­grandchildren have come forward to contest the perquisites of the scientific retention and study of his brain. The fragmentation of Einstein’s DNA mercifully allows me a quick

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and definitively negative response to the mildly crackpot requests I have received for “just a l­ittle piece” of Einstein’s brain tissue, which could be sequenced and cloned ostensibly to “grow another Einstein.” With the road to Einstein’s DNA blocked, much, but not all, of the inducements to wrest owner­ship of the brain have fallen by the wayside. In brief, HeLa cells justifiably have im­mense commercial value. It is estimated that twenty tons of t­ hese cells have been grown in culture and that eleven thousand patents use HeLa cells.49 For example, as of 2014 if you wanted to test a new vaccine, a commercial laboratory (Sigma-­A ldrich) would sell you a made-­to-­order vial of HeLa cells for $496. In contrast, with the demand of curiosity seekers excepted, t­ here is no comparable commercial potential for the use of Einstein’s tissue (although the digitized images of microscope slides of his brain can be purchased from iTunes for $0.99).50 Lacking the inducements of financial gain or the threat of exposing their genome, no relatives or other interested parties have come forth to demand the 180 remaining brain blocks last reported to be in the possession of Dr. Krauss and the recently relocated University Medical Center of Prince­ton at Plainsboro.51 Given the lack of financial incentive, the paucity of descendants, and Einstein’s fragmented DNA jigsaw puzzle, the owner­ship of Einstein’s brain is unlikely to be contested u ­ nless ­there is yet another sea change in our attitudes governing the possession of ­human tissue. However, from my personal experience in clinical neurology, t­hese ethical, scientific, and cultural mandates can shift relatively quickly. As a first-­year neurology resident at the University of ­Virginia in 1976, I was given a ­whole ­human brain for the purpose of teaching and demonstrating neuroanatomy to medical students. Over the ensuing de­cades, I have used this specimen for the instruction of medical students and even a fourth-­grade science class! Previously, when a specimen such as this had served its purpose, it would be incinerated. With the changing ethical landscape over the last twenty years, a proper burial of this brain (which was once a part of a living sentient ­human being) now seems very appropriate. The medical school



April 18, 1955 37

faculty members who taught me in the 1970s would have regarded the interment of an organ used in the anatomy lab as unorthodox. Change, no less in ­human biology than any other field of endeavor, is inevitable. As 1955 drew to a close, Thomas Harvey was the “owner,” for better or worse, of the aforementioned meticulously prepared photo­ graphs, microscope slides, and blocks of Einstein’s brain. Just what was in the intellectual tool kit of Harvey and t­ hose who presumed to study the brain half-­way through the twentieth c­ entury?

chapter 3

What the Neuropathologist Knew . . . ​ and ­Didn’t Know ­ ere are known knowns: ­there are ­things we know we know. Th We also know ­there are known unknowns: that is to say we know ­there are some ­things [we know] we do not know. But ­there are also unknown unknowns—­the ones we ­don’t know we ­don’t know. —­d onald rumsfeld

The scientific enterprise of studying the postmortem neuroanatomy of an exceptional individual did not originate with Thomas Harvey. Studies of normative ­human neuroanatomy in the West date at least as far back as Vesalius in 1543,1 and Harvey’s training in neuropathology would have ensured extensive expertise in the structure of diseased brains. However, ­there was a paucity of rigorous medical lit­er­a­ture on the brains of geniuses and no personal handson experience with anatomizing virtuoso thinkers when Harvey began his study in 1955. We can only imperfectly speculate on the extent of Harvey’s background knowledge of mankind’s study of the brain over the course of five millennia. Certainly, physicians since the time of Thomas Willis (1621–1675), who coined the term neurology, have been comfortable with the notion of the brain as the seat of the intellect. But it was not always so—­there are few, if any, neuroscientific documents or incunabula preceding the ancient Egyptians, and they believed that the heart, not the brain, was the seat of thought and its weight the key to the afterlife. Although the brain was of minor importance in mummification and did not merit funereal storage in a canopic jar, the dire clinical implications of brain 39

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trauma may have been known to the Egyptians as early as 3000 BC (Third Dynasty). They w ­ ere written down thirteen hundred years ­later in the Edwin Smith Surgical Papyrus, in which “we see the word ‘brain’ occurring for the first time in h ­ uman speech, as far as it is known.”2 Another thirteen centuries would pass before we encountered evidence that the proposed source of sentience had passed from the heart to the brain. Hippocrates and his school (450–350 BC) posited the brain as the source of wisdom and understanding. Epilepsy was to be no longer regarded as a “sacred disease” of demonic possession but rather as an organic affliction of the brain.3 Incredibly, two more millennia elapse before we encounter the clinician-­scientist who bridges the gap between neuroanatomy and neurologic disease. The aforementioned Thomas Willis proposed the cerebrum “as the center for memory, cognition, volition, and imagination.”4 In the seventeenth c­ entury, this was a bold assertion, ­running c­ ounter to the venerable belief (held by Leonardo da Vinci, no less!) that the brain’s hollow cavities, known as ventricles, ­were the loci of the higher regions of thought. Willis’s masterwork, Cerebri Anatome, graced with Christopher Wren’s engravings, was an incalculably impor­tant step down the road of ce­re­bral localization, but even Willis (and his contemporaries) regarded the convolutions of the ce­re­bral cortex as haphazard loops (much like intestines) with no specified areas of cognitive function. Thomas Harvey’s familiarity with Willis’s legacy aside, ­every time he dissected a brain on the autopsy t­ able, he would observe and rec­ord the appearance of the circle of Willis (so named for the anastomosing cir­cuit of collateral blood vessels at the brain’s base that Willis was the first to describe). This whirlwind tour of five thousand years of neuroanatomy has remained curiously ­silent about the microscopic cellular anatomy (neurohistology) of the brain. Simply put, no microscope means no microanatomy, and so the initial forays into the study of the microscopic structure of the brain had to await the advent of the first microscopists, Anton van Leeuwenhoek and Robert Hooke, in the seventeenth ­century. Limited by primitive microscopes and rudimentary



What the Neuropathologist Knew . . . and ­Didn’t Know 41

histologic stains, such as saffron and brandy, Leeuwenhoek searched in vain for the tiny neural canals for the conveyance of animal spirits that Galen had posited in the second ­century AD.5 It took another two centuries for the rudiments of neurohistology—­the dendrite (1890), the axon (1896), and the neuron (1891)—to become part of the anatomical lexicon.6 Despite the adoption of this new detailed nomenclature, a major question about the structure of the ner­vous system remained. Was the ner­vous system an indivisible syncytium, or was it comprised of discrete units? The latter hypothesis was known as the neuron doctrine, and its most effective proponent was Ramón y Cajal, the son of a village surgeon in northeastern Spain. The countervailing hypotheses of neuroanatomy persisted even at the 1906 Nobel Prize lectures, when Cajal described the in­de­pen­dent ele­ments from which the ner­vous system is built, and Camillo Golgi, who shared the prize with Cajal, championed the fused neural net (syncytium) theory. We can distinguish the dif­ fer­ent types of neurons well into the hundreds, so it might be more accurate to call Cajal’s enduring scientific hypothesis the neurons doctrine rather than the monolithic neuron doctrine. By the time Thomas Harvey was attending his preclinical histology courses at Yale in the late 1930s, the cellular ele­ments of the brain w ­ ere known to be divided into glia (astrocytes, oligodendroglia, and microglia) and neurons. As discussed in chapter 2, the synapse, the nearly infinitesimal gap (twenty to forty nanometers) that defines the anatomical limits of the neuron, was not visualized ­until 1954. My brief recap of neuroscientific discovery is to point out that as he embarked on his study of Einstein’s brain in 1955, Thomas Harvey was practicing a brave new science in which the basic unit of the ner­vous system—­the neuron—­was still being characterized. It cannot be overstressed that anatomizing Einstein’s brain was a foray into uncharted regions for Harvey, who was not a clinical or basic neuroscientist. His competence was in general anatomic pathology, although he had under­gone additional training in the neuropathology labs of Harry Zimmerman at Yale and Frederick Lewey at Penn. (As part of Harvey’s immersion into the pathology of the

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ner­vous system, Lewey assigned Harvey the task of teaching neuroanatomy for two years.) Neuropathology was primarily concerned “with the vari­ous methods by which neurons undergo degeneration and death,” and “the pioneers of neuropathology ­were led on by the hope that the study of the diseased brain would lead to the interpretation of all disorders of action and conduct.”7 It was only by the early 1930s that “a few full-­time neuropathologists emerged” in the United States.8 In and of itself, Harvey’s skillful familiarity with the brain tissue changes in neurologic disease would be useful but insufficient when confronted with the ce­re­bral apparatus of a genius. The limitations of a purely structural approach to the mysteries of the mind would not have escaped Harvey’s notice at Yale, where John Farquhar Fulton, the thirty-­one-­year-­old Sterling Professor and Chair of Physiology, had written Physiology of the Ner­vous System—­the first textbook devoted entirely to neurophysiology, particularly of the primate whose “greater encephalization . . . ​is more immediately applicable to the ­human being.”9 In 1941 Harvey’s med­ ical school thesis, “A Developmental Analy­sis of the Rolling Be­hav­ior of Infants,” reflected the growing emphasis on neurologic function, rather than pure neuroanatomy, that was the zeitgeist of neuroscience at Yale during his undergraduate and gradu­ate years.10 ­Under the tutelage of Arnold Gesell—­psychologist, pediatrician, and founder of the Yale Clinic of Child Development—­Harvey studied films of the rolling be­hav­ior of six infants and concluded that ­until one year of age neuromotor maturation is insufficient for infants’ control of rolling and allowing them to be safely left unguarded on a t­ able. This thesis is the longest single-­authored scientific paper that Harvey was to write; paradoxically, for the ­future pathologist of Einstein’s brain, ­there is no mention of neuroanatomy. At this relatively late stage in Harvey’s professional training, we may well won­der ­whether the academic pro­cess had even begun to prepare the young Quaker pathologist for his rendezvous with destiny in the autopsy room of Prince­ton Hospital on April 18, 1955. In retrospect I can see two formidable challenges—­one ahead and one ­behind—­that Thomas Harvey would confront. The challenge



What the Neuropathologist Knew . . . and ­Didn’t Know 43

ahead was the conceptual sea change of neuroscience from the painstakingly detailed but static neuroanatomy of the ­great cortical mapmakers and histologists, such as Oskar and Cécile Vogt, Brodmann, Campbell, and Cajal, to the dynamic neurophysiology that would irrevocably change our view of the brain in the mid-­ twentieth ­century.11 The challenge in his rearview mirror was to see if past investigators had uncovered any defining characteristics of the brains of geniuses. In New Haven, Philadelphia, and Prince­ton of the 1930s to the 1950s, it may have seemed pos­si­ble to tackle the challenge posed by Einstein’s brain (for now we w ­ ill leave Einstein’s mind alone) using the resources of neuroscience available to a lone investigator. (The biomedical ideal of the solitary genius was alive and well once upon a time—­think Pasteur and rabies, Banting and insulin, and Fleming and penicillin.) At pres­ent the big prob­lems of neuroscience require (actually, demand) the specialization and the fragmentation of expert knowledge systems. The late Vernon Mountcastle, who held the post of director of the Johns Hopkins’ Department of Physiology, dismissed the notion of a unitary neuroscience and listed no fewer than nineteen subdisciplines necessary to advance brain science—­“neuroanatomy, neurophysiology, and biophysics; cellular and molecular neurobiology, ge­ne­tic neurobiology, and neurochemistry; evolutionary and developmental neurobiology; experimental psy­chol­ogy and psychophysics; neuropsychology, the clinical neurological sciences, and neuropharmacology; classical cognitive science, cognitive neuroscience, and computational neuroscience; and some areas of epistemology, and philosophy.”12 Mountcastle compiled his list two de­cades ago. In the interval, the neuroscience juggernaut has relentlessly added new subdisciplines such as hodology—­the study of neural connectivity. For now, we can leave Harvey blissfully unaware of the prospects for the ascendance of multidisciplinary neuroscience in the distant ­future, and, taking stock of his working knowledge of the ner­ vous system, both normal and exceptional, we w ­ ill return to the neuropathologist in his prime.

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As already discussed, the neuron theory was dogma for Harvey. The well-­connected but autonomous neuron was described and drawn in exquisite detail by Cajal and was posited in 1887 by Fridtjof Nansen (among o­ thers), who gave up his microscope for Arctic exploration and relief work with World War I refugees.13 (Coincidentally, both ­were Stockholm-­bound—­Cajal received his Nobel Prize in Physiology or Medicine in 1906, and the Norwegian explorer was to receive the Nobel Peace Prize sixteen years l­ater.) Neurons aside, the identification of the other support cells (glia) that comprise the central ner­vous system (CNS) was enveloped in obscurity for ­t hese scientists, and Cajal spoke of an enigmatic “third ele­ment”—­neither neuron nor astrocyte—­when he examined microscope slides of the brain. The reliable identification of microglia (cells that clean up—­phagocytose—­dead brain tissue or infectious microorganisms) and oligodendroglia (cells that make electrical insulation—­myelin—­for axons) had to await del Río-­ Hortega’s and Wilder Penfield’s silver stains in 1919 and 1924.14 In effect, the characterization of glial cells—­a glial doctrine, if you ­will—­was a new technique when Harvey was learning the ropes of neurohistology. Notably, Harvey did not use the newfangled silver stains to differentiate Einstein’s glial cells in 1955. Thirty years would elapse before Marian Diamond would approach the riddle of Einstein’s glia. The neuroanatomy taught to Harvey was conceived as a static arrangement of neurons and of commissures and fiber bundles made of axons and dendrites (elongated cell pro­cesses) connecting the neurons. The under­lying physiology of the brain’s “wiring diagram” has been known to be electrical since the late eigh­teenth ­century, when Galvani observed a frog’s leg contract when a scalpel that had picked up an electric charge touched the sciatic nerve.15 However, the leap from descriptions of “animal electricity” to quantitative neurophysiology came with the first tracings of the action potential in 1939.16 The flow of current from neuron to neuron rested upon the ionic hypothesis, which characterized the brief and migratory depolarization of axonal membranes during which sodium channels



What the Neuropathologist Knew . . . and ­Didn’t Know 45

would open and close, allowing a “brief intracellular sip of (positively charged) sodium ions from a salty extracellular sea.”17 This flow of current—­t he action potential—­had to somehow traverse at least two kinds of anatomical gaps—­t he synapse from nerve to nerve and the neuromuscular junction from nerve to muscle. Two theories vied to explain transmission across the gaps—­neurochemical transmitters at the synapse or electrical continuity via specialized junctional membranes between neurons. Or, more memorably, the competing “soups and sparks” hypotheses. By the 1930s the chemical neurotransmitter hypothesis was beginning to prevail when ­f uture Nobelists Sir Henry Dale and Otto Loewi found the smoking gun for chemical neurotransmission with “the presence of acetylcholine at the nerve-­skeletal muscle synapses.”18 The advent of microelectrodes gave a clearer picture of the spread of synaptic potentials and provided compelling evidence that acetylcholine “acts by increasing the permeability of the postsynaptic membrane to small ions.” ­These pioneering experiments on relatively s­ imple and readily accessible preparations, such as the frog neuromuscular junction, led to the general ac­cep­tance of the soup hypothesis, also known as chemical synaptic neurotransmission, by the 1950s.19 As the events at the synapse became better understood, the door was opened for the hitherto unimaginable dynamic pro­cess of rewiring the ner­vous system. In 1949 the Canadian psychologist Donald Hebb wrote (his italics), “When an axon of cell A is near enough to excite a cell B and repeatedly or per­sis­tently takes part in firing it, some growth pro­cess or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.”20 The first glimmers of the as-­yet-­unseen synapse—­measuring twenty billionths of a meter—as the arena of learning w ­ ere detected while Harvey was plying the pathologist’s trade. Hebb postulated that the neuronal “growth pro­cess” was the development of “synaptic knobs.” (Hebb’s inspired hunch would prove correct in princi­ple, and in 2000 Eric Kandel would receive the Nobel Prize for demonstrating the cellular changes under­lying ­simple forms of learning, such as synaptic growth or pruning with

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Finding Einstein’s Brain

sensitization or habituation of the gill withdrawal reflex in the sea slug Aplysia californica.21) Hebb’s postulate of a dynamic ner­vous system in which learning rerouted neural connections began to chip away at the prevailing repre­sen­t a­t ion of the ner­vous system as a hard-­ wired telephone switchboard. Harvey’s exposure to and familiarity with new conceptions of neurophysiology ­were not reflected in his research agenda for Einstein’s brain. He was, first and foremost, a pathologist, and for a pathologist, anatomy is frequently biological destiny. Clinical generalizations aside, Harvey was very fortunate to learn about the brain at the Yale School of Medicine in the 1930s. Dean Milton Winternitz, himself a pathologist, “brought Yale from a second or third tier to the top ranks of American schools,” largely by following the Johns Hopkins system of recruiting full-­time research-­oriented faculty.22 Thomas Harvey would have learned his pathology from Winternitz and his neuropathology from Harry M. Zimmerman, who we previously encountered waiting in vain to get Harvey’s call to go to Prince­ton for Einstein’s postmortem (but that disappointment lies twenty years in the ­future). When Harvey Cushing, arguably the founder of American neurosurgery, left Harvard, he returned in 1937 to his alma mater in New Haven and brought his collection of two thousand brains and brain tumors—­and the neuropathologist Louise Eisenhardt. Th ­ ese specimens catapulted Yale to the forefront of clinical neuroscience. “When Cushing found something of par­tic­u ­lar interest,” as the story goes, “he would hammer on the wall between his office and that of Harry (Zimmerman) inviting him to come and see, examine, and discuss the patient’s course.”23 Such exposure to world-­class neuropathology would not be lost on Harvey. Neurophysiology at Yale, led by the Sterling professor John Fulton, focused primarily on the frontal lobe and was ably abetted by such accomplished investigators as Margaret Kennard (child neurologist), Robert Yerkes (primatologist and psychometrist), and Karl Pribram (neurosurgeon), as well as de Barenne’s strychnine cortical stimulation research and Warren McCulloch’s attempts “to found a physiological theory of



What the Neuropathologist Knew . . . and ­Didn’t Know 47

knowledge.”24 Although the lessons imparted at Yale would not materialize in Harvey’s structural approach to Einstein’s brain two de­cades ­later, I believe that Harvey’s personal acquaintance with the leading lights of Yale’s ascendency in brain science in the 1930s and his lifelong investigation of Einstein’s brain ­were not mere happenstance. With this compelling introduction to the study of the ner­vous system, Harvey could critically assess the advent of the modular ner­ vous system heralded by Mountcastle’s discovery of the cortical column as an organ­izing princi­ple of CNS anatomy. In 1957 Mountcastle found that “the basic unit of mature neocortex” was the minicolumn, a narrow chain of eighty to one hundred “neurons extending vertically” across layers two through six of the ce­re­bral cortex. Many minicolumns linked by short-­range horizontal connections would comprise a cortical column mea­sur­ing three hundred to six hundred microns in dia­meter across species. With evolutionarily more complex brains, the cortical surface area would expand with increased numbers (but not sizes) of cortical columns. This high degree of columnar organ­ization, which neuroanatomists at first met with disbelief, eventually became a tenet of cortical architectonics. It provided the foundation for the concept of receptive fields, in which a stimulus on the surface of the body would evoke an electrical discharge from the single neurons in columns in the sensory cortex.25 Researchers could now use microelectrodes to impale a single cortical neuron and create a map linking a specific area of the body’s surface to a par­tic­u­lar region of the cortex. This has become a dominant neuroscience technique g­ oing forward to the pres­ent day with the tour de force achievement of Hubel and Wiesel’s cartography of the functional microanatomy of cat and monkey visual systems.26 Although Harvey had doubts as to ­whether the gross morphology (as opposed to the microanatomy) of Einstein’s brain would prove informative,27 he would nevertheless have eagerly followed Wilder Penfield’s groundbreaking explorations of the ce­re­bral cortex. In 1954 Penfield, a Canadian neurosurgeon and founder of the

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Montreal Neurological Institute, reviewed his data on 750 patients who underwent cortical mapping with bipolar electrodes applied to the surface of their brains.28 The brain has no pain fibers, and accordingly, the surgery was performed with local anesthesia on a conscious patient who could tell Penfield when ­there was movement of the left hand as one-­half to three volts were applied to the right motor cortex. Using electrical identification of functioning cortex, Penfield avoided or minimized the loss of normal brain tissue when extirpating a brain tumor. The amassed motor and sensory stimulation data culminated in the classic Penfield illustrations of the motor and sensory “homunculus,” which displayed the inordinately large portions of cortex subserving the astonishingly varied repertoire of motor and sensory functions of the face and hand (see Figure 3.1).29 Just a few years before Einstein’s death, electrophysiological research employing intraoperative bipolar electrodes (for small circumscribed cortical regions) and microelectrodes (for individual neurons) had permitted hitherto “­silent” neural tissue to speak to investigators. Was Thomas Harvey listening? The reductionist approach that had served so well in elucidating the anatomy and physiology of individual neurons and small assemblages of neurons could not be extrapolated to the analy­sis of cognition in the 1950s. (A ­great leap forward in the interrogation and visualization of cortical function in living brains would not appear on the neuroscientific horizon ­until 1975, with the development of one of the earliest functional neuroimaging techniques, positron emission tomography.) The neurophysiological investigation of the embalmed brain of a dead genius was, of course, not an option, and Harvey was compelled to proceed as a cortical “archaeologist” who hoped to disinter living thought from dead neural tissue. To begin to reach even a rudimentary understanding of how Einstein navigated his world of ideas, Harvey needed to target the wellsprings of cognition—­the association cortices. The con­temporary perspective on higher cortical functions holds multimodal association cortices in the frontal, temporal, and parietal lobes to be the essential regions for the highest levels of sensorimotor

Figure 3.1. Wilder Penfield’s sensory (left) and motor (right) homunculi (­little men) are superimposed on cross-­ sections of ce­re­bral hemi­spheres. (The boomerang-­shaped midline structures are the fluid-­filled lateral ventricles.) Derived from de­cades of intraoperative electrical brain stimulation of conscious patients, the homunculi diagrams strikingly show the disproportionately larger cortical areas devoted to the sensorimotor functions of the hands and mouth. (Wilder Penfield and T. Rasmussen, The Cerebral Cortex of Man. New York: McMillan, 1955.)

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integration and cognition.30 But this was not always the case. Sir William Gowers’s A Manual of Diseases of the Ner­vous System—­ the bible of nineteenth-­century neurology—­described “no motor or sensory symptoms” associated with disease of the posterior parietal lobes.31 If we fast-­forward to Harvey’s era, we find that Macdonald Critchley, one of the most astute British clinicians of his time, concluded his magisterial The Parietal Lobes with the admonition that “to seek to establish a formula of normal parietal function is largely a vain and meaningless pursuit, however attractive.”32 Harvey’s active research agenda was winding down as the neuroscience community gained further insight into the role of the parietal lobe not as a mere cortical/homuncular map but as a critical gateway for accessing and integrating the information necessary for motor strategies that exploit extrapersonal space.33 The function of the most acknowledged seat of higher cognition, the frontal lobe, remained equally elusive to Harvey’s mentors. John Fulton studied the be­hav­ior of chimpanzees (“affectionate” Becky and “crotchety” Lucy) ­a fter the bilateral surgical removal of the frontal cortex at Yale in 1934.34 Both animals began to fail learning tasks (the stick and platform test), and Fulton concluded that the frontal lobe lesions diminished the chimps’ learning capacity. He speculated that bilateral destruction of the frontal areas would cause greater intellectual loss in man, where they comprise 30 ­percent of the cortical surface (compared to 10 ­percent in the monkey).35 Fulton also observed that the chimps no longer displayed frustrated be­hav­ior when they w ­ ere not rewarded ­after failing a learning task. Postsurgically, Becky and Lucy seemed “devoid of emotional expression,” and this critical observation contributed to Egas Moniz and Almeida Lima’s decision to perform frontal lobotomies (leukotomies) on twenty patients with anxiety/obsessional states and psychoses.36 The scientific evidence leading to the initial forays of psychosurgery to relieve psychopathology is fascinating in its own right but did not provide Harvey with firm grounding in the physiology of normal frontal lobes, let alone ­those of a genius!



What the Neuropathologist Knew . . . and ­Didn’t Know 51

This lesion-­based approach to neurology had significant limitations in Fulton’s time, and they persist to the pres­ent day. My thorough grounding in the deficits that strokes, ce­re­bral tumors, and multiple sclerosis create are invaluable when I evaluate and treat patients, but that expertise most emphatically does not elucidate the workings of the undamaged brain of a genius. A clinical neurologist knows that symptoms of frontal lobe damage include disinhibition, inappropriate jocularity, emotional lability, poor judgment, distractibility, apathy, indifference, psychomotor retardation, concrete thinking, impaired calculating ability, “forgetting to remember,” motor perseveration and imper­sis­tence, stimulus-­bound be­hav­ ior, motor programming deficits, poor word-­list generation, poor abstraction and categorization, and diminished spontaneous movement.37 However, a litany of such deficits does not comprise a true and comprehensive picture of frontal lobe function, and that same clinical neurologist must never forget “the fallacy of confusing localization of sign-­producing lesions with localization of function.”38 The brain remains an organ of immea­sur­able interconnectivity, and a lesion in one part of the brain may disinhibit functions in a separate but distantly connected area—­the so-­called release phenomena. Given the inability of lesion-­based studies to delineate the normal function of parts of the brain and his training firmly rooted in neuroanatomy/neuropathology, where could Thomas Harvey turn? From the time I was a neurology resident embarking on clinical research, I followed the venerable admonition to consult the German medical lit­er­a­ture before claiming priority for a “new” discovery. And Harvey followed this time-­tested medical adage when he “would say that Vogt’s study on Lenin’s brain was what inspired him to believe that Einstein’s was worth saving.” 39 Oskar and Cécile Vogt ­were neuropathology’s power ­couple for the first third of the twentieth ­ century, and the Kaiser-­ Wilhelm-­ Institut für Hirnforschung was opened for them in the outskirts of Berlin in 1931. Beginning in 1925 their study of the brain of Vladimir Lenin (1870– 1924), at the behest of the Soviet government, was arguably the

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most comprehensive study of a “genius” brain ever undertaken. The Communist leaders charged the Vogts with the task of performing a “cytoarchitectonic investigation [to] provide information on the material substrate of Lenin’s genius.”40 And Professor Vogt did not disappoint them. A ­giant microtome sliced the formalin-­fixed brain into as many as thirty thousand full coronal sections. In 1925 Vogt revealed his findings: “In the third cortical layer (of several brain areas) particularly in the deep portions, I found pyramidal neurons of extraordinary size and number never previously observed by myself . . . ​­these anatomical findings allow us to identify a brain athlete and an association ­giant.”41 In 1928 Wilder Penfield, the savant of cortical histology, had occasion to visit the Vogts’ laboratory and examine microscope slides of Lenin’s brain. Penfield remained skeptical of Vogt’s claim that ­giant pyramidal cells w ­ ere the structural underpinning of Lenin’s genius and wrote that a delay in brain tissue fixation could have brought about artifactual swelling of the neurons.42 Did the Vogts’ study of Lenin’s brain further influence Harvey to scrutinize Einstein’s neurohistology rather than his gross ce­re­ bral anatomy? (Penfield’s technical concerns ­were not published ­u ntil twenty-­t wo years a­ fter Einstein’s death and would play no part in Harvey’s choices.) In this instance, the German medical lit­er­a­ture may have been persuasive, for Harvey irrevocably chose the path of neurohistology when he instructed Marta Keller at the University of Pennsylvania to section twelve sets of two hundred microscope slides per set. Outside the Vogts’ study of Lenin’s brain, we ­will never know how thoroughly Harvey was acquainted with the relatively small body of prior research on elite brains. The discussion of a few earlier reports w ­ ill provide a picture of the field of elite brain research in its infancy. From t­ oday’s neuroscientific perspective, the basis of cognition, gifted or other­wise, is inextricably interlinked with the cortex (gray ­matter) and the connectome (white m ­ atter). But this was not always accepted as neurologic dogma: “Most mediaeval and ­later anatomists played down the role of the cortex and localized



What the Neuropathologist Knew . . . and ­Didn’t Know 53

vital functions of the soul (‘mind’ in modern parlance) within such unlikely parts of the ner­vous system as the meninges (Schabtai-­ Donolo), pons (Lotze), ventricles (Gordon), nerve roots (Meyer), corpus callosum (Lancisi), cerebellum (Dorincourt), or the pineal (Descartes) and corpus striatum (Willis).”43 In Postcards from the Brain Museum, Brian Burrell contended that Rudolf (and l­ater Hermann) Wagner’s laborious mea­sure­ment of the surface area of the brain of the German polymath Carl Friedrich Gauss (as in Gaussian distribution or the unit of magnetic flux density) in 1855 “kicked off the search for the anatomy of genius.”44 Along with this birth announcement for the study of the anatomical trappings of genius, Burrell also wrote a requiem for the search for “something truly distinctive in the brains of ­great men, ­great ­women, depraved hoodlums, or murderers.”45 ­A fter 154 years Gauss’s brain was removed from its sealed jar at the University of Göttingen to undergo MRI scanning. The world was indifferent. No one seized the opportunity to study the scans or “compare Gauss’s brain to Einstein’s” presumably ­because “Gauss’s intricately fissured brain is simply old news.”46 In short, requiescat in pace C. F. Gauss and the materialist perspective on genius. What Burrell d ­ idn’t know was that the brain in the sealed jar was not Gauss’s! The brain in the jar was part of a small collection of elite brains at Göttingen and had an extraordinary cortical anatomy consisting of a bridge of neural tissue connecting the pre-­and postcentral gyrus of each hemi­sphere. This rare anatomical variation of a divided central sulcus of the right hemi­sphere and the more commonly encountered segmented central sulcus of the left hemi­ sphere was rendered in exquisite detail in a lithograph of the brain of C. H. Fuchs (and not C. F. Gauss), which was published in Rudolf Wagner’s 1862 study.47 Sometime ­after 1855 the brains of Fuchs, a physician and pathologist at Göttingen, and Gauss ­were inadvertently switched to wrongly labeled jars. The mix-up was discovered in 2013.48 The foregoing tale of Wagner’s early foray into the neuroanatomy of genius does impart a positive lesson that by 1855 Wagner had

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gone well beyond the standard nineteenth-­century brain metrics of size and weight and was examining the gyri and sulci with a critical eye. And this approach reaped dividends—­Wagner’s detailed cortical observations enabled the brains of two specific individuals (Fuchs and Gauss) to be distinguished a ­c entury and a half ­later. In contrast, the so-­called studies of Gauss that Burrell consigned to scientific oblivion w ­ ere performed on the wrong brain and thus render his verdict inapplicable. Given the comedy of anatomical errors, the question of ­whether Gauss had exceptional neuroanatomy remains open, requiring further study. A comparison of the rediscovered brains of Einstein and Gauss, with the latter hiding in plain sight, might well invigorate the study of the brains of t­ hose with sublime intellect.49 Was Wagner’s study of Gauss r­eally the earliest probe into the anatomy of genius, as Burrell contends? The priority of a scientific discovery or technique can be very difficult to determine, and such for the pursuit of genius is no exception. It is known that nearly thirty years before Wagner’s study, the anatomist and physiologist François Magendie found the brain of Pierre-­Simon Laplace (1749– 1827), “the French Newton,” to be “remarkably small,” with a small amount of cerebrospinal fluid (CSF) in its ventricles. In this case the relatively small amount of fluid in the brain of a genius conformed nicely with Magendie’s theory that intelligence was inversely related to the volume of CSF. This evidence of scientific pre­ce­dence was published a ­century ­after the fact by no less a student of ­human intellect than Karl Pearson, who regretted that “so few brains of ­great thinkers have been available for examination.”50 The foregoing accounts of nineteenth-­and early-­twentieth-­ century investigators of elite neuroanatomy provide a glimpse of Harvey’s intellectual forebears, but if Harvey had a syllabus for anatomizing a genius, many of the citations remain blank for us in the pres­ent day. Before closing the door on the scenes of Harvey’s scholarly preparation for the task of examining Einstein’s brain, we would do well to consider a well-­k nown study that further characterizes the



What the Neuropathologist Knew . . . and ­Didn’t Know 55

zeitgeist of eminent brain studies. In 1907 Edward Anthony Spitzka, editor of Gray’s Anatomy, published a 133-­page article, “The Study of the Brains of Six Eminent Scientists and Scholars Belonging to the American Anthropometric Society, Together with a Description of the Skull of Professor E.D. Cope.”51 In addition to his own detailed anatomic examination of six brains in the American Anthropometric Society’s collection (Walt Whitman’s brain was unavailable and unsalvageable a­ fter being “dropped on the floor by a careless assistant”), Spitzka reviewed the lit­er­a­ture of “notable individuals” (133 men and 4 ­women) ranging from Turgenev, topping out at 2,012 grams, to Ludwig II of Bavaria, “the Mad King.” He conceded that “it is difficult to give an exact expression of the inter-­relation between brain-­ size and ­ mental capacity.” Nevertheless, he subsequently launched into sheer insupportable speculation, invoking the mesial (midline) frontal lobe to cuneus/precuneus ratio as a “true somatic expression of naturally endowed superiority of the powers of conception of the concrete in the one brain [of Joseph Leidy], and of remarkable powers of thought in the abstract in the other brain [of Edward Cope].”52 If Spitzka went off the rails of scientific induction with his conclusions about Leidy and Cope being “so differently endowed by nature,” he was prescient about the critical importance of “myelin-­ development” and the “intricate inter-­connection of the many nerve cells by a multitude of association fibers.” Lacking axons and dendrites, “a brain made up of gray m ­ atter only would be as useless as a telephone system with all its inter-­connecting wires destroyed.” In this case Spitzka got it right, and his views predate our pres­ent focus on the connectome of the ­human brain by roughly a ­century. Ce­re­ bral white m ­ atter can be or­ga­nized into bundles of nerve fibers called commissures. The largest of ­these commissures is the corpus callosum, which is comprised of 250 million or so axons connecting both hemi­spheres of the brain. And Spitzka found that his notable men had “larger callosa,” serving to “distinguish the brain of the genius or talented man.” However, in 1907 conceptions of the functions of the corpus callosum ­were vague, and even de­cades

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l­ater the astute neuropsychologist Karl Lashley “thought that the corpus callosum was merely a structural ele­ment that supported the two hemi­spheres.”53 It was not ­until the 1960s that split-­brain experimentation revealed the corpus callosum’s crucial role: “Severing the entire callosum blocks the interhemispheric transfer of perceptual, sensory, motor, gnostic, and other information in a dramatic way, allowing us to gain insights into hemispheric differences as well as the mechanisms through which the two hemi­spheres interact.”54 Most astonishingly, following a ­simple neurosurgical procedure—­ callosal section for the treatment of epilepsy—­“two minds, each with its own set of controls, could exist in one brain.”55 Spitzka died suddenly in 1922 and did not live to see the experimental elucidation on the corpus callosum and the pos­si­ble implications for his observations on the “larger callosa” of theeminent brains he mea­sured. The revelations of split-­brain research appended an in­ter­est­ing footnote to a century-­old study with no expectations of further developments . . . ​­until 2013, when a physicist in Shanghai discovered that Albert Einstein’s corpus callosum was significantly larger than t­ hose of age-­matched and younger controls.56 This chapter brings the curtain down on Thomas Harvey’s preparedness—­real and i­ magined—to scientifically investigate the postmortem anatomy of Einstein’s brain. By the summer of 1955, Harvey had embalmed and photographed the brain, embedded 240 blocks of neural tissue, and cut twelve sets of microscope slides. Looking to the distant ­f uture, we have glimpsed the most recent (Einstein’s corpus callosum) in a series of startling neuroanatomical findings (with a l­ittle scientific perspective provided by Edward Spitzka and Michael Gazzaniga). But the question remains—­W hat exactly have we learned from Einstein’s brain in the last six de­cades?

chapter 4

The Lost De­cades (1955–1985), the Cider Box, and the Microscope That almost nothing of interest has been learned from the brain [of Einstein] should be no ­great surprise. Too l­ittle is still known about the ­human brain to appreciate what differences, if any at all, exist between ­those that h ­ ouse greater and lesser minds. —­n icholas wade, New York Times

Received wisdom in the art of getting scientific research funded or published is that the investigator’s chances are slim and none when the study in question has negative results. And that’s a shame. The positive finding that penicillin eradicates streptococcal bacterial infections was a landmark microbiological discovery, but the negative result that penicillin does not cure viral infections did not receive the same attention. Perhaps if the negative result received greater acknowl­edgment in the medical journals, I would not get a prescription for penicillin (or a similar antibiotic) when I show up at my doctor’s office with a viral upper respiratory tract infection (i.e., the common cold). To continue the story of Einstein’s brain, I must fly in the face of the received wisdom just cited and recount Harvey’s thirty-­year sojourn into the wilderness of negative (or, worse yet, absent) scientific results. At the outset, as I have recounted, in 1955 Harvey had a painstakingly preserved (and sectioned) brain, multiple photo­graphs, over two thousand microscope slides . . . ​and a consuming interest in the anatomy of Einstein’s genius. What Harvey lacked was an academic position (and its access to resources for research), extensive specialty 57

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training in neuropathology or neuroanatomy, and research funding. Even in the simpler times of the 1950s, when Big Medical Science was not quite so big, Harvey was clearly an outsider to the medical establishment. He was further marginalized when he refused to join the American Medical Association (AMA) ­a fter his name was removed as an author of an article in the Journal of the American ­ asn’t a member.1 Medical Association ­because he w Proscribed by small-­town hospital politics from delivering the brain to his former Yale mentor, Harry Zimmerman at Montefiore Hospital in the Bronx, in the summer of 1955 Harvey warily acquiesced to Lieutenant Col­o­nel Webb Haymaker’s invitation to meet with Amer­i­ca’s “best and brightest” neuroanatomists and neuropathologists in Washington, DC. Suspecting a canard, Harvey did not take the brain with him when he appeared before the gathered éminences grises—­von Bonin (University of Illinois), Rose (Johns Hopkins), Kuhlenbeck (Medical College of Pennsylvania), and Nauta (University of Mary­land). Dr. Haymaker, the chain-­smoking head of neuropathology at the Armed Forces Institute of Pathology (and dissector of Benito Mussolini’s brain) mightily importuned Harvey to relinquish the brain . . . ​to no avail.2 The brain stayed in Prince­ton, although in his early quest for academic expertise Harvey did send slides to some of the Washington attendees—­von Bonin, Nauta, and Kuhlenbeck—as well as Percival Bailey (the coauthor of Harvey’s well-­thumbed-­through The Isocortex of Man), Zimmerman, Sidney Schulman at the University of Chicago, and William Ehrich (Harvey’s old boss at Penn).3 The experts found nothing distinctive in Harvey’s meticulously prepared slides. Kuhlenbeck, a comparative neuroanatomist, inspected the slides but offered no opinion. Zimmerman felt it was all normal, and Bailey and Nauta simply did not respond. Sidney Schulman, an expert on the thalamus—­the gray m ­ atter “relay station” located deep within each ce­re­bral hemisphere—­observed nothing distinctive in Einstein’s thalamic histopathology and returned the slides to Harvey. Schulman’s s­imple act of returning the slides was remarkable. Most of the slides sent out w ­ ere never



The Lost Decades (1955–1985) 59

returned to Harvey, and as of this writing I can account for the whereabouts of less than one-­t hird of the estimated twenty-­four hundred microscope slides sectioned from Einstein’s brain. The last of Harvey’s original slides to turn up was the set (or part thereof ) given to Dr. William Ehrich, which eventually made its way to Dr. Lucy Rorke-­Adams, a neuropathologist at ­Children’s Hospital of Philadelphia. In 2011 Dr. Rorke-­Adams donated forty-­six slides to the Mütter Museum in Philadelphia. She described the brain cells as quite youthful and said the “blood vessels are gorgeous.”4 What about t­hese microscope slides led ­these distinguished investigators to a unan­i­mous negative conclusion that sucked the oxygen out of Einstein brain studies for the next three de­cades? Harvey had used the standard work­horse neuropathology stains—­ Nissl and Weigert—­that had been around since the 1880s. If “the gain in the brain is mainly in the stain” (neuroscience is not averse to doggerel), Harvey took a time-­honored but clearly “no frills” approach to Einstein’s microanatomy. Nissl stain is selective for the subcellular organelles, rough endoplasmic reticulum, and ribosomes. Neurons have more of ­these organelles than do glial cells, and the dif­fer­ent appearance of the stained cells enables the astute microscopist to distinguish neurons from glia. However, it may be impossible to distinguish small neurons from glia without resorting to special stains; for example, silver, and Harvey did not use ­these stains on Einstein’s tissue. Harvey was wagering that regional cell counts of neurons and glia might reveal impor­tant differences in Einstein’s microscopic neuroanatomy when compared to the maps of Bailey and von Bonin or Brodmann, which ­were based on cortical neurohistology (architectonics). His stains, however, could not reliably distinguish dif­fer­ent types of glial cells (astrocytes, oligodendrocytes, and microglia). Harvey’s other stain—­Weigert—­ was selective for the myelin sheaths encircling each neuron’s axon (and facilitating the propagation of the action potentials that allow neurons to “talk” to each other). In the “preconnectome” era, myelin circuitry of the adult brain (as opposed to Paul Flechsig’s nineteenth-­ century studies on myelinogenesis of the developing brain) was not

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on the neuroanatomist’s radar. Hence, Harvey and his enlisted experts may be forgiven for giving myelin short shrift. As of this writing, no investigator in the past sixty years has scrutinized the microanatomy of Einstein’s myelinated axons (or dendrites). It must be conceded that the complexity is daunting—­a single neuron may have a thousand or more axonal connections (synapses). The labor-­intensive nature of manually counting neural cells—­a cubic millimeter of primate cortex contains one hundred thousand cells5—­may well have deterred the scientists who received Harvey’s slide boxes made of pine (see Figure 4.1). When asked to count the cells of Einstein’s thalamus, Sidney Schulman at the University of Chicago declined, telling Harvey, “I just ­don’t want to take the time to do something like that . . . ​I think it would be quite uninformative.”6 Similarly, although Harvey hand-­delivered a slide set to Percival Bailey at the University of Illinois, the renowned neurosurgeon, neuropathologist, and neuroanatomist “was certainly not ­going to drop every­thing ­else he was ­doing just to study Einstein’s brain.”7 Then, as now, the neuroscientific establishment wrestled with the scientific worthiness of the study of an elite, iconic brain. And this may partly account for the silence of the experts for thirty years. With the panel Harvey had called upon proclaiming a verdict of negative results (and a few abstentions), research on Einstein’s brain came to a grinding halt from 1955 to 1985. In the meantime, Thomas S. Harvey’s life moved forward randomly, not unlike the Brownian motion studied by Einstein in 1905.8 The year 1960 was a professional and personal watershed for Harvey. ­A fter eight years his contract at Prince­ton Hospital was terminated, and a twenty-­year marriage dissolved when he walked out of 245 Jefferson Road, leaving his wife, Eloise, and three sons. Throughout the 1960s he worked a variety of pathology and medical jobs in Central Jersey, including positions at two dif­fer­ent private medical labs, a nursing home, the New Jersey Neuro-­Psychiatric Institute, and Marlboro Psychiatric Hospital. For a time, Einstein’s brain remained, much to Eloise’s dismay, in the basement of the Jefferson Road h ­ ouse.9 We can presume that



The Lost Decades (1955–1985) 61

Figure 4.1. The original pine boxes containing microscope slides sectioned by Marta Keller and distributed to select neuropathologists and neuroanatomists by Dr. Harvey. A photo of Dr. Harvey with an open box of slides and his binocular microscope is seen in the upper left. The slides and photo­graphs are part of Dr. Harvey’s personal archives and are curated by the National Museum of Health and Medicine in Silver Spring, Mary­land. (Photo by Frederick E. Lepore, 2011.)

Harvey took the brain to his new home when he remarried in 1963. In 1972, returning to his midwestern roots, Harvey, his new f­ amily, and the brain traveled to Wichita, Kansas, where he was a supervisor at a large commercial lab. Harvey did not confine himself to the practice of anatomical and laboratory pathology but sought out

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clinical work in emergency rooms and general medical practice. In con­temporary medicine it would be unheard of for a pathologist to diagnose and treat living patients; however, when Harvey received his doctor of medicine degree in 1941, the third-­and fourth-­year clinical rotations and subinternships at good medical schools ­were deemed sufficient to allow newly minted gradu­ates to enter general practice without the benefit of a residency. (As late as 1975, I remember that one of my fellow medical interns at the University of Michigan had spent a year working in emergency rooms without any training beyond his MD!) With a hiatus of thirty-­plus years between his Yale School of Medicine clinical rotations and his plunge into Kansas general practice, Harvey soon ran afoul of the relentless changes and pro­gress in clinical patient-­centered medicine. ­A fter administrative meetings with both the Kansas and Missouri State Boards of Healing Arts,10 Harvey, in his eighth de­cade, just barely fell short of a passing grade for a grueling three-­day medical relicensure examination. Unable to return to the medical profession but unbowed and indefatigable, Harvey worked in a plastics extrusion factory (E and E Display Group) when he was eighty-­two and performed charitable ser­vices with other Quakers in soup kitchens.11 Although Einstein’s brain had vanished from public view, it never left Harvey’s sight as he moved from job to job in New Jersey and the Midwest. In 1978 Steven Levy, on assignment for New Jersey Monthly, went to the biological testing lab in Wichita, Kansas, where Harvey worked and revealed to the world that Einstein’s brain currently resided in jars of formaldehyde ensconced in a Costa Cider box in Harvey’s office. A ­ fter dissemination of the “sectioned brain” to “vari­ous specialists,” nothing had been published, but Harvey hoped to be ready to publish in “perhaps a year.”12 Three years l­ater the august journal Science published a vaguely hectoring update that Harvey “has not yet written up his study of the brain.”13 I would be hard put to cite a similar instance in which this internationally known and respected journal took it upon itself to upbraid a nonacademic pathologist for not publishing! The working days of



The Lost Decades (1955–1985) 63

editors at Science are more typically consumed with rejecting manuscripts (and, it goes without saying, discouraging publication) of the research of both lesser scientific mortals and, on occasion, ­future Nobel laureates. But Einstein was (and is) a special case. Nicholas Wade, reporting for Science, compared the journey of Einstein’s brain from Prince­ton to the voyage of the Flying Dutchman, with “no clear end in sight.” Harvey, now hunkered down in Weston, Missouri, parried Wade’s take-­no-­prisoners interviewing technique by characterizing his neuropathological specimen as “small fragments” and conceding that “my ideas about . . . ​[the brain] have not solidified.”14 His published comments notwithstanding, Harvey had never downsized his anatomical holdings (and as late as 1994, BBC documentary footage highlighted Harvey with two large glass specimen containers and one mason jar chockablock with sections of Einstein’s brain).15 Although Harvey did not loosen his grip on the brain or his research aspirations, four more years would pass before Einstein’s brain would spectacularly resurface. The Science article did not go unnoticed by Marian C. Diamond, PhD, a neuroanatomist at the University of California, Berkeley. She regularly called Harvey in Missouri over a span of three years, and her per­sis­tence was rewarded when she received a package enclosing a mayonnaise jar with “four sugarcube-­size pieces of Einstein’s brain.”16 Diamond’s research on the increase of glial cells in rats raised in an enriched environment and the observation that the ratio of glial cells per neuron increases as the phyloge­ne­tic tree is ascended led her to posit that “the more highly evolved area in the ­human brain should have more glial cells per neuron.”17 The mayonnaise jar contained celloidin-­embedded pieces of Einstein’s right and left frontal and parietal lobes. Th ­ ese ­were promptly sectioned and stained with Kluver-­Barrera, luxol fast blue, and cresyl echt violet stains to distinguish neurons from glia (astrocytes and oligodendrocytes). In essence, Diamond’s method was to count neurons and glial cells in a single microscopic field, mark their positions on ruled paper, move the slide . . . ​a nd repeat. ­A fter she crunched the numbers with a l­ittle statistical sleight of hand “to

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pool all glial cells counted to attain statistically significant differences,” she found that in comparison with eleven male control brains, “Einstein had more glial cells per neuron than the average man, but in only the left inferior parietal area did he have statistically significantly more.”18 Possibly, the relative increase of glial cells was in response to greater neuronal metabolic need, and ­going further, differential cell counts constituted a potentially meaningful mea­ sure of the functional status of the brain.19 The thirty years’ drought had ended! A peer-­reviewed study of Einstein’s brain was a part of the scientific lit­er­a­ture at last. Thomas Harvey was listed as a coauthor and hopefully would no longer be derided by scientific journalists or importuned by Einstein’s executor, Otto Nathan, to state “your pres­ent intention to describe and publish your work on Einstein’s brain.”20 Regrettably (and predictably), the seven-­page paper, published in the relatively obscure journal Experi­ hole new critical can of worms. mental Neurology, opened a w The popu­lar press weighed in on September 1, 1985. The Chicago Tribune intoned “­whether the brains of geniuses ­really do work better than ours . . . ​­will prob­ably not hinge on dissecting still more brains and counting their cells.” From academe Walter Reich, MD, delivered this rebuke, which unexpectedly appears to run ­counter to the prevailing currents of investigatory neuroscience at that time ­until one considers that Dr. Reich is a psychiatrist—­a specialist who mainly treats disordered minds (and less so disordered brains). Not content with deriding the neuroanatomical approach, he voiced ethical concerns when he instructed ­future researchers to do geniuses “the decency, at their deaths, of leaving their brains in peace.”21 The accretion of accurate scientific data in journals routinely elicits merciless peer review, and criticism over her choice of tissue stains, her control population, and her statistical methods buffeted Diamond’s paper. By the way, ­t here is no statute of limitations regarding scientific criticism, so eigh­teen years ­a fter publication, Robert Terry, the emeritus neuropathologist, took Diamond to task for staining sections of Einstein’s brain with luxol fast blue, ostensibly to tell neurons apart from glia. According to Terry, “it does



The Lost Decades (1955–1985) 65

not” distinguish them. He also speculated that the normal age-­ related shrinkage of neurons mimicked the appearance of glial cells, leading to an erroneous glia-­to-­neuron cell count.22 This was not Marian Diamond’s first rodeo—­she pointedly wrote that she had relied on the cresyl echt violet stain to address the “frequently cited” prob­lem of differentiating “astroglial nuclei from ­t hose of small neurons.”23 Did Terry choose to ignore Diamond’s technical caveat buried in the torpor-­inducing methods section of her paper . . . ​or was he taking up the cudgels on behalf of his old chief of pathology, Harry Zimmerman, who came oh so close to sectioning Einstein’s brain in 1955? Was this the scientific method in action or a feud of academic bloodlines? The eleven controls that Diamond studied came ­under fire in 1998 when a psychologist, Terence Hines, questioned the comparability of brains obtained from the Veteran’s Administration Hospital in Martinez, California, on the grounds of the veterans’ lower socioeconomic status, c­ auses of death (although Diamond avoided brains with neurologic ailments), and younger average age of sixty-­four years (Einstein was seventy-­six when he died).24 Hines was not through with Diamond (or subsequent investigators of Einstein’s brain) and came back sixteen years l­ ater with a withering broadside provocatively titled “Neuromythology of Einstein’s Brain.”25 He took umbrage at the absence of “blinded” observers (“observer bias”) who would not know which microscope slide came from Einstein and which was sectioned from a control brain. Of the twenty-­eight statistical comparisons available to Diamond, only one, the neuron-­ to-­glia ratio of the left inferior parietal cortex, attained statistical significance at the p = .05 level. As Hines dismissively summarized, “One .05 result out of 28 is not surprising” and “to believe that the analyses of one or a few tiny slices of a single brain could reveal anything related to the specific cognitive abilities of that brain is naïve.”26 In an attempt to propitiate the so-­c alled statistical gods, Diamond conceded that her “findings would be more valid if we had eleven Einstein’s, but at least the study was a first step that no one had taken previously.”27 The histological approach to Einstein’s

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brain was ­here to stay, and Marian Diamond had opened the floodgates. Well, not exactly the floodgates—­the next Einstein study did not trickle in u ­ ntil eleven years ­later. Over the next twenty-­one years AD (­A fter Diamond), four more papers and abstracts appeared, and all studied Einstein’s microscopic neuroanatomy. Investigators ­were reluctant to depart from the well-­trodden path of microscopy, and a peer-­reviewed study of Einstein’s gross brain anatomy would not see the light of day u ­ ntil 1999.28 In 1995 Britt Anderson, then an assistant professor of neurology at the University of Alabama at Birmingham, with much persuasion and a prepaid FedEx mailer kit prevailed upon Harvey to send three celloidin-­embedded blocks and unembedded samples of cerebellum.29 Anderson relied upon the Golgi stain to study microscopic neuronal anatomy. For more than a ­century, this stain has been used to randomly and selectively stain individual neurons (and their axons and dendrites) and glia by impregnation with metallic silver. If the Golgi method w ­ ere to stain all the neurons, cell pro­ cesses, and glia, it would be useless ­because the dense silver precipitate in the neuronal/glial “forest” would obscure the detailed anatomy of the individual neuronal/glial “trees.” Why the Golgi stain “selects” only certain neurons and glial cells to stain has remained a mystery since 1873. Much to his chagrin, Anderson found that when the celloidin of the embedded blocks dissolved, the blocks would not stain properly using the Golgi technique.30 Harvey’s use of celloidin imposed technical limitations that prevented any subsequent researcher from using the Golgi method to study Einstein’s brain. Anderson’s only recourse was to stain the neurons and the glia with cresyl violet, count the neurons, and compute the neuron density in a forty-­micron section of Einstein’s right prefrontal cortex. He stated, “Einstein’s cortex was thinner than the controls and more densely populated with neurons.” Given this denser packing of neurons, did Einstein have a greater quantity of cortical neurons than the controls? Lacking an accurate mea­ sure­ment of Einstein’s total cortical volume, Anderson could not provide an answer but did speculate that the decrease in distance



The Lost Decades (1955–1985) 67

between tightly packed neurons “might be advantageous by decreasing interneuronal conduction time.”31 Ever the dev­il’s advocate, Hines countered that even if Anderson’s findings ­were “real, they would in no way be an indication of a neuroanatomical basis for superior information pro­cessing.”32 Are “faster” brains smarter? Even Britt Anderson had second thoughts on the proposal that “neuron conduction velocity accounts for the individual variation in IQ.” Alternatively, long before connectome became a neuroscience buzzword, he speculated that the likeliest biological candidate for “neural operating efficiency” was “neuronal interconnectedness determined by variation in neuronal arborization.”33 In 2015 he continued to pursue a vigorous research agenda as a member of the psy­chol­ogy faculty of the University of Waterloo, but two de­cades ­after his Einstein paper, he conceded, “I prob­ably w ­ ouldn’t do the Einstein study again,” citing the advantages of studying intellectual ability in hundreds of “living” subjects with functional neuroimaging and genomic analyses.34 Thomas Harvey’s primary role in Einstein research was to provide exquisitely preserved brain blocks and slides to investigators with well-­established neuroscience credentials or promise in the field. This approach failed repeatedly ­until Diamond’s paper broke the mold. Prior to 1985 Harvey would take it upon himself to send unsolicited tissue to vari­ous neuroscience luminaries, such as Zimmerman, Kuhlenbeck, and Bailey. The results of their deliberations never saw the light of day in formal scientific communications. Diamond and Anderson ­were dif­fer­ent: they sought Harvey out, and the resultant papers hit scientific pay dirt. Possibly encouraged by ­these provocative publications, Harvey abandoned his decade-­long passive role in 1995 and went back to the hunt for an investigator he hoped could provide further answers to the riddle of Einstein’s brain. This researcher would have to be well established in academic neuroscience, have expertise in neurohistology, and have access to control brains. Sandra Witelson, PhD, a full professor of psychiatry, biomedical sciences, and psy­chol­ogy only eight years ­after joining

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the faculty at McMaster University, fit the bill perfectly. In 1995 she authored a study demonstrating that w ­ omen had an 11 ­percent greater neuronal density than men in their posterior temporal cortex.35 Her paper did not escape Harvey’s notice, and he faxed her a note that succinctly stated, “Liked your paper on the comparison of the superior temporal gyri of men and w ­ omen. Would you be interested in working on any part of Einstein’s brain?” Her answer was even more succinct: “Yes. Let’s talk—­MONDAY.”36 The conversation must have been mutually agreeable. Harvey drove to Hamilton, Ontario, twice. The first time, in the fall of 1995, was simply to meet and appraise Dr. Witelson, but on the second trip in January 1996, he gave Witelson fourteen blocks of Einstein’s right and left temporal and parietal lobes and an unknown number of microscope slides. He also carried all (possibly “300”)37 of his original photo­graphs of the ­whole brain (and some w ­ ere never 38 returned to him). Witelson’s unique resource at McMaster University in the late 1990s was a brain bank (thirty-­five males and fifty-­ six females of normal cognitive ability) that served as controls for her study of Einstein’s brain.39 Although Sandra Witelson’s study of the permanently “borrowed” photo­graphs would lead to the famous 1999 Lancet paper that posited the exceptional neuroanatomy of Einstein’s parietal lobes, that proj­ect was a distant gleam in her eye at this point. Her first line of attack was to focus her microscope and count the neurons and glial cells that Harvey (and Marta Keller) had stained in 1955.40 Research can be a cautious and frequently plodding incremental pro­cess that refers to and recycles earlier work. To be (not overly) facetious, if your tried-­a nd-­true funding has been awarded for the study of dogs’ fur, olfaction, digestion, hunting methods, fangs, et cetera, as an established investigator your next grant proposal should take on a related topic, such as Fido’s tail wagging, rather than, let’s say, making a risky leap into the novel tree-­climbing habits and “wrong-­way” fur growth of the sloth for which you have no prior track rec­ord of funding. The astute and grant-­hungry researcher is always looking for small (fundable) victories. Einstein could very well shift his m ­ ental gears from the



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Very Big (the space-­time curvature of the universe) to the Very Small (quantum theory), but for most mere scientific mortals, “stay with what you know” is the thought of the day. And so Witelson’s first faltering step into the study of the twentieth c­ entury’s greatest scientific intellect was to publish an abstract (a kind of scientific rough sketch) that was never destined to blossom into a full peer-­reviewed publication. She found that the number of neurons and their packing density in Einstein’s cortex did not differ when compared to the same mea­sure­ments of the superior temporal gyrus (STG) in men with normal cognitive ability. The STG, which is associated with the auditory pro­cessing of sounds and language (in Wernicke’s area) and social cognition, might not be the first place to look for the neuroanatomy of genius, but Witelson had an abundance of STG control data readily at hand from her 1995 paper, and she recycled it for the Einstein abstract.41 Although the neuron count was unexceptionable, she did discover that “the proportion of glial cells was close to unity for Einstein, which differs from controls.”42 Like Marian Diamond twelve years earlier, Witelson had found a relative overabundance of glial cells in Einstein’s cortex. She never speculated in print about the role of the extra glia. ­Going forward, she would relinquish her microscope and turn to the close study of Harvey’s eight-­by-­ten glossy photo­ graphs of Einstein’s intact brain. Old scientific habits die hard, and Witelson had second thoughts in 2005 when she wrote to Harvey requesting additional original slides from the region b­ ehind Einstein’s ascending Sylvian fissure. The old pathologist must have taken grim satisfaction in Witelson’s concession that when her research group resectioned and stained the original celloidin-­ embedded blocks, “we could not get sections stained well enough for counting and our staining attempts are inferior to your original ­ on’t know, slides.”43 ­W hether she received the requested slides we d but by this time the lines of communication had irretrievably broken down. Harvey had twice requested the photo­graphs he had taken to Witelson’s lab and “spoke to her secretary or her assistant but she never called back.”44 As I write this two de­cades ­later,

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Witelson has authored no further papers on Einstein’s neurohistology since 1997. The last hurrahs for the histologic study of Einstein’s brain ­were heard in 2001 and 2006. In 2001 Dr. Witelson asked Dahlia Zaidel, a cognitive neuropsychologist at the University of California, Los Angeles (UCLA), to travel to her lab in Ontario and study slides of Einstein’s hippocampi. Zaidel digitized the slides, and when she returned to California, she performed mea­sure­ments on the digital images of the pyramidal neurons of Einstein’s right and left hippocampi. The hippocampus is ensconced in the temporal lobe and is comprised of the phyloge­ne­tically oldest cortex—­the allocortex—­ which has three or four layers (compared to the six layers of neocortex). It almost seems counterintuitive to search for the trappings of genius in this old and primitive part of the brain that subserves memory and emotion as part of Papez’s limbic cir­cuit.45 And in contrast to all the microscopists (who explored frontal, parietal, temporal, and occipital neocortex), Zaidel systematically mea­sured hippocampal neurons. She found that the Nissl-­stained cell bodies ­were consistently larger in Einstein’s left hippocampus than in his right. She concluded that “the relationship between the hippocampal status at the time of his death and its role in his genius in his most creative years is a m ­ atter for debate.”46 In 2015 Zaidel told me that in retrospect she would not repeat her study, voicing concern that the seventy-­six-­year-­old brain she had examined was not the same as it had been at the height of Einstein’s scientific creativity. She raised the possibility that the smaller and less populous neurons of the right hippocampus w ­ ere linked with atrophy brought about by the ravages of aging or disease. She observed that “it would have been more meaningful to see if t­ here was any atrophy in extra-­hippocampal tissue.”47 Suffice it to say that Sandra Witelson had other plans (regrettably, not to be realized in print) for the extra-­hippocampal tissue in the incomplete slide set provided by Harvey. The very last paper published about Einstein’s microscopic neuroanatomy differed from all the previous cell-­counting studies,



The Lost Decades (1955–1985) 71

which used Nissl stains such as cresyl violet.48 ­A fter removing the celloidin from four brain tissue blocks (the inferior parietal, parietal somatosensory, frontal, and occipital lobes) that Harvey had provided, Jorge A. Colombo stained the tissue with glial fibrillary acidic protein (GFAP) antibody, which binds to the cytoskeleton (internal scaffolding) of most, but not all, astrocytes. In clinical work the neuropathologist relies on this stain to identify brain tumors of glial origin, but neuroanatomists can use GFAP antibody to label astrocytes, their cell body extensions, and their locations in par­tic­u ­lar layers of the ce­re­bral cortex. ­These cell body extensions, or interlaminar astroglial pro­cesses, are found only in the cortex of primates. Colombo had published extensively on interlaminar astroglia in comparative neuroanatomy, ce­re­bral architectonics (structure), and Alzheimer disease. Like any parsimonious researcher with a new proj­ect, he applied his default and signature anatomical technique to Einstein’s brain, concluding that t­here was nothing distinctive about the four blocks he had extracted from celloidin. In the face of Colombo’s sweeping assertion, it should be noted that his extremely specialized technique focused on a very restricted aspect of astrocyte anatomy. Astrocytes in h ­ uman brains are much more complex than ­those in the brains of simpler animals, such as mice, and we have at least four dif­fer­ent types of astrocytes—­i nterlaminar, protoplasmic, polarized, and fibrous. GFAP antibody is selective and does not stain all astrocytes. Selectivity aside, Colombo focused on the one-­millimeter-­long cell pro­cesses of one par­tic­u­lar type of astrocyte (interlaminar) located in the topmost layer of the ce­re­bral cortex and contended that linking “complex ­mental per­for­mance . . . ​to local structural characteristics of a singular cortical area would be ill supported.” The view through the eyepieces of Colombo’s Leica and Olympus photomicroscopes may not have been as clearly delineated as his conclusions implied. The morphology of the astrocytic cell extensions like intricate tree branches was tortuous, and in Colombo’s words, t­ here ­were “massive” (fifteen micron) focal enlargements, or “terminal masses.” (In the world of the microscopist, I guess fifteen microns—­a ­little larger

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than a single bacterium—is considered “massive.”) Also buried in his results was the acknowl­edgment that he found “ a moderate increase of immunolabeled astroglial cells,” but he urged caution in endorsing Diamond’s not dissimilar glial findings of two de­cades earlier.49 In his Buenos Aires lab, Colombo contemplated two diverging interpretations of his data. First, the twisted and enlarged astroglial pro­cesses would, by topographic necessity, “suggest a potential increase in the local numbers of glial channels and receptors” and lead to “a functional upgrading of the cortical neuropil.” So, is it reasonable to surmise that Einstein had a more efficient cellular support system to aid and abet his Nobel prize-­winning neuronal output? Not so fast, hombre. Colombo settled on his second interpretation—­the astrocytic changes reflected “maladaptive—or neurodegenerative—­cellular changes, as observed for example in Alzheimer’s cases.” Even in the data-­driven world of truth-­seeking science, “You pays yer money, you takes yer choice.” In the case of Einstein, Jorge Colombo saw a diseased rather than elite brain, and more fundamentally, he considered earlier structural studies of Einstein to be fraught with “incongruities” and to “raise doubts as to the exact contribution of ­t hese types of analyses.” With that parting shot, Colombo had the last word on Einstein’s cellular landscape . . . ​and brought the curtain down on The Microscopists and Albert Einstein—­a drama in five acts. But did Colombo r­ eally have the last word on the significance or insignificance of glial/neuronal cell counts and the mea­sure­ments of glial pro­cesses as biomarkers of intelligence? Despite the provocative findings of Diamond, Anderson, Witelson, and Zaidel, no one has published on this topic in over a de­cade since Colombo’s paper, which was based on a very limited method of studying astrocyte anatomy.50 Astrocytes, so-­called ­because they resemble stars when their radiating branches appear with silver stains, do not reveal themselves in their entirety when GFAP is used for immunostaining. In rodents only 15 ­percent of astrocyte volume w ­ ill stain with GFAP.51 Before we summarily dismiss the quantitation of glia and neurons as potential clues to the nature of cognition, we need to know a ­great



The Lost Decades (1955–1985) 73

deal more about glia than was known to the neuroscience research community from 1985 to 2006. We have come a long way since the 1920s when the amorphous entity of neuroglia was found to consist of three dif­fer­ent types of cells (astrocytes, oligodendrocytes, and microglia), and yet we have only begun to scratch the surface of the most basic questions about glial anatomy and function.52 Neuroscience my­t hol­ogy is alive and well and has regrettably filled the void in our knowledge of the ratio of glial cells to neurons. Such inaccuracies have major implications for Diamond’s finding that “Einstein had more glial cells per neuron than the average man.”53 Even to this day, standard neuroscience texts teach students that “­there are between 10 and 50 times more glial cells than neurons in the central ner­vous system of vertebrates.”54 Diamond’s hypothesis that the relative increase of glial cells in Einstein’s parietal lobe was in response to the “greater neuronal metabolic need” for “the expression of his unusual conceptual powers” was based on a ratio of roughly one glial cell to each neuron, whereas her controls had roughly one glial cell for ­every two neurons.55 ­Needless to say, her hypothesis is a w ­ hole lot less compelling if the norm is ten to fifty glial cells servicing each neuron, as Kandel would have us believe. Suzana Herculano-­Houzel at the Universidade Federal do Rio de Janeiro (and now Vanderbilt University) is not buying the old glial my­thol­ogy. By homogenizing brains with a tissue grinder and quantitating the tagged DNA of each brain cell’s nucleus, she found “a total average of 86.1 + 8.1 billion neurons and 84.6 + 9.8 billion nonneuronal cells in the w ­ hole brain, yielding a maximal glia/neuron ratio of 0.99, figures that are quite dif­fer­ent from the common quotes of ‘100 billion neurons and 10 to 50 times more glia.’ ”56 Dif­ fer­ent parts of the brain have dif­fer­ent glia-­to-­neuron ratios; for instance, t­here is approximately one glial cell for ­every four neurons in the cerebellum, which does not have a well-­defined part to play in h ­ uman cognition although a cerebellar role in cognition is coming to be acknowledged. Herculano–­Houzel’s work dispels many old glial misconceptions and leaves the door open for another

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look at the glia-­to-­neuron ratio in the currently unexamined portions of Einstein’s cortex. Although Diamond’s work might lead us to a grossly oversimplified rule of thumb that more “successful” brains have a higher glia-­to-­neuron cell count, comparative neuroanatomy throws us a curveball. The ce­re­bral cortex of the minke w ­ hale has a 57 glia-­to-­neuron ratio of 7.7:1! Barring the discovery of a cetacean theory of general relativity encoded in w ­ hale song, it is still premature to reduce cognition to a mere enumeration of glia and neurons. Clearly, the demographics of more than 190 billion brain cells and a glial “head count” do not tell the w ­ hole story. Over a c­ entury ago, neuroglia ­were consigned to filling “the space not occupied by neurons.”58 Out of this passive obscurity, we have found that in addition to the glial Big Three—­astrocytes, oligodendroglia, and microglia—­there is an entirely new class of glial cells, NG2 + glial progenitor cells, which can transform into astrocytes or oligodendrocytes as the circumstances allow. It is gradually dawning on neuroscientists that the brain is far from a pure neuronal machine and that the critical importance of astrocytes has been grossly underestimated. Understanding the other glia is much more straightforward. Oligodendrocytes elaborate the myelin, which acts as insulation to speed the propagation of the action potential (electrical conductivity) between neurons. Microglia make up the immunologic defense forces of the central ner­vous system by scavenging infectious agents and cleaning up the debris of dead and injured brain cells. The function of astrocytes is a ­little more opaque but no less impor­tant. A single protoplasmic astrocyte may physically impinge upon 270,000 to 2 million synapses, and an interlaminar astrocyte can extend from cortical layer one to layer four—­a long-­distance connection in the terrain of cortical cellular anatomy.59 Although astrocytes are not electrically excitable like neurons, they are chemically excitable and do “talk” to each other via gliotransmitters and calcium wave propagation between neighboring astrocytes. Unlike neurons, astrocytes abjure synapses and are wired up via gap junctions (protein channels between two adjacent cells).



The Lost Decades (1955–1985) 75

So just what are Einstein’s (or anyone’s) astrocytes ­doing? They are fundamentally dif­fer­ent from neurons, which signal with rapid-­ fire millisecond all-­or-­none action potentials (“spikes” on neurophysiological recordings). Astrocytes use much slower (on the order of seconds to minutes) intracellular calcium diffusion-­based signaling (“waves” on neurophysiological recordings). “We might speculate,” Kettenmann and Verkhratsky wrote, “that the combination of binary [neurons] and analogue [astrocytes] . . . ​information, handled by the two cellular networks in the brain, is essential for brain function in producing thoughts, setting memories and creating emotions, which, in essence, define our h ­ uman nature.”60 The enigmatic astrocyte raises in­ter­est­ing questions about ­today’s dominant meta­phor for the brain—­the digital computer. Transistors embedded in integrated cir­cuits (or chips) are effectively the silicon “neurons” (or neural networks) of artificial intelligence (AI). As the argument runs, the binary coding of modern computers is equivalent to the all-­or-­none action potentials of neurons. Nevertheless, digital computers are very dif­fer­ent from h ­ uman brains and not just ­because brains use parallel rather than serial pro­ cessing.61 Admittedly, a massively parallel computer, such as IBM’s Deep Blue, can be fabricated, but even “strong” AI die-­hards ­w ill concede that IBM did not produce a silicon doppelganger of the three-­pound thinking machine that allows you to read my turgid prose. Vive la différence!—­but for my money, a major and possibly irreconcilable difference is that ­there are no cybernetic equivalents for astrocytes. As previously noted, the last study of Einstein’s neurohistology was in 2006 (and we have learned a g­ reat deal more about astrocytes in the succeeding de­cade). Can the microscopists tell us more about genius? First, I believe they can if we get an even better ­handle on astrocyte function. An impor­tant clue is that with more complex (okay, smarter) central ner­vous systems, astrocytes get bigger, become architecturally more complex and variable, and signal more rapidly.62 When we see that the mouse astrocyte is a “no-­frills” miniversion compared to its ­human counterpart, we realize that the

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evidence gathered from comparative anatomy is sending a strong message about the vital role astrocytes play in brain evolution. Second, cell counts are in­ter­est­ing and even intriguing, but the connections between neurons are profoundly impor­tant and remain terra incognita even sixty-­t wo springs ­a fter Marta Keller microtomed the first thin section of Einstein’s brain tissue from Thomas Harvey’s celloidin blocks. Although Harvey was prescient enough to use a myelin (Weigert) stain to visualize the axons linking neurons (as well as Nissl stain for the neurons themselves), no investigator has ever reported a study of the length, density, and morphology of Einstein’s axons. As twenty-­first c­ entury neuroscience has come to increasingly appreciate the importance of the connectome (neural circuitry), the missed opportunity of mapping Einstein’s axons and dendrites is bound to become glaringly apparent. In 1996, as neurohistologists mea­sured neurons and glia, Sandra Witelson stepped away from the microscope and studied the glossy eight-­by-­ten photos that Thomas Harvey had hand-­delivered. She realized that Einstein’s parietal lobes appeared larger, and to her trained eye, the cortical anatomy had gone awry. The variant appearance was as striking as a “face with the eyebrows beneath the eyes.”63 The world was about to find out that the brain of Albert Einstein was very, very dif­fer­ent.

chapter 5

The Exceptional Brain(s) of Albert Einstein I feel like some relic in an old cathedral—­one ­doesn’t quite know what to do with the old bones. —­L etter from Einstein to Paul Ehrenfest, September 1919 While every­one agrees that brains constitute the very embodiment of complex adaptive systems and that Albert Einstein’s brain was more complex than that of a ­house­fly, ner­vous system complexity remains hard to define quantitatively or meaningfully —­c hristof koch and gilles laurent, 80 years ­later

Three teams of investigators would dust off Harvey’s half-­century-­ old photo­graphs of Einstein’s brain, beginning with Sandra Witelson in 1996. Not surprisingly, each lead investigator (or first author, in the parlance of academic papers)—­a physiological psychologist, a paleoanthropologist, and a physicist—­would “see” a dif­fer­ent brain. And although it was always the same brain, it can be argued that depending on the researcher’s perspective Einstein had (at last count) three very dif­fer­ent and exceptional brains. For the last four studies published (to date) about Einstein’s brain, the teams did not directly study neural tissue embedded in celloidin blocks or mounted on microscope slides. They relied on photo­graphs, which w ­ ere the only way to observe the complex interrelationships of the brain’s gyri and sulci as they had presumably existed inside Einstein’s 77

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head during his annus mirabilis in 1905. Only Harvey’s meticulous black-­and-­white photo­graphs could allow the teams to “reassemble” the brain’s premortem appearance from the three-­dimensional jigsaw puzzle of 240 tissue blocks.

The “Parietal” Brain When Harvey drove back to New Jersey from Hamilton, Ontario, he left the precious pieces (slides and tissue blocks) and photo­graphs of Einstein with Sandra Witelson, who had received her doctorate in physiological psy­chol­ogy at McGill University. Her far-­ranging interests had led her to study the neuroanatomy of language, sexual preference, handedness, and the differences between the brains of men and w ­ omen. As a trailblazer in a male-­dominated field of science, it is ironic that the then president of Harvard Larry Summers would refer to her research on neuroanatomical sexual differences as “one reason fewer ­women succeed in science and math ­careers.”1 One of Witelson’s overriding tenets was that “­every brain is as dif­fer­ent from another brain as ­every face is dif­fer­ent from another face.” 2 She meticulously reviewed the Einstein materials with par­tic­u­lar scrutiny of five of Harvey’s original photo­graphs. The death of her husband sadly delayed her study, but in February 1998 the manuscript was submitted to the venerable British medical journal the Lancet, which has been published weekly since 1823.3 “The Exceptional Brain of Albert Einstein” appeared in print (not as a research paper but u ­ nder Lancet’s rubric, “The Department of medical history”) on June 19, 1999.4 Witelson conceded that “­there was ­little knowledge about the cortical localization of cognitive function” but proposed that “the neurobiological substrate of intelligence may be facilitated by the comparison of extreme cases with control cases.” And when it comes to intelligence, it is hard to come up with a case that is more extreme than Albert Einstein. ­A fter skirmishing with existing limitations of knowledge about the neurology of genius, Witelson mapped out her core hypothesis—­“the parietal lobes in par­tic­u ­lar might show anatomical differences between Einstein’s brain and the brains of controls.”



The Exceptional Brain(s) of Albert Einstein 79

She dutifully noted that when Harvey placed the brain on the enamel pan of his Chatillon scale overhanging the autopsy ­table, it weighed in at 1,230 grams and was no dif­fer­ent from her age-­ matched controls: “A large (heavy) brain is not a necessary condition for exceptional intellect.” Each hemi­sphere was one centimeter wider than that of the controls, making the brain more spherical. Brains, unlike footballs, are not usually symmetrical in an axial plane. Imagine cutting an undeflatable football (okay, forget the New ­England Patriots in the 2014 AFC Championship Game) lengthwise and exactly in the midline—­both halves would match up precisely. That’s symmetry and not the case with ­human brains. Witelson claimed that Einstein’s brain was more symmetrical than the norm. True or false, this finding would make neuroanatomists and paleoanthropologists, such as Dean Falk, sit up and take note. ­ uman The bilateral hemispheric conformation, or petalia, of most h brains (as opposed to other higher primates) lacks symmetry. The right frontal lobe and the left occipital lobe protrude in most right-­ handed ­people,5 and as Witelson would have it, Einstein was the exception to this rule.6 Most significantly, Witelson traced the meandering courses of the cortical fissures (sulci) of Einstein’s parietal lobes and found that a branch of the Sylvian fissure (separating the temporal lobe from the frontal and parietal lobes) was continuous with the postcentral sulcus, which serves as a line of demarcation between the primary sensory cortex and the rest of the parietal lobe (Figure 5.1).7 The anatomical implications of this confluence of sulci was the absence of the parietal operculum (a lid of cortical tissue folded over the under­ lying parietal lobe), a larger expanse of the inferior parietal lobule, and a “full” undivided supramarginal gyrus. She speculated that the “compactness of Einstein’s supramarginal gyrus within the inferior parietal lobule may reflect an extraordinarily large expanse of highly integrated cortex within a functional network.” Furthermore, the aty­pi­cal anatomy of Einstein’s inferior parietal lobules might be linked to his exceptional intellect in “visuospatial cognition, mathematical thought, and imagery of movement.”8

Figure 5.1. Was Einstein’s “exceptional intellect” related to the “aty­pi­cal anatomy” of his parietal lobes? As compared to the asymmetrical parietal opercula found in control brains (shaded and hatched areas in 3), Witelson found that Einstein’s brain lacked parietal opercula, had anterior displacement of the bifurcation of the sylvian fissure (SF) with resultant expansion of the posterior parietal cortex, and displayed unusual symmetry between his hemi­spheres in this region. (Reprinted from the Lancet, Volume 353, Issue 9170, Sandra F. Witelson, Debra L. Kigar, and Thomas Harvey, “The Exceptional Brain of Albert Einstein,” 2149–2153, 1999, with permission from Elsevier. https://­doi​.­org​/­10​.­1016​ /­S0140​-­6736(98)10327​-­6​.­)



The Exceptional Brain(s) of Albert Einstein 81

Five days ­later the eminent experimental psychologist Steven Pinker, writing for the New York Times, proclaimed the Lancet paper an “elegant study . . . ​consistent with the themes of modern cognitive neuroscience” and demonstrating that “­every aspect of thought and emotion is rooted in brain structure and function.”9 Astonishingly, Witelson and her coauthors (her lab assistant Debra Kigar and of course, Thomas Harvey) had unlocked the secrets of Einstein’s variant cortical surface “using a pair of calipers.” Admittedly, Harvey had wielded the calipers four de­cades before Witelson could perform comparable mea­sure­ments on the controls in her brain bank. Time magazine’s appraisal was more cautious. Michael Lemonick, its se­nior science writer and himself the son of a physicist, wrote, “We know Einstein was a genius, and we now know that his brain was physically dif­fer­ent from the average. But none of this proves a cause-­and-­effect relationship.”10 Once the popu­lar press had its say, Witelson’s scientific peers took off their kid gloves and rigorously appraised her findings. Albert Galaburda questioned the provenance of the photos: “We are given no information to ascertain that the photos indeed came from Einstein’s brain.”11 Even ­today, no ironclad evidentiary chain exists to rebut this charge. All Einstein investigators past and pres­ent have relied on Thomas Harvey’s word as an honorable physician and man of science that the photos are originals (or copies) of the brain he removed on April 18, 1955. (Along the same skeptical lines, if you have doubts that Rembrandt van Rijn’s Aristotle with a Bust of Homer currently on exhibit in Gallery 637 at the Metropolitan Museum of Art is the same one he painted in 1653, you are prob­ably ­going to doubt the authenticity of the Einstein photos. Have faith!) Galaburda, a cognitive neurologist who studied the anatomic lateralization of language in the brain, refuted Witelson by asserting that the right hemi­sphere “commonly” lacked a parietal operculum and that Harvey’s photo­graphs “clearly show a parietal operculum on the left [hemi­sphere].” Witelson disagreed, saying that the cortical fold Galaburda identified as Einstein’s left parietal operculum was

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actually the postcentral gyrus.12 Both investigators possessed stellar academic credentials and had spent countless hours dissecting ­human brains. And yet they could not agree on ­whether Einstein lacked parietal opercula. This question would not be resolved ­u ntil our study was published online in 2012.13 Admittedly, I’m biased . . . ​but how can I persuade you, Dear Reader, that we ­really settled this simmering controversy? (Hint: the five photo­graphs in the Lancet article w ­ ere not sufficient to answer many fine-­grained anatomical questions.) Before severing the Gordian knot of parietal opercula, I want to return to 1999 and the personal impact of Witelson’s findings. On June 18, 1999, I was fascinated by the New York Times’ headline—­ “Key to Intellect May Lie in Folds of Einstein’s Brain . . . ​So, Is This Why Einstein Was So Brilliant?”14 At the risk of repeating myself, most neurologists, myself included, deal with brain diseases, not with the “prob­lem” of superior intellect. ­There are no ICD-10 (International Classification of Diseases, a kind of Linnaean system relied upon for medical billing) diagnostic codes for “genius,” and I have yet to see a patient referred for the chief complaint of “being too smart.” Nevertheless, Witelson’s groundbreaking description of Einstein’s cortex was irresistibly thought-­provoking to a guy who spends a lot of time diagnosing and treating disordered brains. When the Dana Foundation put out a call for manuscripts on neurological topics in 2000, I pitched an account of what we had learned about Einstein’s brain and why it interests us so greatly. (This is a real cart-­before-­the-­horse scenario for a medical school professor. I typically submit a completed manuscript to an academic journal and await the editor’s decision on acceptance—­usually with revision or outright rejection. In the high church of academic publishing, it is quite unorthodox to submit a proposal sans manuscript on “spec.”) Walter Donway, the editor of the Dana journal Cerebrum, was intrigued, and I was off to the races. I ­didn’t know anything about Einstein and had never written a word about him (or his brain). I now had to confront Witelson’s world-­renowned hypothesis of the crucial role played by Einstein’s parietal lobes.



The Exceptional Brain(s) of Albert Einstein 83

As Witelson would have it, was Einstein a “parietal genius” by anatomical criteria? It’s a trifle overstated but a good question nonetheless. My search for an answer became a lot less straightforward when I read Macdonald Critchley’s classic monograph The Parietal Lobes, which cautioned that “the parietal lobe cannot be regarded as an autonomous anatomical entity. Its bound­a ries cannot be drawn with any precision except by adopting conventional and artificial landmarks and frontiers. ­Later it ­will also be seen that it is not pos­si­ble to equate the parietal lobe with any narrowly defined physiological function. In other words, the parietal lobe represents a topographical con­ve­nience pegged out empirically upon the surface of the brain.”15 Anatomical imprecision aside, Critchley’s book was a high-­water mark for the growing acknowl­edgment of the critical neurological (and psychological) roles of the parietal lobe. Critchley reminisced that “a visitor to the prewar neurological centres in Eu­rope might be tempted to remember the Psychiatric Clinic of Vienna as a posterior parietal lobe institute.”16 Undoubtedly, classic pre­sen­ta­tions of right parietal lobe lesions in which patients ignored (parietal neglect) the left side of their environment or contended that their own para­lyzed left arms belonged to other ­people piqued psychiatrists’ intellectual curiosity.17 Critchley’s take on the parietal lobes was very dif­fer­ent from that of his pre­de­ces­sors, such as the Johns Hopkins Medical School neurosurgeon Walter Dandy, who twenty years earlier wrote that the “right parietal lobe (excluding sensory function of the paracentral region) has no known functions” and deemed the left parietal lobe “by far the most impor­tant part of the brain.”18 Neuroscience, no less than other learned disciplines, is subject to the ascendance of schools of thought, and Critchley’s groundbreaking reconsideration of the parietal lobe resonates to the pres­ent day in Oliver Sacks’s “richly ­human clinical tales,” which include an account of a w ­ oman (with a stroke of her right parietal lobe) who ate only from the right half of her plate, neglecting the left.19 Lesion case studies can only take you so far in understanding brain function. And Critchley reminds us that “the fallacy of confusing localization of sign-­producing lesions with localization of

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function still needs reiteration.”20 Lest it be forgotten, in the case of Einstein, Witelson took the mea­sure of presumably supranormal rather than defective parietal lobes. In a l­ater chapter, I w ­ ill sift through the evidence for Einstein’s distinctive brand of creative cognition, but with the anatomical facts we have in hand, I ­don’t think we can reduce Einstein’s core competencies to parietal lobe physiology. For now I ­will simply say that if we agree with cognitive scientist Marsel Mesulam’s analy­sis of the posterior parietal cortex as pivotal in integrating spatial information received via all our senses,21 it becomes difficult to envision Einstein’s parietal lobe as the most crucial ele­ment in the creation of his revolutionary theoretical constructs. Our senses cannot detect the curvature of space (as in the theory of general relativity) or the infinitesimal changes in time and dimension that occur with the velocities encountered in daily existence (as in the theory of special relativity). Lacking direct sensory access to length contraction/time dilation at nonzero velocity and curvature of space, from 1905 to 1915, Einstein relied on thought experiments played out in his imagination or, using the terminology of cognitive neuroscience, in his global neuronal workspace.22 As a neurologist whose occupation is to locate and treat abnormally functioning parts of the brain, I can assure you that currently imagination and global neuronal workspace do not readily localize to specific brain regions, including the parietal lobe. Neuroscience progresses in fits and starts but it is inexorable, and the specific “address” of a neural network under­lying the creativity of an Einstein may yet be discovered. By the summer of 1999, Sandra Witelson’s hunch about the starring role played by Einstein’s parietal lobes seemed vindicated. Steven Pinker agreed with her findings and assured us that “the difference between the inferior parietal lobules of Einstein and of us mortals is not subtle.”23 She was lionized and ascended to academic Valhalla—an endowed chair—­when she became the inaugural Albert Einstein/Irving Zucker Chair in Neuroscience (the donor, Mr. Zucker, was kind enough to give Einstein top billing) a



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mere four days ­after her Lancet paper! Witelson wagered heavi­ly on the primacy of the parietal lobes and stated that she was “guided theoretically on the basis of current information of cortical localization of cognitive functions.”24 The subsequent appreciation of the massive evolutionary increase of cortical connectivity in ­humans25 has increasingly led us to question the doctrines of “pure” cortical localization. Like it or not, most scientific hypotheses (or the way we frame our scientific questions) are biased, and Witelson found the evidence she was looking for in five of Harvey’s photo­graphs (Figure 5.2).26 With ­these in hand, she wrote that “the gross anatomy of Einstein’s brain was within normal limits with the exception of his parietal lobes.”27 As Dean Falk and I came to l­ater appreciate, when you look at two-­dimensional photo­graphs of a three-­dimensional object, such as Einstein’s brain, additional photographic views are invaluable to most accurately reconstructing the object in the mind’s eye. Did Witelson have more than the five photo­graphs she published? You bet she did. Did she weigh all of them in her final scientific conclusions? W ­ e’ll never know but if she did, the beautiful fit of the five canonical views and her preconceptions about the parietal lobe overshadowed them. Could the anatomy of Einstein’s parietal lobes differ in isolation from the rest of his brain? Did Harvey take more than five photo­ graphs during Einstein’s postmortem, and if so, did they hold any surprises? Twelve years would pass before Dean Falk and I could even hope to find the answers to t­ hose very questions.

The Brain with Extraordinary Prefontal Cortex . . . ​and More As recounted in the first chapter, Dean Falk sent me an e-­mail seven years a­ fter the publication of “Dissecting Genius” with an intriguing request: Could I point her to photo­graphs with “vari­ous views (including a frontal view)” of Einstein’s gross brain that w ­ ere not just ­those shown in Witelson’s paper and her rebuttal of Galaburda’s

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Figure 5​.­2​.­Witelson selected five of Harvey’s 1955 photo­graphs of Einstein’s brain (A, both hemi­spheres from above; B and C, left and right hemi­spheres; D, underside of the brain, cerebellum, and brain stem; and E, medial surface of the left hemi­sphere) to demonstrate a relatively spherical brain, moderate age-­appropriate atrophy, and a lack of parietal opercula demarcated by the confluence of the postcentral sulcus and posterior ascending branch of the Sylvian fissure (see arrows, B and C ). (Reprinted from the Lancet, Volume 353, Issue 9170, Sandra F. Witelson, Debra L. Kigar, and Thomas Harvey, “The Exceptional Brain of Albert Einstein,” 2149–2153, 1999, with permission from Elsevier. https://­doi​.­org​/­10​.­1016​/­S0140​-­6736(98)10327​-­6​.­)

criticisms?28 As it turned out, I c­ ouldn’t accommodate her request for another three and a half years, but nevertheless, an improbable collaboration was launched. To better understand Dean’s perspective and motivation, let’s dispense with her formidable academic bona fides—­she’s se­nior scholar at the School for Advanced Research in Santa Fe, New



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Mexico, and a professor (and former chair) of anthropology at Florida State University. She is a paleoanthropologist with a par­tic­u­lar interest in the evolution of the h ­ uman brain—­t he subspecialty of paleoneurology. When confronting neurologic disease, we neurologists ­will infrequently review skull x-­rays to screen for a fracture (in cases of head trauma). To examine the brain inside the skull, we rely on tests (CAT scan, MRI, or ce­re­bral angiography) that visualize soft (neural) tissue. Paleoneurologists’ “patients” may have died more than three million years ago, and n ­ eedless to say, only the bones remain. Without a brain to directly examine, paleoneurologists, who refer to the skull as a braincase, study the markings on the inner ­table of the skull with latex endocasts—­and now CAT scan–­derived virtual endocasts—­that characterize the surface neuroanatomy and size of ancestral hominid brains.29 Given her expertise in paleoneurology, Dean was very familiar with the challenges of neuroanatomical analy­sis in cases lacking a brain to dissect or to neuroimage. In the case of Einstein, the challenge was to map, with unpre­ce­dented detail, the entire cortex of a brain that had been divided into 240 blocks more than half a ­century earlier. In Dean’s words, “Sulci may still be identified and interpreted from the extant photo­graphs of Einstein’s w ­ hole brain, in much the same way that cortical morphology is observed and studied on endocasts from fossils by paleoneurologists.”30 As fascinating as the study of Einstein’s brain would turn out to be, it does not qualify as a day job. Dean’s real job description runs the gamut from teaching Florida State University undergraduates enrolled in ANT 2511—­Introduction to Physical Anthropology and Prehistory—to making and describing latex and virtual endocasts of the brain of a new and recently extinct species of ­human, Homo floresiensis (the so-­called hobbit due to a diminutive stature of three to three-­and-­a-­half feet), discovered in Liang Bua, a cave in Indonesia.31 The hobbit “is now considered the most impor­tant hominim fossil in a generation.”32 Make no ­mistake, Einstein was a detour from Dean’s c­ areer path of innovative academic excellence in paleoanthropology. (And for that ­matter, I keep the wolf from the

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door by seeing patients and teaching neurology to medical students and residents.) ­There are no Einstein-­research grants, and what we accomplished was cobbled together on our own time, with sweat equity. This was “curiosity-­driven research”33 at its purest and most unmarketable. You c­ an’t monetize the study of Einstein, but the exhilaration of scientific discovery was more than sufficient compensation for us both. By January  2008 Dean’s search for any additional photos Harvey took in 1955 (if such existed, and that was not a foregone conclusion) had reached an impasse. Elliot Krauss replied that “Dr. Harvey did not give me the photos,”34 and “Sandra Witelson never answered any of my communications.”35 (Dear Reader, as you may have gathered by now, scholarly altruism and selfless collegiality are not leitmotifs in this tale of Einstein’s brain.) Undeterred, Dean announced that “having soldiered on, I now have a short paper on Einstein’s brain that is trying to find a home.”36 And find a home it did—in Frontiers in Evolutionary Neuroscience.37 By virtue of its subspecialized subject ­matter, this intriguing journal is not destined to reach a wide audience but, emblematic of Dean’s philosophy of getting scientific research into the hands of interested scholars and the public alike, the article was online and open access. More critically, she demonstrated the wealth of new information that could be gleaned from the five grainy postage stamp–­sized brain photos that had been reproduced in Witelson’s article a de­cade earlier.38 Even for an accomplished neuroanatomist, this was not as easy as it looked. Dean had to run the gauntlet of accusations of practicing phrenology and cope with the anatomical limitations of mapping the brain’s sulci (furrows), which “usually do not correlate precisely with the borders of functionally defined cytoarchitectonic fields.” 39 (In other words, specific areas of gross brain anatomy do not necessarily match up neatly with the microanatomy. For example, you can have motor neurons firing happily away in the sensory cortex.40) Dean knew that “gross sulcal patterns have been associated with enlarged cortical repre­ sen­ ta­ tions that subserve functional



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Figure 5​.­3​.­Falk identified the cortical knob (shaded convolution labeled K ), which was an enlargement of Einstein’s right hemispheric primary motor cortex. This omega-­shaped “bend” of cortex has been reported in right-­handed string players. It abuts the central sulcus, which marks the boundary between the frontal lobe and the parietal lobe. (Dean Falk, “Photo­graphs of Einstein’s brain that ­were taken in 1955, adapted from Witelson et al. [1999b],” in “New Information about Albert Einstein’s Brain,” Frontiers in Evolutionary Neuroscience 1 [May 2009], https://­www​.­frontiersin​.­org​/­article​/­10​.­3389​/­neuro​.­18​.­003​.­2009​.­)

specializations in mammals including carnivores.”41 And that begged the question: Could Einstein’s functional specializations be associated with variant cortical anatomy? Even with limited photo documentation at hand, Dean found two anomalies that set Einstein’s brain apart. What Dean saw (and what went unreported in Witelson’s Lancet paper) was a “knob-­ shaped fold of precentral gyrus,” or “omega sign”42 on the surface of Einstein’s right frontal lobe (Figure 5.3). The precentral gyrus is the primary motor cortex controlling movement of the opposite side

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of the body. The cortical knob that Dean had observed corresponded to the portion of the motor cortex that subserved the vast repertoire of Einstein’s left hand movements. As Louis Pasteur famously remarked, “In the fields of observation, chance f­ avors only the prepared mind,” and the oxbow-­shaped extension of Einstein’s precentral gyrus pictured in the superior and right lateral views of Witelson’s first figure (Figure 5.2)43 “jumped off the page” for Dean, who was well versed in the recent lit­er­a­ture defining this cortical landmark. It must be conceded that when Witelson began to pore over Harvey’s photo­graphs in 1996, the classic reference localizing the motor hand area to the precentral gyrus had not been published.44 While training her sights on Einstein’s parietal lobes, the motor cortical knob located in the frontal lobe was likely not on Witelson’s radar. You may well ask what the cortical knob or omega sign has to do with theoretical physics. Is it an anatomical “secret handshake” that identifies physicists? As far as we know, it’s not. (Note to self: with a l­ittle funding and a bunch of physicists willing to spend ten minutes or so in an MRI scanner—­t he question could easily be resolved.) What we do know is that the omega sign is an anatomical landmark for musicianship! When three-­dimensional MRI images of professional musicians’ brains w ­ ere compared with t­ hose of nonmusicians, the musicians had a higher incidence of clearly vis­i­ble omega signs. Moreover, the brains of string players could be distinguished from ­those of keyboard players. The omega sign occurred significantly more often in the left hemi­sphere of keyboard players, whereas the preponderance of omega signs in string players appeared in the right hemi­sphere.45 For the moment lay aside Einstein’s superpower of theoretical physics and recall that he was an enthusiastic and accomplished violinist who delighted in impromptu duets with accompanists ranging from neighbors to Queen Elizabeth of Belgium. The pitch emanating from the precise fingering of Einstein’s left hand on his violin’s fingerboard presumably began with activation of his right cortical knob. Was Einstein born with this par­tic­u­lar cortical variation, or was it acquired as



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his brain “rewired” with hours of practice? This profound question of nature versus nurture ­w ill recur incessantly but ­w ill not be resolved by our study of Einstein’s brain. Suffice it to say that Dean Falk’s identification of Einstein’s cortical knob was further proof of concept that brain structure is not entirely in­de­pen­dent of brain function. (Disclaimer: this is not a prospectus for neuroanatomical mind reading or a twenty-­first-­century iteration of phrenology.) Dean’s other finding regarded the location of Witelson’s “missing” parietal opercula. As organisms ascend in phyloge­ne­tic complexity of the central ner­vous system to become more “brainy,” they (or rather natu­ral se­lection) need to create more and more room for the ce­re­bral cortex. One anatomical pathway is to fold and refold the cortex in on itself and maximize the cortical surface within the confines of a rigid “box”; that is, a bony skull. Opercularization is an example of this folding pro­cess in which expanding portions of frontal, parietal, and temporal lobe cortex fold over a patch of under­ lying insular cortex. Opercula (from Latin) are “lids,” and an apt comparison would be to imagine closing your eyelids over your eyeball. In the parlance of neuroanatomy, your upper eyelid would serve as a fold of parietal lobe cortex and your lower lid as a fold of temporal lobe cortex. Both lids would resemble the opercula covering the submerged patch of cortex known as the insula. Although Dean and Witelson did share common ground in their assessment of Einstein’s “extraordinary parietal substrates,”46 they parted ways in their analyses of the parcellation of parietal cortex. The proximity and connectivity of ­those parcels undoubtedly have implications for brain function, and what at first glance may seem to be an exercise in anatomic hairsplitting may help to explain how one part of the brain “talks” to another part. Dean had enough anatomical evidence to assert that Einstein’s right and left insula ­were covered by opercula, but a crucial prop for her argument would be to determine w ­ hether the posterior ascending limb of the Sylvian fissure was continuous with the postcentral inferior sulcus or ­whether the two sulci ­were separated. Based on the five photo­graphs in Witelson’s figure 1,47 Dean had

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no choice but to fall into line with Witelson’s conclusion that the two sulci ­were confluent. Except they w ­ eren’t . . . ​and it would take us three years to find that out. “New Information about Albert Einstein’s Brain” gave further notice that “the gross anatomy of Albert Einstein’s brain in and around the primary somatosensory and motor cortices was, indeed, unusual.”48 This six-­page study of portions of two lobes of Einstein’s brain was a warm-up exercise for Dean. She would run the t­ able in 2012.

“Dear Professor Falk, I am pleased to let you know that your paper has now been accepted for publication in Brain . . .”49 For an academic facing the dilemma of “publish or perish,” ­there are no sweeter words ­after submitting a manuscript than “has now been accepted.” Our paper had three authors—­Falk, Noe, and myself—­but in the time-­honored protocols of scientific publication, the editor in chief, Alastair Compston, would deliver the good or bad news to the first author, Dean Falk. ­A fter Dean and I prevailed upon Adrianne Noe to let us examine the contents of the late Thomas Harvey’s Einstein archives at the National Museum of Health and Medicine (NMHM) on September 12, 2011, Dean spent months reviewing my digital copies of dozens of Harvey’s original autopsy photo­graphs (eventually, fourteen would be published). She meticulously identified and rendered pen-­and-­ink tracings of ­every gyrus and sulcus vis­i­ble in the pictures and compared them to the standard atlases of normative ­human cortex.50 Anatomical nomenclature had changed a bit in the half c­ entury since Harvey had labeled cortical landmarks on his photos, presumably for a paper on Einstein’s gross anatomy (that he would never write as a first author). So Dean had to dispense with the obsolete terminology of radiate sulcus and replace it with the up-­to-­date inferior frontal sulcus. As we ­shall see, she found some sulci that remain unnamed to the pres­ent day. For her prodigious efforts, Dean unquestionably was the first author of our paper, and Adrianne was designated as the last (or se­nior author), who frequently is “a member of the



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institution ­behind the research” (in this case the NMHM).51 I was comfortably ensconced as second author in the limbo of academic attribution—­“What exactly was your contribution to this manuscript, Dr. Lepore?”—­that exists between first and se­nior authors on the paper’s heading. By April 10, 2012, a detailed paper had been prepared, and in her letter (with manuscript attached) to enlist Adrianne Noe as a coauthor, Dean, in the understated tone of informal scientific communication, mentioned that “the brain is extremely in­ter­est­ ing, as you w ­ ill see.”52 (Another note to self: as Dean well knew in this age of scientific ballyhoos, understatement is in very short supply. For my money, the reigning champion of scientific bon mots was, “It has not escaped our notice that the specific pairing that we postulated immediately suggests a pos­si­ble copying mechanism for the ge­ne­tic material,” drily intoned by James Watson and Francis Crick when they communicated the discovery of DNA in a two-­page paper.53) Although light-­years away from the Nobel Prize–­strewn scientific Elysian Fields of Watson and Crick, in the midst of our exhilaration, we came face-­to-­face with a universal prob­lem of scientific authorship: What journal do we submit our manuscript to? This was not a straightforward choice for denizens of three very dif­fer­ent academic worlds—­Falk (PhD in anthropology), Lepore (MD with board certification in neurology), and Noe (PhD in history). Typically, I would publish in the journal Neurology, while Dean would reach her audience of academic peers in the American Journal of Physical Anthropology. For the Einstein paper, we needed a journal that could reach across the bound­aries of academic disciplines and provide a sense of neuroscientific history that could encompass the brain of a genius who died in 1955 (and a large international readership would be nice, too). Dean, a member in good standing with the sorority/fraternity of neuroanatomists, made discrete inquiries of Albert Galaburda, the formidable and perceptive critic of Witelson’s Lancet paper.54 ­A fter some “background checking,” he advised that we “might submit our article to the journal Brain.”55

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Brain, or more properly Brain: A Journal of Neurology, was first published in 1878 and is the oldest continuous English-­language learned journal of neurology. The term neurology (or neurologie, as it was coined by Thomas Willis in 1681) originally applied to “the cranial, spinal, and autonomic nerves, as differentiated from the brain and spinal cord.”56 Over time neurology would come to encompass the study of the entire ner­vous system in health and disease (and I’m expected to apply this par­tic­u­lar area of medical knowledge when patients come to see me). The explosion of neurological knowledge over the course of three and a half centuries expanded the subject ­matter of Brain, which by 2008 included “behavioural neurology, clinical-­pathological correlation in the dementias and neurodegenerative and inflammatory brain disease, movement disorders, neuroge­ne­tics, epilepsy, nerve and muscle disease, the pathophysiology and modelling of disease mechanisms, and definitive case series that describe patterns of neurological disease or newly identified disorders.”57 One-­off articles, such as our study of Einstein’s brain, had their own category—­“Occasional Papers”—­that was irregularly published. ­Needless to say, we strongly felt our paper was both of compelling interest and neuroscientific merit. (­Don’t all authors feel that way?) Despite the rigor of our scientific approach and the uniqueness of the rediscovered “lost” photo­g raphs of Einstein’s brain, our paper was off the beaten track for mainstream clinical neuroscience . . . ​and we ­were asking to be published in what is arguably the highest-­profile neurology journal in the world. If I can invoke a meta­phor bridging C. P. Snow’s “two cultures,” seeing your paper appear between the baby-­blue covers of a monthly issue of Brain is like the exhilaration of a short-­story writer whose work appears in the New Yorker. (To provide a l­ittle more perspective, the New Yorker turned down fifteen poems, seven short stories, and an excerpt of The Catcher in the Rye of no less a literary icon than J. D. Salinger!) Neither of ­these publications suffers fools gladly, and their reviewers make the classical underworld’s guardian, the three-­headed Cerberus, look like a lapdog.



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Besides setting our sights high, we had two additional prob­lems—­ the length of our paper and institutional attribution. Our manuscript was over eleven thousand words in length. For a scientific publication, you might as well be submitting a rough draft of War and Peace, and most scientific editors consider such length to be a personal affront as they sharpen their red pencils. (Okay, I’m dating myself. Now editors use Microsoft Word document highlighting tools.) The editors ­will invariably and sanctimoniously protest that shortening your manuscript f­rees up more publication room for other impor­tant scientific papers. (In one of my recent reveries, I envisioned Herman Melville bringing a handwritten copy of Moby Dick to a medical journal editor and being brusquely advised to cut out the literary superfluities, such as dramatic foreshadowing, details of life aboard a Nantucket w ­ haler, Biblical symbolism, ­etc., and go straight to the part where Ahab harpoons the White Whale). With the exception of Norman Geschwind’s two-­part, 116-­page magisterial article on the “Disconnexion Syndromes in Animals and Man,” 58 papers in excess of eleven thousand words simply do not get printed on the hallowed pages of Brain in the modern era. Geschwind’s paper was legitimately paradigmatic for our clinical understanding of the brain’s critical internal wiring “cir­cuits” (which we now term the connectome). Our modest study was not even remotely in this class, but one could hope. Would Alastair Compston, a soon-­to-be Commander of the Order of the British Empire (CBE) and the im­mensely erudite editor of Brain, cut our manuscript to shreds or worse, simply reject it? In other words, would we go out with a whimper or a bang? One of the supreme paradoxes in our pursuit of Thomas Harvey’s collection of Einstein artifacts was that the curating institution, NMHM, deliberately suppressed news of its acquisition of “lost” Einstein brain photos and microscope slides in June 2010. ­A fter Dean and I studied and photographed the Einstein archive (now occupying eight boxes) on September 12, 2011, we w ­ ere taken aside by NMHM director (and our ­future coauthor) Adrianne Noe, who requested that “additional access or publication” of our Einstein

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findings would “not [be] occurring ­until ­after our May 2012 opening” of the new NMHM fa­cil­i­ty.59 Aside from my slack-­jawed astonishment that this 149-­year-­old museum chose to hide its most high-­profile (­a fter the Lincoln assassination bullet) acquisition, Dr. Noe’s request for institutional anonymity created yet another stumbling block in the way of our submission to Brain. At Adrianne’s behest Dean and I w ­ ere now in the unenviable position of being unable to say just where in space and time the lost trea­sure trove of Einstein materials was archived. And so, the first draft of the manuscript submitted to Brain somewhat enigmatically reported that Dr. Harvey’s estate was “curated by ‘Institution X’ in 2010.” To compound our credibility prob­lems, a PBS NOVA Science Now documentary titled “How Smart Can We Get” was in production in the latter part of 2012, and of course we had to tell our producer/director, Terri Randall, that we could not divulge where our research materials resided.60 Well, Reader, you know our paper got published, and the documentary aired on October 24, 2012 . . . ​but in the spring of 2012, however, the outcome hung very precariously. Declaring no known institutional attribution for our primary source research materials was tantamount to telling the editor and reviewers that the Einstein photo­g raphs w ­ ere situated somewhere in Atlantis, Shangri-la, or the Big Rock Candy Mountain. Taking Adrianne at her word, the identity of the NMHM as the home of the Einstein materials could only be openly acknowledged when the museum celebrated a ­Grand Opening Open House on May 14, 2012. By mid-­May, the reference to Institution X was expunged from our manuscript, and the NMHM was properly cited.61 Crisis averted . . . ​except for one trifling detail—at its ­grand opening in Silver Spring, Mary­ land, the NMHM did not acknowledge the on-­site presence of its Einstein collection!62 As we came to fully appreciate, anything about Einstein ­will induce a media feeding frenzy. Alastair Compston was well versed in the care and h ­ andling of something (neurologically) new u ­ nder



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the sun and wisely imposed a prepublication embargo on our findings u ­ ntil 00.01 hours GMT on November 16, 2012. Our online paper duly acknowledged the NMHM as the repository of the Einstein materials that had vanished when Harvey packed his bags and left Prince­ton Hospital in 1960.63 And so, buried in the fine print of the introduction of our paper, the NMHM backed into an announcement of its landmark acquisition.64 Clearly, I have never been savvy about institutional public relations, but in stark contrast Einstein’s brain was literally front page news when the Mütter Museum was given forty-­six microscope slides from Einstein’s brain (compared to the 567 slides and dozens of photo­graphs donated to the NMHM) on November 17, 2011. The announcement, along with a full-­color reproduction of a specimen slide and its donor, made the front page of the Philadelphia Inquirer the very next day.65 Eschewing something as prosaic as a press release for the scientific and lay press, the NMHM—­a taxpayer-­funded institution—­after two and a quarter years informed John Q. Public of its owner­ship of five and a half linear feet of Einstein materials . . . ​not with a media blitz but by announcing the sale of an app! In collaboration with the software developer Aperio, the NMHM scanned and digitized 350 of its neuroanatomical images. The announcement was made on September 25, 2012, and would-be researchers or other interested parties could thenceforward purchase the interactive Einstein Brain Atlas app from iTunes for $9.99.66 It has since been deeply discounted at $0.99, and I suspect this may reflect the growing dismay of Tiger Moms who forked over $9.99 and realized ju­nior was interacting with digitized pieces of Einstein’s brain and not the anticipated bold graphics of “My Baby Einstein,” which somehow got lost in the confusion of the app store. (Apparently, even app store economics are not removed from the raging controversy of nature vs. nurture.) The NMHM eventually got around to a press release—­“Never Before Seen Photos and ‘Maps’ of Albert Einstein’s Brain Go on Display at Medical Museum in Mary­land”67 over four months a­ fter

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our paper was published online. Confounding ­factors of institutional attribution and manuscript length aside, Brain (and its publisher, Oxford University Press) assigned noteworthy neuroscientific significance to our discovery and analy­sis of the unpublished photo­ graphs. The “less is more” philosophy of manuscript editing was held in abeyance! For example, rather than abbreviate the anatomical names for all the sulci, we w ­ ere instructed to use full names throughout the text, insert the abbreviations with accompanying full names in the figure legends, and devote ­t able 1 to alternate abbreviations and names of sulci.68 ­Table 1 alone contained a key for ninety-­seven anatomical abbreviations. Dean knew the reader would be inundated with anatomical minutiae but felt that, in the name of clarity (and the limitations of short-­term memory), redundancy of ­these terms throughout the article was essential. This came with the significant editorial cost of increasing the page space of our article. Alastair Compston and his scientific editor, Dr. Joanne Bell, clearly wanted the most definitive and comprehensive analy­sis to date of Einstein’s cortical neuroanatomy to be recorded in the pages of Brain. Dean was encouraged “to err on the side of too much information than not enough.”69 Feeling as if we had entered an alternate editorial universe in which “length is strength,” we complied with alacrity. The paper topped out at twenty-­four pages, and the glossy blue cover of the April 2013 issue was emblazoned with a collage composed of six of Dean’s marvelous color tracings of the brain photo­graphs and a portrait of an atypically formal Einstein attired in a wing collar and cravat. In his editorial Compston commented on the prospect that “variation and asymmetry in gyral and sulcal patterns and hemispheric architecture may also reflect advantages conferred on the individual in terms of cognitive per­for­mance.” He then went a step further and concluded that “in so far as gross anatomy can illuminate the m ­ atter, Einstein did have a better brain than t­hose who still strug­gle conceptually with E = MC2.”70 Was the conclusion that Einstein had a “better brain” the intent of our research, or was Compston overreaching? By way of an



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answer, let me shed further light on the discovery of the extraordinary neuroanatomy (and its implications) described in t­ hose twenty-­ four pages. During the fall and winter of 2011–2012, Dean devoted months of intensive study to the previously unknown or missing photo­graphs that we had brought back from the NMHM. The key to our unpre­ ce­dented cortical findings was intense scrutiny of the multiple views of the brain that Harvey had captured in the spring of 1955. Fourteen of the photo­graphs enabled us to “describe the entire ce­re­bral cortex.” This was a lengthy pro­cess, as Dean had to “visually rotate between dif­fer­ent views of Einstein’s brain to make sure that my identifications w ­ ere consistent from view to view.” She had been ­doing this kind of demanding visuospatial work since her undergraduate days at the University of Illinois (Chicago Circle, as it was then called), when she wrote her honors thesis on the evolution of brain size.71 Her expertise notwithstanding, a­ fter “months of intensive study,” Dean realized that she was “staring at the ceiling at night and seeing sulcal patterns.”72 The upshot was that we “identified the sulci that delimit expansions of cortex (gyri or convolutions) on the external surfaces of all the lobes [my italics] of the brain and on the medial surfaces of both hemi­spheres.”73 With this comprehensive and detailed analy­sis of Einstein’s surface neuroanatomy accomplished, we could compellingly demonstrate that the external cortex (including medial surfaces not vis­i­ble in undissected brains) of ­every lobe (frontal, parietal, temporal, and occipital) of his brain was unusual. Before proceeding any further, a thought uppermost in my mind is, “How many readers of my account of the ‘search and rescue’ of Einstein’s brain have more than a passing familiarity with neuroanatomy?” Not many, I suspect. Accordingly, I ­w ill tailor my description of his ce­re­bral morphology to members of my imagined/ hoped-­for audience who enjoy the Science Times section in Tuesday’s New York Times or anything written by the late Oliver Sacks (Disclaimer: what­ever the merits of this book may be, they fall far short of Oliver, even when he was having a “bad writing day,” which I ­don’t think ever happened.) A related point is that certain types

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of dry scientific jargon w ­ ill suck the oxygen out of the fragile atmosphere that surrounds an interested audience. Stephen Hawking’s editor warned him that he would halve his readership for e­ very equation in A Brief History in Time, and so Hawking included only one: E = mc 2.74 By the same token, reading too much descriptive cortical morphology ­will deaden your senses and instantaneously induce REM sleep. To avoid that pitfall, I ­will guide you through the most fascinating and perplexing aspects of our anatomical study. For t­ hose hardy souls who want to embrace the totality of our findings, our twenty-­four-­page paper awaits you.75 Most striking was his highly unusual right frontal lobe in which the ­middle frontal region was cleaved into two distinct gyri by a relatively long midfrontal sulcus. Where “standard issue” h ­ uman frontal lobes have three gyri, Einstein, with his anomalous divided gyrus had four! (See Figure 5.4.76) This extra frontal gyrus suggested the expansion of Einstein’s prefrontal association cortices. Dear Reader, before g­ oing any further, I implore you to regard this startling variation of anatomy strictly as a fascinating example of structural biology and not a surrogate for Einstein’s intellect. If the unique neuroanatomy I have begun to outline suggests a tangible link to Einstein’s profound grasp of our universe, so be it . . . ​but always remember that not a shred of scientific evidence exists t­ oday that ­will allow us to bridge the explanatory gap between brain and mind. As a clinical neurologist, I frequently try to connect straightforward but far-­from-­simple functions (such as vision) with parts of the brain (such as the occipital lobe). This is known as localization, and it is standard operating procedure when we try to diagnose and treat brain diseases. This approach is not so useful with prob­lems posed by the most complex parts of the brain, such as the frontal lobe. In the words of John F. Fulton, one of the greatest researchers on the functions of the frontal lobe, “In approaching the functions of the frontal association areas one is brought face to face with activities which are difficult to describe in physiological terms.”77 As a working neurologist, I’m in good com­pany when I concede that I ­can’t tell you exactly what the frontal lobes “do.” If



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Figure 5​.­4​.­Einstein’s “extra” frontal gyrus is clearly vis­i­ble in Harvey’s original 1955 photo­graph (with his sulcal labels) of Einstein’s right hemi­sphere. With covering meninges removed, the exposed cortical surface shows four (rather than the usual three) midfrontal gyri. If ­you’re counting, midfrontal gyri number two and number three are to the right and left, respectively, of the labeled midfrontal sulcus (Mid. frontal s). Number one lies to the right of number two, and number four is to the left of number three. (Harvey Collection, National Museum of Health and Medicine.)

the functions of average frontal lobes ascend to the empyrean heights of our “gnostic, mnestic, and intellectual pro­cesses,”78 then in order to grapple with the implications of Einstein’s abnormal frontal neuroanatomy (to quote Jaws), neuroscience is “gonna need a bigger boat.” Lacking such a “bigger . . . ​[connectome mapping? functional neuroimaging?] . . . ​boat,” I ­will return to the new anatomical findings “hiding in plain sight” on Harvey’s old photo­graphs. Dean had been aware of Einstein’s omega sign, the knob-­shaped expansion of his right precentral gyrus, since 2009,79 but we now had four additional photo­graphs to confirm this finding.80 It is said

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that in life you ­can’t be too rich or too thin, but in scientific research you c­ an’t get too much confirmation from (in our case, photographic) data. One photo­graph beautifully demonstrated that Einstein’s cortical knob was larger on the right precentral gyrus and smaller on the left (Figure 5.5).81 This fit nicely with the previously cited study of larger cortical knobs found in the right hemi­spheres of string instrument players.82 As an aside, we have a ­great deal more to learn about the primary motor cortex that resides in the precentral gyrus. The classic Wilder Penfield map of the motor homunculus (Figure  3.1)83 that correlates hand and fin­ger control with a specific portion of the precentral gyrus about two-­thirds of the way between the Sylvian fissure, which sets the uppermost boundary of the temporal lobe, and the “top” of the hemi­sphere is overly simplistic. About one-­quarter of the total length of the precentral gyrus is devoted to the hand and the fin­gers (elongated segments of right and left precentral gyri control the left and right hands, respectively). When Penfield stimulated the hand and fin­gers portion of the primary motor cortex of awake patients undergoing epilepsy surgery, he found that up to five volts applied via bipolar electrodes elicited flexion and extension of the contralateral hand and fin­gers. An impor­tant lesson for clinical localization is that the primary motor cortex controls movements and not individual muscles. We presume that when the digits of Einstein’s left hand w ­ ere pressing on the fingerboard of his violin, neurons in his right cortical knob ­were discharging. However, we still ­c an’t tell you which discrete group of neurons was governing the contraction of his flexor digitorum profundus as it was was crooking his left pinky against the violin’s strings. Of course, fin­ger movements are not ­music. The motor “programs” under­lying Einstein’s per­for­mance of Brahms’s G-­major violin sonata are neuroanatomically “upstream” from his motor cortex. A precise localization of where his or anybody ­else’s ­music “lives” is unknown. (You d ­ idn’t ­really think neuroanatomy would be that ­simple, did you?) The left frontal lobe also revealed an expanded rectangular area of cortex just below the precentral sulcus that had been displaced



The Exceptional Brain(s) of Albert Einstein 103

Figure 5.5. Looking down on the dorsal surface of Einstein’s brain demonstrates the poles of the frontal lobes (top) and the tips of the occipital lobes (bottom). The central sulcus (Central s.) separates the frontal lobes from the parieto-­occipital lobes and nicely illustrates the relatively greater volume of the frontal lobes compared to the other lobes in ­humans (and not just Einstein). The right cortical knob looks like an inverted letter omega abutting the central sulcus. The left cortical knob on the anterior borders of the central sulcus demarcates the smaller motor repre­sen­ta­tion of Einstein’s right hand. (Harvey Collection, National Museum of Health and Medicine.)

“extraordinarily high above the Sylvian fissure.” This effectively increased the amount of motor cortex devoted to the right face and tongue, as pictured in Penfield’s homunculus cartoon.84 This expanded region bordered the diagonal sulcus, which, remarkably, was found in both of Einstein’s hemi­spheres (and is typically a unilateral finding in normal brains). In front of (rostral in anatomical argot) the diagonal sulcus is the pars triangularis, a patch of cortex that subserves the production of language (by speech, writing, and

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signing) and which contains a major portion of Broca’s area. For over 95 ­percent of humankind (99 ­percent of right handers and two-­thirds of left handers), Broca’s area in the left hemi­sphere is dominant for expressive language or speech.85 Einstein’s left pars triangularis was found to be unusually convoluted compared to its fellow in the right hemi­sphere, and this finding goes hand in hand with the greater anatomical complexity of Broca’s area. It would not be unreasonable to expect that this anatomical “upgrade” in Einstein’s brain of the speech area and the face/tongue motor cortex would lead to greater fa­cil­i­t y in expressing language. Paradoxically, ­family lore surrounding Einstein’s childhood argues that this was clearly not the case. Einstein did not begin speaking ­until ­after he was two years old, and when he did it was with a kind of echolalia in which he would softly whisper the words or sentences prior to uttering them aloud.86 If Einstein’s delay in language acquisition was a form of aphasia, most neurologists (including me) would have anticipated the destruction (and not the expansion) of Broca’s area in the left frontal lobe. In a related clinical phenomenon, c­ hildren who become aphasic w ­ ill “switch” the dominance for language from the damaged left hemi­sphere to the right hemi­sphere and become left-­handed in the pro­cess. Such a switch did not occur with Einstein, who was right-­handed, and his expanded and convoluted pars triangularis does nothing to unravel the mystery of his abnormal speech development. Any discussion of parietal lobe anatomy (including our new findings) must be tempered by the remarks of Macdonald Critchley, who devoted an entire book to the topic and stated: “The bound­ aries of the parietal lobe are not altogether satisfactory and that the exact surface-­a rea is often a m ­ atter of conjecture.”87 Gerhardt von Bonin, one of the anatomists who received slides from Thomas Harvey, wrote that “the parietal lobe has at least two spheres, the somatosensory and the parietal association areas, what­ever that may mean.”88 If your wedding ring fits a l­ittle too loosely on your left ring fin­ger, the parietal somatosensory cortex on the right postcentral



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gyrus is activated. Penfield convincingly demonstrated that kind of straightforward localized neurophysiology. However, the perception or consciousness of the loose ring ­can’t be reduced exclusively to the ­simple neurophysiology of action potentials originating in the neurons of the postcentral convolution. Is my feeling, or qualia, of a not-­so-­tight ring the same as yours? The solution to that “hard problem”89 is unknown and is at the root of the profound mystery of consciousness. As long as we hug the coast of sensory neurophysiology and do not sail into the deeper w ­ aters of consciousness, von Bonin’s sphere of parietal somatosensory cortex remains a ­simple proposition. This is not so for the parietal association areas that lie further back (caudal) from the postcentral gyrus. In contrast to the postcentral gyrus, which is unimodal, parietal association cortex is heteromodal and receives inputs from ipsilateral—­t hat is, in the same hemisphere—­ frontal, temporal, and occipital lobes (and from the contralateral hemi­sphere by way of corpus callosum connections).90 This is an inconceivably busy neural crossroads that (especially the superior parietal lobule) constructs maps of our body and extrapersonal space (which in Einstein’s case may have encompassed space-­time). And I almost forgot: the posterior parietal cortex (and the dominant inferior parietal lobule in par­tic­u ­lar) is critical to the understanding of spoken and written language, per­for­mance of mathematical calculations, as well as the interpretation and manipulation of symbols.91 Harvey’s “lost” photo­graphs revealed new and unsuspected anomalies of Einstein’s parietal lobes in the regions previously discussed. The unimodal postcentral gyrus was markedly expanded on the left, parietal heteromodal cortex covered (opercularized) the under­lying insular cortex definitely on the left and likely on the right, the inferior parietal lobule was larger on the left, and the superior parietal lobule was markedly larger in the right hemi­sphere. The presence or absence of parietal opercula hinged on the continuity of the ascending branch of the Sylvian fissure with the postcentral

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sulcus. If t­hese sulci (which join at right a­ ngles to each other) are not continuous, the anatomists declare the presence of opercula. Witelson found that the two fissures ­were confluent and therefore posited the “absence of the parietal opercula.”92 We strenuously objected and asserted that a submerged part of the supramarginal gyrus interrupted the course of the left Sylvian fissure-­postcentral gyrus system. How come? Easy. Dean had access to the newly rediscovered Harvey photos that ­were ­either unavailable or ignored by Witelson. The difference in perspective of the individual photo­graphs cannot be overestimated. By way of comparison, my wife, Lynn, and I love to visit the ­Grand Canyon again and again, and we know that if we stand back from the trail along the South Rim at Mather Point we w ­ on’t see the ribbon of the dark-­green Colorado River cutting through the Vishnu Schist over a mile below us. As we get closer to the edge of the South Rim precipice, the river comes into view at the canyon bottom. Similarly, the vantage point of one of Harvey’s photo­graphs (Figure 5.6) “looks down” several millimeters from the cortical surface to the bottom of the left postcentral gyrus. By closely examining this photo­ graph, Dean identified the submerged supramarginal gyrus hidden from view in Witelson’s published photo­graphs93 taken from more traditional right and left lateral views. Dean also unearthed submerged gyri in both diagonal sulci (Figure 5.6). Our access to additional photographic views allowed greater insight into Einstein’s cortical anatomy—­a nd the more we looked, the more we found! In short, we brought to light the difference between ­every lobe (frontal, parietal, temporal, and occipital) of Einstein’s brain and normal ­human neuroanatomy as set forth in the atlases of Connolly94 and Ono.95 Even the split-­brain views that revealed the medial surfaces of both hemi­spheres uncovered abnormal convolutions of the cingulate gyri curling around Einstein’s corpus callosum. Despite Dean’s exhaustive efforts to identify each and ­every gyrus and sulcus on the photo­graphs, some of the fissures found on the cingulate and postcentral gyri remain unnamed in the

Figure 5.6. Submerged gyri. Another of Harvey’s original 1955 photo­ graphs shows Einstein’s left hemi­sphere from a slightly dif­fer­ent perspective than the left lateral picture that Witelson used). In this photo the frontal lobe is nearer to (and the occipital lobe farther from) the film plane in Harvey’s camera. Dean Falk realized that this perspective opened up her view of the depths of the diagonal sulcus, d, and the posterior ascending limb of the sylvian sulcus, aS, allowing her to appreciate the previously unrecognized submerged gyri in both diagonal sulci (right not shown). Additionally, the vertically oriented linear structure (like an upright “rice grain” adjacent to label aS ) is an anterior part of the supramarginal gyrus. Falk observed that the lower part of the “rice grain” also descended deeper (on a scale of millimeters relative to the cortical surface) and provided anatomical evidence that the posterior ascending limb of the sylvian sulcus and the postcentral inferior sulcus, pti, ­were separate and not confluent, contrary to the lit­er­a­ture. Falk had established that Einstein did indeed have parietal opercula and unusual parietal lobe anatomy. (Harvey Collection, National Museum of Health and Medicine.)

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standard reference brain atlases. Th ­ ese map the cortical surfaces of thirty “White” and thirty “Negro” brains (Connolly) and twenty-­ five Eu­ro­pean brains (prob­ably—­it’s a Swiss study, but then again, Ono was Japa­nese) of unknown sex and age (Ono) in meticulous detail. Both studies focused on the sulci rather than the gyri. Ono, working with the Swiss neurosurgeon M. Yasargil, was charged with mapping the “corridors of the sulci and fissures” essential for performing microsurgical procedures.96 Writing in 1950, Connolly addressed the evolving fissural patterns of lemurs to anthropoids to ­humans and felt that the “size and gross structure of the brain” ­were not reflective of “intellectual capacities.”97 It is unknown ­whether Thomas Harvey was acquainted with Connolly’s cautious stance on “the descriptive reports on the brains of deceased scholars.” In the wake of our Brain publication, we ­were gratified with one referee’s appraisal that “this is a remarkable document describing in ­great detail the surface anatomy of Einstein [sic] brain in a way that has not been done before by any team of experienced anatomists and including new materials.”98 Prior to our study, it was well known that Einstein’s brain was no “bigger” and that his parietal lobes w ­ ere exceptional.99 Our new evidence established that the brain was not spherical in shape but had frontal and occipital bulges (petalias), that e­ very lobe had unusual sulci and gyri, and that the parietal lobes w ­ ere “opercularized.” David C. Van Essen has hypo­ thesized that axons in strongly interconnected brain regions may produce tension that keeps “wiring length short and overall neural circuitry compact.”100 This model suggests that the anomalous folds of Einstein’s cortex may reflect variant white m ­ atter connections and novel axonal architecture. In September 2013 we would see this intriguing hypothesis put to the test.

The “Callosal” Brain Physicists are fascinated by the brain. Right up t­here with quantum mechanics and the big bang, the brain holds its own as one of the ­Great Mysteries, which is irresistible to ­people who follow the



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runs of the Large Hadron Collider with the same intensity as football fans who follow World Cup matches. Eminent scientists who have divided their efforts between physics and neuroscience include Sir Roger Penrose, the mathematical physicist who rejects the notion that thinking is “the action of some very complicated computer”101 and proposed that consciousness arises from quantum gravity effects in the microtubules of the neuronal cytoskeleton.102 A few blocks (not allowing for the athletic fields and a few Gothic quadrangles) from where I’m writing this, Sebastian Seung, formerly on the Mas­sa­chu­setts Institute of Technology (MIT) physics faculty and now a professor at the Neuroscience Institute of Prince­ton University, is attempting to make the leap from reconstructing tiny volumes of neural circuitry in the mouse ret­ina to the complete connectome of a mammalian brain. And that brings us to Weiwei Men, who since his teens has revered Einstein. Dr. Men worked as a postdoctoral physicist at the Shanghai Key Laboratory of Magnetic Resonance at East China Normal University. He realized that among the fourteen photo­ graphs in our paper ­were two of the medial surfaces of the bisected brain that showed a cross section of the corpus callosum with g­ reat resolution and accuracy (Figure 5.7). Dr. Men enlisted Dean’s assistance for a study comparing the mea­sure­ments of Einstein’s corpus callosum with ­those of control groups of fifteen age-­matched and fifty-­t wo younger (aged twenty-­four to thirty years) living men.103 The term mea­sure­ments does not begin to describe the methodology of comparing the analog data from Harvey’s photo­graphs to the digital data from Dr. Men’s MRI brain scans of his control group. How do you adjust for the dif­fer­ent scales of Harvey’s eight-­ by-­ten prints and the MRI images? The shrinkage and distortion of formalin-­preserved neural tissue versus the living brains of the controls? The asymmetry of a corpus callosum cut in half by a pathologist’s “brain knife” versus the virtual bisection of brains created by the data acquisition par­ameters of three dif­fer­ent MR scanners? The nuts and bolts of Men’s methodology alone required five pages in both his Brain paper and his supplementary material!

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Figure 5.7. Einstein’s bigger corpus callosum is apparent on the cut medial surface of the left hemi­sphere, with Harvey’s original labels of the bisected brain ­after removal of the cerebellum and brain stem. The frontal lobe is on the right, and the occipital lobe is on the left. The medial surface of the left hemi­sphere displays the sulci of the frontal, parietal, and occipital lobes. At the center the flattened arc of the bisected white ­matter of the corpus callosum appears lighter than the surrounding cortical gray ­matter. Weiwei Men found that Einstein’s corpus callosum was larger than ­those of sixty-­seven younger and age-­matched controls. (Harvey Collection, National Museum of Health and Medicine.)

Why is the corpus callosum impor­tant? Well, for starters it’s big. It’s the largest white ­matter bundle in the ­human brain and contains over two hundred million axons connecting the right and left hemi­spheres. Although “size does ­matter” in biology, the functional importance of the corpus callosum in h ­ umans was not confirmed ­u ntil the 1960s. Twenty years earlier Akelaitis and Van Wagenen had found that complete transection of the callosum in patients treated for intractable epilepsy produced “no behavioral or cognitive



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effects.”104 As discussed in chapter 3, Michael Gazzaniga’s study of the split-­brain patient W. J. rewrote our understanding of the functional neuroanatomy of the corpus callosum.105 In short, Gazzaniga found that “the h ­ uman brain produced two separate conscious systems” in 1962.106 At the time Gazzaniga was a gradu­ate student in Roger Sperry’s lab at the California Institute of Technology (Cal Tech), and two de­c ades l­ater, in the time-­honored academic tradition of “winner (or in this case, lab chief ) take all,” Sperry went on to receive the 1981 Nobel Prize for ground-­breaking discoveries of the functional specialization of the ce­re­bral hemi­ spheres. Gazzaniga went on to further characterize the startling hypothesis of two minds residing in one brain. This is not as unexpected as you might think. For most of humanity, the capacity for language a­ fter the first few years of life is hard-­wired (less “plastic”) in the left hemi­sphere. We can only guess at how thinking is “transacted” in the right hemi­sphere that lacks innate language. Ergo, the two hemi­spheres are functionally (and anatomically) very dif­fer­ ent. In split-­brain patients, Gazzaniga found that the left hemi­sphere provided logical explanations for right-­handed picture matching but offered implausible explanations for matches performed by the left hand. In this experiment the left hemi­sphere was blind to pictures viewed by the right hemi­sphere, which could not transfer visual information across the severed corpus callosum. As a result, the left hemi­sphere was dubbed “the interpreter”107 and concluded to be “capable of logical feats that the right cannot manage.”108 It requires very specialized experimental techniques to ferret out the altered be­hav­ior of postsurgical split-­brain patients, but what about patients who are born without a corpus callosum? Some patients with this condition—­agenesis of the corpus callosum (ACC)—­can have normal intelligence with subtle neuropsychological defects that are never detected during their lifetimes. O ­ thers are clearly abnormal: Kim Peek, the real-­life inspiration for the film Rain Man, had ACC and savant syndrome characterized by a photographic memory and virtuoso mathematical ability. Both acquired (surgical)

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and congenital defects of the corpus callosum provide varied and fascinating glimpses of abnormal callosal function, but what are the consequences of “supernormal” callosal operations? With more than a half ­century’s revelations about the cognitive science of the corpus callosum as a backdrop, what did Dr. Men’s examination discover? At 1,230 grams, Einstein’s brain was no larger than average . . . ​­t here, I’ve said it again. But his corpus callosum was larger than both young and old controls in seven (out of ten) dif­fer­ent mea­sure­ment categories. The under­lying assumption was that increased callosal area indicated a greater number of axons crossing through the corpus callosum. (Alternative hypothesis alert! You could have a lesser number of axons crossing through an enlarged corpus callosum if they w ­ ere hypertrophied, i.e., big and fat like a squid’s g­ iant axons. This is the way scientists and persnickety reviewers are supposed to think.) One reasonable implication of having a brain of average (or less) size and a corpus callosum of above-­average size is that Einstein had greater neural interconnectivity, or “internal wiring,” than a normal ­human. Einstein’s cortex (gray ­matter) and microscopic cell counts (neurons and glia) had been examined since 1955, but no one prior to Men had performed a scientifically rigorous examination of the largest white ­matter bundle in the brain. This was not Dr. Men’s first neuroanatomical “rodeo.” In his 2013 doctoral dissertation, he devised MRI templates to compare the “wider, higher, and rounder” brains of 120 Chinese with the “longer” brains of 120 Caucasians. The Chinese cohort’s corpora callosa had thicker “front ends” (genu and rostrum) and “back ends” (splenium). No statistical difference between the volumes of Chinese and Caucasian brains was found.109 Applying his methodology to Einstein’s brain, Men was quick to point out that the corpus callosum is not a uniform structure but has regional differences with impor­tant functional implications. Anteriorly, Einstein’s rostrum and genu ­were thicker than ­those of the young and old controls. This callosal region connects the right and left orbital gyri and prefrontal cortices and could conceivably carry greater neural traffic



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between the expanded prefrontal cortices that we had found. Einstein’s callosal midbody linking primary motor and sensory cortex and other parietal lobe regions was thicker, possibly to accommodate a greater interhemispheric transfer of information from Einstein’s omega-­shaped motor cortex knobs and enlarged left motor and sensory (subserving face and tongue) cortices. Bringing up the rear, the splenium is a conduit for neural data between the parietal, temporal, and occipital lobes. The greater bulk of Einstein’s splenium could permit greater integration of output from Einstein’s bigger left inferior and right superior parietal lobules. As Dr. Men and all academics know full well, the editorial pro­ cess is invariably a roller-­coaster ­ride. One referee commended the paper for opening “a new aspect of the study of the Brain of an individual of g­ reat significance for the scientific community and one might say humanity as a ­whole.”110 The editor of Brain was more circumspect. The paper would be accepted with minor revisions, but fearing that two papers on Einstein (ours and Men’s) might ever so slightly transform one of the g­ reat periodicals of neuroscience into a Journal of Einstein Brain Studies, he sensibly advised the authors to wrap any additional findings about Einstein’s brain “into this second communication” rather than submitting a third manuscript (and trying for an Einstein brain “hat trick”). Editorial vicissitudes aside, Dr. Men has approached his research in neuroimaging with infectious enthusiasm and wants to work with MRI and functional MRI “forever.” He has moved nine hundred miles northwest to Peking University, where as a postdoc he is expanding his dissertation’s database with MRI images of two thousand young Chinese ­people.111 Men’s mea­sure­ment technique used four hundred points along the top and bottom edges and the longitudinal m ­ iddle lines of the corpora callosa of Einstein and sixty-­seven controls. Its impact was immediately apparent in the precision of his computer-­generated callosal thickness plot and distribution maps. For example, Men mea­sured the average midsagittal cross-­sectional area of Einstein’s corpus callosum at 7.72 cm2, significantly larger than the controls’

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6.69 cm2. This contrasts with the caliper mea­sure­ments recorded by Thomas Harvey in 1955 and published in Witelson’s paper. The average area of Einstein’s corpus callosum was 6.8 cm2, which is nonsignificantly smaller than the 7.0 cm2 of her thirty-­five controls.112 Dr. Men’s improved method of mea­sur­ing provided a very dif­fer­ent and more detailed picture of Einstein’s corpus callosum, and the hypothesis of Einstein’s greater interhemispheric connectivity was firmly grounded in his robust data. It is ironic that Witelson had produced a rigorous and superb body of work on corpus callosum anatomy for over a de­cade before she studied Einstein’s brain.113 For t­ hose impor­tant studies on callosal anatomy and its implications on hemispheric interconnectivity and specialization, she had employed postmortem brain dissection, tracings from brain photo­ graphs, and digitizing morphometry software. In contrast, when studying Einstein’s corpus callosum, she relied on second­hand caliper mea­sure­ments from forty-­four years earlier. We can only surmise that discovering the exceptional anatomy of Einstein’s parietal lobes eclipsed any thought of a meaningful variation of his callosal anatomy. Intended or not, Dr. Witelson’s oversight was to become Weiwei Men’s scientific gain. Nearly a ­century before the advent of digitally acquired morphometric data, Dr. E. A. Spitzka (1876–1922) found the association between genius and a larger corpus callosum. Spitzka, the physician who examined the autopsied brain of the assassin of President William McKinley, wrote a monograph-­length article on his study of the brains of “six eminent scientists and scholars” in 1907.114 In chapter 3 I have previously remarked on Spitzka’s readiness to leap across the yawning chasm that separates neural structure from function. He used a “new criteria of brain mea­sure­ment and fissural pattern” to study six eminent members of the American Anthropometric Association who gave consent to the postmortem examination of their own brains. Spitzka found that the brains of men “possessing large capacity for d ­ oing and thinking . . . ​[when] compared with ordinary men individually and collectively [the ‘doers and thinkers’] have larger callosa.” Spitzka did data mining on the



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left-­sided slope of the bell-­shaped curve of ­human intellect by using illiterate laborers for comparison. Some readers (including me) might take exception to his use of murderers “executed by electricity” for “normal brains.” He concluded that the size of the corpus callosum was “an index in somatic terms” for distinguishing elite brains. At its best, science is an accumulation of data points that can amass, if need be, over centuries. Hypotheses can change, but good and plentiful data should be the constant from which science reframes its theories. Over a ­century ­after Spitzka’s speculative pronouncement about the corpus callosum of eminent scientists and scholars, Dr. Men added a crucial mea­sure­ment. And w ­ e’re still learning. We can only guess at what neuroscientists a ­century hence ­will consider received wisdom about the corpus callosum and the connectome.

chapter 6

How Does a Genius Think?

The best we can say is that Einstein had the right mind at the right moment to crack a collection of deep prob­lems of physics. And what a moment it was. His numerous but comparatively modest contributions in the de­cades ­after the discovery of general relativity suggest that the timeliness of the par­tic­u­lar intellectual nexus he brought to bear on physics had passed. —­b rian greene, Scientific American For the essential in the being of a man of my type lies precisely in what he thinks and how he thinks, not in what he does or suffers. —­a lbert einstein

As I write this, it is easy to acknowledge the staggering accretion of information about the brain since Cajal framed the neuron doctrine in the years leading up to his Nobel Prize in 1906. The foregoing chapter considered Einstein’s brain as an anatomical specimen. By necessity we turned off the well-­traveled road of con­temporary neuroscience, which has made incredible breakthroughs by employing reductionist techniques from voltage clamp recordings of single-­ axon action potentials to mapping the relatively ­simple (302 neurons) ner­vous system of the roundworm Caenorhabditis elegans. Mind or consciousness is likely related to the complexity of the ner­vous system.1 And ner­vous systems, barring an evolutionary or CRISPR (clustered regularly interspersed palindromic repeats—­a cutting-­edge technique of genomic manipulation) ge­ne­tic engineering leap in the distant f­ uture, prob­ably do not come in much more complex packages than Einstein’s brain. As it stands, the preceding 117

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descriptions of Einstein’s neurohistology and gross neuroanatomy are fairly definitive . . . ​for this moment in time. Other than a few tantalizing glimpses of the structural under­pinnings, such as the motor cortex knobs, of brain function, I cannot hope to extra­ polate Einstein’s ce­re­bral structure into the realms of thought or be­hav­ior. The best I can do is to explore a sampling of Einstein’s feats of mind while conceding that we are a long, long way from specifying how his exceptional neuroanatomy functioned. As I describe a few well-­k nown high points of Einstein’s intellectual landscape, ­these scattered landmarks w ­ ill not convey a faithful portrait of Einstein as a man and a scientist. Let me repeat that it has been my intention to write a “biography of a brain.” It is my fervent hope that this disjointed and anecdotal recounting of Einstein assembling his intellectual tool kit (or epistemology) might just possibly circle back to what t­ hose fading photo­graphs told us about his brain. We s­ hall see. Readers seeking a multifaceted portrait of Einstein should turn to the works of far better biographers than I. In par­tic­u­lar, the books of Ronald Clark,2 Banesh Hoffman,3 and the magisterial study by Walter Isaac­son4 provide compelling accounts of Einstein’s life, world, and science. At the outset of his intellectual journey, it must be acknowledged that Einstein was a smart kid.5 His delay in language acquisition and the temper tantrums aimed at his ­sister Maja or his tutor w ­ ere developmental “bumps in the road” that did not hold him back. Fortuitously, Albert was raised in a technologically ­adept ­family—­his ­father and u ­ ncle’s com­pany ran dynamos that lighted the suburbs of Munich in 1885. (A system of electricity distribution or “utility” that was both a brand new and scientifically sophisticated technology; the Edison Illuminating Com­pany had just begun using direct current to light the streets of Lower Manhattan and London in 1882.) Given his f­ amily’s scientific inclinations, it is no surprise that when Einstein was four or five years old his f­ ather, Hermann, showed



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him a compass. Sixty-­t wo years l­ater in his Autobiographical Notes, in which he was writing “something like my own obituary,” Einstein recalled his astonishment when the compass needle moved in a “determined way” not connected with “direct ‘touch.’ ”6 This experience made a “deep and lasting impression” that “something deeply hidden had to be b­ ehind ­t hings.” The unexpected be­hav­ior of the compass needle “did not at all fit into the nature of events . . . ​in the unconscious world of concepts.” This cognitive conflict was experienced as “won­der” by young Albert. His capacity to won­der in the face of the unknown, the mysterious, the discordant, and the unexpected would never leave him—­twelve pages of equations w ­ ere found at his hospital bedside on April 18, 1955.7 Among his playthings as a child ­were Anchor Stone blocks (Anker-­Steinbaukasten), from which he erected “complex structures,” according to his s­ ister Maja. The brainchild of Friedrich Froebel, innovator of the kindergarten system, t­hese blocks of quartz sand, chalk, and linseed oil w ­ ere im­mensely popu­lar, and forty-­t wo thousand sets sold in 1883 alone. The Lego toys of their day, t­ hese multicolored composite stones came in over one thousand shapes (Figure 6.1). It is intriguing to speculate w ­ hether ­these solid geometrical playthings ­shaped young Albert’s imagination and prepared the way for his next intellectual North Star in 1888, when at the age of twelve “a ­little book dealing with Euclidian plane geometry . . . ​c ame into my hands.”8 Einstein was in good com­pany—­Euclid also heralded an intellectual coming of age for the eleven-­year-­old Bertrand Russell, whose encounter with the Ele­ments “was the first time it had dawned upon me that I might have some intelligence.”9 The “lucidity and certainty” of the euclidean proofs “made an indescribable impression upon me.”10 Six de­c ades l­ater Einstein mused over the marvel that “man is capable at all to reach such a degree of certainty in pure thinking as the Greeks showed us for the first time to be pos­si­ble in geometry.” The objects of geometry seemed more “real” than abstract thoughts and “no dif­fer­ent” than

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Figure 6.1. Einstein’s building blocks. A box of Anchor (Anker-­Steinbaukasten) stone building blocks like the ones Einstein played with as a child. They ­were manufactured in Rudolstadt, Germany, from 1880 to 1963 and ­were among the toys of Max Born, J. Robert Oppenheimer, and Walter Gropius. (Photo by Frederick E. Lepore, 2017.)

“direct” sensory impressions. (Direct is a loaded term to a neurologist whose bedrock assumption is that our [for example, visual] access to the real world “out t­ here” follows a circuitous route of neural pro­cessing/filtering via ten layers of sensorineural ret­ina to six layers of lateral geniculate body to six layers of primary visual



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cortex to paraoccipital visual cortical areas with innumerable feedback and feedforward connections interspersed. Whew!) Einstein would grapple all his life with the mystery of how man’s intellect imposed order on the chaos of the universe (and its “totality of sense-­experiences”). Long a­ fter his infatuation with Euclid, Einstein described his very slowly evolved “epistemological credo.”11 A “logical system of thought,” such as physics,12 came face-­to-­face with a gaping chasm between “on the one side the totality of sense-­ experiences, and, on the other, the totality of the concepts and propositions which are laid down in books.”13 The thinking of the scientific mind seeking to grasp the relationship of physics to real­ ity was a topic that drew Einstein as a thirteen-­year-­old to the writings of Immanuel Kant (and ­later David Hume). This fascination with epistemology never left him, and he would return to the wondrous realization that “certain truths could be discovered by reason alone”14 repeatedly in his l­ater writings.15 At the end of this chapter, Einstein w ­ ill speak about his own par­tic­u­lar variety of comprehension, but for the pres­ent we w ­ ill return to his early intellectual explorations. Even before he encountered “the holy geometry booklet,” Einstein set about “proving” the Pythagorean theorem (with his u ­ ncle providing a proper introduction). Einstein left no specific rec­ord of his childhood proof, but the physicist Manfred Schroeder related a thirdhand account of the proof that most likely exploited the decomposition and additivity of right triangles. A ­later commentator on this fledgling exercise observed, “His instinct for symmetry, his economy of means, his iconoclasm, his tenacity, his penchant for thinking in pictures—­they’re all ­here, just as they are in his theory of relativity.”16 ­W hether this apocryphal proof was a harbinger of Einstein’s mature cognitive style remains an open and intriguing question. At age twelve Einstein’s “holy” regard for Euclid and “pure thinking as the Greeks showed us for the first time to be pos­si­ble in geometry”17 may have supplanted the “deep religiosity” of his nascent embrace of Judaism. A ­ fter reading popu­lar science books

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and being introduced to Kant and calculus by Max Talmud, a medical student who dined with the Einsteins each week, t­here was no turning back—­“Einstein avoided religious rituals for the rest of his life.”18 In their stead he declared, “I believe in Spinoza’s God who reveals himself in the orderly harmony of what exists, not in a God who concerns himself with the fates and actions of ­human beings.”19 When Einstein was six, Pauline Einstein saw to it that her son would begin violin lessons, and as he progressed she would accompany him on the piano. Although mechanically proficient when he began his lessons (the very least we would expect from the fretwork skills associated with the cortical knob found on Einstein’s right central gyrus!)20 at thirteen he fell in love with Mozart’s sonatas, and his technique improved as “­ music became both magical and emotional to him.”21 The lessons stopped the following year, but Einstein avidly played the violin for the rest of his life, often when seeking solutions to questions of theoretical physics. Unusual cortical anatomy notwithstanding, in his l­ater years, “as he felt fa­cil­i­ty leaving his left hand,” Einstein “laid down his violin and never picked it up again.”22 In his Last W ­ ill and Testament, his beloved instrument was prominently cited and bequeathed to his grand­son, Bernhard Caesar Einstein. Not unexpectedly, legends abound surrounding young Albert’s classroom per­for­mance. In 1935, when asked about a “Ripley’s Believe It or Not!” column regarding an alleged failure in mathe­matics, Einstein averred that such a failure had never occurred and said, “Before I was fifteen I had mastered differential and integral calculus.”23 A pos­si­ble basis for the fable of flunking may be found in his inability to pass a college entrance exam for Zu­rich Polytechnic (­later the Swiss Federal Institute of Technology, or Eidgenossische Technische Hochschule [ETH]) as a fifteen-­year-­old dropout from Luitpold Gymnasium in Munich. His math and science results ­were satisfactory, but he fell short in lit­er­a­ture, French, zoology, botany, and politics. He was advised to spend the next year preparing at a progressive Swiss cantonal school in Aarau. As you may now surmise, Einstein’s early education was not characterized by a linear scholastic ascent.



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His creative intellect never flagged, but he encountered a few academic detours on the way to his annus mirabilis in 1905. I would like to say, “What a difference a year made” in Switzerland, but a few subgenius results when his final exams rolled around ever so slightly dimmed his scientific incandescence. His grades—on a scale of 1 (poorest) to 6 (excellent)—­were desultory in French (a 3) and average in geography (a 4) and technical drawing (a 4) when he took the Swiss matura (high school exit exam) at age sixteen. His math and physics grades w ­ ere uniformly excellent (each a six). He was now qualified to again sit for the entrance exams to Zu­rich Polytechnic, and this time his average was 5.5 (the best of the nine applicants taking the test), although French (appropriately) remained his běte noire. In October 1896 he enrolled at Zu­rich Polytechnic as one of eleven freshmen training to be specialized teachers in mathe­matics and physics. Zu­rich Polytechnic would become a world-­class university counting twenty-­one Nobel laureates among its students and faculty. The transition to college is challenging for any seventeen-­ year-­old (and possibly more so for a wunderkind), and Einstein’s undergraduate days ­were no exception. He was branded a “lazy dog” by his math professor, Hermann Minkowski; he flunked “Physical Experiments for Beginners”; and he was criticized for his “one ­great fault: (that) you’ll never let yourself be told anything” by the head of the physics department.24 We may well ask, “What did Einstein gain from his education in Zu­rich?” For starters he met his classmate Mileva Maric, whom he married in 1903 and divorced in 1919. He freely admitted that as a student he did not realize “that a more profound knowledge of the basic princi­ples of physics was tied up with the most intricate mathematical models.”25 (This shortcoming would become glaringly apparent in 1907 when he began to grapple with the non-­Euclidean geometry of space-­time for his theory of general relativity.) He received his bachelor of science degree in 1900, graduating fourth (out of five) in his section. And he “gained” poor job prospects.

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Einstein was never again to sit as an enrolled student in a university classroom. Ever the relentless autodidact, beginning in 1902 he wrote five research papers that w ­ ere published in the prestigious Annalen der Physik before his annus mirabilis in 1905.26 It is nearly inconceivable, from the perspective of the academic establishment over a ­century ­later, that an individual with only a bachelor’s degree and no doctoral or postdoctoral training or even access to a proper university library could presume to regularly publish in renowned peer-­reviewed journals . . . ​and shift the paradigm of known physics as well. And yet this is precisely what Einstein did. So much for a formal education. (Bill Gates did reasonably well without completing his Harvard bachelor of arts, so maybe the mandate for a college degree applies only to us lesser mortals.) Einstein kept food on his ­table as a private tutor, and it was not ­until 1902 that he landed a job in the Swiss Patent Office as a probationary technical expert class three of the Federal Office for Intellectual Property. The next year he vowed, “I s­hall not become a Ph.D. . . . ​the ­whole comedy has become a bore to me.”27 Einstein recanted, possibly in hopes of better job prospects, and on his second try for a doctoral thesis he submitted a reworking of his least well-­k nown paper from his annus mirabilis. Most scientific historians acknowledge the four masterworks of 1905 (papers on Brownian motion, light quanta, special relativity, and E = mc 2) but t­ here was a fifth: “A New Determination of Molecular Dimensions.” It passed muster as a doctoral thesis at the University of Zu­rich in 1905. Walter Isaac­son concluded that “even though it did not help him get an academic job, it did make it pos­si­ble for him to become known, fi­nally, as Dr. Einstein.”28 It would not be ­until 1908 that Einstein hired on as an academic, when he became a nonsalaried privatdozent at Bern University. His subsequent meteoric ascent to the academic stratosphere of theoretical physics was inevitable—­full professor by 1911 (Charles-­Ferdinand University in Prague), institute director by 1914 at the Kaiser Wilhelm Institute, full professor at the Humboldt University of Berlin, and winner of the 1921 Nobel Prize (bestowed in 1922). It almost becomes meaningless to list the



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further succession of “glittering prizes” and titles. It ­will come as no surprise that the man who considered the PhD pro­cess to be a bore left the academic prestige of Germany (with the storm clouds of Nazism on the near horizon) without a backward glance. By October 1933 he was a resident scholar at the three-­year-­old Institute for Advanced Study in Prince­ton, New Jersey. For the next twenty-­two years, he wrestled with such formidable prob­lems as the formulation of a unified field theory (or theory of every­thing) and the “incomplete” description of nature that he found at the root of quantum mechanics. The Institute for Advanced Study remains a world of ideas; a true Platonic heaven, if you ­will. Physical apparatuses w ­ ere abhorrent, and a­ fter John von Neumann’s death, the Institute regulars sanctimoniously transferred his electronic computer, replete with seventeen hundred vacuum tubes, to the Smithsonian Institution in 1958.29 Einstein’s brand of laboratory-­f ree science fit right in and raised no institutional hackles ­because he had no need for the mid-­ twentieth-­century equivalent of a Large Hadron Collider to ply his trade. (Observing an eclipse in 1919 would suffice to confirm his theory of general relativity, but he could outsource the telescopic photo­ graphy to Arthur Eddington.30) A piece of chalk and a blackboard ­were all the equipment Einstein needed. His “experiments” sans technical equipment ­were conducted in room 115 in Fuld Hall or while walking with Kurt Gödel across the front lawn of the Institute for Advanced Study. At the time of his death in 1955, his light, airy office contained no apparatuses but rather a paper-­strewn desk, shelves of journals, and a blackboard covered with formulae. In short, Einstein’s true “laboratory” was his scientific mind, which he put to brilliant use for seventy-­six years. If I am to remotely hope to address the chapter heading’s question—­“How does a genius think?”—­the workings of Einstein’s thought laboratory warrant detailed scrutiny, and exhibit A is surely Einstein’s miracle year of 1905. It was a year that “in the annals of physics . . . ​ranks with the years 1665–66, when the plague that ravaged E ­ ngland forced Cambridge University to close and caused young Newton

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to leave Cambridge for his home in the quiet village of Woolthorpe, where—­all in secret—he developed the calculus, made major discoveries about light and color, and started on the path that was to lead him years l­ater to his law of universal gravitation.”31 Although the science of fin de siècle Switzerland differed vastly from the natu­ral philosophy (with a ­little alchemy thrown in for good mea­sure) of Restoration E ­ ngland, we w ­ ill to some extent ignore Einstein’s intellectual backdrop and train our sights on his gedankenexperiment. The gedankenkenexperiment has been around for a long time and was part of the intellectual tool kit of the ancient Greeks. Plato’s Dialogues recounts Socrates asking Meno’s slave boy how to find twice the area of a square. Through a series of skillful questions, the boy, who is untutored in geometry, discovers a successful answer using diagonal lines drawn within the original square.32 It is a pure thought experiment par excellence, and twenty-­four centuries ago, Socrates was in the same boat that I am ­today as he looked for the source of the knowledge-­producing thought experiment. For the unlettered slave boy, Socrates looked no further than the boy’s “immortal soul,” which “must have always possessed this knowledge.” With all due re­spect to the ancient Greeks, Socrates’s contention that “the truth of all t­ hings always existed in the soul”33 leaves me in the lurch as I flail away at framing Einstein’s thought experiments in a neuroscientific context. The initial use of gedankenexperiment (a German-­Latin hybrid term meaning an experiment conducted in the thoughts) is attributed to the Danish physicist Hans Christian Orsted (1777–1851). Located somewhere in the no man’s land between scientific empiricism and philosophical speculation, thought experiments have greatly added to the store of h ­ uman knowledge. They display the best aspects of the scientific method while lacking its observational data. Is this a contradiction? Not necessarily, if we recognize that scientific empiricism and gedankenexperiments do share some conceptual DNA. “The characteristic t­ hing about both real and thought experiments is that you control and limit the circumstances



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and conditions for the test, so as to pick out just one variable or one unknown. The key difference is that in the latter, every­thing is set out not in real­ity but merely in the imagination.”34 Sometimes, the line between real­ity and imagination is blurred. As far as we know, Galileo never actually climbed to the top of the Leaning Tower of Pisa to si­mul­ta­neously drop a cannonball and musketball, disproving the Aristotelian belief that heavy objects fall faster than light objects. Four centuries ­after Viviani’s hagiography, the fable of Galileo and the tower became scientific fact despite the under­lying real­ity that Galileo had fabricated “the most beautiful thought experiment ever devised.”35 As he demolished Aristotelian physics, Galileo made his observations not by ascending 296 steps to the top of the tower but by resorting to the tabletop physics methodology of timing balls rolling down an inclined plane. Do thought experiments “provide new knowledge” or “only pres­ ent old knowledge in a new way”?36 We learned that Plato favored the latter in the case of the slave boy, whose geometry problem-­ solving ability only needed to be “awakened into knowledge by putting questions to him” ­because his soul “must have always possessed this knowledge.”37 Taken to an absurd extreme, this is reminiscent of the assertion that if given infinite time a roomful of monkeys with typewriters could, by random chance, bang out Shakespeare’s plays. Certainly, the limitless permutations of rearranging the pre-­existent data contained in the eighty-­five to eighty-­ six billion neurons of the h ­ uman brain strongly argue that a­ fter infinitely “reshuffling the deck” of concepts the end result, strictly speaking, would be derivative, and no truly new idea would see the light of day. However, in my unnuanced philosophical opinion, once in a ­great while an electrifyingly original concept comes along to shift the paradigm, and it is so revolutionary that it seems to be a one-­of-­a-­k ind and first-­ever discovery rather than an ingenious reworking of preexistent concepts. In the words of Thomas Kuhn, such a paradigm is “sufficiently unpre­ce­dented to attract an enduring group of adherents away from competing modes of scientific activity  [and] . . . ​sufficiently open-­ended to leave all sorts of

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prob­lems for the redefined group of prac­ti­tion­ers to resolve.” 38 The theory of special relativity and the theory of general relativity nicely fit Kuhn’s definition, and as we s­hall see, both arose from Einstein’s gedankenexperiments. The world’s, let alone the scientific world’s, attention was riveted by the unparalleled revolution in man’s comprehension of the universe in 1905 (special relativity) and again in 1915 (general relativity). The theory of general relativity remained unproven and exclusively inhabited the realm of Einstein’s thought u ­ ntil he correctly calculated the precession (the minimal rotation of the points nearest and farthest from the sun) of Mercury’s elliptical orbit in 191539 and more dramatically when astronomer Arthur Eddington made the first confirmatory observations of “bending” starlight during a total solar eclipse on May 29, 1919. The usually staid New York Times proclaimed, “Lights All Askew in the Heavens. Men of science more or less agog over the results of eclipse observations.”40 General relativity was a discovery sui generis and not an invention scrabbled up from Einstein’s disor­ga­nized memories. Einstein had discovered something the mind of man had never previously conceived or observed just as surely as Clyde Tombaugh was the first to recognize a planet (­later dwarf planet) averaging 3.67 billion miles from the sun—­Pluto. As Eddington found, the deflection of rays of starlight around the sun calculated using the theory of general relativity was an external real­ity accessible to any observer, not just within the “laboratory” of Einstein’s mind. Given the theory’s predictive powers, Einstein’s under­lying thought experiment (to be described in detail l­ater) is readily regarded as the discovery of something in­de­pen­dent of the mind of man and not an abstract invention. The issue of the thought experiment as “discovery versus invention” is far from resolved by phi­los­o­phers of science,41 and Einstein’s gedankenexperiments may be special cases in which thoughts take on an aspect of “real­ity.” As we review some of Einstein’s virtuoso thought experiments, I leave it to the reader to validate or reject their external real­ity for her-­or himself.



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A study of the “how” of Einstein’s thought experiments ­will hopefully lay bare some of the workings of his coruscating intellect, and coincidentally, t­ hese century-­old gedankenexperiments may not be period pieces relegated to the dustbin of the history of science. The role of thought experiments may become increasingly influential in our pres­ent epoch of “unverifiable science.” A case in point would be superstring (or string, for short) theory, which is the leading candidate to provide a theory of every­thing that unifies all the forces of nature (electromagnetism, strong force, weak force, and gravity).42 Strings are proposed to be the fundamental structures of the universe. Heretofore, the universe was thought to be built of point-­like particles, but beginning in 1968 the oscillating filaments of string theory began to supplant this picture. The catch is that strings are almost unimaginably small . . . ​about one Planck length (10−33 centimeters). Descending down the known scale of atomic and subatomic magnitudes, a string would be smaller than an atom, a proton, a neutron, an electron, or a quark. As if the impossible size of strings w ­ asn’t enough to preclude scientific verifiability, the mathe­matics under­lying string theory requires eleven (ten space and one time) dimensions. Possibly, current technology might detect three-­dimensional “shadows” of higher dimensional objects, but the incredibly tiny size of strings remains an insuperable obstacle to verification. And so we ­can’t see, touch, taste, smell, or hear strings. ­There is no such t­hing as a string-­visualizing microscope or an accelerator that is sufficiently power­ful to directly reveal that a string is not a point particle.43 By sheer physical necessity, they may only exist in the realm of gedankenexperiments. Are unverifiable strings a description of real­ity (a loaded term to be sure)? I ­will studiously avoid a discussion of ­whether the compelling mathe­ matics of string theory is real in some kind of Platonic heaven, but my central point is that for now string theory (and for that m ­ atter, multiverses or the singularity at the inception of the big bang) remain critically impor­tant to our comprehension of the universe but approachable exclusively through thought experiments.

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Before we get to the annus mirabilis as a culmination and proof of concept of gedankenexperiments, let’s return to 1895 and the sixteen-­year-­old Einstein, who had defiantly left the Luitpold Gymnasium in Munich a year earlier. The “dropout” lived with his parents outside Milan, worked at the struggling ­family utility firm, and read extensively in Jules Violle’s Lehrbuch der Physik 44 (translated from the French into German in 1892 by Helmholtz’s assistants and a godsend for Einstein’s linguistic shortcomings). Most importantly, he returned to formal education at the cantonal school in Aarau, west of Zu­rich. The progressive educational philosophy of the school was a perfect fit for Einstein, and it was ­there that he wondered what he would see if in hot pursuit (nacheile) of a beam of light while speeding along at the same velocity of light, c, in a vacuum.45 Contrary to the popu­lar retelling of this juvenile thought experiment, Einstein never described “what it would be like to ­ride alongside a beam of light,”46 and his use of the term hot pursuit suggests that he (or his imagination) never could quite catch up with a light beam. In point of fact, objects with mass cannot attain the speed of light, thought to be in the neighborhood of 299,792,458 meters per second. Photons travel at the speed of light, but they have no mass. Infinite energy would be required for an object with mass, such as a sixteen-­ year-­old boy, to reach c, the speed of light. A subtext throughout his gedankenexperiments is that Einstein had unsurpassed intuitions for physical phenomena, and it may well be that ten years before he wrote E = mc 2 Einstein sensed the physical impossibility of drawing abreast of a beam of light. An impor­tant ele­ment in one type of thought experiment is the ability to invoke t­hings that can never happen (or counterfactuals in the parlance of phi­los­o­ phers). The counterfactual argument Einstein offered is that if he ­were speeding (impossibly) along at c he would perceive (wahrnemen) “such a beam of light as a spatially oscillatory electromagnetic field at rest.”47 This c­ an’t happen “since change is essential for a light wave; if e­ ither the electric or the magnetic field is static it w ­ ill not give rise to the other and hence ­there ­will be no electromagnetic



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wave.”48 Einstein was well aware that ­there was “no such ­thing” as “frozen” electromagnetic waves according to Maxwell’s equations. And for that ­matter, how does the h ­ uman eye detect a frozen (presumably immobile) massless photon? Answer: it ­doesn’t. The rod cells of the h ­ uman ret­ina can detect light when a single photon’s impact deforms the shape of a rhodopsin molecule (known as visual purple). The effect of light on the ret­i­nal pigments was discovered in 1876,49 and when Einstein said he would “perceive” rather than “see” a stationary beam of light, he may have deliberately based his choice of words on the rudimentary ret­i­nal physiology of his era. Visual physiology aside, Einstein was equally concerned that the observer of the immobile light beam would be unable to determine “that he is in a state of fast uniform motion.” At the end of the day, this par­tic­u­lar gedankenexperiment framed a paradox in which “the germ of the special relativity theory is already contained.”50 Malcolm Gladwell has pop­u ­lar­ized the notion of the “10,000 Hour Rule” in which “ten thousand hours of practice is required to achieve the level of mastery associated with being a world-­class expert—in anything.”51 Einstein’s youthful light beam paradox took ten years to attain the full maturity that would shake the very foundations of physics with the publication of “Zur Electrodynamik bewegter Korper”—­the opening salvo of the theory of special relativity in 1905.52 “And what’s ten years? Well, it’s roughly how long it takes to put in ten thousand hours of hard practice. Ten thousand hours is the magic number of greatness.”53 The theory of special relativity was well worth the ten thousand hours. It was “special” b­ ecause it applied to the special circumstance of inertial systems that moved at a constant velocity. (Another de­cade would elapse before Einstein could “solve” the prob­lem of accelerating systems with his theory of general relativity.) No advanced mathe­matics was required for the theory of special relativity; “high school algebra” sufficed. The intellectual challenge would arise from “the degree to which the ideas are foreign and apparently inconsistent with our everyday experiences.” To meet the

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challenge, Einstein had “to show precisely how one person’s mea­ sure­ments of distances and durations must differ from t­hose of another in order to ensure that each mea­sures an identical value for the speed of light.”54 To pry open Newton’s two-­century-­old grip on the conceptualization of space and time, Einstein’s now legendary and dramatic thought experiment required a “very long train travelling along the rails with the constant velocity v,” a railway embankment, an observer sitting in the train, two simultaneous lightning strokes, and an outside observer supplied with two mirrors inclined at ninety degrees to scan up and down the railway tracks at the same time.55 The choice of trains was no accident. The accurate scheduling of railway travel was a significant challenge in fin de siécle Eu­rope, and time coordination “was not merely an arcane thought experiment; rather, it critically concerned the clock industry, the military, and the railroads.”56 During the first three years of Einstein’s stint (1902– 1909) as a Swiss patent clerk, no fewer than thirty patents on electric clocks ­were granted. Electrosynchronization of the railways was a new marquee technology that posed a daily and real-­life prob­lem for Einstein. And it was no won­der that signal exchange, the speed of light, and train travel would be juxtaposed in his thought experiment. With the stage set and dramatis personae front and center, the thought experiment commences with the deceptively s­ imple question: If two lightning strikes at two separate places along the train line are “simultaneous with reference to the railway embankment,” are they “also simultaneous with reference to the train?” The meteorologically inclined passenger is seated precisely at the midpoint of the moving train, which just happens to be equidistant from the two spots where the simultaneous lightning bolts strike. The train is “hastening t­ owards the beam of light coming” from one bolt (bolt B) farther up the tracks and “riding on ahead of the beam of light coming” from the other bolt (bolt A) that struck b­ ehind the train’s last carriage. The light from bolt B ­will register on the train passenger’s ret­i­nas before the light from bolt A. ­Simple, right? Einstein



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concluded that “observers who take the railway train as their reference-­body must therefore come to the conclusion the lightning flash B took place earlier than the lightning flash A.” Th ­ ere is another side to this story, and it comes from the other observer situated on the embankment at a point equally distant from the two simultaneous lightning strikes. “The light rays emitted by the flashes of lightning A and B would reach him si­mul­ta­neously.”57 Einstein spelled out the impor­tant result of this instructive one-­ act play and linchpin of the theory of special relativity: Events which are simultaneous with reference to the embankment are not simultaneous with re­spect to the train, and vice versa (relativity of simultaneity). ­Every reference-­body (co-­ordinate system) has its own par­tic­u ­lar time; ­u nless we are told the reference-­body to which the statement of time refers, t­ here is no meaning of the time of an event.58

Time was not absolute, and it was dif­fer­ent for dif­fer­ent observers! That stunning theory was hard to swallow in 1905. It was still hard to swallow even in 1921 when the Nobel Prize Committee, finding that the “­whole issue was so encrusted with controversy,” circumvented the dispute by awarding Einstein the 1921 (accepted in 1922) Nobel Prize for the discovery of the law of the photoelectric effect, which was explained by Einstein’s mathematical description “assuming that light was absorbed and emitted in discrete quanta.” 59 (This scientific-­political compromise for the award was particularly ironic in light of Einstein’s l­ater voluble skepticism regarding quantum mechanical theory, which he regarded to his ­dying day as an incomplete description of physical real­ity.60) Although my discussion is confined to the railway gedankenexperiment, it and its formalized descendant—­the theory of special relativity—­shattered “our common-­sense, Newtonian concept of a universal time providing a universal simultaneity.”61 Although his reasoning (and mathematical proof ) w ­ ere rigorous, Einstein realized that the triumph of reason over experience in this par­tic­u­lar arena

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was “condemned to failure as long as the axiom of absolute time, viz., of simultaneity, unrecognizedly was anchored in the unconscious”62 (my italics). If Einstein actually knew the whereabouts of the unconscious (unbewussten) and its content of absolute time, he never let that par­ tic­u­lar cat out of the bag. It is no overstatement to attribute the discovery of the unconscious to Sigmund Freud, who Einstein personally knew and corresponded with. In essence, Freud proposed that “only a small content [of the mind] is embraced by consciousness at any given moment” and that “unconscious pro­cesses can only be observed by us u ­ nder the conditions of dreaming and neurosis” and (Freudian) “slips” of the tongue. The unconscious according to Freud was not an anchoring site for absolute time . . . ​far from it—­ the pro­cesses of the unconscious w ­ ere “timeless; i.e. they are not ordered temporally, are not altered by the passage of time, [and] in fact bear no relation to time at all.” In 1915 Freud conceded that the “­mental topography” of consciousness and the unconscious had “nothing to do with anatomy.”63 Freud’s inability to anatomically localize consciousness (and its counterpart, unconsciousness) has stood the test of time; over a c­ entury ­later, the neural basis of consciousness remains the Holy Grail of neuroscience. Not surprisingly, Einstein remained unconvinced of the validity of the psychoanalytic model of the mind, declining to be analyzed64 and twice refusing to support Freud for a Nobel Prize in medicine.65 The ac­cep­tance of the theory of special relativity (and its gedankenexperiment foundations) faced many obstacles at the outset, to be sure, but the content of Freud’s psychoanalytically derived model of the unconscious was not one of them. For the rec­ord ­there is no neurobiologic absolute timekeeper in h ­ umans. ­There is a circadian clock that regulates a multitude of bodily functions in a roughly twenty-­four-­hour cycle. The suprachiasmatic nucleus—­a group of roughly twenty thousand neurons located in the hypothalamus just above the optic chiasm (where the optic nerves cross)—­controls our circadian rhythm. As noted, the circadian clock does not keep absolute time; it must be regularly “reset” (entrained) by the daily



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cycles of night and day. Neural connections between the ret­ina and the suprachiasmatic nucleus via the optic chiasm allow light-­dark cycles to entrain the circadian clock. If the ­human circadian clock is exposed to an experimental environment where it is ­free r­ unning, the circadian day of twenty-­four hours and eleven minutes66 goes out of synchronization with the solar day, and each day the lab subject’s cycles of temperature regulation and hormonal (cortisol) secretion would occur eleven minutes ­later. As far as we know, ­there is no biological clock for absolute time as posited by Newton nor does it reside in the unconscious, as Einstein speculated. If we are incredulous about the profound implications of the theory of special relativity, ­don’t blame a (non­e x­is­tent) internal absolute timekeeper! Special relativity is simply a profoundly unsettling discovery that runs c­ ounter to our intuitions of “real­ity.” Even veteran physicist Brian Greene has averred that whenever he thinks about the relativity of space and time, “I am amazed. From the well-­ worn statement that the speed of light is constant, we conclude that space and time are in the eye of the beholder. Each of us carries our own clock, our own monitor of the passage of time. Each clock is equally precise, yet when we move relative to one another, the clocks do not agree. They fall out of synchronization.”67 Another arena where neurobiology and physics may lock horns is on the nature of the observer. In quantum theory the role played by the observer is not held to be passive, and that role raises profound philosophical questions. On the one hand, John Archibald Wheeler, paraphrasing Niels Bohr’s view of quantum real­ity, wrote, “No elementary phenomenon is a phenomenon u ­ ntil it is an observed phenomenon”68 and on the other Einstein scoffed, “Do you r­ eally believe the moon is not ­there when you are not looking at it?”69 Without the least flicker of remorse, I concede that I lack the physics/philosophy “chops” to resolve this quandary, which has been raging since Bohr and Einstein gracefully took up their quantum theory cudgels in the 1920s,70 but it is evident that the term observer in physics is shorthand for a single point of consciousness. When Einstein describes an “observer sitting” in a train traveling

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at constant velocity, that observer serves as a homogeneous and discrete viewpoint of sentience that happens to be moving relative to a similar observer standing on the railway embankment. So far, so good . . . ​except that as any neurologist w ­ ill tell you, the brain’s physiology has lots of moving parts, and brain function built up out of numerous sensory and motor subsystems, such as language, extrapyramidal and pyramidal motor systems, proprioception, vision, hearing, olfaction, memory, emotion, and much more is far from homogeneous. Our individual consciousness is frequently characterized as unified, but even that seemingly monolithic entity can be parsed, as in Gazzaniga’s split-­brain experiments in which the right and left hemi­spheres demonstrate very dif­fer­ent cognitive capacities (see chapter 5).71 Not only is the observer brain compartmentalized into cortical modules; for example, Brodmann’s fifty-­t wo areas (Figure 2.2), its circuitry does not permit instantaneous perception. A commonly used clinical test of vision, the visual evoked response (VER), mea­ sures the velocity of the signal that begins when a subject looks at a checkerboard pattern. It takes that electrical signal (made up of advancing neuronal action potentials) about one hundred milliseconds to traverse the central ner­vous system visual pathways, starting with the ret­ina and ending in the primary visual cortex—­a distance of (very) roughly sixteen centimeters. The signal moves along axons and multiple synapses at about 1.6 meters per second; however, the elapsed time of signal transmission may vary with the physical length of visual pathways in bigger and smaller brains, with the core temperature, with the complexity of the visual stimuli, and with the state of axonal myelination. The signal arriving at primary visual cortex is not accessible to consciousness. Conscious vision requires additional cortical pro­cessing (and more elapsed time) upstream of the primary visual cortex.72 Accordingly, designating an observer in Einstein’s railway thought experiment as an indivisible entity in an inertial framework presupposes that the only significant movement is that of a train carriage relative to the railway embankment. This oversimplification ignores both the complexity



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of neuronal physiology that occurs during an act of observation and the dynamic variation of the relative movements of neural signals within the observers’ central ner­vous systems. In this gedankenexperiment both interobserver and intraobserver movements occur, but the analytic insights of special relativity are not applied to the intraobserver/intracranial propagation of action potentials traversing the visual pathways. The equation single observer = single mind permits a simpler thought experiment but at the cost of unforeseen inaccuracies arising from not acknowledging neuroanatomy/ neurophysiology as the most likely basis of mind. (Again, my apologies [­really!] to the philosophical dualists who propose that brain cannot account for mind.) Physics in general and thought experiments in par­tic­u­lar seek to describe a real­ity that is deeper than what limited ­human sensory systems can access, and some of the sensory “biases” imposed by the ­human visual system and circadian clock have already been discussed. In a nutshell, it is very hard to transcend our sensory limitations, and for a very long time, this transcendence has been the demanding task of physics as it approaches the prob­lems of the Very Big and the Very Small. In 1640 Henry More, an En­glish phi­los­o­ pher and con­temporary of Isaac Newton, wrote “Sense pleads for Ptolemee.”73 Although Copernicus, with the unaided eye in 1543, and Galileo, with the telescope in 1610, both proposed a heliocentric system of the earth moving around the sun, More, who may have lived long enough to read the first printing of Newton’s Prin­ uman senses (unaided by a telecipia Mathematica, argued that h scope) would more readily embrace the venerable Ptolemaic system of geocentrism, in which the sun revolves around the earth. More, a Cambridge fellow, was not renouncing the new truths of scientific pro­gress. Rather, he was underscoring the narrow perspective of h ­ uman senses epitomized by Ptolemy’s not unreasonable conclusion that a­ fter watching the sun rise in the East, arc across the sky, and set in the West, it is the earth that is standing still, and it is the sun that moves. The epicycles of Ptolemy, gazing at the Alexandrian sky during the second ­c entury AD, sufficed to explain heavenly

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movements for the learned and unlearned alike for nearly a millennium and a half. Simply put, “seeing is believing,” but to advance our understanding of physical real­ity, the mind’s eye must look beyond the bound­aries imposed by the ­human senses. In the words of Thomas Carlyle, “To Newton and to Newton’s dog Diamond, what a dif­fer­ent pair of universes while the painting on the optical ret­ina of both was, most likely, the same!”74 Physics existed for Einstein in the realm of pure thought and was “an attempt conceptually to grasp real­ity as it is thought in­de­pen­ dently of its being observed.”75 Although not expressly stated, the narrow scope and fallibility of the ­human senses ineluctably led to Einstein’s reliance on gedankenexperiments and mathematical abstraction, which ­were best viewed by the mind’s eye. Where ­else could he envision overtaking a beam of light? Einstein’s use of his gedanken techniques required appropriate questions about the external world, and ­these soon arose in the wake of his completion of the theory of special relativity. In the words of Brian Greene: “And so, around 1907, Einstein became obsessed with the goal of formulating a new theory of gravity, one that would be at least as accurate as Newton’s but would not conflict with the special theory of relativity. This turned out to be a challenge beyond all ­others. Einstein’s formidable intellect had fi­nally met its match.”76 Einstein was fascinated by gravity and would remain so all his life. Greene cites three insistent gravitational questions that irresistibly attracted Einstein a­ fter his annus mirabilis: First, his theory of special relativity “completely ignored gravity.” Could a generalization of special relativity encompass gravity to demonstrate how ­matter creates the force we experience as acceleration? Second, gravity as Isaac Newton described it was a force that exerted its effects “instantaneously” throughout the extent of the universe. For Newtonian gravity to pervade the universe with immediacy would necessitate exceeding the velocity of light, and this would violate special relativity’s speed limit on c. And last, how does gravity exert action at a distance across the unimaginably vast reaches of space?



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­Those profound scientific questions set the stage for Einstein’s “happiest thought” (glucklichste Gedanke), prompted by witnessing a rooftop fall. Happiest may be a mistranslation on two counts: (1) ­There is nothing “happy” about watching an accident in pro­gress, and (2) glucklich can be translated from the German to mean “lucky” or “fortunate.” Given Einstein’s belief that scientific thinking was of the “nature of ­free play of concepts”77 and that the “connection” of the concepts of everyday thinking with sense experiences “can only be comprehended intuitively,”78 his description of the thought leading to general relativity as his luckiest allows us a glimpse of the role he assigned to chance in his thinking. Undoubtedly, t­ here is an ele­ ment of serendipity in many scientific breakthroughs, but we should not for a moment underestimate Einstein’s formidable combination of “seat of his pants” physical intuition and rigorous training in mathematical formalism. In the words of Pasteur, “Chance only favours the prepared mind.”79 And Einstein’s mind was superbly prepared by the instructive lessons of his f­amily’s electrical utility business, his bachelor of science degree from Zu­rich Polytechnic, and his seven years in the Swiss Patent Office. Einstein clearly had ­great self-­confidence in his intellectual abilities, and he never flinched in the face of acquiring fa­cil­i­ty with the complex mathe­matics of non-­Euclidean geometry and tensor calculus. Although possessed of this confidence, he could be preternaturally modest, and so when he speaks of his “luck,” we should take that remark with a grain of salt. Einstein’s unassuming approach to the competing goals of scientific fame and scientific discovery, leavened with a l­ittle luck, was nicely encapsulated by Walter Isaac­son: “Years ­later, when his younger son, Eduard, asked why he was so famous, Einstein replied by using another s­ imple thought experiment to describe his insight that gravity was the curving of the fabric of space-­time. ‘When a blind beetle crawls over the surface of a curved branch, it ­doesn’t notice that the track it has covered is indeed curved,’ he said. ‘I was lucky enough to notice what the beetle ­didn’t notice.’ ”80

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Back to the rooftop. As befits a g­ reat legend, some mystery surrounds it, and we ­don’t ­really know where the rooftop was. For that ­matter, where exactly on the grounds of Woolsthorpe Manor in ­England’s Midlands was Isaac Newton’s apple tree? The coordinates of both are well demarcated on the intellectual landscape (but are not to be found in a Baedeker Guide). In December 1919 Einstein told a New York Times correspondent that while looking out from the top floor of his fash­ion­able Berlin apartment he spied “a man dropping from a neighboring roof—­luckily on a pile of soft rubbish—­and escaping almost without injury. This man told Dr. Einstein that in falling he experienced no sensation commonly considered as the effect of gravity, which, according to Newton’s theory, would pull him down violently t­ oward the earth.”81 Einstein moved to Berlin in 1914 to become director of the Kaiser Wilhelm Institute of Physics, and in his 1919 interview, he recalled observing the man’s (a ­house­paint­er?)82 plummet “years ago.”83 Einstein told a dif­fer­ent story when lecturing at Kyoto University in 1922: “The breakthrough came suddenly one day. I was sitting on a chair in my patent office in Bern. Suddenly a thought struck me. If a man falls freely he should not feel his weight. I was taken aback. This ­simple thought experiment made a deep impression on me. This led to the theory of gravity.”84 In this version, it was a dif­fer­ent time (likely 1907), a dif­fer­ent place (Switzerland), and (unlike Wile E. Coyote contending with his archnemesis Roadrunner) nobody got hurt from the fall. Time and place notwithstanding, Einstein’s happiest (or luckiest) thought in 1907 led him to deeply consider the sensations of the falling man experiencing “the accelerated frame of reference.” ­There and then, Einstein seized the opportunity to extend the theory of “[special] . . . ​relativity to the reference frame with acceleration. I felt in ­doing so I could solve the prob­lem of gravity at the same time.”85 The falling man opened Einstein’s eyes to “the deep connection between gravity and accelerated motion,”86 and his course to the



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theory of general relativity was set for the next eight years. Along the way he constructed yet another compelling gedankenexperiment that proceeds along the following lines: Imagine “a large portion of empty space . . . ​far removed from stars and other appreciable masses.” Now “imagine a spacious chest resembling a room with an observer inside who is equipped with apparatus. Gravitation naturally does not exist for this observer. He must fasten himself with strings to the floor, other­wise the slightest impact against the floor w ­ ill cause him to rise slowly t­owards the ceiling of the room.” “To the ­middle of the lid of the chest is fixed externally a hook with rope attached and now a ‘being’ (what kind of being is immaterial to us) begins pulling at this with a constant force. The chest together with the observer then begins to move ‘upwards’ with a uniformly accelerated motion. In course of time their velocity ­will reach unheard-of values—­provided that we are viewing all this from another reference-­body which is not being pulled with a rope.” “But how does the man in the chest regard the pro­cess? The acceleration of the chest w ­ ill be transmitted to him by the reaction of the floor of the chest. He must therefore take up this pressure by means of his legs if he does not wish to be laid out full length on the floor. . . . ​The man in the chest w ­ ill thus come to the conclusion that he and the chest are in a gravitational field which is constant with regard to time. Of course he w ­ ill be puzzled for a moment as to why the chest does not fall in this gravitational field. Just then, however, he discovers the hook in the ­middle of the lid of the chest and the rope which is attached to it, and he consequently comes to the conclusion that the chest is suspended at rest in the gravitational field.”87

From his omniscient point of view as creator of this par­tic­u­lar gedanken universe, Einstein has inquired, “­Ought we to smile at the man and say that he errs in his conclusion?” Like Galileo’s Simplicio in Dialogue Concerning Two Chief World Systems, written three centuries earlier, the hapless man in the chest has been cast in the stock role of a not-­too-­bright onlooker/participant caught in

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physical phenomena beyond his ken. (This is doubly ironic b­ ecause the man in the chest was hurtling through “Galileian Space.”) Einstein has taken pity on the man in the chest and has conceded “that his mode of grasping the situation violates neither reason nor known mechanical laws.”88 In this elegant deep-­space exercise (with a ­little bit of scientific morality play thrown in for good mea­sure), Einstein has combined the observational vantage points of special relativity (namely ­those inside and outside the chest) with the interchangeabilty of acceleration and gravity. The man in the chest had come face-­to-­face with the equivalence princi­ple, which embodied the indistinguishability between accelerating velocity and gravity. When not reviewing patent applications (tragically, nearly all patent papers that Einstein pro­cessed ­were destroyed ­after eigh­teen years by the routine of Swiss bureaucratic efficiency),89 Einstein was preoccupied in 1907 with thoughts of men in chests or falling from rooftops. Their i­magined encounters with the force of gravitation and changing velocities blazed the trail that led the twenty-­ eight-­year-­old patent examiner to deeper intuitive insights into the basic premise of “what goes up must come down.” “Having forged the link between gravity and acceleration,” according to Brian Greene, “Einstein was now ready to take up Newton’s challenge and seek an explanation of how gravity exerts its influence.”90 It took him eight years to learn the necessary math. As late as 1911, Einstein “focused on developing a consistent theory of the static gravitational field based on the equivalence princi­ple” (of gravity and acceleration). He was headed down a blind conceptual alley. A ­ fter trying to generalize “his preliminary theory of the static gravitational field in 1912 . . . ​he realized that gravitation must be described by a much more complicated mathematical object than in classical physics.”91 Somehow Einstein had to depart from Newton’s construct of a static universe and come to grips with the notion that the physical universe is a very complicated place with dynamical gravitation and rotating frames of reference. Euclid’s Ele­ments—­ Einstein’s boon companion since the age of twelve—­had to be left ­behind in the face of a curved and nonstatic universe where the sum



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of a­ ngles in a triangle could be greater than 180 degrees and where the acceleration of a rotating system caused the ratio of circumference to dia­meter to differ from π. In Newton’s static universe where space and time ­were absolute (and separate), his theory of gravitation could be expressed by a single field equation for a single gravitational potential.92 In the curved, four-­d imensional space-­time of Einstein’s universe, “10 numbers are needed to calculate the distance from one point to any neighboring point,” and hence “the gravitational potential in his theory was described by a ‘metric tensor,’ a mathematical object with 10 in­de­pen­dent functions.”93 Faced with the task of finding ten corresponding gravitational field equations, “how did Einstein manage to find them?” Einstein’s collaborator, Banesh Hoffman wrote, “Could he have guessed the vari­ous terms—­hundreds of thousands of them, or in one form millions, and all of them highly unpleasant? Impossible.” In the end, “we can only marvel at the intuition that guided him to his masterpiece.”94 In 1912 tensors ­were known to only a few specialists, such as crystallographers, and so it w ­ ill come as no surprise that even Einstein needed a guide to enter this very rarified realm of higher mathe­matics. Einstein turned to Marcel Grossman, a friend from his Zu­rich Polytechnic days and a professor of descriptive geometry at their alma mater. “Together they plunged into the absolute differential calculus of Riemann, Ricci, and Levi-­Civita, leading from Gaussian . . . ​[non-­Euclidean] . . . ​ geometry of surfaces in a three-­dimensional space to Riemannian geometry in higher dimensions.”95 Reader, I apologize for both my inordinate reference to (and my lack of a fundamental understanding of ) the preceding eponymic maths that w ­ ere the under­pinnings of the theory of general relativity. My twofold purpose is to convey a sense of the complexity and the mathematical tour de force that was embodied by general relativity and how it arose (partially) from two iconic gedankenexperiments in which men plummet from rooftops or are hauled up in chests. Conceptually, it’s a long, long way from the man in the chest to general relativity, and maybe it’s better to consider ­these

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gedanken exercises as inspirational or qualitative starting points rather than direct road maps to the field equations of gravitation (Rµv − 1/2 gµvR = 8πTµv ).96 This par­tic­u­lar epistemologic trail grows cold as we try to follow Einstein from cinematic visions of a man falling from a rooftop to the mathematical abstraction of tensor calculus. Not unexpectedly, the neuroscience of cognition ­can’t keep up. Einstein’s brand of physics is readily accessible as he relates the tale of the man in the chest, but Einstein the professional theoretician needed more than just the vivid imagery of his intuition to get to the theory of general relativity. He needed the capacity to generate and manipulate high-­order mathematical formalisms. A neurologist of a very speculative bent (I plead guilty) would be treading on extremely suspect terrain if he pointed to precisely localized portions of the brain for the generation of thought experiments or mathematical abstraction. On the other hand, I believe that we ­will miss the mark if we model the brain as some kind of homogeneous, equipotential organ utterly lacking in structural parcellation of functions, such as language, calculations, visuospatial perception, et cetera. A truer picture lies somewhere between, in the realm of widely “distributed networks” that interconnect disparate brain areas into neural cir­cuits combining ele­ments of local and diffuse repre­sen­ta­tion. Neurologically “parsing” the ­human condition is a formidable, if not impossible, undertaking, and more than three centuries ­after this rhyming couplet was uttered on the stage of the Globe Theatre, neuroscience still cannot answer Shakespeare’s basic question: Tell me where is Fancy bred Or in the heart, or in the head? —­The Merchant of Venice, Act 3, Scene 297

Clearly, the localization of “fancy” (love) was a mystery then (when Shakespeare penned The Merchant of Venice in 1596–1599), and it still is (even now) in the age of oxytocin (aka the “love



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hormone”). However, a few neuroscience landmarks may prove helpful in the case of Einstein. Functional neuroimaging provides some clues as to what portions of the brain demonstrate increased blood flow during ­simple mathematical operations, such as multiplication and number comparison. (Remember, changes in ce­re­bral blood flow are felt to reflect changes in neuronal energy use.) Dehaene used positron emission tomography (PET) to image the brain metabolism of eight medical students asked to perform multiplication and number magnitude comparison tasks. The inferior parietal cortex (the left more so than the right) was activated during multiplication, and activity was more equally distributed across both hemi­spheres during number comparison. (Possibly, multiplication relied more heavi­ly on left hemispheric language capacity for the rote memorization of multiplication t­ ables.) Dehaene concluded that “arithmetic is not a holistic phrenological ‘faculty’ associated with a single calculation center. . . . ​Even an act as ­simple as multiplying two digits requires the collaboration of millions of neurons distributed in many brain areas.”98 Dehaene’s contention that “as soon as we have to manipulate numerical quantities mentally, the neural cir­cuits of the inferior parietal cortex play an essential and very specific role” resonates with our anatomical description of Einstein’s brain (see chapter 5). Einstein’s “entire inferior parietal lobule, is ­shaped differently in the two hemi­spheres, and appears to be relatively expanded on the left side.”99 In Einstein’s case a pos­si­ble correlation between his structurally exceptional inferior parietal lobule and the under­pinnings of his mathematical genius is thought provoking. However, it remains to be seen w ­ hether functional neuroimaging findings for basic multiplication can be extrapolated to the recondite mathe­ matics of tensor calculus and non-­Euclidean geometry so essential to Einstein for his theory of general relativity. Leaving aside the very speculative and very unresolved neurology of higher mathematical reasoning, it is instructive to consider

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the “rudimentary” sensory capacity to detect the forces of gravity and acceleration. Recounting the attempts of “the h ­ uman mind to find a connection between the world of ideas and the world of phenomena,” Einstein revisited his man in the chest in 1938 and this time described the sensations of an observer moving upward with constant acceleration in “a ­great elevator at the top of a skyscraper.” As you might expect, the equivalence princi­ple led the observer “to not see any reason for believing that my elevator is in absolute motion.” The observer concludes, “My watch, my handkerchief, and all bodies are falling ­because the ­whole elevator is in a gravitational field.”100 Again, in Einstein’s thought experiments, the observer in an accelerating chest/elevator or in a gravitational field becomes oriented by watching bodies fall to the floor; he must use his sense of sight, or he must “take up this pressure . . . ​[of acceleration] . . . ​by means of his legs if he does not wish to be laid out full length on the floor”101; that is, he must rely on his proprioception or position sense. To be sure, we all employ vision and position sense to indirectly gauge the pull of gravity or acceleration, but our most direct access to ­these everyday forces is through a very specialized sensory system—­the vestibular system: “Expressed simply, the role of the vestibular sensory organs is to transduce the forces associated with head acceleration and gravity into a biologic signal.”102 In his gedankenexperiment the closest and very nonspecific acknowl­edgment of vestibular sensation is in the Kyoto account of the falling man who “does not feel his weight.”103 ­W hether we are in motion or standing still, the vestibular apparatus is incessantly operative and detects two kinds of sensory stimuli essential for equilibrium and orientation. The peripheral vestibular apparatus is comprised of three fluid-­filled semicircular canals that detect angular acceleration and two globular sacs, the utricle and the saccule, that detect linear acceleration, gravity, and head tilt. The semicircular canals are filled with fluid (endolymph), which maintains a neutral buoyancy with the specialized vestibular receptors—­the hair cells. When the flow of endolymph bends the hair cells in the semicircular canals, angular acceleration of the head is detected but not gravity



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or linear acceleration.104 The utricle and the saccule contain calcium carbonate crystals (with a density more than twice that of ­water) that are subject to the “pull” of gravity. (Bad choice of words . . . ​ Einstein proved that gravity is not a force that pulls.) If you have damaged your bilateral vestibular end organs (a well-­described complication of streptomycin treatment for tuberculosis), you “do not experience a turning sensation when rotated in the dark” without visual or tactile cues.105 The upshot of this lengthy disquisition on the inner ear is that when Einstein’s observer in an elevator senses the “equivalence” of gravitation or linear acceleration he is relying on only part of his vestibular apparatus—­the utricle and the saccule. The complex neurobiology of the observer takes nothing away from the compelling Truth and Beauty of the theory of general relativity, but it ­doesn’t hurt to be aware of the “shorthand” in Einstein’s gedankenexperiment that reduces the neurologic complexity of an observer to a single uniform point of sentience. (Once again, my earlier remarks about the observer, w ­ hether outside an elevator or on a train embankment, as an embodiment of diverse neurologic subsystems should not be confused with the controversial observer effect, in which the act of observation or mea­sure­ment seems to affect the outcome of experiments, such as the be­hav­ior of photons in a double-­slit apparatus. We [and myself in par­tic­u­lar] are a long way from positing the basis of a causal effect of observant brains and consciousness on the be­hav­ior of photons). To a neurologist the bridge between our sense of balance and the phenomenon of gravity is the vestibular system. Although he himself could experience linear and angular acceleration (Figure 6.2), Einstein’s reductionist “take” on the observer effectively ignored the vestibular system. Was this a standard convention for thought experiments, or did it reflect an insufficient knowledge of ­human biology? In the late nineteenth ­century, “the w ­ hole field of diseases of the semi-­circular canals in ­humans” (and by extension vestibular physiology) “was veiled in obscurity.” The 1914 Nobel Prize in Physiology or Medicine was awarded for the elucidation of vestibular physiology to the Austrian otologist Robert Barany, who could

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Figure 6.2. Inertial and noninertial frames of reference as experienced by Einstein. In a New York City parade in 1921 and subject to the whims of his driver, Einstein’s vestibular system would detect linear and angular acceleration, gravity, and head tilt. Relativistic lengthy contraction, time dilation, and the curvature of spacetime ­were accessible to Einstein’s gedanken musings and transformative mathematical formalisms but not his vestibular apparatus. (Photo courtesy of Brown Brothers.)

not go to Stockholm ­until 1916 when Prince Carl of Sweden interceded for his release from a Rus­sian prisoner-of -­war camp. We ­will never know ­whether Einstein’s 1907 thought experiment of a man falling off a rooftop was informed by Barany’s seminal vestibular research conducted in Vienna during the first two de­cades of the twentieth ­century.106 Neurology notwithstanding, the theory of general relativity was a mathematical tour de force launched by uncanny physical intuition. Einstein’s friend and colleague Max Born called it “the greatest feat of ­human thinking about nature, the most amazing combination of philosophical penetration, physical intuition and



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mathematical skill.”107 Influences? ­There ­were plenty—­“Newton’s theory and the special theory of relativity of course, and Minkowski’s idea of a four-­dimensional world, and Mach’s power­ful criticisms of Newton’s theory.” How did he decide which physical and mathematical hypotheses could provide sturdy handholds for his ascent to general relativity, and “Where did Einstein acquire this ability to sift the essential from the non-­essential?”108 Try as we might to ­factor in his intellectual precursors, cognitive style, intuitions, and ready embrace of higher mathe­matics, “­there was no logical path t­oward” the theory of general relativity!109 But at the end of that path, the view of the universe was both breathtakingly unexpected and beautiful. The theory of general relativity “offered a profound recasting of gravity in terms of a startling new idea: warps and curves in space and time. Instead of Earth grabbing hold of a teacup that slips from your hand and pulling it to an untimely demise on the floor, general relativity says that the planet dents the surrounding environment, causing the cup to slide along a space-­ time chute that directs it to the floor. Gravity, Einstein declared, is imprinted in the geometry of the universe.”110 Or in the words of John Wheeler, whose enduring interest in relativity may have been sparked by a “small, quiet, unpublicized” seminar with Einstein in 1933, “Space tells ­matter how to move and ­matter tells space how to curve.”111 It almost goes without saying that the curvature of space-­ time is inaccessible to h ­ uman senses, and its real­ity (­there’s that dangerous term again) exists by necessity on a plane of abstract thought removed from our tangible or visual perceptions. In order to “see” the curvature of light in space-­time, the naked eye is inadequate, and we rely on the comparison of photo­graphs made with a telescope during a total eclipse (as Eddington did in 1919). I ­can’t see beams of light bending (but maybe honeybees, who can detect the polarization of light with their compound eyes, can). Lacking an innate spectrophotometer, I ­can’t appreciate a gravitational redshift of light emitted from massive stars. If the wavelength of light is ultraviolet or infrared, it is outside the vis­i­ble range of my ret­i­nal cones, and I’m effectively blind to it. I c­ an’t feel the ebb and flow of

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gravitational waves rippling through the fabric of space-­time; I need a ­laser interferometer to take the critical mea­sure­ments at “about a thousandth the dia­meter of a proton.”112 In the face of my normal sensory “handicaps,” my utricle and saccule do sense that my feet are impelled t­ oward the ground that I stand on (or my face if I stumble). I’ve learned to call this sensation gravity, but my vestibular apparatus in isolation c­an’t begin to inform me w ­ hether I’m experiencing a Newtonian action-­at-­a-­d istance type of gravity or Einstein’s warped space-­t ime curvature type of gravity. ­Those distinctions ­were made by ­human cognition at its best and purest and at a remove from the thralldom of our senses, exquisite though they may be. As we navigate the universe that we can contemplate but not always touch directly, gedankenexperiments may be our surest guide. Leaving Einstein’s relativistic field equation for gravitation ­behind us, ­here’s another . . . ​L  = mV 2. Recognize it? Me neither (and I’m supposed to have a passing acquaintance with Einstein’s physics). It’s based on his assertion that if a body releases the energy L in the form of radiation, its mass is made smaller by L/V 2 (with V being the speed of light).113 This was the 1905 version of what is arguably the most famous equation ever written, E = mc 2, which Einstein ­ ntil two years l­ater. Combining the prerelativity did not publish u princi­ple of the conservation of mass and the princi­ple of the conservation of energy, he calculated, in the space of three pages, that “if a body gives off an amount E of in the form of light [in 1905 this energy was designated as ‘L’] . . . ​its mass in kilograms diminishes by an amount E/c 2.” (E is mea­sured in joules and c is the speed of light in meters per second.) Einstein had informed the world that “all energy of what­ever sort has mass.”114 On July 16, 1945, the implications of E = mc 2 would be cataclysmically realized in Alamogordo, New Mexico, when “man for the first time transmuted a substantial quantity of m ­ atter into the light, heat, sound, and motion which we call energy.”115 In recreating his thought pro­cesses from the world of 1905, Einstein wondered, “If ­every gram of material contains this tremendous energy, why did it go so long unnoticed?”



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­ fter all, any quantitation of energy based on multiplication by the A speed of light (squared, no less!) is bound to be staggeringly huge. To Einstein the answer was “­simple enough: so long as none of the energy is given off externally, it cannot be observed. It is as though a man who is fabulously rich should never spend or give away a cent: no one could tell how rich he was.”116 In 1907 Einstein had made the audacious claim that “­every speck of dust” was “a prodigious reservoir of entrapped energy. ­There was no way of verifying this at the time.”117 The mushroom-­cloud “proof” of the interchangeability of m ­ atter and energy would not arise over the desert sands of New Mexico for another four de­cades, and at the dawn of the twentieth c­ entury, the continuous surfeit of energy produced by the radioactive decay of certain ele­ments, such as radium, was regarded as an unprovable example of E = mc 2 due to the inability to “actually weigh the atoms individually.”118 But in the world of gedankenexperiments, atomic particles could be weighed individually, and Einstein proposed this to Niels Bohr at the sixth Solvay conference in 1930. It is not commonly appreciated that Heisenberg’s uncertainty princi­ple in the realm of quantum mechanics extends beyond the inability to determine the position and velocity of a particle si­mul­ta­neously. This indeterminacy also applies to time and energy. As is well known, once Einstein opened Pandora’s box of the quantum in 1905,119 he could never accept what he felt was an “incomplete” description of nature posited by quantum mechanics. Beginning in the 1920s, Einstein and Niels Bohr lit up the Valhalla of physics as they hurled intellectual lightning bolts at each other in a titanic scientific debate to establish the truth or artifice of quantum mechanics. (Spoiler alert: most judges would assert that Bohr and quantum mechanics prevailed.) However, in 1930 the outcome of the quantum controversy still hung in the balance, and Einstein called into question the indeterminacy of time and energy with a diabolically clever thought experiment now known as Einstein’s box. The box would contain electromagnetic radiation and a clock that would precisely time the opening of a very, very tiny shutter, allowing precisely one photon

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to exit the box. The escape of a photon’s worth of energy provided Einstein with the opportunity to use E = mc 2 in a peaceful application. (In the bygone innocence of 1930, nuclear fission for military use was not on the distant horizon.) To proceed with the experiment: weigh the box, which is exactly lighter by one photon’s worth of energy, plug the change in the box’s mass into E = mc 2, and voila, you have mea­sured the photon’s energy. The clock in the box provides the exact time of the photon’s exit, and by Einstein’s reasoning the combined knowledge of the exact time and particle energy invalidated this par­tic­u ­lar quantum princi­ple of indeterminacy. Bohr was deeply troubled by this frontal assault on quantum mechanics: “During the w ­ hole eve­ning he was extremely unhappy, ­going from one [scientist] to the other and trying to persuade them that it ­couldn’t be true, that it would be the end of physics if Einstein ­were right.”120 ­A fter a sleepless night, Bohr was able to shore up the now shaky edifice of quantum mechanics by using Einstein’s greatest achievement, the theory of general relativity, against him. In the gedanken lab, Einstein’s box hung from a spring attached to an outside frame. The box was effectively a weighing scale, and if it became lighter with the escape of the photon, the spring would ever so slightly pull it up, and a pointer attached to the box would infinitesimally ascend relative to a scale on the frame. By the rules of general relativity, this acceleration irrevocably doomed the accuracy of the clock inside the box. In Einstein’s universe, time is variable and ­will slow (relatively speaking, of course) in a moving frame of reference or in a stronger gravitational field. If the box is lightened, it w ­ ill elevate, and gravity is weaker the higher it gets from the lab floor. By the tenets of gravitational time dilation, a clock would run faster at the lab’s ceiling than on its floor. The inaccuracy of the clock in the box would prevent the determination of the precise time the shutter opened and the photon escaped: “Bohr showed that Einstein’s light box experiment could not si­mul­ta­neously mea­sure exactly both the energy of the photon and the time of its escape.”121 Checkmate, Bohr.



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Grounded in the precepts of classical (prequantum) physics, Einstein’s faith in the under­lying real­ity of physical phenomena was unshakeable, and in 1935 Einstein and his two colleagues Boris Podolsky and Nathan Rosen launched another gedanken assault at the Institute for Advanced Study.122 Conceding that Heisenberg’s uncertainty princi­ple forbade the simultaneous mea­sure­ment of the position and velocity of their gedanken “particle having a single degree of freedom,” their thought experiment (the so-­called EPR paradox) subtly argued that the quantities of position and velocity at any given moment do not vanish ­because of the inability to mea­ sure them at the same time. The fault lay in the limitations of quantum mechanics, which Einstein believed was an incomplete description of real­ity that would have to suffice ­until a better one came along. Philosophical (e.g., in physics it is pointless to talk about what you cannot mea­sure) and experimental (e.g., the verification of Bell’s astounding hypothesis123 that two particles separated by vast distances could influence each other, aka nonlocality) arguments aside, no better explanation of the Very Small has come down the road. If Einstein was having prob­lems with fragmentary descriptions of particle be­hav­ior, his powers of credulity w ­ ere further bedev­iled by the idea of spooky action at a distance—­a dismissive label for the quantum mechanical foundational concepts ­later known as nonlocality and quantum entanglement. ­These would come to refute a core princi­ple of the EPR paradox, which was that an observed object in one place does not “care” about an observed object in another place.124 Where Einstein’s formidable powers of reason did not prevail, his faith weighed in (and its examination may shed some light on his par­tic­u­lar philosophy of science that led both to his triumphs and to his setbacks). Although Einstein made a break with the formal tenets of Judaism when he was twelve years old, he frequently invoked der Alte (the Old One) as a meta­phor in his thought experiments . . . ​most memorably in his inability to accept quantum mechanics. At the close of 1926, Einstein wrote to his colleague Max Born, “Quantum

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mechanics is certainly imposing. But an inner voice tells me that it is not yet the real t­ hing. The theory says a lot but it does not r­ eally bring us any closer to the secrets of the ‘Old One.’ I, at any rate, am convinced that He is not playing dice.”125 Fearing (correctly, as it turns out) that using his “inner voice” would be insufficient to persuade Born that quantum mechanics was flawed, Einstein meta­ phor­ically sought divine intervention. Why? “As was his custom when facing deep prob­lems of science, he tried to regard ­things from the point of view of God. Was it likely that God would have created a probabilistic universe? Einstein felt that the answer must be no. . . . ​He would not have created a universe in which he had to make chance-­like decisions at ­every moment regarding the be­hav­ ior of ­every individual particle.”126 And Einstein took ­great pains to discount the notion of a personal God: “I believe in Spinoza’s God, who reveals himself in the lawful harmony of all that exists, but not in a God who concerns himself with the fate and d ­ oings of mankind.”127 Not unexpectedly, Einstein’s declaration of faith in Spinoza’s God was put to the test by a dev­il’s advocate, Niels Bohr. When addressing Einstein’s objections to a dice-­playing God, Bohr (apocryphally) advised him to stop “telling God what to do.” Again, as he translated Einstein’s “Gott wurfelt nicht” (God does not play dice), Bohr substituted “the providential authorities” for God.128 I do not mean to take a cheap shot at the profundity of the Einstein-­ Bohr dialogues129 or pres­ent them as latter-­day medieval mystery plays. My intent remains to shed light on the thought pro­cesses of two geniuses and their deep discussions surrounding the gestation of quantum mechanics. ­W hether Einstein’s unwavering belief in the order of the universe constitutes a faith-­based religion or science (or both), I w ­ ill leave to my theologically inclined readers. The last gedankenexperiment we w ­ ill examine heralded the looming menace of the atomic age. On August 6, 1945, “a tremendous [noiseless] flash of light cut across the sky” of Hiroshima, traveling from east to west. “It seemed a sheet of sun.” One hundred thousand ­people ­were killed by the atomic bomb, which detonated nineteen hundred feet above the courtyard of Shima Hospital. On



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the ground as much of Hiroshima as an observer could see “through the clouded air was giving off a thick, dreadful miasma.”130 The explosive force was estimated at between thirteen thousand and twenty thousand tons of TNT, and the destructive yield of the uranium 235 (U235) critical mass in the ­Little Boy atomic bomb was calculated with the formula Einstein had derived four de­cades earlier—­E = mc 2. Did he see this coming? Prob­ably not . . . ​and he needed a ­little help from Leo Szilard. Szilard, winner of the Hungarian national mathe­matics prize, had attended Einstein’s seminars at the University of Berlin, and the two men had collaborated on twenty patent applications. A ­ fter fleeing the Nazis, Szilard eventually went to Columbia University, where despite the early skepticism of Enrico Fermi he began to grasp the possibility of a chain reaction sustained by neutrons emitted by the fission of uranium.131 Convinced of the destructive potential of nuclear fission and aghast at the German head start with Hahn and Strassman’s successful (but unrecognized ­until Lisa Meitner plugged the results into E = mc 2) fission of uranium in December 1938, Szilard hoped to warn the U.S. government of the impending peril by enlisting the aid (and influence) of Einstein. On July 16, 1939, Szilard, with the f­ uture Nobelist Eugene Wigner ­behind the wheel, caught up with Einstein in his summer cottage on the north fork of Long Island and outlined the potential for a nuclear chain reaction arising from uranium interleaved with layers of graphite. According to Arthur C. Clarke’s third law, “Any sufficiently advanced technology is indistinguishable from magic,”132 and this may be as good a reason as any for Einstein’s response—­ “Daran habe ich gar nicht gedacht” (I never thought of that).133 ­W hether he was surprised or not by the implications of mankind’s discovery of the first source of energy that did not depend on the sun, Einstein did not hesitate to craft a letter with Szilard that would apprise Franklin Delano Roo­se­velt of the “vast amounts of power” that could be generated by “a nuclear chain reaction in a large mass of uranium.” In his most ominous gedanken vision, Einstein foretold

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the construction of the atomic bomb and warned that a “single bomb of this [fission] type, carried by a boat and exploded in a port, might very well destroy the w ­ hole port together with some of the surrounding territory.” Even Einstein’s prognostications could err, and he went off the rails when he speculated that “such bombs might well prove to be too heavy for transportation by air.”134 He would be proven wrong when the B-29 Superfortress Enola Gay, laden with the ninety-­seven-­hundred-­pound ­Little Boy, took off from Tinian and set its bearings for Hiroshima on August 6, 1945. The Einstein-­Szilard letter was read to Roo­se­velt on October 11, 1939. The clear and pres­ent danger becoming obvious to the physics community did not galvanize FDR into action immediately. With bureaucratic aplomb in the face of claims of a Buck Rogers infernal contraption, the president called for the formation of a government advisory committee. The nexus of science and policy ground on inexorably, and ­there was to be no fanfare or “smoking gun” official document when Roo­se­velt made “the fateful decision to expedite research ­toward an atomic bomb.” Let the rec­ord show that Amer­i­c a began its first faltering steps ­toward the A-­bomb industrial complex of the Manhattan Proj­ect on January 19, 1942, with the president’s handwritten memo (“OK—­returned—­I think you had best keep this in your own safe.”) to his science advisor, Vannevar Bush.135 Einstein’s name has been inextricably linked with the image of the atom bomb’s mushroom cloud136 (Figure 6.3), the 4.1 square miles of Hiroshima destroyed by fire and blast (maximized by an aerial detonation with no crater to dissipate the bomb’s destructive ­ ere lost. Ironforce),137 and the many tens of thousands of lives that w ically, “except for some minor theoretical calculations for the Navy, Einstein had been excluded from war­time nuclear development” due to security concerns over “his earlier out­spoken politics—­his pacifism and prob­ably also his Zionism.”138 ­Those links to the terrible destruction wreaked by the atomic bomb ­were forged by the 1939 letter forewarning FDR of “the construction of bombs” and the use of E = mc 2 as a mea­sur­ing stick for explosive devastation. Einstein’s

Figure 6.3. Ernest Hamlin Baker’s portrait of Einstein was used for the July 1, 1946 cover of Time magazine (on which he had appeared twice before, in 1929 and 1938), and Einstein was indelibly linked with E = mc 2 to the atomic bombs detonated over Hiroshima and Nagasaki barely eleven months earlier. Although Time conceded that “Albert Einstein did not work directly on the atom bomb,” it could not refrain from identifying him as “the ­father of the bomb” on the eve of the world’s fourth atomic bomb explosion in a test 520 feet above Bikini Atoll. (Ernest Hamlin Baker, 1946, gouache, ink and graphite pencil on paperboard. National Portrait Gallery, Smithsonian Institution; gift of Time Magazine © Ernest Hamlin Baker.)

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greatest intellectual legacy, the theory of general relativity, was not particularly necessary for the “nonrelativistic theory” of fission, “meaning that relativistic effects are too small to affect the dynamics of the fission pro­cess significantly.”139 And so Einstein’s gedanken nightmare played out in an airborne B-29, and the implacable energetics of E = mc 2 took effect one-­third of a mile above Hiroshima, where two masses (38.5 kilograms and 25.6 kilograms) of enriched Uranium 235 (U235) ­were “shot” at each other within the casing of ­Little Boy. A supercritical mass was attained instantaneously, but less than a kilogram fissioned, and of that kilogram only six-­tenths of a gram actually transformed into energy.140 Mercifully, due to the limitations imposed by atomic metallurgy, neutron capture, and the explosive scatter of fissile materials, only a tiny fraction of L ­ ittle Boy’s U235 was “available” for the interconversion of ­matter to (destructive) energy. Overwhelmed by the specter of nuclear overkill, the world did not take note of the inefficiencies of atomic bomb explosions, but it never forgot that “Einstein was the f­ ather of the bomb in two impor­tant ways: 1) it was his initiative which started U.S. bomb research; 2) it was his equation (E = mc2) which made the atomic bomb theoretically pos­si­ble.”141 Posterity is capricious even (or maybe especially) for geniuses, and the fearful prospect of the world ending with a bang rather than a whimper has occupied mankind’s thoughts since that fateful day in August 1945. In an unfathomable twist of fate, Einstein, the ardent pacifist and antimilitarist, has been held accountable in no small part for the malaise of the atomic age b­ ecause his “trademark” formula charts the primordial and ferociously exothermic reaction whereby a single atom of uranium unleashes the chaos of 170 million electron volts.142 The foregoing cook’s tour of some of Einstein’s gedankenexperiments highlights just how effective they could be in the creation of his science. The free-­falling man unaware of gravity or the observer in hot pursuit of a beam of light have become parables of physics in which we catch sight of the earliest glimmers of Einstein’s theories of general relativity and special relativity, respectively. Most



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gedankenexperiments ­were resoundingly successful, but some w ­ ere not—­Einstein’s photon-­emitting box could not withstand Bohr’s withering scrutiny. When describing a “non-­rigid reference-­body” equivalent to a four-­dimensional coordinate system,143 he chose the “curious and confusing analogy of a mollusc . . . ​indicating he apparently thought of a coordinate system as a physical ­thing, swimming around like some soft marine invertebrate which could change its shape with time.”144 At best Einstein’s thought experiments are case studies in his inspired ability to frame a prob­lem in physics and start finding a creative solution. They served admirably as what phi­los­o­pher Daniel Dennett has termed intuition pumps, which are effective and less rigorous thought experiments in the guise of “­little stories designed to provoke a heartfelt, table-­thumping intuition—­‘Yes, of course, it has to be so!’—­about what­ever thesis is being defended.”145 In and of themselves, Einstein’s thought experiments stop short of “ ‘­going meta’—­thinking about thinking, talking about talking, reasoning about reasoning.”146 In other words, even a thoroughgoing study of Einstein’s written accounts of his gedanken output tells us very ­little about his metacognition. By necessity, preverbal ­mental operations must be translated into words that distort the purity of thought, or in the words of T. S. Eliot, “I gotta use words when I talk to you/But if you understand or if you don’t/that’s nothing to me and nothing to you.”147 If we seek to access Einstein’s thoughts directly and cut out the “middleman” of his words, we come face to face with qualia (singular quale), which are the “elemental feelings and sensations making up conscious experience.”148 Is my sensation of a curved line or the color red the same as Einstein’s? Lacking the technology to mea­sure and compare the qualia experienced in the brains of two dif­fer­ent individuals, the question is unanswerable. And my bedrock assumption that brain tissue can generate qualia (remember, I’m a neurologist whose job description entails equating mind and brain) leads us to David Chal­mers’s more profound “hard prob­lem” of how “subjective experience seems to emerge from a physical pro­cess.”149 At this point t­here is a yawning explanatory gap

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separating Einstein’s scientific attainments from the deepest understanding of his cognitive operations. It may well be that in the second de­cade of the twenty-­first c­ entury that par­tic­u­lar (or any) mind-­brain chasm cannot be bridged. Even Wittgenstein acknowledged that “explanations come to an end somewhere.”150 Before we can irrevocably “curse the darkness” enveloping the operations of Einstein’s genius, we should turn again to his introspective writings in which his scientific curiosity sought to make sense out of his ­mental pro­cesses. Introspection allows us to regard the order (and the chaos) of our conscious thoughts, but I’m not convinced that James Joyce’s consummate rendering of Molly Bloom’s stream of consciousness (as the “raw stuff” of introspection) ­ ental operations.151 In this case in Ulysses lays bare the logic of her m art ­will not further the goals of cognitive science. Introspection’s other shortcoming is that it is limited to conscious thought. When I look at the elegant geometry of a Mondrian painting, its borders, straight edges, and intersections daubed on the canvas elicit an increased frequency of action potentials from neurons with center-­ surround, complex, and end-­stopped receptive fields in the striate (visual) cortex of my occipital lobes. I remain blissfully unaware as the neuronal firing rate ramps up, and I sit back undistractedly to enjoy the artist’s creation. The neurophysiological activity in my visual cortex is inaccessible to my conscious thought. Although we must concede that unconscious/subconscious/preconscious (or what­ever) ­mental operations are outside the purview of introspection, it is instructive to listen to what Einstein had to say when he “looked ­u nder the hood” at his own methods of (conscious) cognition. Unlike John Maynard Keynes (as recounted by Daniel Dennett) who when asked, “Do you think in words or pictures?” somewhat unhelpfully replied, “I think in thoughts.”152 Einstein was more specific (and a lot more helpful) when he reported that “the words or the language, as they are written or spoken, do not seem to play any role in my mechanism of thought.”153 Einstein felt that he was not unique in this regard and surmised “that our thinking goes on



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for the most part without use of signs (words).”154 Having disavowed words as his par­tic­u­lar psychical vehicles, Einstein specified that the ele­ments of his thought w ­ ere “of visual and some of muscular type.” A likely neuroanatomical candidate for the maneuvering of “muscular” or “motor” images would be the parietal lobes, which pro­cess and integrate visuospatial and kinesthetic sensory information. At the risk of ­going over old ground, our study of Einstein’s cortical topography clearly confirmed the exceptional nature of his parietal lobes, with a larger than normal left inferior parietal lobule and a markedly enlarged superior parietal lobule in the right hemi­ sphere.155 Another part of the brain, the cerebellum, may also be involved in the manipulation of ­these images.156 This signifies a sea change in our understanding of the pro­cess of cognition. The cerebellum (or “­little brain”) is nestled between the occipital lobes and the brain stem. U ­ ntil three de­cades ago, it was thought to exclusively coordinate the planning and execution of the body’s movements. To learn about the cerebellum, I studied the classic papers of Gordon Holmes, who described the cerebellar syndrome arising from gunshot wounds to the heads of En­glish soldiers in the trenches of the western front during World War I.157 The changes in motor function of ­these patients included tremor, incoordination of limb movements and walking, abnormal eye movements, slurring of speech, and loss of muscle tone. But by 1991 the perception of the role of the cerebellum had greatly expanded: “It may also transpire that in the same way as the cerebellum regulates the rate, force, rhythm, and accuracy of movements, so may it regulate the speed, capacity, consistency, and appropriateness of ­mental or cognitive pro­cesses.”158 Did Einstein have an exceptional cerebellum? We ­don’t know. When Thomas Harvey began the postmortem study of Einstein’s brain in 1955, the cerebellum was not on the radar for cognitive function and, not surprisingly, neither detailed photo­ graphs nor histologic slides of the cerebellum ­were ever produced. Unlike the ce­re­bral cortex, which provides a unique variability for each person’s gyri and sulci, “the cerebellar cortex is principally identically structured all over.”159 If any distinguishing features of

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the cerebellum of a genius exist, they are not to be found in the surface anatomy but more likely in the multisynaptic pathways connecting the cerebellum to ce­re­bral association regions.160 Regrettably, the viral tracers used for mapping ­these transneuronal pathways are not an option for devitalized blocks of brain tissue over sixty years old. The complexity of the prob­lems that Einstein encountered in his daily routine as a theoretical physicist made him aware of his personal cognitive boundary lines—­“It seems to me what you call full consciousness is a limit case which can never be fully accomplished.”161 His recognition of his own “narrowness of consciousness” was in lockstep with William James’s declaration that “every­one knows what attention is. It is the taking possession by the mind, in clear and vivid form, of one out of what seem several si­mul­ta­neously pos­si­ble objects or trains of thought. Focalization, concentration of consciousness are of its essence. It implies withdrawal from some t­ hings in order to deal effectively with o­ thers.”162 Both Einstein and James had encountered a basic cognitive property that neuroscience subsequently labeled the attentional spotlight or searchlight. The neuroscientist Christof Koch, in an effort to invest consciousness studies with scientific probity, has opined that “attention is evolution’s answer to information overload; it is a consequence of the fact that no brain can pro­cess all incoming information . . . ​the brain deals with this deluge of data by selecting a small portion for further pro­cessing.”163 The neural wiring diagram for the attentional searchlight is still up for grabs. Koch collaborated on this prob­lem with Francis Crick, who, not content with unravelling the ge­ne­tic code, went on to pursue the mystery of consciousness. Crick proposed that the neural circuitry of the attentional searchlight was to be found in the connections of the thalamic nuclei deep in each hemi­sphere under­lying the ce­re­bral cortex.164 Protestations of “narrowness of consciousness” aside, ­were Einstein’s thalamocortical pathways dif­fer­ent? Again . . . ​not known. With the exception of Weiwei Men’s study of Einstein’s corpus callosum,165 no research on Einstein’s connectome has been forthcoming.



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­W hether connections between neurons have anything to do with connections between thoughts is a profound question that runs through this “biography of a brain” and occupies my more contemplative moments as a clinical neurologist. My occupationally driven “brain = mind” (materialist) biases aside, I remain open to other—­for example, the brain and the mind are dif­fer­ent—­ hypotheses. This remains a Big (and possibly the Biggest) question in neuroscience. Even Sir Charles Sherrington, the discoverer of one of the most basic features of neural wiring—­the synapse—­affirmed that “the physical, although it correlates with the psychical, need not resemble it.”166 Einstein did not unequivocally declare himself as a member in good standing of the materialist camp but he may have hinted at where his true sympathies lay when he admiringly spoke of his intellectual North Star, Baruch Spinoza, as “the first phi­los­o­pher to deal with the soul and body as one, and not two separate ­things.”167 Despite (or maybe b­ecause of ) the shortcomings of mid-­ twentieth-­century neuroscience, Einstein thought long and hard about how his mind assembled his sense experiences and concepts. In his 1949 Autobiographisches, Einstein at his most introspective tried to explain his own “striving and searching.” He began the fifth paragraph with a ­simple question: “What, precisely, is ‘thinking’?” And he began to answer that “when, at the reception of sense-­ impressions, memory pictures emerge, this is not yet ‘thinking.’ And when such pictures form series, each member of which calls forth another, this too is not yet ‘thinking.’ When, however, a certain picture turns up in many such series, then—­precisely through such return—it becomes an ordering ele­ment for such series, in that it connects series which in themselves are unconnected. Such an ele­ ment becomes an instrument, a concept. I think the transition from ­free association or ‘dreaming’ to thinking is characterized by the more or less dominating role which the ‘concept’ plays in it . . . ​ all our thinking is of this nature of a f­ ree play of concepts.” He specified that “the concepts and propositions get ‘meaning’ . . . ​only through their connection with sense experiences.”168 At this point

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Einstein draws a curtain blocking further view of his cognitive pro­cess: “In my opinion, nothing can be said concerning the manner in which the concepts are to be made and connected, and how we are to coordinate them to the experiences.” This coordination and ordering of sense-­experiences with concepts “by means of thinking” is a “fact . . . ​which leaves us in awe, but which we w ­ ill never understand. One may say ‘the eternal mystery of the world is its comprehensibility.’ ”169 As a schoolboy Einstein delved extensively into the works of Immanuel Kant, but in his maturity he became increasingly preoccupied with the importance of epistemology in physics and parted ways with Kant’s a priori categories of knowledge derived from logic and pure reason rather than observation.170 In 1922 he expressed his reservations regarding Kant as he acknowledged that “arbitrary concepts are necessary in order to construct science; as to w ­ hether ­these concepts are given a priori or are arbitrary conventions, I can say nothing.”171 Einstein studied philosophical writing throughout his life, and the question of what he believed to be the philosophical under­pinnings of his epistemology is best left to the considered judgment of phi­los­o­phers (not a clinical neurologist). Suffice it to say that Einstein’s epistemological w ­ aters ­were muddied. “Ele­ments of all ­these ‘isms’ . . . ​[realism, idealism, positivism, Platonism, Pythagoreanism] . . . ​a re clearly discernible in Einstein’s thinking.”172 In the end Einstein’s professed philosophy of an objective real­ity in­de­pen­dent of our circumscribed ability to observe it directly had profound implications for his pursuit of physics. He sought a deeper theoretical framework to provide a complete description of natu­ral phenomena, and b­ ecause “objective real­ity is incompatible with the assumption that quantum mechanics is complete,”173 Einstein turned his back on the near universal success, dominance, and ac­cep­tance of quantum mechanics. So did this par­tic­u­lar genius simply think like the rest of us, only better and more industriously (along the lines of “genius” described by Thomas Carlyle as the “transcendent capacity of taking trou­ble, first of all”)?174 Or did he think in a truly dif­fer­ent way? An



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alternative overview of h ­ uman cognition can reasonably posit that given an average allotment of eighty-­five to eighty-­six billion neurons and ongoing neuroplasticity of their myriad connections maybe e­ very individual thinks differently from every­one e­ lse. Einstein was no exception to this doctrine of cognitive individualism, but unlike the rank and file of most humanity, he left ­behind some tantalizing sketches of his one-­off ­mental landscape—­and his ce­re­bral architecture, as judged from the “lost” photo­graphs, r­ eally was unique.175 To recap some distinguishing features of his cognitive profile: “I very rarely think in words at all,” he told a psychologist. “A thought comes, and I may try to express it in words afterwards.”176 The neuroscientist V. S. Ramachandran has asked, “Can we think without ­silent internal speech?”177 Neurologists are very familiar with aphasic patients who lose normal language capacity with the onset of a dominant (usually left) hemispheric cerebrovascular accident. A par­tic­u­lar kind of aphasia, expressive (or Broca’s) aphasia, is characterized by a retained understanding of written or spoken language but a loss of the ability to speak or write grammatical phrases. I ­don’t have a precise idea of the thought pro­cesses of my aphasic patients who ­can’t generate internal speech, but I do know that their thinking is impaired, or at least very dif­fer­ent from what it was before the stroke. We are compelled to take Einstein’s description of wordless thought at face value. My encounters with a stroke victim’s diminished nexus of language and thought do not shed much light on the nonverbal brainstorms of a genius. “Only gradually ­after years of in­de­pen­dent scientific work” did it dawn upon Einstein “that the approach to a more profound knowledge of the basic princi­ples of physics is tied up with the most intricate mathematical methods.”178 As a student at Zu­rich Polytechnic, he “worked most of the time in the physical laboratory, fascinated by the direct contact with experience.” At this early stage, he honed his unerring intuitive sense about the workings of physical phenomena and “learned to scent out that which was able to lead to fundamentals and to turn aside from every­thing ­else.” His

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reliance on his seat-­of-­the-­pants physical intuitions was tempered by the historical lessons of physical inquiry: “In the beginning (if ­there was such a ­thing) God created Newton’s laws of motion together with the necessary masses and forces. This is all; every­thing beyond this follows from the development of appropriate mathematical methods by means of deduction.” The application of partial differential equations in the nineteenth c­ entury led to the “more precise development of the mechanics of discrete masses, as the basis of all physics.” However, “the mechanical point of view broke down. It was impossible to explain all phenomena by assuming that s­ imple forces act between unalterable particles,” and as a consequence, “a new concept appears in physics, the most impor­tant invention since Newton’s time: the field.”179 For Einstein the idea of the “field” was brought to life by James Clerk Maxwell’s (1831–1879) equations, which w ­ ere laws representing the structure of the electromagnetic field. Firmly ensconced in the zeitgeist of Maxwell’s field equations, it is hardly surprising that Einstein would bring forth the field equations describing gravitation as “something fundamentally geometrical.”180 And that brings us full circle to Einstein’s late-­blooming appreciation of mathe­matics and his “growth spurt” (at age thirty-­ three) as a theoretical physicist cum mathematician when he enlisted Marcel Grossmann’s help in mastering tensor calculus. Twenty years a­ fter the theory of general relativity, Einstein reflected on the increased distance between the abstract nature of field theory (in this case Maxwell’s) and “what can be experienced by means of our five senses.”181 Throughout his ceaseless working life, as he explored the intangibilities of the Very Small (quanta and Brownian motion), the Very Big (curvature of space-­time and the orbit of Mercury), and the Very Fast (the speed of light), Einstein came face-­to-­face with the bound­aries of “the plebeian illusion of naïve realism, according to which t­ hings ‘are’ as they are perceived by us through our senses.”182 ­A fter detecting two-­dimensional patterns of photons hyperpolarizing the rods and cones, the h ­ uman ret­ ina transmits this raw photic data to the visual cortex, which links to other cortical visual “modules” with massive feedforward and



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feedback to create internally generated visuospatial maps. Put it all together, and normal h ­ uman vision sees a panoramic world limned by and imbued with bold and subtle outlines, stereopsis, color, the fine detail of 20/20 visual acuity, and movement . . . ​but the near-­ miraculous perspicacity of the eye-­brain combination cannot “see” the curvature of space-­time in the way it sees the downward arc of wires strung between two utility poles. What Einstein’s eyes could not see, his intellect could envision. The equations of general relativity take the amount of m ­ atter and energy in the universe as input, and “as output they give the curvature of space.”183 Lacking a definite quantification of the amount of ­matter and energy in the universe, the equation is not informative, and Richard Feynman confided in 1964 that “unfortunately, we d ­ on’t have the slightest idea about the overall curvature of our universe on a large scale.”184 Depending on the distribution of ­matter and energy throughout the universe, Einstein’s equations allow for three pos­si­ ble curvatures of space: (1) positive curvature (like a sphere), (2) zero curvature (flat), or (3) negative curvature (like a s­ addle). The “shape of the cosmic fabric”185 remains invisible to our direct observational powers and becomes accessible to us only through general relativity’s mathematical strategy of the metric tensor. Was Einstein able to explain how he crossed over “the gulf—­ logically unbridgeable—­ which separates the world of sensory experiences from the world of concepts and propositions”?186 In a word, he felt that his cognitive leaps w ­ ere “unknowable.” “The very fact that the totality of our sense experiences is such that by means of thinking (operations with concepts, and the creation and use of definite functional relations between them, and the coordination of sense experiences to ­these concepts) it can be put in order, this fact is one which leaves us in awe, but which we ­will never understand”187 (my italics). From Einstein’s perspective the creative and cognitive pro­cesses that led to his work in physics ­were “attained by f­ree invention” and intuitively. Even for the rest of us “non-­ Einsteins,” the lack of deep insight into our own cognitive pro­cesses is a routine part of the ­human condition. On a daily basis, we deal

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with explicit knowledge (Which sequence of buttons on the remote do I press to program a DVR?) and implicit knowledge (How do I ­ride my bicycle?). I can tell my ­daughter exactly how to push the right DVR buttons, but she had to figure out how to ­ride a bike pretty much on her own, with Dad on standby for scraped knees. (How do you “instruct” somebody to keep their center of gravity upright?) Einstein did a lot of soul-­searching to convey a ­little of the mystery b­ ehind his thinking. (Attention Tiger Moms! “How to” manuals with explicit instructions for your Baby Einstein are very likely a canard, and you heard it from Einstein himself!) So if the roads to Einstein’s Truths are unknowable, are they Beautiful? He thought so. Science, among o­ thers ­things, was “the longing to behold . . . ​pre-­existing harmony.”188 One of the foundations of the theory of general relativity was the princi­ple of general covariance, which placed all space-­time coordinate systems on an equal footing. This was in no small part due to Einstein’s conviction “that the princi­ple had content if one asked for the simplest and most beautiful tensor equations to fit the occasion.”189 Beauty did indeed lead to Truth for Einstein and his absolute certainty in the authenticity of his formulation of general relativity. When Eddington’s photographic plates of the eclipse of 1919 confirmed that starlight was “bent” by the amount that Einstein (and not Newton) had predicted, one of Einstein’s students asked Einstein how he would feel if the En­glish astronomer “failed to confirm the deflection of light. Einstein’s faith was unshakeable. If the eclipse proved the theory wrong, ‘then I would feel sorry for the dear Lord. The theory is correct.’ ”190 Lest we come away from this with the notion that Einstein was exclusively a scientific aes­t he­ti­cian or a forerunner of new age physics, I can assure you that he was a gimlet-­ eyed skeptic who was equally at home when rejecting flawed patent applications or driving Bohr to distraction with criticisms of quantum mechanics. Though the theory of general relativity might be his triumphal achievement and the apple of his eye, let’s listen to Einstein dispassionately dissect his generally covariant equation for the gravitational field, R µv − 1/2gµvR = −kTµv. He ­d idn’t pull any



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punches as he judged: “The theory . . . ​is similar to a building, one wing of which is made of fine marble (the left wing of the equation), but the other wing of which is built of low-­grade wood (the right wing of the equation). The phenomenological repre­sen­ta­tion of ­matter is, in fact, only a crude substitute for a repre­sen­ta­tion which would do justice to all known properties of ­matter.”191 Nevertheless, over a c­ entury ­later, the ser­viceable “edifice” of general relativity is still standing. ­W hether beautiful or unknowable, Einstein’s thought pro­cesses ­were a lifelong means to the end of discovering the laws of nature. “His realism and optimism are illuminated by his remark: ‘Subtle is the Lord, but malicious He is not.’ When asked by a colleague what he meant by that, he replied: ‘Nature hides her secret b­ ecause of her essential loftiness, but not by means of ruse.’ ”192 ­Those thought pro­cesses served him well, particularly for the first fifteen years of the twentieth c­ entury, when he formulated some of the highest intellectual attainments of mankind . . . ​but did his thoughts soar consistently into the empyrean reaches of intellect throughout the seventy-­six years of life granted to him? “Conventional wisdom is that big scientific discoveries are made by the supple minds of the young. Albert Einstein famously said, ‘A person who has not made his ­great contribution to science before the age of 30 ­will never do so.’ ”193 He was clearly speaking from personal experience; his annus mirabilis took place when he was twenty-­six. And his genius continued to increase (maybe evolve is the better term, assuming that adults d ­ on’t “grow” extra IQ points). It took another de­cade for the thirty-­six-­year-­old Einstein to put the finishing touches on the theory of general relativity, arguably his most difficult and renowned attainment. No universe-­shattering theorems w ­ ere to follow, and the remainder of his scientific ­career devolved upon critical (and unsatisfied) scrutiny of quantum mechanics, unified field theory (tying together electromagnetism, gravity, and quantum mechanics), the awesome implications of E = mc 2 over the skies of Hiroshima and Nagasaki in 1945, and the question of ­whether the universe is infinitely expanding or

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constant . . . ​still one of the eternal cosmic mysteries. Does this abbreviated timeline reflect the “inevitable” cognitive decline of an aging genius (albeit the intellectual cynosure of our times)? Possibly. Einstein’s ­career followed a fairly classic trajectory for elite scientific productivity. Virtuoso per­for­mance in science and the creative arts “peaks in m ­ iddle age: the life-­cycle begins with a training period in which major creative output is absent, followed by a rapid rise in output to a peak, often in the late 30s or 40s, and a subsequent slow decline in output through ­later years.” The specific field of endeavor also had implications: “A classic finding is that peak per­for­mance has come earlier on average in mathe­matics and the physical sciences than in fields like medicine.”194 Notwithstanding the coruscating brilliance of Einstein’s scientific achievements, can we reasonably speculate as to the basis of the ebb and flow of his genius? Psychological testing over the life span of individuals has shown that not all aspects of intelligence decline as we grow older. Echoing Dylan Thomas, psychometrists assure us that in senescence each and e­ very ­mental capacity does “not go gentle into that good night,” and some “rage, rage against the ­dying of the light.”195 Apropos of cognitive resilience, 101 subjects out of the 87,498 ­children who took the Scottish M ­ ental Survey on a summer’s morning in 1932 w ­ ere retested sixty-­six years ­later, demonstrating that “largely speaking, the ­people who did well in 1932 also tended to do well in 1998.” In par­tic­u­lar, “on tests that mea­sure vocabulary, general information, or verbal reasoning, t­ here is ­little or no age-­related decrement in ability.” The contention that smart ­people tend to remain smart across the h ­ uman life span should be qualified by K. Werner Schaie’s Seattle Longitudinal Study, which between 1956 and 2013 studied the progression and regression of the ­mental abilities of nearly five thousand ­people from their late teens to their eighties. Schaie found “a fairly straight decline from age 25 to 80 years in inductive reasoning (discovering a rule from a limited number of instances), spatial orientation (making decisions about complex shapes in two or three dimensions), perceptual speed (the ability to notice fine visual



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details quickly), and verbal memory.”196 Diminished capacity in ­these cognitive domains would pose a prob­lem for a theoretical physicist (or anyone ­else). If Einstein was no exception to the intellectual downslide of time as charted by longitudinal psychological testing, we have one (but not the only) plausible explanation for his inability to generate further scientific breakthroughs in his fifth, sixth, seventh, and eighth de­c ades. Also, some normal m ­ ental changes can unfold in time frames considerably shorter than de­cades. In Einstein’s case, cramming to pass his final examinations at Zu­rich Polytechnic had such a “deterring effect” that the twenty-­one-­year-­old “found the consideration of any scientific prob­lems distasteful to me for an entire year.”197 Fortunately, he recovered his intellectual curiosity. Such was not exactly the case for thirty-­eight-­year-­old Bertrand Russell and Alfred North Whitehead, who spent a de­cade writing Principia Mathematica, their magisterial collaboration for “deducing mathe­ matics from logic.” A ­ fter Whitehead’s death, Russell wrote that “the effort was so severe that at the end we both turned aside from mathematical logic with a kind of nausea.”198 Their distinguished l­ater ­careers went “in dif­fer­ent directions,” but mathematical logic’s loss was philosophy’s gain. I cannot offer a neurological localization for shorter-­term ­mental exhaustion or midcareer course corrections, but do neurological findings provide a physical basis for long-­term, age-­ related psychological changes? Okay . . . ​­we’re back to the contentious arena of mind-­brain correlation, but let’s see if neuroanatomy and neuropathology have anything informative to offer. The brains of nondemented seventy-­five-­year-­old males weigh significantly less than the brains of men u ­ nder fifty.199 Ditto brain volume.200 The brains of normal older adults have lower volumes of gray ­matter than do the brains of younger adults. This is attributed to lower synaptic densities and not cell death. Some specific brain areas are more likely to be affected by age. The frontal white m ­ atter tracts subserving the prefrontal cortex “undergo an age-­related loss of integrity that might affect memory cir­cuits involving the frontostriatal cortices.” Another age-­targeted region of volume loss is the

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entorhinal cortex, which acts as an impor­tant relay between the hip­ umans, the entorhipocampus and the association cortices.201 In h nal cortex is located at the frontal portion of the temporal lobe and is surrounded by the bony contours of the skull base. In the brains of rats (and men, as frequently is the case), the entorhinal cortex is critical for memory and directional navigation. Could entorhinal atrophy have been operative as Einstein aged? It’s unknown and, for the rec­ord, studies of the synaptic density of Einstein’s cortex have not been pursued (or at least published). Our gross anatomical study showed that Einstein’s inferior temporal gyrus abutting the entorhinal cortex was relatively expanded.202 This raises the out-­ on-­a-­limb speculation that neighboring temporal lobe cortical surplus might compensate for entorhinal shrinkage. A dilemma facing anatomical research on the aging brain is the sometimes indistinct border separating normal aging from early Alzheimer disease. One microscopic hallmark of Alzheimer disease is the senile plaque—an extracellular fifty-­micron accumulation of amyloid beta in the brain’s gray ­matter. ­Don’t look now, but senile plaques ­were found in the autopsied brains of twenty-­two out of twenty-­eight seventy-­five-­year-­old intellectually normal men and ­women.203 In limited numbers and circumscribed distribution, amyloid plaques (as well as other microscopic changes, such as neurofibrillary tangles inside neurons) may reflect normal aging of the brain. However, “the most striking feature of the cerebral cortex in Alzheimer’s disease is the presence of neuritic [senile] plaques which may occur in vast numbers.”204 Most cases of dementia can be explained on morphologic grounds,205 but the precise cutoff for senile plaque density that divides normal and pathologic brain aging remains elusive.206 Truth be told, clinical neurologists (myself included) rarely establish a diagnosis of Alzheimer disease in living patients by resorting to an invasive brain biopsy and having a ­neuropathologist examine microscopic sections of the biopsy tissue. Although not 100 ­percent accurate, the less invasive techniques, such as a thoroughgoing history and clinical examination, laboratory tests, and neuroimaging, ­will often suffice.



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This then leads us back to ­whether Einstein’s brain showed signs of aging or Alzheimer disease. None of the five papers written (see chapter 4) about the microscopic structure of his cortex found the histologic stigmata of Alzheimer disease, and it is germane to point out that all of the authors ­were neuroscientists rather than clinicians. None of t­hese research scientists was a neuropathologist trained to diagnose Alzheimer disease and other diseases of the aged brain, such as stroke or Parkinson’s disease. One neuropathologist, Dr. Lucy Rorke-­Adams, who did examine the slides, commented that his brain cells looked quite youthful, the “blood vessels looked gorgeous,” and the neurons had “­little or no lipofuscin” (a pigment associated with aging and “wear and tear”).207 ­A fter examining one set of microscope slides sent along by Harvey, Harry Zimmerman, who had taught Harvey neuropathology at Yale Medical School, was reported to remark that “Einstein’s brain cells appeared to be in pretty good shape for a man of his age.”208 If Einstein’s brain was not showing its age or signs of a degenerative neurological disease a­ fter the theory of general relativity and the quantum “wars,” how do we account for his apparent late ­career doldrums, other than by invoking the “normal” intellectual involution that comes with increasing age? Rather than attach blame to Einstein’s unverified (but likely) waning intellectual prowess, it may well be that the prob­lem of a unified field theory was simply too difficult. It might have been an instance of a “twenty-­second ­century” physics prob­lem being addressed by twentieth-­century physical sciences. (Along the same lines, British author Martin Amis, when pondering the eternal mystery of the universe’s existence, remarked, “I’d say ­we’re at least five Einsteins away from answering that question.”209) And the prob­lem of the consolidation of the forces of nature became progressively more complex as he devoted the last thirty years of his ­career (and life) to its solution. Initially, he set out to understand how electromagnetism and gravity are regulated by a single set of physical laws much in the way that “with his two theories of relativity Einstein united space, time, and gravity.”210 His quest for an indivisible unified theory (or

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Theory of Every­t hing) became even more formidable by the 1920s with the dawning recognition of the incompatibility between quantum mechanics and general relativity. As described by physicist Brian Greene, “The g­ ently curving geometrical form of space emerging from general relativity is at loggerheads with the frantic, roiling, microscopic be­hav­ior of the universe implied by quantum mechanics.”211 As if the synthesis of the rules governing the infinitesimally tiny quantum world and the all-­encompassing vastness of the fabric of space-­time was not a sufficient challenge, two new fundamental forces of nature operating on an atomic/subatomic scale w ­ ere recognized in the 1930s: (1) the strong nuclear force holding the components (dubbed quarks in 1963) of protons and neutrons together, and (2) the weak nuclear force that is instrumental in radioactive decay. If anything, the map of physics was becoming increasingly Balkanized as Einstein hit his fifties. And in the end, Einstein could not stitch the quartet (quintet . . . ​if you throw in quantum mechanics for good mea­sure) of physical forces into a single Truth. However, even as late as 1953, the formulas for his failed attempts at a unified field theory ­were printed on the front page of the New York Times!212 In the sixty-­t wo years (at the time of this writing) since his death, have we done any better? As previously discussed, the leading contender for a unified field theory/theory of every­thing is the string (short for superstring) theory that began to hit its stride in the mid-1980s. It proposes that atomic and subatomic particles, such as neutrons, protons, and their building blocks (quarks), are made up of vibrating loops of string of Planck length (about one hundred billion billions times smaller than an atom’s nucleus). They are beyond the resolving power of any imaging technology currently extant, and that is why we perceive the subatomic world as point particles and not as oscillating, infinitely thin filaments. As if infinitesimally tiny size did not pose enough of a conceptual obstacle, in the mid-1990s a leading string theorist, Edward Witten, posited strings as “two-­d imensional membranes living in an eleven-­ dimensional universe.”213 If strings are too small to see (or probe)



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and are hidden in an eleven-­dimensional universe, we have just left the city limits of Realityville and entered the precincts of mathematical idealization and observationally unverifiable science. Setting aspirations for this par­tic­u ­lar theory of every­t hing aside, it should be stated that string theory is not a theory that “has been completely worked out, confirmed by vigorous experimental tests, and fully accepted by the scientific community.”214 As should befit a prob­lem insoluble to Einstein, the math is daunting. “The mathe­matics of string theory is so complicated that, to date, no one even knows the exact equations of the theory.” But Einstein was a quick study . . . ​to put together the theory of general relativity, he became ­adept at Riemann’s geometry of curved surfaces and tensor calculus. As he matured scientifically, he relied less on his superb seat-­of-­the-­pants intuitive feel for physical phenomena and more on “pure” mathe­matics. His gravitational field equations ­were “the result of a mathematical strategy rather than . . . ​the outcome of an intricate search for the convergence of physical and mathematical strategies.”215 At the risk of indulging in the “what ifs?” of alternative history, could Einstein have mastered the math necessary to establish string theory as the unified field theory? Riemannian geometry applies to im­mense distances of space-­time, but the manipulation of the vanishingly short Planck length distances of strings requires a “new geometrical framework . . . ​called quantum geometry.”216 W ­ e’ll never know if Einstein could have pulled it off, but for my money the unified field theory/theory of every­thing was a bridge too far for twentieth-­century math and physics. ­Will string theory lead the way to the Holy Grail of physics? Maybe . . . ​but not tomorrow or the next day. Brian Greene has cautiously predicted “that it could be de­cades or even centuries before string theory is fully developed and understood.”217 When you come right down to it, ars longa, vita brevis (the art of solving prob­lems, in this case physics, is a long and arduous pro­cess, and life with its biological limitations is a brief “candle” of illuminating insight. My apologies to Hippocrates and his aphorism). Einstein

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was the best and brightest (and most creative) mind in twentieth-­ century physics, but he was no match for the prob­lem of the theory of every­thing. Did he run out of time or brains or was the scientific milieu of the early twentieth c­ entury simply too primitive? The prob­lem won (and is still winning). We cannot reasonably expect that even a physicist of Einstein’s inestimable gifts would continue to reach intellectual personal bests year a­ fter year. How do you top the annus mirabilis or the theory of general relativity? The answer: you d ­ on’t . . . ​but in the voyage of scientific discovery, sometimes you can get lucky. For instance, Gregor Mendel’s discovery from 1857 through 1864 of discrete inheritable units (labeled genes by 1909) would remain a biological “black box” ­until Watson and Crick had the good luck (and ingenuity) to characterize the structure of DNA in 1953. Einstein caught a lucky break when astronomers made observations that breathed life into the field equations of general relativity. His own confidence in his theory aside, Einstein’s scientific certainty increased (with heart palpitations, no less) immeasurably when he learned that the forty-­three-­a rc-­seconds-­per-­century shift of the perihelion of Mercury’s orbit was a perfect fit for his ­ idn’t hold for his pursuit of a unified field equations.218 His luck d field theory. Luck changes, and the scientific wheel of fortune inexorably turns. For us, the theory of every­thing may await affirmation with a breakthrough that we can only guess at—­t he observation of extra dimensions, or a dif­fer­ent kind of higher mathe­matics, or new modes of supercomputing/artificial intelligence, to name a few candidates. As Einstein related his first-­person account of the gedankenexperiments that embodied a small but significant portion of his scientific method, we scratched the surface of the marvelous capacity for creative and analytical thought in not just any genius but in the genius of our (and maybe for all) time. I have given short shrift to the breadth of his thinking by focusing on his work in theoretical physics. Einstein would likely take me to task for my narrow perspective in this biography of a brain. He believed that “the ­whole of science is nothing more than a refinement of ­every day thinking.”



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In his view “the critical thinking of a physicist” should not be constrained to “concepts of his own specific field.” It was of paramount importance to analyze “the nature of everyday thinking.”219 Granted that epistemology was an area of intense personal interest for Einstein, he cast his net very widely when he invoked “everyday thinking,” which mirrors the wide world around us and not just our vocational priorities. The depth, range, and emotional coloring of Einstein’s everyday thinking can be roughly inferred from his statements on topics such as religion and antimilitarism and are vital ele­ments of his portraiture in far-­ranging biographies.220 We can only conjecture at the mixture of optimism, won­der, disillusionment, and discouragement in his commonplace thoughts as he walked the streets of Berlin from March 1914 u ­ ntil he left forever in December 1932. He ran the gauntlet beginning with his recruitment by the Nobelists, Max Planck, and Walther Nernst, to a university chair in Berlin—­the “world’s most notable scientific center”221—­and ending in Pasadena, when Einstein learned that Adolf Hitler had become chancellor of Germany on January 30, 1933.222 And what of the dark thoughts surrounding his life’s discontents and tragedies, such as the dissolution of his marriage with Mileva Maric in 1919, the out-­of-­wedlock birth of their ­daughter Lieserl in 1902 followed by her never-­explained disappearance, and the schizo­phre­nia of his youn­gest son, Eduard, which led to institutionalization in 1932? Though not the stuff of heroic scientific biography and certainly downplayed in his own writings, ­these setbacks in life ­were as much a part of his ­mental landscape as his scientific triumphs. Photo­graphs of the 1,230-­gram convoluted “stage” on which Einstein’s thoughts, ranging from sad to sublime, played out w ­ ere the subjects of our neuroanatomical research. Based on our current concepts of neuroplasticity, in which neural “wiring” is physically altered as we think and perceive, we can safely assume that the seventy-­six-­year-­old brain that Thomas Harvey photographed in 1955 was not exactly the same as the brain that had ushered in the annus mirabilis fifty years earlier. Let me state it once more for the

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rec­ord: we cannot match Einstein’s or anybody e­ lse’s neuroanatomy (no m ­ atter how distinctive) with their thoughts. The photo­graphs studied most as­suredly do not convey the specific thought content of Albert Einstein in his seventy-­sixth year of life. They are, nonetheless, images of the brain of an iconic genius, and they evoke the deep and intertwined mysteries of the ner­vous system and ­human thought. ­W hether you are a genius or not (and most of us ­aren’t), this par­tic­u­lar category of h ­ uman potential exerts its own peculiar and inescapable fascination—­a topic we w ­ ill explore in the next chapter.

chapter 7

The Pursuit of Genius We do not know how or why genius is pos­si­ble, only that—to our massive enrichment—it has existed, and perhaps (waningly) continues to appear. —­h arold bloom, Genius

In 2000 when I embarked on what would prove to be a haphazard program of research on Einstein’s cerebrum, I posed a straightforward question: “Why does Einstein’s brain exert such irresistible attraction for neuroscientists and ­people from all walks of life?”1 My explanation for the unflagging interest in a brain preserved in formalin for over six de­cades was, and still is, best encapsulated in a single word—­genius. And as we seek to understand what makes a genius tick, is ­there any more promising place to begin than with “the twentieth c­ entury icon of genius, Albert Einstein?”2 On the surface, I answered a ­simple question with a breezy answer, to be sure . . . ​but just how do we go about defining genius? In this book about a brain, I must own up once again to the prob­lems that inevitably arise when discussing one of the highest attainments of the h ­ uman mind—­genius. My default stance as a neurologist is that the brain has a lot to do with the mind, but this chapter does l­ittle or nothing to bridge the explanatory gap separating brain science and mind science (of which genius is a topic par excellence). So why read on? I can only presuppose that you are turning t­hese pages b­ ecause of your interest in: A) Einstein, B) brains, or C) genius. C now takes the stage, front and center, ­because it is emblematic of our personification of Einstein, it is a scarce and remarkable outcome for the ­human condition, and even if we 179

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disregard neuroscience with the concession that “a materialist definition of genius is impossible,” 3 we are transfixed by it. Why? Pick your favored cultural “carrots” (as opposed to “sticks”) along the lines of “fame, fortune, and happiness,” and it ­won’t be long before you seize upon genius as an effective means of grabbing a bunch. Genius as practiced by Einstein or Shakespeare can leave an indelible imprint on posterity (fame). Genius wielded by the likes of Steve Jobs or Bill Gates can lead to the accrual of staggering wealth (fortune). The happiness part of the genius triad is a l­ittle more uncertain and problematic . . . ​a s in tortured geniuses. The psychologist Kay Redfield Jamison studied the incidence of mood disorders and suicide in thirty-­six En­glish and Irish poets born from 1705 to 1805. Byron, Keats, Shelley, Words­worth, Samuel Johnson, Coleridge, and Blake ­were among ­these creative geniuses, and their ­mental health “scorecard” was discouraging—­more than half suffered mood disorders, two committed suicide, and four w ­ ere institutionalized in asylums.4 Okay, two out of three ­isn’t bad . . . ​and t­ here are undoubtedly some happy and emotionally stable geniuses. For example, Einstein told C. P. Snow that “in his experience, the best creative work is never done when one is unhappy.” 5 Emotional storm warnings aside, genius is simply an impor­tant subset of global cultural imperatives. Just ask the Tiger Mom sending ju­nior to the “Mozarts and Einsteins” preschool. Just ask the teenager cramming for a perfect sixteen hundred (yup, they brought back the old scoring scheme in 2016) on her SATs. Just ask the job applicant who wants to ace her Google interview. Just ask the young assistant professor who receives an unsolicited $625,000 “genius” grant from the MacArthur Foundation for “extraordinary originality.” And like Enron, every­one wants to be “the smartest guy in the room,” Faustian bargain or no. If ­you’re convinced that our con­temporary perception of genius is an unchanging legacy from the time that humankind began to appreciate the life of the mind, you’d be mistaken. Our characterization of genius shifted from external to innate likely sometime in the eigh­teenth c­ entury. Prior to that time, genius (from the Latin



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geno, meaning “beget”) in Roman my­thol­ogy was a generative and protecting spirit or deity allotted to each man at birth. “The genius of a man, as his higher intellectual self, accompanies him from the cradle to the grave. In many ways he exercises a decisive influence on the man’s character and way of life.”6 It is in­ter­est­ing but entirely unfounded to speculate that the Arab word jinn (­later to become the genie of A Thousand and One Nights) for a super­natural being may have shared common etymologic ground with the Latin genius when the Roman Empire encompassed Syria. A snapshot of the changeover from the old version of genius to the new appears in Samuel Johnson’s A Dictionary of the En­glish Language in 1755. Five dif­fer­ent definitions are listed u ­ nder the entry for genius, and the first epitomizes the ancient Roman conceit of “the protecting or ruling power of men, places, or ­things.” The new order of innate genius can be found in the second and third definitions: “A man endowed with superior faculties” and “­mental power or faculties.”7 Possibly, the Enlightenment (from 1715 to 1789 for the Francophiles among us) set the stage for genius as an inborn h ­ uman capacity, but certainly by the eigh­teenth c­ entury, the modern sense of genius was off to the races (and this bears out statistically). According to a cursory Google Books Ngram Viewer search of greater than five million books as of 2008, the use of the term genius on the printed page increased over 2,600 ­percent, between 1700 and 1774.8 As further testimony to the shape-­shifting idea of genius, it should be recalled that Isaac Newton (1642–1727) was a first-­rank genius in e­ very sense of the modern word, and he performed his greatest scientific work in the seventeenth ­century. Newton, with whom Einstein is pretty much in a dead heat for the title of Greatest Scientist bar none, died in 1727 and was interred in Westminster Abbey. In 1731 the seventy-­t wo word Latin inscription on the monument in the nave never cited “genius” in its brief hagiography. Alexander Pope’s epitaph was never chiseled into the monument but remains memorable: “Nature and nature’s laws lay hid in the night; God said ‘let Newton be’ and all was light.”9

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The seventeenth-­century idealization of genius of divine origin dated back nearly two millennia and was incisively expressed by what was left unwritten in the Westminster Abbey inscription. Pope obligingly upped the ante for divinely granted genius when he invoked the majesty of (Newton’s heretical non-­Trinitarian vs. Pope’s Catholic) God rather than a minor tutelary deity of the ancient Romans. It is safe to say that by the time Einstein came on the scene, the modern conception of innate genius held sway but lacked an operative definition. It took a while before Einstein was recognized for the genius he was. ­Going back to his miracle year in 1905, “it is pretty safe to say that, so long as physics lasts, no one ­will again hack out three major break-­throughs in one year. . . . ​It took about four years for the top German physicists, such as Planck, Nernst and von Laue, to begin proclaiming that he was a genius.”10 Once Einstein got started, his ascent was steep, but it took a l­ittle while to garner the initial academic recognition. He d ­ idn’t make it to the academic big time u ­ ntil he was offered a full professorship in Prague in 1911, six years ­a fter he had established the existence of atoms, affirmed quantum theory, and created special relativity. C. P. Snow’s objections aside, although early-­t wentieth-­century physics was a close-­ knit and fast-­moving field, recognition of Einstein’s genius was not instantaneous. This takes us back to the prob­lem of imprecision in a working definition of genius. Additionally, in Einstein’s case, the lack of a university affiliation in 1905 may have slowed down recognition by the old boys’ club of academic physicists. And the revolutionary nature of his discoveries may have been off-­putting to the physics establishment. If the Nobel Prize can be regarded as a benchmark for genius, one of the supreme ironies of Einstein’s ­career is that he did not receive his 1921 (actually awarded in 1922) Nobel Prize in Physics for his greatest intellectual accomplishments—­ the theories of special and general relativity. The Nobel Prize Committee assigned the influential report on relativity to Alvar Gullstrand, an academic ophthalmologist who won the 1911 Nobel Prize in Physiology or Medicine for his work on accommodation



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(how the eye changes its focus from far to near and vice versa). “With l­ittle expertise in e­ ither the math or physics of relativity, he criticized Einstein’s theory in a sharp but unknowing manner.”11 This is evocative of Cambridge astronomer Arthur Eddington’s initial silence when told that ­people believed that only three scientists in the world (including Eddington) understood general relativity. Eddington then drily intoned, “I’m just wondering who the third might be.”12 Suffice it to say that Gullstrand was not one of ­those three, and “Einstein would not, as it turned out, ever win a Nobel Prize for his work on relativity and gravitation, nor for anything other than the photoelectric effect.”13 Over a ­century’s worth of hindsight assures us that Einstein was a genius of the first rank “but pressed to be more precise, we find it remarkably hard to define genius, especially among individuals of our own time.”14 Pertaining to genius, “we may very well know it when we see it,” but the following trenchant questions may put it into sharper focus. Is ­there more than one kind of genius? In 1904, as Einstein was setting the stage for his imminent annus mirabilis, the En­glish psychologist Charles Spearman “noted as the data from many dif­fer­ent ­mental tests w ­ ere accumulating, a curious result kept turning up: If the same group of p ­ eople took two dif­fer­ent m ­ ental tests, anyone who did well (or poorly) on one test tended to do similarly well (or poorly) on the other.”15 This statistically positive correlation led Spearman to propose “a unitary ­mental f­ actor, which he named, g, for ‘general intelligence.’ ” The hypothesis of g has weathered the buffets of scientific inquiry for nearly a ­century—­“the g ­factor . . . ​ accounts for about half of the variability in ­mental ability in the general population.”16 The pronouncement of Lord Rutherford, the proton’s discoverer, to the effect that “all science is ­either physics or stamp collecting” can be loosely applied to the foregoing classification of intelligence. In just about any scheme of classification (including

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philately), t­ here are “lumpers and splitters,” and in contrast to g, which lumps intellect into a unitary m ­ ental entity, ­t here is a dissenting categorization, according to Howard Gardner’s theory of multiple ­ uman intelligence into ten (at last intelligences.17 Gardner “splits” h count) abilities: 1. Spatial 2. Linguistic 3. Logical-­mathematical 4. Bodily-­k inesthetic 5. Musical 6. Interpersonal 7. Intrapersonal 8. Naturalist 9. Spiritual 10. Existential 11. Moral? (The jury is still out on this one.) Gardner readily acknowledges that multiple intelligence theory “questions not the existence but the province and explanatory power of g . . . ​and centers on ­those intelligences and ­those intellectual pro­ cesses that are not subsumed ­under g.”18 In Gardner’s view, “creators” are not one-­t rick ponies but “exhibit an amalgam of at least two intelligences. . . . ​Like most physicists, Einstein had outstanding logical-­mathematical intelligence, but his spatial capacities w ­ ere extraordinary even among physicists.” As a neurologist I frequently work with a modular construct of brain anatomy. If a patient has impaired speech (expressive aphasia) or trou­ble recognizing ­faces (prosopagnosia), I review the MRI for signs of damage to Broca’s area in the (usually) left inferior frontal convolution and the fusiform gyrus of the ventral occipital lobe, respectively. In t­hese cases ­there is diagnostic utility to embracing a splitter approach . . . ​but the modular scheme is not as successful when grappling with ­human capacities, such as creativity or judgment. We are a long way from sussing out stand-­a lone structural bases of multiple intelligences, and it may make “more sense now



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to speak of several brain areas involved in any complex intellectual activity.”19 To a neurologist in the early twenty-­first c­ entury, any ­mental map such as Gardner’s (or for that ­matter, Freud’s venerable triad of ego, superego, and id) cannot be superimposed on our current knowledge of neuroanatomy. Can genius be mea­sured with IQ tests? Right off the bat, let me state that I ­don’t perform IQ (intelligence quotient) tests on my patients; most neurologists conduct abbreviated neuropsychological (as opposed to psychological) tests to screen for brain (as opposed to mind) disorders. I ­will administer a Mini-­Mental State Exam, a Mini-­CogTM, or the Montreal Cognitive Assessment to evaluate a patient for cognitive impairment, memory disorders, or disorders of language, such as aphasia. The mea­sure­ment of IQ is not on my clinical “radar,” which is trained on neurologic disease and not on determining f­uture academic or job per­for­mances (or, for that ­matter, eligibility for Mensa). The Wechsler Adult Intelligence Scale, version IV (WAIS IV) most commonly assesses ­these occupational and scholastic capacities. Th ­ ese tests have been around since 1939, and the latest iteration, WAIS IV (WAIS V is in the works), has ten core subtests and five supplemental subtests. It may be a benchmark (along with its closely correlated cousin, the SAT) for intelligence, but it has no subtest to mea­sure creativity or wisdom.20 David Wechsler defined intelligence as “the aggregate or global capacity of the individual to act purposefully, to think rationally and to deal effectively with the environment.” Definitions and mea­sure­ments are two dif­fer­ent issues, and Wechsler observed that “the entity or quantity which we are able to mea­sure by intelligence tests is not a ­simple quantity” and “that intelligence tests do not and cannot be expected to mea­sure all of intelligence.”21 Shortcomings aside, intelligence tests could mea­sure scholastic achievement in ­children, assess ­mental deficiency in adults, and classify drafted soldiers. However, interleaved with discussion of “defective” and “dull-­normal” subjects Wechsler’s remarks on the psychometric characterization of genius are cautiously limited to “levels of be­hav­ior which pres­ent certain patterns [that] . . . ​reach the other

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end of the scale where they are labelled very superior, precocious or genius.”22 The “I.Q. Range” assigned to “genius or near genius” (“140 and above”) was reproduced in a ­table from the educational psychologist Lewis Terman’s research thirty-­three years earlier in 1916. While Wechsler was reticent to elaborate on the identification of genius by his intelligence test methodology, one of Terman’s gradu­ate students, Catherine Cox, had no such qualms in 1926 when she compiled a ranking of 301 “young geniuses” who had lived between 1450 and 1850.23 Lists have a way of catching the public’s eye—­for example, David Wallechinsky’s best-­selling Book of Lists ­ hether flawed or spot-on, is no in 197724 —­and a list of geniuses, w exception. No one on Cox’s list was around to take the ur-­intelligence tests, such as the Binet-­Simon test (1905), which begat Terman’s Stanford-­Binet test in 1916. She improvised her own methodology of historiographic IQ testing, which combined two intelligence ratings for each individual, the first based on the subject’s mastery of basic skills, such as speaking, reading, or writing, and the second on academic rec­ords and early professional ­careers. ­These ­were combined with personality characteristics25 and, for better or worse, Cox’s list was born. The Top Ten:26 1. Goethe (IQ = 210) 2. Leibnitz (IQ = 205) 3. Grotius (IQ = 200) 4. Wolsey (IQ = 200) 5. Pascal (IQ = 195) 6. Sarpi (IQ = 195) 7. Newton (IQ = 190) 8. Laplace (IQ = 190) 9. Voltaire (IQ = 190) 10. Schelling (IQ = 190) Every­one (geniuses not excepted) likes to make it to the medal round. Einstein is not on the list (even eleven years ­after general



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relativity) likely b­ ecause of Cox’s 1850 cutoff date. However, scientists and mathematicians are inordinately well-­represented in the top ten on her list of Worthies, and number seven, Isaac Newton, is pretty much the all-­time poster boy for scientific genius. Only three (Grotius, Cardinal Wolsey, and Voltaire) had nothing to do with math, science, or natu­ral philosophy. Lists, by virtue of their selectivity, can be capricious, and this is affirmed by Cox’s series that omitted Pasteur, Maxwell, Shelley, and Tolstoy, to name a few. Taking Cox’s retrospective IQ estimates at face value, many scientific geniuses had “stratospheric” IQs, but is a high score on an IQ test alone sufficient to designate a genius? Wechsler waggishly recounted the tale of “a prominent psychologist” who “answered an inquiry as to what he meant by intelligence by saying that it is what intelligence tests mea­sure.”27 This “intelligence = intelligence test results” tautology makes no mention of the defining spark of true genius, and, for my money, that spark is creativity. Cox’s study on genius employed the methodology of historiometry and recognized psychological indices. Her subjects ­were dead, and in academic medical research, we would classify this as a retrospective or chart review study based on the past rec­ords of living or dead patients. Another fundamental approach is termed prospective study, which was precisely the undertaking of her PhD supervisor, Lewis Terman. Beginning in 1921 Terman collected data on 1,528 “gifted” ­children in California. The so-­called “Termites” had average IQ scores above 150, and Terman’s successors collected follow-up data on some of them for sixty-­five years a­ fter the inception of the Ge­ne­tic Studies of Genius.28 With the exception of the physicist J. Robert Oppenheimer, as “the cohort matured, its members did not produce a significant number of creative individuals.”29 Conversely, two ­future Californian Nobel laureates in physics, Luis W. Alvarez (for particle physics) and William Shockley (for discovery of the transistor effect), did not qualify to become “Termites.” Few, if any, longitudinal prospective studies have ever exceeded Terman’s magnum opus, which established that “genius (in the sense of creativity) was not the same as a high level of intelligence”

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(as mea­sured by IQ tests). In the words of the neuroscientist and neuropsychiatrist Nancy Andreasen, “Intelligence is somewhat related to creativity but it is also dif­fer­ent.”30 As if the lack of correlation between IQ testing and creativity did not pose enough of an obstacle to ferreting out creative p ­ eople, in the 1980s James R. Flynn, a professor of po­liti­cal studies at the University of Otago, found that intelligence as mea­sured by IQ testing was a moving target! It was well known that some IQ test scores change with age, but Flynn rigorously demonstrated that standardized IQ tests, such as the Wechsler, Stanford-­Binet, and ­others, have shown that “the ‘average’ person of the ­later generation was scoring way above the ‘average’ person of the earlier generation. . . . ​Flynn makes the telling point when he asks us to reflect on the fact that being born a generation or so apart can make a difference of fifteen IQ points. We have no good account for this change; it is officially mysterious.”31 Given that “beyond an IQ of about 120 . . . ​mea­sured intelligence is a negligible f­ actor in creativity,” are t­ here any better tests to identify creative genius? “Divergent or lateral thinking” tests of creativity have been around for over sixty years. They differ from standardized IQ tests that mea­sure logical or convergent thinking, but “­there is no correlation between high scorers on divergent thinking tests and their creativity in real life.”32 However, one recently touted bellwether metric of creativity is the conjoint application of the SATs and tests of spatial ability from the DATs (Differential Aptitude Tests). The forty-­five-­year-­old and still g­ oing strong longitudinal Study of Mathematically Precocious Youth found “a correlation between the number of patents and peer-­refereed publications that ­people had produced and their earlier scores on SATs and spatial-­ability tests.”33 Is genius hereditary? To modern sensibilities raised on the nature versus nurture debate, this is a most dangerous question, bristling with implications of DNA/racial/gender elitism. In 1869 as far as Francis Galton, Charles Darwin’s cousin and a reader before he was



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three years old, was concerned the answer could not have been more obvious. The title of his book, Hereditary Genius: An Inquiry into Its Laws and Consequences, leaves l­ittle doubt as to his conclusion. The first sentence on the first page declares, “I propose to show in this book that a man’s natu­ral abilities are derived by inheritance.”34 Even this “eminent” Victorian had qualms as to the precise nature of the subject of his book’s title, decrying “the uncertainty that still clings to the meaning of the word genius in its technical sense.” (Author’s note: my sentiments exactly . . . ​125 years ­later.) In the prefatory chapter of his 1892 reprint of Hereditary Genius, Galton wondered ­whether Hereditary Ability might have served as a better title. In 1869 he used the word genius to describe “an ability that was exceptionally high, and at the same time inborn.” If genius was a ­mental power sui generis or qualitatively dif­fer­ent than high ability, Galton did not inform us, but he did set out to mea­sure it.35 And his par­tic­u­lar metric of intellect was that “high reputation is a pretty accurate test of high ability.” He sought to elucidate the “laws of heredity in re­spect to genius” by surveying familial relationships of what was in essence a Victorian slant on Alexander Pope’s hierarchical “Vast chain of being,”36 beginning with judges of ­England (1660–1868), statesmen at the time of George III, and premiers (prime ministers) of the last one hundred years. ­These ­were followed “in order” by illustrious commanders, men of lit­er­a­ture and science, poets, paint­ers, divines, modern scholars, and, in the realm of “physical gifts,” oarsmen, and wrestlers.37 When Galton “crunched the numbers” of “no less than three hundred families containing between them nearly one thousand eminent men, of whom 415 are illustrious,” he was convinced that if ­there was “such a t­ hing as a deci­ded law of distribution of genius in families, it is sure to become manifest when we deal statistically with so large a body of examples.” The upshot was that “exactly one-­ half of the illustrious men have one or more eminent relations.” The chances of rising to eminence for a kinsman of an illustrious man varied from one out of four (son), to one out of seven (­brother), to one out of one hundred (first cousin).38

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Once he had established that heredity was the dominant f­ actor for h ­ uman ability and genius, he could resolutely declare all hope of improving the natu­ral gifts of ­future generations to be “­under our control.” The admonition that “we may not be able to originate, but we can guide” 39 opened a Pandora’s box for the “benefits” of selective h ­ uman breeding for “desirable” traits or, as it came to be known—­eugenics—­a term coined by Galton in 1883. Far from being repelled, his Victorian audience embraced his message, and the first edition (1869) of Hereditary Genius sold out, becoming “unpur­chas­ able except at second­-­hand and at fancy prices.” Galton’s vision of the dominance of intellectual pedigrees and cognitive bloodlines has not withstood the passage of nigh on 150 years. Ironically, he memorably delineated a major, if not the major, battleground of cognitive psy­chol­ogy when he coined the phrase/meme/war cry of “nature and nurture” which “separates ­under two distinct heads the innumerable ele­ments of which personality is composed.”40 Galton’s view of heredity as the prime mover of intellect has been largely supplanted by the twentieth-­ century belief that nurture assumes the commanding role in the formation of intellect. Society’s commitment to this “can do” philosophy, centering on the most potent form of nurture, education, can be seen in the proliferation of Head Start programs or in the online curricula conferring doctoral degrees. Was Galton (wielding an IQ of 200, as estimated by Louis Terman)41 dead wrong and the modern educational credo that bright kids are “made, not born” 100 ­percent right? It’s a leading question that ­will not be answered in a book about the neuroscience of Einstein’s brain, but psychological studies of identical twins may shed some light on the topic of the wellsprings of intelligence. The Minnesota Study of Twins Reared Apart (MISTRA) tested fifty-­six sets of identical (monozygotic—­i.e., with 100 ­percent of their genes in common) twins and found that “70 ­percent of the observed variation in IQ in this population can be attributed to ge­ne­tic variation.”42 “Identical twin pairs who spent their lives apart end up just about as similar in intelligence as ­those who spent their lives



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together.”43 Taken at face value, psychological studies of the modern era suggest that in the arena of IQ, nature dominates nurture. Although MISTRA seemingly did not get the memo that nurture inscribing a cognitive blank slate was the exclusive mechanism of assembling intellect, the investigators left a ­little wiggle room for educators and concerned parents when they allowed that their “findings do not imply that traits like IQ cannot be enhanced.” Before we can wholly consign our intellectual destiny to the genome, it bears mentioning that if ­mental ability genes exist, we “have no idea what ­those genes are. . . . ​The best guess among researchers is that m ­ ental abilities are influenced by an unquantifiable number of genes, each of which ­w ill have a small effect.”44 And what’s more, the sizes of the genome and the brain d ­ on’t match up. As of 2014 it is generally accepted that the three billion DNA base-­pairs of the ­human genome contain nineteen thousand to twenty thousand protein-­encoding genes. (Caveat: ­don’t focus on numbers. The one-­millimeter roundworm Caenorhabditis elegans has 20,470 genes, albeit with a “no-­frills” one hundred million base-­ pair count). In stark contrast to the magnitude of our genome, the ­human brain has eighty-­five billion to eighty-­six billion neurons, with one thousand to ten thousand synaptic connections per neuron. The sheer quantity of pos­si­ble arrangements of neuronal connectivity is staggering! Clinical neurologists are definitely not savants of ce­re­bral architectonics (Read “wiring diagrams” of the brain), but if we insist (and I ­don’t) that nature/heredity/genome is the only game in town vis a vis neural organ­ization, how can the genome possibly contain enough instructions to hardwire the currently unfathomable complexity of the brain? The DNA “true believers” ­will insist that protein-­encoding genes are not the ­whole story b­ ehind “building” a brain. ­There may well be operating instructions for regulating gene expression in the other 98.5 ­percent of the genome that d ­ oesn’t assem­ble our amino acids into building-­ block proteins. Or, epige­ne­tic mechanisms in which the environment alters gene expression without changing the DNA sequence may be in play.

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My somewhat informed hunch is that our genes, although incorporating basic organ­izing princi­ples of the mammalian brain, fall short of containing a completely specific blueprint of central ner­ vous system (CNS) architecture. And ­here nurture comes to the rescue. When Francis Galton wrote in 1874 that “nature is all that a man brings with himself into the world,” the two most basic ele­ments of the nature of brain microanatomy, Cajal’s neurons and Sherrington’s synapses, would not be brought to light ­until 1906 and 1897, respectively. As knowledge of neurons, axons, dendrites, and synapses accrued, they w ­ ere seen as constituent parts of the early-­twentieth-­ century hardwired model of the brain that was likened to a telephone switchboard. Donald Hebb’s proposal of a dynamic synapse in 1949 called into question this static conception of brain wiring, and Hebb’s theory of synaptic plasticity as a basis for learning was confirmed in 2000 by Eric Kandel’s Nobel Prize–­winning demonstration of the growth of new connections between motor and sensory neurons with the induction of long-­term memory in the marine snail Aplysia.45 The neural paradigm changed for good with the recognition of neuroplasticity, which showed the brain’s wiring to be a dynamic pro­cess at the beck and call of nurturing influences, such as what we see and hear or think or learn in school. Nature versus nurture as the origin of genius (or intellect for that ­matter) remains a question that is as contentious as it is complex. In-­depth knowledge of the biological bases—­the h ­ uman genome and neuroplasticity—of Galton’s dyadic proposal have been on the scene for less than twenty years. The implications of this newfound biology are not confined to sequencing base-­pairs of intertwined strands of DNA or tracing axonal connections. Extrapolating from Kandel’s synthesis of the data from his ­humble sea snail, the ­human genome and neuroplasticity may address the essence of ­human thought if we presume to equate the inborn ge­ne­tic instructions for neural circuitry with Kant’s inborn a priori knowledge and neuroplasticity with Hume’s empiricism, in which knowledge is not innate but must be learned from sensory experience.46 Even Einstein’s penetrating introspection c­ an’t help us choose between ­these two



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schools of philosophy of the mind. He rejected the tenets of both Kant’s and Hume’s philosophies47 (although Hume’s empiricism was a closer fit for Einstein’s approach to physics). Did our examination of the “lost” photo­graphs of Einstein’s brain land us firmly on the side of nature or nurture? Neither. We straddled the line and wrote that “the enlarged [motor cortex] ‘knob’ that represents the left hand . . . ​is prob­ably associated with his early and extensive training on the violin. This par­tic­u­lar feature of Einstein’s gross anatomy was likely the result of both nature and nurture”48 (italics added). Does genius have a structural basis? Leaving aside the foregoing debate as to ­whether the unimaginable complexity of ­human neuroanatomy arises from the genomic instruction manual, sensory-­driven neuroplasticity, or both, we come face-­to-­face with the question of the relationship of intelligence and brain structure. This par­tic­u­lar question can be sidestepped if y­ ou’re a dualist who regards the mind and the brain as separate entities (and never the twain ­shall meet). As a neurologist dealing with structural brain disorders on a daily basis, I d ­ on’t know how to apply the princi­ples of neuroscience to the “prob­lem” of finding a basis for noncorporeal “mind-­stuff,” spirit, or soul, which likely reside outside the bound­aries of paleontologist Stephen Jay Gould’s “magisterium of science.”49 The concluding thrust of our research was that Einstein’s exceptional brain was the basis of his genius. This may well be a scientific truth that is forever unprovable, or in the words of the phi­ los­o­pher Colin McGinn, “The bond between the mind and the brain is a deep mystery. Moreover it is an ultimate mystery, a mystery that h ­ uman intelligence ­will never unravel.”50 McGinn’s “depressingly negative conclusion” is straight out of the playbook of mysterianism, in which our species’ intellectual shortcomings “filter out what is crucial [to understanding] the brain’s real nature.”51 While McGinn has said dismissively that w ­ e’re not smart enough to realize that “­there has to be some aspect of the brain that we are blind to, and deeply so,” the mathematician Brian Burrell has piled

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on and observed that no Einstein brain study “has revealed a credible anatomical basis for the man’s aptitude.” Not content with disparaging our peer-­reviewed (scientific-­ese for the Good House­keeping seal of approval) anatomical findings, Burrell editorialized that the so-­called failure of Einstein brain studies is a good t­hing b­ ecause “discovery of substrates of talent—or lack thereof—in the brain would have troubling practical and ethical implications.”52 If y­ ou’re keeping track of the critical “slings and arrows” aimed at the philosophical under­pinnings of our study, the list includes: (1) The brain is not the place to look (dualism), (2) If it is the place to look, w ­ e’re too dumb to recognize the physiological/anatomical “signature” of genius (mysterianism), and (3) It’s unethical. Wow. That’s a discouragement “hat trick” for what seemed like a pretty good curiosity-­driven piece of brain science that produced some fascinating and verifiable findings. Undeterred, Dean Falk took a direct and effective idea and ran with it when she drew a parallel between paleoanthropology and her analy­sis of Thomas Harvey’s photo­graphs of Einstein’s ce­re­bral hemi­spheres: “In order to glean information about hominin (or other) brains that no longer exist, details of external neuroanatomy that are reproduced on endocranial casts (endocasts) from fossilized braincases may be described and interpreted. . . . ​A lbert Einstein’s brain no longer exists in an intact state, but ­there are photo­graphs of it in vari­ous views. Applying techniques developed from paleoanthropology, previously unrecognized details of external neuroanatomy are identified on ­these photo­graphs.”53 Putting the straightforward, transparent, and honest premises of our study aside, what is the evidence for a legitimate link between intelligence and brain structure? Nancy Andreasen used MRI scans to compare the brain size of sixty-­seven healthy, normal volunteers with their IQ as mea­sured by the WAIS. Her conclusion was, “The larger the brain, the higher the IQ.”54 The general term brain size subsumes disparate ele­ments, including neurons, three types of glial cells, axons, myelin sheaths, dendrites, synapses, blood and blood vessels, meninges, and cerebrospinal fluid (CSF). Andreasen mea­sured



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volumes of gray m ­ atter, white ­matter, and CSF separately and found a significant positive correlation between gray ­matter volume, verbal per­for­mance, and full-­scale IQ. This was an impor­tant study ­because it mea­sured the size of the functioning brains in living ­people, as opposed to autopsied brains or indirect mea­sures, such as head circumference or hat size. Writing well a­ fter the advent of sophisticated neuroimaging, Stephen Jay Gould impugned craniometry—­the mea­sure­ment of the skull and its contents—as a particularly egregious “mismea­sure of man” in his book of the same title.55 A de­cade ­later Andreasen’s data flew in the face of Gould’s despairing observation that “the supposed intellectual advantage of bigger heads refuses to dis­appear entirely as an argument for assessing h ­ uman worth.” As t­ hese two scientific hypotheses cudgel each other, I ­will again interject that Einstein’s brain weighed in at 1,230 grams, a ­little less than expected for a seventy-­six-­year-­old man. The brain-­size wars ­will undoubtedly continue. Read on. Does evolution have anything to teach us about brain size and intelligence? “The 1.35 kg brain of Homo sapiens supposedly the smartest creature on earth, is significantly exceeded by the brains of elephants and some cetaceans. Thus, a larger brain alone does not necessarily assure greater intelligence.”56 Bigger bodies require bigger brains. It stands to reason that a male African elephant weighing more than five tons and mea­sur­ing ten feet tall at the shoulder needs a bigger brain to ­house the additional sensorimotor neurons and connections required to innervate yards of elephant hide, massive limb joints, a trunk, and thousands of pounds of muscle. Leaving aside the distinguishing (and mostly unknown) features of the intelligences of ­whales, pachyderms, and primates, it may be argued that absolute brain size provides ­little if any insight and that relative brain (the ratio of brain to body mass) weight may be a more useful index. ­Humans score highly on this index, with a relatively large brain at 2 ­percent of body mass, but we c­ an’t hold a candle to shrews, which have brains weighing in at 10 ­percent of body mass. (Some shrews have the fairly unique ability to echolocate, but if they have g­ reat intelligence they are holding their cards pretty close to

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their chests.) When neurobiology ­doesn’t deliver on our aspiration to be the smartest guys in the room . . . ​I mean, animal kingdom), statistics come to the rescue with the encephalization quotient (EQ), a ratio that compares the departure of the brain size of a par­tic­u­lar mammalian species, such as Homo sapiens, from the size of a “standard” mammal—­the cat. “­Humans have the highest EQ of 7.4–7.8, indicating that the h ­ uman brain is 7–8 times larger than expected.”57 Despite this self-­affirming finding, contradictory results with capuchin monkeys and chimpanzees led German neuroscientists Roth and Dicke to caution that “EQ is . . . ​not the optimal predictor of intelligence.” Or, we may be at the threshold of an alternative anatomical index for intellect if we count neurons rather than weigh ­whole brains. Primate (and by extension) h ­ uman brains may have a greater density of neurons than ­whale or elephant brains: “Our superior cognitive abilities might be accounted for simply by the total number of neurons in our brain, which, based on the similar scaling of neuronal densities in rodents, elephants, and cetaceans, we predict to be the largest of any animal on Earth.”58 If the lessons of evolutionary brain development fail to validate the premise that (brain) “size does m ­ atter,” uncertainty only increases when we consider the cases for the G ­ reat Leap Forward and a hydrocephalic genius. Around forty thousand years ago, Western Eu­rope was populated by Neanderthals lacking art and much in the way of cultural innovation. “Then ­there came an abrupt change, as anatomically modern ­people appeared in Eu­rope, bringing with them art, musical instruments, lamps, trade, and pro­gress. Within a short time, the Neanderthals w ­ ere gone.” Physiologist/evolutionary biologist/­biogeographer Jared Diamond declared this Upper Paleolithic revolution “The ­Great Leap Forward.” 59 The relentless pressure of natu­ral se­lection consigned the less fit Neanderthals to oblivion as the Cro-­Magnons superseded them. ­These anatomically modern h ­ umans arose in Africa one hundred thousand years ago but initially had no cultural or technological advantage over the Neanderthals. However, during the last sixty



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thousand years, Cro-­Magnon technology and culture “leapt forward,” and ­these early modern ­humans migrated into Eu­rope, sweeping away the doomed Neanderthal world. For the neurologic determinist, the “secret” to Cro-­Magnon success would be bigger and better brains. “One might therefore expect the fossil rec­ord to show a close parallel between increased brain size and sophistication of tools. In fact, the parallel is not at all close. This proves to be the greatest surprise and puzzle of ­human evolution.”60 The neurologic determinist position is further eroded by the finding that as recently as forty thousand years ago, Neanderthals had brains even larger than ­those of modern h ­ umans. If “anatomically modern Homo sapiens populations living in southern Africa 100,000 years ago ­were still just glorified chimpanzees as judged by the debris in their cave sites,” what caused the ­Great Leap Forward sixty thousand years ­later?61 Diamond’s guess is “the perfection of our modern capacity for language.”62 Please indulge this inveterate neurologist when I protest that language does not appear “out of the blue”; ­there must be neural under­pinnings, such as asymmetry of the planum temporale, Broca’s area in the frontal lobe, Wernicke’s area in the temporal lobe, and the arcuate fasciculus, connecting the “eloquent” cortices of Broca and Wernicke. Although changes in laryngeal anatomy, allowing growls to become protowords and then h ­ uman elocution, has been proposed as the origin of language, language is more than what comes out of your mouth. Language originates in the brain and is not restricted to oral expression. ­People who are unable to speak can express language by writing or signing. My best surmise is that the G ­ reat Leap Forward, ­whether associated (or not) with the emergence of language, was neurally “engineered.” Paleoanthropology, by necessity, cannot directly examine hominin brains forty thousand years old; the soft tissue neural constituents have long since decomposed, and only the skulls or skull fragments remain. From endocasts of braincases, the size of the brain and some cortical landmarks, such as the lunate sulcus, can be approximated. When revisiting the G ­ reat Leap Forward,

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paleoanthropology can only reckon if brains ­were bigger (they ­weren’t) but ­can’t determine if they ­were better or, to be more precise, intrinsically dif­f er­ent. The most painstaking inspection of the mineralized matrix of a Cro-­Magnon skull that has weathered forty millennia would be blind to profound changes in cortical neuronal/glial cell count, synaptic density, myelination, and axonal pathways. I do not mean to downplay the profound role of culture and social interaction in advancing humankind by leaps and bounds. I strongly doubt that the brains of p ­ eople during the Re­nais­sance or the Enlightenment ­were anatomically dif­f er­ent from ­those of a generation or more earlier, but the magnitude and sweeping changes of the G ­ reat Leap Forward—­finely wrought stone tools, body adornments, art, burial rituals, language—­more than countenance the necessity of neurologic reor­ga­ni­za­tion, which remains, for the most part, invisible to pres­ent neuroscientific investigations. Lacking an Upper Paleolithic brain to study, my hypothesis remains unproven, and the field remains open to differing interpretations, such as that of cognitive archaeologist David Lewis-­Williams, who cautions us to “not seek a neuronal event as the triggering mechanism for the west Eu­ro­pean ‘Creative Explosion,’ ”63 his term for the cultural upheaval forty thousand to fifty thousand years ago. He points us to “social circumstances” and the “role of art in social conflict, stress and discrimination.” About thirty-­six thousand years ­after an Upper Paleolithic “Michelangelo” began painting polychrome bison on the walls of Altamira Cave on the northern Spanish coast, Professor John Lorber of Sheffield University described a young university student who gained a first-­class honors degree in mathe­matics. We ­w ill likely never know the neuroanatomy of the early (presumably non-­ Neanderthal) h ­ umans adorning the Western Eu­ro­pean caves, such as Chauvet, Lascaux, and Altamira, “where ‘art’ began,” but we are acquainted in detail with the paradoxical brain of the gifted math student. Dr. Lorber’s patient had hydrocephalus (or more colloquially, ­water on the brain). Except it r­ eally ­isn’t w ­ ater—­it’s CSF, a complex



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biological substance, cerebrospinal fluid, which is secreted by the choroid plexuses inside the brain’s hollow cavities (ventricles). If the ­free flow of CSF is obstructed, it backs up in some or all of the four ventricles pres­ent in ­every anatomically normal h ­ uman’s brain. As the CSF accumulates, the intracranial pressure exceeds the normal upper limit of 150 millimeters of w ­ ater, which can be mea­sured with a manometer when I perform a spinal tap (a bad term—­let’s call it a lumbar puncture . . . ​I studiously avoid the spinal cord during the bedside procedure) on a patient. The increased CSF pressure expands the ventricles like balloons and compresses the brain tissue. In the case of the math student, Lorber saw “that instead of the normal 4.5-­centimeter thickness of brain tissue between the ventricles and the cortical surface, ­there was just a thin layer of mantle mea­sur­ing a millimeter or so. His cranium is filled mainly with cerebrospinal fluid.”64 Despite the profoundly altered cortical anatomy of his hydrocephalic brain, Lorber’s patient had an IQ of 126! ­Needless to say, it is difficult to accept the premise that the brain generates mind or that intelligence is exclusively brain-­based ­after encountering a severely hydrocephalic and intellectually gifted individual as just described. Before you enroll in Lorber’s school of cortical nihilism, consider an ill-­fated embryologic experiment of nature known as anencephaly. Anencephalic ­humans have eyes, a brain stem, a cerebellum, and a spinal cord but no ce­re­bral hemi­spheres. During the few days to weeks of survival, they exhibit ste­reo­t yped, reflexive movements, including decerebrate posturing (the rigid extension of the arms and the legs).65 They ­really have no brain above the level of the high brain stem (mesencephalon), and in contrast to Lorber’s hydrocephalic mathematician, the absent hemi­spheres of ­humans with anencephaly profoundly reduce their ­mental life and behavioral repertoire to a short-­lived assemblage of automatic and involuntary fragments of movement. I ­will not presume to disallow dualism (in which the mind is unharnessed from the brain) as a plausible interpretation for Lorber’s regrettably unpublished case study. It could be argued that if (substance) dualism, which distinguishes mind from ­matter, was

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good enough for René Descartes (1596–1650), why not for us? As an almost obligate materialist by way of my occupation, I w ­ ill play the dev­il’s advocate on this highly charged mind/spirit point and offer some opposing contentions from the neurologist’s conceptual tool kit. Possibly, ce­re­bral cognitive “reserves” and intact noncortical structures, including the thalami, are sufficient to compensate for the structural alterations of hydrocephalus. Alternatively, the compressive thinning of the neurons and the connecting white m ­ atter of the cortical mantle may not be a mortal wound on the cellular level, and t­ hese neural ele­ments may continue to function. ­Needless to say, not ­every brain disease targets intelligence. For example, amyotrophic lateral sclerosis (ALS) does cause the death of motor neurons in the spinal cord, brain stem, and frontal lobes. In most cases the pyramidal cells (so-­called due to their triangular appearance ­under the microscope lens) of the precentral gyri of the frontal lobes atrophy and die. About 10 ­percent of ALS patients develop dementia. However, a notable exception to the features of ALS, which may jeopardize intelligence, is Stephen Hawking, arguably the world’s most renowned theoretical physicist and cosmologist. Hawking has had an unusual form of ALS, with protracted survival, for well over five de­cades. I can only speculate that his par­ tic­u­lar variant of ALS has been confined to the motor neurons, sparing the “intellectual” portions of his frontal lobes involved with abstraction, association, and executive functions. The selective vulnerability and the selective resilience of par­tic­ u­lar neuronal subsystems are opposite sides of the same coin for many neurologic diseases. In Parkinson’s disease (PD), a subset (called extrapyramidal) of the motor pathways is damaged, and the sensory pathways are spared. In PD selected neurons are marked with a distinctive neuropathologic “signature” of damage (Lewy bodies), but we lack a basic understanding as to why one (motor) portion of the CNS dies, and another (sensory) portion thrives. Or how intellect can be preserved in the face of brain disease not ­because it exists in a shadowy “sanctuary” of nonphysical mind stuff but rather ­because the disease’s biology exempts cognitive ce­re­bral networks.



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Any ringing endorsement of dualism and the nonphysical mind should be tempered by what e­ very clinical neurologist learns over time. To wit, the ­human brain and its myriad functions are awe-­ inspiring in their complexity, and consequently, we are unable to all-­inclusively correlate CNS structure and functions. The absence of such correlations for par­tic­u­lar functions may be more illustrative of our neuroscientific ignorance and should not serve as compelling proof of the mind loosed from the body. To a dyed-­in-­the-­wool ce­re­bral materialist, it is tempting to downplay our lack of knowledge and contemplate a seemingly reasonable proposition such as: More brain cells = More mind It’s a very rough assertion of parity in an unproven biological structure-­function relationship. It may be dressed up as an equation, and we can certainly count neurons, but bear in mind that a neuronal census raises other questions. If we posit the total number of cortical neurons of each ce­re­bral hemi­sphere to be the seat of intellect, it is perplexing to note that for each cortical neuron we have four cerebellar neurons66 (and although t­ here is some evidence of cerebellar cognition, it does not ­factor in as a major player for ­human intellect).67 Moreover, we are at a loss when it comes to “counting” non­ex­is­tent units of the mind. Does “more” mind mean “higher” intelligence, “deeper” insight, “broader” perspective, or something e­ lse entirely? Assuming we can assign valid mea­sure­ ments to something as abstract as the mind, ­we’re still left with the discordant observation that plus-­size w ­ hale and elephant brains do not ­house an overpowering intelligence that we can recognize at pres­ent. Putting aside the formidable methodological questions raised by interspecies IQ comparisons, consider a well-­known aspect of brain development that defies my materialist catchphrase: “You ­c an’t be too rich, too thin, or have too many neurons.” At least as far as it applies to neurons, apparently you can, and early on we do have too many nerve cells. “Remarkably, almost half the neurons generated in the mammalian ner­vous system are lost through a pro­ cess known as programmed cell death.” This is in effect a suicide

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program known as apoptosis, which when activated shrinks the neuron, condenses the chromatin (DNA + RNA + protein), and fragments the cell body, which is gobbled up (phagocytosed) by scavenger cells such as microglia.68 Not only do neurons die in the developing ner­vous system, the connections (synapses) are pruned back in a separate pro­cess in­de­pen­dent of neuronal apoptosis. Why evolution has, teleologically speaking, employed a “less is more” (as applied to neurons and synapses) developmental strategem for growing brains is a profound mystery even (or especially) for non-­Cartesian neurologists. Regardless of their functionality, bigger brains pose another prob­lem that is purely mechanical. “What­ever its cause the ongoing increase in hominin brain size caused parturition to become increasingly difficult.”69 Even with anatomical work-­arounds, such as open skull fontanelles (“soft-­spots”) and head molding, ­human head circumference at birth may be “topped out” at thirty-­five centimeters in order to traverse a bony birth canal selected millions of years earlier to accommodate both the smaller hominin cranium of the baby and the upright bipedal locomotion of the mom. Bigger brains require bigger heads, and therein lies the “obstetrical dilemma” that may impose a biological limit on the size of neonatal brains. On a population-­wide basis, the increasing global rate of cesarean sections, from 6.7 ­percent in 1990 to 19.1 ­percent in 2014, may validate this limit.70 Many medical ­causes, such as eclampsia, other than cephalopelvic disproportion serve as indications for cesarean section, and obstetricians may very reasonably object to my focus on the rising rate of cesarean sections as further proof of the obstetrical dilemma and its evolutionary implications. Nevertheless, the increase of c-­sections is a thought-­provoking data set, even if a clinical study encompassing twenty four years71 is remarkably brief compared with the sweep of h ­ uman evolution. If bigger brains confer an evolutionary advantage (leaving aside the relationship, if any, of bigger brains to intellect), pos­si­ble biological solutions would include the enlargement of the pelvic outlet and an increase in postnatal brain growth. Th ­ ere is already significant brain



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(and head) growth a­ fter we are born. The pediatric neurologist’s rule of thumb for head circumference is “35-45-55” (thirty-­five centimeters at birth, forty-­five centimeters at one year old, and fifty-­five centimeters as an adult). Even with the developmental thinning of synapses and neurons, the brain’s bulk increases over time with more neurons, glia, and myelin. A third solution would be the “neurological reor­ga­ni­za­tion”72 of the connectome to permit enhanced or repurposed brain functions without adding to brain bulk. One last obstacle blocking the evolution of bigger, better-­wired, and more intelligent brains is the energy cost. This is not intuitively obvious. ­A fter a vigorous cardiovascular workout, we heat up, perspire, flush red as our capillaries dilate, feel the “burn” as lactic acid builds up, and breathe faster as our heart and respiration rates increase. Nothing so viscerally obvious occurs during intense intellectual exercise (so ­don’t expect to see a ten-­gallon Gatorade cooler at your next chess tournament). Nevertheless, your eighty-­five billion to eighty-­six billion neurons and eighty-­five billion glial cells consume a whopping 25 ­percent of your body’s total energy output. The formidable energy consumption of the average ­human brain is currently estimated to be 516 kilocalories daily (about what your body burns up during a four-­mile run), leading Brazilian neuroscientist Suzana Herculano-­Houzel to conclude that the “metabolic cost is a more limiting f­ actor to brain expansion than previously suspected.”73 At the end of the day (or at least the end of this chapter), are we any closer to assigning the mind’s intelligence (or its high-­end relative, genius) to a par­tic­u­lar portion or the entirety of the brain? The search continues, and I w ­ ill briefly point out three dif­fer­ent lines of inquiry—­philosophy, psychologic testing, and neuroscience. We do not have a localization for “the ghost in the machine,” which was Gilbert Ryle’s term for the concept of mind put forth by Descartes. The ghost was demoted to a category ­mistake of logic, and Ryle assured us that “the hallowed contrast between Mind and ­Matter w ­ ill be dissipated.”74 Stephen Jay Gould, an articulate opponent of biological determinism and the belief that worth can be assigned to an individual

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by “mea­sur­ing intelligence as a single quantity,” warned that Charles Spearman’s g (general intelligence) fell prey to “reification, or our tendency to convert abstract concepts into entities.” Gould continued “Once intelligence becomes an entity,standard procedures of science virtually dictate that a location and physical substrate be sought for it.”75 Twenty years l­ater Ian Deary reminded us that the analy­sis of the WAIS subtests for g “classifies the tests’ statistical associations: it does not discover the systems into which the brain ­ eedless to say, the search for the neural partitions its activities.”76 N location of g continues apace. Christof Koch, chief scientific officer for the Allen Institute for Brain Science, has provided a “commonsense” definition in which consciousness is equated “with our inner m ­ ental life.” Intellect and consciousness are members-­in-­good-­standing of our inner ­mental life and finding the neural basis for one is likely to abet the search for the other. Koch has pointed out that the ­whole brain in its entirety is not required for consciousness (or in my experience, intelligence). The cerebellum, nestled between the ce­re­bral hemi­spheres and brain stem, contains sixty-­nine billion neurons, and yet when I evaluate patients with cerebellar strokes or degeneration from hereditary or nutritional ­causes, their coordination may be impaired but not their consciousness or intelligence. Eschewing the hypothesis that you use your entire brain to achieve a conscious state, Koch began to seek out the neuronal correlates of consciousness (NCC) with Francis Crick in the early 1990s.77 The hunt for “the minimal neural mechanisms jointly sufficient for any one specific conscious percept” is ­going strong nearly thirty years ­later.78 (Yes, I know ­we’re a long way from a credible accounting for the scope and breadth of intelligence, but starting small with scientific reductionism is a well-­ trodden path.) Along the way, candidate NCCs have included thalamocortical relay cir­cuits, the claustrum (a wafer of neurons sandwiched between the deep temporal lobe cortex and a wedge-­ shaped island of gray m ­ atter [putamen]), and most recently “a more restricted temporo-­parietal-­occipital hot zone.”79 We may hope that the NCC ­will blaze the trail to intelligence, but as I write this in



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2017, “No single brain area seems to be necessary for being conscious . . . ​but a few areas are good candidates for both full and content-­specific NCC.”80 Koch allows that “the sheer number of causal interactions in the brain together with the fleeting nature of many experiences pose challenges to even sophisticated experimental approaches to NCC.”81 Winnowing the wheat of consciousness from the chaff of ongoing cross talk between eight-­six billion neurons ­will require an unexpected, unforeseeable, and unpre­ce­dented breakthrough. No guarantees are forthcoming, but the history of science tells us that this has happened before. The solution to the puzzle of the circulation of the blood was announced a week before Shakespeare’s death in 1616 by William Harvey, who did not publish his finding ­until twelve years ­later when a “miserably printed l­ittle book of seventy two pages” (De motu cordis) appeared and “described the greatest discovery in the annals of medicine.”82 Harvey did not know how blood traveled from the arterial side of the circulatory tree to the venous side or how substances ­were exchanged between the blood and tissues. He may have suspected “that minute vessels would be found connecting arteries with veins; but he did not commit himself and referred merely to an indefinite soakage of blood through the ‘Porosities of the tissue.’ ”83 The discovery of the “minute vessels” had to await a new technology—­the compound microscope—­ just coming into its own, with Leeuwenhoek’s refinements, in the latter half of the seventeenth ­century. Wielding the new technology in 1661, Marcello Malpighi found the missing puzzle piece—­ capillaries—­linking the arteries to the veins by intensely studying the lungs of frogs (and by his own admission, “I have destroyed almost the ­whole race of frogs”).84 Is ­there a twenty-­first-­century neural “missing link,” (akin to the capillaries discovered in the seventeenth ­century) just waiting to be discovered by a new technology (like a latter-­day version of Leeuwenhoek’s microscope) that w ­ ill bridge the explanatory gap dividing the mind (of an Einstein or other­wise) and the brain? The advent of Big Science, brought to bear on the brain, ­will continue to provide

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tantalizing glimpses of the frontiers of the brain and the mind. For example, in February 2017 Koch’s group took ten thousand cross-­ sectional images of mouse brain to create a three-­dimensional reconstruction of the branches of a par­tic­u­lar neuron arising from the claustrum (see candidate NCCs above) and wrapping around the circumference of the murine brain like a “crown of thorns.” Koch had “never seen neurons extend so far across brain regions.” This hitherto unknown and far-­reaching connectivity of the claustrum and the outer parts of a simpler mouse ner­vous system has rekindled Koch and Crick’s hypothesis that the “claustrum could be coordinating inputs and outputs across the brain to create consciousness.”85 Unlike physicists, who have framed an expert and effective knowledge system laying out the forces of nature (electromagnetic, weak, and strong) and elementary particles, neuroscientists still have no standard model of the brain even 110-­plus years since Ramón y Cajal set forth the neuron doctrine. However, guiding princi­ples (the propagation of the action potential and synaptic transmission) and anatomical units (neurons and glia) have allowed us to glimpse the grandeur and the im­mense complexity of the ­human brain. The task at hand is to gain a better intellectual purchase on the most complex (to date) biological structure in the universe—­a structure that was “devised” by the blind forces of evolution, working over unimaginably long epochs of “deep” time. The next and final chapter ­will describe and appraise some of the ­future directions and limiting ­factors for neuroscientific research . . . ​a nd ­whether the contemplation of Einstein’s brain can take us any further.

chapter 8

Where Do We Go from ­Here? (And Where Have We Been?) Similar techniques helped crack the code used in the visual thalamus and early visual cortical areas, as the onion layers of the brain began to be peeled back, one by one. A complete cellular-­ based working model of how the mouse moves through a maze in response to what it sees, together with the ontology of the approximately one thousand dif­fer­ent cell types that make up the brain, was achieved in the mid 2020s. The sense of touch, hearing, and smell ­were decrypted a few years ­later. —­F rom an i­ magined conversation with a traveler from the f­ uture as recalled by Christof Koch and Gary Marcus in “Neuroscience in 2064: A Look at the Last C ­ entury,” in The ­Future of the Brain

Is the study of Einstein’s brain relevant to twenty-­first c­ entury neuroscience, or is it a “period piece” showcasing the limitations of the clinicopathologic methods of nineteenth-­and twentieth-century brain science? Can we expect a few dozen photo­graphs, a c­ ouple of thousand microscope slides and 240 blocks (if we could find them all) of brain tissue soaked in formalin for more than sixty years to inform us about the genius of Albert Einstein? Or as I attempt to extract living thought from dead neural tissue, am I like Samuel Taylor Coleridge’s guide, who “points with his fin­ger to a heap of stones, and tells the traveler, ‘That is Babylon, or Persepolis’ ”?1 My starting points are the polar opposite definitions of brain as pure anatomy and mind as pure function. In a living person, ­there is likely some overlap of t­ hese presumably conjoined concepts. And 207

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then we are again brought face-­to-­face with Chal­mers’s importunate “hard prob­lem” and the quandary of determining how much the brain and the mind overlap.2 If this par­tic­u­lar exercise in neuroscience is to prevail as a credible endeavor, at some point we must take the bull by the horns and posit as a first princi­ple that Einstein’s genius was sufficiently dif­fer­ent from the ­human “norm”—­whatever that may be—to be reflected in the physical architecture of his brain. I simply cannot state the materialist stance of brain-­mind equivalence with greater clarity. I scrupulously avoid qualified phraseology such as “brain enables mind,” which leaves the door open just a crack for notions of nonphysical mind-­stuff to slip in. Any dualist who has trudged through the previous seven chapters hoping in vain for a clear Mason-­Dixon Line separating the mind and the brain may depart now. If it’s any consolation to the Cartesians snapping this volume shut, the mind of man should be regarded as no less miraculous despite its physical trappings. Why Einstein’s brain? If we are looking for a brain functioning at the highest levels of ­human thought, the brain of a world-­class physicist is not a bad place to begin. C. P. Snow avers that ­t here may be even further intellectual gradations when considering the cohort of all physicists: “First of all, g­ reat theoreticians are even rarer animals than ­great experimentalists. That kind of conceptual skill is one of the most uncommon of all h ­ uman gifts.” 3 Also, the availability of “specimens” played a determining role in our par­tic­u­lar line of research; ­there are no brains of Newton, Galileo, Darwin, et cetera, to be had for neuroanatomical study. The technology (photographic cortical macroanalysis, systematic brain dissection, and cortical histology with selective staining) available for our study4 of Einstein’s brain has existed for anywhere from one c­ entury (Cajal’s microscopy), to nearly two centuries (Daguerre’s photography), to nearly six centuries (Vesalius’s detailed engravings of the brain dissection in De Humani Corporis Fabrica5). A neuroscientist working in his lab a ­century ago would not be discomfited by our approach. Before we relegate old-­school brain science to a quaint footnote in the history of the study of the ­human ner­vous



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system and proceed to bleeding edge and Big Science neuroscience (with an estimated price tag of $5 billion through 2025 for the U.S. BRAIN [Brain Research through Advancing Innovative Neurotechnologies] Initiative),6 a backward glance at the power­ful insights generated by past studies of “paradigm-­shifting brains” w ­ ill provide perspective on the lessons of Einstein’s brain. I ­will propose that the brains that most profoundly changed our shared way of viewing brain function and anatomy ­were all damaged. Lesion-­induced loss of function has been the mainstay of brain localization of function for over 150 years (or maybe thirty-­seven centuries if we include the Sixteenth/Seventeenth Dynasty hieroglyphic accounts of penetrating head wounds in The Edwin Smith Surgical Papyrus).7 Research methods underwent a sea change with the advent of electrical and chemical (strychnine) stimulation of the cortex and microelectrode recordings of receptive fields of neurons in the visual cortex in the early to mid-­t wentieth c­ entury. Beginning in the 1970s with positron emission tomography (the PET scan), functional neuroimaging has become the dominant (read: “grant getting”) methodology for large-­scale (as opposed to cellular/ molecular) neuroscience. Part of the uphill climb in presenting the undamaged brain of Einstein as a persuasive neuroanatomic avatar for genius is that we are most accustomed to gleaning our ce­re­bral structure-­ f unction insights from wounded brains selectively “assaulted” by the surgeon’s scalpel, encephalitis, shrapnel, epilepsy, “accidents of nature,” and even an iron tamping bar. Our nascent understanding of frontal lobe function began on September 13, 1848, when Phineas Gage, a twenty-­five-­year-­old railroad construction foreman, began tamping a blasting hole filled with explosive powder, which inadvertently had not been covered with a cushioning layer of sand. Following a loud detonation, the 109-­centimeter long iron tamping bar “enters Gage’s left cheek, pierces the base of the skull, traverses the front of his brain, and exits at high speed through the top of his head. The rod has landed more than a hundred feet away, covered in blood and brains.”8 Miraculously, Gage survived another thirteen years, and despite his gruesome

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brain injury he never demonstrated any paralysis or speech impairment. Strikingly, this “most efficient and capable” young man became “irreverent and capricious,” expressed himself with “abundant profanity,” and “had taken leave of his sense of responsibility.”9 Lacking an autopsy (although he examined the exhumed skull), Gage’s physician, John Harlow, could not definitively uncover the missing link between the frontal lobe and be­hav­ior. One hundred forty-­six years l­ater Hanna Damasio reconstructed the events on that fateful day in 1848 and found that Gage had sustained an injury to the ventromedial region (above the eye sockets and close to the space separating the ce­re­bral hemi­spheres) of both frontal lobes. What we now know (and Harlow ­didn’t) is that Gage’s neuroanatomical trauma fits the pattern of other patients with frontal lobe pathology whose “ability to make rational decisions in personal and social m ­ atters is invariably compromised and so is their pro­ cessing of emotion.” We now fathom that somehow the frontal lobes envelop many of the defining capacities of the ­human condition and that the journey to our still incomplete understanding of the expanse of cortex directly b­ ehind our foreheads began with Phineas Gage’s “Horrible Accident.”10 Among the obstacles facing John Harlow and the elucidation of Gage’s frontal lobe function in the neuroscientific arena of the mid-­ nineteenth ­century was Gage’s dearth of clear-­cut neurologic signs and symptoms, such as hemiparesis (weakness on one side of the body) or language disturbance . . . ​and no brain to examine. (Gage had been dead for five years when Harlow requested his exhumation.) No such barriers impeded the French physician, anatomist, and anthropologist Paul Broca in 1861 when he demonstrated the uncut brain of Louis Victor Leborgne at a meeting of the French Society of Anthropology. Leborgne had developed seizures in his youth, language loss (aphasia) at age thirty, and paralysis (hemiplegia) on his right side by his forties. His intelligence and understanding of speech w ­ ere unimpaired; however, his verbal output consisted of the monosyllable, “tan,” and an occasional curse when he was exasperated. (Aphasic patients may retain emotional speech when



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they are unable to retrieve the rest of their vocabulary.) When the brain of Tan (as he came to be called) was examined, a fluid-­filled depression the size of a chicken egg with surrounding brain softening was found in the third frontal convolution of the left frontal lobe. Modern research has attributed Tan’s brain damage to a focal inflammation of the brain termed Rasmussen’s encephalitis.11 ­Others (Marc Dax, for one) had previously reported in 1836 the association of language with the brain’s left hemi­sphere, but as is frequently the case with eponymous fame, the laurels of scientific discovery went to a latecomer, and Broca’s aphasia became part of our clinical lexicon. Broca’s aphasia is notable for the loss of expressive language. In Tan’s case it was a profound loss, while in milder cases the patient’s verbal output may lack articles (such as a, an, the) and conjunctions (such as and, or, but), resulting in so-­called telegraphic speech. Neurologists recognize Broca’s aphasia as a nonfluent speech disorder, and this contrasts with fluent aphasia, in which the patient retains flowing and at times nonsensical (word salad) speech. Additionally, fluent aphasics may be unable to comprehend spoken or written language—­the hallmark of a receptive aphasia. In 1874 Carl Wernicke described this other g­ reat disorder of ­human language in patients with left temporal lobe lesions. But it all began with Tan. By the latter half of the nineteenth ­century, the brain of Tan had laid the foundation for all subsequent work on the neuroanatomy of language with Broca’s convincing demonstration that the expression of language was linked to the frontal lobe and the left ce­re­bral hemi­sphere, which is dominant for language in over 90 ­percent of individuals. Like Tan, Henry Molaison began having seizures when he was young, possibly due to a childhood concussion. Although his language and motor functions ­were unimpaired, his epilepsy relentlessly progressed, and by the time he was twenty-­seven, he was having several daily seizures, both the generalized type in which he would fall to the ground, and the nonconvulsive type in which he became unresponsive, staring vacantly into space. The seizures ­were not controlled despite the combined use of the most power­ful

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anticonvulsant medi­cations in the 1950s—­diphenylhydantoin, phenobarbital, mephenytoin, and trimethadione.12 With his ability to earn a livelihood and maintain an in­de­pen­ dent existence jeopardized by his worsening epilepsy, Henry Molaison sought a desperate cure. On August 25, 1953, lacking a clear-­cut cortical focus for seizures on electroencephalography (EEG), Dr. William Beecher Scoville performed a bilateral medial temporal lobectomy in the hope that the source(s) of Moliason’s seizures ­were pres­ent (but electroencephalographically s­ ilent) in his temporal lobes. Although Scoville’s frankly experimental operation greatly reduced but did not completely eliminate Moliason’s seizures, the benefit came at an unimaginable price: “The defining deficit in H.M.’s case was an inability to form new declarative memories.” (Declarative, or explicit, memory is our recall for facts and events. This differs from implicit memory, which is called upon when we ­ride a bicycle.) Moliason could “carry on a conversation proficiently but several minutes l­ater would be unable to remember having had the exchange or the person with whom he spoke.”13 ­Until his death in 2008, Henry Gustav Moliason’s identity and name ­were closely held secrets, and he was known only as H. M. in dozens of research papers and book chapters. At postmortem serial sectioning of his brain, 2,401 digital anatomical images revealed that Scoville had almost completely removed the entorhinal cortex (EC) of the medial portion of both temporal lobes. The EC is memory’s “gateway to the hippocampus for the inflow of information from the ce­re­bral cortex and subcortical nuclei.” Jacopo Annese, the neuroscientist who sectioned the brain, observed that “during life, H.M. was the best-­k nown and possibly the most studied patient in neuroscience.”14 His brain established beyond reasonable doubt that bilateral resection of the hippocampus, its input, or neighboring medial temporal lobe structures can halt the consolidation and storage of explicit information in long-­term memory.15 It took over half a ­century to link the name of a real person (Henry Moliason) to the brain of an amnesiac but, for better or worse, ­t here have been other iconically localizing brains of anonymous



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patients known only to posterity by their initials. This was the case when Canadian neurosurgeon Wilder Penfield (1891–1976) explored other functions of the temporal lobe. His electrical stimulation studies of motor and sensory cortex during epilepsy surgery produced the classic “homunculus” (­little man) maps that correlated parts of the ­human body to discrete areas of cortex. (See Figure 3.1.) Penfield performed unilateral (as opposed to Scoville’s bilateral) temporal lobectomies to treat some of his epileptic patients at the Montreal Neurological Institute. As he attempted to localize an area of epileptogenic cortex, Penfield would perform a craniotomy and use bipolar electrodes to briefly (for milliseconds) apply two to four volts of electricity to exposed cortex. The patient, ­under local anesthesia, would verbally report the sensations or movements elicited by the electrical stimulation. In 1936 Penfield operated on J. V., a fourteen-­year-­old-­girl with seizures, and she reported dread-­ imbued flashbacks of a menacing man when the lateral portion of her right temporal lobe was stimulated. Moving the electrodes a few centimeters forward along her temporal cortex summoned auditory (not visual) hallucinations of accusatory f­amily voices. When the electrodes w ­ ere shifted posteriorly to the adjacent border of her right occipital lobe, she saw ­simple photopsias (“stars”) in her left field of vision, rather than the complex, almost cinematic, visions emanating from her previously damaged temporal lobe. In this remarkable case, Penfield glimpsed the temporal lobe’s capacity to re­create traumatic memories and to generate auditory and visual “psychical” hallucinations of im­mense sensory and emotional complexity.16 Although excitatory stimulation of the temporal lobes, ­whether by epilepsy or electrodes, is a well-­known cause of hallucinations, Penfield’s pathfinding work explains only a small percentage of the hallucinations that I encounter in clinical practice. We still have a long way to go in fleshing out our understanding of the hallucinations that occur with schizo­phre­nia, visual loss (Bonnet’s syndrome), and psychedelic drugs.17 We do not know the identity of J. V., who remains cloaked in the anonymity of Penfield’s charts of 1,132 patients who went to the

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Montreal Neurological Institute to undergo operations for epilepsy from 1934 to 1960.18 Penfield’s cortical cartography was based on a series of patients that could likely never be assembled ­today. In the 1930s the indication for seizure surgery was epilepsy that could not be controlled by the era’s limited pharmacopoeia of phenobarbital and bromides. Even the subsequent mainstay of anticonvulsant medi­cations, Dilantin (diphenylhydantoin), did not come upon the scene ­u ntil 1938. In contrast, more than twenty approved anticonvulsant medi­cations and four neuromodulation devices, which electrically stimulate cranial nerves, “deep” thalamic nuclei, and “eloquent” nonresectable cortex, are currently available to treat seizures.19 Pro­gress in pharmacology over nine de­cades, electrical neuromodulation, and more sophisticated EEGs have obviated much of the need for seizure surgery (and intraoperative cortical mapping). This is not to deny the present-­day need for cortical mapping using a single electrode or electrode grid and the utility of seizure surgery such as temporal lobectomy, cortical excision, or sectioning the corpus callosum in patients with intractable epilepsy. It is simply to point out that the clinical win­dow of opportunity for a golden age of brain exploration opened by Penfield’s desperate cure for epilepsy has subsequently greatly narrowed. For the last anonymous patient, Private F., the term unknown soldier might be more appropriate. Private F. was a British soldier on the western front when he sustained a through-­and-­through bullet wound to the back of his skull (occiput) on July 11, 1915. At this point in World War I, Gordon Morgan Holmes (1876–1965) was serving as a con­sul­tant neurologist to the British Expeditionary Force, and Private F. was brought to the field hospital in France where Holmes was stationed. Holmes, destined to become a Fellow of the Royal Society in 1933 (and one of the last practicing clinicians to gain the distinction) was intensely interested in the ce­re­bral repre­sen­ta­tion of vision. The concept that portions of each ret­ina mapped anatomically onto specific regions of the visual cortex in the occipital lobes had been proposed in the late nineteenth



Where Do We Go from ­Here? 215

c­ entury, but the precise cortical location of macular vision subserving the central visual field remained elusive. As you read this text, you are relying on a small and circumscribed portion of your ret­ina known as the macula lutea due to the yellowish tint seen during ophthalmoscopy performed by your eye doctor. The anatomy of the macula enables our highest-­ resolution vision (for fine print), and its brain connections ­were sorted out by Gordon Holmes (and his study of Private F.) during the ­Great War. Tragically, it took the high-­muzzle-­velocity gunshot wounds of World War I (and the Russo-­Japanese War during 1904– 1905) to create the straight entry-­to-­exit wounds that extirpated portions of soldiers’ visual cortices with almost surgical precision. In the relatively primitive conditions of a field hospital such as Boulogne, where ten physicians would care for nine hundred acutely wounded soldiers, Holmes would treat and examine the neurologically wounded. At night, wrapped in his British “warm,” he would pore over his case notes and formal visual fields mea­sured by bringing a small hand perimeter to patient cots or bedsides. From 1914 to 1918, Holmes assessed the visual field defects of several hundred men with gunshot wounds of the occipital lobes. Lacking the resources of modern neuroimaging (CT scans lay sixty years in the ­future), Holmes relied on the primitive technology (from our modern perspective) of stereoscopic x-­ray examinations of the skull showing the bony defects created by the trajectories of bullets and shrapnel to gauge the areas of damaged brain. The Swedish neurologist Salomon Henschen (1847–1930) had found that the visual cortex of one hemi­sphere subserved vision in the contralateral hemifields of both eyes; for example, a patient with a tumor of the left occipital lobe ­will lose peripheral vision on the right in both eyes (in neurologic argot, a right homonymous hemianopsia). Although Henschen got the cortical repre­sen­ta­tion of peripheral vision right, he went off the tracks when he localized central, or foveal, vision to the anterior or medial portion of primary (calcarine) visual cortex. And this is where Private F. provided the

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crucial finding that foveal vision resided in the “poles” (most rearward projecting tips) of the occipital lobes. His skull x-­ray delineated a “large flake” of the inner t­ able of the skull displaced against the poles of the occipital lobes. Visual fields demonstrated “a large absolute central scotoma” (blind spot) in each eye. Holmes concluded that macular vision was lost when the tips of the occipital lobes ­were “bruised” as the depressed skull fracture created by the bullet wound exerted pressure on them.20 Private F. and hundreds of other unknown soldiers enabled Holmes to infer “that each point of the ret­ina is sharply represented in a corresponding point of the visual cortex”21 and to establish, once and for all, the anatomical locus of macular vision. Holmes modestly contended that his map of the cortical repre­sen­ta­tion of vision was a “schema” or a “diagram [that] does not claim to be in any re­spect accurate.”22 Holmes, “indubitably an Irishman . . . ​in complexion, physique and predominantly temperament,”23 was being overly cautious, and a ­century ­after its publication I still rely upon his “schema” of vision when evaluating a patient with abnormal visual fields. (Although Holmes’s “schema” needs a slight tweak to align with ­later findings of greater so-­called cortical magnification of central vision,24 it r­ eally has withstood the test of time.) While alive, ­these five patients taught Drs. Harlow, Broca, Scoville, Penfield, and Holmes fundamental lessons about the organ­ ization of the ­human brain that had never been made clear or, at best, had been dimly recognized in the 1.9 million years of h ­ uman sentiency since Homo erectus. All w ­ ere aware and cooperative and coping as best they could with the loss of part of the neurological repertoire they had been born with. To a greater or lesser extent, this is how clinical neurology is taught (or at least how I learned the craft). For example, if the ulnar nerve is compressed, the patient has difficulty spreading her fin­gers apart, and if the fusiform gyrus of the occipital lobe is damaged by a cerebrovascular accident, the patient may not recognize familiar f­ aces (prosopagnosia). This is classic lesion-­based or clinicopathologic neurology in which the neurologist relies on the patient’s account of her symptoms (the clinical



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history), examines the patient for signs of impaired neurological function, and may demonstrate altered neuroanatomy with tests ranging from neuroimaging (CT, MR, or angiography), to tissue biopsy, to (in cases of a fatal outcome) autopsy. The clinical history is paramount. I teach medical students that if they have ten minutes to evaluate a patient, allocate nine minutes to taking a history, which ­w ill point to the specific part of the neurologic exam they should perform to arrive at an accurate diagnosis. Unfortunately, the methods of clinical neurology do not work so well with Einstein, who was not seeking a neurologic diagnosis and whose brain did not demonstrate any lesions ­after multiple reviews by neuropathologists and anatomists (including our close analy­sis of postmortem brain photo­graphs). For Einstein, in the stead of a chief complaint and first-­person patient history, we must content ourselves with his body of scientific work in physics. It is incorporated into his voluminous papers and less plentiful writings about his examined life and personal epistemology that are scattered in sources such as his autobiographical notes25 and his letter to Jacques Hadamard citing the ele­ments of “muscular type” in his thought.26 Moreover, can we somehow correlate Einstein’s achievements and personal testimony with the one-­off gross anatomical arrangement of his 1,230-­gram brain circa 1955? I confess that despite my years of study with gifted, canny, and at times visionary neurologists, neuroanatomists, neuropathologists, and neurosurgeons who spend inordinate amounts of time with the h ­ uman brain as they hold, dissect, repair, medicate, and peer at it through a microscope and rec­ord its electrical activity, I must have missed the lecture on “How to Identify the Brain of a Genius.” Nor, for the rec­ord, am I prepared to give that lecture, but is our neuroanatomical study a good, bad, or indifferent place to begin? This begs the question: “Does neuroanatomy as observed by the ­human eye have more to teach us about brain function in the twenty-­first c­ entury?” The anomalous cortical anatomy of Einstein’s brain was a surprise both for us and the world at large. Dean Falk strongly believed that a closer look at Einstein’s cortex was warranted, and when

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Harvey’s “lost” photo­graphs w ­ ere unearthed, her expertise and unique skill set as a paleoneurologist discovered something new and exciting that had been hidden in plain sight since 1955. Putting our discovery aside, the prevailing belief in biology is that the gross anatomical features of the h ­ uman body have been completely mapped. Reflecting that notion, the medical school I work at, Rutgers-­Robert Wood Johnson Medical School, has not had a Department of Anatomy among its twenty-­one departments and three institutes for well over a de­cade! (However t­ here are a few “stealth” anatomists still teaching first-­year medical students u ­ nder the aegis of the Department of Neuroscience and Cell Biology, but the stand-­a lone Department of Anatomy is g­ oing the way of the dodo and the passenger pigeon.) Before we shut the door on research into neuroanatomy, the discovery of lymphatic vessels within the brain in 2014 bears mentioning. The body’s lymphatic drainage system was discovered in the mid-­seventeenth c­ entury, and as a medical student I was taught that the brain uniquely lacks lymphatics. This anatomical “truth” was relegated to oblivion when Louveau and colleagues at the University of ­Virginia found brain lymphatic vessels acting as conduits for fluid and immune cells from the cerebrospinal fluid to deep cervical lymph nodes.27 The lymphatic drainage vessels nestled in the dural sinuses of the brain had eluded anatomists’ prying eyes from the time of Vesalius, nearly six hundred years ago. Before dismissing “observational” normal neuroanatomy (such as Louveau’s lymphatics), which is subtler and ­doesn’t grab the scientific headlines as readily as its close relative, lesion-­based neurology, let’s contemplate a few structures on the brain’s surface (or just below it) that have informed us about the brain’s function. Some have been known for centuries and o­ thers since 2015. In the nineteenth c­ entury ­after examining the diseased brains of their patients, both Paul Broca and Carl Wernicke came to grips with the critical role played by the brain’s left hemi­sphere in the expression and comprehension of language. A c­ entury ­later Norman Geschwind, possibly the most gifted behavioral neurologist of my



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generation, wondered if normal brains displayed anatomical evidence for language function. He questioned the received wisdom that “­there ­were no significant anatomical asymmetries between the hemi­spheres and that the cause of ce­re­bral dominance [for language] would have to be sought in purely physiological or in subtle anatomical differences between the two sides.”28 What he found was “a highly significant difference between the left and right hemi­ spheres in an area known to be of significance in language functions” in the course of postmortem examinations of one hundred adult h ­ uman brains f­ ree of significant pathology. A single, sweeping cut of ­whole brain from front to back revealed that the planum temporale, a wedge-­shaped portion of temporal lobe within the Sylvian fissure and bordered in front by Heschl’s gyrus, was demonstrably larger in subjects’ left hemi­spheres. This expanse of left temporal cortex encompassed Wernicke’s area, which is critical for understanding language. ­A fter noting the absence of such asymmetry in anthropoid apes and its presence in the endocranial cast of a Neanderthal man, Geschwind speculated that the in­equality of the right and left planum temporale was “the first solid piece of evidence as to the evolution of changes in the brain responsible for language.”29 In 1968 asymmetry of the planum temporale was seen best with an axial (front to back) slice (literally, a slice . . . ​neuropathologists carry a large knife for that exact purpose when students and residents attend a teaching exercise known as brain cutting). The asymmetry of the temporal lobes can now be assessed in living patients’ MRI or CT scans but in 1968 Geschwind relied on postmortem dissection. In contrast, Dean Falk’s discovery of Einstein’s cortical knob (and its signature inverted omega shape) required a thoughtful inspection of Harvey’s photo­graphs (and not a brain knife).30 The cortical knob is an example of observational surface neuroanatomy par excellence. Originally, it was declared to be a new anatomical “landmark” for the purposes of identifying the brain’s precentral gyrus, which controls movements.31 The knob itself proved to be a region of variant motor cortex anatomy specializing

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in hand movements, but it was not u ­ ntil l­ ater that it was found to be significantly associated with musicians, whose brains are endowed with larger right cortical knobs in string players and larger left cortical knobs in keyboard players.32 The original description of the cortical knob was based on functional magnetic resonance imaging (fMRI) of eleven subjects and not ­actual brains.33 ­A fter reviewing five of Harvey’s photo­graphs reproduced in Witelson’s Lancet article,34 Dean Falk recognized that Einstein’s brain had a cortical knob on the right, and based on Bangert’s study of musicians,35 she made the first connection between Einstein’s variant precentral gyrus anatomy and his violin proficiency.36 As I write this in 2017, if you google cortical knob, most of the pictures are ­either MRI or fMRI images. ­Actual photo­graphs of brains with cortical knobs are few and far between, but of ­t hose, the Google search algorithm strongly ­favors Harvey’s pictures of Einstein’s autopsied brain to epitomize the cortical knob. It goes without saying that in this age of rampant technology, most ­people learn about the easily observable macroanatomy of the cortical knob from the technical wizardry of nuclear magnetic resonance imaging rather than a ­simple snapshot of postmortem brain. On February 2, 1776, Francisco Gennari, a medical student at the University of Parma, also sliced an ice-­hardened brain from front to back. (­Don’t assume that ice hardening is a quaint and antiquated technique . . . ​just ask any surgeon who takes frozen sections of tissue in the operating room.) Gennari stared intently at the cut surface of the occipital lobe and spied a whitish line paralleling the sinuous course of the interhemispheric portion of both occipital lobes (Figure  8.1).37 Thus was the debut of ce­re­bral architectonics—­the study of regional differences in cortical structure. As it turns out, Gennari’s “stripe” was comprised of myelinated nerve fibers (which would appear white on gross inspection) located in the fourth of the six layers of the occipital cortex. Most importantly (and what Gennari would not know), is that his line demarcates the primary visual (or calcarine) cortex. It would not be ­until 1892 that Henschen would deduce that the occipital cortex



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Figure 8.1. Francesco Gennari’s illustration of the prominent white band seen in the ce­re­bral cortex of both occipital lobes (“D” and “F” in the lower portion of the plate) which would ­later be found to demarcate the primary visual cortex. (Mitchell Glickstein and Giacomo Rizzolatti, “Francesco Gennari and the Structure of the Cerebral Cortex,” Trends in Neurosciences 7, no. 12 [1984]: 464–467.)

encompassing Gennari’s line was “no less than the primary visual center of the brain.”38 The incremental increase in our understanding of occipital lobe neuroanatomy vis­i­ble to the naked eye and subsequently its function was built upon the work of Gennari, then Henschen, and then Holmes, among o­ thers. (Actually, many ­others. My apologies to the legacies of the numerous students of the eye and brain throughout neurohistory.) Before we get too comfortable with the occipital lobe and the neurology of vision, consider Maller et al.’s discovery that the occipital lobe “bends” in patients with depression.39 Eschewing a brain knife in the twenty-­first ­century, they used MRI software to “slice” the brains of fifty-­one patients with major depressive disorders and found that eigh­teen had a curving occipital lobe that wrapped around its fellow in the opposite hemi­sphere, while only

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six out of forty-­eight controls displayed such a curvature. In contradistinction to Witelson’s earlier conclusion, we found that Einstein’s brain was not symmetrical, and Harvey’s photo­graphs confirmed the presence of wider left occipital and right frontal lobes.40 Given her extensive experience with endocasts of hominid skulls, Dean Falk judged Einstein’s brain asymmetry to be an example of the most typical petalia (the protrusion of one hemi­sphere relative to another) pattern in ­humans. According to Maller, the increased lobar length and width of petalias differ from occipital bending, which is characterized by one occipital lobe (usually the left) crossing the midline and “warping” the interhemispheric fissure. He went on to speculate that “incomplete neural pruning” in depressed patients diminished the space available for brain growth, and b­ ecause intracranial volume peaks at around age seven, “the brain may become squashed and forced to ‘wrap’ around the other occipital lobe.”41 This new revelation of naked eye neuroanatomy is both puzzling and emblematic of the complex multipotentiality of the brain. If you are looking for a common foundation for emotion and vision in the occipital lobe, keep looking. The larger left occipital lobe withstanding, ­there is no evidence that Einstein suffered from clinical depression. Although he had met and corresponded with Freud, Einstein was uninterested in psychotherapy or delving into the subconscious and declared, “I should like very much to remain in the darkness of not having been analyzed.”42 Maller would contend that “occipital asymmetry and occipital bending are separate phenomena,” and therefore, the par­tic­u­lar anatomy of Einstein’s left occipital lobe cannot be regarded as a surrogate for depression. Although we can correlate neuroanatomical findings with some aspects of be­hav­ior, we are unable to prove causation (to the surprise of no one, including the ghost of David Hume). Why does a deformation of the occipital lobe “cause” depression, or why does a one-­centimeter shortening of the paracingulate gyrus in the medial prefrontal cortex increase the likelihood of hallucinations in schizophrenics?43 The answers are unknown at pres­ent, but the observations are thought-­provoking. Unlike Broca, we w ­ ill not have to await a



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present-­day Tan’s death to ascertain the site and extent of the brain lesion. Neuroimaging and its refinements (e.g., increase the strength of the MR magnetic field from 1.5 to 3.0 tesla and more detailed brain images result) provide details of in vivo brain anatomy that ­were unimaginable when I was a neurology resident in the 1970s, and the University of V ­ irginia School of Medicine did not have a CT scan! Even the dominance of ge­ne­tics may come up short when we scrutinize ce­re­bral architecture. Portions of the genome are partially informative as to the sequence of embryologic steps and building-­ block proteins used to construct and deconstruct (by means of apoptosis) a brain. As I have previously remarked, twenty thousand or so genes cannot reasonably be expected to contain enough information to completely hardwire the thousands of connections per neuron in a brain with eighty-­five billion neurons. To bring this point home, consider the brain surface anatomy of identical (monozygotic) twins. ­A fter studying the MR brain imaging of twenty pairs of monozygotic twins, a research team at Heinrich Heine University in Germany found that the gyral and sulcal patterns in all the twin pairs ­were dissimilar. In other words, despite their identical genomes, each member of the twin pair had a grossly dif­fer­ent neuroanatomy, leading the investigators to surmise “that the development of the convolutions of the brain is strongly influenced by nonge­ne­tic ­factors—­that is, by environment, experience, or chance.”44 This is not to downplay the ascendancy of genomics in ­human biology, particularly since the watershed achievement of mapping out the entire sequence of h ­ uman DNA in the first few years of the twenty-­first c­ entury. For example, rare familial disorders of language have been linked to mutations of the FOXP2 gene.45 Although we know that this par­tic­u­lar DNA sequence on chromosome seven is critical for language, we are in the dark regarding the details of neuroanatomy and neurophysiology that connect the dots from gene to be­hav­ior (in this case, language). We know some tantalizing generalities about how FOXP2 gene mutations lead to abnormal branching and length of axons and dendrites, but we are a long way from grasping (or imaging) how a normal FOXP2 gene fabricates a normal Broca’s area in a h ­ uman frontal lobe.

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My analy­sis has concentrated on the lessons of gross neuroanatomy and neuropathology b­ ecause in the case of Harvey’s photo­ graphs that is the vein we have mined. (I ­will briefly revisit the prospect of a re-­e xamination of the microscopic neuroanatomy preserved and stained in Harvey’s slides before we bid adieu to Einstein.) As the sun sets on the ancient regime of the clinicoanatomic study of the brain, consider what twenty-­first ­century neuroscience might do if a new Einstein was proclaimed to be walking in our midst. I w ­ ill gladly entertain nominations for the intellectual cynosure of our time (aka, the smartest guy in the room, albeit from a global perspective) from the floor. How about Stephen Hawking and the explanation of black holes? Or Andrew Wiles, who formulated the proof of Fermat’s last theorem, which had remained unresolved for 358 years? And self-­proclamations aside, let’s please agree to definitely not nominate Kanye West; both he and his publicists might profit from reading my chapter on genius. Assuming we have identified and agreed upon the Genius of Our Age, what technology should we bring to bear on the study of his/her brain? Before we can embark on our latter-­day Einstein research proj­ect, it’s de rigueur to craft a grant proposal including a scientific rationale and a bud­get estimating the proj­ect’s direct costs for materials, ­labor, construction, et cetera (and more importantly, the additional indirect costs, which are levied at 20 to 85  ­percent of the amount of, for instance, a National Institutes of Health grant). The indirect costs pay for the overhead expenses, such as the lighting and heating bills for the lab, and bring a lupine smile to the university administrator contemplating the manna about to rain down from grant-­giving heaven). Just how much is the financial bite to “look ­under the hood” of brains of geniuses (or other­wise)? How about if we had $4.5 billion to effect “a comprehensive, mechanistic understanding of m ­ ental function”?46 Well, U.S. taxpayer, we do! It’s called the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and it was launched by President Obama in April 2013. Its overarching goal “is to map the cir­cuits of the brain, mea­sure the fluctuating patterns of electrical and chemical



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activity flowing within t­hose cir­cuits, and understand how their interplay creates our unique cognitive and behavioral capabilities.”47 Aspiring to be the neurobiology equivalent of the Apollo man-­on-­ the-­moon missions or the ­Human Genome Proj­ect, the BRAIN Initiative is facing some very formidable obstacles in attempting to image the brain’s circuitry. Numbered among ­these is the im­mense (and uncata­logued) diversity of neurons and glia and the need to image their electrical and chemical activity within a time frame of milliseconds. How do you microscopically image a single cortical neuron and all its synapses that extend for over a meter and span nearly the entire brain volume? Given the pres­ent trade-­off between imaging large volumes or achieving fine-­grained resolution, we lack the capability to depict large volumes of neural tissue at a synaptic level. Viewing the all-­important point of communication between neurons, the synapse, is limited to electron microscopy (EM) of tiny volumes of brain tissue, on the order of one-­tenth of a cubic micron. At the scale accessible to EM, “a full cubic millimeter of brain volume resolved to the level of seeing ­every synapse would require many months or even years to image and far longer to analyze.”48 Facing ­these challenges, the BRAIN Initiative has charted a course for investigative neuroscience for the twenty-­first c­ entury and has bold-­faced the following high priorities: 1. Discovering diversity with a census of neuronal and glial cell types. 2. Maps at multiple scales: generate cir­cuit diagrams that vary in resolution from synapses to the w ­ hole brain. 3. The brain in action: produce a dynamic picture of the functioning brain. 4. Demonstrating causality: link brain activity to be­hav­ior by directly activating and inhibiting populations of neurons. 5. Identifying fundamental princi­ples: produce conceptual foundations for understanding the biological basis of ­mental pro­cesses through the development of new theoretical and data analy­sis tools.

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6. Advancing h ­ uman neuroscience, particularly as it pertains  to understanding the h ­ uman brain and treating its disorders. 7. Integrate new technological and conceptual approaches produced in goals 1–6 to discover how dynamic patterns of neural activity are transformed into cognition, emotion, perception, and action in health and disease.49 Drs. Bargmann and Newsome and thirteen other neuroscience luminaries have provided a 146-­page road map to “a single, integrated science of cells, cir­cuits, brain, and be­hav­ior.” If we arrive at a better generic understanding of the brain, we w ­ ill also likely gain insight into the brain of a genius . . . ​and just maybe the next Einstein when he comes rolling along. One prob­lem with road maps in general is their inaccuracy where stretches of highway are u ­ nder construction (and detours are rife). For the BRAIN Initiative to succeed, w ­ e’ve got u ­ ntil 2025 for a w ­ hole lot of “road building” vis a vis innovative brain technology (e.g., when do we get a “macro-­micro” neuroimaging apparatus working in real time?) to be devised and staggering amounts of data to acquire and analyze. As we place our bets on the BRAIN Initiative’s chances of crossing the finish line to attain a “single, integrated” neuroscience, I ­will review several of the most promising technologies (functional neuroimaging, mapping the connectome, electrical recording/stimulation of neurons, and artificial intelligence simulation of the brain) for our rendezvous with a ­future Einstein. Some are already ­here, all are being refined, and some are “not ready for prime time.” Functional MRI (fMRI) “is currently the best tool we have for gaining insights into brain function and formulating in­ter­est­ing and eventually testable hypotheses.”50 Advocates w ­ ill declare that “[f]MRI enables us to see what is happening in a brain while a subject is thinking, and, u ­ nder certain conditions, even to partially see into the contents of ­those thoughts.”51 However, detractors ­will dismiss fMRI as tantamount to magnetic phrenology. Like it or not, our newly minted Einstein w ­ ill undoubtedly undergo an fMRI.



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Why? Aside from the cool color pictures of parts of the brain “lighting up” during a ­mental task, fMRI is based on the physiologic bedrock of the 127-­year-­old princi­ple of neurovascular coupling.52 In essence, Sir Charles Sherrington, who incidentally coined the term synapse, postulated that the brain’s vascular supply “can be varied locally in correspondence with local variations of functional activity,”53 and the upshot is that if a par­tic­u­lar portion of the brain, cortical module, or a group of neurons is activated by motor, sensory, or cognitive task, the metabolic demands of the neurons ­will increase, and the neuronal blood supply must be augmented in reponse. Fast-­forward to 1991, and the cover of Science is an MRI image of the visual cortex lighting up in a subject undergoing photic stimulation (Figure  8.2).54 We now know that the increased delivery of oxygenated hemoglobin to stimulated neurons ­will increase the magnetization (diamagnetic) effect on ­water molecules in surrounding tissue, and the signal w ­ ill become increasingly vis­i­ble to the detectors in the MRI scanner. For instance, if a subject undergoing fMRI speaks (or even thinks) of words, Broca’s area of her language-­ dominant frontal lobe ­ will produce increased magnetization that appears on the MRI image. So when we encounter our living and breathing Einstein 2.0, we need only to inveigle him or her to undergo an fMRI, think profound thoughts, and voila!—we have a picture of the “genius cir­cuits” of the ­human brain. Or do we? As a point of comparison, when I look at a ce­re­bral angiogram with the column of intra-­arterial contrast interrupted by a blood clot completely occluding the m ­ iddle ce­re­bral artery in a patient with cerebrovascular disease, I can r­ eally see, via old-­fashioned analogue methodology, that a par­tic­u­lar area of the brain is at risk for infarction of neural tissue (in other words, a stroke). If I still have doubts about a­ ctual brain tissue damage due to mitigating ­factors, such as collateral circulation, I can obtain a diffusion-­weighted MRI, which ­will detect a focal area of increased brain signal due to the decreased Brownian motion (diffusion) of ­water “in the ­dying region deprived of blood.”55 Although diffusion-­weighted MRI and

Figure 8.2. Functional magnetic resonance (MR) imaging of vision. This image of primary visual cortex was obtained during MR imaging with the intravenous contrast agent, gadolinium, while volunteers viewed a flashing checkerboard pattern. As demarcated by areas of increased signal midline at the hemispheric posterior poles, ­there was a 32 + /−  10 ­percent increase of ce­re­bral blood volume in the primary visual cortex during visual stimulation. Blood oxygen level–­dependent (BOLD) MR imaging subsequently supplanted MR with gadolinium as the functional MR technique of choice. (American Association for the Advancement of Science “Cover,” in Science, November 1, 1991.)



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fMRI both examine aspects of blood flow in the brain, the imaging line of demarcation between living and infarcted brain tissue is a ­whole lot clearer in the former than in fMRI, which is not used to diagnose stroke but rather to detect very weak differences in blood flow, on the order of 1 ­percent, between activated and nonactivated areas in a living brain. Given the random background activity fluctuations of up to 3 ­percent, extracting signal from noise is a major prob­lem that is relegated to software. The stunning fMRI images depend on statistically based algorithmic detection and would be invisible to a mad scientist inspecting the subject’s brain through a portion of skull replaced with a plexiglass win­dow. So the brain activity we “see” on fMRI is what the software package shows us, and one recent study of three commonly used software packages has shown that the detection of activated areas of the brain lighting up the scan can be overestimated (with a false-­positive rate of up to 70 ­percent).56 Assuming that the area of increased hemodynamic perfusion of brain tissue is a bona fide signal and not some random noise, what does it tell us about the under­lying neurophysiology? Is the fMRI identifying a population of neurons that are repeatedly and rapidly depolarizing with excitatory effect on other synaptically linked neurons in a cir­cuit? Not necessarily. The increased metabolic demands of inhibitory neurons ­w ill produce a signal on fMRI that “may potentially confuse excitation and inhibition.”57 It’s as if functional neuroimaging ­can’t tell the difference between an on switch and an off switch! Leaving the complexities of hardware and software aside, the test subject during an fMRI brain-­mapping experiment f­aces some unique cognitive challenges. The linchpin of effective mapping is correlating changes in fMRI activation with changes in m ­ ental or sensorimotor activity. The tricky part is to establish a baseline ­mental state and then direct the subject to perform an assigned m ­ ental task, such as thinking of words, to assess the activation of Broca’s area in the frontal lobe. Before starting a period of word generation, the subject is asked “to think of nothing” to create a cognitive

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baseline. A l­ittle introspection w ­ ill surely persuade you that allowing your mind to go completely blank might be pos­si­ble for ­adepts of Zen koans with years of meditative training but most definitely is not pos­si­ble for what most fMRI studies deem to be a normal ­human subject; that is, a cash-­strapped college sophomore. Ce­re­bral electrical activity never completely ceases (except in extraordinary neurophysiological circumstances, such as brain death or near-­lethal barbiturate overdose, which display electroce­re­bral silence during an EEG). And this is to say nothing of ongoing unconscious brain activity, which is inaccessible to the subject’s awareness. Making your ­mental landscape a complete tabula rasa is prob­ably not an option for most of us. Assuming the brain works linearly by piling a new cognitive task atop an under­lying ­mental state, we are compelled to regard fMRI activation as a quantitative change in ongoing brain metabolism rather than a qualitative change from no activity to some localized activity.58 As he silently performs serial subtractions inside the ­claustrophobia-inducing confines of an MRI “tube,” the bilateral (L > R) inferior parietal lobules and prefrontal cortices light up in neuroscientist (and volunteer subject) Stanislas Dehaene’s brain.59 Does this pedestrian exercise in basic math have the same neural under­pinnings as any virtuoso mathematical manipulations (akin to tensor calculus of a c­ entury ago) that our latter-­day Einstein carries out? Something ­will surely light up on functional neuroimaging as Einstein redux thinks in eleven dimensions, but is it the “genius math center”? As a hidebound localization-­inclined neurologist, my pulse quickens at the prospect of an fMRI X marking the “math spot” on the ce­re­bral map. My clinical intuition is bolstered as I recall my patients with Gerstmann’s syndrome,60 whose left parietal lobe strokes cause a quartet of deficits, including the inability to: (1) write, (2) distinguish right from left, and (3) identify fin­gers (as in “Show me your left ring fin­ger”). Number four is dyscalculia—­the patient c­ an’t carry out ­simple mathematical operations.61 By the compelling logic of lesion-­based analy­sis the left parietal lobe is our math center. Right?



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Dear Reader, ­don’t buy it! No cortical module is an island. A (maybe the) defining hallmark of brain architecture is connectivity. That is not to gainsay the crucial role played by both parietal lobes in mathematical operations but “only in combining the capacities of several million neurons, spread out in distributed cortical and subcortical networks, does the brain attain its impressive computational power.”62 M.-­Marsel Mesulam, who learned his behavioral neurology as one of Norman Geschwind’s residents at Boston City Hospital, has put “distributed networks” nicely into perspective: “The structural foundations of cognitive and behavioral domains take the form of partially overlapping, large-­scale networks or­ ga­ nized around reciprocally interconnected epicenters.”63 He has identified at least five large-­scale networks subserving spatial attention, language, memory-­emotion, executive function-­ comportment, and face-­and-­object identification. How can we reconcile focal activations summoned forth on fMRI by arithmetic with large distributed neural networks? It seems that the widely distributed networks have relatively discrete areas of maximal activity (and vulnerability), which are eagerly sought out by a neurologist in the pro­cess of diagnosing a circumscribed structural brain lesion. My therapeutic options for “repairing” a damaged distributed neural network are limited, but if I can find a tumor or subdural hematoma overlying the left parietal lobe, neurosurgical excision of the tumor or drainage of the hematoma through a burr hole may dramatically improve the patient’s Gerstmann syndrome by restoring function at the “neural bottleneck” located at the dominant hemi­sphere’s parietal lobe. Other such network bottlenecks well known to clinicians are Wernicke’s area for receptive language function, the hippocampus-­entorhinal complex for explicit memory, and the amygdala for emotion.64 Current functional neuroimaging (including positron emission tomography [PET], to which I have given scant attention) may be coming up short by providing a tip-­of-­the-­iceberg perspective of the function of brain networks. Additionally, fMRI’s perspective on cubes (voxels) of brain tissue reaches levels of significance as

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determined by software (and not the ­human eye).65 The statistical thresholds of that software must be thoughtfully monitored to avoid “voodoo correlations” like the identification of a “cluster of activated voxels in the brain of a dead fish [salmon] that had been ‘asked’ to perform a social-­perspective-­taking task while lying inside a functional MRI scanner.”66 That said, I can assure you that the royal road for studying the next Einstein’s brain w ­ ill be functional neuroimaging and not dissection with a brain knife or a microtome. If the BRAIN Initiative’s priority list can serve as a crystal ball for advances in MRI in the first half of the twenty-­first ­century, our “genius study team” w ­ ill obtain higher-­resolution images by increasing the strength of the magnetic fields generated by the superconducting magnets in the MRI scanners. With greater field strength, the pres­ ent two-­millimeter resolution could be improved to less than one millimeter—­the spatial level of cortical columns and laminae (layers). Not confined to the detection of strokes alone (vide supra), the finer-­ grained resolution of diffusion-­weighted MRI (DW-­MRI), which exploits the physico-­a natomical characteristic of ­water molecules diffusing more rapidly lengthwise along axons, ­will refine maps of white ­matter connectivity. The extent of the “unseen underwater iceberg” of network distribution alluded to earlier can be elucidated further by the ongoing use of fMRI to detect task-­initiated ce­re­bral activation and the resting state fMRI (rfMRI). The latter reveals that “functionally-­related areas that are co-­activated during per­for­ mance of a task also exhibit correlated spontaneous fluctuations when subjects are simply ‘resting’ in the MR scanner.”67 Last, even the highest-­resolution fMRI with graphic patterns of activation in the most beguiling colors is only as good as the neuropsychological task set forth for the subject. The neuropsychological paradigm could not be more effective in its straightforward simplicity, as in the case in which the subject is asked to tap his left ring fin­ger (and his right precentral gyrus lights up). However, our intrepid neuropsychologist, armed with the best fMRI that NIH—­ read taxpayer—­money can buy, w ­ ill face a formidable task in charting the wellsprings of unconscious creativity. How did Albert Einstein



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recognize that a man falling from a roof would reveal “the deep connection between gravity and accelerated motion”68 and ultimately lead to the theory of general relativity? Is t­ here a creative pro­c ess residing in the unconscious mind or ineffable “protothought” that is beyond the reach of current functional neuroimaging? In the words of Wittgenstein, “Whereof one cannot speak, thereof one must be ­silent.”69 While fMRI and PET “give insights into the location of functionally defined cortical fields, tractography goes beyond this to reveal how such fields are connected.”70 Since 1985 we have been able to obtain images of the orientation of myelinated fibers connecting neurons in the living brain through the evolution of DW-­MRI into diffusion tensor (DT) tractography “in which white ­matter tracts are reconstructed in three dimensions” based on ­water’s six-­to eightfold higher anisotropic diffusion rate in a direction parallel (as opposed to perpendicular) to the pathways of myelinated axons. With the advent of DT imaging, we began to explore the connectome, which “is the totality of connections between the neurons in a ner­vous system.” Prince­ton’s Sebastian Seung has offered a sweeping and profound corollary: “Minds differ b­ ecause connectomes differ.”71 Actually, the connectome can be approached from two dif­ fer­ent perspectives, macro-­and micro-­, and Seung has trained his sights on neuronal connectomes, which I would consider to be the microconnectome. Clinical neurologists of my ilk have learned to understand many neurobehavioral and language disorders as disconnection syndromes framed by the nineteenth-­century “diagram makers” such as Wernicke and Dejerine. The seminal research on disconnection was forgotten ­after WWI but was revived in Geschwind’s 1965 classic paper “Disconnexion Syndromes in Animals and Man.”72 Although the term connectome would not be coined ­until 2005,73 Geschwind and his intellectual pre­de­ces­sors ­were nevertheless studying its diseases and lesions. However, u ­ ntil the last de­cade of the twentieth ­century, death was a prerequisite for visualizing the white ­matter connectivity of the h ­ uman brain. The pathologist could see and feel

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the softening (encephalomalacia) or hardening (sclerosis—as in multiple sclerosis) of the brain lesions that disrupted neural circuitry and caused scarcely believable behavioral syndromes, such as being able to write but not read (alexia without agraphia). Pathologists also used microscopy to visualize the pathways of d ­ ying neurons and axons marked by retrograde and anterograde (Wallerian) degeneration. Mapping connectivity with white m ­ atter tract degeneration is a postmortem technique. Radioactive neuronal tracers, such as tritiated proline-­fucose, injected into the eyes of macaque monkeys are transported along the axonal and transsynaptic highways from the ret­ina to the optic nerve to the lateral geniculate body to the striate (visual) cortex. This technique of tracing the visual pathways led to David Hubel and Torsten Wiesel’s 1981 Nobel Prize but would be an unethical way to explore the connectome in living and breathing ­humans. With the advent of DT imaging, mapping the connectome of living brains (known as hodology, from the Greek hodos, “path” or “road”) became real­ity. We have learned “that ­every area of the neocortex is linked with other cortical and subcortical areas by pathways grouped into five fiber bundles.”74 ­These bundles of axons include (1) association fibers r­ unning to ipsilateral cortical areas; (2) corticostriatal fibers linking cortex and the basal ganglia deep in the ce­re­bral hemi­spheres; (3) commissural fibers that cross to the opposite hemi­sphere, with the corpus callosum being the largest; (4) corticothalamic fibers projecting to the thalamic nuclei, which are other deep hemispheric masses of gray ­matter; and (5) corticopontine fibers passing to the pons (Latin for “bridge”), which is the portion of the brain stem linking the midbrain to the lower brain stem (medulla oblongata).75 ­Every neurologist has to be familiar with diseases, such as multiple sclerosis, that target the central white ­matter exclusively, and the evolving hodologic maps go a long way ­toward clarifying why a demyelinating lesion at a par­tic­u­lar white ­matter location ­causes a specific neurologic sign or symptom. Moreover, DT images of the connectome illustrate distributed neural



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cir­cuits in vivo with startling clarity unimaginable to neuroscientists a mere generation ago. Is ­there a downside? I may be looking a neuroimaging gift h ­ orse in the mouth, but if we are to pro­gress in studying the connectome, current limitations (and f­ uture goals) c­ an’t be swept ­under the rug. DT tractography is an anatomical exercise that cannot inform us w ­ hether a synapse is inhibitory or excitatory or point out the direction of biological “electricity” flowing (propagation of the action potential) along bundles of axons. When white ­matter pathways turn sharply, as in Wilbrand’s knee in the optic chiasm, or crossed fibers (decussations) mingle with uncrossed fibers, the resolving power of DT tractography may not be up to the task of delineating the a­ ctual neuroanatomy. And DT imaging is blind to the anatomical details of the synapse. MRI resolves one-­cubic-­millimeter voxels of brain tissue, but to “see” synapses EM must resolve tissue volumes that are a trillionfold smaller (less than one hundred cubic nanometers!).76 The upshot is that currently with DT tractography “­there is no way of being sure that diffusion pathways synapse in the grey ­matter at all.”77 In the words of the self-­confessed “neuronal chauvinist” Sebastian Seung, “We need to see neurons to find regional connectomes.”78 The intrepid souls who wish to obtain absolutely faithful repre­sen­ta­tions of the microconnectome parcellate the neural tissue into one-­cubic-­millimeter blocks reconstructed from 33,333 sections cut to a thickness of thirty nanometers by microtomes or focused ion beams. A far cry from Cajal’s tracings of Golgi stained neurons, axons, and dendrites by light microscopy over a ­century ago, connectomics is arguably the most demanding investigation (sequencing of the three billion base-­pairs of the ­human genome not excepted) of biologic structure ever attempted (Figures 8.3 and 8.4). Harvard’s Jeffrey Lichtman has upped the ante on Koch’s estimate of one hundred thousand cells per cubic millimeter of primate cortex79 and has conceded that “the ­actual number of dif­fer­ent objects and their synaptic interconnections in a volume of brain

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Figure 8.3. The connectome as depicted in 1909. Cajal’s 1909 drawing of a microscopic section of mammalian cortex used the Golgi technique to selectively stain a random sample of pyramidal neurons (b and c) and their connecting of axons and dendrites. (Santiago Ramòn y Cajal, Histologie du système nerveux de l’homme et des vertébré [Paris: A. Maloine, 1909].)

tissue is unknown and, at the moment, even difficult to estimate or bound.”80 Each thirty-­nanometer slice is teeming with axons, segments of myelin sheaths bounded by nodes of Ranvier, dendrites, synapses, synaptic vesicles, mitochondria, glia, et cetera. Despite the staggering complexity of the anatomy crammed into a very tiny space, acquiring microscopic images of the neural cross-­sections is not the hardest part. The g­ oing gets tough with “labelling and tracing each neuronal pro­cess as it wends its way through the stack of images.”81 The only connectome completely mapped to date is to be found in the previously cited roundworm Caenorhabditis elegans, a one-­ millimeter hermaphroditic soil-­dweller that has neither a respiratory or a circulatory system. C. elegans has 302 neurons, and it took South African biologist and 2002 Nobel Prize–­w inner Sidney Brenner and his team over a dozen years to analyze the electron microscope images of fifty-­nanometer worm slices “to sort out which



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Figure 8.4. The connectome as depicted in 2011. Stacked images of Daniel Berger’s 2011 electron microscopy of layer five of mouse sensorimotor cortex reconstructs a 6 × 6 × 7.5 micron cube comprised of neurons, glia, axons, dendrites, and subcellular organs such as mitochondria. (Daniel Berger, “Stack of Tissue Images Ready for Construction,” Connectome, 2011. http://­connectomethebook​.­com​ /­​?­portfolio​=­atum​-­cortex​-­reconstructions​.­)

synapses belong to which neurons.”82 With the 1986 publication of its complete 340-­page connectomic road map (“The Structure of the Ner­vous System of the Nematode Caenorhabditis elegans”83), C. elegans joined the group of work­horse lower organisms—­fruit fly (ge­ne­tics), squid (axonal action potential), and sea hare (synaptic basis of learning)—­that have just the right anatomy and physiology to catapult scientific research. If it took a dozen years to complete the wiring diagram for a creature that has a paltry 302 neurons, the prospects for mapping larger ner ­vous systems, including the eighty-­five-­billion-­neuron ­human brain, become formidable (if not impossible). If done manually, plotting out the connectome “would take a trained technician a million working years for each cubic millimetre of brain; luckily computer vision and machine-­learning algorithms speed ­things

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up.”84 Additionally, neuroscientists, such as Seung, and computer scientists, such as Zoran Popovic, have crowdsourced connectome science by creating videogames in which gamers with no par­tic­u ­lar neuroscience background compete at reconstructing three-­ dimensional images of neurons and their connections. Using a mouse to click onto an errant axon pictured in an Allen Institute for Brain Science electron micrograph of ­human or murine brain, the citizen scientists have increased “the number of neuron reconstructions from 2.33 a week that a team of professional analysts ­were ­doing on their own, to 8.3 reconstructions a week.”85 Faster reconstructions aside, “in connectomics, the size of the input set is at the high end of the big data range, and possibly among the largest data sets ever acquired ” (my italics).86 Simply put, “neuroscientists cannot claim to understand brains as long as the network level of brain organ­ization is uncharted.”87 On the road to the connectome, we may encounter unimagined structures, such as the “crown-­of-­thorns” neuron that wraps around the entire circumference of the mouse’s brain. Could the unpre­ ce­dented length of yet-­to-­be-­discovered ­human analogs of this class of neuron extending from the small, thin sheet of neurons in the claustrum coordinate “inputs and outputs across the brain to create consciousness”?88 Fundamental questions about the finest-­grained large-­scale anatomical study ever proposed remain unanswered. Does neuroanatomy tell us anything about neurophysiology? It is believed that “the structural wiring details [of neural cir­cuits] per se are insufficient to derive the firing patterns” of neurons. Or even pure morphology of neurons may have its limits—­neurons that look alike may be in dif­ fer­ent molecular classes that are apparent only on immunofluorescent staining with EM.89 Moreover, the “moving parts” of vesicle release of neurotransmitters at the synapse would elude connectomic electron micrographs. The image of a vesicle being released (exocytosed) from the presynaptic membrane would be similar to a freeze-­ action photo of a curveball leaving a pitcher’s fingertips. The photo



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­ ill not tell you if the pitch ­will be a ball or a strike, and EM canw not predict what the neurotransmitter contents of the vesicles w ­ ill do at the postsynaptic receptors. “­There is the possibility that the wiring is normal but the receptors are not.”90 The sheer magnitude of connectomics and its daunting prospects may compel us to trim in our sails and “consider the possibility of reconstructions of neuronal substructures as opposed to ­whole brains and hope that testing t­ hese substructures ­will reveal enough modularity and regularity to allow deductions of in­ter­est­ing general orga­nizational princi­ples and overall function.”91 Although Thomas Harvey’s dissection of Einstein’s brain preceded the debut of the conception of the connectome by fifty years, the applicability of this neuroscientific approach is readily apparent when we review Dr. Weiwei Men’s research on Einstein’s corpus callosum, as discussed in chapter 5. The corpus callosum, the largest commissure in the ­human brain, is effectively a white ­matter bridge connecting the right and left ce­re­bral hemi­spheres. Dr.  Men mea­sured the midline structures exposed by Harvey’s photo­graphs of Einstein’s bisected brain and established that Einstein’s corpus callosum was significantly larger compared to young and old controls.92 This must be regarded as proof positive that Einstein’s connectome (like his cortex) was exceptional. Can the same assertion be made regarding Einstein’s microscopic connectome? Not yet. Of the two-­thousand-­plus microscope slides sectioned by Thomas Harvey and Marta Keller in 1955, many (the precise number is unknown) ­were pro­cessed with Weigert stain, which reveals myelinated axons u ­ nder light microscopy. Despite the plentiful availability of slides that displayed the myelinated connections of Einstein’s brain, white ­matter was largely ignored in the five peer-­reviewed studies (published between 1985 and 2006) of Einstein’s neural microanatomy that focused on cell counts and glial morphology (see chapter  4). Although David LaBerge (in chapter  1) has speculated about the pos­si­ble salubrious role on cognition played by longer apical dendrites in

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layer five of the neocortex,93 Einstein’s microconnectome remains uncharted territory. If our hy­po­thet­i­cal twenty-­first-­century Einstein should permit neuroscientists to get “up close and personal,” even dyed-­in-­the-­wool connectomists concede that “the ideal brain-­imaging technology would provide both a complete map of the activity of all neurons and synapses in real time during normal be­hav­iors. Even better would be to do this in a ­human being who can report on their thoughts while behaving. Unfortunately we are a long way from such technologies.”94 When a clinical neurologist ponders a disturbance of the “activity of all neurons and synapses,” her/his test of choice is the EEG. In a routine EEG, sixteen to twenty-­five (actually, twenty-­three at our hospital) silver, tin, steel, or gold electrodes coated with silver chloride are placed on the scalp. They do not rec­ord the electrical activity of eighty-­five billion neurons; what the montages of electrodes detect is “an attenuated [by layers of scalp, skull, and meninges] mea­sure of the extracellular current flow from the summated activity of many neurons.”95 Each electrode detects the activity of neurons populating approximately six square centimeters of under­ lying cortex; synaptic activity (mea­sured in microvolts) of the pyramidal neurons is a princi­ple source of EEG activity. The normal EEG has been studied since Hans Berger’s recording of “brain waves” with a string galvanometer in 1924. The frequency of the waves ranges from one to thirty hertz (Hz) (cycles per second), and for clinical purposes is divided into: delta (one-­half to four hertz), theta (four to seven hertz), alpha (eight to thirteen hertz), and beta (thirteen to thirty hertz) rhythms. The summation of the neuronal synaptic currents accessible to surface electrodes provides no insight into the thought content. We do know that alpha rhythms are associated with “relaxed wakefulness” and that lower-­amplitude beta activity may be elicited by “intense ­mental activity.” A slowed frequency in the delta range occurs transiently when we fall asleep or are in a coma. Lest you assume that the slower EEG frequencies are



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an exclusive marker for impaired cognition, I occasionally encounter patients who make no meaningful response to external stimuli (coma) and whose EEG rec­ords a predominant rhythm of eight to twelve hertz. This is a so-­called “alpha coma,” which can be seen in patients with brain stem lesions or diffuse hypoxic brain damage. Electroencephalography is an invaluable diagnostic tool for determining if a patient has epilepsy or certain types of altered m ­ ental status. For example, it’s g­ reat for detecting cognitive dysfunction associated with liver failure (hepatic encephalopathy) but is insensitive to the m ­ ental ravages of Alzheimer disease or schizo­phre­nia. Although over ninety years of electroencephalographic research has taught us that brain “rhythms do not equal reasoning,” the possibility of a genius signature on EEG recordings was taken very seriously when Einstein, his Institute for Advanced Study colleague John von Neumann, and Norbert Wiener, the author of Cybernetics, underwent EEGs sometime in late 1950.96 It has long been known that alpha rhythm can be “blocked” or desynchronized when the subject focuses his or her attention. The eminent neurosurgeon Wilder Penfield related an account that “Einstein was found to show a fairly continuous alpha rhythm while carry­ing out rather intricate mathematical operations, which, however, ­were fairly automatic for him. Suddenly his alpha waves dropped out and he appeared restless. When asked if t­ here was anything wrong, he replied that he had found a m ­ istake in the calculations he had made the day before.”97 The blocking of the alpha rhythm reflected Einstein’s “concentration of attention” rather than his thought content per se. Nevertheless, Alejandro  P. Arellano, the National Institute of ­Mental Health investigator who recorded Einstein’s, von Neumann’s, and Wiener’s brain wave tracings, found dif­fer­ent distributions of alpha and theta rhythms during “intense m ­ ental work,” such as thinking about relativity during Einstein’s session. Arellano theorized that the changing distribution and synchronicity of ­these rhythms comprised dif­fer­ent “scanning mechanisms” that could facilitate “brightness and originality, creative and abstractive thinking.”98

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This “scanning” theory of higher ­mental function remains mostly meta­phorical (and unconfirmed). If routine EEGs cannot deduce ­mental content, does finer-­ grained micro-­EEG technology hold promise? Rather than the relatively crude recording of the summated activity of millions of neurons in six square centimeters of cortex under­lying each scalp electrode, the Brain Activity Map Proj­ect aspires “to rec­ord e­ very action potential from ­every neuron within a cir­cuit.”99 Is it pos­si­ ble to parse the eight-­to-­t welve-­hertz alpha waves detected on routine EEG into millions of mea­sure­ments of constituent neuronal and synaptic electrical events? More likely, a breakthrough technology is requisite to attain the critical goal of creating an accurate map of the brain’s functions, which depend “on rapid reversals of membrane potential, known as action potentials, to transmit signals between one part of a neuron and another distant part and . . . ​ [are contingent] on smaller, slower changes in [membrane] potential at sites of synaptic contact (i.e. synaptic potentials) to mediate the exchange of information between one cell and the next.”100 A current mapping technology is a four-­by-­four-­millimeter, one-­ hundred-­silicon-­electrode grid that is implanted permanently in the cortex of rats, monkeys, and h ­ umans (for neural prosthetics ­trials). ­These can mea­sure the extracellular action potentials from tens to hundreds of individual neurons.101 The anticipated advances in penetrating electrode design have led the neuroscientists of the Brain Activity Map proj­ect to predict monitoring capabilities of hundreds of thousands of neurons by the mid-2020s. And d ­ on’t forget . . . ​ electric current can flow in two directions, allowing electrodes to rec­ord and “influence the activity of e­very neuron individually in ­t hese cir­cuits, ­because testing function requires intervention.”102 One caveat: As the Brain Activity Map initiative brings new understanding to cir­cuit neuroscience, it aspires to develop “novel devices and strategies for fine control brain stimulation”103 which is g­ reat when treating the “diseased cir­cuits” of Parkinson’s Disease but worrisome if it lifts the lid on the Pandora’s Box of mind control. The latter option is not usually spelled out in NIH grant proposals



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(but could be a real selling point for Defense Advanced Research Proj­ects Agency [DARPA] funding). If “shocking” neurons with invasive electrodes seems regrettably crude and destructive, the adroit manipulation of neuronal circuitry with light became part of the neuroscience tool kit in 2005 with the arrival of optoge­ne­tics.104 Microbial opsins are light-­sensitive proteins that can control ion channels in cell membranes. If an opsin gene is inserted (transfected) into a neuron, light can now turn the neuron on or off with millisecond precision by opening (and closing) ion gates and triggering (or suppressing) neuronal depolarization, which underlies action potentials by which nerve cells communicate. Stanford’s Karl Deisseroth, who introduced channelrhodopsin-2 into mammalian neurons, has also combined fiber optics and electrodes (optrodes) to mea­sure the electrical activity of neural cir­cuits turned on by exposing “opsin-­ized” neurons to light. Recording the neural electricity at microlevels of neurons with opsin genes and ­every action potential spike mea­sured in millivolts ­will create an unpre­ce­dented data deluge, and if we are to sift any meaning from a petabyte (a million gigabytes) of data, we ­w ill become increasingly dependent on computer analy­sis and conclusions drawn from the machine-­learning recognition of data patterns. “When they [computers] come up with t­ hese conclusions, we have no idea how, we just know the general pro­c ess.” Venki Ramakrishnan, a Nobelist and a student of the deep biological structure of the ribosome, has encapsulated our growing dilemma: “So ­we’re in a situation where ­we’re asking, how do we understand results that come from this [computer] analy­sis? This is g­ oing to happen more and more as datasets get bigger.”105 Data sets of this magnitude may be like Jorge Luis Borges’s apocryphal “Map of the Empire” whose size was that of the Empire, and which coincided point for point with it. The following Generations, who w ­ ere not so fond of the Study of Cartography as their Forbears had been, saw that the vast Map was Useless.106 The invaluable standby of the neuroscientist’s intuitive grasp of the phenomena (as in corn ge­ne­ticist Barbara McClintock’s “feeling for the organism”) that he/she is

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encountering ­will be beset by the difficulty inherent in the vast complexity of the neural data generated by brain activity mapping, connectomics, and fMRI. By itself the acquisition of unimaginably im­mense data ­will not solve the “prob­lem” of the ­human brain. Cognitive scientist and veteran subject of 84 fMRIs Russell Poldrack contends that “we know the entire connectivity of C. elegans . . . ​but we still d ­ on’t understand how C. elegans does what it does.” Data alone does not assure understanding and “­people are coming to realize that theory is impor­tant.”107 The most basic questions remain to be answered: “We need to know what level of cellular activity produces thought. ‘Does it take 1000 cells? 10 million? 100 million?’ ”108 ­Every era has drawn on its own complex technological zeitgeist to devise a working model of the brain. Candidate technologies have included Descartes’s clock, the loom, the telephone exchange, a chemical plant, a radar scanner, a hologram, and currently the computer.109 Setting aside the massive programmatic studies underway on the brain’s biologic structure and function, can we combine our exponentially accruing knowledge of h ­ uman neurobiology with the twenty-­first-­century dominance and ubiquity of the computer to begin to understand (and presume to re­create) the brain of an Einstein? The audacious proposal to build and program a machine capable of replicating any ­human’s (let alone Einstein’s) mind is the ultimate quest of “strong” artificial intelligence (AI). Strong AI proposes that the brain is a very clever computer that runs a program to produce the mind. Simply put, computers can think . . . ​or, at least, proponents of AI believe that they can. In 1936, newly arrived in Prince­ton (and about four blocks from Einstein’s ­house), Alan Turing was g­ oing over the proofs of his “On Computable Numbers, with an Application to the Entscheidungsproblem”110 and ushering in the ur-­computer, the universal Turing machine.111 Turing’s “thirty-­five pages would lead the way from logic to machines.”112 By 1950 Turing confided that another fifty years in the f­ uture “one ­will be able to speak of machines thinking without expecting to be contraindicated”; however, in 1950 he considered the question “Can machines think?” to be “too meaningless to deserve discussion.”



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Rather than attempt to define the terms machine and think, he replaced the questions of machine intelligence with the questions posed by “the imitation game,”113 which came to be known as the ­ ere a man, a w ­ oman, and Turing Test.114 The players in the game w an “interrogator” in a separate room. By asking questions and receiving responses via teletype (to preclude auditory cues), the interrogator had to judge which subject was the man and which was the ­woman. Turing then changed the rules of the game when “a machine [a digital computer] takes the part of A [a man],” and the interrogator’s charge became to distinguish the remaining h ­ uman from the computer. Although Turing’s strong AI prophecy was that in a half-­century’s time the interrogator would have a 30 ­percent or more chance of confusing man and machine a­ fter posing questions for five minutes, he had an inkling that “machines carry out something which ­ought to be described as thinking but which is very dif­fer­ent from what a man does” (my italics]).115 Let’s fast-­forward to 1980 and find out how very dif­fer­ent machine thinking can be. Phi­los­o­pher John Searle at Berkeley proposed a thought experiment in which you are locked in a room with “baskets full of Chinese symbols” (ideograms). You do not speak Chinese. You are given a rule book in En­glish that specifies the manipulation of the Chinese symbols “purely formally, in terms of their syntax, not their semantics.” Unbeknownst to you some of the Chinese symbols passed into your room by ­people outside are “questions,” and the rulebook allows you to select symbols that are “answers to the questions.” In time you get so good at symbol manipulation that the answers you pass out of the room are “indistinguishable from ­those of a native Chinese speaker.” You have become adroit at formal syntactical manipulations of Chinese symbols without learning or understanding a single word of Chinese! Now imagine that the sole denizen of the Chinese room is a digital computer. “All the computer has, as you have, is a formal program for manipulating uninterpreted Chinese symbols.” Searle has driven home his compelling argument against the strong AI position “with a very ­simple logical truth, namely, syntax alone is not sufficient for

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semantics, and digital computers insofar as they are computers have, by definition, a syntax alone.” Furthermore, he concluded that “no computer program by itself is sufficient to give a system a mind. Programs, in short, are not minds, and they are not by themselves sufficient for having minds.”116 The cyberneticist and the phi­los­o­pher have expressed diverging views on the limits of machine intelligence and ­whether the brain is a computer. Inherent in Turing’s and Searle’s dialogues across de­cades is the common ground of defining the limits of the computer-­like qualities of the ­human brain. How so? Superficially, the appearance of three pounds of biological wetware chockablock full of neurons, glia, vessels filled with blood, and cerebrospinal fluid is strikingly dif­fer­ent than a box filled with silicon chips and effecting a user interface with a video display terminal, a keyboard, and a mouse. (Supercomputers such as the Cray Titan at Oak Ridge National Laboratory are a l­ittle bigger. It’s about the size of a basketball court filled with two hundred cabinets.) Appearances can be deceiving, but when did we begin to bracket brains and computers together? The design for the world’s first general-­purpose computer, the Analytical Engine, was drafted in 1837 by Charles Babbage, the then Lucasian Professor of Mathe­ matics at Cambridge. This mechanical marvel would likely have been steam-­powered and considerably heavier than its fifteen-­ton prototype (Difference Engine No. 1). It was never built, and posterity has no rec­ord of Babbage’s musings over mind and machine. Neither Babbage nor his cyberneticist descendant, Alan Turing, ­were biologists, and we must look to a savant of the life sciences for an initial scholarly foray into the computability of the brain. That multifaceted scientist/clinician was Warren Sturgis McCullough (1898–1969), who trained in 1928 as a neurologist at Bellevue, then in 1932 as a psychiatrist at the Rockland State Hospital for the Insane, and then in 1934 as a Sterling Fellow in neurophysiology at Yale, which was the epicenter for American brain science (see chapter 3). In this era before rigid distinctions ­were imposed by medical specialty board certification, McCullough would best be designated



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as a neuropsychiatrist, but his “avowed intent of learning enough physiology of man to understand how brains work”117 would tear down the interdisciplinary barriers between cybernetics and neuroscience. Working in Dusser de Barenne’s lab at Yale, he became ­adept at cortical localization using strychnine neuronal stimulation. When he moved to the Illinois Neuropsychiatric Institute in 1941, Mc­Culloch’s expertise in neurophysiology and exposure to mathematical biology was foundational in envisioning the all-­or-­none properties of neuronal discharges as equivalent to the propositional logic of Boolean functions (AND [conjunction], OR [disjunction], and NOT [negation]).118 In 1943 his collaboration with Walter Pitts brought forth the landmark paper “A Logical Calculus of the Ideas Immanent in Ner­vous Activity.”119 They sought nothing less than to bring “work on mathematical logic and prob­lems in computability to bear on our understanding of the brain.” This paper may have heralded the onslaught of the “brain-­as-­a-­computer” meta­phor, and McCullough l­ater conceded that he and Pitts had been inspired by “Turing’s idea of a ‘logical machine.’ ”120 From his study of functional cortical organ­ization, McCulloch regarded the ner­vous system as “a net of neurons, each having a soma and an axon . . . ​[and] adjunctions or synapses.” Launched by McCulloch’s tenet that the brain was built of discrete anatomical/functional units known as neurons, the ensuing de­c ades would propose vacuum tubes and ­later, transistors, as the equivalent of neurons for computer “brains.” Setting wiring diagrams or neural nets aside for the moment, if we hope to “build” a brain of normal ­human or even Einsteinian capacity we need to know if our synthetic neuronal building blocks are the same as the ones that ­Mother Nature provides. It does not require a gradu­ate degree in solid-­state physics or cellular biology to apprehend that transistors, with their tripartite base, collector, and emitter fashioned out of silicon and tweaked with electron donor dopants, are at best ersatz neurons and very dif­fer­ent from the real ­thing. The profound difference in the functional repertoire of transistors and neurons accounts for the radical difference in the architecture of ­these man-­made artifacts and living cells.

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Transistors are semiconductors that can switch or amplify signals. They do not create their own energy or repair/modify/reproduce their physical structure. Neurons do. They reproduce themselves (and carry around nuclear DNA for the purpose) and produce energy as they break ATP bonds in their mitochondria. Neurons manufacture proteins in their ribosomes to repair and modify their structure, which in the case of spinal anterior horn cells can extend a meter or more, requiring an elaborate axonal transport system to ferry proteins from cell body to distant synapse. “If the dream of a bacterium is to become two bacteria,”121 the dream of a neuron is to synapse with another neuron, and this requires very “untransistor-­ like” capacities, such as elongating and branching dendrites and axons or the learning-­induced remodeling of synapses. Neurons collaborate with other cells (oligodendroglia) to acquire myelin insulation wrapped around axons to ensure the rapid conduction of action potentials. Neurons even have their very own cytoskeletons necessary for mitosis and motility. Are you convinced of the irreconcilable differences between inert silicon chips (integrated cir­cuits with numerous tiny transistors) and living carbon cells? I am . . . ​but I fear that I’m swimming against the riptide of strong AI. Even Christof Koch, a spokesman for the neurobiology side of the equation, endorsed the proposition that “synapses are analogous to transistors.”122 The neuroscientist Gary Marcus has not foreseen “any in-­principle limitation” to machine thinking and has averred, “Carbon ­isn’t magical, and I suspect silicon ­will do just fine.”123 Notwithstanding the assertions of Koch and Marcus that silicon and carbon-­based chemistries are both plausible options for fabricating brains, evolution clearly did not ­favor silicon as a platform for biochemistry. Astrophysicist Neil deGrasse Tyson has explained that carbon and silicon atoms “have similar outer orbital structures of their electrons.” “Why not imagine silicon-­based life [and brains]? Nothing stopping you in princi­ ple. But in practice, carbon is about ten times more abundant in the universe than silicon. Also, silicon molecules tend to stay tightly



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bound, making them unwilling players in the world of experimental chemistry that is life.”124 Despite the visions of sci-fi authors and aspirations of strong AI, biological variation and natu­ral se­lection over the unfathomable epochs of deep time (to be discussed l­ater) have not brought forth a silicon neuron. Nature does not exploit ­every opportunity and dif­fer­ent outcomes might result if we could start over from the point when life emerged on earth 3.7 billion years ago, but if the lessons of evolutionary history are to be heeded, a silicon ner­vous system identical to the ­human brain never was and never ­will be. Let me climb down from my soapbox and assume that we can conflate neurons and transistors. If so, how many transistors are required to meet the specifications of an Einstein brain? If we allot eighty-­five billion neurons to a “base model” h ­ uman brain, that milestone has been surpassed by IBM’s TrueNorth, which simulates 530 billion neurons. And yet, although supercomputers can defeat chess grandmasters and prevail over Jeopardy! champions, “­things ­every dummy can do, like recognizing objects or picking them up, are much harder.”125 It appears that despite the advent of an infernal machine comprised of 530 billion ersatz neurons, the “singularity”—­a kind of cybernetic End of Days in which AI surpasses h ­ uman intelligence and takes over—­has yet (if ever) to transpire. One critical difference between brain and computer may lie at the level of synaptic connections. “The typical gate of a transistor in the central pro­cessing unit is connected to a mere handful of other gates, whereas a single cortical neuron is linked to tens of thousands of other neurons.”126 Moreover, Cambridge physiologist Dennis Bray has been led to speculate that “in an artificial machine, we must consider that something is missing from the canonical microchip.”127 Duly noted, but hope springs eternal in the hearts of the strong AI congregation. If we are ever to reach the Holy Grail of a bona fide thinking machine, New York University’s Gary Marcus has envisioned three routes to success: (1) “Bigger and faster machines,” (2)

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Better “learning algorithms” and “Bigger Data,” and (3) “Understand what it is that evolution did in the construction of the h ­ uman 128 brain.” Q. Bigger and faster machines? A. I suppose that if TrueNorth’s 530 billion surrogate neurons are insufficient, we can hope that Moore’s law (which states that the number of transistors on a microchip w ­ ill roughly double e­ very two years) ­will lead to even bigger supercomputers, but microchips may “hit the wall” when the miniaturization of cir­cuit features “get to the 2–3 nanometre limit,” which is about ten atoms across.129 Q. Better learning algorithms? A. Marcus’s query presupposes a machine that gets smarter as it accrues experience, also known as learning, and AI based on deep learning has largely supplanted “Good Old-­Fashioned AI” (GOFAI), which was based on symbolic repre­sen­ta­tions and required top-­down programming. Machines that can learn on the fly without superimposed algorithms accomplish this very h ­ uman skill set with interconnected layers of silicon neuron stand-­ins. ­These neural networks (nets) can modify the connections of their layers with backpropagation as they detect error signals. Learning takes place as neural nets modify their own codes “to find the link between input and output—­ cause and effect—in situations where the relationship is complex or unclear.”130 As far as we know in neurobiology, the final common pathway in the brain’s modification of its connections is increased synaptic growth or neurotransmitter release131 and not purely informational; that is, neural code changes. “Unfortunately, such [neural] networks are also as opaque as the brain. Instead of storing what they have learned in a neat block of digital memory, they diffuse the information in a way that is exceedingly difficult to decipher.”132 Or we could be barking up the wrong binary code “tree” in the search for the brain’s real and true algorithm. With the its all-­or-­ none action potentials, neuronal intercommunication has been equated for better or worse with the binary code of classical digital



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computation based on bits that are e­ ither zero or one. In contrast, quantum computing uses qbits, which can represent zero and one at the same time (superposition). A quantum algorithm exploits superposition to scan multiple data sets at the same time rather than in the serial sequencing of classical computation.133 Does the brain operate along the lines of quantum computing, which holds the promise of unpre­ce­dented speed and capacity to pro­cess huge amounts of information? Does quantum computing in its infancy offer a bold insight into our neural real­ity or, like Descartes’s clock,134 is it the latest technocultural meta­phor for brain physiology?135 Q. How did evolution construct the brain? A. As Daniel Dennett and Richard Dawkins take ­great pain to explain, we must appreciate the cosmic paradox that the most complex organ extant was created by the “blind, uncomprehending, and purposeless pro­cesses” of ge­ne­tic variation and natu­ral se­lection.136 In essence, our intelligence arose from Unintelligent Design. (I speak as a practitioner of the field of applied biology known as medicine and a student of the nuts and bolts of Darwinian evolution as it applies to the brain. I make no attempt to address the profound questions posed by religion with scientific answers nor vice versa; in the words of paleontologist Stephen J. Gould, ­these domains of ­human knowledge and faith are separate, nonoverlapping magisteria137 that, for what it’s worth, I believe can coexist to the benefit of thoughtful and devout ­people.) In stark contrast, the digital computer is an example of Intelligent Design par excellence, and so right out of the starting blocks, we must recognize that machine intelligence and biological intelligence got to where they are via very dif­fer­ent routes (top-­down technical design vs. bottom-up evolution) and time frames (eighty years counting down from Turing vs. 3.7 billion years counting down from the appearance of life on earth). The brain-­computer analogy comes up short again when we acknowledge the generalizations that “brains are parallel (they execute many millions of ‘computations’ si­mul­ta­neously, spread over the w ­ hole fabric of the brain);

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computers are serial (they execute one single s­imple command ­after another, a serial single-­file stream of computations that makes up for its narrowness by its blinding speed).”138 ­These apparent discrepancies between biologic and machine intelligences pres­ent formidable obstacles to the AI modeling of brain functions. In the words of George Box: “Essentially all models are wrong but some are useful.”139 If we turn to evolutionary biology for answers, according to Dennett we are engaged in an exercise in “reverse engineering.”140 A major prerequisite for reverse engineering the final product of brain evolution is a detailed grasp of correlative ­human neuroanatomy, by which I mean our knowledge of the function of a given neural structure. For example, as best we can experimentally surmise, a creature with a single type of ret­i­nal photoreceptor ­will not see colors. Dogs have two kinds of ret­i­nal cones and can see colors (surprise! I too used to think that Lassie was colorblind), albeit not as well as ­humans with three kinds of cones. Freud said, “Anatomy is Destiny,” and in this par­tic­u­lar case he got it right.141 However, the ­human brain is a ­little more complex than the canine ret­ina, and our pres­ent knowledge of h ­ uman neuroanatomy may not suffice for reverse engineering. In 1993 Francis Crick decried the “backwardness of h ­ uman neuroanatomy” as compared to the detailed maps of macaque brains142 (please d ­ on’t ask what has to be done to a macaque and his brain to obtain that map, but in the interests of full disclosure the procedure goes along the lines of: (1) open macaque’s skull, (2) inject ­horse­radish peroxidase tracer into brain, (3) kill the animal a­ fter a few days, and (4) examine sections of the brain with a microscope to determine what axonal pathways ­were traversed by the tracer).143 Twenty-­four years l­ater, we still have a long way to go in our efforts to anatomize the ­human brain, as implied by this chapter’s review of the ongoing efforts of the BRAIN Initiative, fMRI, connectomics, the Brain Activity Map Proj­ect, et cetera. We find ourselves faced with the dilemma voiced by Francis Collins, who led the ­Human Genome Proj­ect (and no stranger to complex



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biological prob­lems). He observed that when looking at pictures of the connectome, “It’d be like, you know, taking your laptop and prying the top off and staring at the parts inside, you’d be able to say, yeah, this is connected to that, but you ­wouldn’t know how it worked.”144 Gary Marcus’s bet is that we need to look at the evolution of the brain to “solve” strong AI, and I enthusiastically concur that to best understand the brain, you need to start by studying the brain. What ­else would you expect a neurologist to think? But before you depart from the ranks of the cybernetics “true believers” and embrace evolution as the royal road to understanding the brain, please heed biologist Leslie Orgel’s Second Rule: “Evolution is cleverer than you are.”145 To bring the curtain down on my chapter-­opening interrogatory—­ “Where do we go from h ­ ere?”—we need two t­ hings: a rearview mirror and a crystal ball that can foretell the discoveries of aspirational neuroscience. In the mirror we see that our rediscovery of the “lost” photo­ graphs of Einstein’s brain raised many questions . . . ​some profound and some of mainly historical interest. Only further study of the brains of off-­t he-­charts geniuses w ­ ill affirm ­whether our careful examination was the last gasp of clinicopathologic correlation (soon to be forgotten in the wake of con­temporary neuroscience replete with functional neuroimaging and connectomics) or a Rosetta stone for the neural under­pinnings of genius (if such exist). Posterity w ­ ill not afford us the opportunity for anatomical study of the brains of Newton, Galileo, Picasso, Clerk Maxwell, Darwin, Shakespeare, or Da Vinci, to test the hypothesis that a common and distinctive neural thread runs throughout genius. And, as I edit this, the death of Stephen Hawking on March 14, 2018 (the one-hundredthirty-ninth anniversary of Einstein’s birth!) beckons further study of an elite brain, cortical changes of his amyotrophic lateral sclerosis of fifty-five years duration notwithstanding. Regrettably (for the hypothesis), the most intensively studied brain in the last

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hundred years has been that of Vladimir Lenin (see chapter  3). The resulting thirty-­thousand-­plus microscope slides led the Vogts to attribute Lenin’s po­liti­cal genius to numerous “jumbo” pyramidal neurons observed in cortical layer three—­a finding (and conclusion) that Wilder Penfield questioned. Before dismissing the exceptional-­ neuron-­a s-­a-­hallmark-­of-­intelligence theory out of hand, consider the very distinctive Von Economo neurons, which are large spindle-­ shaped nerve cells found in the large “intelligent” mammalian brains of h ­ umans, ­great apes, elephants, and cetaceans.146 It is a cruel irony that as I conclude my account of finding Thomas Harvey’s lost cache of photo­graphs and microscope slides of Einstein’s brain, I must own up to the unfortunate occurrence that sometime a­ fter May 15, 2000, the remaining 180 or so celloidin-­ embedded brain blocks dis­appeared! The last color photo­graphs of the two glass specimen jars containing the gauze-­shrouded tissue blocks w ­ ere taken by me (see Figure 1.4) on that spring day in 2000 at the Medical Center of Prince­ton and are readily found on the Internet and in textbooks. In December 2011 I was reminded and reassured that Thomas Harvey had left “part of the brain” to Prince­ ton.147 However, as I write this on a beautiful spring day six years ­later, t­ hose blocks are officially AWOL. A spokeswoman for the Medical Center of Prince­ton at Plainsboro (the latest iteration of Prince­ton Hospital, where Thomas Harvey undertook Einstein’s autopsy) informed me that the “Prince­ton HealthCare System [PHCS] does not have the ­legal right to the brain, nor do we have possession of it. It is our unconfirmed belief that Dr. Krauss does.”148 PHCS had previously closed the door on further inquiries regarding the whereabouts of Einstein’s brain with the declaration that Elliot Krauss, Prince­ton’s chief of pathology (see chapter 1) “does not wish to be interviewed.”149 However, in the first week of February 2018, Dr. Krauss broke with precedent and met with Japanese broadcast media. Lest you get your hopes up, he declined to be filmed and would not divulge the location of the brain blocks.150 If the motherlode of Einstein’s brain tissue has been lost or declared off-­limits by the Medical Center of Prince­ton, the legacy



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of Einstein’s brain w ­ ill recede from view that much more quickly. But what of the tissue that we have preserved and made available for scholarly inquiry? A large portion of Harvey’s microscope slides remain both mounted on glass and in digital form. The new neural science of connectomics may help avert the last rites being given to Thomas Harvey’s meticulously sectioned and stained microscope slides. Histologic studies to date have been confined to counts of the density of neurons and glial cells. No investigator has published studies of the axonal anatomy visualized on the Weigert-­stained slides. By repurposing/repro­cessing the slides for scanning EM, could the greater detail of connectomic-­level imaging be brought to bear on slides that Harvey intended for light microscopy? Shifting my gaze from the rearview mirror to the crystal ball holding the neuroscientific hopes and dreams summoned forth by Einstein’s brain, three aspirational questions emerge from the mists: Q. Can we “grow” another Einstein? A. When I published my first paper on Einstein in 2001, it was mistakenly believed that I had access to the same brain blocks that I had photographed151 and could provide tissue samples. The interested parties ­were ­either molecular biologists skilled at PCR (polymerase chain reaction) or would-be employers of such scientists for the sole purpose of sequencing Einstein’s genome. With a complete Einsteinian DNA sequence in hand, the prospect of cloning would exert a strong attraction. Recalling the thermodynamics of DNA, I quickly disabused them of their cloning notion. As discussed in chapter 2, the room-­temperature formaldehyde that Harvey used to perfuse Einstein’s brain on April 18, 1955, led to the irreversible denaturation of his DNA into fragments one hundred to two hundred base-­pairs in length.152 At pres­ent we lack the technology to reassemble ­those fragments into the continuous three-­billion base-­pair sequence of Einstein’s genome. We d ­ on’t even have a complete list of which genes interspersed among t­ hose three billion base-­pairs subserve intelligence. Intelligence is a classic polygenic ­human trait, and a recent study of 78,308 individuals found fifty-­two genes (forty

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new and twelve confirmed) influencing h ­ uman intelligence.153 Further data-­mining ­will inevitably identify more intelligence-­linked genes. With sizeable gaps in the ge­ne­tic blueprint (aka, nature) for intelligence, that is, the fifty-­two genes account for less than 5 ­percent of variance in intelligence and the im­mense variability of the environmental impact on the brain’s wiring (aka, nurture)—­cloning another Einstein remains a distant (if not unrealizable) prospect. Q. Can we “build” (program) another Einstein? A. As outlined in my earlier discussion of strong AI, we have no definitive evidence that the brain operates in a manner analogous to serial, parallel, or quantum computing . . . ​or w ­ hether the brain’s cognitive architecture is sui generis. I ­will piggyback my opinion onto Gary Marcus’s “bold claim” that “I d ­ on’t think we w ­ ill ever understand [or build] the brain ­until we understand what kind of ­ ill propose a biological justicomputer it is.”154 At chapter’s end, I w fication for the elusive nature of attaining Marcus’s sine qua non of understanding the “kind of computer” that is operative during ­human cognition. Q. How about enhancing ­human intelligence to approach Einsteinian levels? A. ­We’re prob­ably not ­going to reach that goal by following my parents’ admonitions, such as studying hard, getting plenty of sleep, and not watching tele­vi­sion or reading comic books. Parents of the current generation of digital natives prob­ably have formulated their own updated rules, such as “no computer gaming and try to express your thoughts in more than 280 characters” (sorry, Twitter). An in­ter­est­ing and germane development has not unexpectedly been brought to you by modern medicine. No longer content with “treating disease” (“therapy”), my colleagues in neurology are branching into “improving normal abilities” (“enhancement”).155 Do we have an Einstein pill? Not yet . . . ​but ­we’re working on it. Need to be on point at that morning meeting ­after four hours of sleep? How about modafinil? C ­ an’t concentrate ? Try



Where Do We Go from ­Here? 257

methylphenidate. Experiencing memory loss associated with early Alzheimer disease? Anticholinestase inhibitors are just the ticket. Anxious? Selective serotonin reuptake blockers (SSRIs) can come to the rescue. No big surprises are found ­here. Doctors treat neurologic or psychiatric disease with appropriate pharmacotherapy. In the latter part of my clinical ­career, t­ here has been mission creep from therapeutic indications to the demand for quality-­of-­life enhancement. Patients with normal intellect, memory, and no sleep deprivation want to think and remember better (or have the option to maintain peak per­for­mance on four hours of sleep nightly). Do t­ hese drugs ­really work for normal ­people, or is this a pharmacologic Faustian bargain that exposes the patient/client/lifestyle perfectionist (you choose) to side effects and no benefit? Maybe. Scientific uncertainty aside, this is a place where cultural expectations and medicine increasingly collide. Is ­there anything e­lse on the cognitive enhancement menu besides drugs? In a word, it’s electricity. Walt Whitman may have presciently sung about “the body electric” in 1855,156 nearly a ­century before Hodgkin and Huxley157 explained the ionic basis of the axonal action potential, but recently the brain’s electricity has been annexed from the provinces of poetry and physiology to become the realm of do-­it-­yourself cognitive enhancement. On eBay for $39.95, you can purchase a transcranial direct current stimulation (tDCS) kit containing two scalp electrodes with a two-­milliamp power supply and then y­ ou’re all set to apply low-­voltage direct current to your brain. Simply strap the saline-­soaked sponges containing the electrodes to your scalp and turn on the current for usually about twenty minutes. Remember to allow at least forty-­eight hours between sessions. Depending on the polarity of stimulation, the resting neuronal membrane potential is hyperpolarized (refractory to firing) or depolarized (the neuronal action potential spikes or fires). W ­ ill tDCS make you into another Einstein or at least a l­ittle smarter? It may help with depression but the cognitive benefits are unproven. Due to the brain’s connectivity, tDCS may affect parts

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of the brain distant from the cortex under­lying the electrodes and “changes initiated during stimulation can be longlasting and even self-­perpetuating.”158 As opposed to the scattershot effects of tDCS on the under­lying cortex, could the greater precision of stimulating electrodes applied to circumscribed areas of the cortex elicit profound thoughts worthy of an Einstein? In the heyday of cortical mapping in the 1930s and 1940s, Wilder Penfield applied from one half to five volts of electrical stimulation through bipolar electrodes, with the points three millimeters apart. From the temporal lobes, the electrodes summoned forth quasi-cinematic fragments of the patients’ memories, and from the anterior bank of the precentral gyrus, movements of the opposite side of the face and body ­were evoked. In contrast, Penfield’s electrodes failed to summon forth language when current was applied to Broca’s area (for expressive speech). The anterior frontal lobes, the seats of higher intellect, planning, and initiative, ­were “usually resistant to electrical stimulation,” which was turned off when it became painful.159 The higher realm of thought, with its foundational basis in language, has eluded the “interrogation” of eloquent cortex by electrode, and the prospect of evoking words and thoughts befitting an Einstein with external application of electricity remains a long way from realization. I have enumerated the formidable, if not insuperable, barriers to mapping both anatomically and physiologically the brain(s) of Einstein(s) past and f­ uture or creating proxy Einsteins through ge­ne­ tic, cybernetic, and electric technology. Is it within the powers of the ­human brain to understand itself on the deepest levels, or ­will our very own thought pro­cesses remain perpetually beyond our ken? Have I been exploring an absurd proposition akin to asking a dog to understand calculus? As was (very) apocryphally attributed to Zhou Enlai when asked about the impact of the French Revolution nearly two centuries earlier, he responded, “It may be too early to say.” I lay the profound difficulty of the “prob­lem” of Einstein’s (or any) brain squarely at the feet of the unimaginably power­ful



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conjunction of natu­ral se­lection and deep time. Deep time is an essential part of the intellectual tool kit of geologists, and an acquisition of this sensibility is a hard-­won perspective for nongeologists or for ­those of us working with biological phenomena. In Basin and Range, John McPhee conceded that we may be able to mea­sure deep time, but “the ­human mind may not have evolved enough to be able to comprehend deep time.” “A sense of geologic time is the most impor­tant ­thing to suggest to the nongeologist: the slow rate of geologic pro­cesses, centimetres per year, with huge effects, if continued for enough years.”160 If the seafloor spreads four centimeters per year for eighty million years (or roughly the duration of the Cretaceous period), the sea bottom w ­ ill have expanded to separate continental coastlines by nearly two thousand miles! (I apologize if my linear dead-­ reckoning runs roughshod over the complexity of plate tectonics.) Now forget about magma migrating up through the oceanic crust and consider the rate of spontaneous mutations occurring throughout the primordial biomass, commencing with the appearance of life on earth. Assume that significant mutations for structural proteins or enzymes transpire at a par­tic­u ­lar chronologic frequency and multiply that mutation rate by deep time. The rate of mutation (or variation) of DNA/RNA varies according to the organism and the size of its genome. Fruit flies, our old friend the roundworm (C. elegans), and mice have higher mutation rates per base pair for specific chromosomal loci than ­humans.161 For the ­human genome it is estimated that each zygote (fertilized egg) has sixty-­four new mutations! Not all mutations change the structure/physiology (phenotype) of ­people, and of ­those that do, some are adaptive, some are harmful, and some are neutral, with no observable impact. It is mind-­boggling to consider the structural impact on the evolving brain that is orchestrated by the cumulative genomic change accruing over countless eons. In contrast, ­don’t assume that the rate of ge­ne­tic change is so gradual and incremental that it can be viewed only from the perspective of deep time and must be imperceptible on an everyday timescale. In some circumstances phenotypic evolution can be directly

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observed over periods as short as two years (in the case of the climate-­induced changes in the beak size of ground finches in the Galapagos Islands, for example).162 If mea­sur­able change can be observed in as ­little as two years, imagine what can transpire on the scale of deep time! To evolve ner­vous systems to the current top-­of-­the-­line ­human brain, biological deep time began 3.4 to 3.8 billion years ago with the debut of bacteria. About two billion years ago, the first complex cells with a true nucleus (eukaryotes) appeared, and 1.4 billion years ­later, complex multicellular eukaryotes came on the scene.163 Is it any won­der that over the inconceivable expanse of deep time countless generations of all living organisms reproducing with differing mutation rates would produce innumerable incremental changes (with the occasional macromutation or “hopeful monster” thrown in for good mea­sure) to lead to the most complex biological structure to date (as far as the fossil rec­ord permits us to know)? For neuroanatomists the brain is the mother-­of-­a ll palimpsests teeming with shortcuts (U fibers), detours (optic nerve crossover at the optic chiasm), cir­cuits with no clear beginning or end (feedforward/feedbackward of the afferent visual system), blind alleys (rods and cones located furthest from the image focused on the ret­i­nal surface), workarounds (thoracic motor neurons can be relied upon to control breathing muscles when the cervical spinal cord is damaged), redundant systems (two motor systems—­pyramidal and extrapyramidal), dead-­ends (when more than 90 ­percent of cells in the substantia nigra die off, we ­can’t regrow them, and Parkinson’s disease results), add-­ons (the phyloge­ne­tically “new” color-­sensitive parvocellular visual system added to the “old” black-­a nd-­white sensitive magnocellular system), waves of neuronal migration, both chemical and electrical synapses, myelinated and unmyelinated axons, et cetera. The irresistible force of natu­ral se­lection imposed on ge­ne­tic variation produced by copying errors, DNA damage, and recombination over the course of deep time could be headed in one direction only—­complexity. In the words of Gary Marcus: “From the 100 + cortical areas in the h ­ uman brain, with vast numbers of



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apparently orderly connections between them, to the hundreds of neuronal types, to the enormous amount of molecular complexity within individual cells and synapses, the dominant theme of the brain is not simplicity (as so many computational neuroscientists seem to hope) but complexity.”164 Seeking to bring order out of the chaos of this daunting complexity are two seminal concepts of the “young sciences” of neurology and cybernetics—­the neuron doctrine (1906) and Turing’s universal machine (1936). Am I proposing that our analytical concepts must be as venerable as the phenomena studied? Of course not, but I am sanguine that as a field of scientific inquiry matures, the accretion of knowledge at least demarcates more clearly the known, the partly speculative, and the truly unknown. The platform of a mature science may provide the launch site for a true breakthrough. Although scientists knew about x-­ray crystallography and deoxyribonucleic acid before 1953, biology was never the same ­a fter Watson and Crick unveiled the double helix. At this point in the race (or maybe ultramarathon), to understand the brain, we are just beginning to hit our stride out of the starting blocks. We may be interested in some brains more than o­ thers, but I’m afraid that further study of Einstein’s brain may well be an off ramp, diverging from the superhighway of twenty-­first c­ entury neuroscience. ­There ­will likely never be an Institute of Einstein Brain Studies that ­will underwrite research addressing the “obvious” questions. Was Einstein’s connectome unique? Is the cortical morphology of all geniuses exceptional? ­Will neuroanatomists ever encounter a doppelganger (or phenocopy) of Einstein’s brain that in life was the seat of nongenius intellect? The questions may remain unanswered, but our fascination with Einstein’s achievements and their connection to his brain remains undiminished for over six de­cades ­after Thomas Harvey presumed to grasp the brain in his hands, plunge it into formalin, and begin the Promethean quest for physical traces of unparalleled genius in 1,230 grams of neural tissue.

Notes

p refac e Epigraph: John Steinbeck, Log from the Sea of Cortez (New York: Penguin Books, 1995), 61–62. 1. Dean Falk, Frederick E. Lepore, and Adrianne Noe, “The Ce­re­bral Cortex of Albert Einstein: A Description and Preliminary Analy­sis of Unpublished Photo­graphs,” Brain: A Journal of Neurology 136, no. 4 (2012): 1304–1327. 2. J. Maslin, “John Grisham: An Interview,” New York Times Book Review, June 4, 2017. 3. Lewis Carroll, Alice’s Adventures in Wonderland (London: Thomas Nelson and Sons, 1916), 81–82. 4. K. Brodmann, Brodmann’s Localisation in the Ce­re­bral Cortex, trans. and ed. Garey J. Laurence (New York: Springer, 2006), i–298. 5. Lisa Harris, “The Dogs Bark,” New York Times, October 28, 1973.

1   a neurologi s t wa lks in p ri n ce t­ on 1. Abraham Pais, Einstein Lived ­Here (Oxford: Clarendon, 1994), 199. 2. Sandra F. Witelson, Debra L. Kigar, and Thomas S. Harvey, “The Exceptional Brain of Albert Einstein,” Lancet 353, no.  9170 (1999): 2149–2153. 3. Steven Pinker, “His Brain Measured Up,” New York Times, June 24, 1999. 4. Frederic Golden, “Albert Einstein,” Time, December 31, 1999. 5. Frederick E. Lepore, “Dissecting Genius—­Einstein’s Brain and the Search for the Neural Basis of Intellect,” Cerebrum 3, no. 1 (2001), http://­ www​.­dana​.­org​/­Cerebrum​/­Default​.­aspx​?­id​=3­ 9337.

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Notes to Pages 7–19

6. Michael Paterniti, “Driving Mr. Albert: A Trip across Amer­i­ca with Einstein’s Brain,” Harper’s Magazine, October 1997, 35–58. 7. Michael Paterniti, Driving Mr.  Albert: A Trip across Amer­ic­a with Einstein’s Brain (New York: The Dial Press, 2000). 8. Ibid., 183. 9. Thomas S. Harvey, interview by Frederick E. Lepore, 2000. 10. Lepore, “Dissecting Genius.” 11. Carolyn Abraham, Possessing Genius: The Bizarre Odyssey of Einstein’s Brain (New York: St. Martin’s Press, 2001), 345–347. 12. Jorge A. Colombo et al., “Ce­re­bral Cortex Astroglia and the Brain of a Genius: A Propos of A. Einstein’s,” Brain Research Reviews 52, no. 2 (2006): 257–263. 13. Sandra Witelson, personal communication to Thomas S. Harvey, December 2005. 14. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 15. Dean Falk, “New Information about Einstein’s Brain,” Frontiers in Evolutionary Neuroscience 1, no. 3 (2009), https://­doi​.­org​/­10​.­3389​/­neuro​.­18​ .­003​.­2009. 16. Jane Bosveld, “Re-­analyzing One of the Greatest Brains in History,” Discover, December 17, 2009. 17. Lepore, “Dissecting Genius.” 18. M. A. Ledger, “What Ever Happened to Einstein’s Brain?,” Penn Medicine, Fall 2011, 22–25. 19. Thomas S. Harvey, interview by Frederick E. Lepore, 2000. 20. Abraham, Possessing Genius, 347. 21. David LaBerge, “Sustained Attention and Apical Dendrite Activity in Recurrent Cir­cuits,” Brain Research Reviews 50, no. 1 (2005): 86–99. 22. David LaBerge, e-­mail message to author, May 21, 2009. 23. David LaBerge, e-­mail message to author, 2011. 24. LaBerge, e-­mail message to author, July 1, 2009. 25. Katrin Amunts, Axel Schleicher, and Karl Zilles, “Outstanding Language Competence and Cytoarchitecture in Broca’s Speech Region,” Brain and Language 89, no. 2 (2004): 346–353. 26. Alison McCook, “Shelved,” Nature 476, no. 7360 (2011): 270–272. 27. Thomas J. Harvey, personal communication to Frederick E. Lepore, 2010. 28. Frederick E. Lepore et al., “Supranuclear Disturbances of Ocular Motility in Lytico-­Bodig,” Neurology 38, no. 12 (1988): 1849.



Notes to Pages 21–25

265

2   apr il 18, 195 5 1. Jon R. Cohen and L. Michael Graver, “The Ruptured Abdominal Aortic Aneurysm of Albert Einstein,” Surgery, Gynecol­ogy & Obstetrics 170 (1990): 455–458. 2. Kevin P. Conway et al., “Prognosis of Patients Turned Down for Conventional Abdominal Aortic Aneurysm Repair in the Endovascular and Sonographic Era: Szilagyi Revisited?,” Journal of Vascular Surgery 33, no. 4 (2001): 752–757. 3. Cohen and Graver, “The Ruptured Abdominal Aortic Aneurysm of Albert Einstein.” 4. Walter Isaac­son, Einstein: His Life and Universe (New York: Simon & Schuster 2007), 543. 5. “Dr. Albert Einstein Dies in Sleep at 76: World Mourns Loss of a ­Great Scientist,” New York Times, April  19, 1955; R. Apple, “Einstein Dies! Scientist, 76, Succumbs After Brief Hospital Illness,” Daily Prince­ tonian, April 18, 1955. 6. Carolyn Abraham, Possessing Genius: The Bizarre Odyssey of Einstein’s Brain (New York: St. Martin’s Press, 2001), 68. 7. Thomas S. Harvey, interview by Frederick E. Lepore, June 4, 2000, Titusville, New Jersey. 8. J. J. Chandler, “The Einstein Sign: The Clinical Picture of Acute Cholecystitis Caused by Ruptured Abdominal Aortic Aneurysm,” New ­England Journal of Medicine 310, no. 23 (1984): 1538. 9. Abraham, Possessing Genius, 59. 10. “Dr. Albert Einstein Dies in Sleep at 76.” 11. James D. Watson and Francis H. C. Crick, “Molecular Structure of Nucleic Acids,” Nature 171, no. 4356 (1953): 737–738. 12. Abraham, Possessing Genius, 230. 13. “Dr. Albert Einstein Dies in Sleep at 76.” 14. Harvey, interview by Lepore, 2000. 15. Abraham, Possessing Genius, 74. 16. Isaac­son, Einstein: His Life and Universe, 544. 17. Abraham, Possessing Genius, 75. 18. Robert Allen Farmer, The Last ­Will and Testament (New York: Arco, 1968), 24–29. 19. Jacques Hadamard, The Mathematician’s Mind: The Psy­chol­ogy of Invention in the Mathematical Field (Prince­ton, NJ: Prince­ton University Press, 1996), 142–143.

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Notes to Pages 25–34

20. “Geniuses Aid Tests of Brain Pro­cesses; Einstein’s Brain Waves Being Recorded,” New York Times, February 24, 1951. 21. Paul A. Schilpp, ed., Albert Einstein: Philosopher-­Scientist (New York: MJF Books, 1970), 33. 22. “Son Asked Study of Einstein Brain: Scientist’s ­Will Includes No Specific Bequest of Body—­ His Neighbors Mourn,” New York Times, April 20, 1955. 23. William L. Laurence, “Key Clue Sought in Einstein’s Brain,” New York Times, April 20, 1955. 24. Harvey, interview by Lepore, 2000. 25. “Son Asked Study of Einstein Brain.” 26. “Einstein Study Called,” New York Times, April 22, 1955. 27. Abraham, Possessing Genius, 85. 28. Harvey, interview by Lepore, 2000. 29. Percival Bailey, Up from Little Egypt (Tryon, NC: Buckskin Press, 1984), i–265. 30. Percival Bailey and Gerhardt von Bonin, The Isocortex of Man (Champaign: University of Illinois Press, 1951), ix. 31. Korbinian Brodmann, Localisation in the Ce­re­bral Cortex (New York: Springer, 2006), 108. 32. Alfred Walter Campbell, Histological Studies on the Localisation of Ce­re­bral Function (Cambridge, UK: Cambridge University Press, 1905), 292–293. 33. Bailey and von Bonin, The Isocortex of Man, 189. 34. Nobel Lectures: Physiology or Medicine 1901–1921 (Amsterdam: Elsevier, 1967), 220–253. 35. Ibid., 189–217. 36. Abraham, Possessing Genius, 33. 37. Michel Goedert et al., “100 Years of Lewy Pathology,” Nature Reviews Neurology 9, no. 1 (2013): 13–24. 38. M. A. Ledger, “What Ever happened to Einstein’s Brain?,” Penn Medicine 23 (Fall 2011): 22–25. 39. Ibid. 40. Harvey, interview by Lepore, 2000. 41. Einstein Brain Atlas, http://­nmhmchicago​.­org​/­harvey. 42. Loane Skene, “Owner­ship of H ­ uman Tissue and the Law,” Nature Reviews Ge­ne­tics 3, no. 2 (2002): 145–148. 43. Unpublished correspondence, National Museum of Health and Medicine, Otis Historical Archives, Harvey Collection, Silver Spring, MD.



Notes to Pages 34–42

267

44. Abraham, Possessing Genius, 111–114. 45. Rebecca Skloot, The Immortal Life of Henrietta Lacks (New York: Crown, 2010), 317. 46. Rebecca Skloot, “The Immortal Life of Henrietta Lacks, the Sequel,” New York Times, March 23, 2013. 47. Ewen Callaway, “Deal Done over HeLa Cell Line,” Nature 500, no. 7461 (2013): 132–133. 48. Kathy L. Hudson and Francis S. Collins, “Family ­Matters,” Nature 500, no. 7461 (2013): 141–142. 49. D. W. Batts, “Cancer Cells Killed Henrietta Lacks—­Then Made Her Immortal,” Virginian-­Pilot, May 5, 2010. 50. “Einstein Brain Atlas,” https://­itunes​.­apple​.­com​/­us​/­app​/­einstein​ -­brain​-­atlas​/­id555722456​?­mt​=8­ . 51. A. E. Nutt. “The Secret Life of Einstein’s Brain,” Star Ledger Inside Jersey Magazine, March 2013.

3   what the ne uropat h olog i s t kn ew  .  .  .  ​a n d ­d idn’t know Epigraph: Donald Rumsfeld, Known and Unknown: A Memoir (New York: Sentinel, 2011), xiii. 1. Andreas Vesalius, De Humani Corporis Fabrica, book 7 (Padua, Italy: Padua School of Medicine, 1543). 2. James Henry Breasted, ed. The Edwin Smith Surgical Papyrus: Published in Facsimile and Hieroglyphic Transliteration with Translation and Commentary in Two Volumes, vol. 4 (Chicago: University of Chicago Press, 1930). 3. Stanley Fin­ger, Minds ­behind the Brain: A History of the Pioneers and Their Discoveries (New York: Oxford University Press, 2000), 30. 4. Ibid., 92–93. 5. Frederick E. Lepore, “The Beer-­Glass Full of ­Water—­Leeuwenhoek and the Optic-­Nerve,” Neurology 36, no. 4 (1986): 534. 6. Fin­ger, Minds ­behind the Brain, 197. 7. J. G. Greenfield and A. Meyer, “Preface” and “General Pathology of the Nerve Cell and Neuroglia,” in Greenfield’s Neuropathology (Philadelphia: Lippincott Williams and Wilkins, 1963): v–70. 8. Orville T. Bailey, “Neuropathology—­Then and Now,” Journal of the American Medical Association 260, no. 19 (1988): 2891–2893. 9. John. F. Fulton, Physiology of the Ner­vous System (New York: Oxford University Press, 1949), viii.

268

Notes to Pages 42–47

10. Thomas Stoltz Harvey, “A Developmental Analy­sis of the Rolling Be­hav­ior of Infants” (diss., Yale University, 1941). 11. Cécile Vogt, “Allgemeinere Ergebnisse unserer Hirnforschung,” Journal für Psychologie und Neurologie, no. 25 (1919): 279–462; Karl Zilles and Katrin Amunts, “Centenary of Brodmann’s Map—­Conception and Fate,” Nature Reviews Neuroscience 11, no. 2 (2010): 139–145; Constantino Sotelo, “Viewing the Brain through the Master Hand of Ramón y Cajal,” Nature Reviews Neuroscience 4, no. 1 (2003): 71–77. 12. Vernon B. Mountcastle, “Brain Science at the ­Century’s Ebb,” Daedalus 127, no. 2 (1998): 1–36. 13. Gordon M. Shepherd, Foundations of the Neuron Doctrine (Oxford: Oxford University Press, 1991), 117–126. 14. Alastair Compston, “Dorsal Column: From the Archives,” Brain 138 (2015): 232–236. 15. John F. Fulton, Selected Readings in the History of Physiology (Springfield, IL: Charles C. Thomas, 1930), 209–213. 16. Alan L. Hodgkin and Andrew F. Huxley, “Action Potentials Recorded from Inside a Nerve Fibre,” Nature 144, no. 3651 (1939): 710–711. 17. Mountcastle, “Brain Science at the ­Century’s Ebb,” 282–283. 18. Fin­ger, Minds ­behind the Brain, 275. 19. Stephen W. Kuffler and John G. Nicholls, From Neuron to Brain (Sunderland, MA: Sinauer, 1977), 145–176. 20. Donald O. Hebb, Organ­ization of Be­hav­ior: A Neuropsychological Theory (New York: John Wiley & Sons, 1957), 62. 21. Eric R. Kandel, In Search of Memory: The Emergence of a New Science of Mind (New York: W. W. Norton, 2006), 187–197. 22. Howard M. Spiro and Priscilla ­Waters Norton, “Dean Milton C. Winternitz at Yale,” Perspectives in Biology and Medicine 46, no. 3 (2003): 403–412. 23. Robert D. Terry, “Harry M. Zimmerman,” Surgical Neurology 21, no. 5 (1984): 425–426. 24. Warren S. McCulloch, Embodiments of Mind (Cambridge, MA: MIT Press, 1970). 25. Vernon B. Mountcastle, “The Columnar Organ­ization of the Neocortex,” Brain: A Journal of Neurology 120, no. 4 (1997): 701–722. 26. David H. Hubel, “Evolution of Ideas on the Primary Visual Cortex, 1955–1978: A Biased Historical Account,” Nature 299, no. 5883 (1982): 515–524.



Notes to Pages 47–53

269

27. Thomas S. Harvey, interview by Frederick E. Lepore, June 4, 2000, Titusville, NJ. 28. Wilder Penfield and H. Jasper, Epilepsy and the Functional Anatomy of the ­Human Brain (Boston: ­Little, Brown, 1954). 29. Wilder Penfield and T. Rasmussen, The Ce­re­bral Cortex of Man (New York: McMillan, 1955), 44, 57. 30. Eric  R. Kandel, James  H. Schwartz, and Thomas M Jessell, Princi­ples of Neural Science, 4th  ed. (New York: McGraw-­Hill, 2000), 349–380. 31. William Richard Gowers, A Manual of Diseases of the Ner­vous System (Philadelphia: Blakiston, 1888), 711. 32. Macdonald Critchley, The Parietal Lobes (London: Edward Arnold, 1953), 406–421. 33. M.-­Marsel Mesulam, Princi­ples of Behavioral and Cognitive Neurology (Oxford: Oxford University Press, 2000), 174–255. 34. John F. Fulton, Functional Localization in the Frontal Lobes and Cerebellum: . . . ​Being the William Withering Memorial Lectures Delivered at the Birmingham Medical School, 1948 (Oxford: Clarendon, 1949), 62–66. 35. John F. Fulton, Frontal Lobotomy and Affective Be­hav­ior, a Neurophysiological Analy­sis (New York: W. W. Norton, 1951), 90–95. 36. Fulton, Functional Localization in the Frontal Lobes and Cerebellum. 37. Michael R. Trimble, “Psychopathology of Frontal Lobe Syndromes,” Seminars in Neurology 10, no. 3 (1990): 287–294. 38. Critchley, Parietal Lobes, 407. 39. Carolyn Abraham, Possessing Genius: The Bizarre Odyssey of Einstein’s Brain (New York: St. Martin’s Press, 2001), 71. 40. Jochen Richter, “Pantheon of Brains: The Moscow Brain Research Institute 1925–1936,” Journal of the History of the Neurosciences 16, no. 1–2 (2007): 138–149. 41. Robert J. White, “Lenin’s Brain,” Journal of Neurosurgery 110, no. 6 (2009): 1327–1328. 42. Wilder Penfield, No Man Alone: A Neurosurgeon’s Life (Boston: L ­ ittle, Brown, 1977), 172–174. 43. Macdonald Critchley, “Neurology’s Debt to FJ Gall (1758–1828),” British Medical Journal 2, no. 5465 (1965): 775–781. 44. Brian Burrell, Postcards from the Brain Museum: The Improbable Search for Meaning in the ­Matter of Famous Minds (New York: Broadway, 2004), 71.

270

Notes to Pages 53–58

45. Ibid., 305. 46. Ibid., 88. 47. R. Wagner, Über den Hirnbau der Mikrocephalen mit vergleichender Rucksicht auf den Bau des Gehirns der nomalen Menschen und der Quadrumanen. Vorstudien zu einer wissenschaftlichen Moorphologie und Physiologie des menschlichen Gehirns als Seelenorgan (Göttingen, Germany: Verlag der Dietrichschen Buchhandlung, 1862). 48. “Variation Newly Identifies the Brains of CF Gauss and CH Fuchs in a Collection at the University of Göttingen,” Brain: A Journal of Neurology 137, no. 4 (2014): e269–­e269. 49. Ibid. 50. Karl Pearson, “The Brain of Laplace,” Nature 119 (1927): 560. 51. Edward Anthony Spitzka, “The Study of the Brains of Six Eminent Scientists and Scholars Belonging to the American Anthropometric Society, Together with a Description of the Skull of Professor E.D. Cope,” Transactions of the American Philosophical Society 21, no. 4 (1907): 175–308. 52. Ibid. 53. Michael S. Gazzaniga, Tales from Both Sides of the Brain: A Life in Neuroscience (New York: Ecco, 2015), 42. 54. Michael S. Gazzaniga, “Forty-­Five Years of Split-­Brain Research and Still ­Going Strong,” Nature Reviews Neuroscience 6, no.  8 (2005): 653–659. 55. Gazzaniga, Tales from Both Sides, 113. 56. Weiwei Men et al., “The Corpus Callosum of Albert Einstein’s Brain: Another Clue to His High Intelligence?,” Brain: A Journal of Neurology 137, no. 4 (2014): e268–­e268.

4   the lost de c ­ a des (1 9 5 5 – 1 9 85 ), t h e c i d e r b ox, and the mic ro s cope Epigraph: Nicholas Wade, “The Editorial Notebook: Einstein’s Papers, and Brain; The Physicist’s Legacy Remains Veiled to Millions,” New York Times, July 27, 1987. 1. Carolyn Abraham, Possessing Genius: The Bizarre Odyssey of Einstein’s Brain (New York: St. Martin’s Press, 2001), 113. 2. Ibid., 87–91. 3. Thomas S. Harvey, interview by Frederick E. Lepore, June 4, 2000, Titusville, NJ.



Notes to Pages 59–65

271

4. Tom Avril, “Albert Einstein’s Gray M ­ atter Finds a Home in Philadelphia,” Philadelphia Inquirer, November 18, 2011. 5. Christof Koch, Biophysics of Computation (New York: Oxford University Press, 2004), 87. 6. Abraham, Possessing Genius, 115. 7. Ibid., 108. 8. Albert Einstein, Investigations on the Theory of the Brownian Movement (New York: Dover, 1956). 9. Abraham, Possessing Genius, 124. 10. National Museum of Health and Medicine, Otis Historical Archives 00008: Medical Licensing 9, Silver Spring, MD. 11. Abraham, Possessing Genius, 250. 12. Nicholas Wade, “Brain That Rocked Physics Rests in Cider Box,” Science 201, no. 4357 (1978): 696. 13. Nicholas Wade, “Brain of Einstein Continues Peregrinations,” Science 213, no. 4507 (1981): 521. 14. Ibid. 15. Relics: Einstein’s Brain, Dir. Kevin Hull. Perf. William S Burroughs and Kenji Sugimoto. BBC Films, 1994. 16. Marian C. Diamond, “Why Einsten’s Brain?,” lecture at Doe Library, School of Education at Johns Hopkins University—­Gradu­ate Education Programs, School of Education, Johns Hopkins University, January 8, 1999. 17. Ibid. 18. Marian C. Diamond et al., “On the Brain of a Scientist: Albert Einstein,” Experimental Neurology 88, no. 1 (1985): 198–204. 19. Ibid. 20. Abraham, Possessing Genius, 178. 21. Walter Reich, “Scientists Probe Brain Cells for Keys to Genius,” Chicago Tribune, September 1, 1985, 15, 17. 22. Robert Terry, “Response to a Brief History of Einstein’s Brain,” Einstein Quarterly Journal of Biology and Medicine 19 (2002): 79. 23. Diamond, “Why Einsten’s Brain?” 24. Terence Hines, “Further on Einstein’s Brain,” Experimental Neurology 150, no. 2 (1998): 343–344. 25. Terence Hines, “Neuromythology of Einstein’s Brain,” Brain and Cognition 88 (2014): 21–25. 26. Ibid. 27. Diamond, “Why Einsten’s Brain?”

272

Notes to Pages 66–72

28. Sandra F. Witelson, Debra L. Kigar, and Thomas Harvey, “The Exceptional Brain of Albert Einstein,” Lancet 353, no. 9170 (1999): 2149–2153. 29. Britt Anderson, personal communication to author, 2015. 30. Abraham, Possessing Genius, 253–254. 31. Britt Anderson and Thomas Harvey, “Alterations in Cortical Thickness and Neuronal Density in the Frontal Cortex of Albert Einstein,” Neuroscience Letters 210, no. 3 (1996): 161–164. 32. Hines, “Neuromythology of Einstein’s Brain,” 21–25. 33. Britt Anderson, “G Explained,” Medical Hypotheses 45, no. 6 (1995): 602–604. 34. Britt Anderson, personal communication to author, 2015. 35. Sandra F. Witelson, Ilya I. Glezer, and Debra L. Kigar, “­Women Have Greater Density of Neurons in Posterior Temporal Cortex,” Journal of Neuroscience 15, no. 5 (1995): 3418–3428. 36. Thomas Harvey and Sandra Witelson, personal communication, October 26, 1995. 37. Eri Schubert, personal communication to author, December  1, 2017. 38. Abraham, Possessing Genius, 301–302. 39. Witelson, Kigar, and Harvey, “The Exceptional Brain of Albert Einstein.” 40. Debra L. Kigar et al., “Estimates of Cell Number in Temporal Neocortex in the Brain of Albert Einstein,” Society for Neuroscience Abstracts 23 (1997): 213. 41. Ibid. 42. Ibid. 43. Thomas Harvey and Sandra Witelson, personal communication, October 26, 1995. 44. Abraham, Possessing Genius, 316. 45. James W. Papez, “A Proposed Mechanism of Emotion,” Archives of Neurology and Psychiatry 38, no. 4 (1937): 725–743. 46. Dahlia Zaidel, “Neuron Soma Size in the Left and Right Hippocampus of a Genius,” 2001, http://­cogprints​.­org​/­1927​/­. 47. Dahlia Zaidel, personal communication to author, October 8, 2015. 48. Jorge A. Colombo et al., “Ce­re­bral Cortex Astroglia and the Brain of a Genius: A Propos of A. Einstein’s,” Brain Research Reviews 52, no. 2 (2006): 257–263. 49. Ibid. 50. Ibid.



Notes to Pages 72–79

273

51. Nancy Ann Oberheim, Steven A. Goldman, and Maiken Nedergaard, “Heterogeneity of Astrocytic Form and Function,” Methods in Molecular Biology 814 (2012): 23–45. 52. Helmut Kettenmann and Alexei Verkhratsky, “Neuroglia: The 150 Years ­After,” Trends in Neurosciences 31, no. 12 (2008): 653–659. 53. Diamond, “Why Einsten’s Brain?” 54. Eric R. Kandel, James H. Schwartz, and Thomas M. Jessell, Princi­ ples of Neural Science, 4th ed. (New York: McGraw-­Hill, 2000), 20. 55. Diamond, “Why Einsten’s Brain?” 56. Suzana Herculano-­Houzel, “The Glia/Neuron Ratio: How It Varies Uniformly across Brain Structures and Species and What That Means for Brain Physiology and Evolution,” Glia 62, no. 9 (2014): 1377–1391. 57. Ibid. 58. Kettenmann and Verkhratsky, “Neuroglia: The 150 Years ­After.” 59. Oberheim, Goldman, and Nedergaard, “Heterogeneity of Astrocytic Form.” 60. Kettenmann and Verkhratsky, “Neuroglia: The 150 Years ­After.” 61. Patricia S. Churchland, Christof Koch, and Terrence J. Sejnowski, “What Is Computational Neuroscience?,” in Computational Neuroscience, ed. Eric L. Schwartz (Cambridge, MA: MIT Press, 1990), 46–55. 62. Oberheim, Goldman, and Nedergaard, “Heterogeneity of Astrocytic Form.” 63. Abraham, Possessing Genius, 301–302.

5   the exc e ption a l b ra in (s ) of a lb ert e i n st e i n Epigraphs: B. Hoffmann and H. Dukas, Albert Einstein, Creator and Rebel (New York: New American Library, 1972), 139. Christof Koch and Gilles Laurent, “Complexity and the Ner­vous System,” Science 284, no. 5411 (1999): 96–98. 1. Rebecca Blumenstein, “It’s Partly in Your Head,” Wall Street Journal, April 11, 2011. 2. Elizabeth Ghaffari, ­Women Leaders at Work: Untold Tales of ­Women Achieving Their Ambitions (New York: Apress, 2011), 143–160. 3. Carolyn Abraham, Possessing Genius: The Bizarre Odyssey of Einstein’s Brain (New York: St. Martin’s Press, 2001), 307. 4. Sandra F. Witelson, Debra L. Kigar, and Thomas Harvey, “The Exceptional Brain of Albert Einstein,” Lancet 353, no. 9170 (1999): 2149–2153. 5. D. Falk, “Hominin Paleoneurology: Where Are We Now?,” Pro­gress in Brain Research 195 (2012): 255–272.

274

Notes to Pages 79–86

6. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 7. Ibid. 8. Ibid. 9. Steven Pinker, “His Brain Mea­sured Up,” Op-­Ed, New York Times, June 24, 1999. 10. Michael D. Lemonick, “Was Einstein’s Brain Built for Brilliance?,” Time, June 28, 1999. 11. Albert M. Galaburda, “Albert Einstein’s Brain,” Lancet 354, no. 9192 (1999): 1821–1823. 12. Ibid. 13. Dean Falk, Frederick E. Lepore, and Adrianne Noe, “The Ce­re­bral Cortex of Albert Einstein: A Description and Preliminary Analy­sis of Unpublished Photo­graphs,” Brain: A Journal of Neurology 136, no. 4 (2013): 1304–1327. 14. Lawrence K. Altman, “Key to Intellect May Lie in Folds of Einstein’s Brain . . . ​So, Is This Why Einstein Was so Brilliant?,” New York Times, June 18, 1999. 15. MacDonald Critchley, The Parietal Lobes (London: Edward Arnold, 1953), 55. 16. Ibid., v. 17. Frederick E. Lepore, “Dissecting Genius—­Einstein’s Brain and the Search for the Neural Basis of Intellect,” Cerebrum 3, no. 1 (2001), http://­ www​.­dana​.­org​/­Cerebrum​/­Default​.­aspx​?­id​=­39337Q. 18. Ibid. 19. Oliver Sacks, The Man Who Mistook His Wife for a Hat and Other Clinical Tales (New York: Summit Books, 1985), 73–75. 20. Critchley, Parietal Lobes, 407. 21. M.-­Marsel Mesulam, Princi­ples of Behavioral and Cognitive Neurology (Oxford: Oxford University Press, 2000), 174–255. 22. Stanislas Dehaene, Reading in the Brain: The Science and Evolution of a ­Human Invention (New York: Viking, 2009), 317–324. 23. Pinker, “His Brain Mea­sured Up.” 24. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 25. Dehaene, Reading in the Brain. 26. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 27. Ibid. 28. Dean Falk, e-­mail message to author, 2007.



Notes to Pages 87–93

275

29. Dean Falk, The Fossil Chronicles: How Two Controversial Discoveries Changed Our View of ­Human Evolution (Berkeley: University of California Press, 2011), 23–28. 30. Dean Falk, “New Information about Albert Einstein’s Brain,” Frontiers in Evolutionary Neuroscience 1 (2009): 1–6. 31. Falk, Fossil Chronicles, 76–187. 32. Ewen Callaway, “Tales of the Hobbit,” Nature 514 (2014): 422–426. 33. Hope Jahren, Lab Girl (New York: Knopf, 2016), 116. 34. Elliot Krauss, e-­mail message to Dean Falk, 2008. 35. Falk, e-­mail message to author, 2008. 36. Ibid. 37. Falk, “New Information.” 38. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 39. Falk, “New Information.” 40. Alf Brodal, Neurological Anatomy in Relation to Clinical Medicine (New York: Oxford University Press, 1981), 188. 41. Falk, “New Information.” 42. Ibid. 43. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 44. T. A. Yousry et al., “Localization of the Motor Hand Area to a Knob on the Precentral Gyrus. A New Landmark,” Brain: A Journal of Neurology 120, no. 1 (1997): 141–157. 45. Marc Bangert and Gottfried Schlaug, “Specialization of the Specialized in Features of External H ­ uman Brain Morphology,” Eu­ro­pean Journal of Neuroscience 24, no. 6 (2006): 1832–1834. 46. Falk, Lepore, and Noe, “Ce­re­bral Cortex of Albert Einstein.” 47. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 48. Falk, “New Information.” 49. Alastair Compston, e-­mail message to Dean Falk, September 17, 2012. 50. Cornelius J. Connolly, External Morphology of the Primate Brain (Springfield, IL: Charles C. Thomas, 1950); Michio Ono, Stefan Kubik, and Chad D. Abernathey, Atlas of the Ce­re­bral Sulci (Stuttgart, Germany: Thieme Verlag, 1990). 51. Dean Falk, e-­mail message to Adrianne Noe, April 10, 2012. 52. Ibid.

276

Notes to Pages 93–99

53. James D. Watson and Francis H. C. Crick, “Molecular Structure of Nucleic Acids,” Nature 171, no. 4356 (1953): 737–738. 54. Galaburda, “Albert Einstein’s Brain.” 55. Dean Falk, e-­mail message to author and Adrianne Noe, May 22, 2012. 56. Stanley Fin­ger, Minds ­behind the Brain: A History of the Pioneers and Their Discoveries (New York: Oxford University Press, 2000), 91–92. 57. Alastair Compston, “Editorial,” Brain: A Journal of Neurology 131, no. 7 (2008): 1675–1676, doi: 10.1093/brain/awn057. 58. Norman Geschwind, “Disconnexion Syndromes in Animals and Man,” Brain: A Journal of Neurology 88, no. 3 (1965): 237–294, 585–644. 59. Adrianne Noe, e-­mail message to author and Dean Falk, September 16, 2011. 60. “How Smart Can We Get?,” Nova, Public Broadcasting Ser­vice, October 24, 2012, http://­www​.­pbs​.­org​/­wgbh​/­nova​/­body​/­how​-­smart​-­can​-­we​ -­get​.­html. 61. Falk, Lepore, and Noe, “Ce­re­bral Cortex of Albert Einstein.” 62. “National Medical Museum Celebrates 150th  Anniversary with ­Grand Opening Cele­bration, New Exhibits in New Mary­land Home,” http://­w ww​.­m edicalmuseum​ .­m il​ /­i ndex​ .­c fm​ ?­p ​= ­m edia​ .­n ews​ .­a rticle​ .­celebrating​_­150th​_­anniversary. 63. Abraham, Possessing Genius, 123–124. 64. Falk, Lepore, and Noe, “Ce­re­bral Cortex of Albert Einstein.” 65. Tom Avril, “Albert Einstein’s Gray ­Matter Finds a Home in Philadelphia,” Philadelphia Inquirer, November 18, 2011. 66. “Einstein Brain Atlas,” https://­itunes​.­apple​.­com​/­us​/­app​/­einstein​ -­brain​-­atlas​/­id555722456​?­mt​=8­ . 67. National Museum of Health and Medicine, “Never Before Seen Photos and ‘Maps’ of Albert Einstein’s Brain Go on Display at Medical Museum in Mary­land,” March 20, 2013, http://­www​.­medicalmuseum​.­mil​ /­index​.­cfm​?­p​=­media​.­news​.­article​.­never​_­before​_­seen​_­photos​_­of​_­albert​ _­einsteins​_­brain. 68. Joanne Bell and Dean Falk, e-­mail correspondence, July 25, 2012. 69. Ibid. 70. Compston, “Editorial,” 987–989. 71. Dean Falk, e-­mail message to author, June 18, 2014. 72. Gary Stix, “Einstein’s Brain: New Insights into the Roots of Genius,” Scientific American, November 16, 2012, https://­blogs​.­scientificamerican​ .­com​/­talking​-­back​/­einsteins​-­brain​-­more​-­special​-­than​-­we​-­ever​-­knew​/­.



Notes to Pages 99–108

277

73. Falk, Lepore, and Noe, “Ce­re­bral Cortex of Albert Einstein​.­” 74. Stephen W. Hawking, A Brief History of Time: From the Big Bang to Black Holes (London: Bantam Press, 1990), vi–viii. 75. Falk, Lepore, and Noe, “Ce­re­bral Cortex of Albert Einstein.” 76. Ibid., 1307. 77. John Farquhar Fulton, Physiology of the Ner­vous System, 3rd ed. (New York: Oxford University Press, 1951), 447. 78. Ibid. 79. Falk, “New Information.” 80. Falk, Lepore, and Noe, “Ce­re­bral Cortex of Albert Einstein.” 81. Ibid., 1306. 82. Bangert and Schlaug, “Specialization of the Specialized.” 83. Wilder Penfield and Theodore Rasmussen, The Ce­re­bral Cortex of Man: A Clinical Study of Localization of Function (New York: MacMillan, 1955), 57. 84. Ibid. 85. Antonio R. Damasio, “Aphasia,” New ­England Journal of Medicine 326 (1992): 531–539; Richard L. Strub and F. William Black, The ­Mental Status Examination in Neurology, 2nd ed. (Philadelphia: F. A. Davis, 1985), 58. 86. Walter Isaac­son, Einstein: His Life and Universe (New York: Simon & Schuster 2007), 8. 87. Critchley, Parietal Lobes, 10. 88. Gerhardt von Bonin, The Evolution of the ­Human Brain (Chicago: University of Chicago Press, 1963), 60. 89. David J. Chal­mers, “The Puzzle of Conscious Experience,” Scientific American 273, no. 6 (1995): 80–87. 90. Maurice Victor and Allan H. Ropper, Adams and Victors’ Princi­ples of Neurology, 7th ed. (New York: McGraw-­Hill, 2001), 482–487. 91. Critchley, Parietal Lobes, 356–377. 92. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 93. Ibid. 94. Connolly, External Morphology of the Primate Brain. 95. Ono, Kubik, and Abernathey, Atlas of the Ce­re­bral Sulci. 96. Ibid., 1. 97. Connolly, External Morphology of the Primate Brain, 180. 98. Alastair Compston, e-­mail message to Dean Falk, July 2012. 99. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.”

278

Notes to Pages 108–114

100. David C. Van Essen, “A Tension-­Based Theory of Morphogenesis and Compact Wiring in the Central Ner­vous System,” Nature 385, no. 6614 (1997): 313–318. 101. Roger Penrose, The Emperor’s New Mind: Concerning Computers, Minds, and the Laws of Physics (New York: Penguin, 1991), 447. 102. Christof Koch, The Quest for Consciousness: A Neurobiological Approach (Englewood, CO: Roberts & Co., 2004), 7–8. 103. Weiwei Men et al., “The Corpus Callosum of Albert Einstein’s Brain: Another Clue to His Intelligence?,” Brain: A Journal of Neurology, September 21, 2013, doi:10:1093/brain/awt252. 104. “Michael S. Gazzaniga” in Larry R. Squire, ed., The History of Neuroscience in Autobiography, vol. 7 (New York: Oxford University Press, 2011), 98–139. 105. Michael S. Gazzaniga, Joseph E. Bogen, and Roger W. Sperry, “Some Functional Effects of Sectioning the Ce­re­bral Commissures in Man,” Proceedings of the National Acad­emy of Sciences 48, no.  10 (1962): 1765–1769. 106. “Michael S. Gazzaniga.” 107. Ibid. 108. Michael S. Gazzaniga, “Ce­re­bral Specialization and Interhemispheric Communication: Does the Corpus Callosum Enable the H ­ uman Condition?,” Brain: A Journal of Neurology 123, no. 7 (2000): 1293–1326. 109. Weiwei Men, “Research of Ce­re­bral Morphology between Chinese and Caucasian and Construction of Large Sample Chinese Brain Templates” (PhD diss., East China Normal University, 2013). 110. Alastair Compston, e-­mail message to Weiwei Men, July  29, 2013. 111. Weiwei Men, e-­mail message to author, March 21, 2016. 112. Witelson, Kigar, and Harvey, “Exceptional Brain of Albert Einstein.” 113. Sandra F. Witelson, “Hand and Sex Differences in the Isthmus and Genu of the ­Human Corpus Callosum: A Postmortem Morphological Study,” Brain: A Journal of Neurology 112, no. 3 (1989): 799–835; Sandra F. Witelson, “The Brain Connection: The Corpus Callosum Is Larger in Left-­ Handers,” Science 229, no. 4714 (1985): 665–668. 114. Edward Anthony Spitzka, “A Study of the Brains of Six Eminent Scientists and Scholars Belonging to the American Anthropometric Society, Together with a Description of the Skull of Professor ED Cope,” Transactions of the American Philosophical Society (1907): 175–308.



Notes to Pages 117–122

279

6   how doe s a g en i us t h i n k? Epigraphs: Brian Greene, “Why He ­Matters,” Scientific American 313, no. 3 (2015): 34–37. Paul Arthur Schilpp, ed., Albert Einstein, Philosopher-­Scientist (New York: MJF Books, 1970), 1–95. 1. Christof Koch and Gilles Laurent, “Complexity and the Ner­vous System,” Science 284, no. 5411 (1999): 96–98. 2. Ronald Clark, Einstein: The Life and Times (New York: Avon, 2007), 1–864 3. Banesh Hoffmann and Helen Dukas, Albert Einstein, Creator and Rebel: (New York: New American Library, 1972), 1–272. 4. Walter Isaac­son, Einstein: His Life and Universe (New York: Simon & Schuster, 2007), 1–675. 5. Ibid., 8–31. 6. Schilpp, Albert Einstein, Philosopher-­Scientist. 7. Isaac­son, Einstein: His Life and Universe, 543. 8. Schilpp, Albert Einstein, Philosopher-­Scientist. 9. Bertrand Russell, The Autobiography of Bertrand Russell: 1872–1914 (Boston: ­Little, Brown, 1967), 37–38. 10. Schilpp, Albert Einstein, Philosopher-­Scientist. 11. Ibid. 12. Albert Einstein, “Physics and Real­ity,” Journal of the Franklin Institute 221, no. 3 (1936): 349–382. 13. Schilpp, Albert Einstein, Philosopher-­Scientist. 14. Isaac­son, Einstein: His Life and Universe, 79–84. 15. Albert Einstein and Leopold Infeld, The Evolution of Physics: The Growth of Ideas from Early Concepts to Relativity and Quanta (New York: Simon & Schuster, 1954), 310–313. 16. Steven Strogatz, “Einstein’s First Proof,” New Yorker, November 19, 2015, https://­www​.­newyorker​.­com​/­tech​/­elements​/­einsteins​-­first​-­proof​ -­pythagorean​-­theorem. 17. Schilpp, Albert Einstein, Philosopher-­Scientist. 18. Isaac­son, Einstein: His Life and Universe, 8–31. 19. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 94–95. 20. Dean Falk, Frederick E. Lepore, and Adrianne Noe, “The Ce­re­bral Cortex of Albert Einstein: A Description and Preliminary Analy­sis of Unpublished Photo­graphs,” Brain: A Journal of Neurology 136, no. 4 (2012): 1304–1327.

280

Notes to Pages 122–131

21. Isaac­son, Einstein: His Life and Universe, 8–31. 22. Brian Foster, “Einstein and His Love of M ­ usic,” Physics World 18, no. 1 (2005): 34. 23. Isaac­son, Einstein: His Life and Universe, 8–31. 24. Ibid., 32–49. 25. Ibid. 26. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 37–42. 27. Ibid., 55–59. 28. Isaac­son, Einstein: His Life and Universe, 90–106. 29. Ed Regis, Who Got Einstein’s Office?: Eccentricity and Genius at the Institute for Advanced Study (Amsterdam: Addison-­Wesley, 1987), 112–114. 30. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 103–133. 31. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 37–42. 32. Plato, translator Benjamin Jowett, The Dialogues of Plato (New York: Random House, 1937), 349–380. 33. Ibid. 34. Martin Cohen, Wittgenstein’s Beetle and Other Classic Thought Experiments (Oxford:Blackwell, 2005), viii–­ix. 35. Philip Ball, “Tall Tales,” News@nature (2005). http://­www​.­nature​ .­com​/­news​/­2005​/­050613​/­full​/­new050613​-­10​.­html. 36. Cohen, Wittgenstein’s Beetle, 1–14. 37. Plato, Dialogues of Plato. 38. Thomas  S. Kuhn, The Structure of Scientific Revolutions (Chicago: University of Chicago Press, 1963), 10–22. 39. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 103–133. 40. “Lights All Askew in the Heavens,” New York Times, November 10, 1919. 41. James Robert Brown, “Peeking into Plato’s Heaven,” Philosophy of Science 71, no. 5 (2004): 1126–1138. 42. Brian Greene, The Elegant Universe: Superstrings, Hidden Dimensions, and the Quest for the Ultimate Theory (New York: Vintage Books 2000), 135–165. 43. Ibid. 44. Jules Violle, Lehrbuch der Physik (Berlin: Springer, 1892). 45. Isaac­son, Einstein: His Life and Universe, 8–31. 46. Ibid. 47. James Robert Brown, Laboratory of the Mind: Thought Experiments in the Natu­ral Sciences, Philosophical Issues in Science Series (London: Routledge, 1993), 1–32. 48. Ibid.



Notes to Pages 131–136

281

49. William A. Rushton, Visual Pigments in Man (Springfield: Charles C. Thomas, 1962), 1–7. 50. Brown, Laboratory of the Mind. 51. Malcolm Gladwell, Outliers: The Story of Success (New York: L ­ ittle, Brown and Com­pany, 2008), 35–68. 52. Albert Einstein, “Zur Elektrodynamik bewegter Körper,” Annalen der Physik 17, no. 10 (1905): 891–921. 53. Gladwell, Outliers. 54. Brian Greene, The Fabric of the Cosmos: Space, Time, and the Texture of Real­ity (New York: Vintage, 2005), 39–76. 55. Albert Einstein, Relativity: The Special and General Theory (New York: Henry Holt, 1921), 25–33. 56. Peter Galison, Einstein’s Clocks, Poincaré’s Maps: Empires of Time (New York: W. W. Norton, 2003), 221–293. 57. Einstein, Relativity: The Special and General Theory. 58. Ibid. 59. Isaac­son, Einstein: His Life and Universe, 313–314. 60. Albert Einstein, Boris Podolsky, and Nathan Rosen, “Can Quantum-­ Mechanical Description of Physical Real­ity Be Considered Complete?,” Physical Review 47, no. 10 (1935): 777–780. 61. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 60–82. 62. Schilpp, Albert Einstein, Philosopher-­Scientist. 63. Sigmund Freud et al., “The Unconscious,” in Sigmund Freud, Collected Papers: Volumes I–­V, vol. 4 (London: Hogarth, 1953), 98–136. 64. Isaac­son, Einstein: His Life and Universe, 357–383. 65. Thomas Levenson, Einstein in Berlin (New York: Bantam, 2003), 306–325. 66. William J. Cromie, “­Human Biological Clock Set Back an Hour,” Harvard Gazette (Cambridge, MA), July 15, 1999, https://­news​.­harvard​.­edu​ /­gazette​/­story​/­1999​/­07​/­human​-­biological​-­clock​-­set​-­back​-­an​-­hour​/.­ 67. Greene, Fabric of the Cosmos. 68. “Albert Einstein,” in Biographical Memoirs, vol. 51 (Washington, DC: National Academy of Sciences, 1980), https://­www​.­nap​.­edu​/­read​/­574​ /­chapter​/­7. 69. Jeremy Bern­stein, “Einstein: An Exchange,” New York Review of Books, August 17, 2007. 70. Schilpp, Albert Einstein, Philosopher-­Scientist, 199–242. 71. Michael S. Gazzaniga, “Ce­re­bral Specialization and Interhemispheric Communication: Does the Corpus Callosum Enable the ­Human Condition?,” Brain: A Journal of Neurology 123, no. 7 (2000): 1293–1326.

282

Notes to Pages 136–145

72. Francis Crick and Christof Koch, “Are We Aware of Neural Activity in Primary Visual Cortex?,” Nature 375, no. 6527 (1995): 121–123. 73. Henry More, A Platonick Song of the Soul (Lewisburg, PA: Bucknell University Press, 1998). 74. Thomas Carlyle, French Revolution (New York: A. L. Burt, 1925), 5. 75. Schilpp, Albert Einstein, Philosopher-­Scientist, 1–95. 76. Greene, Fabric of the Cosmos. 77. Schilpp, Albert Einstein, Philosopher-­Scientist, 1–95. 78. Einstein, “Physics and Real­ity.” 79. René Dubos and J. Louis Pasteur, ­Free Lance of Science (Boston: ­Little, Brown and Com­pany, 1950), 19. 80. Walter Isaac­son, “The Light-­Beam Rider,” New York Times, October 30, 2015. 81. “Einstein Expounds His Theory,” New York Times, December 2, 1919. 82. Isaac­son, Einstein: His Life and Universe, 145. 83. “Einstein Expounds His Theory.” 84. Albert Einstein, “How I Created the Theory of Relativity,” trans. Y. A. Ono, Physics ­Today 35, no. 8 (1982): 45–47. 85. Abraham Pais,“Subtle Is the Lord . . .”: The Science and the Life of Albert Einstein (Oxford: Clarendon, 1982), 177–183. 86. Greene, Elegant Universe, 53–84. 87. Albert Einstein, Relativity: The Special and General Theory, 78–83. 88. Ibid. 89. Peter Galison, Einstein’s Clocks, Poincaré’s Maps, 347. 90. Greene, Fabric of the Cosmos. 91. H. Gutfreund and Jürgen Renn, The Road to Relativity: The History and Meaning of Einstein’s “The Foundation of General Relativity” Featuring the Original Manuscript of Einstein’s Masterpiece (Prince­ton, NJ: Prince­ton University Press, 2015), 37–139. 92. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 103–133. 93. Gutfreund and Renn, The Road to Relativity. 94. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 103–133. 95. Gutfreund and Renn, The Road to Relativity. 96. Isaac­son, Einstein: His Life and Universe, 189–224. 97. William Shakespeare, The Merchant of Venice (Baltimore: Penguin, 1964). 79. 98. Stanislas Dehaene, The Number Sense: How the Mind Creates Mathe­ matics (New York: Oxford University Press, 1997), 207–230. 99. Falk, Lepore, and Noe, “The Ce­re­bral Cortex of Albert Einstein.”



Notes to Pages 146–153

283

100. Einstein and Infeld, The Evolutuion of Physics, 220–235. 101. Einstein, Relativity: The Special and General Theory, 78–83. 102. Robert W. Baloh and Vincente Honrubia, Clinical Neurophysiology of the Vestibular System (Philadelphia: F. A. Davis, 1990), 3–19. 103. Einstein, “How I Created the Theory of Relativity.” 104. Thomas Brandt, “Man in Motion: Historical and Clinical Aspects of Vestibular Function: A Review,” Brain: A Journal of Neurology 114, no. 5 (1991): 2159–2174. 105. Baloh and Honrubia, Clinical Neurophysiology of the Vestibular System, 44–87. 106. R. Barany, “Some New Methods for Functional Testing of the Vestibular Apparatus and the Cerebellum: Nobel Lecture September 11, 1916,” in Nobel Lectures: Physiology or Medicine 1901–1921 (Amsterdam: Elsevier, 1967), 500–511. 107. Isaac­son, Einstein: His Life and Universe, 189–224. 108. “Albert Einstein,” in Biographical Memoirs. 109. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 103–133. 110. Greene, “Why He ­Matters.” 111. “Albert Einstein,” in Biographical Memoirs. 112. Nicola Twilley, “Gravitational Waves Exist: Inside the Story of How Scientists Finally Found Them,” The New Yorker, February 11, 2016. 113. Albert Einstein, “Ist die Trägheit eines Körpers von seinem Energieinhalt abhängig?,” Annalen der Physik 323, no. 18 (1905): 639–641. 114. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 60–82. 115. Lincoln Barnett, The Universe and Dr. Einstein (New York: William Sloane, 1948), 55–60. 116. Albert Einstein, “E = MC2: The Most Urgent Prob­lem of Our Time,” Science Illustrated, April 1946: 16–17. 117. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 60–82. 118. Einstein, “E = MC 2.” 119. Albert Einstein, “Über einen die Erzeugung und Verwandlung des Lichtes betreffenden heuristischen Gesichtspunkt,” Annalen der Physik 17 (1905): 132–148. 120. Manjit Kumar, Quantum: Einstein, Bohr, and the ­Great Debate about the Nature of Real­ity (London: Icon Books, 2014), 281–287. 121. Ibid. 122. Hoffmann and Dukas, Albert Einstein, Creator and Rebel, 60–82. 123. John S. Bell, “On the Einstein Podolsky Rosen Paradox,” Physics 1, no. 3 (1964): 195–200.

284

Notes to Pages 153–159

124. Zeeya Merali. “Toughest Test Yet for Quantum ‘Spookiness,’ ” Nature 15 (2015): 14–15. 125. Albert Einstein, Max Born, and Hedwig Born, The Born-­Einstein Letters: Correspondence between Albert Einstein and Max and Hedwig Born from 1916 to 1955 (New York: Walker, 1971), 90–91. 126. Hoffman and Dukas, Albert Einstein, Creator and Rebel, 193–196. 127. “Einstein Believes in ‘Spinoza’s God,’ ” New York Times, April 25, 1929. 128. Hoffman and Dukas, Albert Einstein, Creator and Rebel, 193–196. 129. Schilpp, Albert Einstein, Philosopher-Scientist, 201–241. 130. John Hersey, Hiroshima (New York: Alfred A. Knopf, 1946), 25. 131. Richard Rhodes, The Making of the Atomic Bomb (New York: Simon & Schuster, 1986), 233–317. 132. Arthur C. Clarke, Profiles of the ­Future: An Inquiry into the Limits of the Pos­si­ble (London: Macmillan, 1973), 36. 133. Rhodes, Making of the Atomic Bomb, 233–317. 134. William Lanouette, Genius in the Shadows: A Biography of Leo Szilard: The Man ­behind the Bomb (New York: Charles Scribner’s Sons, 1992), 194–213. 135. Rhodes, Making of the Atomic Bomb, 357–393. 136. “Science Crossroads” and cover, Time, July 1, 1946. 137. “The War,” Time, August 20, 1945, 8–10. 138. Rhodes, Making of the Atomic Bomb, 617–678. 139. Robert Serber, The Los Alamos Primer: The First Lectures on How to Build an Atomic Bomb (Berkeley: University of California Press, 1992), 5–9. 140. Samuel Glasstone and Philip J. Dolan, Effects of Nuclear Weapons, no. TID-28061 (Washington, DC: Department of Defense, 1977), 12. 141. “Science: Crossroads,” Time, July 1, 1946. 142. Serber, Los Alamos Primer, ix–­xxi. 143. Einstein, Relativity: The Special and General Theory, 115–118 144. Roger Penrose, “Introduction,” in A. Einstein, Relativity (New York: Plume, 2006), ix–­xxvi. 145. D. C. Dennett, Intuition Pumps and Other Tools for Thinking (New York: W. W. Norton, 2012), 1–16. 146. Ibid. 147. T. S. Eliot, The Complete Poems and Plays: 1909–1950 (New York: Harcourt, Brace and World, 1971), 74–85.



Notes to Pages 159–163

285

148. Christof Koch, The Quest for Consciousness: A Neurobiological Approach (Englewood, CO: Roberts, 2004), 343. 149. David Chal­mers, “The Puzzle of Conscious Experience,” Scientific American 273, no. 6 (1995): 80–86. 150. Ludwig Wittgenstein, Philosophical Investigations, trans. G.E M. Anscombe (Oxford: Basil Blackwell, 1953), 2. 151. James Joyce and Hans Walter Gabler, Ulysses (New York: Random House, 1986), 608–644. 152. Daniel Dennett, “A Difference That Makes a Difference,” Edge, November 22, 2017, https://­www​.­edge​.­org​/­print​/­node​/­27405. 153. Jacques Hadamard, The Mathematician’s Mind: The Psy­chol­ogy of Invention in the Mathematical Field (Prince­ton, NJ: Prince­ton University Press, 1996), 142–143. 154. Schilpp, Albert Einstein, Philosopher-­Scientist. 155. Falk, Lepore, and Noe, “The Ce­re­bral Cortex of Albert Einstein.” 156. Randy  L. Buckner, “The Cerebellum and Cognitive Function: 25 Years of Insight from Anatomy and Neuroimaging,” Neuron 80, no. 3 (2013): 807–815. 157. Frederick E. Lepore, “Harvey Cushing, Gordon Holmes, and the Neurological Lessons of World War I,” Archives of Neurology 51, no. 7 (1994): 711–722. 158. Jeremy D. Schmahmann, “An Emerging Concept: The Cerebellar Contribution to Higher Function,” Archives of Neurology 48, no. 11 (1991): 1178–1187. 159. Alf Brodal. Neurological Anatomy in Relationto Clinical Medicine, 3rd ed. (New York: Oxford University Press, 1981), 301–306. 160. Buckner, “The Cerebellum and Cognitive Function.” 161. Hadamard, The Mathematician’s Mind. 162. William James, The Princi­ples of Psy­chol­ogy, vol. 1 (New York: Henry Holt, 1890), 402–458. 163. Christof Koch, Consciousness: Confessions of a Romantic Reductionist (Cambridge, MA: MIT Press, 2012), 41–57. 164. Bernard J. Baars, “Meta­phors of Consciousness and Attention in the Brain,” Trends in Neuroscience 21 (1998): 58–62. 165. Weiwei Men et  al., “The Corpus Callosum of Albert Einstein’s Brain: Another Clue to His High Intelligence?,” Brain: A Journal of Neurology 137, no. 4 (2014): 1–8. 166. Charles Scott Sherrington, Goethe on Nature and on Science (Cambridge, UK: Cambridge University Press, 1949), 16.

286

Notes to Pages 163–171

167. Isaac­son, Einstein: His Life and Universe, 384–391. 168. Schilpp, Albert Einstein, Philosopher-­Scientist, 1–95. 169. Einstein, “Physics and Real­ity.” 170. Isaac­son, Einstein: His Life and Universe, 79–84. 171. Abraham Pais, ‘Subtle is the Lord . . .’:The Science and Life of Albert Einstein (New York: Oxford University Press, 1982), 318–320. 172. Pais, ‘Subtle is the Lord . . . ​,’ 5–25. 173. Pais, ‘Subtle is the Lord . . . ​,’ 454–457. 174. “Genius,” Encyclopaedia Britannica, 11th ed., vol. 11 (New York: The Encyclopedia Britannica Com­pany, 1910), 594–595. 175. Falk, Lepore, and Noe, “The Ce­re­bral Cortex of Albert Einstein.” 176. Isaac­son, Einstein: His Life and Universe, 8–31. 177. Vilayanur S. Ramachandran, The Tell-­Tale Brain: A Neuroscientist’s Quest for What Makes Us H ­ uman (New York: W. W. Norton, 2011), 183–191. 178. Schilpp, Albert Einstein, Philosopher-­Scientist. 179. Einstein and Infeld, The Evolution of Physics, 129–260. 180. Hoffman and Dukas, Albert Einstein, Creator and Rebel, 103–133. 181. Einstein, “Physics and Real­ity.” 182. Albert Einstein, Ideas and Opinions (New York: Crown, 1954), 18–24. 183. Greene, Fabric of the Cosmos, 219–250. 184. Richard P. Feynman, Robert B. Leighton, and Matthew Sands, Lectures on Physics, vol. 2 (Reading, MA: Addison-­Wesley, 1964), 42-1–42-14. 185. Greene, Fabric of the Cosmos, 219–250. 186. Einstein, Ideas and Opinions, 18–24. 187. Einstein, “Physics and Real­ity.” 188. Levenson, Einstein in Berlin, 208–217. 189. Hoffman and Dukas, Albert Einstein, Creator and Rebel, 103–133. 190. Levenson, Einstein in Berlin, 208–217. 191. Gutfreund and Renn, The Road to Relativity. 192. Pais, ‘Subtle is the Lord . . . ​,’ vi. 193. David Wessel, “The ‘Eureka’ Moments Happen L ­ ater,” Wall Street Journal, September 5, 2012. 194. Benjamin Jones, E. J. Reedy, and Bruce A. Weinberg, “Age and Scientific Genius,” in The Wiley Handbook of Genius, ed. D. K. Simonton (New York: John Wiley & Sons, 2014), 422–451. 195. Margaret W. Ferguson, Mary Jo Salter, and Jon Stallworthy, The Norton Anthology of Poetry (New York: W. W. Norton, 2005), 1572–1573. 196. Ian J. Deary, Intelligence (New York: Oxford University Press, 2001), 19–42.



Notes to Pages 171–177

287

197. Schilpp, Albert Einstein, Philosopher-­Scientist. 198. Bertrand Russell, “Whitehead and Principia Mathematica,” Mind 57, no. 226 (1948): 137–138. 199. Bernard E. Tomlinson, Garry Blessed, and Martin Roth, “Observations on the Brains of Non-­demented Old ­People,” Journal of the Neurological Sciences 7, no. 2 (1968): 331–356. 200. Trey Hedden and John D. E. Gabrieli, “Insights into the Ageing Mind: A View from Cognitive Neuroscience,” Nature Reviews Neuroscience 5, no. 2 (2004): 87–96. 201. Ibid. 202. Falk, Lepore, and Noe, “The Ce­re­bral Cortex of Albert Einstein.” 203. Tomlinson, Blessed, and Roth, “Observations on the Brains.” 204. J. H Adams and L. W. Duchen, Greenfield’s Neuropathology, 5th ed. (New York: Oxford University Press, 1992), 1284–1410. 205. Ibid. 206. Tomlinson, Blessed, and Roth, “Observations on the Brains.” 207. T. Avril, “Albert Einstein’s Gray M ­ atter Finds a Home in Philadelphia,” Philadelphia Inquirer, November 8, 2011; Lucy Rorke-­Adams, personal communication to author, 2011. 208. Carolyn Abraham, Possessing Genius: The Bizarre Odyssey of Einstein’s Brain (New York: St. Martin’s Press, 2001), 110. 209. Jim Holt, Why Does the World Exist?: An Existential Detective Story (New York: Liveright, 2012), 10–11. 210. Greene, Fabric of the Cosmos, 3–22. 211. Greene, Elegant Universe, 3–20. 212. William L. Laurence, “Einstein Offers a New Theory To Unify Laws of the Cosmos,” New York Times, March 30, 1953. 213. Greene, Elegant Universe, 283–319. 214. Ibid., 3–20. 215. Gutfreund and Renn, The Road to Relativity. 216. Greene, Elegant Universe, 231–262. 217. Greene, Elegant Universe, 3–20. 218. Isaac­son, Einstein: His Life and Universe, 189–224. 219. Einstein, “Physics and Real­ity.” 220. Clark, Einstein: The Life and Times; Hoffmann and Dukas, Albert Einstein, Creator and Rebel; Isaac­son, Einstein: His Life and Universe. 221. Levenson, Einstein in Berlin, 1–7. 222. Isaac­son, Einstein: His Life and Universe, 394–424.

288

Notes to Pages 179–185

7   the pur s ui t of g en ius Epigraph: Harold Bloom, Genius: A Mosaic of One Hundred Exemplary Creative Minds (New York: Warner Books, 2002), 1–12. 1. Frederick E. Lepore, “Dissecting Genius—­Einstein’s Brain and the Search for the Neural Basis of Intellect,” Cerebrum 3, no. 1 (2001), http://­ www​.­dana​.­org​/­Cerebrum​/­Default​.­aspx​?­id​=3­ 9337. 2. Ibid. 3. Bloom, Genius. 4. Kay R. Jamison, Touched with Fire: Manic-­Depressive Illness and the Artistic Temperament (New York: Simon & Schuster, 1993), 49–99. 5. Charles Percy Snow, Variety of Men (New York: C. Scribner’s Sons, 1966), 87–122. 6. “Genius,” Encyclopaedia Britannica, 11th ed., vol. 11 (New York: The Encyclopedia Britannica Com­pany, 1910), 594–595. 7. Samuel Johnson, A Dictionary of the En­glish Language (London: W. Strahan, 1755). 8. Frederick E. Lepore, unpublished research, 2017. 9. Alexander Pope and Henry Walcott Boynton, The Complete Poetical Works of Alexander Pope (Boston: Houghton Mifflin, 1931), 135. 10. Snow, Variety of Men. 11. Walter Isaac­son, Einstein: His Life and Universe (New York: Simon & Schuster, 2007), 309–335. 12. Ibid., 262. 13. Ibid., 309–335. 14. Andrew Robinson, Genius: A Very Short Introduction (Oxford: Oxford University Press, 2011), 1. 15. Richard J. Herrnstein and Charles A. Murray, The Bell Curve: Intelligence and Class Structure in American Life (New York: ­Free Press, 1994), 1–24. 16. Ian J. Deary, Intelligence: A Very Short Introduction (Oxford: Oxford University Press, 2001), 1–18. 17. Howard Gardner, Intelligence Reframed: Multiple Intelligences for the 21st ­Century (New York: Basic Books, 1999), 1–292. 18. Gardner, Intelligence Reframed, 79–114. 19. Ibid. 20. Deary, Intelligence. 21. David Wechsler, The Mea­sure­ment of Adult Intelligence (Baltimore: Williams and Wilkins, 1944), 3–48.



Notes to Pages 186–193

289

22. Ibid. 23. Catharine M Cox, The Early ­Mental Traits of Three Hundred Geniuses (Stanford, CA: Stanford University Press, 1926), 1–842. 24. David Wallechinsky, Irving Wallace, and Amy Wallace, The ­People’s Almanac Pres­ents the Book of Lists (New York: Morrow, 1977), 1–521. 25. Robinson, Genius, 40–53. 26. http://­www​.­eoht​.­info​/­page​/­Cox+IQ 27. Wechsler, Mea­sure­ment of Adult Intelligence. 28. Lewis M. Terman, ­Mental and Physical Traits of a Thousand Gifted ­Children (Stanford, CA: Stanford University Press, 1925). 1–648. 29. Nancy C. Andreasen, The Creative Brain: The Science of Genius (New York: Plume, 2006), 1–17. 30. Ibid. 31. Deary, Intelligence, 102–113. 32. Robinson, Genius, 40–53. 33. Tom Clynes, “How to Raise a Genius,” Nature 537 (2016): 152–155. 34. Francis Galton, Hereditary Genius: An Inquiry into Its Laws and Consequences (London: Julian Friedmann, 1978), 1–3. 35. Ibid., vii–­xxvii. 36. Alexander Pope, An Essay on Man: Epistle I in The Complete Works of Pope (Boston: Houghton Mifflin, 1931), 141. 37. Galton, Hereditary Genius, 316–335. 38. Ibid. 39. Ibid., vii–­xxvii. 40. Francis Galton, En­glish Men of Science: Their Nature and Nurture (London: Macmillan, 1874), 12. 41. Robinson, Genius. 42. Thomas J. Bouchard Jr. et al., “Sources of H ­ uman Psychological Differences: The Minnesota Study of Twins Reared Apart,” Science 250, no. 4978 (1990): 223–228. 43. Deary, Intelligence, 67–90. 44. Ibid. 45. Eric R. Kandel, Reductionism in Art and Brain Science (New York: Columbia University Press, 2016), 41–58. 46. Ibid. 47. Isaac­son, Einstein: His Life and Universe, 79–84; Paul Arthur Schilpp, Albert Einstein, Philosopher-­Scientist (New York MJF Books 1970), 1–95. 48. Dean Falk, Frederick E. Lepore, and Adrianne Noe, “The Ce­re­bral Cortex of Albert Einstein: A Description and Preliminary Analy­sis of

290

Notes to Pages 193–202

Unpublished Photo­graphs,” Brain: A Journal of Neurology 136, no. 4 (2013): 1304–1327. 49. Stephen Jay Gould, “Nonoverlapping Magisteria,” Natu­ral History 106, no. 2 (1997): 16–22. 50. Colin McGinn, The Mysterious Flame (New York: Basic Books, 1999), 1–29. 51. Ibid., 31–76. 52. Brian D. Burrell, “Genius in a Jar,” Scientific American 313, no. 3 (2015): 82–87 53. Dean Falk “New Information about Albert Einstein’s Brain,” Frontiers in Evolutionary Neuroscience 1 (2009): 1–6. 54. Nancy C. Andreasen et al., “Intelligence and Brain Structure in Normal Individuals,” American Journal of Psychiatry 150, no. 1 (1993): 130–134. 55. Stephen Jay Gould, The Mismea­sure of Man (New York: W. W. Norton, 1981), 73–112. 56. Gerhard Roth and Ursula Dicke, “Evolution of the Brain and ­Intelligence,” Trends in Cognitive Sciences 9, no. 5 (2005): 250–257. 57. Ibid. 58. Suzana Herculano-­Houzel, “The Remarkable, Yet Not Extraordinary, ­Human Brain as a Scaled-­Up Primate Brain and Its Associated Cost,” supplement 1, Proceedings of the National Acad­emy of Sciences 109 (2012): 10661–10668. 59. Jared Diamond, The Third Chimpanzee (New York: Harper Perennial, 1993), 32–57. 60. Ibid., 11–13. 61. Diamond, Third Chimpanzee, 363–368. 62. Ibid. 63. David Lewis-­Williams, The Mind in the Cave (London: Thames and Hudson, 2002), 96–100. 64. Roger Lewin, “Is Your Brain ­Really Necessary?,” Science 210, no. 4475 (1980): 1232–1234. 65. John H. Menkes, Textbook of Child Neurology, 3rd ed. (Philadelphia: Lea and Febiger, 1985), 197–199. 66. Herculano-­Houzel, “The Remarkable, Yet Not Extraordinary, ­Human Brain.” 67. Randy  L. Buckner, “The Cerebellum and Cognitive Function: 25 Years of Insight from Anatomy and Neuroimaging,” Neuron 80, no. 3 (2013): 807–815. 68. Eric R. Kandel, J. H. Schwartz, and T. M. Jessell, Princi­ples of Neural Science, 4th ed. (New York: McGraw-­Hill, 2000), 1041–1062.



Notes to Pages 202–208

291

69. Dean Falk, “Evolution of Brain and Culture: The Neurological and Cognitive Journey from Australopithecus to Albert Einstein,” Journal of Anthropological Sciences 94 (June 2016): 1–14. 70. A. P. Betran et al., “The Increasing Trend in Caesarean Section Rates: Global, Regional, and National Estimates: 1990–2014,” PLOS One 11, no. 2 (2016), doi:e0148343.doi:10/1371/journal.pone.0148. 71. Ibid. 72. Dean Falk, “Evolution of Brain and Culture.” 73. Herculano-­ Houzel, “The Remarkable, Yet Not Extraordinary, ­Human Brain.” 74. Gilbert Ryle, The Concept of Mind (Chicago: University of Chicago, 1949), 11–24. 75. Gould, Mismea­sure of Man, 19–29. 76. Deary, Intelligence. 77. Christof Koch, Consciousness: Confessions of a Romantic Reductionist (Cambridge, MA: MIT Press, 2012), 41–57. 78. Christof Koch et al., “Neural Correlates of Consciousness: Pro­gress and Prob­lems,” Nature Reviews Neuroscience 17, no. 5 (2016): 307–321. 79. Ibid. 80. Ibid. 81. Ibid. 82. John F. Fulton, Selected Readings in the History of Physiology (Springfield, IL: Charles C. Thomas, 1930), 37–105. 83. Ibid. 84. Ibid. 85. Sara Reardon, “­Giant Neuron Encircles Entire Brain of a Mouse,” Nature 543 (March 2017): 14–15.

8   whe re do we g o from ­h ere? (a n d wh e re have we bee n?) Epigraph: Christof Koch and Gary Marcus, “Neuroscience in 2064: A Look at the Last C ­ entury,” in The ­Future of the Brain: Essays by the World’s Leading Neuroscientists, ed. Gary Marcus and J. Freeman (Prince­ton, NJ: Prince­ton University Press, 2015), 255–284. 1. Samuel Taylor Coleridge, The Complete Works of Samuel Taylor Coleridge, vol. 1 (New York: Harper and ­Brothers, 1871), 357. 2. David J. Chal­mers, “The Puzzle of Conscious Experience,” Scientific American 273, no. 6 (1995): 80–86. 3. Charles P. Snow, The Physicists (Boston: ­Little, Brown, 1981), 35–50.

292

Notes to Pages 208–216

4. Dean Falk, Frederick E. Lepore, and Adrianne Noe, “The Ce­re­bral Cortex of Albert Einstein: A Description and Preliminary Analy­sis of Unpublished Photo­graphs,” Brain: A Journal of Neurology 136, no. 4 (2013): 1304–1327. 5. Andreas Vesalius, De Humani Corporis Fabrica, Book Seven (Basel: Johannes Oporinus, 1543). 6. Z. Josh Huang and L. Luo, “It Takes the World to Understand the Brain,” Science 350, no. 42 (2015): 42–44. 7. James H. Breasted, The Edwin Smith Surgical Papyrus, vol. 1 (Chicago: University of Chicago Press, 1930), 78–224. 8. Antonio Damasio, Descartes’ Error (New York: G. P. Putnam’s Sons, 1994), 3–19. 9. Hanna Damasio et al., “The Return of Phineas Gage: Clues about the Brain from the Skull of a Famous Patient,” Science 264, no. 5176 (1994): 1102–1105. 10. Damasio, Descartes’ Error. 11. O. Devinsky and M. A. Samuels, “The Brain That Changed Neurology: Broca’s 1861 Case of Aphasia,” Annals of Neurology 80, no. 3 (2016): 321–325. 12. Luke Dittrich, Patient H.M.: A Story of Memory, Madness, and ­Family Secrets (New York: Random House, 2016), 201–218. 13. Jacopo Annese et al., “Postmortem Examination of Patient H.M.’s Brain Based on Histological Sectioning and Digital 3D Reconstruction,” Nature Communications, January 28, 2014, doi:10.1038/ncomms4122. 14. Ibid. 15. Ibid. 16. Wilder Penfield and T. Rasmussen, Ce­re­bral Cortex of Man: A Clinical Study of Localization of Function (New York: Macmillan, 1955), 164–167. 17. Frederick E. Lepore, “When Seeing Is Not Believing,” Cerebrum: The Dana Forum on Brain Science 4 (2002): 23–38. 18. R. Elder, “Speaking Secrets: Epilepsy, Neurosurgery, and Patient Testimony in the Age of the Explorable Brain,” Bulletin of the History of Medicine 89, no. 4 (2015): 761–789. 19. A. Z. Crepeau and J. I. Sirven, “Management of Adult Onset Seizures,” Mayo Clinic Proceedings 92, no. 2 (2017): 306–318. 20. G. Holmes and W. T. Lister, “Disturbances of Vision from Ce­re­bral Lesions, with Special Reference to the Cortical Repre­sen­ta­tion of the Macula,” Brain: A Journal of Neurology 39 (1916): 34–73.



Notes to Pages 216–221

293

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294

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Notes to Pages 230–235

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296

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80. J. W. Lichtman, H. P. Fister, and N. Shavit, “The Big Data ­Challenges of Connectomics,” Nature Neuroscience 17, no. 11 (2014): 1448–1454. 81. Christof Koch, “The Connected Self,” Nature 482 (February 2012): 31. 82. Seung, Connectome, 155–169. 83. J. G. White et al., “The Structure of the Ner­vous System of the Nematode Caenorhabditis elegans,” Philosophical Transactions of the Royal Society of London B 314, no. 1165 (1986): 1–340. 84. Koch, “Connected Self.” 85. Nick Wingfield, “Video Games Help Model Brain’s Neurons,” New York Times, April 24, 2017. 86. Lichtman, Fister, and Shavit, “Big Data Challenges of Connectomics.” 87. J. I. Morgan and J. W. Lichtman, “Why Not Connectomics?,” Nature Methods 10, no. 6 (2013): 494–500. 88. Sara Reardon, “­Giant Neuron Encircles the Entire Brain of a Mouse,” Nature 543 (March 2017): 14–15. 89. Morgan and Lichtman, “Why Not Connectomics?” 90. Richard E. Passingham, “What We Can and Cannot Tell.” 91. Lichtman, Fister, and Shavit, “Big Data Challenges of Connectomics.” 92. Weiwei Men et al., “The Corpus Callosum of Albert Einstein’s Brain: Another Clue to His Intelligence?,” pt. 4, Brain: A Journal of Neurology 137 (2014): 1–8. 93. D. LaBerge, unpublished e-­mail to author, 2009. 94. Morgan and Lichtman, “Why Not Connectomics?” 95. Eric R. Kandel, J. H. Schwartz, and T. M. Jessel, Princi­ples of Neural Science, 4th ed. (New York: McGraw-­Hill, 2000), 910–935. 96. Alejandro P. Arellano, “EEG of the Genius,” Electroencephalography and Clinical Neurophysiology 3 (1951): 373; “Geniuses Aid Tests of Brain Pro­ cesses,” New York Times, February 24, 1951. 97. Wilder Penfield and H. Jasper, Epilepsy and the Functional Anatomy of the ­Human Brain (Boston: ­Little, Brown, 1954), 189–190. 98. Arellano, “EEG of the Genius.” 99. A. P. Alivisatos et al., “The Brain Activity Map Proj­ect and the Challenge of Functional Connectomics,” Neuron 74, no.  6 (2012): 970–974. 100. Andreas Steck and Barbara Steck, Brain and Mind: Subjective Experience and Scientific Objectivity (Cham, Switzerland: Springer, 2016), 15–16.



Notes to Pages 242–247

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298

Notes to Pages 247–251

119. Warren S. McCulloch and Walter H. Pitts, “A Logical Calculus of the Ideas Immanent in Ner­vous Activity,” Bulletin of Mathematical Biophysics 5, no. 4 (1943): 115–133. 120. Abraham, Rebel Genius, 86–94. 121. Nick Lane, Power, Sex, Suicide (New York: Oxford University Press, 2005), 114. 122. Christof Koch, Consciousness: Confessions of a Romantic Reductionist (Cambridge, MA: MIT Press, 2012), 15–17. 123. Gary Marcus, “Machines ­Won’t Be Thinking Anytime Soon,” in What to Think about Machines That Think, ed. J. Brockman (New York: Harper Perennial, 2015), 405–407. 124. Neil deGrasse Tyson, Michael A. Strauss, J. Richard Gott, Welcome to the Universe: An Astrophysical Tour (Prince­ton, NJ: Prince­ton University Press, 2016), 146–170. 125. Alison Gopnik, “Can Machines Ever Be as Smart as Three-­Year-­ Olds?,” What to Think about Machines That Think, ed. J. Brockman (New York: Harper Perennial, 2015), 321–324. 126. Koch, Consciousness, 113–135. 127. Dennis Bray, “Brain Emulation Requires Cells,” Nature 482 (2012): 462–463. 128. Marcus, “Machines Won’t Be Thinking Anytime Soon.” 129. M. Mitchell Waldrop, “The Chips Are Down for Moore’s Law,” Nature 530, no. 7589 (2016): 144–147. 130. L. Dormehl, Thinking Machines (New York: TarcherPerigree, 2017), 29–56. 131. Eric R. Kandel, Reductionism in Art and Brain Science (New York: Columbia University Press, 2016), 41–58. 132. Davide Castelvecchi, “Can We Open the Black Box of AI?,” Nature 538 (October 2016): 20–23. 133. Andreas Trabesinger, “Quantum Leaps, Bit by Bit,” Nature 543 (March 2017): S2–­S3. 134. R. Descartes, “Treatise on Man” in The Philosophical Writings of Descartes, vol. 1 (Cambridge, UK: Cambridge University Press, 1999), 99–108. 135. Carandini, “From Cir­cuits to Be­hav­ior.” 136. Daniel Dennett, From Bacteria to Bach and Back (New York: W. W. Norton, 2017), 371–410; Richard Dawkins, The Blind Watchmaker (New York: W. W. Norton, 1987), 21–41. 137. Stephen Jay Gould, “Nonoverlapping Magisteria,” Natu­ral History 106, no. 2 (1997): 16–22.



Notes to Pages 252–257

299

138. Dennett, From Bacteria to Bach, 150–175. 139. George Box and N. Draper, Empirical Model Building and Response Surfaces (Hoboken, NJ: John Wiley, 1987), 424. 140. Dennett, From Bacteria to Bach, 23–32. 141. Sigmund Freud, Collected Papers, vol. 4 (London: Hogarth Press, 1953), 215. 142. Francis Crick and Edward Jones, “Backwardness of H ­ uman Neuroanatomy,” Nature 361 (1993): 109–110. 143. Ibid. 144. Morgan and Lichtman, “Why Not Connectomics?” 145. Daniel Dennett, “Show Me the Science,” New York Times, August 28, 2005. 146. Franco Cauda, G. C. Geminiani, and A. Vercelli, “Evolutionary Appearance of Von Economo’s Neurons in the Mammalian Ce­re­bral Cortex,” Frontiers in ­Human Neuroscience 8 (March 2014): 1–11. 147. Terri Randall, e-­mail message to author, December 5, 2011. 148. Carol Norris, e-­mail message to author, June 2, 2017. 149. Randall, e-­mail message to author, December 5, 2011. 150. Eri Schubert, e-mail message to author, February 11, 2018. 151. Frederick E. Lepore, “Dissecting Genius: Einstein’s Brain and the Search for the Neural Basis of Intellect,” Cerebrum: The Dana Forum for Brain Science 3, no. 1 (2001): 1–26. 152. Carolyn Abraham, Possessing Genius: The Bizarre Odyssey of Einstein’s Brain (New York: St. Martin’s Press, 2001), 214–230. 153. S. Sniekers et  al., “Genome-­Wide Association Meta-­analysis of 78,308 Individuals Identifies New Loci and Genes Influencing H ­ uman Intelligence,” Nature Ge­ne­tics 49 (2017): 1107–1112. 154. Gary Marcus, “The Computational Brain,” in The ­Future of the Brain: Essays by the World’s Leading Neuroscientists, ed. Gary Marcus and J. Freeman (Prince­ ton, NJ: Prince­ton University Press, 2015), 205–218. 155. A. Chatterjee, “Cosmetic Neurology: The Controversy over Enhancing Movement, Mentation, and Mood,” Neurology 63, no.  6 (2004): 968–974. 156. Walt Whitman, Complete Poetry and Collected Prose (New York: Library of Amer­i­ca, 1982), 250–258. 157. A. L. Hodgkin and A. F. Huxley, “A Quantitative Description of Membrane Current and Its Application to Conduction and Excitation in Nerve,” Journal of Physiology 117, no. 4 (1952): 500–544.

300

Notes to Pages 258–261

158. Rachel Wurzman et al., “An Open Letter Concerning Do-­It-­Yourself Users of Transcranial Direct Current Stimulation,” Annals of Neurology 80, no. 1 (2016): 1–4. 159. Wilder Penfield and T. Rasmussen, The Ce­re­bral Cortex of Man (New York: Macmillan, 1955), 203–235. 160. John McPhee, Basin and Range (New York: Farrar, Strauss, Giroux, 1982), 109–129. 161. John W. Drake et al., “Rates of Spontaneous Mutation,” Ge­ne­tics 148, no. 4 (1998): 1667–1686. 162. Rosemary B. Grant and Peter. Grant, “What Darwin’s Finches Can Teach Us about the Evolutionary Origin and Regulation of Biodiversity,” BioScience 53, no. 10 (2003): 965–975. 163. Nick Lane, Life Ascending (New York: W. W. Norton, 2009), 88–117. 164. Marcus, “The Computational Brain,” in The ­Future of the Brain, 205–218.

Index

parietal lobe, 104–108, 161. See also neuroanatomy Anchor Stone blocks, 119–120 ancient Egypt, 39–40 ancient Greeks, 126 ancient Romans, 180–181 Anderson, Britt, 66–67 Andreasen, Nancy, 188, 194–195 anencephaly, 199 Annalen der Physik, 124 Annese, Jacopo, 212 anticonvulsant medi­cations, 214 aorta, 21, 23 aphasia, 165, 210–211 apical dendrites, 12–13 apoptosis, 201–202 April 18, 1955. See death a priori knowledge, 164 Arellano, Alejandro P., 241 Armed Forces Institute of Pathology (AFIP), 8–9, 16–17 artificial intelligence (AI), 75, 244–246, 248–249, 253 association cortices, 48, 50 astrocytes, 71–72, 74–76; extensions of, 71–72 astronomy, 176 atomic bomb, 154–158

abdominal aortic aneurysm, 21, 23 Abraham, Carolyn, 9, 12 Abrams, Henry, 23 absolute time, 133–135 academic institutions, 12–13 acceleration, 140–142, 146–147 age, 224; Alzheimer disease and, 172–173; discovery related to, 169–177; IQ tests and, 188; neuropathology and, 171–172 agenesis of the corpus callosum (ACC), 111 algorithms, 250–251 allocortex, 70 “alpha coma,” 240–241 alpha rhythm, 240–242 Alzheimer disease, 172–173 Amenta, Peter, 16–17 American Medical Association (AMA), 58 Amis, Martin, 173 amnesia, 212–213 Amunts, Katrin, 13, 16 amyotrophic lateral sclerosis (ALS), 200 anatomical studies, 5–6 anatomy, 161, 218, 252; microanatomy, 47, 88–89, 192; 301

302

Index

atrophy, 70, 86 auditory hallucinations, 213 Autobiographical Notes ­(Einstein, A.), 25–26, 119, 163 autopsy, 22–24 axons, 76 Babbage, Charles, 246 Bailey, Percival, 28, 60 Bangert, Marc, 220 Barany, Robert, 147–148 Becky (chimpanzee), 50 be­hav­ior, brain injuries and, 209–210 Bell, Joanne, 98 Berger, Daniel, 237 Berger, Hans, 240 Berks, Robert, 2, 4 bias, 65, 85 bilateral medial temporal lobectomy, 212 Binet-­Simon test, 186 birth, brain size and, 202–203 blood circulation, 205 blood flow, 227, 229 blood oxygen level–­dependent (BOLD), 228 Bloom, Harold, 179 Bohr, Niels, 135, 151–154 von Bonin, Gerhardt, 28, 104–105 Book of Lists (Wallechinsky), 186 Borges, Jorge Luis, 243 Born, Max, 148–149, 153–154 Box, George, 252 brain: “callosal,” 108–115; computers and, 245–252, 256; disposal of, 36–37; evolution of, 75–76, 251; language function and, 218–219; lymphatic vessels and,

218; mind and, 207–208; of observer, 136–137; specimen of, 36–37; thought experiments related to, 144–145. See also Einstein, Albert, brain Brain Activity Map Proj­ect, 242 Brain: A Journal of Neurology (Brain), 94–98 braincutting, 5, 24, 28; planum temporale and, 219 brain diseases, 100, 200; neuropathology and, 39, 82 brain injuries, 209–210, 214; x-­rays of, 215–216 brain lesions, 233–234 Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, 224–226 brain scans, 109, 113 brain size, 55, 79, 85, 194; birth and, 202–203; cells and, 201–202; energy cost and, 203; intelligence and, 195–197; paleoanthropology and, 196–198 brain tissue, 149, 225 “brain waves,” 240–241 Bray, Dennis, 249 Brenner, Sidney, 236–237 Broca, Paul, 210–211 Broca’s aphasia, 165, 211 Broca’s area, 16, 103–104, 184, 197 Brodmann, Korbinian, 28–29, 136 Bucky, Gustav, 25 Burrell, Brian, 53, 193–194 Burroughs, William S., 7 bust, 2, 4



Index 303

Caenorhabditis elegans, 12–13, 117, 119, 236–237, 259 Cajal, Santiago Ramón y, 31, 41, 44, 206, 235–236 calculus, 122 “callosal” brain, 108–115 callosum, epilepsy and, 110–111. See also corpus callosum Campbell, Alfred Walter, 28, 30 “canonization,” 2 Carlyle, Thomas, 138, 164 Caucasian brains, 112 causality, 225 Cavendish Laboratory (University of Cambridge), 3 celloidin, 32, 66 cells, 52, 74; astrocytic, 71–72; brain size and, 201–202. See also glial cells cellular change, 45–46, 72 central ner­vous system (CNS), 44, 192 cerebellar neurons, 201 cerebellum, 161–162; Anderson on, 66–67; of Einstein, A., brain, 32–33 ce­re­bral architectonics, 220–221, 223 ce­re­bral cortex, 47–48, 99 ce­re­bral hemi­spheres, 15; homunculi and, 49 ce­re­bral repre­sen­ta­tion, 214–215 Cerebri Anatome (Willis), 40 cerebrospinal fluid (CSF), 54, 194–195; hydrocephalus and, 198–199 cerebrum, 40 Cerebrum, 6, 82 Chal­mers, David, 159, 207–208

chemical neurotransmitter hypothesis, 45 chemical synaptic neurotransmission, 45 childhood: compass in, 118–119; Euclidian plane geometry, 119–121; playthings in, 118–120 chimpanzees, 50 Chinese brains, 112 Chinese symbols, 245 cholesterol, 23 circadian rhythm, 134–135 Clark, Ronald, 118 Clarke, Arthur C., 155 clinical neurology, 216–217; electroencephalography in, 240–242 clinical work, 61–62 cloning, 255–256 cognition, in elite brain research, 52–53 cognitive individualism, 164–165 cognitive resilience, 170–171 Coleridge, Samuel Taylor, 207 collaboration: with Krauss, 14, 16; with LaBerge, 13–14 college entrance exam, 122–123 Collins, Francis, 252–253 Colombo, Jorge A., 71–72 commercialization, 36, 97 commissures, 55 communication, of astrocytes, 74–75 Compston, Alastair, 92, 95–98 computers, 75; brain and, 245–252, 256; supercomputers, 246, 249–250 connectomes, 67, 76, 162; of Caenorhabditis elegans, 12–13,

304

Index

connectomes (cont.) 117, 119, 236–237, 259; diffusion tensor (DT) tractography and, 234–235; genome compared to, 235–236; mice and, 237–238; mind and, 233 Connolly, Cornelius J., 106, 108 consciousness, 162; “­mental topography” of, 134; neuronal correlates of consciousness, 204–206; observer as, 135–137 Cope, Edward, 55 corpus callosum, 55–56; in Einstein, A., brain exceptional anatomy, 109–115, 162, 239; of Einstein, A., brain, 56; lack of, 111–112; size of, 109–110, 112–114 cortex, 26, 47, 70, 99, 145; entorhinal cortex, 171–172, 212; electrical identification of, 48–49; lateral ­human, 29–30; parietal somatosensory, 104–105; posterior parietal, 105; prefrontal, 85–92; visual, 215–216, 227–228 cortical column, 47 cortical knob, 101–103; Falk and, 89–90, 219; musicians and, 219–220 cortical neurons, 201 counterfactuals, 130–131 Cox, Catherine, 186–187 creativity, 180; in genius, 187–188 cremation, 24–25 cresyl echt violet stain, 64–66 Crick, Francis, 24, 93, 162, 176, 204, 206, 252 Critchley, Macdonald, 50, 83–84, 104

criticism: of elite brain research, 194; of peer-­reviewed paper, 65–66; against Witelson, 81–82 Cro-­Magnon, 196–198 “curiosity-­driven research,” 88 Cushing, Harvey, 27–28, 46 Dale, Henry, 45 Damasio, Hanna, 210 Dana Foundation, 5, 82 Dandy, Walter, 83 Dawkins, Richard, 251 Deary, Ian, 204 death, 10; from abdominal aortic aneurysm, 21, 23; autopsy ­a fter, 22–24; choice for, 21; moment of, 22; programmed cell, 201–202; written calculations before, 21–22 deep time, 258–260 Dehaene, Stanislas, 145, 230 Deisseroth, Karl, 243 dementia, 172–173 dendrites, 12–13, 59–60 Dennett, Daniel, 159–160, 251 deoxyribonucleic acid (DNA), 24, 35–36, 255, 260–261 depression, 221–222 Descartes, René, 199–200, 203 descendants, 35; heredity and, 188–193 diagnosis, 241 Dialogue Concerning Two Chief World Systems (Galileo), 141–142 Dialogues (Plato), 126 Diamond, Jared, 196–197 Diamond, Marian, 14; on cresyl echt violet stain, 65; on glial



Index 305

cells, 63–64, 73–74; peer-­ reviewed study by, 63–66 Dicke, Ursula, 196 A Dictionary of the En­glish Language (Johnson), 181 diffusion tensor (DT) tractography, 233–235 diffusion-­weighted MRI (DW-­MRI), 232–233 digital computers, 75, 251–252 directives, 25 “direct” sensory impressions, 119–121 discovery: age related to, 169–177; of general relativity, 128; luck and, 176; peak per­for­mance of, 170–171 “Dissecting Genius: Einstein’s Brain and the Search for the Neural Basis of Intellect” (Lepore), 5, 10 dissection, 6, 26 distributed networks, 231 doctorate, 124 documentary (PBS NOVA Science Now), 96 Donway, Walter, 82 “Driving Mr. Albert: A Trip across Amer­i­ca with Einstein’s Brain” (Paterniti), 7, 11–12 dualism, 199–201 Dukas, Helen, 25 dyscalculia, 230 Eddington, Arthur, 128, 168, 183 education, 171; calculus in, 122; at cantonal school, 122–123, 130; college entrance exam, 122–123; doctorate in, 124; drop out,

123, 130; employment in, 124–125; geometry in, 119–121, 123; grades in, 123; nurture in, 190; preparation as, 139 The Edwin Smith Surgical Papyrus (Breasted), 40, 209 Ehrenfest, Paul, 77 Ehrich, William, 58–59 Einstein, Albert, 148. See also specific topics Einstein, Albert, box (thought experiment), 151–152, 158–159 Einstein, Albert, brain, 179, 255–256, 261; atlas app (iTunes), 97; celloidin for, 32; cerebellum of, 32–33; clinical neurology and, 217; corpus callosum of, 56; dissection of, 26; mathe­matics and, 145; ner­vous system and, 117–118; owner­ship of, 33–34, 36–37; permission related to, 25–26, 33–34; public relations about, 27; removal of, 23–24; sectioning of, 31–32; self-­interest in, 25–26; stain for, 28, 30–32; technology and, 208–209; temperature and, 24; thalamus of, 60; treatment of, 28, 31. See also slides Einstein, Albert, brain exceptional anatomy: Broca’s area in, 103–104; corpus callosum in, 109–115, 162, 239; frontal gyrus in, 100–101; frontal lobes in, 100–103; frontal lobe volume in, 103; language acquisition and, 104; left frontal lobe in, 102–103; left pars triangularis in, 104; neural interconnectivity

306

Index

Einstein, Albert, brain exceptional anatomy (cont.) in, 112–113; omega sign in, 101–103; paleoanthropology and, 194, 217–218; parietal lobe anatomy and, 104–108, 161; parietal opercula in, 105–107; petalia in, 108; postcentral inferior sulcus in, 107; precentral gyrus in, 102; right frontal lobe in, 100; splenium in, 113; submerged supramarginal gyrus in, 106–107; unimodal postcentral gyrus in, 105 Einstein, Albert, brain removal: formalin bath ­a fter, 23–24; news about, 24; pro­cess of, 23 Einstein, Albert, materials, at NMHM, 17–19, 92–93, 95–96, 99 Einstein, Bernhard Caesar, 122 Einstein, Eduard, 24, 139, 177 Einstein, Hans Albert, 24 Einstein, Hermann, 118–119 Einstein, Maja, 118 Einstein, Margot, 24 Einstein, Pauline, 122 Eisenhardt, Louise, 46 electrical identification, of cortex, 48–49 electricity, 118, 133, 258; intelligence related to, 257–258; neuroanatomy related to, 44–45 electrodes, 240 electroencephalography (EEG), 25, 212, 240–242 electromagnetic waves, 130–131 electron microscopy (EM), 225, 235, 238–239

Eliot, T. S., 159 elite brain research, 253–254; Burrell on, 53, 193–194; cognition in, 52–53; criticism of, 194; on Lenin, 51–52; pyramidal cells in, 52; Spitzka on, 54–55; Wagner on, 53–54 E = MC 2, 3; atomic bomb and, 155–158; in thought experiments, 150–152 employment: in education, 124–125; equipment for, 125; as patent clerk, 132, 142 encephalization quotient (EQ), 196 energy, mass and, 150–151 energy cost, brain size and, 203 Enola Gay, 2–3 entorhinal cortex (EC), 171–172, 212 epilepsy, 56, 211–212; callosum and, 110–111; temporal lobe and, 213 “epistemological credo,” 121 EPR paradox, 153 equivalence princi­ple, 142, 146 Van Essen, David C., 108 Euclid, 119–121, 142–143 Euclidean plane geometry, 119–121 eugenics, 190 evolution, 253, 259–260; of brain, 75–76, 251 “The Exceptional Brain of Albert Einstein” (Witelson), 78 Experimental Neurology, 64 explicit memory, 212 external cortex, 26 extrapyramidal, 200 eyes, 23. See also vision



Index 307

Falk, Dean, 10, 12, 14; background of, 86–87, 217–218; cortical knob and, 89–90, 219; manuscript of, 92–98; motivation of, 85–87; neuroanatomy and, 16; on parietal opercula, 91; publication and, 94–95; terminology and, 92; Witelson compared to, 106 fame, 180 ­father, 118–119 Feynman, Richard, 167 fission, general relativity and, 156, 158 Flechsig, Paul, 59–60 Flynn, James R., 188 focalization, 162 formalin bath, 23–24 Fort Detrick, 18 foveal vision, 215–216 FOXP2 gene, 223 Freud, Sigmund, 134, 222, 252 Froebel, Friedrich, 119–120 frontal gyrus, 100–101 frontal lobes: of chimpanzees, 50; deficits of, 51; in Einstein, A., brain exceptional anatomy, 100–103; pathology of, 210 frontal lobotomies, 50 Frontiers in Evolutionary Neuroscience, 88 Fuchs, C. H., 53–54 Fuld Hall, 1–3 Fulton, John Farquhar, 42, 46, 50, 100 functional magnetic resonance imaging (fMRI), 220, 226; magnetic resonance imaging compared to, 227, 229;

mathe­matics and, 230–231; random background activity in, 229; in Science, 227–228; subjects in, 229–230; task in, 232–233; thinking and, 227, 229–230; of visual cortex, 227–228; voxels and, 231–232 functional neuroimaging, 209 Gage, Phineas, 209–210 Galaburda, Albert, 81–82, 93 Galileo, 127, 141–142 gallbladder, 23 Galton, Francis, 188–190, 192 Galvani, Luigi, 44 Gardner, Howard, 184–185 Gates, Bill, 124 Gauss, Carl Friedrich, 53–54 Gazzaniga, Michael, 56, 111 gedankenexperiment. See thought experiments gender, 245; neuronal density and, 68 general covariance, 168–169 general relativity, 140–141; discovery of, 128; fission and, 156, 158; general covariance in, 168–169; influences related to, 149; significance of, 149–150; solar eclipse and, 168; in thought experiments, 143–144, 148–150 Ge­ne­tic Study of Genius, 187–188 genius: corpus callosum of, 114–115; creativity in, 187–188; current perception of, 180; definition of, 189; electroencephalography and, 241; happiness and, 180; heredity

308

Index

genius (cont.) and, 188–193; interest in, 179–180; IQ tests and, 185–188; kinds of, 183–185; lists of, 186–187; modular construct and, 184–185; multiple intelligence theory and, 184; of Newton, 187; prospective study on, 187; recognition of, 182–183; in seventeenth c­ entury, 181–182; structural basis of, 193–206; study of, 12–13, 186–187, 189–190 Genius (Bloom), 179 Genius of Our Age, 224 Gennari, Francisco, 220–221 genome, 252–253; connectome compared to, 235–236; HeLa, 35; intelligence and, 191 genomics, 223 geology, 259 geometry, 119–121, 123, 143, 175 Gerstmann’s syndrome, 230–231 Geschwind, Norman, 218–219, 231, 233 Gesell, Arnold, 42 Gladwell, Malcolm, 131 Glenn, Frank, 21 glia, 44, 71–72, 74, 225; neurons and, 59, 63–64 glial cells, 72; Diamond, M., on, 63–64, 73–74; per neuron, 73–74; Witelson on, 69 glial fibrillary acidic protein (GFAP), 71–72 global neuronal workspace, 84 God, 153–154; laws of nature and, 169 Gödel, Kurt, 1–2, 25 Golgi, Camillo, 31, 41

Golgi stain, 66, 235–236 Gould, Stephen Jay, 193, 195, 203–204, 251 Gowers, William, 50 gravity: acceleration and, 140–142, 146–147; interview on, 140; special relativity theory and, 138, 140–141; in thought experiments, 138–144; universal gravitation, 125–126. See also general relativity gray ­matter, 28, 31 Gray’s Anatomy, 55 Greeks, ancient, 126 Greene, Brian, 117, 135, 138, 142; on string theory, 174–175 Grossman, Marcel, 143, 166 Gullstrand, Alvar, 182–183 Hadamard, Jacques, 25, 217 hallucinations, 213 Hamlin, Earnest Baker, 157 hand dominance, 111 happiness, 180 Harlow, John, 210 Harper’s Magazine, 7 Harvey, Arthur, 11–12, 16 Harvey, Eloise, 60 Harvey, Thomas, Jr., 11–12 Harvey, Thomas Stoltz, 6, 11–12; Armed Forces Institute of Pathology and, 8–9; autopsy by, 22–24; background of, 27–28, 31–32, 41–42, 46–47; challenges of, 42–43; clinical work for, 61–62; death of, 10; disadvantages of, 57–58; dissection by, 26; experts and, 58–59; ­family life of, 60–61; findings of, 23;



Index 309

interview with, 63; on neurohistology, 7–8; owner­ship by, 33–34, 37; pencil sketches by, 14–15; on researchers, 26–27; slides from, 67; Witelson and, 68. See also photo­graphs Harvey, William, 205 Hawking, Stephen, 100, 200, 224, 253 Haymaker, Webb, 8, 17, 58 Hebb, Donald, 45–46, 192 Heisenberg’s uncertainty princi­ ple, 153 HeLa: cells, 34–36; genome, 35 hemi­spheres, 15, 49, 111 Henschen, Salomon, 215 Herculano-­Houzel, Suzana, 73–74, 203 Hereditary Genius: An Inquiry into Its Laws and Consequences (Galton), 189–190 Hines, Terence, 65, 67 hippocampus, 70 Hippocrates, 40 Hiroshima, Japan, 2–3, 154–158 historiometry, 187 history: of neuroanatomy, 39–41; of science, 205 hodology, 234 Hoffman, Banesh, 118, 143 Holmes, Gordon Morgan, 161, 214–216 home, 1–2 homunculus, 48–49, 103 Hooke, Robert, 40–41 ­Human Genome Proj­ect, 252–253 ­human organ owner­ship, 34–36 Hume, David, 121, 192–193 hydrocephalus, 198–199

ideograms, 245 immunolabeled astroglial cells, 72 implicit memory, 212 inferior parietal cortex, 145 inferior parietal lobules, 5 inheritance, 188–193 inhibitory neurons, 229 Institute for Advanced Study, 3, 125 intellects, of physicists, 208 intelligence, 184, 255–256; artificial intelligence, 75, 244–246, 248–249, 253; biological determinism and, 203–204; brain size and, 195–197; definition of, 185; electricity related to, 257–258; genome and, 191; IQ tests and, 185–188; Minnesota Study of Twins Reared Apart and, 190–191; neuronal correlates of consciousness and, 204–205; pharmacotherapy and, 257; Wechsler Adult Intelligence Scale, version IV, 185, 188 intelligence quotient (IQ), 185–188, 194–195, 199 interlaminar astroglial pro­cesses, 71 introspection, 160–161 intuition, 130; general relativity from, 148–149; science and, 139 ionic hypothesis, 44–45 IQ tests, 185–188 Isaac­son, Walter, 118, 124, 139 The Isocortex of Man (Bailey and von Bonin), 28 James, William, 162 Jamison, Kay Redfield, 180

310

Index

Johnson, Samuel, 181 journals, 93; Brain, 94–98 Judaism, 34, 121–122 Kandel, Eric, 45–46, 73, 192 Kant, Immanuel, 121, 164, 192–193 Kasevich, Ray, 14 Keller, Marta, 11, 31–32 Kennard, Margaret, 46–47 Kettenmann, Helmut, 75 Keynes, John Maynard, 160 Kigar, Debra, 81 knowledge, 164, 167–168 Koch, Christof, 77, 107, 162, 204, 206–207, 248 Krauss, Elliot, 5, 8–9, 88; collaboration with, 14, 16; custodian of Einstein’s brain, 12, 34, 254 Krebs, Emil, 16 Kuhn, Thomas, 127–128 LaBerge, David, 12–13, 239–240 Lacks, Henrietta, 34–35 Lancet, 4–5, 10, 68, 78, 220 language acquisition, 118, 197, 218; aphasia and, 165, 210–211; Einstein, A., brain exceptional anatomy and, 104; split-­brains and, 111 language function, 218–219 languages, 16, 223 Laplace, Pierre-­Simon, 54 ­laser interferometer, 149–150 Lashley, Karl, 55–56 Last W ­ ill and Testament, 18–19, 25, 122 lateral ­human cortex, 29–30 Laurent, Gilles, 77 laws of motion, 166

laws of nature, 169 learning, cellular change in, 45–46 Leborgne, Louis Victor, 210–211 van Leeuwenhoek, Anton, 14, 40–41 left frontal lobe, 102–103 left pars triangularis, 104 Lehrbuch der Physik (Violle), 130 Leidy, Joseph, 55 Lemonick, Michael, 81 Lenin, Vladimir, 51–52, 254 Levy, Steven, 62 Lewis-­Williams, David, 198 Lewy, Fritz Heinrich (Frederick Henry Lewey), 31–32 Lichtman, Jeffrey, 235–236 light, speed of, 130–133, 136 Lima, Almeida, 50 lists, of geniuses, 186–187 L = mV 2, 150–151 localization, 100, 102, 153 Loewi, Otto, 45 logic, mathe­matics and, 171 Lorber, John, 198–199 Louveau, A., 218 luck, 139; discovery and, 176 Lucy (chimpanzee), 50 lymphatic vessels, brain, 218 macular vision, 215–216 Magendie, François, 54 magnetic resonance imaging (MRI), 90; brain scans and, 109, 113; depression and, 221–222; functional magnetic resonance imaging compared to, 227, 229; strength of, 232; twins and, 223 Maller, J. J., 221–222



Index 311

Malpighi, Marcello, 205 A Manual of Diseases of the Ner­vous System (Gowers), 50 manuscript, 78; for Brain, 92–98; credibility of, 95–96; editorial comment on, 98; length of, 95, 98 Marcus, Gary, 207, 248–250, 253, 256, 260–261 Mariana Islands (Western Pacific), 19 Maric, Mileva, 123, 177 mass, energy and, 150–151 materialism, mind and, 163 mathematical biology, 247 mathe­matics: functional magnetic resonance imaging and, 230–231; logic and, 171; metric tensors, 143–144; physics and, 165–166; of string theory, 175; thought experiments related to, 129, 142–146 Maxwell, James Clerk, 166 McClintock, Barbara, 243–244 McCulloch, Warren, 46–47, 246–247 McGinn, Colin, 193–194 McPhee, John, 259 medial h ­ uman cortex, 29–30 Medical Center at Prince­ton (MCP), 5, 9, 12, 16, 254 Melville, Herman, 95 memory, 2; amnesia, 212–213 Men, Weiwei, 109–110, 112, 115, 239; Witelson compared to, 113–114 Mendel, Gregor, 176 “­mental topography,” of consciousness, 134 Mesulam, M. Marsel, 84, 231 metacognition, 159–160

metric tensors, 143–144 mice, connectomes and, 237–238 microanatomy, 47, 192; gross brain anatomy and, 88–89 microbial opsins, 243 microbiology, 57 microglia, 44, 74 microscopic neuroanatomy, 66 microscopists, 40–41, 71; electron microscopy, 225, 235, 238–239 mind: brain and, 207–208; connectome and, 233; materialism and, 163; ner­vous system and, 117 mind control, 242–243 Minkowski, Hermann, 123 Minnesota Study of Twins Reared Apart (MISTRA), 190–191 miracle year (1905), 124–126, 131, 150–151, 182 Molaison, Henry Gustav, 211–213 Moniz, Egas, 50 Montreal Neurological Institute, 213–214 mood disorders, 180 More, Henry, 137 Mountcastle, Vernon, 43, 47 multiple intelligence theory, 184 mummification, 39–40 musicians, 219; violin, 90–91, 102, 122, 193, 220 mutations, 259 myelin: development, 55; sheaths, 59–60 my ­thol­ogy, Roman, 180–181 Nathan, Otto, 22–24, 27, 33, 64 National Institutes of Health (NIH), 35

312

Index

National Museum of Health and Medicine (NMHM), 9; access to, 18–19; answers from, 19; attribution of, 96–97; Einstein, A., materials at, 17–19, 92–93, 95–96, 99; press release from, 97–98; relocation of, 18; suppression from, 95–96 natu­ral se­lection, 260–261 nature versus nurture, 90–91, 190–193 Nazis, 1 Neanderthals, 196–197 ner­vous system, 42, 44, 50, 192, 247; Einstein, A., brain and, 117–118; mind and, 117 von Neumann, John, 241 neural interconnectivity, 112–113 neuroanatomical maps, 28–30 neuroanatomy, 16, 26, 66; correlations in, 221–222; electricity related to, 44–45; history of, 39–41; lymphatic vessels in, 218; neurophysiology and, 238–239; thinking related to, 177–178 neurodegenerative cellular changes, 72 neuroglia, 73 neurohistology, 7–8, 40–41, 52 neurologist, 3–4 neurology, 31, 94 “Neuromythology of Einstein’s Brain” (Hines), 65 neuronal correlates of consciousness (NCC), 204–206 neuronal density, gender and, 68 neuron conduction velocity, 67 neuron doctrine, 41, 206

neurons, 31, 229; electrodes and, 240; glia and, 59, 63–64; programmed cell death and, 201–202; reconstruction of, 237–239; transistors compared to, 247–249 neuron theory, 44 neuropathology, 8, 42; age and, 171–172; brain diseases and, 39, 82 neurophysiology, 238–239 neuroplasticity, 177, 192 neuroscience, 12–13, 73; changes in, 42–43; subdivisions in, 43; videogames for, 238 “Neuroscience in 2064: A Look at the Last C ­ entury” (Koch and Marcus), 207 neurosurgery, 27–28 neurotransmitters, 238–239, 250 “A New Determination of Molecular Dimensions” (Einstein, A.), 124 “New Information about Albert Einstein’s Brain” (Witelson), 10, 92 news, front page, 24, 97–98 Newton, Isaac, 125–126, 137–138, 140; genius of, 187; gravity of, 143; laws of motion of, 166 New Yorker, 94 New York Times, 81–82 NG2 + glial progenitor cells, 74 Nissen, Rudolph, 21 Nissl stain, 28–29, 31, 59, 70 Nobel Prize, 31, 41, 44–46, 187, 234; for Einstein, A., 182–183; for photoelectric effect, 133; of Sperry, 111; for vestibular system, 147–148



Index 313

Noe, Adrianne, 9, 17–18; publication and, 92–93, 95–96 nomenclature, neuroanatomical, 41 nonlocality, 153 observer, 139, 141; brain of, 136–137; as consciousness, 135–137; gravity and, 146–147; reductionism and, 147 “observer bias,” 65 observer effect, 147 occipital lobe, 221–222 office, 1–2 oligodendrocytes, 74 oligodendroglia, 44 omega sign, 101–103 Ono, Michio, 106, 108 opercularization, 91, 108 Oppenheimer, J. Robert, 187 optoge­ne­tics, 243 Orgel, Leslie, 253 Orsted, Hans Christian, 126–127 paleoanthropology, 87; brain size and, 196–198; Einstein, A., brain exceptional anatomy, and, 194, 217–218 paleoneurology, 87 “parietal” brain, 78–92 “parietal lobe genius,” 5 parietal lobes: anatomy, 104–108, 161; glial cells in, 63–64; LaBerge on, 12–13; role of, 83–84; significance of, 84–85; size of, 76; Witelson on, 79–80 The Parietal Lobes (Critchley), 50, 83–84 parietal neglect, 83

parietal operculum, 79–82; in Einstein, A., brain exceptional anatomy, 105–107; Falk on, 91 parietal somatosensory cortex, 104–105 Parkinson’s disease (PD), 200 Pasteur, Louis, 90, 139 patent clerk, 132, 142 Paterniti, Michael, 7, 11–12 pathologists, Yale School of Medicine, 46 peak per­for­mance, 170–171 Pearson, Karl, 54 peer-­reviewed study: from Anderson, 66–67; controls for, 65; by Diamond, M., 63–66; statistics in, 65 pencil sketches, 14; as “road maps,” 15 Penfield, Wilder, 44, 102, 105, 213–214, 241; ce­re­bral cortex and, 47–48; electricity and, 258; homunculi of, 49, 103 penicillin, 57 Penrose, Roger, 109 personal discontents, 177 Person of the C ­ entury, 5 petalia, 79–80, 86, 108, 222 pharmacotherapy, 214; intelligence and, 257 Philadelphia Inquirer, 97 philosophy, 164 photoelectric effect, 133 photo­graphs, 5–6, 8, 88, 254; assessment from, 26; authenticity of, 81; ce­re­bral cortex in, 99; external cortex in, 99; researchers and, 76–78; search for, 10–12; Witelson and, 85–86, 200

314

Index

photomicroscopes, 71 photons, 131 physicists, intellects of, 208 physics, 121; Galileo on, 127; mathe­matics and, 165–166; Plato on, 127; reading, 130; thought experiments and, 137–138 Physiology of the Ner­vous System (Fulton), 42 pictures: pencil sketches, 14–15. See also photo­graphs; slides Pinker, Steven, 5, 81, 84 planum temporale, 219 Plato, 126–127 playthings: Anchor Stone blocks, 119–120; compass, 118–119 Podolsky, Boris, 153 Poldrack, Russell, 244 Pope, Alexander, 181–182, 189 Popovic, Zoran, 238 positron emission tomography (PET), 48, 145, 231 Possessing Genius (Abraham), 9 Postcards from the Brain Museum (Burrell), 53 postcentral inferior sulcus, 107 posterior parietal cortex, 105 postmortems, 233–234 precentral gyrus, 102 prefrontal cortex, 85–92 Pribram, Karl, 46–47 Prince­ton, New Jersey, 1–4; Medical Center at Prince­ton, 5, 9, 12, 16, 254 programmed cell death, 201–202 prospective study, 187

Ptolemy, 137–138 publication ac­cep­tance, 92–108 publishing, as education, 124 pyramidal cells, 52 Pythagorean theorem, 121 qualia, 105 quantum computing, 251 quantum entanglement, 153 quantum geometry, 175 quantum mechanical theory, 133 quantum mechanics, 151–154 quantum theory, 135 quarks, 174 railway travel, 132 Rain Man, 111–112 Ramachandran, Vilayanur S., 165 Ramakrishnan, Venki, 243 random background activity, 229 Rasmussen’s encephalitis, 210–211 real­ity, 129 receptive fields, 47 Reich, Walter, 64 relative brain weight, 195 release phenomena, 51 Rembrandt van Rijn, 81 researchers, 26–27; Anderson, 66–67; Colombo, 70–72; Diamond, M., 14, 63–66, 73–74; photo­graphs and, 76–78; Zaidel, 70. See also Witelson, Sandra research proposal, 13–14, 34 resting state functional magnetic resonance imaging (rfMRI), 232 right frontal lobe, 100 Robert Wood Johnson Medical School, 5



Index 315

Rogers, Eric, 3 Roman my ­thol­ogy, 180–181 Roo­se­velt, Franklin Delano, 155–156 Rorke-­Adams, Lucy, 59, 173 Rosen, Nathan, 153 Roth, Martin, 196 Rozsel, Alberta, 22 Rumsfeld, Donald, 39 Russell, Bertrand, 119, 171 Rutherford, Lord, 3, 183–184 Ryle, Gilbert, 203 Sacks, Oliver, 83, 99 SATs. See Scholastic Aptitude Tests Schaie, K. Werner, 170–171 Scholastic Aptitude Tests (SATs), 180, 188 Schroeder, Howard, 11 Schroeder, Manfred, 121 Schulman, Sidney, 58, 60 science: beauty of, 168; everyday thinking and, 176–177; history of, 205; intuition and, 139. See also neuroscience Science, 62–63, 227–228 Scoville, William Beecher, 212 Searle, John, 245 senile plaque, 172 senses: auditory hallucinations, 213; thinking and, 166–167. See also vision Seung, Sebastian, 109, 233, 235, 238 Shakespeare, William, 144–145 Sherrington, Charles, 163, 227 silicon, 248–250 simultaneity, 132–134 Skloot, Rebecca, 35

slides, 7, 9–11, 14, 16, 33; availability of, 255; boxes of, 61; commercialism of, 36, 97; from Harvey, T. S., 67; returning of, 58–59 Snow, C. P., 180, 182, 208 Socrates, 126 solar eclipse, 4, 128, 168 soul, body and, 163 space-­time curvature, 149–150, 167 Spearman, Charles, 183, 203–204 special relativity theory: challenge of, 131–132; Freud and, 134; gravity and, 138, 140–141; light in, 130–131; perception in, 132–133; result in, 133; simultaneity in, 132–134; speed in, 132; speed of light and, 130–133; as thought experiment, 128–135 speed of light, 130–133; visual evoked response and, 136 Sperry, Roger, 111 Spinoza, Baruch, 122, 154, 163 Spitzka, Edward Anthony, 54–56; corpus callosum and, 114–115 splenium, corpus callosum, 113 split-­brains, 56; language acquisition and, 111 spooky action at a distance, 153 stain, 30, 32, 69; cresyl echt violet, 64–66, 71; glial fibrillary acidic protein, 71–72; Golgi, 66; Nissl, 28–29, 31, 59, 70, 76; Weigert, 59–60, 76, 239 Stanford-­Binet test, 186, 188 string instrument players, 90–91, 102, 122, 193, 220 string theory, 129, 174–175

316

Index

submerged supramarginal gyrus, 106–107 sulci, 91–92 Summers, Larry, 78 supercomputers, 246, 249–250 superior temporal gyrus (STG), 69 suprachiasmatic nucleus, 135 Sylvian fissure (SF), 79–80, 102 symbols, Chinese, 245 synapses, 41, 45, 136, 202, 225, 227 synchronization: absolute time and, 135; circadian rhythm and, 135 syncytium, 31 syntax, 245–246 Szilard, Leo, 155–156 Talmud, Max, 121–122 technology: Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative and, 224–226; Einstein, A., brain, and, 208–209; supercomputers, 246, 249–250. See also functional magnetic resonance imaging; magnetic resonance imaging temperature, 24 temporal lobe, 213 “10,000 Hour Rule,” 131 Terman, Lewis, 186–188 Terry, Robert, 64–65 thalamus, 60 Theory of Every­thing, 173–176 thinking, 117, 163–164, 176; a priori knowledge and, 164; cognitive individualism, 164–165; “epistemological credo,” 121; functional magnetic resonance

imaging and, 227, 229–230; geometry and, 119–121; Judaism and, 121–122; knowledge about, 164, 167–168; neuroanatomy related to, 177–178; philosophy and, 164; senses and, 166–167; Truth and, 168; words related to, 160–161 Thomas, Dylan, 170 thought experiments (gedankenexperiments): atomic bomb and, 154–158; brain related to, 144–145; counterfactuals in, 130–131; description of, 126–127; E = MC 2 in, 150–152; equivalence princi­ple in, 142, 146; general relativity in, 143–144, 148–150; gravity in, 138–144; Kuhn and, 127–128; L = mV 2 in, 150–151; luck and, 139; mathe­matics related to, 129, 142–146; metacognition and, 159–160; observer in, 135–137; physics and, 137–138; quantum mechanics in, 151–154; real­ity and, 129; special relativity theory as, 128–135; string theory and, 129; “thought versus invention” of, 128; unconscious in, 133–134; verifiability of, 129; vestibular system and, 146–148, 150 “thought versus invention,” 128 time, 132–135; deep, 258–260; space-­time curvature, 149–150, 167 Time magazine, 5, 81; Einstein portrait on cover, 157 Tinian, 2–3



Index 317

Tombaugh, Clyde, 128 transcranial direct current stimulation (tDCS), 257–258 transistors, 247–249 TrueNorth, 249–250 Truths, Einstein’s, 168 Turing, Alan, 244–246 Turing Test, 245 twins, 190–191; functional magnetic resonance imaging and, 223 Tyson, Neil deGrasse, 248 unconscious, 133–134 understatement, scientific, 93 unified field theory, 173–176 unimodal postcentral gyrus, 105 universal gravitation, 125–126 unknown soldier, 214–215 uranium, 155–158 ventricles, 40 Verkhratsky, Alexei, 75 vestibular system, 146–148, 150 videogames, 238 da Vinci, Leonardo, 40 violin, 90–91, 102, 122, 193, 220 Violle, Jules, 130 viral infections, 57 vision, 166–167, 252; ce­re­bral architectonics and, 220–221; ce­re­bral repre­sen­ta­tion, 214–215; foveal, 215–216 visual cortex, 215–216; functional magnetic resonance imaging of, 227–228 visual evoked response (VER), 136 visual pathways, 234 Vogt, Cécile, 51–52

Vogt, Oskar, 51–52 voxels, 231–232 Wade, Nicholas, 57, 63 Wagner, Rudolf, 53–54 Wallechinsky, David, 186 Watson, James, 24, 93, 176 Wechsler, David, 185–187 Wechsler Adult Intelligence Scale, version IV (WAIS IV), 185, 188 Weigert stain, 59–60, 76, 239 Wernicke, Carl, 211 Wernicke’s area, 219 Wheatley, Cleora, 10–11 Wheeler, John Archibald, 135, 149 Whitehead, Alfred North, 171 white m ­ atter, 28, 31, 239 Whitman, Walt, 55 Wiener, Norbert, 241 Wigner, Eugene, 155 Wiles, Andrew, 224 Willis, Thomas, 39–40 Winternitz, Dean Milton, 46 Witelson, Sandra, 4–5, 70, 92; abstract from, 69; background of, 78; on brain size, 79, 85; controls for, 68; criticism against, 81–82; endowed chair for, 84–85; Falk compared to, 106; on glial cells, 69; Harvey, T. S., and, 68; hypothesis of, 78; manuscript submission by, 78; Men compared to, 113–114; on parietal lobes, 79–80; on petalia, 79–80; photo­graphs and, 85–86, 220; pro­cess for, 68–69; request from, 9–10; stain and, 69;

318 Witelson, Sandra (cont.) superior temporal gyrus and, 69; on Sylvian fissure, 79–80; on ­women’s brains, 68; Zaidel and, 70 Witten, Edward, 174–175 Wittgenstein, Ludwig, 160, 233 won­der, 119 words, 165; thinking related to, 160–161 World War I, 214–215 Wren, Christopher, 40

Index x-­rays, 25; of brain injuries, 215–216 Yasargil, M., 108 Yerkes, Robert, 46–47 Zaidel, Dahlia, 70 Zhou Enlai, 258 Zilles, Karl, 16 Zimmerman, Harry M., 26–27, 46, 173 Zu­rich Polytechnic, 122–123

About the Author

Frederick E. Lepore, MD, is a professor of neurology and ophthalmology at the Robert Wood Johnson Medical School at Rutgers University. He is a clinical neuro-­ophthalmologist, designer of the Optic Nerve Test Card, and has written over 125 scientific publications, including “Dissecting Genius—­Einstein’s Brain and the Search for the Neural Basis of Intellect.”