Ward 4: The Mallinckrodt Research Ward of the Massachusetts General Hospital [Reprint 2014 ed.] 9780674420083, 9780674420076

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The Bulfinch Building of the Matsachusells General Hotpital. A drawing by the author.

The M a l l i n c k r o d t Research W a r d of the M a s s a c h u s e t t s G e n e r a l Hospital

JAMES HOWARD

MEANS

With a Forword by Charles Sidney Burwell

Harvard University Press Cambridge 1958

©

Copyright 1958 by the President a n d Fellows of H a r v a r d College Distributed in Great Britain by O x f o r d University Press, London

Library of Congress Catalog C a r d N u m b e r 5 8 - 8 9 9 8 Printed in the United States of America

To the Investigators, the Patrons, and the Patients of W a r d 4

Preface

I he story which I shall tell is one of the growth of medical knowledge in a favorable medium. The purpose behind the telling is to bring home to the general reader the significance which the acquisition of such knowledge has for him personally, to make him conscious of a personal obligation to do his bit toward the support and defense of medical research, not on the basis of philanthropy alone, but of enlightened self-interest also. By telling the story of a certain investigative enterprise, I want to convince the reader that medical research in general is his own personal concern, no less than good government, education, or protection against accident, fire, or invasion. Some years ago Dr. Victor Heiser of the Rockefeller Foundation wrote of his medical adventures in forty-five countries. In the present case I shall write of medical adventures in a single ward. The breadth of the two experiences, however, is not dissimilar. In our case the mountain has come to Mahomet. Specifically, the book is the history of a hospital ward — a very special hospital ward — namely the Mallinckrodt Research Ward of the Massachusetts General Hospital, more familiarly known as Ward 4. While the work in this ward does not by any means encompass the entire collaborative research effort of the Harvard Medical School and the Massachusetts General Hospital, nevertheless it does represent a reasonable sample of the whole, and I believe that the personality of the ward — for wards, like hospitals, can

viii>

Preface

have personalities — dramatizes for the general reader the nature of the over-all investigative activity in a way that a more comprehensive and prosaic account could not do. The account, so far as my direct personal experience goes, extends over the period from the opening of Ward 4 in 1925 to 1951, when I retired from my active work as chief of medical services of the hospital. Under my successor, Dr. Walter Bauer, the ward has continued to flourish, and I have informed myself of its recent activities and have made some comments on them in Chapter XII. During my active tenure, Ward 4 as part of the medical services was under my general supervision, and I had responsibility for policy-making and administration. The policy that I followed was to invest in investigators of high promise and then to give them as much freedom of inquiry as possible. The ramifications of modern research become ever more complex. As the mass of our knowledge grows, the point of attack upon the unknown by research must be more sharply focused. The competence of individual research workers becomes more and more restricted, or, if you please, more specialized. At the same time, with ever more powerful instruments, the possibility of penetration is ever deepened. Thus we find nowadays an increasing tendency for research, both in medicine and in other fields, to be done by teams of workers of diverse skills. Each worker approaches the chosen problem from the point of view determined by his particular skill. The unifying force is the problem, and the problem itself, to be sure, may be of various degrees of specificity. The several skills represented in the team are unified by the problem. The contributions of each member must be integrated and interpreted through the joint action of the team. Such indeed has been the pattern in Ward 4. Investigators have spontaneously and informally allied themselves in teams for the pursuit of objectives of common interest. Such teams have

Preface

ix

had leaders, and the events in the ward's history can for the most part be tied to these leaders or principal investigators who have through the years made use of the ward. Such guiding minds will be identified as the narrative runs along; so too will be their pupils, many of whom, as they have grown to full research stature in their own right, have taken off to attain distinction elsewhere. As the story unfolds, indication will be given of whither they have carried the Ward 4 gospel. It should be emphasized that Ward 4 is not dedicated to the elucidation of any particular problem, such as the cause of cancer, or arthritis, or of degenerative cardiovascular disease. These may be studied, of course, along with any other appropriate problems, but at the election of the investigator; there is no must about it. In telling the tale, I have eschewed, insofar as possible, such terms as "project," "program," or "study design," which are bandied about so freely in our present-day promotional jargon. They imply an element of direction of research that I do not like very much; under some circumstances it becomes necessary. The only criterion for the admission of patients to Ward 4 is that its special facilities are needed to accomplish certain studies on them which competent investigators, with the patient's cooperation, wish to undertake. An enterprise to foster clinical research in medicine is what Ward 4 actually is. In the preparation of this book I have had the kindly cooperation of friends at the Massachusetts General Hospital, to all of whom I am deeply grateful. Dr. Bauer has shown continuing interest in this undertaking. He has read the entire manuscript both meticulously and critically, and has made many very helpful suggestions. Dr. Joseph C. Aub also has been over the manuscript and given me good advice on some important points. Mr. David C. Crockett, associate director for resources and development of the hospital, has been a great source of strength and encouragement to me, giving generously of his time in the gather-

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Preface

ing of material and, in general, easing the pangs of bookbirth. The following also have read the manuscript in whole or in part, and have given me the benefit of their opinions: Mr. Francis C. Gray, chairman of the hospital's board of trustees, Drs. N. W. Faxon, Dean A. Clark, Harriet L. Hardy, Chester M. Jones, John B. Stanbury, William H. Baker, and Mahlon B. Hoagland. Finally, for help in assembling the case material given in Chapter XII, my thanks are due again to Drs. Baker and Stanbury, and also to Drs. Anne P. Forbes, P. H. Henneman, William V. McDermott, Jr., and E. P. Maynard. Indirectly to many others I am grateful. J.H.M. December

18,1957

Contents Forward by Charles Sidney Burwell I 11

On the Nature of Research

xv 1

Origins and Organization of W a r d 4

10

III

Taking Off with Lead

21

IV

Charles Martell Shows the W a y

32

V

Bones, Stones, and Parathyroids

42

O n the Thyroid Beam

55

Highway to Sustenance

71

Integration by Endocrines

86

VI V11 VIII IX

Cohesion and Mobility

102

X

Enter Mr. Mallinckrodt

114

Divers Other Uses

126

Ward Round

140

What Does It Signify?

161

Literary Background

166

Glossary

173

Index

183

XI XII XIII

Illustrations

The Bulfinch Building D a v i d Linn Edsall Plan of W a r d 4 from 1924 to 1952

frontispiece 10 16

Commemorative Tablet

120

Plan of Mallinckrodt W a r d 4 after 1952

124

Foreword

During the middle twenties of the present century, a new type of professor of medicine began to appear in the medical schools of the United States. In general, these professors were young, but two things that distinguished them from most of their predecessors were that they were trained in some basic medical science as well as in the care of patients and that under one or another of several formulas they accepted the important principle of full-time academic responsibility. The author of this volume is one of these early full-time professors, trained in physiology as well as in clinical medicine. In his new position, he accepted the multiple responsibilities of such a post in academic medicine — namely, teaching, research, the care of patients, and administration. He continued to perform these duties effectively throughout his twenty-seven years as Jackson Professor of Clinical Medicine at Harvard University and Chief of the Medical Services at the Massachusetts General Hospital. He did distinguished work and wrote a distinguished book on the thyroid. He taught a generation of medical students, of house officers, and of developing associates. He played a leading and productive part as a member of the faculty of medicine and its important groups and so had a sizable role in the growth and development of the Harvard Medical School. He played a corresponding and leading role in the evolution and change of the Massachusetts General Hospital. This hospital is the oldest of

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Foreword

the eleven teaching hospitals affiliated with the Harvard Medical School and has a long and distinguished history of teaching and research as well as of the care of patients. The present volume is concerned with the Mallinckrodt Research Ward of the Massachusetts General Hospital, a joint enterprise of the hospital and the Harvard Medical School. It is fitting that such a volume should be written at this time. As one looks at the history of medicine and considers what contributions the present century has made, it becomes apparent that the major contribution of the twentieth century is a growing understanding of chemical and physiological mechanisms associated with the body's reactions to disease and injury. This growing understanding is based on the advance of the basic medical sciences and on the application of these advances to the problems of disease in patients. This growth of understanding means that the recognition, the management, and the prevention of disease can be rational in many more situations than in 1900. When one contemplates the history of research in general, in industry, and in medicine, it appears that there are advantages to having research on a broad spectrum going on in a group of people where communications are good and where ideas can be exchanged. It is particularly good to have what is called basic or fundamental research going on in the same place as applied research. It has been learned that ideas developing at any point of this spectrum may illuminate other parts. Fundamental advances may be transferred into application. Observations in practical situations may have implications for the understanding of fundamental problems. This important principle is illustrated by the history of the Mallinckrodt Ward. The distinguished history of this ward is summarized in Dr. Means's book and the productivity of the unit is clearly demonstrated. It is worth asking why it has continued to be so pro-

Foreword

• xvii

ductive throughout twenty-six years. This record suggests that some of the factors which have led to the maintenance of productivity and quality are as follows: First, the workers in this laboratory have had freedom to follow their problems where they took them. They were not obliged to limit themselves to a specialty field. It was probably a happy circumstance that even the title — whether it be Ward 4 or Mallinckrodt Ward — is an unrestricted title and had no tendency to limit or restrict work or ideas. Second, the ward was never allowed to get too big. Third, groups of diverse workers were permitted to utilize it in their research so that the stimulus of change and variety was present. Fourth, this story is an interesting testimony to the importance of the participation of patients in research — not only as possessors of diseases worth studying, but as active members of the research team. Finally, it does seem that universities, medical schools, and hospitals, where students are present, where active teaching is going on, and where both basic and applied work is done simultaneously and often by the same people, constitute highly favorable environments for research — quite possibly superior to isolated and specialized environments. The book is written with a valuable sense of historical perspective. Too much modern writing about medicine is written by individuals who seem not to understand that medical discoveries do not spring fully armed from anybody's head. They grow from the work of previous workers in the field, and each productive scientist stands on the shoulders of those who worked before him. This is clearly brought out in Dr. Means's book not only in relation to the advance of medicine but also to the evolution of the principles of operating the research ward itself.

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Foreword

Thus the book is testimony to the character and capacity of James Howard Means and to the validity of the ideas represented in the organization and operation of the Mallinckrodt Ward. CHARLES SIDNEY BURWELL

February 24, 1958

I

On the Nature of Research

In its essence research may be said to be man's conscious effort to find new facts by exploration, to relate them one to another, and to derive from them new principles and generalizations. It is the consequence of man's insatiable curiosity, and of his innate desire to improve his own lot. In the long-range view, progress through research discloses itself as an evolutionary process. We may draw an analogy between the research performed consciously and with intent by man and unconscious research on the part of nature. As man sets up experiments to find new truth, so nature, in the case of living organisms, at least, makes experimental types through the process of mutation and tests them out in the struggle for existence. Thus, we believe, has the evolution of species come about, and in similar fashion man has acquired new knowledge and learned to improve his ways of approaching his objectives. As nature, under an irresistible drive to procreate, forces life to adapt itself to every environment capable of supporting it at all, no matter how inimical that environment may be, so man, under his drive to know, inquires into and explores every region of his cosmos to which his sensibilities and his intelligence direct him. It is only through such acquisition of new knowledge and discernment of its meaning that man makes material progress. Some progress is merely the result of unplanned, often bitter, experience, but a much more important portion is the result of planned experiment or at least of conscious and controlled ob-

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servation of nature followed by the search for the meaning of what has been observed. These statements hold for medicine no less than for any other field in which men seek for a deeper understanding of life. Not always, however, has the indispensable quality of research been adequately recognized. Indeed some otherwise intelligent people profess to see no good in research. A few even try to sabotage it. In scattered fields, to be sure, its fruits have been put to nefarious purposes, as by aggressors in warfare, but the fruits of medical research have in general been used beneficently. Then there are also those people who, although in favor of research, pessimistically believe that it is falling into a state of deleterious regimentation or misdirection. There is some ground for such opinion, but it has no application to the work done in Ward 4. The success of research depends on many factors. Foremost of these is the degree of scientific curiosity and imagination possessed by investigators; next in importance is the opportunity for observation and experiment with which they are provided. The masterminds of science have made great discoveries and formulated great concepts alone and with nought but self-made opportunity and facility. Nevertheless the growth of scientific knowledge and theory is accelerated by fertile environment. Abundance of material for study and the means of studying it are elements of such fertility. So too is the juxtaposition of creative intellects. When contiguous, one intellect stimulates another, and the two produce more than they would if separated. Professor Walter B. Cannon aptly called this phenomenon the fecundity of aggregation. In scientific research one idea begets another; one mind fertilizes another; one discovery leads to another. At every step in the process hypotheses must be formed in the attempt to explain the phenomenon observed; these hypotheses

On the Nature of Research

-3

must then be tested further by making more observations, and modified when necessary. J. B. Conant, in his Modern Science and Modern Man (1952), indicates that scientific inquiry began to rise above mere empiricism only when abstract reasoning and experimentation came together. Conant uses Tyndall's definition of empiricism, namely that it is "the observation of facts apart from principles which explain them, and which give the mind an intelligent mastery over them." No one can quarrel with this contention, but the point must be made that, in human experience, observation has to precede abstract thinking. One cannot seek to explain facts until he has acquired them. It is inconceivable that creative thought can take flight from a fact-free vacuum. The growth of scientific understanding of nature follows from the constant endeavor to find meaning in actual experience. In brief, the scientific objective is not merely to discover what happens, but why, and to relate one happening to another. The first step is empiricism, but unless further steps are taken no deepening of understanding will occur. In such a place as Ward 4 the aim is always to go beyond the empiric level. In medicine the manifestations of disease found in patients present to the investigator an ever-expanding array of facts crying for interpretation, and the mass of theory arising from all this enhances also the understanding of the nature of normal biological processes. Thus pathology augments physiology, but without physiology pathology is meaningless. The direction and organization of research follow various patterns, but the ultimate objective, the discovery of new facts and the determination of their broad significance, is the same for all. We may have, for example, what I would call on the one hand "method-centered," and, on the other hand, "object-centered," research, or again we may have utterly free and unrestricted research. In method-centered research, man invents a method or instrument with which he can penetrate new regions never

4-

Ward 4

accessible before and then explores its every possible utility. In object-centered research he becomes aware of an important problem to solve and looks about for the best methods or instruments with which to solve it. In present-day parlance this latter form is called "categorical research," and it has its limitations. In free research a seemingly brilliant investigator is given an opportunity to go whither his scientific imagination and acumen lead him. A good example of method-centered research is that which results from the discovery of the Rontgen rays or x-rays; of object-centered or categorical research, the ever-present and pressing cancer problem. I shall hope to show that much of the work being done in Ward 4 properly belong to "free research." We may also call this type "investigator-centered research." The x-rays discovered back in 1895, quite accidentally but by an observer keen enough to sense their importance, were at once taken up, and in the sixty years since their discovery their nature has been studied and their field of usefulness explored in every conceivable direction. They have been found of value in basic and applied science in such divergent fields as medicine, biology, industry, crystallography, and nuclear physics. In medicine they have been used both in diagnosis and treatment and in the basic research from which diagnosis and treatment are derived. Like many good things, they may do great mischief when misused. The cancer problem, which has long been with us, has lately expanded in importance because, through publicity, education, or whatever you want to call it, the facts concerning the depredations of malignant neoplastic disease have terrified the people, and they are clamoring for its control. Money pours forth from both private and governmental sources, and medical investigators and basic scientists are importuned to stretch every nerve to conquer the dread malady. The same is true of coronary heart

O n the Nature of Research

•5

disease. The great Sloan-Kettering Institute for Cancer Research in New York City is an excellent example of object-centered or categorical research; so too are the National Institutes of Health of the United States Public Health Service at Bethesda, Maryland. In the Sloan-Kettering Progress Report for June 1956, we read that the "Sloan-Kettering Institute, in all of its investigations, has a single and simply defined purpose: the better control and ultimate prevention of cancer in man." The Sloan-Kettering and the National Cancer Institutes and countless other research laboratories are in hot competition to discover the cause, control, and cure of cancer, and this is all to the good insofar as it accelerates the attainment of the goal. Competition, however, also can have ill effects, for example when investigators become more interested in the fame and kudos that come from great discovery than in the happiness that comes from extending knowledge and understanding for their own sake. Briefly, then, we can recognize three orientations to research, which can be identified in these words: 1. Here is an instrument or method — what is it good for? 2. Here is a problem — how shall we solve it? 3. Here is a worker of high promise — let's give him every opportunity to make the optimum use of his talents. This last could well be used as a motto for Ward 4. I have no intention of suggesting that any particular investigative undertaking is a simon-pure example of any of these three approaches. Nearly always each orientation will be present in some measure. But I do believe that usually one of these three predominates. Nor am I prepared to say that any one of the three is altogether preferable to the others. Each has its usefulness. Because it is easier, however, to gain support for categorical than for free research, there is danger that free research will not receive adequate support. It is one of the major purposes of this book to make the point that without some free research there is

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Ward 4

always the chance that certain vital areas will not be explored at all. Great islands of ignorance will be passed by untouched, despite an incoming flood of new knowledge. For an understanding of how medical research peculiarly serves the public interest, it is necessary to identify the place that medicine in its totality occupies in the whole structure of our society. What indeed is medicine as we use the word today? Since the turn of the century a rapid evolution has taken place in what medicine can do, as well as in the meaning and significance of the term. As a direct result of research the medical armamentarium both for the diagnosis and for the treatment of disease has expanded explosively in many directions. The concept of the role of medicine in the social structure has also undergone reinterpretation. The old concept that the function of the physician was merely to heal his patient has given way to the newer one that the ultimate objective of medicine is to abolish disease and keep the people well, and, more than that, positively to promote health. The care of the individual patient remains a prime duty of the medical profession, but medicine in its modern meaning involves social, political, ethical, economic, and educational responsibilities as well. In all of these areas, moreover, research is necessary to progress; education is necessary to development and growth. It has come about, therefore, that in medicine, as in other great structural and functional systems of the social organism, practice, education, and research must be sweetly blended in order that progress can be made as effectively as possible toward the ultimate human good. All this has been called total or great medicine. In the field of medical research the term "clinical" is constantly popping up, and it is important that we know precisely what we mean by it. Sometimes it is used as antithetical to "basic," but actually the terms are by no means mutually exclusive. Basic research in medicine may be clinical, and clinical research may

On the Nature of Research

•7

be basic. The term "clinical" we may take to apply nowadays to anything having to do with patients. The term "basic" research implies research designed to discover fundamental truth without any intent of immediate or direct practical application. It is sometimes inaccurately thought of as research conducted only in laboratories by means of planned experiments on animals or otherwise, but equally basic research can be done on patients, and, conversely, laboratory experiments can have very practical objectives. Scientific research in medicine is for the most part within the areas of such disciplines as chemistry (physical and biological), biology (including genetics), physics, and psychology. The social sciences are necessary too — sociology, economics, and anthropology. The personnel for medical research may be drawn from any of these disciplines. A diminishing fraction are doctors of medicine. Medical training alone is no longer enough to solve the problems that medical practice presents. Of course nowadays an increasing number of M.D.s acquire further education in basic sciences and become basic scientists in their own right as well as being physicians. A collaboration of persons with widely different skills and scientific approaches focused on an object of common interest has become essential. To make things clear to the layman it is necessary, I believe, to point out that medicine, though often so called, is not a science sui generis. Neither is it in my opinion an art, at least in the creative sense, as are the fine arts. Medicine rather is a professional calling with the broad but definite objectives that I have already indicated. Any creative element that it possesses is derived from whatever area of knowledge, including its own practical experience, can contribute to the reaching of its goals. For the most part such areas will be encompassed by the sciences, both natural and social, rather than by the aesthetic and religious sources from which the fine arts get their inspiration.

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Ward 4

In the type of medical research that originates in a hospital ward or clinic (hence clinical in contrast to that arising in a laboratory of physiology or biochemistry) the investigator is less concerned with thinking up questions to put to Nature than with trying to solve the problems that Nature puts to him in the form of patients with maladies crying for understanding. Since patients are required for clinical research, and since hospitals are the places where patients can most easily be found and studied, it is in hospitals that clinical research proceeds. But laboratories are just as necessary to clinical research as hospital wards, and they must be in close proximity to patients; therefore recent decades have seen a great development of research laboratories within the confines of certain hospitals. As will appear, there has been a great ebullition of clinical research in the last half-century. Younger in one sense than basic research in medicine, in another it is older. It is younger in that the development of research laboratories in hospitals, and more particularly the discovery and training of competent clinical investigators and the setting up of formal research programs, is of more recent origin than research in the preclinical departments. It is older in the sense that the great physicians and surgeons of the past by pure bedside acumen acquired some of the most fundamental scientific knowledge of disease that we possess from simple observations that they made upon their patients as they cared for them, or later as they performed operations or postmortem examinations upon their bodies. For example, our knowledge of the function of the adrenal glands began when Addison, a clinician, in 1855 related a certain combination of phenomena that he had observed in his patients to a destructive process in their adrenal glands which he found in postmortems. No notion whatever of the function of these organs existed until they became diseased and produced symptoms, thus calling attention to themselves. But the scientific

On the Nature of Research

>9

development of Addison's discovery has led us to cortisone in our day. Such, then, in outline is the nature and purpose of research in general and of medical research in particular. The research performed in Ward 4 and its adjacent laboratories has of course been of the clinical type. But it also has been basic, that is to say, while it has dealt with patients, the findings in patients have been further explored by experiment. It has risen above the purely empiric level. The ward is truly dedicated to free inquiry in the field of medicine. It provides a soil in which such inquiry can flourish. Use is made of the intellectual gifts of the staff of the great teaching hospital and of the wealth of problems inviting solution that the clinic turns up. Patients flock to such university clinics from near and far, knowing that expert treatment is available there. A place like Ward 4 provides the newest that is known in the care of the sick while it advances the boundaries of knowledge in the field concerned. Experts in many disciplines contribute to such studies. The story of the founding of the ward and of its organization and operation will be told in the next chapter, and the fruits of the labors of the scientists who worked in it will be indicated in subsequent chapters.

I I

Origins and Organization of Ward 4

fVledical research was first put on the Massachusetts General Hospital map in a continuing and professional way by David Linn Edsall when in 1912 he came to Harvard as Jackson Professor of Clinical Medicine and to the Massachusetts General Hospital as chief of one of its two medical services. Before getting into all that, however, it is necessary for the sake of true perspective to mention certain antecedents. The hospital itself was opened in 1821 for the double purpose of providing hospital care for sick people of Boston and for supplying the Harvard Medical School with a place to teach medical students at the bedside. It stood near the site of a military hospital of the War of Independence. It was designed by Charles Bulfinch, and he intended it to endure. It has endured. For many years it was the only building of the hospital, but gradually newer buildings sprang up around it. Many of these have since been scrapped to be replaced by yet newer ones, but the Bulfinch, as it is now called, remains as useful as the newest. I have given you my aesthetic interpretation of its venerable beauty in the frontispiece. Many years ago a very delightful and learned Mexican physician, Dr. Francisco Miranda, was making ward rounds with me. He paused before the Bulfinch. "When was it built?" said he. "In 1821," said I, swelling with pride. "It is nothing," said he; "my hospital in Mexico City was opened in 1526. It was founded by Cortez." Thus was I properly squelched, but only

David

Linn Edsall, M . D .

After a crayon portrait Pietro Pezzati.

made

in

1926

by

Origins and Organization of Ward 4