November 2020. Vol. 41, Issue 7 Discover

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NOVEMBER 2020

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MIND-GUT MYSTERY » Probiotics, bacteria and how they rule the brain p.40 » Autism’s puzzling link p.30

FARMING WITH FALCONS p.60 QUEST FOR A QUANTUM INTERNET p.22

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CONTENTS

Website access code: DSD2011

NOVEMBER 2020 VOL. 41, ISSUE 7

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COVER: LIGHTSPRING/SHUTTERSTOCK. THIS PAGE: M1 INTERACTIVE/SHUTTERSTOCK

Feral chickens rule the roost, but what’s the science behind them?

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The Quest for a Quantum Internet

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Here’s what the entangled wackiness of an ultra-secure web might look like. DAN HURLEY

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Gut Feeling Mounting evidence shows bugs in your digestive system influence the brain. Experts are now testing psychobiotics as mental health remedies. ELIZABETH SVOBODA

Bacteria and the Brain Researchers are finding clues to autistic behavior — in patients’ microbiomes. ADAM PIORE

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Where the Wild Things Crow There’s a man who loves chickens — almost as much as he loves science. He’s probing the depths of evolutionary biology, genetics and the unexpected benefits of feral birds. JOAN MEINERS N OVEM B ER 2 0 2 0 . D I S C OV ER

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CONTENTS

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p. 10

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EDITOR’S NOTE

We’re Exploring That Gut Feeling The science behind the phrase, “You are what you eat.”

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INBOX Our readers chime in about the awesome and the not-so-awesome.

HOT SCIENCE

P. 9

Saving the mangrove tree and the white-cheeked gibbon, the first image from Solar Orbiter’s mission, meat’s role in humans’ diets, the best science books to read now and much more.

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VITAL SIGNS

from field pests and foodborne pathogens.

Beyond the Blues “Everything was fine” for this salesman, but he couldn’t shake his funk. His hormones may have had something to do with it. DOUGLAS G. ADLER

54 HISTORY LESSONS Cracking the 414s In 1983, a group of young adults from Milwaukee became famous for hacking into several high-profile computer systems, introducing the country to the world of cybercrime.

JEFF KRONENFELD

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20 THINGS YOU DIDN’T KNOW ABOUT ...

Wilderness The great outdoors is good for our overall health, but this precious resource is in danger. JONATHON KEATS

ALEX ORLANDO

60 PLANET EARTH Farming With Falcons Trained raptors are protecting our produce

p. 54 4

D I S C O V E R M A G A Z I N E .C O M

CLOCKWISE FROM TOP LEFT: ROLAND IJDEMA/SHUTTERSTOCK; JARMO PIIRONEN/SHUTTERSTOCK; ARDA SAVASCIOGULLARI/SHUTTERSTOCK

C OL UMNS & DEPA R T MEN T S

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EDITOR’S NOTE ®

BY BECKY LANG

M AG A ZINE

BECKY LANG Editor In Chief ELIZABETH M. WEBER Design Director

We’re Exploring That Gut Feeling ou are what you eat. How many of us have heard this phrase, rolled our eyes, said “yeah, yeah,” and moved on? Yet it’s a beautifully simple saying that cuts straight to the point: What you put into your body has a direct effect on your overall health. I was curious about the origin of the saying, which we’ve heard in the U.S. for much of the 20th century. The idiom’s original version first appeared in 1825 in a famed French book about food, by Jean Anthelme Brillat-Savarin. He was a lawyer and judge, as well as a celebrated food writer. His original line, translated into English: “Tell me what you eat and I will tell you what you are.” At that time, Brillat-Savarin was commenting on the connection between food, society and culture — how intertwined food is in our sense of identity. Since then, we’ve managed to boil that down (ha) to a clear connection between a diet of whole food and general health. In other words, put junk in your body, and expect not-sogreat things to happen. But our health goes far beyond just food. As you’ll read in this issue’s cover stories, researchers are discovering just how much power is wielded by the trillions of bacteria that populate our guts. Scientists have found that particular strains of bacteria in our intestines — those that are part of the gut microbiome — can shape how we think, how we feel and how our brains operate. We’re finding more evidence that this gut-brain axis can affect mental health, such as depression and anxiety. The microbiome also may be linked to symptoms of autism. And preliminary studies show that replacing the microbiome with specific bacterial strains affects an animal’s behavior. So perhaps we could tweak that original phrase: Tell me what’s in your gut and I will tell you how you feel.

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EDITORIAL TIMOTHY MEINCH Features Editor ELISA R. NECKAR Production Editor ANNA FUNK Associate Editor ALEX ORLANDO Assistant Editor JENNIFER WALTER Assistant Editor MCLEAN BENNETT Copy Editor HAILEY MCLAUGHLIN Editorial Assistant ALLISON WHITTEN AAAS Mass Media Fellow

Contributing Editors BRIDGET ALEX, TIM FOLGER, JONATHON KEATS, LINDA MARSA, KENNETH MILLER, STEVE NADIS, JULIE REHMEYER, DARLENE CAVALIER (special projects)

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INBOX SPECIAL BONUS

CONTENT FROM

MAGAZIN ASTRONOMY

E

OUT THERE

AWESOME CONNECTIONS

A Universe of Galaxies

of matter — awash in islands The universe is galaxies make up the basic some 100 billionof the cosmos. building blocks

near of Oct. 4, 1923, n the evening astronomer got Los Angeles, a young a motorized began into his car and he Wilson. There, trek up to Mount y that housed arrived at the observator time the largest Telescope, at the the 100-inch Hooker world. er telescope in the fourth-year astronom a was the Hooker Edwin Hubble he enjoyed using at Mount Wilson; was interested in, among other he s because mysteriou Telescope These spiral “nebulae.” the sky, and no things, studying scattered across of gas clouds were In the early days d their nature. the task of one understoo had assigned himself the 1920s, Hubble out. figuring them toward his favorite great telescope He pointed the M31. This spiralin Andromeda, nebula under the eye object: the naked faintly visible to its image shaped cloud is sky. He then captured the a clear, moonless was excited by hic plate. Hubble on a photograp nova, an exploding found a suspected hed M31 again, result. On it, he night, he photograp it under better star. The next the nova and record did indeed hoping to catch The second plate atmospheric stability.little did he know, he also had but legendary in the record the nova, that would become captured a plate to history of science. over, he returned to his office His observing time made an astonSuddenly, Hubble but analyze the catch. not a nova at all, : The nova was ishing realization

O

(“Awe-Struck,” “A Universe of Welcome to the Galaxies” and “Welcome to the Neighborhood Neighborhood,” June 2020) The June 2020 issue’s juxtaposition of “AweStruck” with the two articles on galaxies is A an amazing example, intentional or not, of one article demonstrating the unrelated one before it. You can’t get more awe-inspiring than the universe, and this section on galaxies did a beautiful job of presenting galaxies in a way that puts a lot of stuff into perspective. As I read the articles, I kept thinking back to our small place in all of that. — Joel Amromin, Chatsworth, Calif. 63

OUT THERE

62

SPECIAL BONUS

CONTENT FROM

ASTRONOMY MAGAZIN

E

The Milky Way and Androme da rule over a collection of a motley few dozen galaxies.

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MINING RIGHTS (“Out of Our Mines,” June 2020)

I love Discover! However, I was disturbed by the article “Out of Our Mines.” While I am all for reclaiming those essential elements from tailings, waste dumps, ocean water, et cetera, I am unhappy with the implied attitude that mining the moon, asteroids and the deep sea bottom are all acceptable in the name of progress. It seems especially wrong to me to use up all Earth’s

resources and then go on to deplete off-planet resources. — Elizabeth Rumley James, Marshfield, Mo.

CONTEXT, PLEASE (“History of Pandemics,” June 2020)

Your infographic in The Crux summarized various pandemics across the ages — great article, with wonderful graphics to convey the information clearly. But the death counts were given in numbers; this information would be even more useful if given

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as a percentage of the global population at the time of the pandemic, because this is the figure that allows the reader to understand the true impact that the pandemic had on society. Fifty million deaths today (less than 1 percent of the world’s population) is very different than 50 million deaths 100 years ago (2.7 percent of the population) or 50 million deaths in 1340 (12 percent). — Carlin Otto, Palo Alto, Calif.

CORRECTIONS

• In our May 2020 story “It’s Not That Easy Being Green,” readers were urged to

TIGERBALM.COM

keep plastic bags, which can clog machinery, out of single-stream recycling bins. A few readers reached out to inform us that some locales do accept plastic bags for recycling, usually when bagged together. As always, check your local regulations to be sure you’re recycling everything you can — and nothing more.

• In “When the Fever Doesn’t Break,” from the July/August 2020 issue, we

NEW!

indicated that Takeda’s new dengue vaccine, TAK-003, was based on an existing yellow fever vaccine. This is incorrect; TAK-003 is built on a dengue serotype that’s common to all four serotypes. .

Deadly S.N.A.F.U.,

Marine Corps Base Camp Lejeune, N.C. From the acclaimed investigative author who brought you the non-fiction Railroad Collisions, A Deadly Story of Mismanaged Risk, George Swimmer returns with a systematic playbook of understanding the exposure to water contamination faced by about one million Marines, Sailors, their dependents and others who were stationed, lived or worked at Camp Lejeune. As a Marine veteran, Swimmer’s evident passion for and knowledge about the subject shine through. He does an excellent job of making military reports and unfamiliar terms understandable of novices. A thoroughly researched investigative journey, Swimmer’s non-fiction Deadly S.N.A.F.U., Marine Corp Base Camp Lejeune, N.C. spells out the irrefutable scientific and medical evidence that connects the dots between the decades-long exposure to water contaminants during military service at Camp Lejeune and the development of certain diseases later on. This is an impassioned indictment of the United States Marine Corps for its decades of mismanagement that caused extreme quantities of toxic pollutants to enter the potable water supply, then followed by years of lies, coverups, combined with an inept and infective notification process experienced by 100,000’s of Marines and others. Yet, Swimmer prevails as he focuses on the human spirit that connects all Marines. Semper Fi!

Amazon.com/author/georgeswimmer Paperback $14.99, Kindle eBook $3.99

HOT SCIENCE TH E L AT E ST N E WS A N D NOT E S GIBBON GUARDIANS • SEEING SUNSPOTS • WANDERING STARS • MEAT-EATERS • BOOK REVIEWS

MAN VS. MANGROVES

These trees love beachfront views. Mangroves live in the salty shallow waters between land and sea across thousands of miles of the world’s coastlines — at least, for now. High carbon emissions are causing sea levels to rise, and soon mangroves won’t be able to stay above water. Earlier this year, researchers estimated that once the annual rate of sea level rise reaches just a quarter of an inch, mangroves will begin to drown. Without changes to emissions, these forests of the ocean will be in grave danger by 2050. And if they lose their homes, they may not be the only ones. The tropical trees protect coastal land and the people who live there from natural disasters like tsunamis, by reducing storm surges and flooding. — ALLISON WHITTEN; IMAGE BY DAMSEA/SHUTTERSTOCK

N OVEM B ER 2 02 0 . D I S C OV ER

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HOT SCIENCE

DESPITE THREATS FROM POACHERS, A CRITICALLY ENDANGERED SPECIES OF GIBBON RECENTLY DOUBLED ITS NUMBERS.

SPECIES WATCH

BARELY 10 YEARS AGO,

the plight of the northern white-cheeked gibbon looked dire. The gibbon’s territory had once spanned old-growth rainforests across China, Laos and Vietnam, but decades of habitat loss and hunting had left only a few dozen isolated communities. By 2013, the gibbon was declared effectively extinct in China — and today, no one knows how many are left in Laos. A few secluded reserves in Vietnam now appear to be the

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gibbon’s holdout. Just 127 animals remained in 2011 in one of the country’s last strongholds for the species — Xuan Lien Nature Reserve and the adjacent forests — according to La Quang Trung, a primate expert with the Center for Nature Conservation and Development in Hanoi. But things might be turning around for the gibbon. Since last year, La and his team have been revisiting Xuan Lien and the surrounding areas and have found that gibbon numbers have almost doubled. The researchers

count the primates by listening for their calls; since they’re territorial and rarely move out of their home turf, La says, it’s a highly accurate way to estimate their numbers. The researchers attribute this dramatic increase to the efforts of local villagers: Xuan Lien hired people living around the reserve to patrol the forest for poachers and to educate their neighbors on the importance of gibbon conservation. However, not all the news from Xuan Lien is good.

Poachers are still active in the area, motivated by the ongoing market for food, traditional medicines and illegal pets. During a field trip in December, the team came across five illegal wildlife-hunting camps where the poachers were selling their catch to restaurants. Forest rangers who had accompanied the researchers chased away the poachers and razed their camps, but it was a stark reminder that the gibbons’ future relies on their continued protection. — TROY KIPPEN

ROLAND IJDEMA/SHUTTERSTOCK

White-Cheeked Gibbon

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HOT SCIENCE

SNAPSHOT

SEEING SUNSPOTS Spurts of hot gas (seen in bright yellow, above) highlight the sun’s active areas — basically, the parts with particularly strong magnetic fields. Photographed by NASA’s Solar Dynamics Observatory, these areas of magnetic activity are involved in the emission of solar wind, streams of charged particles flowing from the sun, as well as more extreme plasma bursts called coronal mass ejections. When these particles, sent into space at speeds up to 1,800 miles per second, collide with Earth’s atmosphere, they can manifest as the dazzling aurora borealis, also known as the Northern Lights. — ALEX ORLANDO; IMAGE BY NASA SOLAR DYNAMICS OBSERVATORY/AIA

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Un o 13 pen 8 Y ed ea fo rs! r

Discovered! Unopened Bag of 138-Year-Old Morgan Silver Dollars Coin experts amazed by “Incredible Opportunity” The Morgan Silver Dollar is the most popular and iconic vintage U.S. coin. They were the Silver Dollars of the Wild West, going on countless untold adventures in dusty saddlebags across the nation. Finding a secret hoard of Morgans doesn’t happen often—and when it does, it’s a big deal. How big? Here’s numismatist, author and consultant to the Smithsonian® Jeff Garrett: “It’s very rare to find large quantities of Morgan Silver Dollars, especially in bags that have been sealed... to find several thousand Morgan Silver Dollars that are from the U.S. Treasury Hoards, still unopened, is really an incredible opportunity.” -Jeff Garrett

3 Historic Morgan Silver Dollars 3 Minted in New Orleans 3 Struck and bagged in 1882 3 Unopened for 138 years 3 26.73 grams of 90% fine silver 3 Hefty 38.1 mm diameter 3C ertified Brilliant Uncirculated by NGC 3C ertified “Great Southern Treasury Hoard” pedigree 3 Limit five coins per household Actual size is 38.1 mm

the southern gentleman by giving the coins the pedigree of the “Great Southern Treasury Hoard.”

But where did this unique hoard come from? Read on...

These gorgeous 1882-O Morgans are as bright and new as the day they were struck and bagged 138 years ago. Coins are graded on a 70-point scale, with those graded at least Mint State-60 (MS60) often referred to as “Brilliant Uncirculated” or BU. Of all 1882-O Morgans struck, LESS THAN 1% have earned a Mint State grade. This makes these unopened bags of 1882-O Morgans extremely rare, certified as being in BU condition—nearly unheard of for coins 138 years old.

Morgans from the New Orleans Mint

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In 1859, Nevada’s Comstock Lode was discovered, and soon its rich silver ore made its way across the nation, including to the fabled New Orleans Mint, the only U.S. Mint branch to have served under the U.S. government, the State of Louisiana and the Confederacy. In 1882, some of that silver was struck into Morgan Silver Dollars, each featuring the iconic “O” mint mark of the New Orleans Mint. Employees then placed the freshly struck coins into canvas bags...

The U.S. Treasury Hoard Fast-forward nearly 80 years. In the 1960s, the U.S. government opened its vaults and revealed a massive store of Morgan Silver Dollars—including full, unopened bags of “fresh” 1882-O Morgan Silver Dollars. A number of bags were secured by a child of the Great Depression—a southern gentleman whose upbringing showed him the value of hard assets like silver. He stashed the unopened bags of “fresh” Morgans away, and there they stayed...

The Great Southern Treasury Hoard That is, until another 50 years later, when the man’s family finally decided to sell the coins—still in their unopened bags—which we secured, bag and all! We submitted the coins to respected third-party grading service Numismatic Guaranty Corporation (NGC), and they agreed to honor

Regular 1882-O Morgans sell elsewhere for as much as $133, and that’s without the original brilliant shine these “fresh” 138-yearold coins have, without their special NGC hoard designation, and without their ability to tell their full, complete story from the Comstock Lode all the way to your collection. Given the limited quantity of coins available from this historic hoard, we must set a strict limit of five coins per household. Call quickly to secure yours today as supplies are sure to sell out quickly! 1882-O Morgan Silver Dollar NGC Certified BU from the Great Southern Treasury Hoard — $99 ea.

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HOT SCIENCE

THE TOP STORIES FROM DISCOVERMAGAZINE.COM

WEB REPORT

When astronomers spotted Scholz’s Star (seen at right with its binary brown dwarf), it was moving away at a breathtaking pace — and its path showed that it had flown right by us.

The Wandering Stars That Pass by Our Solar System EVERY 50,000 years or so,

a nomadic star passes near our solar system. Most brush by without incident. But, every once in a while, one comes a bit closer to home. The most famous of these stellar interlopers is called Scholz’s Star. This small binary star system (two stars in orbit together) was first spotted in 2013. Its orbital path indicates that, about 70,000 years ago, it passed through the Oort Cloud, the extended sphere of icy bodies that surrounds our solar system. We now know that these kinds of encounters happen far more often than once expected, thanks to a European

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Space Agency spacecraft called Gaia. Gaia was built to map the precise locations and movements of over a billion stars, and has alerted astronomers to hundreds of close encounters past and future. A few of these will be close enough to actually dislodge a significant amount of debris from the Oort Cloud, potentially leading to a cosmic bombardment of Earth. Most notable is the massive star Gliese 710, which will steamroll through the outer solar system 1.3 million years from now. It could pass within 17,000 astronomical units (1 AU is equal to the average Earthsun distance of 93 million miles) of

Earth, well within the outer edge of the Oort Cloud. At two-thirds the mass of the sun, Gliese 710 is much larger than Scholz’s Star, which is just 15 percent the mass of the sun. This means Gliese 710’s hulking gravity could potentially wreak havoc on the orbits of icy bodies in the Oort Cloud. And while Scholz’s Star was so tiny it would have been invisible to the naked eye — unless it flared — Gliese 710 is larger than our current closest neighbor, Proxima Centauri. So when Gliese 710 reaches its closest point to Earth, it will burn as a brilliant orange orb that will outshine every other star in our night sky. — ERIC BETZ

MICHAEL OSADCIW/UNIVERSITY OF ROCHESTER

OUR SUN HAS HAD ENCOUNTERS WITH OTHER STARS IN THE PAST, AND IT’S DUE FOR A DANGEROUSLY CLOSE ONE IN THE NOT-SO-DISTANT FUTURE.

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DO WE NEED TO EAT MEAT?

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ALTHOUGH HUMANS evolved to eat meat, it’s not essential to the human diet, says Ginger Hultin, a Seattle-based registered dietitian nutritionist and spokesperson for the Academy of Nutrition and Dietetics. The only vitamin in the human diet that must come from animal sources is B12 — but this requirement can be met with a supplement. And, in case you’re wondering, protein deficiencies are uncommon in America, even among vegetarians, says Hultin. Undeniably, many people cannot imagine Thanksgiving without turkey. And a healthy diet can certainly include animal protein. But current surveys show we’re leaving little room for much else on our plates. Annual red meat and poultry consumption in America has reached over 200 pounds per person on average — an amount that has increased dramatically since the 1960s. Only 1 in 10 American adults gets enough fruits and vegetables in their daily diets, the Centers for Disease Control and Prevention has found. The recommendation is 1 to 2 cups of fruit and 1 to 3 cups of vegetables per day. A healthier diet is plant-based. “These are not diets where you just eat salad, for example. If a person is unsatisfied on a plant-based diet, they’re missing something,” said Hultin. “It’s important to know how to meet your needs on a plant-based diet, just like you should on an omnivorous diet.” — MEGAN SCHMIDT

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WHAT WE’RE READING Breath From Salt: A Deadly Genetic Disease, a New Era in Science, and the Patients and Families Who Changed Medicine Forever By Bijal P. Trivedi WHAT STARTED in 2012 as research for a single article for Discover led science journalist Trivedi down a rabbit hole of information about the ongoing fight against cystic fibrosis (CF). At the time, the FDA had approved a new drug to treat the life-threatening condition, which fills the lungs with fluid and hinders the pancreas’ ability to help with digestion. Roughly 80 years after scientists first identified the condition, it remains incurable. In Breath From Salt, Trivedi starts with people — specifically, the O’Donnell family, who lost their 12-year-old son, Joey, to CF. She weaves the story of the Joey Fund, the O’Donnells’ nonprofit that has raised more than $250 million for cystic fibrosis research, into a sensitive and informative account of how our understanding of CF has transformed, and how it still impacts families today. As a reader who knew very little about CF, I was gripped by Trivedi’s curiosity and attention to detail. Anecdotes and explanations about the condition’s medical history were illuminating and easy to follow. And reading about the O’Donnells made me ache for their loss, and long to see where this ongoing quest to cure CF will go next. — JENNIFER WALTER

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More Pages to Turn Fossil Men: The Quest for the Oldest Skeleton and the Origins of Humankind By Kermit Pattison

To the outside observer, science — in particular, the science of human origins — might seem like a methodical, unbiased practice. But even the most significant findings in the fossil record were fueled by personal and political incentives. Journalist Pattison details the stories of the people and places involved in expeditions that led to the discovery of Ardi, thought to be the oldest known skeleton of a human ancestor found to date. Equal parts biography and adventure novel, Pattison illustrates the colorful characters — flaws and all — whose research has shaped our origin story as we know it today.

Seven and a Half Lessons About the Brain By Lisa Feldman Barrett

You might think you know your brain, but faulty science and popular myths have left us with a misunderstanding of our most powerful organ. Neuroscientist Barrett takes readers on a journey from the first earthly creatures, through the musings of ancient philosophers, and to present-day neuroscience. Her lens reveals how we grew to think, and debunks the fallacies — such as the famous idea of being left- or right-brained — that we’ve embraced in popular culture.

What to Expect When You’re Expecting Robots: The Future of Human-Robot Collaboration By Laura Major & Julie Shah

Are robots out to steal our jobs and information and make human knowledge obsolete? Probably not, argue Major and Shah. Rather than world domination, future bots will struggle to navigate the world that humans have built. They will likely require our expertise to help them interact in public and become effective communicators. The two tech experts describe a future where humans and machines work together to make progress, and where an increasingly bot-aided society isn’t something to fear.

Kill Shot: A Shadow Industry, a Deadly Disease By Jason Dearen

When a string of strange fungal infections popped up in the brains of otherwise healthy patients in 2012, investigators blow the roof off of a contamination outbreak caused by a dangerous, yet legal, pharmaceutical operation. Journalist Dearen documents the loopholes, the lack of oversight from regulatory boards, and the profit-hungry characters who caused over 100 victims to succumb to a swift and puzzling death at the hands of unknowing doctors. This unnerving true tale is a crowd-pleaser for fans of true crime and medical mysteries. — J.W.

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VITAL SIGNS BY DOUGLAS G. ADLER

‘EVERYTHING WAS FINE’ FOR THIS SALESMAN, BUT HE COULDN’T SHAKE HIS FUNK. HIS HORMONES MAY HAVE HAD SOMETHING TO DO WITH IT. eggie, a 30-year-old pharmaceutical salesman, appeared in my office one afternoon to follow up on his cholesterol levels and other routine bloodwork. While the tests were all normal, I noticed he seemed to be in a bit of a funk, for lack of a more scientific term. Ordinarily an upbeat and positive person, he seemed to be down in the dumps. When I asked if anything was going on at home or at work, he said everything was fine. Still, he couldn’t deny that he did not feel like himself. “It’s hard to describe,” he told me. “Everything is fine, and I should feel fine, but I don’t. My marriage is fine, my kids are doing well in school, and I have money in the bank.” Nonetheless, Reggie told me that sometimes he got confused for no reason and he felt tired all the time. Plus, his muscles and joints ached. “It all came on out of nowhere a few weeks ago and I can’t seem to shake it,” he continued. “At first, I thought I had the flu, but I don’t.” I immediately thought he may have thyroid troubles. The thyroid gland, located in the neck, produces a hormone known

R

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HORMONES: HELPFUL AND HARMFUL Finasteride is a 5-alpha reductase inhibitor; these types of drugs can affect the way hormones are processed and transformed by our bodies. The male

KELLIE JAEGER/DISCOVER

Beyond the Blues

When people don’t experience pleasure, it is known as anhedonia — often a sign of depression. But Reggie insisted he didn’t feel sad in the usual sense of the word.

as thyroxine, which has a profound effect on a person’s overall metabolic rate. When the thyroid gland produces too little thyroxine — a condition known as hypothyroidism — patients often describe a similar set of symptoms. Confident that I had nailed the diagnosis, I ordered blood tests to check his thyroid. A few days later, the results came back, and I was stunned to see they were perfectly normal. Scratching my head, I asked Reggie to return to my clinic for more tests. He told me his symptoms had not improved. He’d had an episode of what he called “brain fog” on an important conference call for work, performed poorly and been deeply embarrassed. I asked about any other symptoms he hadn’t mentioned before. He told me that “nothing was fun anymore.” Movies and TV shows that he liked now bored him, and music that he usually liked listening to sounded grating to his ears. When people don’t experience pleasure, it is known as anhedonia — often a sign of depression. But Reggie insisted he didn’t feel sad in the usual sense of the word. “I don’t feel sad or depressed,” he told me. “I just don’t feel anything at all.” Lastly, in hushed tones, Reggie said he was having trouble getting and maintaining erections, something he had never experienced before. “I feel like an 80-year-old man in a 30-year-old body,” he lamented. Changes in mood and sex drive can sometimes suggest a neurologic problem. But Reggie’s neurologic exam was normal. To be safe, I ordered a CT scan of his brain; it was also perfectly normal. One evening, I was alone in my office and thinking about possible side effects. I went through his list of medications, one by one, and saw nothing worrisome until I noticed something: A few months ago, Reggie had started taking finasteride.

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VITAL SIGNS

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place: If you read online that a drug can help regrow hair but can also cause impotence, you may be more likely to subjectively feel like you’re having a sexual side effect. Regardless, the symptoms Reggie was describing to me sounded like they could be attributed to the adverse side effects of finasteride.

A TOUGH CHOICE

The fact that the most common side effects from the drug are sexual has scared many patients off from even trying it to treat hair loss.

I reviewed all of this with Reggie at his next visit. He looked skeptical. I then suggested he stop taking his finasteride. He immediately refused. “No way,” he angrily told me. “Forget about it. Seeing all of that hair in my hands when I shampooed each morning was the worst. It was all I could think about for the rest of the day. I’ve lost so much hair in the past year, and now I’m finally starting to get it back.” I understood where he was coming from. I had experienced more than a little hair loss myself and knew how upsetting it could be. Still, I was worried about him. I suggested he think on it, read about finasteride’s side effects and PFS, and see me in a week. He agreed, but he left my office that day more upset than when he arrived. Reggie returned the following week. He had done a lot of research about finasteride, even going so far as joining an online message board to discuss his symptoms. “I have to admit,” he said, “a lot of those other guys on the message board sounded just like me.” With a sigh, he told me he would try stopping his finasteride for a while. Two weeks later, Reggie came back to see me. His mood was better, he had more energy, his aches had faded, and his libido was returning, though admittedly not as quickly as he would have liked. It seemed the finasteride was the culprit. Still worried about balding, Reggie had started taking minoxidil, the other FDA-approved treatment for hair loss. It wasn’t as strong of a hair loss drug as finasteride, but at least it was something. Weighing the pros and cons of finasteride, he decided he had more to lose by taking the drug than he stood to gain — even on top of his head. D Douglas G. Adler is a gastroenterologist and professor at the University of Utah School of Medicine. The cases described in Vital Signs are real, but names and certain details have been changed.

KELLIE JAEGER/DISCOVER

sex hormone testosterone helps men build muscle and have a healthy sex drive, but it also produces hair loss in genetically susceptible individuals. Finasteride blocks the conversion of testosterone to its more potent cousin, dihydrotestosterone (DHT). High levels of DHT can cause hair loss, so drugs that halt that hormone’s production can help combat it. Finasteride was first marketed over 20 years ago as a treatment for urinary symptoms in men with enlarged prostate glands. Since then, the drug has also found use as a treatment for male pattern baldness. Many men who are losing their hair can slow — or even reverse — the process by taking a much lower dose of finasteride than is used to treat an enlarged prostate. Reggie had obtained his finasteride from an online pharmacy after he’d noticed his hair was falling out and became worried about his appearance. Since taking the drug, his hair loss had largely stopped. In addition, he told me that he was definitely starting to see some new hair growth — a welcome sight. But finasteride, while highly effective, is also a controversial drug. Not long after it was released commercially, some users began to complain of a plethora of symptoms not unlike Reggie’s. Patients could develop neurologic, sexual, emotional and musculoskeletal symptoms that, strangely, sometimes persisted for months or even years after stopping the drug. When symptoms continue even after stopping finasteride, patients are referred to as having post-finasteride syndrome, or PFS. The fact that the most common side effects from the drug are sexual — and that these could be longlasting — has scared many patients off from even trying it to treat hair loss. The medical literature on finasteride is also far from clear; some studies of finasteride have documented these side effects, but others have not. Plus, patients who have good results on finasteride swear by it in online hair loss forums, while those who feel it has harmed them deride it as poison on those same sites. Most men who take finasteride have no side effects at all. And those who do develop issues usually see them resolve after stopping the drug. Still, some who take finasteride do experience longlasting side effects. In part, this may have something to do with anxiety about using the drug in the first

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THE QUEST FOR A

BY DAN HURLEY 22

D IS C O V E R M A G A Z I N E .C O M

HERE’S WHAT THE ENTANGLED WACKINESS OF AN ULTRA-SECURE WEB MIGHT LOOK LIKE.

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PREVIOUS SPREAD: JURIK PETER/SHUTTERSTOCK

objects can exist in two or more states at the same time, called superpositions; they can interact with each other instantly over long distances; they can flash in and out of existence. Scientists like Figueroa want to harness that bizarre behavior and turn it into a functioning, new-age internet — one, they say, that will be ironclad for sending secure messages, impervious to hacking. Already, Figueroa says his group has transmitted what he called “polarization states” between the Stony Brook and Brookhaven campuses using fiber infrastructure, adding up to 85 miles. Kerstin Kleese van Dam, director of Brookhaven Lab’s Computational Science Initiative, says it is “one of the largest quantum networks in the world, and the longest in the United States.” Next, Figueroa hopes to teleport his quantum-based messages through the air, across Long Island Sound, to Yale University in Connecticut. Then he wants to go 50 miles east, using existing fiber-optic cables to connect with Long Island and Manhattan. Kleese Van Dam says that although other groups in Europe and China have more funding and have been Laboratory, Eden Figueroa is one of the world’s pioneering gardeners working much longer planting the seeds of a quantum internet. Capable of sending on the technology, in enormous amounts of data over vast distances, it would work not the U.S. “[Figueroa] is just faster than the current internet but faster than the speed of light leading when it comes to having the knowledge — instantaneously, in fact, like the teleportation of Mr. Spock and and the equipment Captain Kirk in Star Trek. necessary to put together a quantum network in the next year or two.” Sitting in Brookhaven’s light-filled cafeteria, his David Awschalom, a legend in the field who is a shoulder-length black hair fighting to free itself from the professor of spintronics and quantum information at clutches of a ponytail, Figueroa — a Mexico native who is the University of Chicago’s Pritzker School of Molecular an associate professor at Stony Brook University — tries Engineering and director of the Chicago Quantum to explain how it will work. He grabs hold of two plastic Exchange, calls Figueroa’s work “a fantastic project being coffee cup lids, a saltshaker, a pepper shaker and a small done very thoughtfully and very well. I’m always cautious cup of water, and begins moving them around on the about saying something is the biggest or fastest,” he says. lunch table like a magician with cards. “It’s a worldwide effort right now in building prototype “I’m going to have a detector here and a detector here,” quantum networks as the next step toward building he says, pointing to the two lids. “Now there are many a quantum internet.” Other efforts to build quantum possibilities. Either those two go in here” — he points to networks, he says, are underway in Japan, the U.K., the the saltshaker — “or the two go in there,” nodding at the Netherlands and China — not to mention his own group’s cup of water. “And then depending on what happened project in Chicago. there, that will be the state,” he says, holding up the black U.S. efforts have lately been given a boost by the U.S. pepper shaker, “that I’m preparing here.” Department of Energy’s announcement in January that it Got that? Me neither. But don’t worry. Only a few hunwould spend as much as $625 million to fund two to five dred or so physicists in the U.S., Europe and China really quantum research centers. The move is part of the U.S. comprehend how to exploit some of the weirdest, most National Quantum Initiative signed into law by President far-out aspects of quantum physics. In this strange arena, Donald Trump on Dec. 21, 2018.

Eden Figueroa (right) has worked for several years on technology that would extend the distance that quantum particles can travel and still be entangled. Here Figueroa and researchers Mehdi Namazi (left) and Mael Flament (center), part of his team at Stony Brook University back in 2018, stand behind one prototype of technology that’s impervious to hacking.

But what, really, is this thing called a quantum internet? How does it work? Figueroa, enraptured by his vision, told me of his plan with contagious enthusiasm, laughing sometimes as if it were all so simple that a child (or even an English major) could understand it. Not wanting to disappoint, I nodded my head and pretended that I knew what the hell he was talking about. And, after spending two days with Figueroa last summer, following him around the campus of Brookhaven and the nearby Stony Brook, getting a firsthand look at his futuristic equipment, talking with other physicists around the world, reading a few books and perusing dozens of articles and studies, I began to kind of, sort of, get it. Not in all its unsettling depths, but in the general way that I understand how an internal-combustion engine goes vroom or why a toilet bowl flushes. And you can, too.

STONY BROOK UNIVERSITY

UNTANGLING ENTANGLEMENT Leading me to the back room of his laboratory at Stony Brook, where he heads the quantum information technology group, Figueroa shows me a large table covered with a labyrinth of tiny mirrors, lasers and electronics. “This is where we create these photons that carry superpositions,” he says, “that then we can send into the fiber. OK? It’s very simple.” Right. Curiously, all the implications of the quantum internet can be traced back to an experiment so straightforward you can do it in your living room. Called the double slit

experiment, it was first performed more than 200 years ago by British polymath Thomas Young. When shining a beam of light at a flat panel of material cut with two slits side-by-side, Young saw that the light passing through the slits created an interference pattern of dark and bright bands on a screen behind the panel. Only waves — light waves — emanating from the two slits could make such a pattern. Young concluded that Isaac Newton, who published a particle theory of light in 1704, was wrong. Light came in waves, CURIOUSLY, not in particles. ALL THE But by the early 20th century, scientists IMPLICATIONS had confirmed that light also came in OF THE particles — what physicist Gilbert N. QUANTUM Lewis called photons, or quanta. And INTERNET CAN incredibly, researchers found that even BE TRACED when single photons of light were sent flyBACK TO AN ing one at a time at the double-slit panel, EXPERIMENT the interference pattern still appeared on SO STRAIGHTthe other side. Each particle, they realized, FORWARD YOU was also a wave, spread out like a schmear CAN DO IT IN of cream cheese, and so traversed both YOUR LIVING slits simultaneously, thereby interfering ROOM. with ... itself on the other side. Think on that. A single particle of light was in two places at once. That meant tickling a particle in one place should make it giggle in the other. Observing it in one place should reveal something about its twin.

“

N OVEM B ER 2 0 2 0 . D I S C OV ER

25

Erwin Schrödinger called the phenomenon entanglement — the very thing that Figueroa and other researchers are harnessing now to send information. Simply put, adding information, such as a message or data, to a particle in one location will make the data appear at the other location: the essence of teleportation. But how, I ask Figueroa, do all these wild ideas work in practice, with nuts and bolts and physical devices? “Let me show you where the magic happens,” he says.

THANKS FOR THE QUANTUM MEMORIES “It’s just equipment and optics,” he tells me, pointing to an array of lasers and mirrors configured on a large table. “This is what people call Lego for adults.” On one end, a laser aims high-energy blue photons at a crystal, which

breaks each one into a pair of lower-energy red photons; each of the two resulting red photons is now entangled with the other. Figueroa points out the path the photons take from mirror to mirror. “They do boop, boop, boop, boop, boop-boop-boop-boop. This is why we have this beautiful system. This is working, actually. This is beautiful,” he says. Once entangled, one red photon is sent a short distance to a detector in Figueroa’s lab down the hall, while the other can be sent a dozen miles away to a detector at the Brookhaven National Lab. The differing distances would cause the two photons’ arrival times to fall slightly out of sync, which would disrupt their entanglement. To prevent that, Figueroa had to find a way to coordinate the arrival times of each down to the sub-nanosecond. But how? Other quantum labs freeze their stay-at-home photons to near-absolute zero as a way of tapping the brakes. Figueroa’s innovation, by contrast, works at room temperature: an inch-long glass tube containing a fog of trillions of rubidium atoms. That first morning when I visit Figueroa’s lab, he puts one of these tubes in my hand. “What is it?” I ask him. He smiles and says, “A quantum memory.” Back when he was pursuing his doctorate at the University of Konstanz in Germany, Figueroa tells me, he had asked his professor if it would be possible to build a system that would work at room temperature without costly, complex freezers. “I don’t think so,” he was told. “But prove me wrong.” So, he did. By bouncing photons off a series of carefully placed mirrors and bombarding a mist of rubidium atoms with a network of lasers, Figueroa discovered that he could tune the wavelengths of entangled photons to broadcast a signal that electrons in the rubidium fog could receive. Voila! The entangled state of the photon is transferred, momentarily, into the entire cloud of atoms. A fraction of a nanosecond later, the entangled photon moves on, arriving at the detector at the same moment as its twin. Incredibly, since completing his doctorate in 2012,

A DIY QUANTUM INTERNET IN 3 EASY STEPS

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into two lower-energy red photons. Now those photons are permanently entangled. Kind of like Brad Pitt and Angelina Jolie, entangled till the end of time as Brangelina. Now go ahead and send one of those photons to your pal, Steven Spielberg, and keep the other one for yourself. Which one did you send,

Brad or Angelina? Until Spielberg looks through his peephole to see who’s on the other side of the door, you both have a random, 50-50 chance of seeing one or the other. In the quantum world, everything exists in a statistical blur. But that’s OK, because Brad and Angelina are just your conduit for

sending information from one to the other.

STEP 2

To send a meaningful message from Brad to Angelina, you need a third photon. Let’s call this one Jennifer Aniston. Put Jennifer through a polarizer — like the polarized lenses used

SAKKMESTERKE/SHUTTERSTOCK

STEP 1

To build a quantum internet, you begin by entangling two photons so they behave like a single unit, no matter how far they might be separated. Easy peasy. To do this, take one high-energy blue photon, generated by a laser, and put it through a crystal that splits the photon

TESTING ENTANGLEMENT Particle strikes detector B

Particle strikes detector A

Vertically polarized

Light source

1

Researchers test entanglement with light particles of different polarizations, meaning they vibrate in different directions. Vertically polarized light particles can pass through a vertical slit to strike a detector on the other side.

3

A pair of particles polarized the same way but not entangled have predictable behavior. Rotate one of the slits, and a particle will sometimes pass through it, sometimes bounce off. How often pairs set off the same detector can be calculated based on how much the slit is rotated.

Horizontally polarized

2

Horizontally polarized light cannot pass through a vertical slit. Instead, it bounces off and strikes a different detector.

Dual light source

Particle will sometimes hit A, other times B

4

Quantum physics changes the odds. It allows for pairs of particles that have the same polarization but don’t decide until after they pass through their slits. These particles cheat, and set off the same detector more often.

Entangled particles can cheat

ROEN KELLY/DISCOVER

Polarization not yet determined

in sunglasses — to set her atomic pole to a particular position on the vertical and horizontal axes. This gives you a quantum bit, or qubit, which can be a 0 or 1 at the same time. Similar to the 0s and 1s of digital data, qubits can be strung together to encode any message you want to send — say, the script for a new movie.

STEP 3

You’re almost there! Now you need to entangle the qubit called Jennifer with the photon called Brad, who you’ve been hanging onto ever since you sent Angelina to Spielberg. To do that, put both Jennifer and Brad into a beam splitter. When you do, Jennifer becomes entangled

not only with Brad, but also with Angelina, by virtue of the preexisting Brangelina connection. All three of them are entangled with each other. Now get this: Because photons are so sensitive, the very act of measuring them (to be sure that they are in fact entangled) destroys them. So, both Brad and Jennifer vanish in your lab. But wait:

Spielberg still has Angelina. And Angelina is still entangled with the information that Jennifer had. This means — ta da! — the information Jennifer was carrying has now been teleported, instantaneously, to Spielberg’s photon. You did it! Now you can only hope Spielberg remembers to thank you at the Oscars. — D.H. N OVEM B ER 2 0 2 0 . D IS C OVER

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These substations will shoot one photon of the pair toward each other and the other toward the closest of the two labs. When one photon from each of the two pairs meets at the 50-mile mark, they will become entangled, automatically entangling the other remaining photons in the distant laboratories. Once this entanglement has been shared, the information Figueroa wanted to send can be teleported to the lab 100 miles away, overcoming the barrier. “You see?” he says with charming enthusiasm. “Easy.”

ENTANGLEMENT SWAPPING Another problem remains, however — one that neither Figueroa nor Katramatos (nor any other quantum engineer in the world) has fully figured out so far: how to successfully transmit quantum-entangled photons via fiber-optic cables past a barrier that appears around the 60-mile mark. Beyond it, photons unintentionally interact with the cable, its housing or even sunlight from above-ground, thereby destroying its entanglement. The proposed solution, Figueroa explains, is something called “entangleAND WHAT ment swapping.” And quantum engineers ABOUT around the world are competing to apply the concept to a working prototype. TELEPORTING “The idea has by now been around for NOT JUST 20 years,” says Mikhail Lukin, a leading INFORMATION, quantum theoretician and experimentalNOT JUST ist at Harvard University. “Up to now, MESSAGES, no one has succeeded in building one BUT ALSO capable of being used in a practical PARTICLES, application. As far as I understand, that’s MOLECULES, what [Figueroa]’s group is trying to do.” CELLS OR To explain his plan, Figueroa leads me CAPTAIN KIRK? into a small meeting room, where he has it all mapped out on a whiteboard. “Let me show you something really cool,” he says. Instead of creating only one pair of entangled photons and trying to send it to a lab 100 miles away, he explains, a second set of entangled pairs are created in two different substations located at the 25-mile and 75-mile marks.

“

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THE QUANTUM FUTURE And what about teleporting not just information, not just messages, but also particles, molecules, cells or Captain Kirk? When the first experimental demonstration of entanglement was reported in December 1997, IBM physicist Charles H. Bennett told The New York Times: “It would be utterly infeasible to do it even on something as small as a bacterium.” (Bennett, it should be pointed out, had coined the term quantum teleportation four years earlier, so you would think he would be correct.) But 21 years later, in the fall of 2018, Oxford University researchers reported exactly what Bennett had said was “utterly infeasible”: the entanglement of a living bacterium with a photon of light. Not all physicists were persuaded by the findings, however, based as they were on the Oxford team’s analysis of another group’s experiment. But then, nobody knows how far the quantum revolution will go — certainly not Figueroa. “Many of the things these devices will do, we are still trying to figure it out,” he tells me. “At the moment, we are just trying to create technology that works. The really far reaches of what is possible are still to be discovered.” Before leaving him, I ask Figueroa how his friends, family and neighbors try to understand his cryptic work. He tells me a story about his father-in-law. Back when Figueroa was conducting postdoctoral research in Germany, his wife’s father came to visit. After giving him a two-hour tour of the lab, Figueroa asked him what he thought of it all. “I didn’t understand a word you said in there,” his father-in-law said, “but I know it’s the most amazing thing I have ever seen.” I could empathize. That’s how I felt before visiting Figueroa, interrogating him repeatedly over the phone, and reading his papers with far-out titles like “A SingleAtom Quantum Memory” and “Quantum Memory for Squeezed Light.” But after all that, the whole thing began to make sense to me. And I hope it does now for you, too. Kind of. D Dan Hurley is a science reporter and longtime contributor to Discover.

THIS PAGE: STONY BROOK UNIVERSITY. OPPOSITE PAGE: YURCHANKA SIARHEI/SHUTTERSTOCK

Figueroa has miniaturized the entire system for holding quantum memories into a portable device smaller than a carry-on suitcase, small enough to mount on an ordinary rack of computer servers at a data center — a crucial innovation if a quantum internet is ever to go mainstream. As his colleague and collaborator Dimitrios Katramatos tells me later that day: “They are portable, right? So, we loaded some of them up in a van one day and brought them from Stony Brook to Brookhaven.” “He drove his wife’s van,” Figueroa says with a laugh. “Ever since we have called it the Quantum Van.”

Researchers are finding clues to autistic behavior — in patients’ microbiomes.

BACTERIA AND THE BRAIN BY ADAM PIORE

It’s not always easy to convince people that the human gut is a sublime and wondrous place worthy of special attention. Sarkis Mazmanian discovered that soon after arriving at Caltech for his first faculty job 14 years ago, when he explained to a local artist what

JAY SMITH

he had in mind for the walls outside his new office.

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The resulting mural greets visitors to the Mazmanian Lab today. A vaguely psychedelic, 40-foot-long, tube-shaped colon that’s pink, purple and red snakes down the hallway. In a panel next to it, fluorescent yellow and green bacteria explode out of a deeply inflamed section of the intestinal tract, like radioactive lava from outer space. The mural is modest compared with what the scientist has been working on since. Over the last decade or so, Mazmanian has been a leading proponent of the idea that the flora of the human digestive tract has a far more powerful effect on the human body and mind than we thought — a scientific effort that earned him a $500,000 MacArthur Fellowship “Genius Grant” in 2012. Since then, Mazmanian and a small but growing cadre of fellow microbiologists have amassed a tantalizing body of evidence on the microbiome’s role in all kinds of brain disorders, including schizophrenia, Alzheimer’s disease, Parkinson’s disease and depression.

But the results they’ve seen in autism could, in the end, prove the most transformative. Autism affects about 1 in 59 children in the U.S., and involves profound social withdrawal, communication problems, and sometimes anxiety and aggression. The causes of the brain disorder have remained speculative. Now, Mazmanian and other researchers are finding that autism may be inextricably linked to — or even caused by — irregularities in the gut microbiome.

A BIOLOGY STORY At 47, Mazmanian — with his shaved head, flannel shirt and skinny jeans — resembles a young, urban hipster on his way to write at the local café. Originally, literary life was his plan. Born in Lebanon to two Armenian refugees, neither of whom had more than a first-grade education, Mazmanian landed in the class of an energetic high school English teacher in California’s San Fernando Valley, where his family first settled. The teacher recognized his gift for language and encouraged him to pursue

CALTECH

Sarkis Mazmanian, shown in front of a mural that celebrates the human gut, is part of a group of microbiologists researching the effects of the digestive tract on a range of disorders.

This colorized close-up of a mouse’s gut reveals the tight relationship between the gut microbe Bacteroides fragilis (red) and the epithelial surface of the colon (blue).

a career in literature. Mazmanian enrolled at UCLA in 1990, planning to major in English. Everything changed when he took his first biology class. Hunched over his new, thick textbook in the library, reading about basic biological concepts like photosynthesis, Mazmanian felt a vast new world opening up to him. “For the first time in my life, I wanted to turn the page and see where the story was going to go,” he says. “I think I decided that minute to become a scientist.” Mazmanian was most fascinated by the idea that tiny organisms, invisible to the naked eye, could function as powerful, self-contained machines — powerful enough to take over and destroy the human body. After graduating with a degree in microbiology, Mazmanian joined a UCLA infectious diseases lab and began studying bacteria that cause staph infections. As his dissertation defense approached, Mazmanian read a one-page commentary penned by a prominent microbiologist, highlighting the fact that our intestines are teeming with hundreds, if not thousands, of different species of bacteria. But it was still largely unknown what they are and how they affect the human body. When Mazmanian dug further, he found that no one had yet answered what seemed to him to be the most obvious question: Why would the human immune system, designed to attack and destroy foreign invaders, allow hundreds of species of bacteria to live and thrive in our guts unmolested? To him, the bacteria’s survival implied that we had evolved to coexist with them. And if that were so, he reasoned, there must be some benefit to both the microbes and the human body — a symbiotic relationship. But what was it?

CALTECH

GUT INVADERS Mazmanian set out to study the link between gut microbes and the immune system. As a postdoctoral researcher, he joined the lab of Harvard University infectious disease specialist Dennis Kasper. To start, Mazmanian examined how the immune systems of germ-free mice — lab mice completely protected, starting at birth, from all microbes — differed from those of mice with either few or normal levels of microbes. He expected this initial census would be just a first step in a long and arduous quest

for scientific pay dirt. But when he went to examine a printout of his results in the lab, he realized immediately he might already be onto something big. The germ-free mice had a 30 to 40 percent reduction in a specific type of immune cell known as helper T-cells. Since helper T-cells play a key role in coordinating attacks against invading pathogens, the finding suggested that the immune systems of the germ-free mice were far less robust than those found in peers with normal levels of microbes. “That was exciting, right?” Mazmanian recalls. “Obviously I repeated it and tested it in a number of different ways. Then I asked the next question: ‘Can I restore the [immune] function in an adult animal?’ ” Mazmanian colonized the guts of the immunocompromised, germ-free mice with microbes from standard lab mice. After receiving the fecal transplant, their T-cell counts shot up. Within a month, their numbers were identical to mice raised outside the germ-free bubble. Resolving to identify the microorganisms causing this transformation, Mazmanian resorted to trial and error. One by one, he added strains of bacteria found in the guts of mice to the guts of germ-free mice.

“

THESE TINY ORGANISMS FUNCTION AS POWERFUL, SELF-CONTAINED MACHINES — POWERFUL ENOUGH TO TAKE OVER AND DESTROY THE HUMAN BODY.

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A HEALTHY GUT, A NEW OUTLOOK Prior to his fecal transplant at age 7, Ethan Woods suffered from chronic and severe diarrhea, constipation and cramping, symptoms so extreme that to his mother, Dana, he sounded like “a bit like a woman in labor when he was trying to have a bowel movement.” “It was just awful watching your child go through this,” she says, explaining that when she enrolled her autistic son in the Arizona State study, her “only goal was to fix his gut.” Remarkably, Ethan’s agony began to disappear just a few weeks into the trial. But that was not the most dramatic difference. Before the transplant, Ethan’s speech was drawn out and slow, his language

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skills rudimentary. He seemed to live in his own bubble. He had frequent outbursts. For as long as Dana could remember, her mornings with Ethan had been marked by arguing, fighting, pushing and anger. But then one morning, something shocking happened. “He woke me up one morning with his face right in my face with this big smile and he said, ‘Morning, Mom!’ ” she recalls. “And he

was just excited and happy and ready to go about his day with this big smile. It choked me up to the point where I teared up because

“

WITHIN A YEAR OF THE STUDY, HIS SPEECH THERAPIST GRADUATED HIM FROM SPEECH THERAPY BECAUSE HE HAD MET ALL HIS GOALS.

I had never experienced a happy kid in the morning.” Later, Ethan carried over an iPad and opened an app with a talking cat that repeats back the words children speak aloud. He played back a video recording of himself from just a few weeks earlier. “[He] looks me in the eye and says, ‘Mom, why did I talk like that? What is wrong with me?’ And as soon as he did that, I caught my breath. I had to compose myself and say, ‘I don’t know. But do you feel better? Do you feel different? Why do you think?’ ” Ethan’s communication skills had already begun to improve. Within a year of the study, his speech therapist graduated him from speech therapy because he had met all his goals. “He went from one end of the rainbow all the way to the other end of the rainbow,” she says. “Prior to the study, I was very afraid. My biggest fear was ‘how is he going to navigate the world when I’m not here?’ And I think I have a lot of hope now that he is going to be OK now on his own.” — A.P.

DANA WOODS (2)

Ethan Woods had GI issues and symptoms of autism until researchers introduced new microbes to his gut. His mother says the treatment changed everything.

Many children with autism have some type of gastrointestinal problem, which led researchers to search for links between the two.

He got nowhere with the first five or six species he examined. Then, simply because it was convenient, he decided to test one more that was readily available in his lab. Mazmanian’s adviser, Kasper, had been studying a gut microbe called Bacteroides fragilis. When Mazmanian implanted one of Kasper’s specimens into the gut of his germ-free mice, the results were dramatic: The T-cell numbers spiked to normal. Eventually, Mazmanian demonstrated he could reproduce this effect simply by adding a single molecule that these bacteria produce, called polysaccharide A, to their guts. “There was no logic in the choice whatsoever,” Mazmanian recalls. “[B. fragilis] was available, it came from the gut.” In other words, he got lucky. Mazmanian dug deeper and discovered that the biggest impact B. fragilis had was on the population of a subtype of helper T-cells called regulatory, or suppressor, T-cells. These cells play a key role in preventing the immune system from attacking its host body, protecting against autoimmune or inflammatory diseases. It was the first time any scientist had demonstrated that a single compound from a single microbe could reverse a specific problem with the immune system. To Mazmanian, the finding, published in 2005 in the journal Cell, alluded to new approaches to treating a wide array of autoimmune, inflammatory and allergic disorders. What if it were possible to help a faulty immune system by tweaking a patient’s microbiome? It was with this exploration in mind that he arrived in Pasadena in 2006 to set up his lab at Caltech.

JAY SMITH

A CONVENIENT COLLABORATION A few years later, Mazmanian was having lunch on campus with neuroscientist and colleague Paul Patterson. Patterson had been preoccupied with a mystery that had, for years, confounded those studying autism in humans: When pregnant mothers have a severe infection in the second trimester, their babies are much more likely to develop autism. As Mazmanian tells it, Patterson was a man of few words, and at lunch Mazmanian was “going on and on” about his own work.

“You know,” Patterson interjected thoughtfully, “I think kids with autism have GI issues.” Patterson recalled reading that something like 60 percent of children with autism had some form of clinical GI problem, such as bloating, constipation, flatulence or diarrhea. Was it possible, he wondered, that there was a microbiome connection? As they talked, Mazmanian’s excitement grew. A few years earlier, Patterson had discovered that when he exposed pregnant mice to pathogens like the influenza virus, they gave birth to pups that grew up more likely to be startled by loud noises, to shy away from social contact and to groom themselves repetitively — symptoms that resemble those of autism. Patterson was in the process of comparing the brains of these autism-mimicking mice with their neurotypical cousins to see if he could detect any differences that might explain how the maternal immune system was somehow interfering with the pups’ brain development. Mazmanian had a suggestion: The next time Patterson sacrificed one of his autistic mice to study their brains, what if he set the intestines aside for his colleague down the hall? When the guts arrived in Mazmanian’s lab, he found that the intestines of the neurotypical mice looked normal. But the guts of the autismmimicking offspring were almost uniformly inflamed. Could it be that the microbiome was the cause of this inflammation? And could that, in turn, be somehow connected to the behavioral symptoms?

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THE GUTS OF THE AUTISMMIMICKING MICE WERE ALMOST UNIFORMLY INFLAMED. COULD IT BE THAT THE MICROBIOME WAS THE CAUSE?

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Rosa KrajmalnikBrown, microbiologist

THE ASD RAINBOW The autism spectrum describes people with a wide range of developmental disorders. Many who were highfunctioning used to be diagnosed separately, such as having Asperger syndrome. Now, medical experts use a series of levels to figure out where patients lie on the spectrum.

AUTISM SPECTRUM DISORDER (ASD)

HIGH-FUNCTIONING AUTISM LEVEL 1 Needs support

Patient’s social and communication skills and repetitive behaviors are only noticeable without support.

AUTISM

SEVERE AUTISM

LEVEL 2 Needs substantial support

LEVEL 3 Needs very substantial support

Patient’s social and communication skills and repetitive behaviors are obvious to the casual observer, even with support in place.

Patient’s social and communication skills and repetitive behaviors severely impair daily life.

FROM TOP: CALTECH; ELIZABETH M. WEBER/DISCOVER

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AT THE END OF THE DAY, WHAT WE CARE ABOUT IS HEALING PEOPLE AND HOW THE MICROBIOME AFFECTS PEOPLE.”

Throughout the winter and mice with autism-like symptoms. spring of 2012, Mazmanian and The researchers published their Patterson continued their conversaresults in Cell in 2013. tion. Mazmanian found distinct Though surprising, the data differences in the microbiomes of made sense in some ways. Many the mice. And, they noticed, the drug companies rely on smallmice with the features of autism molecule drugs that can be taken had leaky gut syndrome, an orally, but still manage to cross increased permeability of the gut the blood-brain barrier and affect lining that can allow pathogens behavior. It seemed entirely posand allergens to leach out. This sible that small molecules, created condition had also been reported by bacteria in the gut, could enter The late Paul Patterson laid in children with autism. the bloodstream and reach the important groundwork in So Mazmanian and Patterson brain. And they don’t even have mice for Mazmanian. turned their attention outside the to leak out of the gut to do so. gut. They took blood samples to see if any gut OF MICE AND MEN microbes, or the compounds they produce, Patterson died in 2014, at age 70, just six months were circulating in the rest of the body. They after the publication of the duo’s groundbreakhomed in on one molecule in particular, called ing Cell paper. Around the same time, a series 4-ethylphenyl sulfate, which was roughly of parallel experiments in a clinic hundreds of 45 times as abundant in the mice that had miles away was already paving the way forward. symptoms of autism. And it looked familiar: While Patterson and Mazmanian had been Structurally, it was almost identical to a molworking in mice, Rosa Krajmalnik-Brown, ecule recently found to be significantly elevated a microbiologist at Arizona State University, in human children with autism. had teamed up with Jim Adams, who directs It was enough to take the next step. Every the university’s autism and Asperger’s research day for three weeks, Mazmanian injected program, to study humans. the molecule, harvested from the mice with The researchers were conducting a detailed autism-like symptoms, directly into the analysis of the microbiome of human autism bloodstream of 5-week-old normal lab mice patients and found that the bacteria were far less (the age at which the autistic mice normally diverse in the children with autism. Notably, developed leaky gut). Then Mazmanian and his several important species involved in the digesteam gave them a series of behavioral tests. The tion of carbohydrates were severely depleted. mice were far more easily startled and were less Krajmalnik-Brown and Adams launched comfortable in large empty spaces than their a preliminary trial to test the effects of fecal untreated peers, indications of an increase in transplants on 18 children between the ages anxiety-related behaviors commonly seen in the

Autism in the U.S., by the numbers:

44%

FROM LEFT: CALTECH; SABUHI NOVRUZOV/SHUTTERSTOCK

Children on the spectrum with average or above-average intellect (IQ higher than 85).

of 7 and 16 with severe autism, who also had severe GI issues. The researchers administered powerful antibiotics to kill off the microbiomes of the children and followed them with a bowel cleanse. They then replaced the microbes with transplanted flora taken from the guts of healthy neurotypical adult volunteers. The results were better than anyone could have expected. The procedure resulted in a large reduction in GI symptoms and increased the diversity of bacteria in the children’s guts. But more significantly, their neurological symptoms were reduced. At the onset of the study in 2017, an independent evaluator found 83 percent of participants had severe autism. Two years after the initial trial, only 17 percent were rated as severely autistic. And 44 percent were no longer on the autism scale. “[My child] did a complete 180,” says Dana Woods, whose then-7-year-old son Ethan enrolled in the initial study five years ago. “His ability to communicate is so much different now. He’s just so much more present. He’s so much more aware. He’s no longer in occupational therapy. He’s no longer in speech therapy. After the study, he tested two points away from a neurotypical child.” In their first report on the trial in 2017, the team highlighted a number of distinct changes in the microbiome after the transplants, in

particular a surge in the populations of three types of bacteria. Among them was a fourfold increase in Bifidobacterium, a probiotic organism that seems to play a key role in the maintenance of a healthy gut. But figuring out what was happening on a cellular level — to really look inside some guts — would require another vehicle. The ASU team needed Mazmanian’s mice. “At the end of the day, what we care about is healing people and how the microbiome affects people,” explains Krajmalnik-Brown. “That’s why we work with people. But with mice you can do things that are more mechanistic.”

THE GREAT MOUSE DETECTIVE Together, Krajmalnik-Brown, Mazmanian and their collaborators would uncover some tantalizing new insights that go a long way to solving the mystery. In May 2019, the team published another high-profile paper in Cell, after they transplanted stool samples from KrajmalnikBrown’s severely autistic patients into the guts of Mazmanian’s germ-free mice. The offspring of these mice showed the autism-like symptoms, such as repetitive and compulsive behavior. This time, the team dug even deeper into the biochemical processes playing out in the brain, looking not just at behavior but at the chemicals involved in creating it. The mice that developed

10% Children who also are savants, or patients showing remarkable memory and skill in a specific area, such as music.

20% Children with enlarged brains as infants and toddlers.

Girls Boys 1 in 189.

1 in 42.

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AUTISM AND THE BRAIN

Years of studies in children on the autism spectrum suggest they have an increased brain volume that may correlate with the severity of their symptoms. But the brain returns to normal size, or smaller, by the time a child is an adolescent. Studies have also indicated various brain regions as playing a role in autism spectrum disorder (ASD), and that these areas may fluctuate in size compared with brains of kids without ASD, but the work is still inconclusive.

Caudate nucleus Stores and processes memories, acting as a feedback mechanism to regulate future behavior. Amygdala Regulates emotions, especially those for survival, such as fear and aggression; there’s conflicting evidence that neurons in this brain area can be overor underconnected.

Hippocampus Deals with memory and learning; in mouse models, it’s sometimes enlarged.

Pars opercularis Involved in language comprehension.

Cerebellum Controls motor skills, including muscles for speech.

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FROM LEFT: SCIEPRO/GETTY IMAGES; EVAN OTO/SCIENCE SOURCE

Superior temporal sulcus Involved in perception of emotions and facial cues; shown to have structural abnormalities.

Prefrontal cortex (includes the cerebral cortex) Responsible for cognitive and social learning; may cause faulty connections to other parts of the brain.

Corpus callosum Connects the right and left brain hemispheres; one-third of people born without this structure are on the spectrum.

MASTER1305/SHUTTERSTOCK

Though the first fecal transplant trial only had 18 participants, many other studies explain a possible mechanism for how gut health could affect autistic behavior.

autism-like behaviors had measurably lower levels of two substances called taurine and 5-aminovaleric acid (5AV). When they dug into the literature, the team learned that these two substances are known to mimic activity of a key signaling agent in the brain called gamma-aminobutyric acid (GABA) — a neurotransmitter that other studies have found is deficient in the brains of children with autism. What’s more, some have speculated that the tendency of children with autism to experience sensory overstimulation may stem from the inability to tamp down overexcited neurons. A lack of GABA could lead to just that. The scientists next orally administered high levels of taurine and 5AV to pregnant mice with the autistic children’s microbiomes. When their pups were born, the researchers continued to feed the young the substances until they reached adulthood. Compared with untreated animals, the second-generation mice had significantly fewer behavioral symptoms. Taurine reduced repetitive behavior, as measured by marble burying, increased the level of social interaction, and relieved anxiety. Mice administered 5AV were more active and social. “We healed humans with behavioral problems,” says Krajmalnik-Brown. “[And we] transferred some of those deficits and behaviors to mice — basically the opposite. It’s huge.” Mazmanian hopes to take the next step in the months ahead. “I can flip a switch, turn on a light, I know that switch turns on that light. I don’t know the circuit, I don’t know where the wire is,” Mazmanian says. “Exactly how that’s happening … we just don’t understand that.” This most recent study, by itself, hardly proves that dysregulated microbiomes cause the brain disorder — a point that plenty of other scientists skeptical of Mazmanian’s work are happy to make. “The paper made a big splash, but trying to model psychiatric-related human conditions in mice, in my view, is a little bit of a stretch,” says Sangram Sisodia, a neurobiologist at the University of Chicago who studies the microbiome. “A mouse with autism?”

Nor was that the only criticism. Several researchers have suggested that the group didn’t give proper attention to one of their tests — one whose results conflicted with their thesis — while others found flaws in the statistical methods they used to assess their results. Mazmanian downplays these criticisms, but agrees the work is not yet conclusive. Meanwhile, the ASU trial has also engendered skepticism, mainly due to its tiny sample size, the lack of a control group and the methods by which the children were assessed for autism severity. Krajmalnik-Brown and Adams say they stand by their results, but agree more research is needed. In recent months, they have launched two new studies that will address these issues. Adams insists the work is already changing lives. “We followed up with every one of our 18 participants,” he says, referring to the children who received fecal transplants. “Sure enough, we found that most of the GI benefits had remained. And family after family said their child just slowly, steadily continued making more improvement.” They published the update in Scientific Reports in spring 2019. “I’m not ready to say the case is closed,” says Mazmanian. “Healthy skepticism is a good thing. I believe the preclinical data, I believe the mouse data. But there’s a lot of studies that still need to be done.” D

“

I’M NOT READY TO SAY THE CASE IS CLOSED. HEALTHY SKEPTICISM IS A GOOD THING. I BELIEVE THE DATA. BUT THERE’S A LOT OF STUDIES THAT STILL NEED TO BE DONE.” Sarkis Mazmanian, microbiologist

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ANXIETY? PANIC DISORDER? DEPRESSION?

COVER STORY

It’s not just in your head. Mounting evidence shows bugs in your digestive system influence the brain. Experts are now testing psychobiotics as mental health remedies.

GUT FEELING COOLGRAPHIC/SHUTTERSTOCK

BY ELIZABETH SVOBODA

Every muscle fiber in Tom Peters’ body seemed to be conspiring to keep him in bed. His depression — an occasional visitor for more than a decade — had reemerged in the summer of 2019, and his legs and arms felt like concrete. The thought of spending another 12-hour day at his computer filled him with dread. As a technical day trader for stocks, he responded to demanding clients constantly. That felt impossible when his brain kept blaring his past failures at top volume.

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MORE THAN A FEELING Anyone who’s sprinted to the bathroom moments before a speech or felt a wave of nausea after public humiliation knows the gut and the brain are connected. Doctors have

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speculated about this linkage since ancient times. Hippocrates, who is credited with saying “all disease begins in the gut,” speculated that black bile spilled from the spleen into the intestines and brought on dark moods. Theories like these grew more sophisticated over the centuries as scientists learned more about the microorganisms in the human gut. (We now know there are literally trillions of them.) By the late 19th century, doctors argued that “melancholia,” a then-common term for depression, arose from overgrowth of intestinal microbes. But physicians at the time understood little about what these microbes did in the body. So, early gut-based treatments — including major abdominal surgery for schizophrenia — were doomed to fail. Fast-forward a century, and data from speedy genome sequencing of gut bacteria in the 2000s revealed that microbes perform an array of bodily tasks. Further studies showed how some might affect mental health. Each of us, it turns out, is more microbe than human: Bacterial cells outnumber human cells in the body by a factor

SEANIDSTUDIO/SHUTTERSTOCK

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BACTERIA IN YOUR GUT PRODUCE ABOUT 90 PERCENT OF THE SEROTONIN IN YOUR BODY — THE SAME HAPPY HORMONE THAT REGULATES YOUR MOODS.

Fielding the volley of work messages became a Sisyphean task. “There’s always the overriding fear that I’m not going to come out of it, that I’m always going to feel this way,” Peters says. “That probably is the scariest thing.” Peters, 50, had read about mood probiotics, gut bacterial strains marketed to help with depression and anxiety, but never felt like they were for him. “I was very skeptical,” he says. When his wife, who was battling panic attacks, tried mood probiotics and saw her episodes diminish, he began to reconsider. After his depression symptoms returned last summer, and the Prozac he’d tried in the past had lost its potency, his wife went online and ordered him a bottle of the same oatmeal-colored capsules she was taking. For decades, experts scoffed at the idea that gut bacteria affect our mental health. Many called it a fringe theory. Yet mounting evidence suggests that intestinal microbes profoundly shape our thinking and behavior. Human trials are now underway to investigate how these microbes boost our overall well-being. If the results hold up, new bacteria-based therapies could expand a mental health treatment landscape that has been mostly stagnant for decades. “Current treatments [for mental health] are not great,” says University of Calgary psychiatrist and microbe researcher Valerie Taylor. “When they do work, many of them are intolerable. People are desperate.”

NATTAPAT.J/SHUTTERSTOCK; INSETS: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY (3)

of at least 1.3 to 1. The human gut plays host to more than 100 trillion of these bacteria — a complex, interdependent microbial universe wedged between your ribcage and spine. While the human genome consists of roughly 25,000 genes, the swarm of microbes in your gut expresses about 3 million distinct genes. Many of these bacterial genes help build molecules that let you digest food, keep harmful microbes at bay, and even feel emotions. For starters, the bacteria in your gut produce about 90 percent of the serotonin in your body — yep, the same happy hormone that regulates your moods and promotes well-being. For Peters, the prospect of a new path looked tantalizing after enduring the marathon of traditional options. He had gone through multiple stints on Prozac — a selective serotonin reuptake inhibitor (SSRI) — and wondered if he’d maxed out the drug’s potential. “I went off them for a while, then I went back on them, and I felt like I developed a resistance of sorts,” he says. It’s a familiar tale for almost anyone who takes SSRIs for long-term depression.

Years earlier, when Peters’ old dose of Prozac wasn’t working as well, his psychiatrist had prescribed him a new, higher dose, one that brought on annoying side effects. “On the higher dose, I felt like I was more sluggish,” Peters says. “It drove me crazy.” The memory of that unrelenting brain fog helped persuade him to give probiotics a try.

Scientists have identified thousands of unique bacteria strains that live in the gut.

WHAT HAPPENS IN THE VAGUS In the mid- to late 2000s, John Cryan of Ireland’s University College Cork was among the first to explore gut microbes’ effects on the brain. A neurobiologist by training, Cryan had shown that rats stressed from birth later showed signs of both irritable bowel syndrome (IBS) and mood disturbance. “When they grew up,” Cryan says, “they had a whole-body syndrome.” This finding echoed doctors’ observations that many patients with digestive symptoms also had mental health issues, and vice versa. When researchers at Cryan’s lab sampled gut bacteria from stressed-out rats in 2009 and sequenced them, they hit on something N OVEM B ER 2 02 0 . D IS C OV ER

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A HEALTHIER GUT

It’s becoming clearer that some probiotics help make your gut happy. A major review of recent studies shows they can treat irritable bowel syndrome (IBS) and various types of diarrhea. But navigating the options (and false claims) can be, well, a crapshoot. For example, a probiotic that treats influenza or common cold symptoms? There’s little evidence to support this. As for the impact on mental health, larger human trials will help determine their effectiveness. Meanwhile, a decade-plus of experimental study has helped researchers assemble a firststring lineup of promising bacterial strains. But those interested should proceed with caution. The probiotic supplement industry in the U.S. is “not FDA-regulated, so there could still be a risk,” says Lauren Bylsma, a University of Pittsburgh clinical research psychologist. Common treatments include:

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Fermented foods: Foods like sauerkraut, yogurt and kefir — a type of fermented milk — naturally contain bacterial strains tied to anti-depressive effects, such as Lactobacillus helveticus or Lactobacillus acidophilus. That might explain the mood lift some people report from eating them. L. helveticus and Bifidobacterium longum: This bacterial duo — a common combo in products marketed as mood probiotics — has shown some mettle in both human and animal

studies. In one human trial, people taking these two bacteria reported a greater drop in depression symptoms than those on a placebo. The bacteria may boost mood by lowering levels of stress hormones like cortisol. L. acidophilus: This much-touted probiotic strain activated moodstabilizing gut opioid receptors in one animal study. It also helps strengthen the intestinal lining, which prevents inflammatory compounds from migrating to the brain.

INTESTINES: DANIELA BARRETO/SHUTTERSTOCK. BACTERIA: MICROONE/SHUTTERSTOCK

WHAT WE KNOW ABOUT PROBIOTICS

CLUSTERX/SHUTTERSTOCK

surprising: Stressed-out animals — those more prone to mental health issues — had a less diverse assortment of gut microbes, or microbiome, than their more relaxed counterparts. “It got us thinking — if you stress an animal, [maybe] there’s a signature in the microbiome that’s persisting,” Cryan says. In the past decade or so, more labs have started reporting that gut bacteria produce a smorgasbord of compounds that affect the mind in surprising ways, both good and bad for your emotional health. Some bacteria in the Clostridium genus generate propionic acid, which can reduce your body’s production of mood-boosting dopamine and serotonin. Microbes like bifidobacteria enhance production of butyrate, an anti-inflammatory substance that keeps gut toxins out of the brain. Other species produce the amino acid tryptophan, a precursor to mood-balancing serotonin. Rather than passing from the gut to the brain via bloodstream, some of these chemicals affect the brain through intermediate channels, says University of Pittsburgh clinical research psychologist Lauren Bylsma. A major one, the vagus nerve, functions like a communication superhighway between the brain, gut and other organ systems in the human body. Recently discovered neuropod cells can activate or deactivate the vagus nerve, which interfaces with neurons in the brain. Research shows that certain gut bacteria help activate those neuropod cells. While researchers continue to map the workings of what they’ve dubbed the “gut-brain axis” — the two-way communication link between the GI tract and the central nervous system — many already think it creates a major potential avenue for mental health treatment. Talk to psychiatrists about what causes mental illnesses like depression and “you get a list of 10 mechanisms,” says Philip Strandwitz, co-founder and CEO of biotech company Holobiome. “When you talk to microbiome folks and ask them if you can affect those mechanisms, the answer is largely yes.” Since the concept of the gut-brain axis went mainstream, labs have accumulated even more evidence to support the notion. Earlier this year, Cryan and a team of international colleagues gave a group of stressed mice regular doses of a Bifidobacterium gut microbe for five weeks. By the end, the mice were more mobile and active than before. They were also more willing to interact and explore new areas. The whole time, Cryan tracked changes in the mice’s gut bacteria. During a treatment with Bifidobacterium breve, their gut bacteria started making more tryptophan. Treated mice also

produced more of a protein called brain-derived neurotrophic factor (BDNF), which helps new neurons grow. Even as scientists highlight these kinds of connections between gut microbe treatments and symptom improvement, the question of causality has lingered: Do gut bacterial changes actually drive mood and behavioral changes? A growing body of research suggests they do. Several innovative studies since 2016 show that fecal transplants can shape behavior profoundly, according to Bylsma and Taylor. When mice in one Chinese study got transplants of feces from other healthy mice, their behavior remained unchanged. But when mice received fecal transplants from donors with signs of anxiety and depression, the mice started to show signs of mood disturbance. A separate study published in Molecular Psychiatry showed mice that received fecal transplants from depressed humans also developed depressive symptoms. On the other hand, stressed-out mice in a 2019 study received transplants from unstressed animals and began acting less depressed. By changing the intestinal microbiome, researchers “can actually change the rodents’ behavior,” says Bylsma, who was not involved with the studies. “That implies there is a causal effect.”

“

THE VAGUS NERVE FUNCTIONS LIKE A COMMUNICATION SUPERHIGHWAY BETWEEN THE BRAIN, GUT AND OTHER ORGAN SYSTEMS IN THE HUMAN BODY.

FROM PETRI DISH TO HUMAN BODY Of course, dialing back depression-like symptoms in mice is a long way from rolling out gut-based mental health treatment to the public. Researchers love to joke about how many diseases they’ve cured in rodents. But Taylor is hopeful about the prospects of replicating gut-bacteria treatment successes in people. Taylor’s current approach is fecal transplantation, which involves exactly what you might guess: a human-to-human poop exchange. Often, people ingest the feces in a pill. Sometimes, doctors offer poo-rich enemas to seed the digestive tract with new microbes. Taylor has started two small-scale fecal transplant trials — the first on people with bipolar disorder, and the second on those with depression — to find out whether feces from healthy human donors boosts recipients’ moods and well-being. She is also taking samples of subjects’ gut microbiomes before, during and after treatment to track any notable changes. Human studies of oral probiotic therapy are a bit further along. A survey of small-scale controlled trials found that Bifidobacterium and Lactobacillus strains improved depressive symptoms overall, while other studies show similar effects on anxiety. One Australian N OVEM B ER 2 02 0 . D IS C OVER

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study published in 2017 even suggests that a diet higher in beneficial bacteria can banish depression in more than a third of people. Microbes have also shown promise for less common mental health disorders: In a 2019 paper on a Japanese trial, 12 of 29 participants with schizophrenia who ingested a specific Bifidobacterium strain saw their depression and anxiety symptoms lift within four weeks. Microbiologist Jeroen Raes thinks the

human clinical trials. But they have shown some mood-lifting promise in smaller human studies. Even so, before Peters popped one of the capsules for the first time, he felt his natural skepticism rearing up. About a week into his new regimen, though, he began to notice a subtle mood shift that soon became more pronounced. “I felt sharper, more energetic — just a more positive outlook in general,” he says. “I felt like I was more relaxed at night.” Putting in a day at his desk no longer felt like rolling boulders up a hill. It wasn’t that he was abnormally happy, or that he had endless reserves of enthusiasm. Instead, what he felt was an anchoring inner calm, as if the choppy waves he’d been riding had receded.

JEROEN RAES

“

WHO’S MAKING THE MONEY? IT’S NOT AS OBVIOUS AS IN OTHER AREAS. IF THIS WAS A PHARMACEUTICAL STRATEGY, IT WOULD BE VERY CLEAR.” John Cryan, neurobiologist

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cosmos of gut microbes that affect the human brain may be even larger than these initial trials suggest. Raes and his team at Belgium’s VIB-KU Leuven Center for Microbiology have harvested poop samples from more than 1,000 people, scanning for gut microbe profiles that accompany their reported mood symptoms. So far, he’s found that people with more butyrateproducing gut microbes — such as certain types of Faecalibacterium and Coprococcus — have a higher quality of life, while people with lower levels of Coprococcus are more likely to be depressed. Ultimately, Raes predicts the emergence of a kind of probiotic therapy that researchers are calling “psychobiotics.” In that potential treatment universe, people with depression, anxiety or other mental health issues would routinely have their gut microbiomes sequenced. Those with high levels of bacteria tied to poor mental health, or low levels of bacteria that healthy people have in abundance, could receive a tailored probiotic or fecal transplant to fix the imbalance. The probiotic strains Peters began taking — Lactobacillus helveticus and Bifidobacterium longum — hadn’t been vetted in large-scale

The next psychobiotics milestone, scientists say, will be full-scale clinical trials that show whether microbes or microbial cocktails boost well-being beyond placebo effects common in psychiatric treatment studies. “You need trials, and you need placebo control in those trials,” Raes says. “If you have a trial that works, you need to replicate it in an index population.” We’ll likely be waiting at least two years for those definitive results. One sticking point in the outcome could come from drug companies, and whether they can identify a substantial profit. Many gut-based remedies contain naturally occurring bacteria, which makes them difficult to patent. “Who’s making the money? It’s not as obvious as in other areas,” Cryan says. “If this was a pharmaceutical strategy, it would be very clear.” (Strandwitz plans to get around this problem by patenting compositions of microbes and a particular way of delivering them to patients.) Another issue is that, while certain types of bacteria have more profound effects on the brain than others, there probably won’t be any magicbullet strains that work for everyone. Some gut bacteria function best alongside a constellation of varieties, complicating the picture further — especially since gut bugs number in the trillions and represent more than 500 different species. “One bacterial profile might be good for one person and one for another person,” says Bylsma. “The findings are not always consistent.” And with fecal transplants, it can be difficult to control exactly which bacterial species a patient receives. If the mix of probiotics, fecal transplants and diets do prove their mettle, Raes says, gut-based therapies will likely be considered an adjunct to treatments like medication and counseling, not

GREETJE VAN BUGGENHOUT

A PROVING GROUND

necessarily a replacement. “It’s going to be part of the story. It’s not going to be the whole story.”

PARAMEPRIZMA/SHUTTERSTOCK

INCHING TOWARD INTERVENTIONS Since current psychiatric drugs don’t work well for many people, DIY spins on gut research findings have already begun. In some circles, at-home fecal transplantation has exploded in popularity, fueled by testimonials that sing praises. But experts strongly discourage this, as stool samples that have not been tested could contain bacteria that cause life-threatening illness. “It is extremely dangerous,” Raes says. “You do this at home, you have no control.” Over-the-counter probiotics offer a more mainstream DIY options. While doctors generally regard common strains like B. breve and L. acidophilus as safe for human consumption — they appear in foods like yogurt, kombucha and kefir — bacteria are bioactive substances, so ingesting them involves some level of risk. And in the U.S., the supplement industry is largely unregulated. That means consumers have to take companies’ word that probiotics contain the strains listed on the label. Given the rapidly evolving state of gut-brain

research, experts don’t all agree on how to advise patients seeking treatment options. Raes won’t recommend any gut-based therapy before it goes through full clinical trials. But Taylor contends that even if probiotic strains’ effects on mood remain unproven, they don’t appear harmful. When patients ask about probiotics, she doesn’t discourage them from trying them out. Peters avoids dissecting the sequence of internal events that banished his depression; he’s just thrilled it’s gone. Stress and time pressures remain constant in his work life, but he feels like he navigates these bumps more gracefully. “There are days I’m able to focus a thousand percent and there are days I’m not as productive, but there’s more stability,” he says. “It’s not like a yo-yo, way up one day and way down another.” Along with the probiotics, he takes a Prozac dose that’s a fraction of what he took in the past. It has kept his old brain fog at bay. “To be able to get an extra hour or two out of my day so I can be present for my kids — to me, that’s amazing.” D

Gut experts say probiotics and fecal transplants might join antidepressants as prescribed mental health remedies.

Elizabeth Svoboda is a science writer in San Jose, California. Her latest book is the Life Heroic: How to Unleash Your Most Amazing Self. N OVEM B ER 2 0 2 0 . D IS C OV ER

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C O

BY JOAN MEINERS

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THERE’S A MAN WHO LOVES CHICKENS — ALMOST AS MUCH AS HE LOVES SCIENCE. HE’S PROBING THE DEPTHS OF EVOLUTIONARY BIOLOGY, GENETICS AND THE UNEXPECTED BENEFITS OF FERAL BIRDS.

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These tourist-laden seaside towns are full of feral chickens. They roam the graveyards. They strut the beaches. They peck at leftovers beneath busy tables on restaurant patios. Legends about the birds abound, including that one flock arrived on the wings of a Pan Am jet and that some were bred to have extra toes. But are they good for anything besides waking us up? Eben Gering thinks so. He’s been chasing free-roaming fowl around beaches across the globe for almost a decade. An assistant professor of biology at Nova Southeastern University in south Florida, Gering is convinced that these birds hold answers to core questions about gene evolution and disease resistance. Though he tracks many wild animals that hold scientific secrets, feral chickens are his favorite. Eben Gering uses feral chickens, like this research subject in Key West, to answer questions about evolution.

Q: There are so many animals in the world; how did you end up focusing on chickens? A: From a practical perspective, they’re easy to watch. They don’t fly great distances, and they’ll perform all kinds of interesting behaviors right in front of you. So, we’re able to get data on chickens that would be much harder to get if we were studying other kinds of organisms. We’re even able to use geo-referenced photographs of chickens that people post on their social media while on vacation to track things like when the hens have chicks and the prevalence of genetic traits like yellow legs.

Q: And why feral chickens? A: In biology right now, we have some really interesting research on evolution that’s done under really artificial conditions, like people looking at the evolution of bacteria in vials. And then we have some researchers that go deep into the Amazon rainforest, or Papua New Guinea, to look at how organisms are evolving in these much more complex and fluctuating conditions. But I’m fascinated by these feral organisms because they seem to live in the margins between those two extremes. So, on the one hand, they are subject to a complex environment where they’re interacting with lots of other organisms. They deal with weather and competitors and predators and all that complicated stuff that we don’t see in lab settings. But, on the other hand, they also start from a point of human influence, because their genomes have been modified by the domestication process.

Q: About how many chickens are we talking here, that live in these beach towns? A: Fun fact: Between August 2012 and October 2013, the tiny archipelago of

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PREVIOUS SPREAD: RISINGTIMBER/SHUTTERSTOCK. THIS PAGE FROM LEFT: KAYLEIGH CHALKOWSKI, COURTESY EBEN GERING; ANDRIY BLOKHIN/SHUTTERSTOCK

Q A

IF YOU’VE EVER HIT THE BEACHES OF KEY WEST, BERMUDA OR HAWAII LOOKING FOR A TRANQUIL VACATION, YOU MAY HAVE EXPERIENCED A RUDE AWAKENING. BY A ROOSTER, THAT IS.

Bermuda removed something like 11,500 chickens. [The government of Bermuda estimates its current feral chicken population to be between 20,000 and 25,000 across the territory’s mere 20.5 square miles.]

FROM TOP: ANDRIY BLOKHIN/SHUTTERSTOCK; VENTU PHOTO

Q: That’s a lot of chickens. Where on Earth did all these birds come from? A: A lot of them were introduced over time from trading ships. But there’s this amazing story about this person who really wanted to introduce red junglefowl as game birds to the U.S. from India. I think the story is that this person from India held this huge party, and got all the birds in this courtyard, and brought all these airline agents to convince them they should get a Pan Am jet and fill it up with junglefowl to In many beachside towns, feral chickens are considered a nuisance. At least they’re easier to study than feral cats.

bring to the U.S. as game birds. I believe these junglefowl introductions were the last time that the U.S. Fish and Wildlife Service tried to import a terrestrial vertebrate into the wild for people to chase around with guns. This practice has fallen out of favor because so many species that were imported intentionally have become invasive.

Q: Do the people who live in these areas now get annoyed having so many chickens around? A: It depends. In Ybor City, Florida, there’s a chicken society and a guy who takes care of the birds. He knows every individual chicken, and which one had babies with which one. He runs all this social media stuff and sells shirts. If a chicken has babies, they have a social media update. But there’s conflict within the local business community.

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SOME PEOPLE SEE THE CHICKENS AS A WAY TO MAKE PEOPLE COME VISIT. OTHER PEOPLE JUST SEE THEM AS THINGS THAT POOP ON THEIR CARS.”

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DON’T FEAR THE FELINES?

T

he parasite Toxoplasma gondii infects many warm-blooded animals, including humans — and feral chickens. Eben Gering, biologist at Nova Southeastern University, is interested in how we could study the parasite in chickens to learn about its distribution across the globe. Recently, he’s taken his work beyond the fowl. You may know T. gondii better from its effects — both real and imagined — on humans. It’s the reason pregnant women shouldn’t scoop their cat’s litter box. But it’s also been blamed for what some refer to as “crazy cat lady syndrome.” Though evidence on whether the parasite can cause schizophrenia and psychosis is currently mixed, there’s no evidence that it ramps up a person’s affection toward cats. Brief flulike symptoms are more likely. In nature, when T. gondii infects an animal — like a mouse — it rewires their brain to make them less afraid of the smell of cat urine, explains Gering. This makes them an easier snack, so when a cat eats the infected mouse, the parasite produces millions of spores that end up in the cat’s poop. Thanks to the worldwide colonization of mice, feral cats, house pets and their litterbox-scooping human owners, the parasite infects around a third of all humans, as well as wild animals in just about any ecosystem, says Gering. It’s been called the most successful parasite in the world. But despite its abundance, scientists don’t really know how the parasite affects the behavior of most animals. In a new study, Gering looked to hyenas, and found that T. gondii has an effect on their cat-related behavior, too: Infected hyenas get closer to lions. “This shows that this parasite is affecting the behavior of wild animals under natural conditions,” says Gering. “That’s really cool.” — ANNA FUNK & JEN MONNIER

Some people see the chickens as a way to make people come visit. Other people just see them as things that poop on their cars.

Q: Do people eat them? A: Well, in Hawaii, they say that the recipe for cooking a feral chicken is “put a rock and the chicken into water and boil it for two days. Then eat the rock.” So, most people would not want to eat one. They wouldn’t like the flavor or the toughness. But some feral birds fetch a high price in Asian markets; people eat them there. I haven’t been lucky enough to try it. The Gates Foundation is really interested in chickens as a resource that empowers women in parts of Africa. It’s a lot easier for women to give each other chickens than, you know, a cow. Then if somebody has a crop failure, they can kill one of the chickens and it’s a good source of protein.

The parasite Toxoplasma gondii infects warm-blooded animals worldwide, and reproduces in the digestive systems of cats. It’s transferred between hosts when a cat eats an infected animal, and when animals — or humans — are exposed to cat feces.

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chickens, we could find microbes that can be used as probiotics to keep chickens in agriculture settings healthier without relying on antibiotics. Compared to other meat sources, chickens have a small carbon footprint. So if we can make poultry farming

ILLUSTRATION: JAY SMITH

Q: What are some benefits of letting these chickens continue to roam in the U.S.? A: It’s possible that by studying feral

FROM LEFT: YAKONSTANT/SHUTTERSTOCK; CHERI ALGUIRE/SHUTTERSTOCK

A: I usually trap chickens with a spring-loaded

more successful and healthier, maybe we can reduce the carbon footprint of livestock production overall. There also might be a lot we can learn about the genetic basis of behavioral variation, including behavioral disorders, by studying these tractable animals and how they respond to dramatic changes in their social environment as they go feral.

net that’s deployed by manually pulling a very long string after a long period of waiting for birds to step into a corn-baited trap zone. These animals are very wary of unfamiliar objects, so I miss most of the shots I take. The process resembles Sylvester and Tweety more so than Rocky Balboa.

Q: Have you come across any totally unexpected results in your research? A: My favorite finding so far is we caught

Q: What do you say to people who might not be that interested in chickens? Do you have a way of winning them over? A: I like to tell people to think about the

several chickens in Bermuda that had extra toes. I learned afterward from some poultry breeders there that there are different breeds that have an extra toe. And some researchers have looked at what genes affect this trait, which is called polydactyly. Turns out this used to be pretty popular in chickens bred in the Atlantic region but has fallen out of fashion. So I’ve entertained the idea that these feral populations contain some mutations that have been lost as different domesticated breeds went out of fashion. Finding this trait in the feral chickens was unexpected.

Q: I want to know how you catch feral chickens so you can study them. I’m envisioning you training like Rocky Balboa to catch the flighty birds. Accurate?

dog and the wolf — same species, but one has been domesticated. Same thing with backyard chickens and the red junglefowl. So, which traits are the more wolflike or junglefowl-like traits, and which traits are somewhere in between? And where in the genome is that domestication process controlled? Just like with wolves and dogs, the junglefowl and the domesticated chicken have very different behaviors that relate to genetic variation and variation in the brain. I just think chickens are a great tool for asking all these really neat questions. D

The closest living relative of the Tyrannosaurus rex is none other than Galllus gallus — the chicken.

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THESE ANIMALS ARE VERY WARY OF UNFAMILIAR OBJECTS, SO I MISS MOST OF THE SHOTS I TAKE. THE PROCESS RESEMBLES SYLVESTER AND TWEETY MORE SO THAN ROCKY BALBOA.”

Joan Meiners is a freelance writer and ecologist based in Utah. Connect with her on Twitter @beecycles. N OVEM B ER 2 0 2 0 . D IS C OVER

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HISTORY LESSONS

Cracking the 414s IN 1983, A GROUP OF YOUNG ADULTS FROM MILWAUKEE BECAME FAMOUS FOR HACKING INTO SEVERAL HIGH-PROFILE COMPUTER SYSTEMS, INTRODUCING THE COUNTRY TO THE WORLD OF CYBERCRIME. n the 1983 techno-thriller WarGames, David Lightman, played by a fresh-faced Matthew Broderick, sits in his bedroom, plunking away on a boxy computer using an 8-bit Intel processor. As text flashes across the screen, David’s face lights up; he believes he’s hacking into a video game company, but the unwitting teenager is actually facing off against a military supercomputer. “Shall we play a game?” the computer asks ominously. In the film, the subsequent showdown triggers a countdown to World War III. The same year the film was released, a group of teenagers and young adults from Milwaukee were playing a game of their own. Much like Broderick’s character, these suburban tech savants — who dubbed themselves the 414s — hacked into large, networked computer systems used by high-profile organizations, looking for new games to play. And

I

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For much of the American public, the 1983 Matthew Broderick/Ally Sheedy film WarGames (top) and the 414s’ antics were their first introductions to the idea of “hackers.” At the time, personal computers like the Commodore 64 (below) were just becoming popular.

similarly, what started out as innocuous fun had some very real consequences. The group eventually was caught by the FBI for raiding around a dozen government and industry systems. Among these were Memorial Sloan Kettering Cancer Center and the Los Alamos National Laboratory, a nuclear weapons research site that produced atomic bombs used during World War II. While the 414s’ antics didn’t spark a nuclear conflict, they did ignite a national conversation on computer security — long before cyberwarfare made headlines and modern-day hackers like Edward Snowden became household names. Plus, the media frenzy fueled by the group alerted U.S. legislators that new laws were needed to combat computer crime. Ultimately, the group would help introduce the nation to the possibilities — and problems, like sloppy security protections — that come with computer connectivity. After the group was exposed, member Neal Patrick was asked on NBC’s Today show if he had any regrets.

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HISTORY LESSONS

“In hindsight, I really wish that accessing those systems just wasn’t so easy,” he replied.

WHIZ KIDS In the early 1980s, computer culture was having a moment. The first IBM personal computer came on the scene in 1981, popularizing the term PC. The next year, the Commodore 64 was introduced; it would later become the best-selling computer model of all time. By 1983, both tech aficionados and more cautious adapters were warming up to the PC’s potential. That same year, The New York Times went digital with the organization’s first newsroom computer. By today’s standards, however, these simple machines still had a long way to go. “One of the most relevant things here is just how early this was in the technology age,” says Alan J. Borsuk, who was a reporter at The Milwaukee Journal at the time and covered the 414s. “It was before there was a popular concept of the internet or email or anything like that. It was really very rudimentary — just the beginnings of things.” But for many, these proto-computers were a portal into previously uncharted territory. Tim Winslow, who would become a member of the 414s, first tapped into their potential as a junior high school student in the mid-1970s. His math teacher had brought in a primitive computer to test out some problems. The device, called a teletype, was essentially a mechanical typewriter that displayed

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text on a glass screen. Combined with an acoustically coupled modem, which transmitted signals through a telephone network, the system was able to send and receive typed messages. Winslow didn’t have a chance to test the computer during class. But he stayed after school that night to try it out for himself. As soon as his teacher dialed into the network and revved up the math program, Winslow was hooked. “I fell in love with just trying to learn and create with this new technology,” he says. Winslow found he wasn’t the only one who gravitated to these early computers. In high school, he joined an Explorer Scout program focused on computing and tech, sponsored by IBM, where he met most of his fellow would-be hackers. The members met right after school in downtown Milwaukee to program computer code together. Over time, many of them became friends, eventually deciding their group needed a name. In the 1980s, gangs in Milwaukee would identify themselves by the names of the streets they ran, like the 2-7s, who were active on 27th Street — numbers that were carved on the picnic tables where the hackers sometimes met for dinner. Since their turf was Milwaukee, the group took its name from the local area code and became “the 414s.”

LET THE GAMES BEGIN Over at least a year, the 414s used their home computers and telephone modems to connect to major computer installations across the country. By using basic passwords and login information — which were written in the instruction manuals for various computer systems and never updated or changed — they were able to penetrate these larger networks. For example, says Winslow, the login and password for one of the systems were simply that: system and system. “It was so easy to get logged into them because people didn’t read their own manuals,” he says.

FROM LEFT: PATRICK FAMILY; DOUG MCLEAN/SHUTTERSTOCK

Above: Neal Patrick became the face of the 414s, even testifying before Congress. Right: Early modems used acoustic couplers to send information over phone lines.

“I fell in love with just trying to learn and create with this new technology,” Winslow says.

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