drt de56tr h

HOW TO REMEMBER BETTER p.26

®

SCIENCE

THAT MATTERS

JULY/AUGUST 2021

EVERYTHING WORTH KNOWING:

MEDICAL BREAKTHROUGHS WHAT COVID TAUGHT US p.36 UNLOCKING THE POWER OF YOUR IMMUNE SYSTEM p.50 THE SECRETS OF UNDIAGNOSED DISEASES p.30 MUSHROOMS TO HEAL THE MIND p.44

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Mysteries at the Edge of Medicine

COVER STORY

The Future of Psychotherapy?

When Viruses Heal

Psychologist Alex Belser says psychedelic medicine could herald a mental health renaissance. He’s on the forefront of a boom in research and experimental treatments.

After more than a century of risky trials and medical advances, a viral cure for cancer could be on the horizon.

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That’s where the Undiagnosed Diseases Network comes in.

The most important COVID-19 takeaways are shoring up our collective defenses and priming the medical world for the next rogue pathogen.

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J U LY/ AU G UST 2 02 1 . D IS C OV ER

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COLUMNS & DEPARTMENTS

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Every week we receive and review lots of interesting story ideas from science writers around the world. Although it’s sometimes a time-consuming process, it’s one I’ve enjoyed for years: sitting down with my editors to evaluate the merits of each idea and deciding which stories we’ll assign from across the broad range of scientific endeavor.

Since the beginning of 2019, however, it won’t surprise you to learn that a very great many of the story ideas we’ve received (and generated on staff) have been related in some way to COVID-19. The ideas were good, the stories important, but the subject matter was getting to be wearisome.

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Ultimately, that’s what this issue is about: shining a light on research that delves into things unprecedented, grappling with mysteries that may be difficult, frightening and even wearisome to try and understand. But in that struggle, a path towards a better future emerges.

Stephen C. George, Editorial Director Feel free to send comments and questions to editorial@discovermagazine.com

Contributing Editors HOW TO REMEMBER BETTER p.26

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EVERYTHING WORTH KNOWING:

MEDICAL BREAKTHROUGHS WHAT COVID TAUGHT US p.36 UNLOCKING THE POWER OF YOUR IMMUNE SYSTEM p.50 THE SECRETS OF UNDIAGNOSED DISEASES p.30 MUSHROOMS TO HEAL THE MIND p.44

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social Emojis and birth the media didn’t proverbial facepalm. has But the internetfrontier opened a new for public shaming.

DEALING WITH

SCIENCE AND SOLUTIONS “When Shame Goes Viral,” Mar/Apr 2021

DIGITA L SHAM E

SOME ARGUE SHAME can be a forceful tool for change need — to respond. Instead, parents when wielded against powerful figures and institutions.

WHEN and educators should consider But A LEWINSKY when it’s weaponized againstMONIC others in shared helping theirED digital spaces, EMERG kids prepare for such IN 2014 these same tactics can morphEinto insidious behaviors, DECAD AFTER A situations beforehand. “Give like OF QUIET EXISTE them a cyberbullying or online harassment. situation,” he says, “to just practice NCE, SHE HAD A MESSA Getting called TO those skills of deflecting, ignoring out, insulted or bullied isn’t exactly new. But SHARE GE or the internet’s ability to amplify and. SHE ALSO making a joke of it.”

HAD A [even] permanently document MASTE R’S DEGREE IN those messagesSOCIA is. And thisLtool is now in the hands of most PSYCH OLOGY, EARNE Stop and stay calm. It’s young people: A 2020 report by the Cyberbullying Research D easy IN forLONDO even subtle digital Center shows that N WHERE SHE 95 percent HUNKE of U.S.RED teens are online, clashes to make your blood DOWN most tweens (ages 9 through 12) FOR GRAD have personal devices and boil.

“If you’re SCHOO upset, realize that 9 L. VANITY out of 10 of themFAIR used social PRINT media or the threat response center of your EDgaming in the past HERapps EXCLU year. Here’s how experts recommend brainFIRSThas taken over,” Willard says. guiding kids and teens SIVE PERSO through this digital N COME “Unfortunately, when this happens, landscape.

BACK STORY

3

HAME 4 S GOES

IN 2014. THEN

your emotional regulation and your thinking centers go offline.” But Think before you post. In the when they describe you,” Willard there are ways to remain zen. Take digital age, what we share says. “Then, when you’re posting some deep breaths. Step away from can become permanent. something, [ask yourself], ‘Does the keyboard. Go for a walk outside.

It’s also a way of presenting that reflect those qualities?’ ” ourselves to others, says web safety expert Nancy Willard, Put yourself in the other author the stage of of to tell Work through scenarios life after becoming Cyberbullying and person’s shoes. If you’re “that woman” in Cyberthreats. one of history’s most widely in advance.

If someone director broadcast atbeing OpenMind, In short, consider belittleda online, sex scandals: “I what went it yourbeing psychology-b social from lashes out at ased educational a completely private you online, says platform. may say The media footprint says result more figure to about is a the humiliated other about you. steady a publicly flow of new names Justin W. Patchin, codirector one, worldwide,” targets of the and — both Lewinsky says in her person “Write down theTED than high-profile it does aboutand key words you, says citizens Talk, which that now 2015 everyday flooding hasCyberbullying more than 18 Research — our media psychologist you would like other Sherry million Center, you feeds “I waspeople Turkle, and rage founding patient tozero use of losing cycle. Some call it might feel the desire —views. cancel culture; a personal the director others of the reputationeven MIT embrace global scale, almost Initiative itonas a social on the instantaneously.”

Whatever reckoning. you call Technology andthis Selfnew The infamous 1998 andwave author of of public shaming, researchers incident with President are evaluating The Empathy occurred at the dawn Diaries. “Ifwhether Bill Clinton you canthe ancient is benefiting of the internet age emotion Social media sites, or keep — that on a in harming mind, humans today — fact Lewinsky, who says such as Instagram, and to what extent. The results ” she says, “then her name has appeared not lost may hold the whole experience in “almost TikTok and Snapchat, 40 rap songs.” Her actions willsome seemkeys lessto our collective future. as a 24-year-old intern can be common bewildering to you, emotionally.” viral pre-social media. went In recent

1

SHE TOOK

Monica Lewinsky was a 24-year-old intern when public shaming changed her life forever. Since her scandal with Bill Clinton — then president of then, social media the United States has slung shame — went viral at countless other targets.

2

VIRAL years, the rise of Facebook potential for public

EMOonTION AL shaming internet, motivated EmpowerHUMILIATI SOCI yourself with the.

ON Lewinsky Long before ENT to speak up. “A PLEX the internet, people ANCI has emerged marketplace If you do find who violated moral THIS COM where public humiliation in a societytools. codes would is a commodity, ON IT. YS BEEN and shame yourself,get to a pillar, stocks or orfastened is an industry,” your child, ALWA FUEL device in which she pillory, a HAS says inRED the offender’s head the video.

POU One can only speculate being cyberbullied, and hands were locked often the tech RNETwhether IA.have INTE Lewinsky been met would THE MED itself can provide a number of with criticism SOCI E or empathyAL on today’s digital stage. In some CAM simple ways to respond: Blocking cases, this internet-base THEN

d outrage culture results in positive change. It has exposed grave offenses, elevated Y MEINCH political movements

BY TIMOTH U.S. and beyond. Hollywood and toppled abusers in the giant Harvey Weinstein, example, was ousted, for charged and imprisoned of the widely broadcast on the heels #MeToo campaign.

For better or worse, the internet and social have significantly media amplified humanity’s means of public shaming, taking victims from the town square global network of to a connected screens.

“The internet now allows hundreds or thousands of people to participate in collective shaming, in a way that wasn’t possible before,” says Takuya Sawaoka, a social psychologist 42 D IS C OVER MAG A Z I N E .C O M and research Organized public shaming with the pillory designed dates back more than 1,000 years, specifically to make society’s offensive a spectacle out of characters.

40

D IS C OVER MAG

A Z I N E .C O M

THE ROOTS OF

5

the offender. Reporting hurtful exchanges. Taking screenshots.

Saving message threads. Patchin says having that evidence can help if the behaviors do escalate beyond one hurtful offense to repeated, long-standing harassment. “It’s a lot easier for authorities to get involved when they can see exactly what’s going on,” he says. — ALEX ORLANDO

CLARKANDCOMPANY/GETTY

and Twitter, and the

AYK_SHALUNTS/SHUTTERSTOCK

avenues for cyberbullying.

In recent years, multiple national

in 1998. She says

protests and civil rights rallies

emerged from hashtags, such as in avia spread primarily wooden social media #BlackLivesMatter and #MeToo, frame.platforms The masses online. that would gather to taunt jeer them, hurling and rotten food at their case, disgust directed heads along with at the self as a source the masses. insulting words. boarding Minutes before This dual punishment tion for the group. of contaminaan 11-hour and flight to spectacle aptly [social media] is that it’s devoid of named South Africa, —problems with pillorying Sacco posted a tweet— her 170 experts continue to followers) more than 1,000 years context,” saysWhile ago in parts of Europe. (tostarted Lisa Feldman probe the origins that permanently a neuroscientist changed her many And it lasted contemporarBarrett, to Africa. well into Hope psychologists classify andof shame, century, when, you life: “Going the 19thpsychologist at NortheasternyUniversity I don’t get AIDS. could Just kidding. I’m and author itofas a selfconscious, moral emotion say, it got canceled. white!”

How Emotions Are Made: worth noting that this practice By the time“It’s The Secretassociated Life of the with Sacco feelings of powerlessnes worthlessness landed, Brain. ofwas people eventually This is compounded bys,the outlawed because tens of thousands and media other psychologica had responded fact that social became turmoil in the individual. to and sharedither doesn’t tweet.regarded l The hashtag to be Sawaoka too cruel,” always allow “Maybe it’s this thing says. the same back-and-forth England #HasJustineLandedYet fromforgroup-level discourse thatthat came went viral fully abolished the with processes and certainly pillory by 1837, people use with many nearbyaround the world, in itreal life to talk a barrage ofalong about their problems.had But criticism its benefit. countries really Instead, her racist. can wreak and mostwas The moment ries by that calling havoc on the individual U.S. territoplatforms such time. as Twitter The fueled in part and and make things worse, Facebook are mostly by the fact that shestate level Delaware was a last wasof airborne in the Western ” says Michael Slepian, holdout designed psychologist for broadcasting, she says, world, outlawing it and would remain oblivious rather than actual a social to the fallout at Columbia University. until she reconnected as recently Whether to as 1905. communication and exchange or not it involves the internet. She Slepian’s work buildsbetween people: “It’s mostly as a seniora literal pillory, shame about has also worked on a popular theory speaking, run parallel with communicaand it’s not tions director, generally that guilt, in ”psychology very much which created about listening. humanofcivilization when the perfect storm compared social irony to its relative, order through publicrole shame, takes on moral a distinct and internet memes. outrage ages. Some anthropologi and However, is not always Sacco wasthe aimed in the immediately at human evolutionary fired from sts and psyche. reforming psychologists Essentially, a specific feelings offender. her job, and became the subject of endless guilt stirs The goal might be solidarity of regret the caseand or remorse that shame universal and biological, makearticles toward a specific incident group behavior a book. One as an evolved mechanism iswith a victim, cause, and someone thatorhas shifting cultural of the overwhelming questions or affected values ensure in her case, our survival. to in anyone else. Shame, witnessing other the outrage. and many similar instances, on the hand, brings up broader feelings is to what degree any single The idea is that adaptations of worthlessness “The person and self-judgmen who has done blunder should favoring define a person’s reputation. t. [the offense], say, Harvey and mutual whencooperation aid stretch as far back Andgroup Weinstein,“That’s may bethe a lost does Twitter ” Cohen as early human foragers, key cause, shaming explains. “But, by distinction or any pile-on of criticism according between to — toward a 2018 guilt and shame,” making him study published in says Carnegie an example, someone — it sets the standards for our Mellon the Proceedings of University thebecome Nationalbullying? organizationasociAcademy of Sciences. gistcodes. l psycholoTaya Cohen.

What is“ acceptable As you that Researchers suggestedety. Moral might andthing, ‘You did a bad expect, non-acceptable complicated. “One feelings ofit’s the shame ’ vs. ‘You are a bad behavior.person.’ in an individualofare ” ” For example, if you nature’s way of “encoding the social post an angry rant cost” of certain behaviors a friend on social media, about stealing. The study you might feel guilty — such as PUBLIC tested this idea in apologize. A so-called MORAL OUTRAGE and later 15 remote, IS NOT dent communities ALWAYS shame indepenAIMED AT REFORMING to the same situaaround the world tion Aresponse would SPECIFIC OFFENDER. make you feel like and found THE patterns in the same a horrible, worthless SOLIDARITY each.GOAL MIGHT BE WITH SlepianAsays VICTIM, person.

GROUP he questions AND SHIFTING ConsideringCULTURAL whether OR thereCAUSE, how societies areVALUES. is any healthy place for shame today: “I built on norms and don’t know whether archy, a 2020 study hiermaking people feel published in Frontiers small and powerless and helpless is ever in Behavioral Neuroscience framed a good thing.” shame as “an evolved disease avoidance architecture” wherein the emotion SLINGING SHAME MARCH/APR I L 2 02 1 . D IS C OVER 43 helps to protect individuals from undesirable Just as Lewinsky was social circumstance patient zero for instant as being an outsider s, such humiliation, Justine to a group. The study global Sacco presented some evidence that shame for viral Twitter shaming, in 2013 became a poster child may be linked to disgust — in this now common practice platform built for on a rapid-fire input (often criticism) from

PREVIOUS SPREAD: LEXEY WWJESSE GRANT/GETTY PEVNEV/SHUTTERSTOCK. THIS SPREAD, FROM LEFT: IMAGES; REUTERS/ALAMY STANISLAVA KARAGYOZOVA/SHUTTE STOCK PHOTO RSTOCK;

WHEN

MARCH/APR I L

2 02 1 . D IS C OVER

41

I have been a subscriber to Discover for a few decades, and notice a distinct drop in “hard” science reporting of late. While cyberbullying is real, you needed to have sociologists formulate studies on how to counteract this. Soft news reporting and editorialization is not good enough for Discover.

Tejas Godiwala Metairie, LA

the U.S., look at the differences in values and beliefs of the two major political parties, and even within the individual parties in regard to respect for the “others.” When different peoples are not treated with respect, how can digital beings be treated with respect? I remember HAL the movie 2001: A Space Odyssey; yes, computers have changed, but most people haven’t.

Fred School Cincinnati, OH

I’M SORRY, DAVE. I’M AFRAID I CAN’T DO THAT. “Big Idea: Embracing the Singularity,” Mar/Apr 2021

I suggest when Nick Bostrom, et al., teach “human morality” to a nascent superintelligence, they make sure that this new sentient entity is NEVER given access to any of our history or any current news media.

Human treatment of fellow humans has never been very moral.

Tucker Spolter

The article “Embracing the Singularity” I think that concept of fails where all other having a single AI to speculations about deal with all intelligent of humanity machines do: is delusional.

How do you I have not first explain observed to a machine any common what ideas PSYCHOLOGY CYBERBULLYING moral code such as value accepted and want are? within the These are U.S., let alone emotional the whole concepts, used world. The differences to define intelligence. between different nations Harold Parks or religions in their Minden, NV values is vast. Within DEMENTIA MYSTERY SOLVED p.22

®

SCIENCE

THAT MATTERS

THE

OF

NAVIGATING ONLINE SHAMING AND SOCIAL BACKLASH p.38

HUNTING THE FIRST STARS p.52 SECRETS OF URBAN WILDLIFE p.46

8

MARCH/APRIL 2021

D I S C OV ER M A G A Z I N E .C O M

FROM THE WEB

INBOX

36% WE CONTROL TECHNOLOGY

64% TECHNOLOGY CONTROLS US

We asked our Facebook followers: Do we still have control over technology or is it already controlling us?

SPACE WASTE “Out There: Medicine for Mars,” Mar/Apr 2021

Why do we waste such immense amounts of money and effort trying to figure out how to live on Mars when we cannot even manage our existence on Earth?

Phil de Anguera Woodcliff Lake, NJ

AVOIDING VIRTUAL SHAME “Editor’s Letter: Shame on Me,” Mar/Apr 2021

I love humor. I have avoided most of the internet, other than watching some YouTube that interests me. But from reading about it in advice columns, I’m amazed at the emotional wars waged on the internet! So much — way too much — of modern life is lived online. People can be vicious when anonymous, sort of the way people in crowds often act in ways they would not if alone.

Humans … not as evolved as we would like.

Christi Driggs Tucson, AZ

Sally Harding: I think we are giving control to technology. How many of us remember phone numbers anymore, rather than relying on phones? How many of us can go a full 24 hours without the internet? How many of us can look in the mirror with brutal honesty and saw we did not develop one or more opinions based entirely on something read on social media? I don’t think it’s all bad, but I think we need to teach critical thinking in schools.

Lesley Mcgilvary: The rich and powerful people who own and control technology are using technology to try to control us, as they have throughout history.

Jim Hanson: It is starting to control us, though not as a conscious entity. Our dependence on it has penetrated every aspect of our lives, to the point where many people today are naturedeprived. But we can break free by getting “back to nature”!

Loran McCormick: Take the modern phone as an example; has it not became an extension of your mind? An augmentation to your brain? If you had to put it down RIGHT NOW and NEVER use that technology in that way ever again, could you?

HOT SCIENCE T H E L ATE ST N E WS A N D N OTE S GLACIAL GADGET • THE SCIENCE OF DECAF COFFEE • BACKYARD ANT DISCOVERY ONLINE SHOPPING ADDICTION • MUSIC’S ORIGINS • HAIL ALLEY • REVIEWS

COLORFUL COMMUNICATION Iridescent colors in animals, like the shimmering hues of this hummingbird’s feathers, have long entranced humans. The colors we see partly depend on the angle they’re viewed from, though, which is why some species have developed unique adaptations to get the right message across. According to a March study in Trends in Ecology and Evolution, researchers at the University of Melbourne suggest that animals with iridescent color patches can only use them as reliable signals by pairing them with certain structures or behaviors. For example, male Anna’s hummingbirds position their opalescent throat patches during courtship rituals so that females perceive them as bright pink. Vibrant rose-red head feathers, meanwhile, may show rival males that they enjoy protein-rich diets. — MOLLY GLICK; IMAGE BY WADE TREGASKIS

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Michael Prior-Jones untangles more than 3,000 feet of wire cable at Store Glacier in Greenland.

Plumbing the Depths RESEARCHERS HAVE DEVELOPED A WIRELESS DEVICE CALLED CRYOEGG TO PEEK INTO MELTING GLACIERS. THEY HOPE THE EGGLIKE GADGET WILL SOMEDAY REVEAL THE SECRETS BEHIND FUTURE SEA-LEVEL RISE. On a rainy day in July 2019, Michael Prior-Jones spent eight hours slip-sliding across a Greenland glacier.

To help a colleague test the conditions deep beneath the ice’s surface, he played an intricate game of cat’s cradle with over 3,000 feet of wire cable. Pacing back and forth, he placed the cable on the ice to smooth out tangles and attach sensors that help indicate the speed at which the glacier is melting and moving toward open water.

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By the end, he was cold and soggy, but the wire was snarl-free and prepped for its descent into the glacier.

For decades, researchers like Prior-Jones have affixed instruments to cables, dropped them down cracks and boreholes, and analyzed the data that streams back through the wires. By extracting secrets from the depths below, scientists aim to understand the channels that melting water carves on its way from the glacier’s surface to the sea. Glaciologists’ work is critical, because

the relationship between these inner meltwater channels and the fate of glaciers remains poorly understood — a key mystery in predicting how the world’s oceans will change as the climate warms. Gauging certain characteristics of the meltwater, like temperature and electrical conductivity, can reveal just how quickly we can expect glaciers to disappear and add to global sea-level rise.

But collecting these crucial measurements is no small feat. Stringing

sensors on wires is a common technique, but cables can be cumbersome. Prior-Jones was well aware of the frustrations associated with the traditional data-collection methods before his day of cat’s cradle. His Greenland experience underscored his ultimate goal: avoid cables at all costs.

That’s why he teamed up with fellow Cardiff University researcher Liz Bagshaw to develop a wireless subglacial probe — leveraging the same radio technology from utility meters that some countries employ to report gas and water usage. Although it’s fondly named Cryoegg, the instrument is more akin in size, shape and weight to a grapefruit. Researchers will lower it into a crack

or borehole and set it free to bump along the glacial “plumbing” that carries the lubricating meltwater to the glacier bed, and eventually to the sea. Along its journey, the probe will transmit hourly pressure, temperature and electrical conductivity measurements to an antenna at the surface for a year.

Best of all, there are no strings attached.

Gauging certain characteristics of the meltwater can reveal just how quickly we can expect glaciers to disappear.

FROM LEFT: ELIZA DAWSON; MAURO WERDER

HATCHING A PLAN This free-range egg was the brainchild of glacial biogeochemist Jemma Wadham and aerospace engineer Stephen Burrow at the University of Bristol, where Bagshaw completed her postdoctoral research. While working with Wadham and Burrow, Bagshaw studied glacial drainage using “drifter” sensors that float along sans cable.

Unfortunately, they were not equipped with a wireless transfer system like Cryoegg.

Sometimes, the sensors would remain stuck inside the ice, chirping away as they collected measurements that would never see the light of day. “That was the point that made me think, ‘We need to get serious about this data transfer,’ ” Bagshaw says.

By 2013, the Bristol team had a rough prototype to begin elucidating the dynamic environment within the ice. It couldn’t have been more timely: During Cryoegg’s development over the last decade, the Greenland Ice Sheet has lost over 2,000 gigatons of ice.

In the summer of 2019, Bagshaw and Prior-Jones first tested their newest design with three trials

across Greenland and Switzerland. In a study published in the Journal of Glaciology, they demonstrated that Cryoegg could transmit important data through more than 4,000 feet of ice. While the borehole doesn’t yet connect to subglacial water channels, it’s a significant milestone for climate change research.

During its subglacial dive, Cryoegg measures temperature to indicate whether there’s liquid water present, as well as electrical conductivity to signify the amount of dissolved minerals. This reveals the meltwater’s speed:

If the meltwater is flowing quickly, it will be relatively pure. But if it’s stagnant, the water spends more time interacting with the bedrock, dissolving more minerals and increasing conductivity.

The egg’s pressure data may be most telling. If the pressure is relatively high, there’s likely a lot of meltwater pooling in the bed’s cavities, forming the lubricating film that propels the ice forward. During melt season, the water tunnels beneath the glacier, alleviating the pressure and decelerating the glacier’s glide toward open water. The Cryoegg’s pressure measurements can help researchers infer the structure of this hidden drainage system, and how the meltwater streaming down from the surface will hasten the glacier’s journey to the sea.

A WELL-ROUNDED TOOL While Cryoegg’s spherical shape makes it ideal for rolling along with the meltwater and withstanding pressure, it’s the wrong fit for most electrical

Prior-Jones holding a Cryoegg probe at the Rhône Glacier in Switzerland.

components. Bagshaw and Prior-Jones jokingly call this conundrum an engineer’s “worst nightmare,” so they’re still resolving design vulnerabilities.

The researchers are also working with a relatively inefficient data-transmitting antenna, because it’s the only one short enough to fit inside the spherical case.

But while their Greenland trials demonstrated that Cryoegg could wirelessly transmit data through more than 4,000 feet of ice, it was still over half a mile short of reaching the bed of the Greenland Ice Sheet at their testing location.

With most other glaciers, Cryoegg’s transmission record would be more than enough to reach the bed, according to Thomas Schuler, a glaciologist at the University of Oslo who was not involved with the study. He says it would be “an enormous step forward” to have a wireless device like Cryoegg for traversing perilous glacier interiors.

But, short of erecting a trail of receiving antennas across the ice, the question remains how best to track the egg once it’s on the move.

For now, half a mile of ice still stands between Cryoegg and the truth about glacial plumbing — and the future of our oceans. Because nobody knows what’s going on at the bottom of glaciers, modelers are left to make assumptions based on what limited data exist, PriorJones says. “Having new data will improve those models and improve forecasts of sea-level rise. That’s the idea.”

— RALEIGH MCELVERY

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HOT SCIENCE

Coffee without caffeine: It’s less bold, but won’t leave you with the jitters. The production process requires chemicals, filters and a lot of work.

Healthy or Not Scan this code with your phone’s camera for more: Health Benefits to Coffee? The Science Looks Promising.

REMOVING CAFFEINE FROM COFFEE IS COMPLICATED, BUT THE PROCESS HASN’T CHANGED MUCH IN THE PAST HUNDRED YEARS. For many of us, a cup of coffee is the first thing on our minds in the morning.

It’s such a ritual that we’ll still down a mug of joe even when that coffee is missing the thing it’s known for: caffeine.

Decaf coffee has been around for over a hundred years, and the process for making it has been roughly the same the whole time.

Caffeine is locked inside coffee beans alongside the complex blend of compounds that give roasted coffee its distinctive taste; removing one of its most notable molecules is, naturally, a labor-intensive process.

Some techniques take the caffeine directly out of the

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beans themselves, leaving flavor compounds behind.

That procedure starts with steaming or boiling green, unroasted coffee beans to free up the caffeine in their interiors. Then, coffee manufacturers typically use solvents like methylene chloride or ethyl acetate to wash out the caffeine molecules. Like sugar in water, caffeine dissolves into

Genetically caffeine-free coffees aren’t on the market yet, but hope remains.

these compounds, leaving behind a bean with little to none of the compound left.

Others brew what is essentially strong coffee, use solvents to remove the caffeine and then soak the already-brewed beans in the decaf liquid to reinfuse them with their flavor and aroma.

A newer method, called the Swiss Water Process, uses a carbon filter, rather than solvents, to remove the caffeine from the beans.

And a more technologically advanced (read: expensive) version of the decaffeination process relies on supercritical carbon dioxide. Under very high pressures, CO2 will adopt properties of multiple states at once, flowing like a gas, but maintaining the density

of a liquid. In this form, the CO2 can bind to and remove the caffeine after the beans are soaked in water.

As many coffee lovers note, decaf coffee often falls a bit short in terms of taste.

Despite over a hundred years of innovation, coffee manufacturers still haven’t been able to extract caffeine from coffee without altering its flavor profile to some degree.

If you think there should be an easier way to produce decaf coffee, you’re right.

Scientists have discovered a few different strains of coffee plants that are naturally decaffeinated, but scaling up commercial production hasn’t quite worked out yet.

For a variety of reasons, genetically caffeine-free coffees still aren’t on the market, but hope remains for a bolder (decaf) brew.

— NATHANIEL SCHARPING

LEFT: CAMMERAYDAVE/DREAMSTIME. RIGHT: JACK LONGINO/UNIVERSITY OF UTAH (2)

DISSECTING DECAF

A NEW ANT IN TOWN Jack Longino, seen here on Washington state’s Mount Rainier, spent much of his career digging for ants in Central American rainforests.

BIOLOGIST JACK LONGINO DISCOVERED A NEW SPECIES RIGHT IN HIS OWN BACKYARD. The work of finding

IN HIS OWN WORDS …

and classifying new species — taxonomy — shows a strong regional bias. As Jack Longino, a biologist at the University of Utah, describes it, most of the species native to Europe and North America already have been discovered. So, most modern taxonomists, no matter where they’re from, tend to conduct their research in tropical climates, where the less-studied landscapes house a greater diversity of organisms. Longino himself has spent most of his career traveling to the rainforests of Central America.

Hunting for ants nesting in dead wood, he has found over 100 new species. But when Longino discovered a new ant species, Strumigenys ananeotes, in the summer of 2018, the real surprise wasn’t that he found it so much as where he found it: at home in his own backyard.

Here I am, an expert, going off to these exotic tropical locations to find new species. And I live in this suburban house in Salt Lake City near the University of Utah, with a little garden in the back. I went out one evening and got down on my hands and knees looking for springtails [small arthropods] that come out at night. I was looking at the soil, and I saw these ants walking by. I couldn’t tell what species they were — for that sort of detail you

have to put them under the microscope — but I knew they belonged to a group of ants that shouldn’t have been there. The group occurs either in the tropics or deciduous forests of the eastern U.S. — not in Utah.

My jaw dropped.

My first thought was that this is an introduced species. I collected a bunch and took them into the lab, fully expecting to identify them as some species from somewhere else. But, lo and behold, they were different

enough from known ants to be a distinct species.

For me, it was mind blowing that I had found a new species in my own backyard. It was one of the odder occurrences in my life.

Just two weeks ago, one of my undergraduate students found the second-ever record of these ants under a

paving stone in his backyard.

You could say the experience reinforced something I’ve always felt, which is that it pays to be observant wherever you are, to expect the unexpected.

There are still plenty of mysteries in the world, and some of them are right under our noses. I’ve been urging people to head out into their backyards on early summer evenings, and crawl around and see what they can see. — AS TOLD TO WILSON CHAPMAN

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WHY IS ONLINE SHOPPING SO ADDICTIVE? CAN’T STOP GOING ONLINE AND BUYING STUFF YOU DON’T NEED? THE URGE TO SPLURGE IS A CONSTANT TEMPTATION FOR MANY, AND COVID-19 STRESS HAS ONLY FUELED ONLINE SHOPPING ADDICTION. In the past year of pandemic, millions of people turned to the internet to order groceries, household supplies and other goods they’d typically purchase in person. Our phones and laptops became sanitary havens of commerce. But for some, online shopping can easily transform from a convenient consumer strategy into an excessive, harmful behavior.

The Diagnostic and Statistical Manual of Mental Disorders — the handbook for the diagnosis of mental health disorders used by health care professionals in the U.S. — doesn’t officially classify shopping addiction (or, more technically, “compulsive buying” or “oniomania”) as a disorder.

Nevertheless, professionals have recognized it as a problem for more than a century; the influential German psychiatrist Emil Kraepelin first described it in the early 1900s.

Compulsive buying has only grown more effortless with the advent of computers.

Today, surveys suggest 6 percent of Americans struggle to control their spending,

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and that many prefer to buy via the internet. “Online shopping is easy,” says Melissa Norberg, an associate professor of psychology at Macquarie University in Australia. “It’s right there at home, and you’re stuck there.

‘Let’s see what Amazon has to offer me.’ ”

PROBLEMATIC PURCHASING Of course, we all avail ourselves of Amazon and its ilk now and then. Like any behavior, this one exists on a spectrum. So how do you know when you’ve reached the extreme?

Online shopping addiction is more than spending a bit too much time browsing the web. It’s a constant preoccupation, an overwhelming urge to shop, and precisely to shop — gratification comes from the process, not from the possessions themselves.

The reward is divorced from the purchase’s practical purpose. In a 2015 review of research on compulsive buying, the authors write that patients report they “rarely or never use the bought items.”

The pleasure of acquiring superfluous shoes and

kitchenware is, predictably, fleeting. “Shortly after they make a purchase, they often feel really bad,” Norberg says.

This shame and disappointment is another hallmark of an unhealthy habit — and it also feeds that habit. “It’s this reinforcing cycle,” she adds.

“You feel good, then you feel bad, so then you want to feel good again.”

A spree of compulsive buying often begins, as it ends, with negative emotions: loneliness, depression, anxiety. A person may turn to shopping because they are unable to deal with some stress in their life, or to boost their own sense of self. But it can also begin with a more neutral state of mind, like boredom.

Surveys suggest 6 percent of Americans struggle to control their spending, and that many prefer to buy via the internet.

The underlying principle is that humans seek to enhance their mood, and in a year of isolation and uncertainty, many are more in need of coping mechanisms than ever before. We often refer (quite flippantly) to this emotional spending as “retail therapy.”

The name is misleading, as it implies the act will improve

FROM TOP: MELPOMENEM/DREAMSTIME; VADIM GINZBURG/DREAMSTIME

Online shopping can veer into addiction when the rush of purchasing supersedes the item’s practical purpose.

mental health. The opposite is far more likely.

Compulsive buying can disrupt more than your mental health, too. The financial consequences are self-evident, and many people have shopped themselves into debt. But as the behavior consumes more time and attention, it can just as easily spark conflicts with family and friends, or interfere with work, school and other social obligations.

In fact, an online shopping addict need not spend a single dollar for the habit to

become problematic — the endless scrolling alone is often enough.

DEALING WITH ADDICTION There’s been little research into the causes of compulsive buying, though researchers guess that it hijacks our body’s reward system in the same way as other behavioral addictions, like gambling.

The activity of shopping and purchasing delivers a rush of dopamine, and the brief euphoria associated with it, then leaves us feeling as low as ever.

Internet vendors wield an arsenal of clever sales tactics

against our meager brains, making it all the more difficult to resist the desire to buy. “Marketers know, perhaps better than the clinical psychologists, what drives purchaser behavior,” Norberg says. Algorithms present you with unsolicited advertisements based on your search history. Amazon automatically suggests items to pair together. E-tailers offer flash sales and “buy now, pay later” schemes.

No medications have yet been proven effective in treating shopping addiction — though, considering its close ties to other mood disorders, like anxiety and depression, it may be possible to treat both problems with one pill. A few studies

have found that group cognitive behavioral therapy helps, and guided self-help can sometimes achieve the necessary intervention.

For some, a simpler, do-it-yourself strategy may suffice. Norberg favors a mindfulness approach.

First, she recommends reflecting on your behavior and whether you are buying things you don’t need. One obvious — and highly common — indication is that the purchase never even leaves the box it arrived in.

Next you need to identify what triggers you to shop.

Some triggers, like shopping apps that enable unhealthy behaviors, can quickly be removed from your life.

Others can’t. “You’re not going to be able to throw away your laptop,” Norberg says. “You’re going to have to learn, how do I use my laptop, but not engage in excessive purchasing?”

For that, she suggests facing the problem boldly.

“It’s about opening up our laptop, going to Amazon, looking at the things we want, letting ourselves feel that discomfort, and just sit with it and be very mindful.”

Then, find healthier ways to fill the psychological void: Call a friend, go for a run, read a book, practice a hobby. All of these can relieve the emotional problems that fuel shopping addiction, Norberg says.

“It’s finding different ways to get your needs met.”

— CODY COTTIER

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Where Did Music Come From?

DID HUMANS EVOLVE TO SING AND DANCE, OR DID WE INVENT OUR MUSICAL PASTIMES? SCIENTISTS ARE STILL DEBATING THE ORIGIN OF THIS UNIVERSAL BEHAVIOR.

L

Ear Worms Scan this code with your phone’s camera for more: Why These Catchy Songs From 2016 Are Still Stuck in Your Head.

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ook anywhere and you’ll find music. Without a single exception, every culture produces some form of it; like language, it’s a universal trait in our species, and over the millennia it has bloomed into a diverse and stunning global symphony.

Yet music’s origin remains one of the great secrets of human history.

The oldest known instruments are 42,000-year-old bone flutes discovered in caves in Germany. Vocal music surely predates these, but the problem, according to University of Amsterdam musicologist Henkjan Honing, “is that music doesn’t fossilize and our brains don’t fossilize.” With little hard evidence, scientists still debate what evolutionary purpose music serves. And because its purpose is obscure enough to warrant debate, some skeptics question whether it serves any purpose at all.

Charles Darwin thought it did.

In music, he found evidence for his lesser-known theory of sexual selection.

Drawing a comparison with birdsong — which is partially a courtship tactic — he proposed in his 1871 book The Descent of Man that although our melodiousness doesn’t help us survive from day to day, it could have evolved “for the sake of charming the opposite sex.”

This view of music as a primitive love song is less fashionable today. (Although, as Keio University musicologist Patrick Savage jokes, it may find a compelling “poster child” in Jimi Hendrix and his many romantic liaisons.) But an array of new ideas has taken its place as psychologists, cognitive scientists, anthropologists and others continue to confront the mystery of music.

“CHEESECAKE” OR SOCIAL GLUE? For decades, music researchers have more or less settled into two camps: those who believe their subject of study is a biological adaptation, and those who believe it’s a cultural invention.

In the latter argument, the rhythms, melodies and harmonies we cherish are no more than frivolous luxuries — “auditory cheesecake,” as evolutionary psychologist Steven Pinker memorably put it in his 1997 book How the Mind Works. Rather than a biological adaptation in its own right, music is a coincidentally pleasing byproduct of other adaptations, such as language.

“As far as biological cause and effect are concerned, music is useless,” Pinker wrote. “Music could vanish from our

OLGA KOSTENKO/DREAMSTIME (2)

Rather than an adaptation in its own right, music may be a coincidentally pleasing byproduct of other adaptations.

species and the rest of our lifestyle would be virtually unchanged.”

Some found this verdict too dismissive. After all, the capacity to make and enjoy music seems ingrained in each of us, just like other valuable adaptations.

These days music is a profession, but even “ordinary mortals who never had a music lesson have implicit knowledge of the structure of the music of their culture,” says Sandra Trehub, a psychologist at the University of Toronto. They may not know an arpeggio from an interval, but they can keep a beat, copy a pitch and move their bodies to sound.

Trehub studies music perception in infants. “They’re quite captivated by music,” she says, and their aptitude for distinguishing differences in pitch and timing is, in many ways, similar

to adults. They can even remember melodies months after hearing them.

“You see these amazing abilities,” she says, “and you have to think … there is a biological foundation for it.”

That doesn’t necessarily mean we evolved that foundation for music, specifically, but many scientists have offered explanations for why we might have. Some argue music is a mechanism for social bonding, helping us to coexist in cohesive, well-functioning groups.

For millions of years, our primate relatives have engaged in a form of bonding known as social grooming, where they clean each other’s bodies and release endorphins in the process. But in bigger, more complex human cultures, grooming wasn’t enough. Collective singing and dancing (as well as laughter, to a lesser extent) can serve the same purpose on a far larger scale.

Another possibility is that music sprang from the soothing sounds parents make to communicate with infants. If prehistoric lullabies improved parent-infant bonds and offspring survival, there could have been an evolutionary incentive for the caregiver’s cooing.

Some researchers even argue that the earliest version of music — whatever it entailed — may have given rise to language itself. (Darwin also believed this.) Others think that music and language share a common ancestor. In University of Reading archaeologist Steven Mithen’s book The Singing Neanderthals, this ancestor is an ancient communication system bearing the onomatopoeic acronym “Hmmmmm” (Holistic, manipulative, multi-modal, musical and mimetic). Steven Brown, a neuroscientist at McMaster University, dubs it “musilanguage.”

BEYOND THE BINARY Some have sought a way around the adaptation-invention dichotomy, a debate musicologist Savage believes has “outlived its usefulness.” He and others distinguish between music (a cultural product) and musicality (the biological underpinnings that allow us to create

and perceive music). This alone doesn’t explain the ultimate origin of music, but it does allow room for both nature and nurture.

In August, in an effort to reconcile many previous theories, Savage and a group of cross-disciplinary co-authors published a paper presenting what they deem “the most comprehensive theory to date.” (Savage admits it may even be “too broad.”) They suggest that cultural music and biological musicality have developed in tandem, in a kind of “gene-culture evolution.”

Their idea builds on the work of Aniruddh Patel, a cognitive neuroscientist at Tufts University, who contends that music was initially an invention, but that it proved so useful in social bonding that it kicked off an evolutionary feedback loop. Natural selection began to favor this newfound musicality, a human creation, in the same way that it favored adaptations for digesting cooked food after early humans mastered fire.

Savage and his colleagues also take a broader view of social bonding, encompassing many ways in which we build and maintain relationships with our fellow humans. Music can act as a social glue, they agree, but it’s also helpful in pacifying crying babies and courting mates, among other things. To pigeonhole this versatile behavior, they argue, is a bit like claiming that vision evolved only for spotting predators when it’s clearly “more a cognitive toolkit than a single tool.” — CODY COTTIER J U LY/AU G UST 2 02 1 . D IS C OV ER

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Welcome to ‘Hail Alley’ A FEW UNLUCKY FACTORS MAKE SOME WESTERN STATES MORE PRONE TO PELTING ICE. RESEARCHERS ARE COLLECTING DATA TO BETTER PREDICT WHEN THESE DAMAGING STORMS WILL FALL.

year, a large swath of the country braces for hail.

Known as Hail Alley, the region stretching from Wyoming to Texas receives more hailstorms, and more severe ones, compared to other parts of the country.

Features on land and in the atmosphere make perfect hail conditions for this part of the U.S. But living in the hail sweet spot can get inconvenient.

“My car got really dinged up the

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second year that I was here,” says Sam Childs, a researcher at Colorado State University. After that, “I decided I’d like to take a look at hail,” he says.

Damaged vehicles are one of many consequences of severe hailstorms.

That’s why researchers are trying to improve forecasts for the weather events, to better predict when and what type of icy disruption might be coming.

The skill could get more valuable over time, as climate change might make hailstorms more common in the area.

THE SWEET SPOT For hail to hit the ground, there needs to first be a thunderstorm with strong upward winds. Those updrafts push falling raindrops backward, up into the atmosphere, until it gets cold enough for water to freeze. Like a ping-pong ball hovering over an air vent, the ice pellet falls and gets carried high by the upward winds over and over. The ice collides with other water droplets in the clouds along the way, building frozen layers and growing in size, until it becomes too

MAGICSHAPES/DREAMSTIME

Come summer every

In some parts of the country, like Hail Alley, conditions stay cold enough to keep ice pellets solid until they hit the ground.

heavy for the wind to keep lifting and falls to the ground.

Though Hail Alley sees ice fall relatively often, thunderstorms across the country build these tiny ice balls all the time, says Katja Friedrich, an atmospheric scientist at University of Colorado Boulder. But in most places, the air is too warm to keep the ice intact.

It melts somewhere between the final drop out of the cloud and the ground.

In Hail Alley, conditions are cold enough to keep the ice solid.

Additionally, much of the area is at a higher elevation, Friedrich says. Land in Colorado’s High Plains, for example, is closer to the source of the hail and gives ice pellets less time and space to melt before making contact with the ground. The region prepares for hail in the spring because that’s when warm air from the south meets cold air from the north, creating perfect conditions for thunderstorms.

FROM TOP: LUKAS JONAITIS/DREAMSTIME; LORENZOT81/DREAMSTIME; NADINE SPIRES/DREAMSTIME

THROUGH THE CLOUD Since every thunderstorm is unique, every hailstorm is, too. And about five years ago, the National Weather Service reached out to Friedrich to see if she might help track one particular icy variable: how much hail actually accumulated on the ground.

Storms in Colorado sometimes dump huge volumes of tiny ice pellets, much like snow. ln some cases, so much hail will blanket roads in a short span of time that cities will have to get out snowplows that were already put away for the season to clear the streets.

Ideally, municipalities would be able to anticipate these hailstorms and prepare for them. So Friedrich and her research team set out to collect data on how much hail accumulates during different storms and build prediction models to provide short-term forecasts on whether frozen rain might fall, and what it would look like. The work is still in its early stages.

“The more we investigate, the more

questions we have,” Friedrich says.

While the team knows many of the influential factors — like the amount of moisture in the clouds or how fast the storm moves — transforming those observations into a predictive model is challenging.

While Friedrich and her team iron out the details of forecasting upcoming hailstorms, Childs is looking farther ahead.

Knowing what these storms might look like well into the future can help shape policies meant to address their harm — how insurance companies handle damages, for example, or what farmers might expect for ice-pelted crops.

THE COMING STORM Childs and other researchers have found that in the coming decades,

climate change could push hailstorms to become more frequent and drop larger ice pellets in Hail Alley. One study Childs co-authored, for example, predicts three extra days of hail per year come 2100.

This shift seems likely because a few major hailstorm influences will grow stronger and more common over time. For one, a warming atmosphere will evaporate more moisture into the air. Increasing the amount of water in thunderstorms will potentially make them more likely to develop hail, Childs says.

Research also suggests the upward winds of thunderstorms might grow stronger in an increasingly warmer climate, allowing hail to grow larger and keep reaching the cold-enough atmosphere high above. Larger ice pieces, then, stand a better chance of coming all the way to land, boosting the likelihood that a given storm drops significant ice chunks.

These predictions don’t apply across all of the U.S., and hinge on calculations about future atmosphere conditions that may not pan out either. If lower levels of the atmosphere become increasingly moist, for example, hail could become less of a problem; higher humidity makes melting more common, Childs says. And there are caveats to making predictions about future hail events in the West based on data from storm levels in the past. As the areas became more densely populated over time, the likelihood of someone even being in a hailstorm path and reporting the event rose, too.

Regardless, hail research has gained attention in recent years. And maybe that’s because the storm impacts show an array of damaging consequences, from big hailstones smashing car windshields to tons of tiny pellets clogging storm drains and causing flooding events, such as the 2018 storm that killed animals and injured staff at the Cheyenne Mountain Zoo in Colorado.

As Childs puts it, “I think people are realizing how dangerous hailstorms can be.” — LESLIE NEMO J U LY/ AU G UST 2 02 1 . D IS C OV ER

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HOT SCIENCE

WHAT WE’RE READING The Kissing Bug: A True Story of a Family, an Insect, and a Nation’s Neglect of a Deadly Disease

By Daisy Hernández

W

hen journalist Hernández was growing up, she watched her aunt suffer from a chronic illness. For a while, no one knew what was happening, but her family tried everything they could to get answers. After a desperate hospital visit, one specialist landed on a diagnosis: Chagas, or kissing bug disease.

This parasitic infection, which is carried by the quarter-sized, blood-sucking kissing bug native to the Americas, afflicts at least 300,000 people in the U.S. today. But it hasn’t garnered nearly as much attention as other viruses like Zika, which is also carried by insects, and impacts a handful to a few hundred people every year. The full scope of Chagas infections is unknown, but it predominantly impacts those struggling with larger systemic issues. Rates are overwhelmingly high among Latin American immigrants, many of whom live in poverty and have limited or no access to healthcare.

Hernández thrusts the reader into her own frustrations and grief as she grapples with her aunt’s death and her personal quest to unravel the legacy of Chagas. She travels across the U.S. and Latin America to meet professionals who have studied the disease and worked to document its spread. And she traces the lineage of medical racism in the U.S., which often leaves communities of color to fight diseases without support, even long after they’re eradicated from white communities.

Hernández strikes a difficult balance between medical mystery, memoir and hard-hitting analysis.

While this nuanced and timely take exposes a disease that silently harms hundreds of thousands, it also serves as a prescription for change in our public policies and health care system. — JENNIFER WALTER

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D I S C OV ER M A G A Z I N E .C O M

More Pages to Turn After Cooling: On Freon, Global Warming, and The Terrible Cost of Comfort

By Eric Dean Wilson In 1985, scientists reported a massive hole in the ozone layer above Antarctica. One of the main culprits was a class of compounds called chlorofluorocarbons, or CFCs. These compounds were released mainly by a cooling substance called freon, which has been used for decades in refrigerators and AC units.

But the story of this once-ubiquitous substance, and our desire to control the temperature on a hot day, doesn’t start or end in 1985. Wilson’s research spans decades of history, from the makeshift labs of eccentric inventors to green energy companies buying up old cans of freon to dispose of them safely.

Even though freon production and importation was banned in the U.S. in 2020, some reserves still remain in areas across the country. Wilson deftly tracks freon’s impact, and the trail it left behind, in an expansive, smooth-flowing saga. The story offers a lens to understand how our comforts alter the planet — and might even make you think twice about turning on your AC on a steamy day. — J.W.

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VITAL SIGNS

BY DOUGLAS G. ADLER

procedure known as a Roux-en-Y gastric bypass. This particular operation typically results in the most dramatic and durable weight loss for patients.

The surgery involves the creation of a small “pouch” made from a portion of the stomach. This pouch can only hold a small amount of food at a given time and is connected to a section of small intestine. The remaining portion of the stomach, which is connected to the top of the small bowel, is simply left in place.

But after the procedure, ingested food no longer flows through these regions of the gastrointestinal tract; this is the “bypass” that is referred to in the operation’s name. Food that is swallowed bypasses the beginning of the small intestine and enters the bowel, where it is digested much further down the line. After this surgery, patients lose weight by several means. For one, the surgery restricts how much they can eat at a given time because the pouch is so small compared to a normal stomach.

Beyond that, much of the small bowel, where food is typically absorbed, never sees ingested food anymore. As a bonus, the Roux-en-Y gastric bypass is also very effective at treating GERD. Ann underwent the surgery without any complications.

The first year after the surgery was a very exciting time for Ann. She lost almost 75 pounds, her self-image soared, and she treated herself to an entirely new wardrobe. Victory, it appeared, was at hand.

Slim to None GASTRIC BYPASS SURGERIES CAN OFTEN LEAD TO DRAMATIC WEIGHT LOSS. FOR ONE PATIENT, THOUGH, THERE WERE SOME UNEXPECTED COMPLICATIONS.

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D I S C OV ER M A G A Z I N E .C O M

UNEXPECTED TROUBLE

She had gone from looking robust to, quite frankly, sickly.

I was therefore understandably surprised to see Ann back in my clinic just three months after her one-year surgical anniversary. Looking troubled, she told me that she felt weak and tired all the time. She had noticed a plethora of new problems, including vision changes and easy bruising, with even minor bumps resulting in ugly red blotches on her arms and legs. Most concerning, Ann’s weight loss was continuing beyond the point that would be expected following a gastric bypass. She had now lost over 100 pounds and had gone from looking

KELLIE JAEGER/DISCOVER

nn was a long-standing patient of mine whom I saw for severe gastroesophageal reflux disease, also known as GERD. She was extremely overweight and met medical criteria for morbid obesity.

Doctors consider a patient morbidly obese when they are at least 100 pounds over their ideal body weight — and/or when their weight may significantly contribute to medical conditions, like diabetes, high blood pressure, or fatty liver disease, that put their life in danger. Ann was 5 feet 4 inches tall and weighed 250 pounds. She had been a slim 130-pound athlete as a teenager, but had gained weight with each of her pregnancies.

During one of our clinic visits, the topic of her possibly undergoing surgery to lose weight came up. I was supportive of Ann seeing a surgeon who specialized in this area. Such procedures, known as bariatric surgeries, have become extremely popular with patients, given their high success rates and the often dramatic and life-changing results that they can produce.

Several bariatric surgeries exist, but after meeting with our surgeon, Ann had decided to undergo a specific bariatric

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robust to, quite frankly, sickly. Most patients experience a weight-loss plateau at around the one-year mark, but Ann’s weight had continued to decline.

Ann was seriously worried she had developed a cancerous tumor that would explain her weight loss — a not-unreasonable fear. But a CT scan of her abdomen and pelvis did not disclose any obvious abnormalities.

I also performed an upper endoscopy and a colonoscopy on Ann to make sure nothing was amiss with her gastric bypass and to further make sure she did not have colon cancer; the procedures failed to reveal anything that might explain her weight loss. But blood tests that I performed showed that Ann was suffering from significant malnutrition. In addition, her easy bruising prompted me to check her vitamin levels, since vitamin K deficiency is frequently associated with bruising. Her vitamin K level was extremely low, as was her vitamin A level.

Now we also had an answer for her vision changes, as vitamin A is required for healthy vision.

Both vitamin K and A are among the so-called “fatsoluble” vitamins, meaning that they don’t dissolve in water, but in fat. Vitamin A and K deficiencies are rare, and Ann was taking a multivitamin that included both of these. This suggested that Ann’s intake of the vitamins themselves was sufficient, but her body simply wasn’t absorbing enough of the nutrients they contained.

SYSTEM BREAKDOWN When I asked Ann if she was having diarrhea, she said she was having up to four bowel movements per day. I asked her if her stools looked oily or greasy. Her eyes widened and she nodded. “I haven’t told anyone that yet,” she said. The medical term for greasy stools is steatorrhea, and the presence of fat in stool is concerning. The human body is extremely efficient at absorbing fat from food, likely reflecting earlier eras when fat was a rare dietary commodity. Fat in the stool, however, is a telltale sign that the body is unable to absorb ingested food properly. Fat-soluble vitamins are absorbed passively by the body along with ingested fat, but if you can’t absorb fat, you can’t absorb fat-soluble vitamins, and deficiencies will develop.

While most people think their stomach digests

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D I S C OV ER M A G A Z I N E .C O M

While most people think their stomach digests their food, it’s actually the pancreas that does most of the work.

their food, it’s actually the pancreas that does most of the work. The pancreas produces enzymes that break down carbohydrates, fats, and proteins into their basic building blocks, which the small intestine can then absorb. Steatorrhea is most commonly seen in patients with chronic pancreatitis. That condition usually develops due to alcohol abuse, genetic factors, or other causes.

In these patients, the pancreas becomes scarred and atrophic and can no longer make or release enough pancreatic enzymes.

But Ann did not have chronic pancreatitis — her CT scan had shown a normal pancreas. Still, I began to wonder if Ann was suffering from asynchrony.

Asynchrony can sometimes develop after complex bowel reconstructions, including a Rouxen-Y gastric bypass. In order for normal digestion to occur, all parts of the gut not only have to work the right way, but also at the right time and in the right place, like a finely choreographed ballet. Ann’s gastric bypass meant that her food was going down one limb of small bowel, but her pancreas was dumping digestive enzymes into another, and there was no food going through that area at all. As a result, the food was not interacting with the enzymes that were required to break it down. Her body was simply passing undigested food through her.

I gave Ann a prescription for pancreatic enzymes — pills containing digestive enzymes obtained from pigs, believe it or not. When taken with a meal, these enzymes activate and break down food just like enzymes from a human pancreas. Then, the small intestine can absorb these smaller molecules.

Within a few days of starting the medication, Ann’s stools had normalized and her weight loss stopped.

A blood test obtained a few weeks later showed that her vitamin levels were on the rise.

Ann would need to take supplemental enzymes for the rest of her life, so her body could maintain a desirable weight and her absorption of food would be normal. She was not happy about the additional pills, but they worked. The gastric bypass giveth, and the gastric bypass taketh away. D Douglas G. Adler is co-director of the Center for Advanced Therapeutic Endoscopy in Denver. The cases described in Vital Signs are real, but names and certain details have been changed.

KELLIE JAEGER/DISCOVER (2)

VITAL SIGNS

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PIECE OF MIND

Cinema Amnesia BRAIN SCIENTISTS EXPLAIN WHY MANY OF US FORGET KEY PLOTLINES, OR EVEN THE ENDINGS, OF MOVIES OR BOOKS WE LOVED. pollo Creed knocks black-eyed Rocky Balboa to the mat. Rocky’s trainer, Mickey, pleads with him to stay down so the fight can end. Adrian walks into the arena as Rocky gets back up. Soon, the crowd is chanting Rocky’s name. And I … honestly cannot recall who wins the match.

I have seen every Rocky movie numerous times, which is why my husband and I were thrilled to introduce the original 1976 film to our kids. Somehow, though, I did not remember that the fight ends with a (spoiler alert!) split decision that gives Apollo Creed the victory.

Truth is, it’s not just Rocky. My husband and I have been sharing many classics with our kids, as well as more recent movies. During the viewings, he is constantly telling the kids, “Watch what’s going to happen next.” More often than not, I have no idea what’s about to come. This got me thinking: Why

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D I S C OV ER M A G A Z I N E .C O M

Calling on a memory again and again helps consolidate that memory.

do I forget most of the movies I see? And how does my husband remember every detail?

David J. Linden, a neuroscientist at the Johns Hopkins University School of Medicine, says people differ in memory ability, just like any other skillset.

“There are some people who are quite good at memory for certain kinds of events or certain kinds of facts. Someone else may be really good at putting names to faces or recalling everything they read off a page,” says Linden, the author of Unique: The New Science of Human Individuality.

At least I have that going for me. I am better than my husband at remembering birthdays and when big life events took place.

Individual aptitude aside, many factors affect how well we remember. For example, when you memorize your new home address, it can become difficult to recall your old address. This is called interference. Unless the old memory is recalled again, it might eventually fade. “You have seen many other movies since that [particular] movie. All of these other movies have the potential to interfere with your memory of that original event,” says Sean Kang, a cognitive psychologist at the University of Melbourne.

Repeated similar experiences, such as watching many movies or reading many books, can also render your memories generic. Let’s say you’ve been to the beach 100 times. You are not going to remember the details of each visit — only when something significant or different happened. Linden says this blended memory is more helpful in terms of guiding decisions and future behavior than having a perfect recording of each trip to the beach. So, when someone asks if you want to go to the beach, you can rely on that blended memory to know you would enjoy it. In this way, not remembering everything is actually useful.

KELLIE JAEGER/DISCOVER

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PIECE OF MIND

For example, when recognizing an actor in a movie, most people won’t bother searching their memory for where they’ve seen him, since they can just look it up.

“Give people the opportunity to use Google when answering questions and they are more likely to give up [and turn to their device] than rely on their memory,” Hourihan says.

Why then, do some people manage to remember all the details?

WANDERING THOUGHTS AND RETRIEVAL

NETFLIX AND NULL People are also consuming information in ways that may make recall even more difficult. One hurdle is what experts call the spacing effect. In a paper on spaced repetition, Kang highlights how leaving time between studying and reviewing the same info improves learning, compared to cramming it all in close together. Kang says at least 254 studies have showed that spacing out review is far better for helping recall verbal information.

This might be because repeating an item reminds the learner of when it happened before prompting retrieval, or the act of trying to recall info. That practice, like opening a filing cabinet in your brain, enhances memory. But if the repetitions are too close together and the event is still on your mind, you’re bypassing the retrieval process, which can hinder long-term retention.

Researchers are also considering how fatigue and reduced attention play into our rapid-fire consumption habits. We regularly scroll from one story to

HOW TO REMEMBER BETTER When a friend calls to talk about a movie or book you enthusiastically recommended, do you wish you could actually discuss the details? Here are three tips to help you remember.

General mindfulness: Paying attention is an important part of encoding, which is the first step to creating and storing a memory. This is why some researchers say mindfulness can help improve recall. A 2016 PLoS One study found that mindfulness training helped improve episodic memory, the kind that helps you remember specific events.

To improve mindfulness, the Mindfulness Center at Brown University

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D I S C OV ER M A G A Z I N E .C O M

recommends sitting and focusing on your breath for a few minutes daily or checking in with yourself a few times each day to see what you are thinking and feeling and what body sensations you notice.

Undivided attention: “While you are watching a movie, if you are always thinking about other stuff or looking at your phone, not taking time to reflect, this could be why you are not remembering,” says Kathleen Hourihan, associate professor of psychology at Memorial University of Newfoundland. How much you can

relate to what you see also improves the likelihood of remembering. So, thinking about what you see, like asking if you would have made the same choices as a character, helps that information stick in your memory.

Join a book club: Thinking about a movie you just saw or a book you just read helps you retrieve that information, which helps strengthen your memory, says Sean Kang, cognitive psychologist at the University of Melbourne. So, spending a few minutes contemplating the movie you saw the day before or talking to your book club about the novel you just finished can help. — A.C.

TOP AND RIGHT: KELLIE JAEGER/DISCOVER (2). LEFT: LINEAR_DESIGN/SHUTTERSTOCK

“How well you pay attention when you watch a movie or read a book can affect how well you remember,” says Kathleen Hourihan, an associate professor of psychology at Memorial University of Newfoundland. “If you are checking IMDb because you want to look up an actor you recognize, that is going to take away from encoding the information.”

This rings true for me, especially when it comes to reading — another area where my husband frustratingly remembers more than me. When I am reading, my thoughts often wander and I sometimes speed through certain pages. My husband is a slower, more deliberate reader.

He also likely takes more opportunities to retrieve information after the experience, Kang says. “He thinks about the plot twist, what he liked.

Maybe he has conversations about the movie with friends,” he says. “We think of memory as getting something in, but getting the stuff out is equally important.” Calling on a memory again and again helps consolidate that memory. Teachers often use frequent, short quizzes to get students to recall what they have learned. This promotes retention.

In today’s world, retrieval has become less necessary because of all the info at our fingertips.

the next, marathon through a TV series late at night or pack as many books as possible into a single beach trip. Binge watching is a prime example. Participants in a 2017 study watched a TV series at three different rates: one episode a week, one per day or all six episodes in a single sitting. (The show was the BBC America drama, The Game.) All viewers completed content quizzes one day, seven days and 140 days after watching the season. One day after the show, binge watchers scored highest on the quiz. But after 140 days, they scored lower than the weekly viewers. Binge watchers also reported enjoying the show less than people who watched it daily or weekly.

That begs the question of whether enjoying a story hinges on recalling every detail. Linden says no — which is good news for me and fellow detail-forgetters out there. “You don’t have to remember all the plot details for it to have made an

impression on you and to have changed you in some way,” he says. While most of us think of memory as that thing we use to remember explicit facts and events, the majority of our memories and how we encode experiences are actually subconscious.

So, if you were attacked by a dog as a kid, your heart may race when you are near one — even if you don’t remember the attack. “It still leaves a trace behind,” says Linden.

While it would be nice to discuss the specifics of something I saw or read, the experiences definitely have an impact — the satisfaction of finishing a really great book or fond memories of going to the movies with my brother.

That might be even better than remembering that Rocky finally beats Apollo in Rocky II. At least …

I think that’s how it ends? D Abigail Cukier is a health and science writer based in Ontario, Canada.

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MYSTERIES AT THE EDGE OF MEDICINE

MILLIONS OF AMERICANS SUFFER FROM AILMENTS WITHOUT A NAME. THAT’S WHERE THE UNDIAGNOSED DISEASES NETWORK COMES IN.

BY NATHANIEL SCHARPING

PUWADOL JATURAWUTTHICHAI/SHUTTERSTOCK

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lizabeth wouldn’t walk or talk as a toddler. Laura’s hair fell out, and rashes attacked her skin. Angela’s left leg was so swollen it hurt to stand. Emma needed a breathing machine just to sleep. Their suffering may take different forms, but their stories share a common thread: Neither they or their families knew what was actually causing these issues.

Undiagnosed diseases are more common than you might think. Tens of millions of Americans likely suffer from disorders they cannot name. For many, the symptoms are minor. But in some cases, patients come to their doctors with serious problems caused by diseases that defy medical knowledge.

Those cases are precisely where the Undiagnosed Diseases Network (UDN) steps in. Established in 2008 at the National Institutes of Health (NIH), the UDN’s mission is to provide answers for patients with diseases that doctors are unable to diagnose. Anyone can apply to the program — with their doctor’s blessing — and the UDN endeavors to screen every application it receives.

Today, the UDN encompasses 12 clinical sites around the country, and has evaluated over 1,400 patients, says William Gahl, director of the Undiagnosed Diseases Program in Bethesda, Maryland, one of the network’s sites. More than 400 of those patients have received a diagnosis thanks to the UDN and its affiliates. In some of these cases, the network is able to match a patient with an alreadyknown condition. In others, UDN researchers must J U LY/ AU G UST 2 02 1 . D IS C OV ER

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CLINICAL SITES Bethesda, MD (NIH Undiagnosed Diseases Program) Boston, MA (UDN Clinical Site at Harvard Medical School) Durham, NC (Duke University and Columbia University) Houston, TX (Baylor College of Medicine, Texas Children’s Hospital, and Baylor CHI St. Luke’s Medical Center) Los Angeles, CA (UCLA Undiagnosed Diseases Clinic) Miami, FL (University of Miami School of Medicine) Nashville, TN (Vanderbilt Center for Undiagnosed Diseases) Philadelphia, PA (Children’s Hospital of Philadelphia and University of Pennsylvania) Salt Lake City, UT (University of Utah – Intermountain West) Seattle, WA (Pacific Northwest Undiagnosed Diseases Clinical Site at

• • • • • • • • • •

University of Washington and Seattle Children’s Hospital) Stanford, CA (Center for Undiagnosed Diseases at Stanford) St. Louis, MO (Washington University in St. Louis) CENTRAL BIOREPOSITORY Nashville, TN (Vanderbilt University Medical Center) COORDINATING CENTER Boston, MA (Harvard Medical School and University of Alabama at Birmingham) METABOLOMICS CORE Rochester, MN (Mayo Clinic) MODEL ORGANISM SCREENING CENTERS Houston, TX (Baylor College of Medicine and University of Oregon) St. Louis, MO (Washington University in St. Louis) SEQUENCING CORE Houston, TX (Baylor College of Medicine)

• • • • • • • •

MEET THE DOCTORS →

From left: Clinical geneticist Dorothy Grange, who works with Laura Ammann; assistant professor of pediatrics Hsiao-Tuan Chao, who helped diagnose Elizabeth Nagorniak; clinical geneticist Carlos Bacino, Emma Broadbent’s physician; clinical geneticist Fuki Marie Hisama, one of Angela Moon’s lead clinicians.

MAP: ERNESTO DEL AGUILA III, NATIONAL HUMAN GENOME RESEARCH INSTITUTE. PHOTOS, FROM LEFT: DOROTHY GRANGE; HSIAO-TUAN CHAO; CARLOS BACINO; FUKI MARIE HISAMA

SEE THE LOCATIONS →

work to describe an entirely new disease and enter it into the medical lexicon. The program has added at least 25 entirely new diseases in this way, Gahl says. Additionally, the UDN covers the cost of the tests, meaning patients aren’t saddled with crushing medical debt.

“It changed everything,” says Mari Hanada, whose daughter is a UDN patient. “Suddenly I had a direction; I knew which way to go.”

This kind of groundbreaking work helps more than just the patients themselves. Insights from studying rare diseases offer new knowledge about the human body that can benefit all of us. For example, the discovery of statins, a class of drugs commonly prescribed today to help regulate cholesterol, arose from the study of a rare genetic disorder called familiar hypercholesterolemia.

Unraveling these formidable cases requires hours of poring through medical records, batteries of tests, days of examinations and, crucially, close collaboration between specialists in disparate fields.

“I think they’ve really advanced and changed the whole paradigm [for] how we approach many of these illnesses,” says Anne Pariser, director of the Office of Rare Diseases Research at the NIH’s National Center for Advancing Translational Sciences. She says the UDN’s multidisciplinary approach — bringing different specialists together to talk about challenging cases — has helped advance the field of rare disease research, especially when it comes to genetic diseases.

For many patients, the UDN offers something less tangible, too. Living with a disease without a name can be its own kind of suffering. “You grow up feeling like, ‘I’m in this, crazy, all by myself, and no one really understands me,’ ” says Angela Moon, a UDN participant. For patients like her, the UDN offers hope — for treatment, but also for finally being seen.

ANGELA MOON / AGE: 46

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GORDON MOON (2)

or decades, Angela Moon dealt with her baffling condition in silence. Some people didn’t even realize she had a disability, she says, because she hid it so well. But in reality, Angela was often in pain, the result of thousands of hard, purplish lesions called angiokeratomas that grew on her skin and which could burst open bloodily. Her legs were especially painful, as they were constantly swollen with fluid, a condition known as lymphedema.

Though Angela had been evaluated by doctors for her symptoms since birth, there were no real explanations and little respite from the discomfort.

In 2017, everything came to a head. Angela “basically [had] a mental breakdown,” she says, the result of years of coping with stress and physical pain, compounded by the absence of any sort of diagnosis. She had to leave her job at FedEx and spiraled into depression. By 2019, she could no longer enjoy even simple activities with her husband Gordon and daughter Deanna.

“I was like, ‘I can’t do this anymore,’ ” she says.

It was around this time that Angela began working with the UDN. In January of 2020, she went to the University of Washington Medical Center in Seattle for two days of comprehensive tests, including blood work, MRIs, skin biopsies and more. Though they were grueling, she says the exams felt different than the countless medical appointments that came before — more purposeful and compassionate.

“When you’re dealing with a disability, […] you just want someone to understand,” Angela says.

It’s still too early for the UDN to say what might be causing Angela’s symptoms, or whether her disparate symptoms are even related, says Fuki Marie Hisama, a clinical geneticist at the University of Washington School of Medicine and one of Angela’s lead clinicians at the UDN. But Angela has already begun laser treatments for the angiokeratomas, something she says has greatly reduced the discomfort and bleeding. And the UDN connected her with a plastic surgeon specializing in lymphedema who has already operated on her left leg, with positive results.

The possibility of further treatment is giving Angela a sense of optimism that’s largely been missing for more than four decades of her life, she says. And it’s letting her focus on the future, too. An archaeology buff, she imagines one day working at a museum doing project management.

Like others who have worked with the UDN, Angela also anticipates her struggles could help ease the pain of others in the future. Though she once felt embarrassed when doctors brought in medical students to examine her unsolved case, today she’s happy to share. “I want to give someone hope,” she says. “If they figure out what’s going on with me, they can match it with somebody else that comes in in the future.”

Top: Angela, along with husband Gordon and daughter Deanna, on a Boston tour bus in 2017. Bottom: Angela in her backyard in 2019.

The possibility of further treatment is giving Angela a sense of optimism that’s largely been missing for more than four decades of her life.

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ELIZABETH NAGORNIAK / AGE: 6 more dismaying symptoms began to stack up. She kept missing developmental milestones. She could barely hold up her head, let alone walk.

She briefly began to babble at about a year and a half, but soon stopped. “I kept buying toys, trying different things, but she wasn’t interested,” Mari says. “It was really sad to see her not doing anything.”

The family first met with the UDN in 2018, when Elizabeth was 3 years old.

Tests up until that point had been inconclusive, and her parents had little idea how to address their daughter’s symptoms.

But Elizabeth turned out to be lucky. One of the first things the UDN did, according to Hsiao-Tuan Chao, an investigator with the UDN and assistant professor of pediatrics at Baylor College of Medicine, was examine a unique pattern on Elizabeth’s skin. “She was a little bit stripy,” Chao says. Light and dark lines alternated across Elizabeth’s body; almost tigerlike. It was a hint to Chao

that something deeper was amiss.

The cells that go on to form both our skin and our brains start from the same population early on. So, when a mutation shows up on the skin, mutations in the brain are expected, too.

The UDN performed more comprehensive genetic tests on Elizabeth’s skin. The results revealed a mutation to a key gene known as MTOR that regulates how cells proliferate during development. In Elizabeth’s case, the protein produced by the gene wasn’t being turned off properly, meaning some groups of cells that should have stopped growing had failed to do so.

It explained her stripy skin, but also the developmental delays that kept Elizabeth from progressing.

Fortunately for Elizabeth, MTOR has been researched extensively because it’s also involved with tumor growth.

That knowledge led doctors to a diagnosis for Elizabeth

LAURA AMMANN / AGE: 35

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aura Ammann never smiled as a child. She was born with the symptoms of a rare condition known as Moebius Sequence, which restricted her facial and eye muscles from moving properly. The congenital syndrome isn’t exactly common, appearing in less than 1 in 50,000 people. But Laura would prove to be a rarer case still: In addition to her facial symptoms, Laura’s brain was swollen with fluid at birth, a condition known as hydrocephalus. Further testing revealed that some of her neurons hadn’t migrated properly during development.

As Laura grew up, more puzzling

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D I S C OV ER M A G A Z I N E .C O M

symptoms appeared. Her hair fell out in third grade, grew back, and fell out again in eighth grade — this time for good. Skin rashes flared across her body, and her fingernails and toenails wouldn’t seal to their cuticles properly, leading to a string of infections. She started having seizures when she was 20.

“She’s really a medical mystery,” says Dorothy Grange, a clinical geneticist at the Washington University School of Medicine in Louisville who’s worked with Laura for over a decade. “So many

Top: Elizabeth, almost 2, tries on her first kimono, sent by her grandmother in Japan.

Bottom: Elizabeth, at age 5, sits on a chair at a local park.

— and an already-existing treatment.

Elizabeth has a variant of Smith-Kingsmore Syndrome, a rare genetic condition tied to mutations of the MTOR gene. Today, she’s receiving a drug called Sirolimus that’s led to dramatic changes in her development in just a year.

“She’s getting new skills weekly now,” Mari says. “It used to be annually.”

The diagnosis also helped Mari connect to other families with children suffering from the condition. She’s since become active in a Facebook group for Smith-Kingsmore Syndrome. In October of 2019, they met with 17 other Smith-Kingsmore families at Cincinnati Children’s Hospital.

It’s marked a turning point in Elizabeth’s journey, one Mari never stopped fighting for.

Left: Laura, at age 7, celebrates Easter with her family. Right: Laura recovers from infusion therapy at SSM Health Cardinal Glennon Children’s Hospital in St. Louis in 2019.

complex medical issues and not a single unifying diagnosis.” Until 2019, when she began working with the UDN, there was little explanation for Laura’s symptoms.

Meanwhile, Laura got on with her life.

In addition to a daily exercise routine, she began working at a nearby school for disabled children in 2009, helping students with therapy and schoolwork.

Though she has to wear gloves to protect

FROM TOP: MARI HANADA; GYULNARA LOKTEVA; ELIZABETH AMMANN (2)

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n her 26th week of pregnancy, Mari Hanada’s doctor ordered a fetal MRI for her unborn daughter to assess what appeared to be irregular brain development. Those scans and some initial genetic tests were initially reassuring. But soon after Elizabeth, now 6, was born, there was new cause for alarm — the infant’s head was swollen. At six months, she was diagnosed with hydrocephalus, a buildup of fluid in the brain. Multiple surgeries to drain the fluid followed.

As Elizabeth grew older,

EMMA BROADBENT / AGE: 5

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FROM TOP: JAN OSBORN/DALLAS DOING GOOD; JULIA BROADBENT

ver since she was born, Brian Broadbent’s daughter Emma has been severely delayed. Now 5, she’s at the developmental age of a 5-month-old, he says. Brian and his wife, Julia, must give Emma nearly roundthe-clock care to ensure her survival.

She cannot feed herself, and may never walk or talk. Emma sleeps with a BiPAP machine — a portable device that pushes oxygen into a patient’s airways — to help her breathe. She spent Christmas of 2019 in the hospital on a ventilator.

Shortly after their daughter’s birth, the Broadbents embarked on a journey to attempt to understand what their daughter was experiencing. They spent months with a white-matter specialist analyzing Emma’s brain and had her genome sequenced. They traveled to the Mayo Clinic for metabolic testing and twice to the Children’s Hospital of Pennsylvania for exams.

But the results from all that testing weren’t very helpful.

“She’s at the edge of science,” Brian remembers one doctor telling them.

In 2017, their search led them to the Rare Genomes Project at the Broad Institute of MIT and Harvard, and the UDN shortly afterwards. Both

organizations began sequencing Emma’s entire genome, as well as her RNA. And, as it turns out, both groups soon found the same thing: a mutation to the CHD2 gene. Irregularities in this gene are often associated with epilepsy, but Emma’s symptoms were far worse.

Uncovering the true root of Emma’s symptoms took further digging, and a timely coincidence. It turns out Emma has another mutation on a gene near CHD2 called Chaserr. It’s what’s known as a long noncoding RNA, or lncRNA gene, and it affects how CHD2 is expressed.

Nothing had been known about the gene until just months before, when a team of Israeli researchers published a paper on Chaserr and its role. The paper included data on mice genetically engineered to lack Chaserr, which had brain anomalies similar to Emma’s.

In Emma’s case, the combination of mutations appears to affect her brain’s myelin, the protective sheathing that covers our nerves and brain cells, says Carlos Bacino, a clinical geneticist at the Baylor College of Medicine, a UDN site, and Emma’s physician at Texas Children’s Hospital. The result is what Bacino describes as a neurodegenerative disorder affecting her brain’s development and

Top: Emma (right) relaxes at home with her father, Brian, mother, Julia, and older sister, Claire.

Bottom: Emma and Claire play dress-up.

function. Emma is the first patient in the world to ever be diagnosed with a condition resulting from a lncRNA mutation.

There could even be a treatment for her at some point, in the form of a new kind of genetic therapy known as antisense oligonucleotides, which could alleviate some of Emma’s symptoms.

It’s bittersweet news for Brian — his daughter is truly at the forefront of modern-day medicine, and that means the chance for a cure is small. But Emma is also offering scientists potentially groundbreaking knowledge. Perhaps the next child born with a lncRNA defect will have the hope of treatment. “She’s kind of like a gift to science,” Brian says. “It does bring a lot of comfort.”

Researchers with the UDN are currently working with fruit flies genetically engineered to possess Laura’s specific genetic variant. her hands, the work still brings her real satisfaction today. “I hope I have that for the rest of my life,” she says, or at least “until they kick me out.”

But in 2019, after more than two decades of study by various groups, Grange and researchers with the UDN started to inch closer to an answer to Laura’s problems. Grange had already found irregularities in Laura’s sterols,

a class of lipids, including cholesterol, that play a fundamental role in how our bodies develop and function. Whole-genome sequencing through the UDN turned up a unique variant of a gene related to cholesterol in Laura, providing further evidence for Grange’s hypothesis: Her body’s deficits in making sterols could be causing her array of seemingly unrelated symptoms.

Researchers with the UDN are currently working with fruit flies genetically engineered to possess Laura’s specific genetic variant. That work could reveal whether this gene is truly at the root of her problems, and potentially point the way toward her treatment. D Nathaniel Scharping is a freelance science writer based in Milwaukee.

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COVID LES

BY ELIZABETH SVOBODA

As the pandemic mounted a blitzkrieg around the world, killing thousands every day and turning us all into shutins, the entire health care system faced a trial by virus. The stakes were inhumanly high, but doctors, researchers and crisis planners stepped up, advancing the field of public health along the way. Here’s how the most important takeaways from COVID-19 are shoring up our collective defenses and preparing the medical world for

the next rogue pathogen.

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Fierce debate raged in the pandemic’s early months about whether wearing face masks curbed viral transmission. The confusion was understandable: In March 2020, the World Health Organization urged people not to wear a mask unless they were sick with COVID-19 or caring for someone who was ill.

Scores of health officials echoed the organization’s advice, with many now claiming that it was an effort to preserve masks for medical workers.

But this seeming consensus collapsed in the face of more than a dozen new studies showing that masks slowed the virus’ spread.

There was never much science that said masks didn’t work, says Mark Roberts, director of the University of Pittsburgh’s Public Health Dynamics Laboratory. Pre-2020 research already showed masks’ effectiveness, and

COVID-era studies cemented that verdict, setting the stage for more widespread, ongoing mask use.

It’s true that mask layers are porous enough that viral particles alone could pass through them. But most viruses, including COVID-19 and the flu, don’t hang out solo in the air. They’re surrounded by so-called respiratory droplets, globs of fluid that people spew when they cough or sneeze.

Masks effectively block most of those larger droplets, both incoming and outgoing, from your mouth or nose.

“If both people in an encounter are wearing masks, the likelihood of transmission is substantially lower,” Roberts says.

Last year’s crop of studies emphasized just how much lower. One found that N95 masks — the most effective variety on the market — blocked 99 percent of a wearer’s cough droplets from escaping into the surrounding air. That translates into a much lower likelihood of transmission on the population level. Three weeks after authorities in 15 states plus Washington, D.C., announced mask mandates, another study reported, the virus’ daily growth rate in those states slowed by 2 percentage points, ultimately preventing more than 200,000 people from getting the virus.

The broader takeaway of this research is that masks can work for

PREVIOUS SPREAD: CORONA BOREALIS STUDIO/SHUTTERSTOCK. THIS PAGE: KONSTANTIN CHAGIN/SHUTTERSTOCK

MASKS WORK. REALLY.

IMMUNE SYSTEM MAPPING Much of the havoc COVID-19 wreaks doesn’t

MASKS CAN WORK FOR MORE THAN JUST PREVENTING COVID-19.

FLU CASES WERE DOWN MORE THAN 90 PERCENT.

come from the virus itself, but from your immune system’s response to it. This full-scale immune mobilization can unleash a torrent of symptoms, including airway inflammation and the dreaded “cytokine storm,” where your body’s immune cells attack your own tissues. By tracking this tempest from its earliest stages on a patient-by-patient basis, researchers can now predict what course the disease will take and what treatments might work best on a given case. This immune-centered strategy, refined during the pandemic, is poised to transform disease management.

As soon as the pandemic hit, immunologists worldwide began sampling COVID-19 patients’ blood in search of distinct signatures related to the disease. Their sampling yielded a set of immune biomarkers that contained important clues about patients’ prognosis.

Those with high levels of certain cytokines — small proteins that support communication between immune cells — proved more likely to develop severe disease in a King’s College London study. Patients with lower levels of these compounds were able to leave the hospital more quickly. In addition, high concentrations in the blood of certain natural antibodies meant COVID-19 patients were more likely to die or be intubated, according to a Massachusetts General Hospital study.

Results like these could usher in new hospital protocols where COVID-19 patients take a standard immune blood test upon hospital admission, says Adrian Hayday, an immunologist at King’s College London and the Francis Crick Institute. If a patient’s immune signature predicts quick symptom resolution, doctors could more confidently discharge them into home-based care. But if immune markers point to a more severe course, providers could concentrate efforts and expedite intensive therapies like monoclonal antibodies.

Tracking immune biomarkers could 3.3 MILLION also allow bespoke treatment of other GLOBAL COVID-19 diseases, from influenza to cancer to novel DEATHS REPORTED, coronaviruses. Many conditions have AS OF MAY 14. their own distinct immune signatures that SOURCE: WHO may predict disease progression, letting doctors start appropriate treatment when the odds of success are higher. “If I can monitor the immune system and see it deviate from a status quo, we may be in a situation where we could get early warning signs,” Hayday says. “That’s how the future of immune profiling needs to look.”

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more than just preventing COVID-19.

Flu case counts for the 2020–21 season were more than 90 percent lower than the prior year, in large part because people weren’t spewing droplets all over each other. Tom Frieden, former CDC director, recently proposed a new culture of wearing masks around others whenever you don’t feel well — a practice that’s been the norm in many Asian countries for years. If we’re smart, we’ll follow their lead.

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VACCINE PRODUCTION SPEED In early 2020, before most people had even heard of an N95 mask, scientists were working around the clock to develop a COVID-19 vaccine. Large-scale trials of several vaccines were underway by fall, and months later, providers were injecting them into arms by the millions.

It was a vaccine development land-speed record for a virus that claimed hundreds of thousands of lives within months — especially considering that, pre-COVID, typical vaccine timelines ran closer to a decade.

There’s every reason to think we can pull off such feats in the future, says Sharon Nachman, a pediatric infectious disease specialist and director of the Office of Clinical Trials at Stony Brook University. The bottom line, in Nachman’s view, is that after COVID-19 popped up, the system worked exactly the way it was designed to. The medical infrastructure was ready (just like it was for the warp-speed H1N1 flu vaccine, which got less fanfare), and the players involved, from pharmaceutical companies to universities’ steering trials, stepped up and fulfilled their roles.

The messenger RNA (mRNA) technology that debuted in Pfizer and Moderna’s COVID-19 vaccines also bodes well for swift vaccine development. In simple terms, mRNA vaccines give the body’s cells instructions to mount strong defenses against a virus. By making new mRNA in the lab — a low-cost process — scientists can quickly create a vast library of such instructions, each tailored to a different pathogen. This finger-snap customization has experts calling mRNA a new “vaccine on demand” option.

A few caveats mar this rosy outlook, however. Because COVID-19 provokes a robust immune response, it was a good fit for mRNA vaccines that stimulate antibodies against the virus. Time will tell if it proves effective against wilier viruses like HIV, which lurk in hiding and evade antibodies.

Moderna announced earlier this year it is working on two mRNA vaccines against HIV, slated for phase 1 trials this year.

Other fast-track vaccine tripwires are more practical than scientific. Having transformative science doesn’t necessarily mean we’ll use it — chances are, a virus affecting mostly poorer countries won’t spur the 1.26 BILLION accelerated vaccine timeline we saw with COVID-19.

GLOBAL VACCINE And, as the U.S. learned anew this winter, while DOSES INJECTED, having vaccine doses on hand is one thing, getting AS OF MAY 12. them to recipients is a totally different challenge. “We SOURCE: WHO don’t have a ready-made national emergency vaccine delivery system,” says former CDC director Tom Kenyon, now with the humanitarian relief organization Project HOPE. “We’re going to have to get that in place with the next pandemic.” Without such a distribution plan, future state-of-the-art vaccines can’t have the game-changing impact they were meant to produce.

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captioniuntenihit porundaerum ut magnimus vendelessus evelese quaepelignis sitectaqui voluptatia nosaper emodit od ut audant

It’s a reality the pandemic has brought into stark relief: Systemic racism is endemic in U.S. health care. COVID-19 has disproportionately hit communities of color — a June 2020 analysis by health professions found that in one region of Louisiana, 3 in 4 patients hospitalized for the virus were Black, even though only 1 in 3 residents of that region were Black.

Infection and death rates have also been two to four times as high among Black, Latino and Asian peoples as among white people, according to an analysis of 300 hospitals in 21 states.

Behind these numbing statistics are the stories of thousands who might have been saved with better care. In one viral video, Susan Moore, a Black doctor with COVID-19, described how hospital doctors were dismissing her breathing problems. “This is how Black people get killed,” said Moore,

who later died of COVID-19 complications. Tragedies like this, repeated around the country, underscore the need for radical change that long outlasts the pandemic.

Communities of color are in the virus’ direct line of fire because their members often live and work in densely populated areas home to many essential workers. The problems compound as residents get COVID-19 and end up in the hospital or clinic.

Most health workers in these settings aren’t consciously racist, says

Tonia Poteat, a social medicine specialist at the University of North Carolina.

But multiple studies show they have unconscious biases that influence their care, as when doctors downplayed Moore’s shortness of breath. And even well-meaning stop-the-spread tactics often have structural inequity at their core. Drive-up COVID-19 testing sites might be ideal for affluent or suburban residents, but not for those who don’t own a car. “A provider might think, ‘I’m treating everyone the same,’ but everyone’s needs aren’t the same,” Poteat points out.

To address such inequities, health care providers and lawmakers are creating new sets of best practices for equitable care. The Massachusetts Medical Society, which represents 25,000 doctors and medical students in the state, drafted an action plan in

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ADDRESSING RACIAL DISPARITY

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CARE PROVIDERS MUST REBUILD TRUST WITH COMMUNITIES OF COLOR THAT HAVE LONG SUFFERED AT THE HANDS OF THE HEALTH SYSTEM.

late 2020 that includes training providers in culturally adept communication and forging relationships with community groups that support people of color.

On the national level, U.S. House Rep. Ayanna Pressley (D-Mass.) recently introduced the Anti-Racism in Public Health Act, which would fund research into structural racism’s health impacts and create a National Center for Anti-Racism at the CDC. Down the line, U.S. lawmakers will need to allocate more funding to local and national public health agencies, says Kenyon, the chief health officer at Project HOPE. Public agencies can promote equal care by getting life-saving information and vaccines to underserved populations.

As they pursue greater equity, care providers must also rebuild trust with communities of color that have long suffered at the hands of the health system and other forces. “We need to include people of color in research trials and get informed consent from study subjects who have felt marginRep. Ayanna alized,” says Stanford Medicine Pressley called emergency physician Michael structural racism a “public A. Gisondi. The journey ahead health crisis will be demanding, but in this that continues arena, COVID-19 seems to to ravage Black, Brown and have pushed health care in the Indigenous right direction. communities” in early 2021.

MEDICINE FROM HOME COVID-19 restrictions meant doctors-in-training spent less time at bedsides last year. Instead, mentors walked them through a series of virtual consults.

If the person on their screen had severe knee pain, would they send the patient for an MRI or opt for physical therapy? Established providers also scrambled to get comfortable with Zoom and remote exam tools like digital stethoscopes. (Yes, they exist, and are just about as accurate as the real thing.)

Some of the initial telemedicine shift happened out of necessity. Patients, doctors and trainees feared going into public places and getting exposed to the virus. But what began as a short-term workaround morphed into a lasting change to the medical landscape. Alongside “Work From Home,” “Medicine From Home” evolved — a concept that will likely continue to pick up speed post-pandemic.

Once providers started offering virtual visits on a regular basis, doctors and patients liked the results enough that these visits continued even as COVID-19 numbers declined. Pandemic or not, remote consults are often more convenient and safer for everyone involved. “It’s efficiency of practice for us,” says Gisondi. “It does reduce exposure to infectious diseases. Do you really want to visit your doctor in-office in the middle of flu season?”

Even so, shifting full-service care into virtual space comes with its own suite of challenges. While virtual visits help some patients feel safer from infection, others report that these visits feel less personal. Adapting to online consults will be easier for some specialists than for others.

A dermatologist might have an easier time diagnosing a skin lesion virtually than, say, an oncologist would checking on a tumor’s growth.

But even visits that require inperson contact can be streamlined and made safer with telemedicine tools. If a patient shows up with 428 MILLION a contagious virus, one doctor can COVID-19 TESTS enter the exam room with a tablet RECORDED IN U.S. computer and send a video stream LABS, AS OF MAY 14. to specialists who weigh in from SOURCE: CDC a remote location. The challenge ahead for providers will be figuring out just where to set the bar for in-person visits — but it’s safe to say that bar is already much higher than it was before. D

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Elizabeth Svoboda is a science writer in San Jose, California. Her latest book is The Life Heroic: How to Unleash Your Most Amazing Self.

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Q A +

Psychologist Alex Belser says psychedelic medicine could herald a mental health renaissance.

He’s on the forefront of a boom in research and experimental treatments.

THE FUTURE OF

PSYCH

FROM LEFT: NAKEAN WICKLIFF; ALEXANDER_VOLKOV/SHUTTERSTOCK

Sometimes known as “magic mushrooms,” these fungi get their psychoactive properties from the compound psilocybin.

lot has changed since the 1990s.

That’s when Alex Belser, then an undergrad at Georgetown University, first found a book about LSD psychotherapy.

Back then, hardly anyone was talking positively about psychedelics. The U.S. had recently passed a string of strict anti-drug and crime bills, extending the war on drugs that President Richard Nixon started in 1971. By the late 1990s, medical and industry investment in the field was virtually nonexistent.

Two decades — and several degrees — later, Belser has read far more about psychedelics in medicine. He’s also published his own peer-reviewed papers, guided dozens of patients safely through medically sanctioned trips and advised corporations that are suddenly pouring millions of dollars into the promise of psychedelic-assisted therapy. A recent market report from Financial News Media projected the industry in North America will exceed $6.8 billion by 2027.

The business surge in psychedelics has followed a tidal shift in academic research. Since 2006, researchers at Johns Hopkins

University alone have published more than 60 peer-reviewed papers on psychoactive compounds found in magic mushrooms and other plants. In late 2019, the university opened the first-of-its-kind Center for Psychedelic and Consciousness Research. Around the same time, the U.S. Food and Drug Administration (FDA) granted “breakthrough therapy” classification to psilocybin, the so-called “magic” compound found in psychedelic mushrooms. That FDA status helps fast-track the approval of promising pharmaceuticals in trial phases. And Oregon made history in November when the state voted to legalize psilocybin for medical use.

Belser, who holds a doctorate in psychology, has made many contributions to this potential medical renaissance. He’s the founding president of Nautilus Sanctuary, a nonprofit dedicated to psychedelicassisted psychotherapy. He also currently works as chief clinical advisor at Cybin Inc., a biotech company focused on psychedelic therapeutics, like using a sci-filooking helmet that shows real-time blood flow, oxygen levels and other brain activity during a psychedelic experience.

He recently met with Discover

OTHERAPY?

BY TIMOTHY MEINCH

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No, it’s not going to plug you into the Matrix. But new tech, like this helmet from neuroscience startup Kernel that records brain activity in real time, may help scientists develop better psychedelic treatments.

like entheogen, which is “manifesting the spirit within,” because people do have very powerful spiritual experiences under these medicines. Some people prefer the term plant medicines.

Q

Q

A: It’s so hard to know what word to use. This is one of our favorite debates: What do we call these medicines?

Psychedelic means “mind-manifesting.”

They’re not properly hallucinogens. The medical literature uses that term, but that term doesn’t really help describe them. Other people have used terms

A: My research has been focused on interviewing people in-depth, asking “What is it that happens for you when you use these medicines?” We also do pre- and post-measures. And we use something called the Mystical Experience Questionnaire and the Hood Mysticism Scale that have been used in scores of trials.

But we consistently find that when people have a spiritual or mystical

We’re talking about medicine. But terms like psychedelics and magic mushrooms can still sound provocative, or edgy and mystical. Is that language misleading?

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How do you assess and interpret a spiritual experience, both medically and scientifically?

experience with psychedelic medicine, that predicts whether or not they get better in terms of the symptoms they are having for depression, anxiety or something else. This is incredible because it suggests that it’s not just a biomechanical medicine. It’s not just happening in the physiological level. It suggests that people are also having something really important happening in their mind, in their memory and their identity or their history. It’s their relationship to being alive, in the human body and the world.

That helps them get better, and that’s independently predicting their treatment outcome.

Q

Interesting. That sounds a bit more like religion, or an existential belief system, than medicine.

CYBIN

over video chat to explain the current state of magic mushrooms, psilocybin and hallucinogenic medicine — and the unlikely academic path that brought him here.

A: This is a different model than the traditional “take a pill a day and call me later” approach. It really requires a lot from the person who’s taking the medicine to navigate internally what comes up for them. And it also requires a lot from the people they work with, the clinicians.

When people say, “I felt a profound experience of unity, and an interconnectedness with all things,” it’s not the same as a blood draw or getting a level on your blood pressure. It’s not a metric like that, but it is a way for people to tell you what they’re experiencing and to get at what’s happening internally. If we only paid attention to what we could obviously measure, we would lose everything that happens internally for people in their own minds and their own inner experience, which is the vast majority of what people experience in their lives.

This is especially true when you’re dealing with things like depression and addiction and end-of-life distress.

Q FROM LEFT: CYBIN; NAKEAN WICKLIFF

What other symptoms or conditions does this type of treatment work well for?

A: For many psychedelic medicines, they are medicine in search of a condition. So, with psilocybin, it’s potentially effective for a variety of things, including anxiety, major depressive disorder, treatment-resistant depression, obsessive compulsive disorder, smoking cessation, alcohol-use disorder, even potentially other areas like anorexia and eating disorders. I believe that the future of psychiatry will find psychedelic

Many patients choose to lie down or wear eyeshades to better immerse themselves during sessions.

HOW PSYCHEDELIC-ASSISTED PSYCHOTHERAPY WORKS In most clinical studies with psilocybin, MDMA and other psychedelics, the medicine is used alongside talk therapy. Psychologist Alex Belser says most of the trials he has helped facilitate play out something like this: After a thorough screening process, an approved patient works with two or more facilitators — at least one of whom is a licensed psychotherapist.

Before interacting with any psychoactive medicine, that patient has three sessions, minimum, of talk therapy. This preparation time helps both the patient and therapist set goals and intentions while also building trust and understanding. That foundation is vital before introducing any psychoactive substances, which can stir up momentary fear, confusion, panic or paranoia in the human brain.

When the time comes to try the medicine — often in a pill, though oral strips are now in development — that session lasts several hours or a full day, sometimes with overnight care. Clinicians create a safe, comfortable spa-like setting for the patient. They might bring in stones and flowers or other natural objects. Calming music plays through speakers or headphones, and the patient might wear eyeshades or lie down to immerse themselves in the experience.

They often encounter vivid visions, poignant emotions and memories over the course of a few hours. Many people say they have interactions with deceased relatives or loved ones. The therapy team remains present the entire time. “Therapists can hold out a hand, the patient can grab their hand, take a few breaths, and get back in touch with what’s going on,” Belser says, noting that rescue medications like benzodiazepines have never been needed to calm a patient during his sessions. “It’s very intense. There’s often crying, and it can often be very motivating for them.”

After the experience, integration work involves at least a few more talk therapy sessions in the following days. These address what happened mentally and emotionally, how to make sense of it and what the patient wants to learn and integrate into their psyche and life. Belser says that lasting effects often occur after just one use of a psychedelic medicine. A study he was part of at New York University recently showed lasting results in patients four years after treatment. — T.M.

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medicine at its heart. That’s because our old drug classes may not have worked well to begin with and are sort of petering out.

Q

How do you describe the shift in this field over the past decade or so?

A: There’s just been an explosion of research in psychedelics. It used to be that when a new study would come out, we would parcel it out word-for-word, paragraph-by-paragraph, because there was so little research coming out. It was a trickle. Now it’s become a torrent of clinical research studies being initiated and papers being published, demonstrating very promising results for a variety of psychedelic medicines for any number of psychiatric conditions. It’s incredible.

There’s also been this massive interest from the public — from Michael Pollan’s book, How to Change Your Mind, to any number of media outlets that have covered these stories in different ways. It’s because when you talk with patients and when you talk to people doing this work, you realize that the experiences can be beautiful and powerful. The effects for people can be really not only intense, but healing, and

magic mushrooms. These are mushrooms that grow on the six inhabited continents of the world and have been used by human civilizations and peoples in documented anthropological literature for a long time.

We expect this is going to be a rulemaking period, and then,

states around the country.

Are there a lot of parallels to marijuana?

A: Well, I think it’s an experiment in federalism. In 1970, Richard Nixon signed the Controlled Substances Act into law, and it’s been an exemplar law, not just for the U.S., but for countries

Our practice of medicine should mirror and amplify that for the betterment of all people. in ways that don’t work the same way as our conventional medicines work.

Q

And Oregon legalized psilocybin in the November 2020 election. In application, what does that mean immediately and in the near future?

A: They have created a two-year development period. It’s not like the legislation passed, and then, overnight, psychedelic-assisted psychotherapy is legal. The measure is specifically about psilocybin, the active compound in

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psilocybin-assisted psychotherapy treatment for certain conditions will be legal to do by licensed clinicians in the state of Oregon only. And that sort of work may serve as a model for how other states or municipalities could potentially pursue this sort of clinical track. The Oregon approach is like a state-by-state legalization pathway. But psilocybin is still an illegal drug to use from a federal-statutes perspective.

Q

It sounds like the same path we’ve seen with legalizing cannabis in

around the world. But, when states like Oregon can change their state laws regarding how we can return to these medicines, it opens up a new field. And these medicines do show medical and psychiatric benefit for people, and the evidence suggests they are not addictive or dependence-causing.

But there’s an important distinction from cannabis: Cannabis is sold, even if it’s prescribed, as a product without supervision or without working with a facilitator. Psychedelic medicines are a very different class because nobody is seriously proposing that people

Psychoactive drugs, like psilocybin, are the focus of a new master’s program at the University of WisconsinMadison.

How does that foundation inform your work today?

A: I think it’s important to have a social justice framework when working in medicine, broadly and specifically in psychedelic medicine. There’s no way to do this work without attending to our participation in structures that might oppress people and our ability to make changes so that we can treat each other with compassion, dignity and deep respect. Our practice of medicine should mirror and amplify that for the betterment of all people.

Q

You mentioned earlier that psychedelic treatment isn’t really a pill-a-day model. Can you elaborate on that and how it fits into the current system of modern medicine?

should just be prescribed psilocybin for at-home use as we do with cannabis — at least not at significant doses. This is really a combination treatment. It would be a medicine that would be prescribed by a person who has specific training in doing psychedelic-assisted medical intervention work.

Q

OLLYPLU/SHUTTERSTOCK

That’s where practitioners like you come in — in your case, with 20 years of experience. But how did you get here, given the lack of activity in the field when you were in college?

A: I was a kid, an undergrad at Georgetown in the ’90s, and I read a book called LSD Psychotherapy: The Healing Potential of Psychedelic Medicine by psychiatrist Stanislav Grof. I just was so fascinated by these medicines and I flew to my first psychedelic conference and met all of the psychedelic leaders in the field at the time. The research movement [that gained momentum in the 1960s] had largely stalled out, but the traditions were alive and a lot of people knew that these could be promising

medicines. I wasn’t even pursuing psychology at that time. I was doing prison-reform work, working in jails and prisons in D.C., Maryland, Virginia, and then I moved to the United Kingdom for a master’s in criminology.

I tacked from there to working with LGBTQ+ people. My dissertation in psychology was on how to prevent suicide among lesbian, gay and bisexual teenagers. Because in that group, a lot of people feel like they want to end their lives in part because of the shame and stigma that they’ve received. We started a psychedelic research group at NYU in 2006, when I was just a graduate student. I got to help run a number of studies at NYU. I did my clinical research fellowship at Yale. And there I worked on a number of psilocybin studies. I’ve also worked on MDMA therapy studies for people with severe PTSD, including a vet from Afghanistan who had been pinned down in multiple firefights.

Q

That seems like an atypical path, especially for someone now working in pharmaceuticals.

A: I think that these are medicines for the whole person, and I think it’s important that we understand them as such. It’s not going to work to try to fit psychedelic medicine and practice into old models. We have to think differently about how we work with these medicines. When I say the whole person, I really do mean not just the body, but the mind and the person’s experience of their spirit and how they make meaning of their lives.

There is a long lineage of psychedelic plants and medicines being used by people across the planet. Western medicine kind of fell asleep on it for the last 100 years. And not all of those practices are still alive, and maybe not all of them will be helpful for us today.

But the psychiatric possibility of this sort of medicine is really a different way of asking, “What could healing be?” I think that psychedelic medicine and the research suggests we should think very deeply about how we practice medicine. D This interview has been edited and condensed for clarity.

Timothy Meinch is features editor at Discover.

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AFTER MORE THAN A CENTURY OF RISKY TRIALS AND MEDICAL ADVANCES, A VIRAL CURE FOR CANCER COULD BE ON THE HORIZON.

WHEN

VIRUSES HEAL

BY NATHANIEL SCHARPING

S

itting in an isolated room at Beth Israel Deaconess Medical Center in Boston, Frank Nielsen steeled himself for the first injection. Doctors were about to take a needle filled with herpes simplex virus, the strain responsible for cold sores, and plunge it directly into his scalp. If all went well, it would likely save his life.

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dissolved Nielsen’s tumors to the point where Keytruda alone could work. Roughly two years later, he remains free of cancer.

Someday in the near future, dozens of cancer patients could be in remission with similar stories to tell.

Infecting a cancer patient with a virus — a procedure that once would have raised eyebrows, if not malpractice lawsuits — might soon be routine. It’s taken more than a century of work, and a few hairraising experimental trials along the way, but a viral cure for cancer could be emerging.

HIGH RISK In the mid-1800s, doctors treating cancer patients started to notice something odd: People with infectious diseases sometimes saw their tumors shrink.

Case reports of the phenomenon date back to before scientists even understood what viruses were. For example, a leukemia patient in 1896 saw her cancer briefly dissipate, a seeming miracle, after contracting what was likely influenza.

Researchers began an audacious, often risky search for a cancer cure based on pathogens a few decades later, purposefully infecting cancer patients with a variety of viruses to see if they would prove curative.

One 1949 trial gave the hepatitis virus to patients with Hodgkin’s lymphoma. The results were mixed: Seven patients experienced a temporary improvement in their cancer, but at least one died from hepatitis.

Potentially deadly side effects notwithstanding, researchers pressed on. Trials of what we now call oncolytic viruses — pathogens that infect and kill tumor cells — continued through the 1960s.

They included experiments with the viruses

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Nielsen was a cancer survivor and, once again, a cancer patient. His melanoma, which had responded to conventional treatments the first time around, had returned with a frightening aggressiveness. Within weeks, a lump on his scalp had swelled into an ugly mass. Unlike the first time, options like surgery weren’t viable — it was growing too quickly.

As a last resort, his doctors turned to a cutting-edge drug known as T-VEC, approved in 2015 in the U.S. But the treatment, part of a promising field of cancer care known as immunotherapy, doesn’t sound much like a drug at all. T-VEC consists of a genetically modified virus that acts as both soldier and scout within the body, attacking tumor cells directly and calling in reinforcements from the immune system.

Nielsen’s doctors hoped it would team up with the immunotherapy drug Keytruda, which enables the immune system to recognize and destroy tumor cells, to bring his cancer under control.

For nearly a year, Nielsen, a mechanical engineer in central Massachusetts, traveled to Boston every three weeks to have the drug injected into the tumors on his scalp. He would come home with his head swaddled in bloody bandages, aching after as many as 70 separate injections in a single session. There, he would prepare himself for the inevitable fever, nausea and vomiting, as his body reacted to the sudden presence of a live virus.

But the grueling regimen paid off. After the fifth round of treatment, Nielsen says, he began to see a visible change in the lumps on his scalp. It was a moment of relief for the 61-year-old.

“I yelled to my wife and ran to the bedroom and was showing her,” he says.

The T-VEC treatments eventually

In combination with other immunotherapy drugs, oncolytic viruses can help defeat cancer and build the body’s defenses to prevent a recurrence.

HOW ONCOLYTIC VIRUSES WORK

FROM TOP: PHOTOBYTAWAT/SHUTTERSTOCK; JAY SMITH

Tumor cell

that cause West Nile, mononucleosis and a form of encephalitis, among others.

The idea was that a virus would penetrate a tumor cell, replicate, and eventually kill it, then invade other cancer cells throughout the tumor and repeat the process, says Samuel Rabkin, a neuroscientist at Harvard Medical School and Massachusetts General Hospital who works with oncolytic viruses. He says that, hypothetically, “the process would basically go round and round until there were no cancer cells left.”

Many early oncolytic virus trials would never fly today. In some experiments, scientists injected infectious fluids or body tissue directly into cancer patients. One 1974 study in Japan fed patients pieces of bread soaked with infectious liquid. Participants in these trials often got sick, sometimes severely — with fevers, bleeding and brain inflammation as side effects. Though many trials reported promising reductions in tumors treated with viruses, the success was always temporary.

“I don’t think it cured anyone,” says Stephen Russell, a hematologist at the Mayo Clinic and oncolytic virus researcher, of the early experiments. Viruses offered only temporary reprieve from the inevitable.

The virus replicates; immune cells rush to the scene.

The cell dies, virus particles spread to other cells and the immune response continues.

Oncolytic virus

Healthy cell

The virus doesn’t replicate.

The healthy cell is not damaged.

For most patients in those antiquated trials, their immune systems likely cleared the viruses from their bodies before the cancer could be eliminated — if the virus didn’t kill them first. Their stories point to the obvious drawback of oncolytic viruses: The curative agent is a longtime archnemesis of the human race.

We now know that some viruses do indeed go after cancerous cells in the body, with occasionally surprising effectiveness. Cancer cells possess a few traits that viruses tend to like, including rapid reproduction and a high level of metabolic activity, Rabkin says.

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A project aboard the ISS is studying cancer and aging in stem cells.

STEM CELLS IN SPACE

A

couple of hundred miles above your head, thousands of human stem cells will soon orbit Earth in a research lab on the International Space Station. If all goes well, the growing cells — which are due to dock later this summer — could help scientists unlock the mysteries of cancer and aging.

Late last year, researchers from the University of California, San Diego, and Space Tango, an aerospace engineering company based in Lexington, Kentucky, inaugurated the world’s first dedicated stem cell research center on the ISS, thanks to a NASA grant. Researchers have been sending carefully prepped samples to the Integrated Space Stem Cell Orbital Research Laboratory (ISSCOR) to study the effects of microgravity and ionizing radiation on stem cells in lowEarth orbit.

Test tubes containing blood-forming stem cells will depart for ISSCOR in August, packed inside enclosures small enough to fit in the trunk of a car.

Called CubeLabs, the containers are

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designed by Space Tango to replicate the conditions of labs on Earth, such as temperature and lighting, allowing researchers to study how low-Earth orbit impacts stem cell growth without interference from factors that might unintentionally impact results.

The boxes dock into an automated facility at the station, with minimal intervention from the ISS crew. The bulk of the work will be done remotely, with a team of scientists at UC San Diego observing and controlling the experiment from Earth, watching for telltale molecular changes that herald the start of cancer and cause immune cells to malfunction.

Researchers predict that the environment in space will speed up the growth rate and make stem cells differentiate faster into specialized stem cells, like blood, heart or brain cells, “without spending 10 years doing the experiments on Earth,” says Catriona Jamieson, a hematologist specializing in blood diseases from UC San Diego. Along with colleague Sheldon Morris, she’s spearheading a study to figure out how we age

— and how aging becomes malignant, leading to the formation of cancer.

The scientists plan to watch cancer develop step by step, with the hope that a deeper understanding of the process will unravel the secrets of its life cycle. This, Jamieson says, could help predict and prevent cancer progression, and enable early diagnosis and treatment of blood cancers, specifically.

But cracking cancer isn’t ISSCOR’s only mission — according to Jamieson, the space lab will be an ongoing, collaborative workspace to better understand stem cells and develop new therapies that can target other diseases in their infancy.

In December 2020, an experiment to understand how brain stem cells develop in microgravity was launched to the ISS, and an experiment on liver stem cells is scheduled for later this year. By 2025, ISSCOR will be a commercial space for scientists to test new drugs, antibody treatments and cellular therapies, proving that for stem cell research, the sky is no longer the limit. — PAYAL DHAR

NASA

How do cells turn cancerous? Researchers are taking to the skies to find out.

until the virus destroys it and moves on to another cell.

For decades, experts’ knowledge of that biological relationship failed to translate into an effective cancer treatment.

Following numerous trials with steep mortality rates and little real success, research on using viruses as a cancer treatment dropped. In the 1970s, new cancer therapies like radiation treatment and chemotherapy began to mature, giving patients other options. It would take years of significant scientific advances until viruses returned to the forefront of cancer care.

FROM LEFT: FUSEBULB/SHUTTERSTOCK; ANI VINCEK/SHUTTERSTOCK

FRIEND AND FOE In 2013, a Minnesota woman named Stacy Erholtz received an experimental treatment for her multiple myeloma, a cancer of the blood plasma cells.

Doctors injected a massive dose of an attenuated measles virus into her body. The genetically modified pathogen homed in on tumors, killing cancer cells and kickstarting a process that recruited her immune system to finish the job. Her cancer eventually went into complete remission, a startling success for an oncolytic virus, says Russell, who helped develop her treatment.

It’s likely that cases like Erholtz’s, in which the patient is successfully treated with just an oncolytic virus and nothing else, are outliers. But in the last decade, researchers have begun using viruses in combination with other drugs to effectively treat cancer in a wider range of patients. The combination that saved Nielsen’s life — an oncolytic virus and an immunotherapy drug — may soon be a viable treatment for multiple forms of cancer. Dozens of clinical trials are currently testing oncolytic therapies for cancer; recent years have seen a wave of interest in the field, with big pharmaceutical companies investing in or acquiring biotech start-ups. While T-VEC is the only oncolytic cancer drug in the U.S. so far, more will likely follow.

The days of feeding people virus-soaked bread are long gone. Scientists today have the ability to precisely manipulate viruses, as well as a more nuanced understanding of how oncolytics work.

But perhaps most important of all has been the advent of a groundbreaking class of cancer drugs known as checkpoint inhibitors, which enable the immune system to take on cancer. The first drug of this kind, ipilimumab, was approved by the FDA in 2011. The key breakthrough came when researchers discovered that cancer cells depend on a unique cloaking mechanism to survive. The body’s immune cells display on their surfaces proteins called checkpoints, which normally modulate the immune system so that it doesn’t destroy healthy cells. When

an immune cell recognizes a checkpoint, it’s like an automatic off-switch: The cells stop dividing. Tumor cells co-opt this mechanism by displaying matching checkpoints, causing any curious immune cells to stand down.

Checkpoint inhibitor drugs, the backbone of modern immunotherapy, block those checkpoints on immune cells, effectively removing the ability for cancer cells to bind with them. The discovery has led to treatments for advanced cancers, like metastatic melanoma, that were once seen as a death sentence.

When it comes to fighting invaders, the immune system relies on specialized members of its fleet: T cells, which learn to recognize and kill interlopers.

But there aren’t always enough T cells nearby to do the job effectively, something that’s hampered the success of immunotherapy drugs. That’s where the viruses come in — they call more T cells to the site of the tumor.

“When a virus is given to a tumor, the tumor becomes infected tissue,” says Vincenzo Cerullo, an oncolytic cancer vaccine immunologist at the University of Helsinki. That catalyzes swarms of T cells to rush to a tumor, ready to defend the body.

Today, checkpoint inhibitor drugs are effective in only a small percentage of patients. Add in a virus, however, and that percentage can double or triple.

This combination of treatments is marking a turning point for cancer research, says James Allison, an immunologist at the University of Texas

In one early oncolytic trial, researchers fed participants bread soaked in infectious liquid.

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Though some trials have administered oncolytic treatments through an IV, more work is needed to make this method effective.

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tumors itself could offer a cure for even hard-totreat metastatic cancers that spread quickly and lethally.

A BODY IN BATTLE Nielsen was lucky in one sense — the tumors that colonized his scalp were all close together and raised above the surface of his skin. That made it easy for doctors to inject a virus directly into them. But some tumors can be hard to access, and others spread throughout the body as they metastasize, making them more difficult to target with treatments.

Researchers are currently working to better adapt oncolytic treatments to be delivered through an IV. Theoretically, when a virus can move freely throughout the body and spread its immunogenic clarion call, even the most hard-to-access tumors could be targeted and wiped out. Though some trials of oncolytic viruses have used intravenous

GOODBISHOP/SHUTTERSTOCK

MD Anderson Cancer Center. In 2018, Allison was a co-recipient of the Nobel Prize in Physiology or Medicine for his work on checkpoint inhibitors.

For cancer treatments before the advent of immunotherapy, “you had to kill every last tumor cell if you’re going to cure somebody,” he says. Now all doctors need to do is get the immune system involved and give it the tools to take over.

And, as Allison and others have shown, the beneficial effects of a viral infection extend beyond the site of a single tumor. Allison found in experiments that injecting mice with a virus slowed the growth of not only the tumor the researchers targeted, but tumors elsewhere in the body as well. T cells, once marshalled, are primed to move throughout the body, attacking cancer cells wherever they find them. Allison calls this a systemic immunity to cancer, and it’s become a goal for oncolytic virus researchers all over the world.

Giving the body the means to fight off

FROM LEFT: CI PHOTOS/SHUTTERSTOCK; SHUTTERDIVISION/SHUTTERSTOCK

administration, scientists say more work is needed to make them fully effective.

The promise of more flexible treatment methods would help boost another goal in the field: developing so-called vaccines for cancer. The drugs promise to not only fight off tumors, but to turn the body itself into a cancer-killing machine. It’s a tall order, but cancer experts have reason to be hopeful, in part because the tools they’re using to build treatments have proven extraordinarily adaptable.

Russell calls viruses the world’s best Lego set. “You can take any virus and add new genes, engineer the existing genes, dismantle and rebuild,” he says.

Today, oncolytic viruses already make use of a small genetic mutation that helps them avoid infecting normal cells. But there’s potential to make more sweeping modifications to viruses, in turn creating more precise and effective treatments.

Russell, with a biotech company he helped found called Vyriad, is experimenting with adding a gene to a

virus that enhances the immune system’s response. Like the chemicals that stimulate immune cells and attract them to a pathogen, Vyriad’s engineered virus has a similar effect. Here, viruses are being led to human cells that have gone rogue. Russell says the process should help doctors give higher doses of an oncolytic virus without endangering the patient.

A different approach might be to focus on simply making viruses more provocative to the immune system. Cerullo refers to it as arming the virus.

T-VEC, for example, has a genetic modification that allows it to express a compound that the body uses to stimulate the immune system. Like sharks to blood, immune cells mobilize at a whiff of these molecules.

Engineering an oncolytic virus might guarantee it gets noticed, ensuring a strong immune response against the tumor.

Ultimately, the goal is to make it so that a patient’s body is capable of recognizing and fighting cancers it has seen before, resulting in a kind of immunity to cancer. It would remove one of the final legacies of cancer for patients like Nielsen, who must live every day with the unsettling risk of recurrence lurking over them. Oncolytic viruses might turn a cancer diagnosis into something much like a viral infection — frightening and uncomfortable, but treatable. D Frank Nielsen’s name is a pseudonym, to protect his privacy.

Nathaniel Scharping is a freelance writer and editor based in Milwaukee.

THE DRUGS PROMISE TO NOT ONLY FIGHT OFF TUMORS, BUT TO TURN THE BODY ITSELF INTO A CANCER-KILLING MACHINE.

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TECH NOTE

Above: A prototype of the handheld device designed in Yarmush’s lab.

Blood Work AFTER A DECADE OF PLANNING, ONE LAB HAS CREATED A DEVICE THAT MIGHT MAKE A COMMON PROCEDURE SAFER AND SIMPLER.

L

ate one night in 1982, a Yale University medical student named Martin Yarmush witnessed a harrowing scene at a local hospital. A toddler was admitted, and several nurses attempted to insert an IV needle into one of the child’s tiny veins. Each time they missed the vessel, the child screamed more shrilly, and the mother grew more worried.

There has to be a better way, thought Yarmush, now a professor of biomedical engineering at Rutgers University.

The incident changed his outlook on medicine. Thoroughly unnerved by the anguish he’d witnessed, Yarmush started to imagine what would happen if the process of drawing blood could be automated.

At the time, automation was found primarily on assembly lines for cars, where robots were so powerful and dangerous that they were bolted to the ground and enclosed in metal cages. In 1985, a modified robotic arm was used to perform a brain biopsy on a 52-year-old man. But another decade and a half would pass before robots gained regular employment

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Each time they missed the vein, the child screamed and the mother grew more worried.

in hospitals, finding work as surgical assistants in operating rooms.

Today, surgical robots are commonplace in medical facilities around the world. Controlled by doctors wielding virtual forceps and scalpels in front of a computer terminal, they help perform a range of complex procedures, from hip replacements to kidney transplants.

Despite these advances, the deployment of robots in hospitals has been limited: They assist in some of the most highly skilled tasks in health care, while remaining conspicuously absent in scenarios like the one Yarmush witnessed as a medical student.

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Yarmush’s biomedical engineering lab has spent the past decade trying to remedy this imbalance.

Thanks to advances in sensors and artificial intelligence that have improved the quality and lowered the cost of robotics, they are now developing a blood-draw robot small enough for clinicians to carry in their pockets.

THE ROBOT AD-VEIN-TAGE

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The handheld device could be carried around in a lab coat pocket and used to perform blood tests at a patient’s bedside.

Existing systems were powerful, but not living up to their full potential.

loading dock crane, partly encased in smooth, white plastic. The robot could autonomously locate a vein in a gelatin-skinned model forearm with ultrasound technology and artificial intelligence, then precisely pierce the fake flesh with a motor-driven needle. The machine was capable of drawing blood, processing it in an integrated centrifuge and safely discarding the spent needle. All that remained was the gauntlet of human clinical trials required for FDA approval — and the money to fund them.

The lab had interest from investors, but it was hard to convince them to fund the technology for a procedure due to the relatively low compensation from insurers for a blood draw. And without human trials, it wasn’t proven technology.

Companies were reluctant to advance the cash without proof.

But that didn’t mean the work came to a halt. In recent years, the lab has shifted its focus to create a more portable device for medical professionals — a project that’s especially poignant in the era of COVID-19.

A LONG ROAD TO THE HOSPITAL Josh Leipheimer, who has worked in Yarmush’s lab since 2016, has devoted much of his time to scaling down the robot’s size. The result is a handheld device that could potentially be carried in the pocket of a lab coat so that one day medical professionals can perform blood tests at the patient’s bedside.

Leipheimer recently shepherded the robot

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In 2010, nearly 30 years after Yarmush first realized its potential, the blood-drawing robot began to take form. At Yarmush’s suggestion, a Rutgers engineering student named Alvin Chen started to investigate venipuncture — the technical term for any procedure involving a needle inserted in a vein — as an opportunity to use technology to make a common process easier, safer and more effective.

Chen’s research affirmed Yarmush’s suspicions. The most common medical procedure in the world, venipuncture is also the most prone to failure. Nurses and phlebotomists struggle not only to penetrate the blood vessels of small-veined children — as Yarmush observed back in the ’80s — but also have problems with patients who have wrinkled skin, or whose veins are hard to find. And missing the mark can have serious medical consequences, including clotting, infection and nerve damage. Add to this the frequency with which clinicians accidentally stick themselves in an emergency, and the potential benefits of a venipuncture robot becomes obvious.

Chen collaborated with another engineering student in Yarmush’s lab, Max Balter. Together, they found preexisting technologies that could be combined to make a robot capable of semiautomating the entire blood-draw process. As Balter explains, existing systems were powerful, but weren’t living up to their potential because available sensors and robotics hadn’t been effectively combined.

“There are imaging technologies that help clinicians locate vessels that are hard to see,” he says, mentioning infrared and ultrasound as two examples. “But you’re holding the probe in one hand and looking at the screen, away from the patient, and then with the other hand you’re manipulating a needle. It can be very challenging.”

Eventually, the team produced a benchtop device with a rotating arm that moved like a miniature

through a small clinical trial of 31 volunteers. The robot was as good at inserting a needle and drawing blood as a professional phlebotomist, a promising step toward future studies with hundreds of patients in a more realistic setting. “We would assess the device’s performance in an actual clinical environment rather than a lab environment,” he explains.

It’s an expensive proposition, which faces funding challenges akin to those previously encountered

by Balter and Chen. But, as Balter points out, the novel coronavirus presents a novel situation — one where applications for the machine could expand beyond a routine blood draw to include antibody testing and vaccination. In the future, automated venipuncture could also lead to greater safety for both patients and medical personnel by eliminating the need for unnecessary physical contact.

Fortunately, Yarmush’s group never abandoned the full-size machine. “The benchtop and the handheld go hand in hand,” says Leipheimer. “A lot of the development that has been made on the portable can be back-implemented.”

Andra Keay, an industry expert who is the managing director of Silicon Valley Robotics, believes that’s an ideal scenario, because one successful application of an invention can open an entire market. She’s observed this phenomenon with the expansion of surgical robotics from abdominal procedures to pretty much everything that can be done to a body under anesthesia. “Once you’ve solved venipuncture, then you’re going to get all of these variations for free,” she predicts.

Though the future of Yarmush’s blood robot isn’t yet certain, he says the “goal has always been the same: to provide a point-of-care blood draw and diagnostic system that is simple, quick, and efficient.” The nearly 40-year journey has been anything but smooth, but Yarmush’s conviction that there has to be a better way could be a few clinical trials from being vindicated. D Jonathon Keats, a contributing editor to Discover, is the author of You Belong to the Universe: Buckminster Fuller and the Future.

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PLANET EARTH ORIGIN STORY

BY BRIDGET ALEX

The Anthropocene’s Ancient Origins HUMANS AND THEIR ACTIVITIES HIJACKED EARTH. SCIENTISTS INVESTIGATE WHEN THE TAKEOVER BEGAN.

T

here’s no doubt humans are at Earth’s helm, setting the course of future climate and biodiversity. Our species is now the dominant force shaping Earth’s climate and ecosystems, supplanting forces like solar orbit, volcanism and natural selection, which had directed the planet for most of its 4.5 billion years. Welcome to the Anthropocene, a proposed new epoch in Earth history, in which Homo sapiens are blindly steering the ship.

For the past decade, a scientific committee known as the Anthropocene Working Group (AWG) has been investigating when the Anthropocene began. In 2016, they voted for a 1950s start. Most members contend that’s when humans became a global superpower, through both nuclear weapons testing and the post-World War II boom in population and production, known as the Great Acceleration.

The AWG plans to propose adding the Anthropocene to the geological timescale, Earth’s official timeline, which is divided into phases based on dramatic environmental change evident from fossils and rocks. For instance, the Late Cretaceous epoch ended 66 million years ago, with the mass extinction that

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We’re in the midst of a transition from the predictable Holocene to a new epoch in which humans are blindly steering the ship.

killed off the dinosaurs. The melting of mile-high glaciers 11,700 years ago ushered in the Holocene — an epoch characterized by fairly temperate conditions, amenable to agriculture, permanent settlements and civilization as we know it.

But the AWG and others contend that human activities cut the Holocene short. We’re in the midst of a transition, from the predictable Holocene to the uncharted Anthropocene. “There’s never been a geologic epoch that’s been viewed so close up. It wasn’t like scientists were sitting around 10,000 years ago watching the end of the glaciation,” says AWG member Erle Ellis, a professor of geography and environmental systems at the University of Maryland, Baltimore County.

Catastrophic asteroids aside, most transitions unfold over tens of thousands to millions of years. But because the geological timescale covers 4.5 billion years, these long stretches of change are sudden blips between even longer distinct Earth regimes. To geologists studying rock formations, those

RICH CAREY/SHUTTERSTOCK. OPPOSITE PAGE, FROM LEFT: GWOEII/SHUTTERSTOCK; SABLINSTANISLAV/DREAMSTIME

For better or worse, humans are the dominant force shaping Earth’s ecosystems, and have been for a lot longer than you might think.

blips look like sharp boundaries between different sedimentary layers.

Geologists have detected a worldwide marker laid in the 1950s, which could signal the start of the Anthropocene.

During that period, radioactive particles released from nuclear weapons deposited a vivid marker in sediments around the world. A thousand years from now, someone digging could hit that layer and know they’ve reached mid-20th century material. In the coming years, the AWG will send an official proposal to the International Commission on Stratigraphy for a final decision on whether to add the Anthropocene to the geological timescale, with a 1950s start.

But not everyone is in agreement. Ellis was among four of 34 AWG members who voted against the mid-20th century start. He sees the HoloceneAnthropocene transition as more complex and gradual, unfolding at various times and tempos,

The Brazil nut tree (Bertholletia excelsa) would have been useful to early civilizations and cultivated as such. The impact of that cultivation is evident even today.

depending on the type of evidence considered.

While the AWG is interdisciplinary, including chemists, biologists and historians, most members are geologists — trained to analyze vast timespans. In addition to geographer Ellis and one geologist, the dissenting votes came from the group’s two archaeologists, scientists who investigate human-caused changes over (mere) hundreds or thousands of years.

They represent a minority view in the AWG, but

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ORIGIN STORY

In Amazonia, samples from cores drilled into lakes help gauge environmental impacts from early civilizations.

shows people substantially altered the planet long before the Great Acceleration. But she stresses a critical distinction between those ancient modifications and what’s happened since the 20th century.

“Although the scale of change was really huge in the past, it’s just unbelievably massive today,” she says.

“A whole new ballgame.”

To avoid minimizing the current climate crisis, Boivin suggests calling earlier transformations the Paleo-Anthropocene or Proto-Anthropocene.

Studying this phase could help clarify the natural baselines and also reveal the long-term sustainability of various human-environment interactions. For instance, what farming practices lasted millennia and which ones depleted the landscape in decades?

Boivin and colleagues highlighted a major way ancient peoples transformed Earth by shaping species distributions, outlined in a 2016 Proceedings of the National Academy of Sciences paper. For millennia, we’ve driven species to extinction, proliferated others like chicken and corn, and moved creatures around the globe. Reviewing evidence ranging from microscopic plant remains to mammoth bones, the researchers concluded natural ecosystems do not exist, and in most places, haven’t for thousands of years.

outside the group, many experts share their stance.

Together they’ve published papers in Nature, Current Anthropology and other journals that show humanity’s influence extends back millennia — to the dawn of urbanism or agriculture, or even before.

DIGGING DEEPER The matter is more than a philosophical debate.

Models projecting future climate depend on reconstructions of past natural conditions, before significant human modification. To get that data, climate scientists and ecologists often use “preindustrial baselines,” environmental conditions before industrialization, assuming those were natural. Archaeologist Nicole Boivin thinks they need to look deeper in time. “Where’s the baseline?” says Boivin, director of the Max Planck Institute for the Science of Human History, in Jena, Germany.

Like many archaeologists’ work, her research

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Humanity’s influence on our climate and ecosystems extends far beyond the 20th century, to the dawn of urbanism, agriculture or even before.

Supporting the central claim of Boivin’s 2016 paper, scientists are finding that ancient humans remodeled even the most pristine-looking environments, like Amazonia.

“There’s a huge paradigm shift going on in the Amazon,” says paleoecologist Yoshi Maezumi. We now know Indigenous people were there, engineering the landscape, millennia earlier than assumed; they domesticated squash and manioc in the then-treeless savannah bordering Amazon forests 10,000 years ago, according to a 2020 Nature paper.

That’s close in age to the oldest known crop domestication, in the Middle East about 12,000 years back.

Through this planting and dumping of food waste, ancient humans in Amazonia created nutrient-rich soils, leading to the growth of thousands of arboreal islands, still standing in the grasslands of present-day Bolivia.

Deep within the rainforest, strong evidence points to humans cultivating useful tree species close to their homes. While the Amazon Basin contains an estimated 16,000 woody species, half the trees belong to just 227 species, known as hyperdominants. In a 2017 Science study, researchers compared the distribution of 3,348 pre-Columbian archaeological sites with forestry surveys conducted across

YOSHI MAEZUMI (2)

NOT SO NATURAL

the region. The analysis showed oft-domesticated trees, including the Brazil nut, nutmeg and palm, grow in abundance closer to archaeological sites, and overall are five times more likely to be hyperdominant than would be expected. This suggests past people nurtured these trees and discouraged the growth of other species.

Ancient Amazonians had “lasting impacts on the environment, both positive and negative,” says Maezumi, based at the University of Amsterdam.

By analyzing charcoal and pollen grains in deep, layered lake sediments, Maezumi reconstructs changes in ecology and wildfires over time.

Working with archaeologists and other experts, she recently lined up this data with the rise and decline of Amazonian societies. Her work, published in 2019, shows some groups developed sustainable agroforestry: By cultivating diverse, dispersed trees and other crops that enriched the soil, these cultures persisted through different climate conditions. But societies that grew a few species, in concentrated abundance, collapsed during past climate change.

“The practices can definitely provide analogues or lessons for how we could use the land today,” says Maezumi.

While fossil fuels and modern trash leave an obvious mark on the environment, they are points on a continuum stretching back millennia.

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CALLING ON COLLECTIVE KNOWLEDGE To truly characterize the Anthropocene’s emergence, researchers need a global view of the archaeological and environmental records.

To glean that, Ellis, Boivin and others surveyed 255 archaeologists about land use, identifying specific areas of expertise and time periods between 10,000 B.C. and A.D. 1850. The results, published in Science in 2019, suggest that the continents held more human-modified land than wilderness 3,000 years ago. In some areas, like temperate Europe and northeast China, that’s about 2,000 years older than dates for widespread farming and grazing in climate reconstructions made by earth scientists.

A new initiative aims to measure our impact, from early agriculture to modern pollutants.

However, land use is just one component of our species’ footprint, and the survey relied on expert opinion, rather than actual archaeological data.

Using the study as a springboard, an initiative based at the Max Planck Institute in Jena aims to synthesize global data on humanity’s environmental impacts. The project intends to capture “everything from burning regimes and agricultural use, all the way up through microplastics and persistent organic pollutants from things like fertilizer and fossil fuels,” says archaeologist Andrea Kay, a postdoctoral researcher coordinating the effort.

In planned excavations, postponed due to COVID-19, the team will collect all human-made remains — from microplastics to ancient stone tools — from surface level to bedrock. Meanwhile, they’re forging ahead with a massive synthesis of the existing data, stored in notebooks and on hard drives of researchers around the world.

The time is right for such an undertaking. The Max Planck team now has the necessary computing power, and due to the pandemic, they’re parked at home and working to make sense of the accumulated evidence.

The hope is that the archaeological data will tell a more fine-grained history of how and when the Anthropocene began — and what humans must do to steer Earth to a sustainable future. D Bridget Alex is an anthropologist and contributing editor to Discover. She tweets @bannelia.

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PLANET EARTH #ScienceIRL

BY DONNA SARKAR

TAJ MAHAL: THE CORRODING BEAUTY do you picture? History books and airbrushed photos show a pristine, milky white structure situated on the banks of the Yamuna River in the city of Agra. But the 17th-century monument that draws millions of tourists from across the world is under threat.

The aging exterior of the Taj wears a greenish brown tint due to rising pollution, burning trash and insect poop. And the nearby banks of the Yamuna face similar degradation due to chemical waste from factories, raw sewage and heaps of garbage that sustain swarms of breeding flies — the source of the dung on the Taj.

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When Mughal Emperor Shah Jahan built the structure in memory of his wife, Empress Mumtaz Mahal, it was viewed as an act of eternal love. The monument, which took over 15 years and 20,000 workers to construct, holds the tombs of the lovers. Activists are now trying to hold the government accountable

to preserve the UNESCO wonder, after India’s Supreme Court ordered its restoration, closure or demolition in 2018.

Aside from physically scrubbing the Taj clean, efforts include building a new dam to help restore the flow of water to the Yamuna, shutting off some of the 52 discharge pipes pumping waste into the water and improving nearby sewage treatment plants. The number of visitors has also been limited. The future of the Taj Mahal, however, still remains uncertain. D

SCIENCE IN REAL LIFE We want to see your awe-inspiring photos. Tag #ScienceIRL and @Discover.Magazine on Instagram to share encounters with science in your cities, nature, the arts and beyond.

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When you imagine the Taj Mahal, what

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