Sarah Zhang | The Atlantic

The Family That Decided to Have Their Stomachs Removed

2026-03-31T11:45:03-04:00

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“What do you mean, you just take the stomach out?” Karyn Paringatai wondered, when doctors first said her stomach had to be surgically removed. Could she still eat? Yes, but differently. What would replace it? Nothing. She would have to live the rest of her life missing a major organ.

Paringatai was not actually sick, not yet. Her stomach was fine. But her cousin, just a few years older, had recently died of an aggressive stomach cancer at age 33, leaving behind three children. In a video recorded after her diagnosis turned terminal, the cousin told her little kids to be good for their father. “Please don’t be too mean to the lady that he meets,” she added, anticipating how the void left by her death might be filled. But she must have known that this void could not be filled, not ever. The cousin’s own mother had died young of stomach cancer. So had her grandmother. So had her sister.

To the doctors who saw Paringatai’s cousin in Tauranga, New Zealand, this pattern was hauntingly familiar. Her cancer was an unusual and distinct kind called diffuse gastric cancer, in which cancerous cells percolate undetected through the stomach, forming obvious masses only in advanced stages—usually too late to treat. The doctors had witnessed the same rare cancer run through a large Māori family near Tauranga. In that family, one woman lost six of her siblings to stomach cancer; a boy had died at 14. The family now reached out to Paringatai’s. It’s genetic, they said. You have to get tested.

Paringatai, whose father was also Māori, got tested. And indeed, she carried a mutation in the same gene, known as CDH1, as the other family. This gave her a 70 percent lifetime risk of developing advanced diffuse gastric cancer. Because this form of cancer can metastasize so quickly and unpredictably, the only surefire method of prevention is a complete removal of the stomach, or total gastrectomy. It’s analogous to a preventive mastectomy for breast cancer—but far more physically taxing. A number of women with a CDH1 mutation have actually had both their stomach and breasts removed because this mutation can also confer a 40 percent risk of breast cancer. One of them told me, about her gastrectomy, “If you can do that, you can do anything.”

Paringatai’s surgeon could not answer all of her questions about living without a stomach—her total gastrectomy was the first he would ever perform in a healthy person. But she went through with the procedure in 2010, and she credits it with saving her life. In the operating room, her surgeon made a long incision down her abdomen, cut out the fist-size pouch of her stomach, and stitched her esophagus to her small intestine. She was the first in her family to have her stomach removed prophylactically. Others followed. On a recent trip to visit her father’s family, Paringatai found herself sitting on a porch with her aunties and cousins. Of the eight people there, she realized, only one still had a stomach: her partner. “You’re the odd one out,” she teased.

Mutations in CDH1 seem to be unusually prevalent in Māori families, where they arose multiple times, possibly because they once conferred some evolutionary advantage. But mutated versions of CDH1 have been found around the world too, and thousands of patients have likely now had gastrectomies to head off cancer.

In New Zealand, “we’re coming up to nearly 30 years of people living with no stomachs,” says Paringatai, who is now a Māori-studies professor at the University of Otago. For the past several years, she has been documenting the experiences of Māori with CDH1. That people can live this long without a stomach is a testament to the adaptability and resilience of the human body. That doctors resort to such radical measures exposes the limits of what modern medicine can offer.

The first Māori to undergo prophylactic gastrectomies were the family that warned Paringatai’s about the cancer gene. They knew all about the gene because they had helped find it. Back in 1994, Maybelle McLeod contacted a genetics lab at the University of Otago about the premature cancer deaths stalking her relatives. Among themselves, she told me, “nobody even talked about it.” The family believed they lived under a curse for letting their land be sold for a quarry. McLeod grew up listening to the quarry’s warning sirens, learning to take cover indoors before the blasting began. She watched as the hill near her home was stripped bare.

McLeod eventually moved away, became a nurse, and learned of the then-nascent field of cancer genetics. This, she thought, explained the so-called curse. The geneticist she contacted, Parry Guilford, agreed to take the case. But her family still had to be persuaded to trust this pakeha, this white man, with their DNA. Over a series of meetings—attended by as many as 100 members—Guilford explained that his motive was the same as McLeod’s: to find the cause of so much death. They ultimately agreed to a contract where only the family, not Guilford, could directly approach members and gather their DNA samples. From there, the gene mapping went quickly, and scientists homed in on CDH1. The gene encodes a protein that normally orients and aligns cells in the stomach; without it, the cells become lopsided, rogue, and possibly cancerous. Any parent with a mutation in the gene has a 50 percent chance of passing it on to their children.

This breakthrough meant that a genetic test could now reveal who was at risk of diffuse gastric cancer; the family would no longer have to live in fear of where cancer would strike next. McLeod herself tested negative for the mutation. She was in the clear.

But those who tested positive for the mutation now faced an agonizing new dilemma. Doctors could not guarantee that endoscopies, even annual ones, would reliably catch such an aggressive cancer in time. Total gastrectomies had been performed before, in patients whose stomachs were already ridden with tumors—but never routinely in healthy people who did not have cancer and may ultimately never have cancer at all. So now they had to choose: 70 percent chance of deadly cancer or surgery with a 100 percent chance of significant side effects?

Rangi McLeod, who worked alongside Maybelle in urging relatives to join the study, was the first of the family to test positive for the CDH1 mutation. Not long after, doctors found a tumor in his stomach. It’s not all bad news, Guilford recalls Rangi saying. “I can lead my family to the next stage.” His gastrectomy would no longer be strictly prophylactic, but he’d have his stomach out, he’d recover, and he’d show anyone who still feared the surgery that it was safe. Rangi did not recover, though. He fell into a coma after the new connection between his esophagus and intestine grew weak. He died a few weeks later. “The whole project almost fell apart immediately on the spot,” Guilford told me.

In time, the family decided that Rangi would not want them to stop—he would not want for their children and grandchildren to continue to succumb to cancer. The family found a more experienced surgeon in a bigger hospital in Auckland; the next 10 gastrectomies were a success. Since then, stomach cancers in the family have plummeted. And the hill where the quarry once operated is green again. The land, it turned out, had not been sold but taken by the government, and was returned to the family. In any case, the curse, some in the family said, had finally lifted.

A successful gastrectomy looks like this: For at least the first six months, your life revolves completely around food, and not in a fun way. You eat tiny portions 10 times a day. You have to chew, chew, chew food like gum to make up for the lack of a stomach. Your digestive system spews from both ends. Your blood sugar rises and crashes unpredictably; you faint at the worst times. You are tired all the time. You lose a lot of weight, which might feel welcome at first but then feels scary. You are unable to work for a couple of months—longer if your job is physical or your recovery is difficult. About one in 10 patients has complications serious enough to warrant hospitalization, according to studies done in U.S. hospitals.

Gradually, the upper part of the intestine adapts into a sort of stomach. You start eating larger portions, less often. You gain weight. You still need regular shots of B12, which you cannot absorb without a stomach. But several people more than 10 years out from surgery told me they eat almost normally—with only small, lingering quirks. Plain water, for example, can be strangely hard to drink, possibly because of its surface tension, while flavored water goes down fine. Young women who have had their stomach out routinely go on to get pregnant and have healthy children.

Still, those who ultimately recovered well knew of family members who continue to struggle years later with nausea or reflux or fatigue. One of Paringatai’s cousins left her teaching position because she could no longer physically keep up in the classroom. Another cousin, Isaia Piho, was a firefighter. He, too, switched to a less demanding job afterward. Isaia and his younger brother, James, told me they had watched their mother die of stomach cancer. They are fathers themselves now, and they did not want their children to experience the same.

But not everyone who weighs the odds decides on surgery. Guilford knows another guy, also a firefighter, who decided to keep his stomach. “I run into burning buildings every second day,” he told Guilford. “I’m good with risk.” He’s chosen to have regular endoscopies instead. Still others might prefer not to know that they carry a CDH1 mutation. In the McLeod family, a young man in his 30s who went untested recently died of cancer, Guilford said. Diffuse gastric cancer has remained stubbornly difficult to treat over the three decades he’s been studying it. At the stage when it can be easily detected, the survival rate is just 20 percent.

Doctors are still trying to fully grasp the long-term consequences of losing a stomach, which makes it more difficult for the body to take up nutrients. “We’re learning that gastrectomy severely impacts bone health in the long run,” Daniel Coit, a surgical oncologist who recently retired from Memorial Sloan Kettering Cancer Center, told me. The loss of stomach acid may make calcium harder to absorb. As these patients age and continue to lose bone density, they will be particularly vulnerable to fractures.

Coit, who performed numerous prophylactic gastrectomies in his career, thinks the social and psychological consequences of losing a stomach deserve more attention too. He had one family in which multiple people died prematurely of suicide or alcohol use after their surgeries. Did the procedure lead directly to their struggles, or unmask a previous predisposition? His example is only anecdotal, he said, but the issue should be studied.

This is anecdotal as well, but alcohol also came up repeatedly in conversations I had with people who have been through gastrectomies—without me asking. Either they themselves started drinking too much, or they had family members who started drinking too much.

James Piho told me he drank to numb his fear of cancer and then he drank to numb his depression after his surgery, when he was unable to provide for his daughter. James actually works in a drug-and-alcohol rehab center, and his experience had him wondering about a link between total gastrectomy and alcohol. Could it be psychological or biological, or both? For people who find drinking plain water uncomfortable, alcohol seems to literally go down easier. And bariatric surgery, in which the stomach is shrunk but not entirely removed, is correlated with a well-documented increase in alcohol-use disorder. Losing even part of a stomach may make patients’ bodies more sensitive to alcohol—two drinks, according to one study, might feel like four. Haupiua Steventon, a member of McLeod’s family who had her stomach removed at 18, got a job at a bar after the long recovery derailed her university studies. “I fell into alcoholism very easily,” she told me. She eventually found her footing and has two kids now, but looking back, she wishes she had been warned about alcohol post-surgery. She wouldn’t have chosen to work in a bar.

In interviews that Paringatai conducted with different generations of McLeod’s family, she observed that some of the younger members struggled more, mentally, post-surgery. The older generation, she told me, had witnessed the deaths of so many “mothers, sisters, fathers, first cousins, children, grandchildren.” Today, young people in the family have not experienced those tragedies firsthand—a sign of progress that nevertheless made the sacrifice of a stomach harder to bear.

“I think we’ll look back one day and we’ll go, ‘Man, I can’t believe that we did such draconian surgery on those people,’” Guilford said. His lab continues to investigate diffuse gastric cancer, with the hope of developing a treatment or drug that makes a total gastrectomy obsolete. In recent years, doctors have become more open to patients choosing surveillance over surgery, especially as it’s become clear that CDH1 carriers with no family history are at lower risk for diffuse gastric cancer—perhaps a lifetime risk of about 10 to 40 percent rather than 70 percent. But even Coit, who is among the more skeptical of surgery, recommends prophylactic gastrectomies for people with a strong family history. Their risk is high. Surgery is the best solution we’ve got. But of course, Guilford said, “people would love to keep their stomachs.”

Paringatai found that some of the Māori took their stomachs home, rather than allow the hospital to discard the organ as medical waste. In Māori culture, she explained, the body is sacrosanct. They wanted to honor the stomach, thanking it for its service. Several buried theirs on their family land. In a way, this is how they can, for now, keep their stomachs.

American Milk Has Changed

2026-02-04T12:19:51-05:00

In recent years, American milk has undergone a quiet transformation. The milk produced by our dairy cows has become creamier and more luscious as breakthroughs in cow genetics and nutrition have pushed the fat component of milk—also known as butterfat—to all-time highs. In 2000, the average dairy cow made 670 pounds of fat in her milk a year; today, she’s making 1,025 pounds. No single trait in dairy cows has improved as rapidly with genomic selection as fat, according to Chad Dechow, a dairy-cattle geneticist at Penn State. It’s a triumph of dairy science.

Lately, though, all is not well in the world of butterfat. Dairy science has arguably made our cows too good too fast at fat-maxxing.

This past fall, butter prices collapsed as a “tsunami” of butterfat inundated the market. “We really have an oversupply right now,” Corey Geiger, the lead economist for dairy at CoBank, told me. The reason is twofold, he explained: U.S. farmers are keeping a near-record number of dairy cows, which are in turn producing milk with a record level of fat. For customers, this oversupply means cheaper butter. For farmers, “it’s going to be a tough year,” Dechow told me. “The farmers take it on the chin.”

Until last autumn’s crash, farmers had every economic incentive to keep pushing the limit on fat. Butter and cheese consumption have been growing steadily since the 1990s, and butterfat prices were sky-high for several years running. When dairy farmers sell milk, they are generally paid not by volume—milk is mostly water, after all—but by the weight of its solid components, primarily fat and protein. More fat plus more protein adds up to a bigger milk check. Although protein, too, has ticked up in milk, fat has proved more responsive to changes in genetics and diet. After hovering for decades around 3.65 percent, milk fat began rising first slowly and then quickly, reaching 4.24 percent in 2024.

“Genetics sets the ceiling, and nutrition determines the floor,” Dechow said. After the first dairy cow’s genome was sequenced in 2009, the industry started raising the genetic ceiling. By marrying DNA markers to the milk-production records of millions of cows, farmers are able to choose bulls for breeding based on the predicted traits—including milk-fat yield—of their future daughters. And when those daughters are born, some farmers once again DNA-test the young cows, keeping only the ones with the most potential. This precise level of selection has allowed the high-butterfat versions of milk genes to spread far and wide in the American dairy herd over just a few generations. Genetics explains about half to two-thirds of the rise in butterfat levels, experts told me.

For a cow to meet her genetic butterfat potential, though, she needs the right diet. “Cows do not make milk fat from thin air,” Kevin Harvatine, a dairy nutritionist at Penn State, told me. A modern cow’s dietary intake is precisely managed, down to the length of plant fibers optimal for digestion. Even the crops they eat—low-lignin alfalfa, high-oleic soybeans—have been genetically modified or bred to stimulate high milk and milk-fat production in a cow’s body. Farmers can also add specific supplements, such as palmitic acid, a by-product of palm-oil production, to further boost butterfat. (This practice came to widespread attention during Buttergate, in 2021, when Canadians began noticing that their butter had become firmer and less spreadable at room temperature. Palmitic acid does indeed increase the melting temperature of butter.)

You can’t actually buy this extra-rich cow’s milk at grocery stores. Despite its name, the whole milk sold in plastic jugs is not the whole milk, but a standardized fiction: For decades, the U.S. has defined whole milk to meet a minimum of 3.25 percent fat—the low end of what was once a cow’s natural range. That number has remained unchanged even as the actual average fat content of milk has risen a full percentage point above it. Any excess of fat from “whole milk” is instead transformed into high-fat dairy products: the various creams (heavy, whipping, sour, ice), butter, triple-crème Bries, ultra-lush yogurts, and so on.

Today’s 4-percent-plus milk has created problems for certain cheese makers. It is simply too rich for varieties such as cheddar, Colby, and Monterey Jack, which require a lower fat-protein ratio. Cheese makers have had to reconfigure their manufacturing lines, either to receive extra dairy protein in the form of skim milk or to install a million-dollar separator to remove excess fat. “It’s extra cost, extra steps, extra bother,” Dean Sommer, a cheese and food technologist at the Center for Dairy Research at the University of Wisconsin at Madison, told me. “They’re transitioning from the world they knew, when it comes to the fat content of milk, to the world we’re dealing with.”

The unwanted fat from cheesemaking ends up at processors such as Grassland Dairy, a large butter maker based in Wisconsin. Lately, says its president, Trevor Wuethrich, Grassland has had to keep its facility running more often to keep up with all of the leftover fat coming from cheese makers. Cheese makers that used to send a truckload of cream a week, he told me, are now sending “a load a day.” Some days, he has to turn loads away.

Where else can the extra butterfat go? A few years ago, back when butterfat prices were high, Geiger said, some ice-cream makers swapped out dairy cream for cheap gums and air, making “frozen dairy desserts” that contained too little dairy cream to be legally labeled “ice cream.” “I think there’s an opportunity to get more cream back into ice cream,” he told me. Ice-cream makers, naturally, may want to see sustained low prices before jumping back on the butterfat train.

Meanwhile, dairy farmers are already looking to hedge their bets: If not fat, then protein? (And Americans sure love their protein these days.) But breeding cows for milk protein would be more challenging, Dechow said. Milk-protein yield varies less from cow to cow, making it more difficult to make changes through genetic selection. The fat and protein levels of milk are also linked, so enhancing protein would likely enhance fat too.

The high-milk-fat dairy cow won’t be going anywhere, though. At current prices, Harvatine said, “it still makes sense for us to convert feed into butter. It’s just not nearly as profitable as it was a year ago.” If a dairy farmer is doing 10 different things to maximize butterfat, the first nine things might still make sense, he said—only “now I’m questioning the last thing that I’m doing.” And genetically, the American cow is locked in. Breeding decisions made as recently as a few months ago—when butterfat prices were at a peak—will come to fruition only over the next three or four years, as those calves are born, mature into cows, and start producing the super-rich milk of their genetic destiny. The butterfat boom is far from over.

The Best Flu Drug Americans Aren’t Taking

2026-01-12T11:44:58-05:00

Updated at 6:00 PM ET on January 12, 2026

Antiviral drugs for influenza, the best known of which is Tamiflu, are—let’s be honest—not exactly miracle cures. They marginally shorten the course of illness, especially if taken within the first 48 hours. But amid possibly the worst flu season in 25 years, driven by a variant imperfectly matched to the vaccine, these underused drugs can make a bout of flu a little less miserable. So consider an antiviral. And specifically, consider Xofluza, a lesser-known drug that is in fact better than Tamiflu.

The culprit behind this awful flu season is subclade K, a variant of H3N2 discovered too late to be incorporated into this year’s flu vaccine. Early data suggest the shot likely does confer at least some protection against this variant, but the jury is still out on whether that protection is much eroded from usual. What is undeniable, though, is a recent explosion of influenza cases. In New York, which was hit early and hard, the number of people hospitalized for flu broke records. Across the rest of the country, cases have been going up a “straight line,” nearly everywhere all at once, which is highly unusual, Arnold Monto, an epidemiologist at the University of Michigan who has been studying influenza for some 60 years, told me last week. Cases seem to be finally leveling off now, but much misery still lies ahead.

For flu, antivirals are a second but oft-overlooked line of defense after vaccines. “We are dramatically and drastically underutilizing influenza antivirals,” Janet Englund, a pediatric-infectious-disease specialist at the University of Washington, told me. Even the older, more commonly prescribed drug Tamiflu reaches only a tiny percentage of flu patients every year. Actual numbers are hard to come by, but compare the estimated 1.2 million prescriptions for Tamiflu and its generic form in 2023 with the some 40 million people who likely got the flu in the winter of 2023–24. Xofluza is even less popular, and exact prescription numbers even harder to find. But they are possibly somewhere from just 1 to 10 percent that of Tamiflu.

The two antivirals are equally effective at allaying symptoms, both shortening the duration of flu by about a day. But Xofluza, which was approved in 2018, offers some tangible benefits over Tamiflu.

First, Xofluza is simply more convenient, a single dose compared with Tamiflu’s 10, which are taken over five days, twice a day. It also causes fewer of the gastrointestinal side effects, such as vomiting and nausea, that patients on Tamiflu will sometimes experience. All in all, a course of Xofluza might be easier for you—or your kid already queasy from the flu itself—to get down and keep down. (That is, if they are old enough to take it: Xofluza is approved for kids ages 5 and up in the United States, but ages 1 and up in Europe; only Tamiflu is recommended for kids down to newborn age as well as for women who are pregnant or breastfeeding.)

Second, Xofluza makes you less contagious to the rest of your family. It drives down the amount of virus spewed by sick patients more quickly than Tamiflu, possibly because of differences in how the two drugs work. Whereas Xofluza stops the virus from replicating, Tamiflu can only prevent already replicated viruses from exiting infected cells to infect others. In a study that Monto led last year, Xofluza cut household transmission by almost one-third compared with a placebo. Tamiflu might reduce transmission too, according to other studies, but probably to a lesser degree than Xofluza.

Third, Xofluza is better at heading off serious post-flu complications such as pneumonia or myocarditis. Patients on Xofluza needed fewer ER visits and hospitalizations than did those on Tamiflu, according to studies of large real-world data sets from insurance claims and medical records. This means that Xofluza should be the antiviral of choice for high-risk patients, including those over 65, who are most prone to these complications, Frederick Hayden, a flu expert at the University of Virginia who led one of the original Xofluza trials, told me. (Hayden has consulted on an unpaid basis, aside from travel expenses, for the companies behind Xofluza.)

The fourth advantage is less relevant to this season because the dominant subclade belongs to the influenza A family. But Xofluza is noticeably more effective against influenza B than Tamiflu, which tends to falter against this family of viruses.

Despite these benefits, awareness of Xofluza remains low. “It hasn’t been used as much as it should be,” Monto said, for reasons of cost and accessibility. Tamiflu, first approved in 1999, is available as a generic for less than $30 even without insurance. Xofluza is still patented and runs $150 to $200 a person. Because it’s less popular, pharmacies are less likely to stock it, making doctors less eager to prescribe it, and so on. In October, though, the company that markets Xofluza in the U.S. launched a direct-to-customer program that sells the drug for the comparably bargain price of $50 without insurance, along with same-day delivery in some areas. Even the flu-drug experts I spoke with, though, were not all aware of this new, more accessible route. The CDC still lists Tamiflu first and foremost in its recommendations, too.

For flu antivirals to be more widely used would also require better testing. Both Xofluza and Tamiflu are most effective within the first 48 hours of symptoms, and the earlier the better. Traditionally, a sick person would have to get to a doctor, get a flu test, get a prescription, and finally get to a pharmacy—which can easily put them past the first 48 hours. But COVID popularized at-home rapid testing, and combination COVID-flu tests have landed on pharmacies shelves recently. With telehealth and home delivery, you can get an antiviral without ever leaving the house.

Still, the at-home tests are expensive, Englund pointed out, about $20 a pop here, compared with just a couple of bucks in Europe. The expense can add up for a whole family. In Japan, where antivirals are widely used, nearly everyone with a flu-like illness gets a routine rapid test and, if necessary, antivirals, both largely covered by the public health-care system. (Xofluza was developed by the Japanese company Shionogi, which also makes Xocova, a promising COVID antiviral my colleague Rachel Gutman-Wei has written about that is not available in the U.S.)

If the U.S. were better at using antivirals, especially in the high-risk patients, the number of Americans dying of flu—roughly 38,000 last year—would likely drop, Cameron Wolfe, an infectious-diseases expert at Duke, told me. Doctors recommend that people at high risk for flu take antivirals prophylactically, upon exposure to anyone with flu, before symptoms appear. Both Xofluza and Tamiflu as prophylaxis can cut the chances of getting sick by upwards of 80 percent.

For healthy people who fall ill, antivirals can ease the burden of flu, which is nasty even when it is not deadly. “I don’t want you to be out of work longer than you need to be. I don’t want you to not be a caregiver for your kids,” Wolfe said. “Maybe you have business travel coming up, and I don’t want you to be sick still on that plane.” With challenges around access to antivirals, he said that “the best drug is the one you can get.” Both Tamiflu and Xofluza can make this historically bad flu season a little more bearable.

This story originally stated that Xocova, not Xofluza, when given as a prophylaxis for flu, cut the chance of illness by 80 percent. Xocova is a COVID antiviral.

I Bought ‘GLP-3’

2025-12-23T08:00:00-05:00

After Katie started on Ozempic, she got her hairdresser interested, too. This summer, when they saw each other again, she thought that her hairdresser had lost some weight and that she looked “so great.”

“Are you still on a GLP-1?” she asked, referring to the class of blockbuster drugs that includes Ozempic and obesity meds.

“Actually,” her hairdresser replied, “I’m on a GLP-3.”

Okay, so, technically, there is no such thing as a GLP-3 drug. But “GLP-3” is a name used on the underground market for retatrutide, an obesity drug still being studied by the pharmaceutical company Eli Lilly. As the nickname implies, retatrutide is like a GLP-1 drug—but more, more, more. It’s more effective, has more modes of action, and induces more weight loss. It may in fact be the most powerful weight-loss drug ever created.

When early retatrutide data were presented at a medical conference in 2023, a scientist who was there told me, the usually staid audience burst into spontaneous applause. Two weeks ago, the first of the highly anticipated Phase 3 clinical-trial results corroborated the jaw-dropping initial numbers: Patients lost on average 71 pounds, or 29 percent of their body weight—double what people lose on semaglutide, which is better known as Ozempic or Wegovy. Some trial participants stopped retatrutide early because they had lost too much weight; they stopped, in other words, because the drug was too effective. As of now, retatrutide is still not approved, though. The FDA has yet to subject its safety and efficacy data to close scrutiny. You cannot get retatrutide from your doctor. You cannot buy it at a pharmacy.

“I’m a very by-the-book, ‘The doctor gives it to you; you take it’ kind of person,” Katie told me. (The Atlantic agreed to identify some sources by their first names only for reasons of medical privacy.) When her hairdresser first mentioned retatrutide in the summer, the Phase 3 results weren’t even out. “But she was just like, ‘It was incredible,’” Katie said. When she looked up retatrutide online, she came across people posting “insane” before-and-after photos.

Katie, who is 44, had been prescribed Ozempic by her doctor two years ago, but she was ready for something new: Her co-pay had just shot up from $20 to $700 a month. She was nauseated all the time, but she wasn’t losing any more weight after stalling at 30 pounds. So with her hairdresser’s help, Katie began ordering freeze-dried retatrutide online, mixing the white powder with sterile water, calculating dosages, and injecting herself with needles. She paid only a fraction of what Ozempic had cost her. Six months later, she’s lost another 20 pounds.

The catch, of course, is that her drugs do not come from Eli Lilly, nor do any of the drugs on the entirely unregulated underground market. No one is saying exactly where they do come from, but it’s commonly assumed that unnamed suppliers are copying Eli Lilly’s drug in China.

Over the past year, the underground market has only grown, in both size and visibility. What began with early adopters—many of them bodybuilders and biohackers—using crypto to buy the drug through Chinese contacts on Telegram has morphed into a network of slick websites where U.S. resellers take PayPal or credit cards. On social media, influencers openly hawk affiliate discount codes for “GLP-3” and “reta.” And retatrutide is spreading through old-fashioned word of mouth—like with Katie and her hairdresser—because its effects are just so visible.

The true scope of the underground market is by design difficult to know, but dozens of brands have popped up. Forums and group chats devoted to retatrutide have up to tens of thousands of members. In certain circles, retatrutide is almost normalized. Tyler Simmons, 36, who lives in Northern California and is a bit health obsessed, told me he personally knows 30 to 40 people on retatrutide.

Experts who study counterfeit and copycat pharmaceuticals tell me they cannot think of another drug that gained this level of popularity so fast, before its clinical trials even concluded. The people injecting underground retatrutide have entered—willingly, it seems—into an immense biological and social experiment.

This May, to understand the process, I purchased retatrutide from several online vendors I found easily through social media. (I did not intend to use any of the drugs, The Atlantic’s lawyers would want me to note for the record.) The process was disarmingly casual for something people were injecting into their bodies. It felt, in some cases, just like ordering socks. One vendor sent a Shop-app link to track my package.

There were some obvious signs that these are not entirely aboveboard operations, though. For one, the websites were plastered with disclaimers that their products were for “research use only.” These disclaimers satisfy a legal loophole that allows drug compounds to be sold for lab research but not for human use. Hence, sellers and buyers of retatrutide often refer to this as a “gray market.”

But in fact, people are plainly buying it to inject themselves. Though I sometimes saw commenters online use the fig leaf of saying “my lab rat” (which were losing comically large amounts of weight for rodents), most were discussing personal use quite openly. And vendors are not always coy about the true purpose. After the Substacker known as Crémieux wrote a popular guide to buying cheap weight-loss drugs—touting retatrutide as his top pick—one vendor, Peptide Partners, sent a discount code to share with readers: “ScrewTariffs” for 15 percent off.

A package I bought from another company, called Nexaph, originated in Indiana, according to the tracking info, but the return address on its label was in Wyoming. That address leads to a strip-mall office registered to an improbable 20,000 businesses. The cheapest retatrutide tends to come directly from China, though, sold via nebulous entities without websites. I bought one batch from a sales rep on Telegram for Jinan Elitepeptide Chemical Co. A week and a half later, I received a box for a face massager, sealed with a sticker that read, in Chinese, “Original packaging. Authentic product.” Inside were the 10 small unlabeled vials of white powder that I had ordered. (No massager, though.) None of the vendors responded to my subsequent request for comment, except R3JUVEN8, which sent me a statement reiterating that its products, including the retatrutide branded as “Radiant Sculpt” on its site, are “exclusively for laboratory research use.”

The vials I purchased came with no further information about who manufactured the powder or where. But China is home to a large, legitimate drug-manufacturing base, meaning it has the expertise to produce retatrutide. And even before retatrutide caught on, vendors linked to China were selling other peptides—a category of compounds that includes the obesity drugs semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound), as well as substances, such as BPC-157, that are popular in fitness and wellness circles. Making another peptide would not be a huge leap; retatrutide as a molecule is not especially difficult for a knowledgeable chemist to copy.

The drug’s molecular structure has been public for years, since Eli Lilly published it in a research paper in 2022. It is essentially a chain of 39 amino-acid building blocks, its shape cleverly designed to fit into the receptors of three different hormones all at once: GLP-1, GIP, and glucagon. (This triple action is the 3 in GLP-3.) The existing obesity drugs on the market hit GLP-1 receptors or GLP-1 plus GIP receptors. Only retatrutide adds glucagon for the full trifecta.

Where earlier obesity drugs work primarily through appetite suppression, glucagon seems to also boost metabolism by revving up the liver. Put them together and the triple combo might achieve the best of all worlds: “You get a reduction in food intake, and you can turn the dial up and get a little better energy expenditure,” Jonathan Campbell, an obesity researcher at Duke, told me. In other words, fewer calories in and more calories out.

Scientists knew that retatrutide held promise, but when those astonishing preliminary results were shared in 2023, excitement spilled out from labs into the public. A new and more powerful obesity drug was coming, and some people, it turns out, could not wait.

“I’m a risk-taker,” Elizabeth, 62, told me. When she started buying reta in 2024, she had already tried semaglutide and tirzepatide, but she was eager to get her hands on the most effective drug. Back then, the underground market operated much less openly. She had to find a Chinese sales rep on WhatsApp, then transfer hundreds of dollars for several months of supply.

As a biologist herself, Elizabeth was comfortable working with needles and reading scientific papers. She modeled her dosing regimen on the clinical-trial protocol. When her heart began racing, she accepted it as a documented side effect of retatrutide. She has lost more than 100 pounds in the past two and a half years—first on the two older drugs and the last 50 or so pounds on retatrutide. After a lifelong struggle with obesity, she told me in May, these are “some of the most amazing events of my whole life.”

For that, she was willing to risk not just her money, but the potential downsides—both known and unknown—of taking retatrutide, a novel yet clearly powerful drug. The full Phase 3 clinical-trial results should provide a clearer picture soon, but one noteworthy finding so far is dysesthesia, or odd sensations in the skin, such as burning and pain, that suggest unrest in the nervous system. One in five patients on the highest dose of retatrutide experienced dysesthesia, roughly triple its occurrence among patients taking semaglutide’s current maximum dose.

Retatrutide causes many of the other side effects of drugs in its class, too: nausea, diarrhea, vomiting, and more serious ones. Adrian Crook, a fitness influencer on YouTube, made a video about how retatrutide almost landed him in the hospital when his stomach became paralyzed. And Elizabeth says she has lost quite a bit of muscle on the drug. “I’m as weak as a kitten,” she told me.

Then there are the risks of injecting drugs sold for “research use only” on the underground market. These include, but are not limited to, the fact that the vials might contain: a different weight-loss drug or an entirely unknown substance, either benign or harmful; dangerous bacteria or traces of bacteria called endotoxins; the wrong dose, whether too low (and therefore ineffective) or too high (which could cause side effects of alarming intensity, because retatrutide is supposed to be slowly titrated up over as many as 20 weeks as your body acclimates to the drug); or other contaminants, such as solvents used in manufacturing or heavy metals.

“All of this stuff just scares the crap out of me,” Randy Seeley concluded after enumerating the potential dangers to me. Seeley, who studies obesity at the University of Michigan, uses peptides for research in his lab, and even the stuff sourced to legitimate scientific-supply companies doesn’t always work as expected, he said. Compounds manufactured for the petri dish are not held to the same strict standards as those made for human use.

It’s not quite fair to say the underground market comes with zero accountability, though. Certain corners, at least, have developed a robust culture of lab testing. A handful of labs—the Levi Strausses of the peptide gold rush—now specialize in testing these compounds. Many vendors post “certificates of analysis” attesting to their purity and sterility. Buyers can send vials to laboratories themselves, either as part of an organized group test or on their own. Some vendors will even refund batches that fail. Without testing, Marco, 53, told me, he would never have injected retatrutide from the internet. (Marco is his middle name.) The tests may not cover every hypothetical risk, but they make it safe enough to assure him. “There’s a lot of people who just get these things and shoot them,” he said. “I don’t judge them in any way, but I think those people are out of their minds.”

The tests, insofar as they are reliable, do flag problems. According to Finnrick Analytics, a start-up that provides free peptide tests and publicly shares the results, 10 percent of the retatrutide samples it has tested in the past 60 days had issues of sterility, purity, or incorrect dosing. Two other peptide-testing labs, Trustpointe and Janoshik, have said in interviews with Rory Hester, a.k.a. PepTok on YouTube, that they see, respectively, an overall fail rate of 20 percent and a 3 to 5 percent fail rate for sterility alone across all peptides. These are not based on random samples—labs test only what their customers send. On the whole, though, these numbers suggest that, although most of the retatrutide flowing through the underground market is what vendors promise it is, the drugs also fail testing at rates far, far higher than is acceptable in standard drug manufacturing.

As retatrutide has grown in popularity, the people seeking it out are no longer just self-professed risk-takers. “The future of the market is normies,” Hester, who also writes the peptide-focused Substack Gray Market, told me. The world of Telegram, Discord, and WhatsApp—what Hester calls the “dark gray” peptide market—is by design somewhat inaccessible. “Your grandmother is not going to go on Telegram,” he said. The customer-friendly U.S.-based sites that he calls “light gray” can appeal to a much larger audience. Hester is putting his money where his mouth is. Earlier this month, he announced that he co-owns the peptide company Crush Research.

But the size of the gray market may be fundamentally at odds with its viability. The bigger it gets, the more people are injecting themselves thanks to a legal loophole, and the harder it may be for authorities to ignore. (The FDA did not respond to a request for comment. Secretary of Health and Human Services Robert F. Kennedy Jr. has previously promised to reverse the FDA’s “aggressive suppression” of peptides—along with psychedelics, raw milk, sunshine, and other treatments that “can’t be patented”—though it’s unclear how that applies to retatrutide specifically, which is in fact patented.) And not everyone in the gray market welcomes the attention or the scrutiny that follows. As Finnrick has been posting test results by vendor, its COO, Raphaël Mazoyer, told me, online commentators have accused the company of being an agent of the FDA and the Chinese government. (He denied both.)

A week ago, rumors started swirling, as they periodically do, of a coming U.S. crackdown. Some buyers online dismissed them as an attempt to juice panic buying. Several websites did stop selling retatrutide, though.

The “dark gray” market is not as easily within the grasp of U.S. authorities, but it’s been a turbulent few months there, too. In September, two of the most popular retatrutide suppliers from China abruptly disappeared. Their sales reps stopped replying to messages, stranding buyers who had already paid hundreds of dollars. Rumors later spread of arrests in China. Then, in November, a third vendor’s retatrutide allegedly landed two people in the hospital, according to warnings that spread on social media. The company blamed a raid for interfering with the quality of its drugs. Someone started impersonating its sales rep by using a sneakily similar username. Later, when no further details came out, online commentators started wondering if the hospitalizations were just a hoax. It’s hard to know what is real and what is fake, but that is the nature of an underground market. New vendors keep popping up, like a game of whack-a-mole.

Meanwhile, the frenzy over retatrutide has kicked into even higher gear since the Phase 3 results were announced this month. When the FDA approves the drug, which is widely expected, it will arrive as possibly the most hotly anticipated drug ever. The retatrutide buyers I interviewed said they welcome the legitimate stuff—though they expect it to be incredibly expensive. Marco, whose insurance actually covers obesity drugs, told me he will happily keep buying on the underground market for friends who otherwise can’t afford retatrutide. In any case, he’s stocked up. “I have a year’s supply of reta in my freezer,” he said.

GLP-1 drugs are, in general, meant to be taken indefinitely, but recently, Elizabeth told me she was going to quit retatrutide, at least temporarily. She had reached her goal weight—what she weighed in high school 45 years ago. “Incredible but I feel lousy,” she wrote. She was experiencing both extreme fatigue, which she couldn’t directly attribute to retatrutide, and anhedonia, or an inability to feel pleasure, which is anecdotally linked to GLP-1 drugs in some people. “Would you trade happiness for thinness? Does it have to be one or the other?” she wrote. “At this point, I’m beginning to wonder.” The psychological effect of these drugs really needs to be studied, she added. At this point, a year and a half in, she has been taking retatrutide longer than patients in the concluded clinical trials. She’s hoping to try a lower dose, perhaps one at which she can maintain her weight without feeling so lousy.

Elizabeth has never told her doctor about taking an unapproved drug or buying from the underground market. This whole time with retatrutide, she’s been figuring it out on her own.

You’re on Ozempic? How Quaint.

2025-11-28T08:00:00-05:00

“Ozempic is about to be old news,” my colleague Yasmin Tayag wrote in 2023, just before an even more powerful obesity drug, tirzepatide, then best known as Mounjaro, was approved. Well, two years later, Mounjaro is becoming old news, too. A whole slew of next-generation obesity drugs are on the horizon, some already advanced enough in clinical trials to be looking as good as—if not better than—those already on the market. The novel medications continue to push the upward limits of weight loss, now to almost 25 percent of body weight on average, but they also differ in their modes of action. They target different cells and different parts of cells in the brain and body.

Obesity, after all, is not monolithic. “We don’t have a disease of obesity. We have a disease of obesities,” Angela Fitch, chief medical officer at Knownwell, a national obesity-care clinic, and a former president of the Obesity Medicine Association, told me. With the coming explosion of obesity drugs, doctors could soon match each patient’s condition to their optimal medication: A 25-year-old with fatty-liver disease may need a different drug than a 75-year-old with low muscle mass. About 100 million adults live with obesity in just the U.S., a market massive enough for multiple medications to find a niche. “One size will not fit all, and one size will not be best for all,” Richard DiMarchi, a chemist at Indiana University who has worked on obesity drugs at both Eli Lilly and Novo Nordisk, told me.

The most obvious way obesity drugs are not one-size-fits-all is that those on the market do not actually work for all. Although patients on semaglutide, the drug in Ozempic and Wegovy, lost on average 10 percent of their body weight, a third lost less than 5 percent in one clinical trial. Some even gain weight taking the drug. And others suffer such terrible side effects, including constant nausea and vomiting, that they cannot take it at all.

Ozempic functions by mimicking a single hormone called GLP-1; the drug’s mode of action is relatively simple but limited. To improve upon Ozempic, drugmakers have started targeting GLP-1 in combination with other hormones linked to hunger and satiety. The second drug currently on the market, the tirzepatide found in Mounjaro and Zepbound, resembles GLP-1 in addition to another hormone called GIP, hitting receptors for both in the brain. The GIP component may serve a double function, promoting additional satiety while suppressing some of the nausea caused by GLP-1. However tirzepatide truly works—and experts caution that no one knows—it prompts, on average, about 20 percent weight loss. It’s only the first of the “GLP-1 plus” drugs to market.

Other GLP-1-plus drugs in development include GLP-1 plus amylin, GLP-1 plus glucagon, and GLP-1 plus anti-GIP, which surprisingly could work as well as Mounjaro’s combination of GLP-1 plus GIP. (“If you aren’t confused,” Randy Seeley, an obesity researcher at the University of Michigan, told me, “you aren’t paying attention.”) In fact, all of these combinations seem to work—at least based on preliminary data from clinical trials—even as a precise understanding of the science lags. Some of the hormone mimics, such as for amylin, might also work alone. And others could be remixed into combinations of more than two. The drug retatrutide, which is in trials, is a triple hitter that targets GLP-1 plus glucagon plus GIP receptors, all at once. In an early Phase 2 trial, patients lost on average 24 percent of their weight, the highest of any obesity drug so far. The best responders lost upwards of 40 percent.

Even more intriguing than the top-line weight-loss numbers are metabolic changes unique to particular drugs. Glucagon, for example, ramps up liver metabolism; drugs based on this hormone could help break down fat accumulated in the livers of patients who also have fatty-liver disease. (The FDA is expediting review of one such drug, survodutide, for liver-disease patients.) Meanwhile, GLP-1-based drugs appear to protect against cardiovascular disease, even independent of weight loss. Patients prone to heart disease might fare best on medication that includes a GLP-1 component. When it comes to obesity, Seeley said, “your flavor of metabolic disease will be different than the next person’s.” Obesity drugs of the future may finally reflect that diversity, too.

An extensive menu of obesity drugs that work via distinct biological mechanisms means that patients will have more options to try. If they aren’t losing weight on drug A, they can move on to drug B or C. Experts don’t yet understand why the drugs work differently in different people, but hormone receptors in our brains likely vary in subtle yet important ways. The new drugs not only hit distinct combinations of hormone receptors; they also each tickle those receptors in a unique way.

In the near future, doctors and patients will probably have to trial-and-error their way to what works best. Further down the line, experts tell me, they hope to have a test, such as a blood test, that can forecast how patients will fare. Doctors could tell patients that they’ve got five different drugs at the ready, “and if I do this one test on you, I do this one test on you, I can predict which one of these drugs is the best for you,” Jonathan Campbell, an obesity researcher at Duke University, told me.

Maximum weight loss might not always be the goal for everyone though. The 40 percent that some people lose on retatrutide would be far too much for a patient barely over the BMI cutoff for obesity. Patients who don’t need to optimize weight loss may choose to prioritize convenience instead, which drugmakers are also happy to oblige. Most obesity drugs on the market are formulated as weekly injections. But Eli Lilly is developing a daily pill called orforglipron, and Amgen is testing a monthly injection called MariTide. And some patients, especially those who are elderly with already low muscle mass, might need extra help preserving their strength. The powerful appetite suppression that induces fat loss can induce muscle loss too. A number of drugmakers are now trialing obesity drugs in combination with various muscle-preserving drugs.

A mere decade ago, obesity drugs powerful enough for people to routinely drop double-digit percentages of their body weight were unheard-of. Today, there are two, and they feel ubiquitous. In yet another 10 years, this toolbox of just two obesity drugs will likely appear tiny and outdated. The next phase of the obesity-drug revolution is coming, with more drugs to choose from.

The ‘Man-Eater’ Screwworm Is Coming

2025-05-27T09:15:42-04:00

The United States has, for 70 years, been fighting a continuous aerial war against the New World screwworm, a parasite that eats animals alive: cow, pig, deer, dog, even human. (Its scientific name, C. hominivorax, translates to “man-eater.”) Larvae of the parasitic fly chew through flesh, transforming small nicks into big, gruesome wounds. But in the 1950s, the U.S. Department of Agriculture laid the groundwork for a continent-wide assault. Workers raised screwworms in factories, blasted them with radiation until they were sterile, and dropped the sterile adult screwworms by the millions—even hundreds of millions—weekly over the U.S., then farther south in Mexico, and eventually in the rest of North America.

The sterile flies proceeded to, well, screw the continent’s wild populations into oblivion, and in 2006, an invisible barrier was established at the Darién Gap, the jungle that straddles the Panama-Colombia border, to cordon the screwworm-free north off from the south. The barrier, as I observed when I reported from Panama several years ago, consisted of planes releasing millions of sterile screwworms to rain down over the Darién Gap every week. This never-ending battle kept the threat of screwworms far from America.

But in 2022, the barrier was breached. Cases in Panama—mostly in cattle—skyrocketed from dozens a year to 1,000, despite ongoing drops of sterile flies. The parasite then began moving northward, at first slowly and then rapidly by 2024, which is when I began getting alarmed emails from those following the situation in Central America. As of this month, the parasite has advanced 1,600 miles through eight countries to reach Oaxaca and Veracruz in Mexico, with 700 miles left to go until the Texas border. The U.S. subsequently suspended live-cattle imports from Mexico.

After this latest news broke, I spoke with Wayne Cockrell, a Texas rancher who fears the screwworm’s return to Texas is now a matter of when, not if. The anti-screwworm program cannot produce enough sterile flies to stop the parasite’s advance, much less beat it back down to Panama, Cockrell explained. He has followed the outbreak closely as the chair of the cattle-health committee for the Texas and Southwestern Cattle Raisers Association, even visiting the sterile-fly factory recently. “There’s a sense of dread on my part now,” he told me.

At 60, he is too young to remember screwworms himself, but he’s heard the horror stories. Every cut, every scratch, every navel of a newborn calf threatened to turn fatal in the pre-eradication era. If the parasite does take hold in the U.S. again, it could take decades to push screwworms back down to Panama. That is, after all, how long it took the first time. Decades of screwworm vigilance have been undone in just two years.

You only have to glance at a map to understand why the screwworm outbreak is now at an alarming inflection point.

Central America is shaped like a funnel with a long, bumpy tail that reaches its skinniest point in Panama. Back in the day, the USDA helped pay for screwworm eradication down to Panama out of not pure altruism but economic pragmatism: Establishing a 100-mile screwworm barrier there is cheaper than creating one at the 2,000-mile U.S.-Mexico border. Even after screwworms began creeping up the tail of the funnel recently, the anti-screwworm campaign had one last good chance of stopping them at a narrow isthmus in southern Mexico—after which the funnel grows dramatically wider. It failed. The latest screwworm detections in Oaxaca and Veracruz are just beyond the isthmus.

The wider the new front of the screwworm war grows, the more sterile screwworms are needed to stop the parasite’s advance. But the supply is already overstretched. The fly factory in Panama has increased production from its usual 20 million flies a week to its maximum of 100 million, which are now all being dispersed over Mexico. But planes used to drop 150 million flies a week over the isthmus in Mexico during the first eradication campaign in the 1980s. And when the front was even farther north in Mexico, a factory there churned out as many as 550 million flies weekly to cover the huge area. That factory, as well as one in Texas, has long since shut down.

The Texas and Southwestern Cattle Raisers Association is asking the USDA to build a new sterile-fly plant in the U.S., one big enough to produce the hundreds of millions that may soon be necessary. “We are working closely with Mexico to reestablish a biological barrier and prevent further geographic spread,” a USDA spokesperson wrote in response to questions about the adequacy of sterile-fly production. “If the fly spreads further geographically, we will need to reevaluate production capacity.” Several Texas lawmakers recently introduced the STOP Screwworms Act, which directs the USDA to open a new factory, but the whole process could still take years. “The facility needs to start tomorrow,” Cockrell said.

The U.S. cattle industry is unprepared for the screwworm’s return, he said, rattling off more reasons: Certain drugs to treat screwworm infection are not licensed in the U.S., having been unnecessary for half a century. Ranches used to employ 50 cowboys who regularly inspected cattle, and now they might have only five. And routine industry practices such as branding and ear tagging leave the animals vulnerable to screwworm infection. To face the screwworm, the cattle industry will have to adapt quickly to a new normal. The parasite could propel beef prices, which are already sky-high because of drought, even higher.

How screwworms managed to jump the barrier in 2022 is not fully clear. But in the years immediately before, the coronavirus pandemic reportedly created supply-chain snarls at the fly factory in Panama and disrupted regular cattle inspections that might have set off the alarm bells earlier. And the border between Panama and Colombia got a lot busier; the Darién Gap, once a notoriously impenetrable jungle, became a popular route for migrants.

Still, the screwworm advanced relatively slowly through Panama and Costa Rica for the first couple of years. Then it hit Nicaragua, and over just 10 weeks in 2024, it shot from the country’s northern border through Honduras and Guatemala to reach Mexico. This rapid advance was because of the illegal cattle trade, Jeremy Radachowsky, the director for Mesoamerican and the Western Caribbean at the Wildlife Conservation Society, told me. His organization has tracked the practice in Central America, where 800,000 cattle a year are raised illegally in nature reserves and then smuggled by boat and truck up to Mexico. This allowed the screwworm to spread much faster than it can fly. The line of new screwworm cases followed known smuggling routes, Radachowsky said. The constant northward movement of infected cattle could now make re-eradication more difficult. It’s like trying to empty a pool when “the spigot’s still open,” he said.

Decades of screwworm-free existence meant that even ranchers, whose livelihoods are directly affected, were slow to recognize the growing emergency. “We were so successful that literally people forgot,” a U.S. official in Central America familiar with the situation (speaking anonymously due to the delicate politics involved) told me. Inspections, timely reports of infection, and restrictions on cattle movement are important pieces of eradication, in addition to the release of sterile flies.

Over the years, scientists have also proposed more advanced ways of controlling the screwworm through genetics, though none is yet ready for prime time. The USDA supported research by Max Scott, an entomologist at North Carolina State University, to create a male-only strain that could reduce the number of flies needed for dispersal, but funding ended last summer. He has also proposed using gene drives, a still-controversial technique that could rapidly “drive” genetic material that makes females sterile into the wild population. The USDA wasn’t interested, he told me. (A spokesperson says the USDA “continues to research and investigate new tools,” including genetically engineered male-only screwworms.) But he did strike up a collaboration several years ago with scientists in Uruguay studying a gene drive for sterile screwworms.

Uruguay is interested because it never got to benefit from screwworm eradication; the country is located about halfway down South America, deep in screwworm territory. A retired USDA scientist, Steven Skoda, told me that he and his colleagues used to dream of “a world totally free of screwworm.” But eradication never reached South America, and now even the barrier protecting North America is no longer intact. The campaign to push screwworms from the south of Mexico—roughly where the parasite is right now—to the southern edge of Panama took 21 years. The way things are going, Cockrell said, some of his longtime colleagues in Panama might not see screwworms eradicated again in their country in their lifetime.

The Mother Who Never Stopped Believing Her Son Was Still There

2025-05-16T09:00:00-04:00

Photographs by Sarah Blesener

The Toyota pickup hit the tree that May morning with enough explosive force to leave a gash that is still visible on its trunk 39 years later. Inside the truck, the bodies of three teenage boys hurled forward, each with terrible velocity.

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One boy died instantly; a second was found alive outside the car. The third boy, Ian Berg, remained pinned in the driver’s seat, a bruise blooming on the right side of his forehead. He had smacked it hard—much harder than one might have guessed from the bruise alone—which caused the soft mass of his brain to slam against the rigid confines of his skull. Where brain met bone, brain gave way. The matter of his mind stretched and twisted, tore and burst.

When the jaws of life freed him from the wreckage, Ian was still alive, but unconscious. “Please don’t die. Please don’t die. Please don’t die,” his mother, Eve Baer, pleaded over him at the hospital. She imagined throwing a golden lasso around his foot to keep him from floating away.

And Ian didn’t die. After 17 days in a coma, he finally opened his eyes, but they flicked wildly around the room, unable to sync or track. He could not speak. He could not control his limbs. The severe brain injury he’d suffered, doctors said, had put him in a vegetative state. He was alive, but assumed to be cognitively gone—devoid of thought, of feeling, of consciousness.

Eve hated that term, vegetative—an “unhuman-type classification,” she thought. If you had asked her then, in 1986, she would have said she expected her 17-year-old son to fully recover. Ian had been handsome, popular, in love with a new girlfriend—the kind of golden boy upon whom fortune smiles. At school, he was known as the kid who greeted everyone, teachers included, with a hug. He and his two friends in the car belonged to a tight-knit group of seniors. But on the day he would have graduated that June, Ian was still lying in a hospital bed, his big achievement being that he’d finally made a bowel movement.

“What kind of life is that?” Ian’s brother Geoff remembers thinking. When he first arrived at the hospital, he had looked around the room for a plug to pull. The two brothers had talked about scenarios like this before, Geoff told me: “If anything ever happens to me and I can’t wipe my ass, make sure you kill me.” Angry that their mother was keeping his brother alive, Geoff fled, moving for a time to St. Thomas.

Three months after the accident, when doctors at the hospital could do no more for Ian, Eve took him home. She was adamant that he live with family, rather than under the impersonal care of a nursing home. That she had ample space for Ian and all of his specialized equipment was fortuitous. A few weeks before the accident, Eve’s husband, Marshall, had stumbled upon the Rainbow Lodge, an old hotel for hunters and fishers, for sale near Woodstock, New York. He loved the idea of a compound for their big blended family—his two grown children plus nieces and nephews, as well as Eve’s four kids, of whom Ian is the youngest. The sale was finalized while Ian was in the hospital.

At the lodge, Eve and a rotating cast of caretakers kept Ian alive: bathing him, pureeing home-cooked meals for his feeding tube, changing the urine bag that drained his catheter. She also devised a busy schedule of therapies, anchored by up to six hours a day of psychomotor “patterning”—an exercise program she’d read about in which a team of volunteers took each of Ian’s limbs and moved them in a pattern that mimicked an infant learning to crawl. Friends and acquaintances came to help with patterning; some started living in the lodge’s guest rooms, staying for months or even years. They formed a kind of unconventional extended family, with Ian at the center. Every Sunday, Eve cooked big dinners for the crowd.

Sarah Blesener for The Atlantic

The tree Ian struck with a pickup truck in 1986 still bears a scar from the accident.

The patterning exercises, which are not based on science, ultimately did not really help Ian. But his mother didn’t dwell on this. She made regular calls to the National Institutes of Health to inquire about the latest brain-injury research. And where mainstream medicine failed, Eve—who had moved to Woodstock in the ’60s as a “wannabe bohemian slash beatnik”—turned enthusiastically to alternatives. Ian was treated by the spiritual guru Ram Dass; a “magic man” with a pendulum; a craniosacral therapist; a Buddhist monk; Filipino “psychic surgeons”; and a healer in Chandigarh, India. Eve and Marshall took him on the 7,000-mile journey to India themselves, pushing him in a rented collapsible wheelchair. When, after all of this, Ian’s condition still did not improve, Eve became angry. It was one of the rare times that she allowed disappointment to puncture her relentless optimism.

Still, like so many other family members of vegetative patients, she held on to a mother’s belief that Ian could understand everything around him. She took care, when shaving him, to leave the wispy mustache he had been trying to grow. When his high-school friends went to see the Grateful Dead, she brought him along in his wheelchair and a tie-dyed shirt. She kept believing for herself as much as for Ian: If her son was aware, it would mean her gestures of love were not unseen, her words not unheard.

Science would take decades to catch up with Eve, but she turned out to be right in one crucial respect: Ian is still aware. Doctors now agree that he can see, he can hear, and he can understand, at least in some ways, the people around him.

Over the past 20 years, the science of consciousness has undergone a reckoning as researchers have used new tools to peer inside the brains of people once thought to lack any cognitive function. Ian is part of a landmark study published in The New England Journal of Medicine last year, which found that 25 percent of unresponsive brain-injury patients show signs of awareness, based on their brain activity. The finding suggests that there could be tens of thousands of people like Ian in the United States—many in nursing homes where caretakers might have no clue that their patients silently understand and think and feel. These patients live in a profound isolation, their conscious minds trapped inside unresponsive bodies. Doctors are just beginning to grasp what it might take to help them.

Sarah Blesener for The Atlantic; Courtesy of the Baer family

After Ian was discharged from the hospital, Eve and a rotating cast of caretakers and alternative healers tried to help him recover. Throughout, Eve held on to a mother’s belief that Ian could understand everything around him.

For Ian, the signs were there, if not right at the beginning, at least early on. Three years after the accident, he began to laugh.

Eve was in the kitchen with him, idly singing the Jeopardy theme song in a silly falsetto when she heard it: “Ha!” Laughter? Laughter! “Other than a cough, it was the first sound I heard from him in three years,” she told me. In time, Ian started laughing at other things too: stories Eve made up about a cantankerous Russian named Boris, the word debris, pots clanging, keys jangling. Fart and poop jokes were a perennial favorite; his brain seemed to have preserved a 17-year-old’s sense of humor. His friends and family took that to mean the Ian they knew was still in there. What else might he be thinking?

At the time, Ian was not regularly seeing a neurologist. But even if he had been, most neurologists in the ’80s would not have known what to make of his laughter; it flew in the face of conventional wisdom.

Doctors first defined the condition of the persistent vegetative state in 1972, less than a decade and a half before Ian’s accident. Fred Plum and Bryan Jennett coined the term to describe a perplexing new class of patients—people who, thanks to advances in medical care, were surviving brain injuries that used to be fatal, but were still left stranded somewhere short of consciousness. This condition is distinct from coma, a temporary state in which the eyes are closed. Vegetative patients are awake; their eyes are open, and they may be neither silent nor still. They can moan and move their limbs, just without purpose or control. And while their bodies continue to breathe, sleep, wake, and digest, they seem to have no connection to the outside world. Today, experts sometimes refer to the vegetative state as “unresponsive wakefulness syndrome.”

Back then, the two doctors also distinguished it from locked-in syndrome, which Plum had helped name a few years prior. Locked-in patients are fully conscious though immobile, except for typically their eyes. (Jean-Dominique Bauby wrote his famous 1997 memoir about locked-in syndrome, The Diving Bell and the Butterfly, by blinking out one letter at a time.) In contrast, Plum and Jennett considered the vegetative state “mindless,” with no cognitive function intact.

What, then, could the laughter mean? By the ’90s, some of the most prominent experts on consciousness—including Plum and Jennett themselves—had begun to realize that they had perhaps too categorically or hastily dismissed patients diagnosed as vegetative. Researchers were documenting flickers of potential consciousness in some supposedly vegetative patients. These patients could utter occasional words, grasp for an object every now and then, or seem to answer the odd question with a gesture—suggesting that they were at least sometimes aware of their surroundings. They seemed to be neither vegetative nor fully conscious, but fluctuating on a continuum.

This in-between space became formally recognized in 2002 as the “minimally conscious state,” in an effort led by Joseph Giacino, a neuropsychologist who specializes in rehabilitation after brain injury. (Coma, vegetative, and minimally conscious are sometimes collectively called “disorders of consciousness.”)

Sarah Blesener for The Atlantic

One day in spring 2007, Marshall, Ian’s stepfather, slipped on a mossy stone and fractured his hip. As he and Eve waited for an ambulance, the phone rang. Giacino had heard about Eve’s NIH inquiries, and he was interested in meeting Ian—he wondered if the minimally conscious diagnosis might apply to him. If so, Ian could qualify for a new experimental trial.

Giacino didn’t make any promises. Still, after all those years, Eve told me, “he was the first voice of positive possibility that I heard.” So even as Marshall lay next to her with his broken hip, neither of them dared hang up the phone.

Around this time, in 2006, an astonishing case report came out from researchers led by Adrian Owen, a cognitive neuroscientist at the University of Cambridge; it suggested that even vegetative patients could retain some awareness. Owen found a 23-year-old woman who had been in a car accident. Months later, she still had no response on behavioral exams. But in an fMRI machine, her brain looked surprisingly active: When she was asked to imagine playing tennis, blood flowed to her brain’s supplementary motor area, a region that helps coordinate movement. When she was asked to imagine visiting the rooms of her house, blood flowed to different parts of her brain, including the parahippocampal gyrus, a strip of cortex crucial for spatial navigation. And when she was told to rest, these patterns of brain activity ceased. Based on the limited window of an fMRI scan, at least, she seemed to understand everything she was being asked to do.

“Unsettling and disturbing” is how one neurologist described the implications of the study to me. Also: controversial. Another doctor recounted a scientific meeting soon after where the speakers were split 50–50 on whether to accept the results. Was the fMRI finding just a fluke? Owen did not inform the woman’s family of what he found, because the study’s ethical protocol was ambiguous about how much information he could share. He wishes he could have. The woman died in 2011, without her family ever being told that she might have been aware.

[Read: I know the secret to the quiet mind. I wish I’d never learned it.]

Over time, Owen and his group identified more patients with what they came to call “covert awareness.” Some were vegetative, while others were considered minimally conscious, based on behaviors such as eye tracking and command following. The researchers found that outward response and inner awareness were not always correlated: The most physically responsive patients were not necessarily the ones with the clearest signs of brain activity when asked to imagine the tasks. Covert awareness, then, can be detected only using tools that peer at a brain’s inner workings, such as fMRI.

In 2010, one of Owen’s collaborators, the Belgian neurologist Steven Laureys, asked a minimally conscious patient, a 22-year-old man, a series of five yes-or-no questions while he was in an fMRI machine, covering topics such as his father’s name and the last vacation he took prior to his motorcycle accident. To answer yes, the patient would imagine playing tennis for 30 seconds; to answer no, he would imagine walking through his house. The researchers ran through the questions only once, but he got them all right, the appropriate region of his brain lighting up each time.

It is hard to say what experience of human consciousness some colored pixels on a brain scan really depict. To answer intentionally, the patient would have had to understand language. He would also have needed to store the questions in his working memory and retrieve the answers from his long-term memory. In my conversations with neurologists, this was the study they cited again and again as the most compelling evidence of covert awareness.

A few years later, using the same yes-or-no method, Owen found a vegetative patient who seemed to know about his niece, born after his brain injury. To Owen, this suggested that the man was laying down new memories, that life was not simply passing him by. In yet another case, Owen used fMRI not just to quiz a 38-year-old vegetative man, but to actually ask about the quality of his life 12 years post-injury: Was he in pain right now? No. Did he still enjoy watching hockey on TV, as he had before his accident? Yes.

Most researchers I spoke with were reluctant to speculate about the inner life of these brain-injury patients, because the answer lies beyond any known science. The brains of minimally conscious patients do activate in response to pain or music, Laureys told me, but their experience of pain or music is likely different from yours or mine. Their state of consciousness may resemble the twilight zone of drifting in and out of sleep; it almost certainly differs from person to person. Owen believes that some of his vegetative patients may actually be “completely conscious,” akin to a locked-in person who is fully aware, but cannot move even their eyes. Until that is proved otherwise, he sees no reason not to extend them the benefit of the doubt.

Several months after the phone call from Giacino’s office, Ian’s family made the trip to New Jersey to meet the researcher. In the exam room, Giacino put Ian through an intense battery of tests. He found that Ian could intermittently reach on command for a red ball. He laughed at loud noises, such as keys jangling, which Giacino said could be a simple response to the sound. But Ian also laughed appropriately at jokes, especially adolescent ones, as if he understood humor and intent. These behaviors were enough to qualify Ian for a brand-new diagnosis two decades after his accident: not vegetative, but minimally conscious.

Giacino’s collaborators were eager to put Ian in an fMRI machine, to see what might be happening inside his brain. On a separate trip, this time to an fMRI facility in New York City, his family met Nicholas Schiff, a neurologist at Weill Cornell and a protégé of Fred Plum’s. Schiff, too, was intrigued by Ian’s laughter, and the possibility that he understood more than he could physically let on. Schiff’s team showed Ian pictures and played voices—to see whether his brain could process faces and speech—and asked him to imagine tasks such as walking around his house.

Ian’s brother Geoff was also at this scan, having by then returned to New York. Crammed into the small fMRI control room with all the scientists peering at Ian’s brain, he remembers being incredulous at the things they wanted his brother to imagine. “You really think he can understand you?” he asked.

Sarah Blesener for The Atlantic

Left: Nicholas Schiff, a neurologist at Weill Cornell, was intrigued by the possibility that Ian understood more than he could physically let on. Right: A brain scan of Ian’s.

The scientists did. They believed Ian still retained some kind of consciousness. They also thought there was a chance, with luck and the right tools, of unlocking more. This had happened before. In some extraordinary patients, the line between conscious and unconscious is more permeable than one might expect.

In 2003, Terry Wallis, in Arkansas, suddenly uttered “Mom!” after 19 years as a vegetative patient in a nursing home. Then he said “Pepsi”—his favorite soft drink. After that, his mother took him home. Wallis couldn’t move below his neck and he struggled with his memory and impulse control, but he began to speak in short sentences, recognized his family, and continued to request Pepsis. In retrospect, he probably had not been vegetative at all, but minimally conscious during those first 19 years. His mom had seen signs that others at the nursing home had not: Wallis occasionally tracked objects with his eyes, and he became agitated after witnessing the death of his roommate with dementia.

[Read: How people with dementia make sense of the world]

Slowly, over time, Wallis’s brain had recovered to the point of regaining speech. When Schiff and his colleagues later scanned him, they found changes that suggested neuronal connections were being formed and pruned decades after his injury. “Terry changed what we thought about what might be possible,” Schiff told Ian’s family.

There was also Louis Viljoen, in South Africa, who in 1999 began speaking when put on zolpidem, better known as Ambien, a sedative that was, ironically, supposed to put him to sleep. He, too, had been declared vegetative—a “cabbage,” according to one doctor—after being hit by a truck. Within 25 minutes of taking zolpidem, his mother recalled, he started making his first sounds, and when she spoke, he responded, “Hello, Mummy.” Then the effects of the drug faded as rapidly as they’d come on.

Viljoen would continue taking zolpidem every day; he eventually recovered enough to be conscious even without the drug, but a daily dose reanimated him further. “After nine minutes the grey pallor disappears and his face flushes. He starts smiling and laughing. After 10 minutes he begins asking questions,” a reporter who met him in 2006 wrote. Several other drugs, including amantadine and apomorphine, can have similarly arousing effects, though none has worked in more than a tiny sliver of patients. In certain people, for reasons still not understood, they might activate a damaged brain just enough to kick it into gear, “like catching a ride on a wave,” Schiff, who has studied patients on Ambien, told me.

Greg Pearson, in New Jersey, had electrodes implanted in his thalamus in 2005 as part of a study by Schiff and Giacino. The thalamus is a walnut-size region of the brain that sits above the opening at the bottom of the skull, where the spinal cord meets the brain, a position that makes it particularly vulnerable during injury: When a bruised brain swells, it has nowhere to go but down, putting tremendous pressure on the thalamus. Because the thalamus usually regulates arousal—Schiff likens it to a pacemaker for the brain—damage to this region can induce disorders of consciousness. Schiff wondered if stimulating the thalamus could restore some of its function. And indeed, when the electrodes were turned on during surgery, Pearson blurted out his first word in many years: “Yup.” He was eventually able to recite the first 16 words of the Pledge of Allegiance and tell his mother, “I love you.”

A damaged brain, in some cases, might be more like a flickering lamp with faulty wiring than a lamp that has had its wiring ripped out. If so, that circuitry can be manipulated. The neurosurgeon Wilder Penfield realized this decades ago, when he discovered that he could make a conscious patient fall unconscious by gently pressing on a certain area of the brain.

That our consciousness might actually be dynamic, that it can be dialed up and down, is not so strange if you consider what happens every day. We become unconscious when we sleep at night, only to reanimate the next day. Could this dialing back up be artificially controlled when the brain is too damaged to do so itself?

After the publication of the study on Pearson, in 2007, Schiff couldn’t keep up with all the calls to his office. He and his colleagues were now looking for more patients, including people who were even less responsive initially than Pearson—people whose condition would test the extent of what deep-brain stimulation using electrodes could do.

Given his limited but still discernible responses, Ian seemed like the perfect candidate. The researchers were careful not to make guarantees. But Eve harbored hope that Ian could one day tell her, “I love you.” His family agreed to join the trial.

I’ll cut to the chase: Ian’s deep-brain stimulation did not work. At one point during the surgery to implant the electrodes, he said the only intelligible word he’s uttered since 1986—“Down,” in response to being asked, “What is the opposite of up?” Then he lapsed into silence once again. In the months that followed, therapists spent hours and hours asking Ian to move his arm or respond to questions, to no avail.

Geoff, who worked in video production at the time, captured the process on film. He had intended to make a documentary about what he hoped would be his brother’s recovery. In addition to filming Ian in the trial, he’d taped interviews with family members, asking what hearing Ian speak again would mean to them.

He never did make the documentary. Without a miraculous recovery, he felt, the story was just too sad. This past winter, Geoff dug up the old camcorder tapes, and we watched the footage together on the living-room TV. He hadn’t seen it since he filmed it nearly 20 years ago. “Tough to watch,” he said more than once.

Sarah Blesener for The Atlantic

At the time of his accident, Ian—seen here in a video from a high-school class—was a month away from graduation.

After Ian went home, life at the Rainbow Lodge went on largely as it had before. Something did change, though—specifically for Geoff. Knowing that scientists now believed Ian retained some awareness transformed how he related to his younger brother. He started spending more time with Ian, and the two regained a brotherly intimacy. “Ian, are you conscious or are you a vegetable?” Geoff teased during one of my visits. “I think you’re a vegetable. I think you look like a kumquat.”

Geoff eventually took on more and more of Ian’s care; he is now paid through Medicaid as a part-time caregiver, helping Eve, who is 86. Geoff is the one who puts Ian to bed every evening, smoothing out the sheets to make sure he does not lie on a wrinkle all night long. He tucks an extra pillow on Ian’s left side, as his head has a tendency to droop that way.

For Eve, caregiving came naturally; she told me her ambition in life was always to be a mother. She had married at 18 and had three children in quick succession. When their marriage became strained, she and her first husband decided to try an open relationship. In 1964, Eve got a job waitressing at a Woodstock café whose owners let a singer named Bob Dylan live upstairs. She flirted with men. She flirted with Dylan, who took her to play pool and showed her pages of his book in progress, Tarantula. (“Bob was much cuter,” she says of Timothée Chalamet, who starred in the recent Dylan biopic.) Eventually she got divorced; her second husband was Ian’s father. Her third, Marshall, was an artist with a successful marketing career in New York City. Eve and Marshall planned to spend more time there after Ian graduated. The car crash upended everything.

Afterward, Eve threw herself back into the role of devoted mother. (Marshall helped take care of Ian until his death in 2011.) Even now, with Geoff and two nurses who cover five days a week, Eve has certain tasks she insists on carrying out herself. She trims Ian’s nails and hair, now thinning on top to reveal the faint scars from his deep-brain-stimulation surgery. She shaves him. When she speaks to her son, she leans over close, their matching Roman noses almost touching. In these moments, Ian will vocalize—“Aaaaaahh ahhhhhh”—like he is trying to talk with his mother.

Sarah Blesener for The Atlantic; Courtesy of the Baer family

Ian’s stepfather, Marshall, cared for him alongside Eve until his death in 2011.

“I think Ian lived for my mom,” Geoff told me at one point, thinking back to the hospital, where Eve pleaded over his unconscious body, holding on to Ian with her imagined golden lasso. She had promised Ian then that she would do anything for him if he lived—hence the healers, the studies, and her devotion to him for the past 39 years.

While Ian was recovering from the deep-brain-stimulation surgery, Eve came across a poem by E. E. Cummings that affected her so deeply, she took to reading it aloud to him in a morning ritual. The second stanza goes:

(i who have died am alive again today,
and this is the sun’s birthday;this is the birth
day of life and of love and wings:and of the gay
great happening illimitably earth)

Schiff kept probing the outer limits of consciousness in patients with severe brain injuries. Last year, he, along with Owen, Laureys, and other researchers in the field, published the largest and most comprehensive study yet of covert awareness. This is the New England Journal of Medicine study that included Ian, and found one in four vegetative or minimally conscious brain-injury patients to have covert awareness. (Schiff prefers the term cognitive motor disassociation, to highlight the disconnect between the patients’ mental and physical abilities.) “Our experience was Wow, it’s not so hard to find these people,” Schiff told me.

The researchers do not believe that everyone with a disorder of consciousness is somehow cognitively intact—a majority are probably not, according to this study. The most important takeaway, researchers say, is simply this: People with covert awareness exist, and they are not exceedingly rare.

[From the June 2015 issue: Hacking the brain]

These findings raise profound questions about our ethical obligation to people with severe brain injuries. In his 2015 book, Rights Come to Mind, Joseph Fins, a medical ethicist at Cornell who frequently collaborates with Schiff, argues that such patients deserve better than to be “cast aside by an indifferent health care system,” or left to languish as mere bodies to feed and clean. “For so long, I’d been stripped of any identity,” one brain-injury patient, Julia Tavalaro, wrote in her memoir, Look Up for Yes. “I had begun to think of myself as less than an animal.” She was able to write the book after a particularly observant speech therapist finally noticed, six years after her injury, that she could communicate with her eyes. But too often, Fins told me, patients are shunted into long-term-care homes that cannot provide the attention and rehab that could uncover subtle signs of consciousness.

These patients are also especially vulnerable to abuse. In 2019, staff at a facility in Phoenix called 911 in a panic after a patient—who was reportedly vegetative but may have been minimally conscious—unexpectedly gave birth. No one at the facility, where she had lived for years, even knew she was pregnant until a nurse saw the baby’s head. She had been raped by a male nurse.

In some cases, patients with covert awareness may never make it to long-term care—they simply die when life support is withdrawn at the hospital. “If you went back 15, 20 years, there was a tremendous amount of nihilism” among doctors, says Kevin Sheth, a neurologist at Yale. Even as medicine has become less fatalistic about brain injury, hospitals still rarely look for covert awareness using fMRI. ICU patients may be too fragile to be moved to an fMRI machine, and the technology is too cumbersome and expensive to bring into the ICU.

Varina Boerwinkle, a neurocritical-care specialist now at the University of North Carolina, believes the technology should be routinely used with brain-injury patients. She told me about a 6-year-old boy she treated at a previous job in 2021, who had been in a car crash. Her initial impression was that he would not survive, and his first fMRI scan showed no signs of awareness. Boerwinkle began to wonder if doctors were prolonging his suffering. But the team repeated the test on day 10, in anticipation of discussing withdrawal of care with the boy’s parents. To Boerwinkle’s astonishment, his brain was now active: He could respond when asked to perform specific mental tasks in the fMRI.

At first, Boerwinkle wasn’t sure what to say to the boy’s family about the fMRI. Though it implied that he still had cognitive function, it did not guarantee that he would ever recover enough to respond physically or verbally. Her colleagues have seen families struggle to care for a child with a severe brain injury, Boerwinkle told me, and everyone was wary of providing false hope.

The doctors ultimately did inform the boy’s parents about their findings; his mother told me the fMRI gave them the confidence to agree to another surgery. It worked. Four years later, the boy is back in school. He uses an eye-gaze device to communicate and zoom around in his wheelchair, and his reading and math skills are on par with those of other kids his age.

Scientists are now looking for simpler tools to test for covert awareness. Patients who show signs of awareness early on, it seems, tend to have better recoveries than those who don’t. Owen, now based at the University of Western Ontario, recently published a study using functional near-infrared spectroscopy, which shines a light through the skull. A group at Columbia University, led by Jan Claassen, is experimenting with EEG electrodes that sit on the head.

But even after 20 years of research, little has changed in terms of what doctors can do to help patients found to have covert awareness long after their injury—which is still, in most cases, nothing. On his office wall, Schiff has taped the brain scans of five patients to remind him of the human stakes of his work. He is now exploring brain implants, which are already helping certain paralyzed patients control cursors with their mind or speak via a computer-generated voice. The next several years could prove crucial, as a crop of well-funded companies tests new ways of interfacing with the brain: Elon Musk’s Neuralink, perhaps the best-known of these, uses filaments implanted by a sewing-machine-like robot; Precision Neuroscience’s thin film floats atop the cortex; and Synchron’s implant is threaded up to the brain through the jugular vein.

Getting any of these implants to work in people with severe injuries like Ian’s will be particularly challenging. Ian’s age and the electrodes already implanted in his brain also make him an unlikely early candidate. This technology—if it ever works for people like him—may arrive too late for Ian.

Even in 1972, when Plum and Jennett first described the vegetative state, the doctors foresaw that they were barreling toward a “problem with humanitarian and socioeconomic implications.” The vegetative patients they described could now be kept alive indefinitely—but should they be? At what cost? Who’s to decide? Soon enough, Plum himself was asked to weigh in on the life of a 21-year-old woman.

In 1975, Plum became the lead witness in the case of Karen Ann Quinlan, who’d recently fallen into a vegetative state. She had collapsed after taking Valium mixed with alcohol, which temporarily starved her brain of oxygen. Her parents wanted her ventilator removed. Her doctors refused. In the ensuing legal battle, Quinlan’s family and friends testified that she had said, in conversations about people with cancer, that she wouldn’t want to be “kept alive by machines.” But there was no way to know what Quinlan wanted in her current condition. Plum categorically pronounced that she “no longer has any cognitive function”; another doctor likened her, in his court testimony, to an “anencephalic monster.”

In the end, a court granted her parents’ request to remove Quinlan’s ventilator. The controversy surrounding her case fueled interest in then-novel advance directives, which allow people to spell out if and at what point they want to die in the event of future incapacitation. In recognizing that life might not always be worth living, the court’s ruling also inspired a nascent “right to die” movement in the U.S.

By the time Terri Schiavo, in Florida, made national news in the early 2000s, resurfacing many of the same legal and ethical questions, the science had become more complicated. Schiavo had also been diagnosed as vegetative after she collapsed—from cardiac arrest, in her case. When her condition did not improve after eight years, her husband sought to have her feeding tube removed. Her parents fought back, fiercely. Although most experts found her to be vegetative, those aligned with her parents seized on the newly defined minimally conscious state to argue that Schiavo was still aware. The family released video clips purporting to show her responding to her mother’s voice or tracking a Mickey Mouse balloon with her eyes. If she was still conscious, they argued, she should not be made to die.

Schiavo became a cause célèbre for the religious right, and opinions hardened. Where one side saw parents honoring their daughter’s life, the other saw them clinging to illusory hope. Giacino told me that because of his key role in defining the minimally conscious state, he was asked to examine Schiavo by the office of Jeb Bush, then Florida’s governor. The behavioral exam he planned to perform, Giacino said, could have helped discern whether Schiavo’s responses were real or random. He never did go to Florida, though, because a court proceeding made another exam moot.

Schiavo eventually died when her feeding tube was removed in 2005. The general consensus now holds that she likely was vegetative—an autopsy later found that her brain had atrophied to half its normal size—but Giacino still wonders how that correlated with her level of consciousness. Because he never examined her himself, he personally reserved judgment.

If Schiavo—or let’s say a hypothetical patient diagnosed as vegetative, like her—were in fact minimally conscious or covertly aware, would that tip the calculus of keeping her alive one way or the other? Which way? On one hand is the horrifying proposition of snuffing out a human consciousness. On the other hand is what some might consider a fate worse than death, of living imprisoned in a body entirely without choice, without freedom. In memoirs and interviews, brain-injury patients who regained communication—Tavalaro among them—speak of despair, of abuse, and of sheer, uninterrupted boredom. They could not even turn their head to stare at a different patch of wall paint. One young man described the particular agony of being placed carelessly in a wheelchair and forced to sit for hours atop his testicles. Some have tried to end their life by holding their breath, which turns out to be physically impossible. The classical notion of a totally mindless vegetative state offered at least meager solace: a person devoid of consciousness would not experience pain or suffering.

One-third of locked-in patients, who can communicate only using their eyes, have thought of suicide often or occasionally, according to a survey of 65 people conducted by Laureys, the Belgian neurologist. But a majority of these patients have never contemplated suicide. They say they are happy, and those who have been locked in longer report being happier, which squares with other research showing that people with disabilities are in fact quite adaptable in the long term. Of course, those who responded to the survey are not entirely representative of everyone with a brain injury; for one thing, they could still communicate, albeit with difficulty.

What about covertly aware patients, with total loss of communication—are they happy to be alive? As far as I know, only one such person has ever had the opportunity to answer this question. In the 2010 study, after the 22-year-old man answered five consecutive yes-or-no questions correctly, Laureys decided to pose a last question, one to which he did not already know the answer: Do you want to die?

Where the man’s previous responses were clear, this one was ambiguous. The scan suggested that he was imagining neither tennis nor his house. He seemed to be thinking neither yes nor no, but something more complicated—exactly what, we will never know.

I posed a version of this question to the researchers who have devoted their career to understanding disorders of consciousness. Would you choose to live? “If no one was coming to the rescue, if help was not on the way, I wouldn’t want to be in any of these situations,” said Schiff, who has a practical eye toward brain-implant research that could one day help these patients.

Owen was more philosophical. He told me that when people learn about his research, many say they would prefer to die; even his wife says that. But he is less certain. He does not have an advance directive. Perhaps the only thing worse than wanting to die and being forced to live, he said, is to watch everyone let you die when you have decided, in the moment of truth, that you actually want to live.

On one of my trips to the Rainbow Lodge this past winter, Geoff rigged up Ian’s foot switch—one of countless assistive devices his family has tried—to play a prerecorded message for me. “Hey, Sarah, thanks for coming!” it went in Geoff’s singsong voice. “I’m glad to see ya.” His family had hoped, at one point, that Ian’s left foot, which waves back and forth, unlike his permanently fixed right one, could become a mode of communication. But Ian has never been able to push the switch reliably on command. Still, occasionally, he hits the big green button just hard enough to set it off.

Sarah Blesener for The Atlantic

Ian’s brother Geoff has become one of his caregivers, despite his earlier misgivings about their mother’s decision to keep Ian alive.

I cannot know to what extent, if any, this movement is voluntary. But Ian’s foot is certainly more active at some times than others. While his family and I chatted over lunch at the kitchen table one day, it went tap, tap. “Hey, Sarah, thanks for coming!” Was he trying to join the conversation? “Hey, Sarah, thanks for coming!” If so, what did he want to say?

There was one other instance when I saw his foot moving that much—during a previous visit, when we spoke in detail about Ian’s car crash for the first time. The crash took place in the early morning, after the boys had been together all night. Ian was driving. When Eve was asked to identify the body of the boy who died, Sam, she recognized the white shell necklace Ian had brought back for him from a recent trip to Florida. The third boy—the one who survived—eventually stopped keeping in touch with high-school friends, a disappearance they attributed to survivor’s guilt.

I wondered if our conversation would distress Ian, if we should be replaying these events in front of him. To me, it seemed as though his face had turned especially tense. His foot was going tap, tap, tap. Or was I projecting my own thoughts, as it is so easy to do with someone who cannot respond? “Ian knows he killed his best friend,” Geoff said at one point that night. “By accident.”

The next day, Ian was grinding his teeth. It happens sometimes, Eve told me. Perhaps something hurt. Or his stomach was upset. Or an eyelash was stuck in his eye. They tried to rule out causes one by one, but it’s always a guessing game. I thought back to our conversation the night before, and wondered whether the presence of a stranger probing the traumatic events of his life might have agitated him.

Ian could not walk away from a conversation he did not want to have, nor could he correct the record of what we got wrong. If his memories and cognition are more intact than not, then he has had time—so much time—to live inside his own thoughts. Has he come to his own reckoning over his friend’s death? Does he feel his own survivor’s guilt? Does he ever wish for the fate of one of his friends in the car over the one he was actually dealt? Perhaps being incapable of these thoughts would be a mercy in itself.

At one point, Geoff decided to reprogram Ian’s foot switch, in part to cheer up Molly Holm, one of Ian’s nurses since 2008, who had bruised her ribs slipping on ice. Molly had known Ian back in high school; he was friends with her older brother. She started coming to patterning sessions at the Rainbow Lodge after the accident, taking a position at Ian’s right hand. She later became a nurse. Her first job was at a head-trauma center, where she looked after young men with injuries like Ian’s. In some of the vegetative patients, she would see flashes of what seemed like awareness. But who was she, a very green nurse, to question a doctor’s diagnosis? Some of the men at this facility rarely had visitors, Molly says, their isolation so unlike the warmth of Ian’s home.

[From the April 2024 issue: Sarah Zhang on the cystic-fibrosis breakthrough that changed everything]

That’s what originally drew her, a deeply unhappy 14-year-old, to the Rainbow Lodge all those years ago. (Okay, she admits, she’d also had a huge crush on Ian before the crash.) It drew other people too, including those who temporarily moved into the lodge’s guest rooms during the patterning days: Ian’s girlfriend, Valerie Cashen; a friend of Geoff’s, Karen McKenna, who was 21 and pregnant, and had recently split from her boyfriend; and, perhaps most unexpectedly, the mother of the boy killed in the car crash, Renee Montana. Eve had overheard her primal scream of grief in the hospital, and when they later met, the mothers felt connected rather than divided by their respective tragedies.

Sarah Blesener for The Atlantic

Ian, Eve, Geoff, and Geoff’s partner, Molly—also one of Ian’s nurses—gather for cards after dinner at the Rainbow Lodge.

Valerie, Karen, and Renee all arrived at the Rainbow Lodge overwhelmed by their own life circumstances. The two younger women stayed for a year or two and became close friends. Karen hadn’t known Ian at all before his injury. She first came to the hospital as a friend of the family; she offered to watch over Ian for Eve because, well, she didn’t have much else to do. She gave birth to her baby while living at the lodge, Eve by her side as her Lamaze coach. Karen’s time caring for Ian helped inspire her to enroll in nursing school, and she eventually became a nurse at the very ICU where she first met Ian.

Renee stayed for a few years. She did not blame Ian for Sam’s death, though she knew that others did. When I asked her if she ever thought about what might have happened if their fates had been switched, she had an immediate answer: “My poor boy would have been institutionalized.”

She didn’t have the means to care for him at home; she didn’t have the Rainbow Lodge. She was a single mom, living with a boyfriend in a disintegrating relationship. Eve and Marshall’s welcoming her into their community kept her from going adrift. “They just saved my life,” she said. Her life took an unexpected turn there too: Renee ended up having another child—her daughter, Morganne—born in 1988, after Renee had a brief affair with Eve’s brother.

Out of these chaotic circumstances, Eve and Renee found their bond as new friends cemented into that of family. Eve was present at this birth as well; she cut Morganne’s umbilical cord. Back at the lodge, they put the newborn girl in Ian’s lap, letting him hold a new life that would not exist had his own not been thrown off course. Morganne, now 37, told me that her earliest memories are of curling up at Ian’s feet to watch TV.

Reflecting on life after Ian’s accident, Eve prefers to speak not of loss but of gains: a new niece, lifelong friends, the entire Rainbow Lodge community. She decided long ago that she could carry others forward—Ian most of all—on her brute optimism. And in our hours of conversation, I never heard her linger on a negative note.

In this respect, Geoff does not take after his mother. “Geoff’s more like, I see your suffering, brother,” Molly told me. He and Ian have a different kind of bond, she added, “because Geoff recognizes that, sometimes, this sucks.”

“No, I mean, it definitely sucks, right?” Geoff said. “Not to be able to communicate sucks.”

Geoff’s coping mechanism is humor, at times dark, at times juvenile. It helps that Ian’s most reliable response is laughter. When he really gets going, his chuckle turns into a full chest shake. Geoff still dreams about the technology that might help his brother communicate. For now, they have the foot switch.

The message Geoff recorded after Molly’s fall was meant to make her, and everyone else, laugh: He blew a fart noise, scattered objects on the ground, and shouted, “Oh my God! What happened there?” Then he slipped the switch under Ian’s left foot.

Sarah Blesener for The Atlantic

Molly and Geoff care for Ian together, and will continue to do so after Eve is gone.

Geoff was so keen to lift Molly’s spirits because they are a couple, together since 2000. Over the course of their relationship, Geoff had grown close to another of her patients, a spunky boy who eventually died of epidermolysis bullosa, also known as butterfly-skin syndrome, in his 20s. They don’t have children of their own but they had become a caretaking unit, their relationship deepening over their shared love for the boy. Now they care for Ian together, and they will continue to care for him when Eve is gone.

When I was leaving the Rainbow Lodge for the last time, Eve impressed upon me what she hoped people would take away from Ian’s life: “It’s not a sad story.” On this, Molly concurred. Yes, it sucks sometimes. But Ian has been continuously surrounded by people who love him, people who took that love and made something of it.

As if on cue, Ian’s foot switch went off. Fart noise. Objects scattering. “Oh my God! What happened there?” Maybe it was just a random movement of his foot. Maybe he wanted to disagree with his mother’s assessment. Or maybe he agreed that his is not a sad story. If only he could tell us in his own words.

This article appears in the June 2025 print edition with the headline “Is Ian Still In There?” When you buy a book using a link on this page, we receive a commission. Thank you for supporting The Atlantic.

The End of Chicken-Breast Dominance

2025-04-28T09:00:00-04:00

Few things in life are both cheaper and better, but for a long time, this was true of the chicken thigh. Its superiority was passed like a shibboleth among food connoisseurs: Thighs are juicier, tastier, are almost half the price—preferable in just about every way to the boneless, skinless, flavorless breasts that reign supreme in America.

Well, the secret’s out. On a recent trip to the grocery store, I picked up a pack of boneless thighs that cost, pound for pound, some 50 cents more than boneless breasts. In fact, the cost of thighs has crept steadily upward for years now, and surpassed that of breasts for much of last year. In recent months, breasts have gained in price again, but white meat’s continued dominance no longer seems assured. Home cooks have embraced the flavor and versatility of dark meat; fast-casual restaurants such as Chipotle and Sweetgreen have it all over their menus. After a decades-long run, America’s white-meat era may finally be ending.

That era began in the1980s, when the first plant dedicated to deboned breast meat opened in the United States. “Before that, deboned breast meat was very expensive and rare,” Paul Aho, a poultry-industry consultant, told me. Eating chicken used to mean getting whole chickens, skin and bones and all. But when processing plants started atomizing chicken into their parts, the popularity of boneless, skinless breasts exploded. Americans learned to love not only slabs of white meat but also nuggets, patties, and tenders—processed products made possible by the ubiquity of deboned breasts. In an era obsessed with low-fat, low-cholesterol diets, white meat was deemed the healthier option too. Demand for breasts drove the expansion of the entire American poultry industry, Aho said.

The billions of chickens being raised for breast meat of course also have billions of thighs, legs, wings, and organs, arguably by-products of breast production. U.S. producers learned to export minimally processed leg quarters—an entire thigh and leg with skin and bones—overseas, where consumers did not mind, or even preferred, dark meat. Russia was a major customer, then China, and then Mexico.

The boneless and skinless chicken thigh, however, did not exist as a widespread meat product in the United States until the 2000s. This is also partially a story of industrial innovation: Over time, the thigh-deboning process has become more automated, making boneless dark meat less labor-intensive to produce. The Baader 632 Thigh Filleting System, for example, boasts of processing 230 thighs a minute, by yanking the meat straight off the bone. Aho points out that automation tends to work better with thighs, which have only a single straight bone, than with breasts, which cling to multiple curved bones. Machines that debone breasts usually can’t get the muscle off as cleanly, leaving more meat behind.

With the rise of the boneless thigh, American chicken producers saw an opportunity to sell dark meat at home, at prices higher than intact thighs can get overseas. They started producing more deboned thighs. In 2019, the chicken producer Sanderson Farms told the Los Angeles Times that it would soon have thigh-deboning capacity at all seven of its plants for large birds, compared with just one or two a couple of years earlier.

If a fully intact thigh is unmistakably a thigh, the boneless, skinless version is more approachable for Americans raised on similarly processed breasts. Deboned thighs are just as easy to throw on a grill, put in a sandwich, shred, or chop into bite-size pieces for burritos. In fact, they’re easier to cook than breasts, because they’re less prone to drying out from being left in the pan for five minutes too long. Recipe developers optimizing for easy and quick can tout their “mass appeal.” “I certainly see a lot more praise of dark meat than there used to be,” J. Kenji López-Alt, the food writer and cookbook author, told me. (He personally prefers a perfectly cooked chicken breast, but said it’s hard to get right.)

Matt Busardo, who heads up North American poultry for the market-intelligence firm Expana, points to two other reasons for the popularity of thighs: the diversification of the American palate, thanks to the popularity of Asian and Latin American cuisines that prize dark meat, and the rise of fast-casual restaurants, which considered thighs a tastier, more forgiving, and until recently cheaper cut. Chicken breasts are still popular; their sales have been rising this whole time, too. But “thigh meat has kind of overshot that by leaps and bounds,” Busardo told me. Sales of chicken breast by volume are up 3.9 percent in the past three years, but sales of thighs are up 15.9 percent, according to the marketing-research firm Circana.

The historically single-minded focus on breeding chickens for white meat has, ironically, made it less appealing in some ways. Anecdotally, I’ve heard of shoppers put off by woody breast or spaghetti meat—muscle disorders that result from the breast growing too big too fast. Chicken breasts have nearly doubled in size since the 1950s, and these muscle irregularities became common enough to worry the industry about 20 years ago. Woody breast causes an unappetizing, almost crunchy texture; spaghetti meat comes out mushy and stringy. Tinkering with diets to slow growth or slaughtering birds at lower weights can mitigate woody breast, Casey Owens, a poultry scientist at the University of Arkansas, told me. But a small, slower-growing chicken is a less profitable chicken. Owens has also studied how to make woody breasts more palatable through extra processing. When ground up into patties, she said, the extra connective tissue found in woody breasts makes for a less dense, maybe even preferable, texture.

If the demand for dark meat continues to rise, chickens selected for their big breasts may no longer be economically optimal. Could the industry start breeding birds with bigger thighs? “I’ve actually brought that up to breeding companies, and 10 or 15 years ago, they would just scoff at the idea,” Aho said. “Now they say, ‘We might need a more balanced bird.’”

What Makes Modern Measles Outbreaks Different

2025-04-07T10:51:41-04:00

Updated at 12 p.m. on April 7, 2025

The current U.S. measles outbreak follows, in some ways, a classic pattern: The virus first found a foothold where childhood vaccination is low—among Mennonites in Texas, in this case—before rapidly spreading to other communities and states. It has sickened mostly children and has now killed a second child, whose death was reported this weekend. With cases still ticking up, experts expect the outbreak to persist for a year.

Look closely at the outbreak’s edges, though, and the patterns are more unusual: It’s not just children getting measles. Where Texas’s outbreak has spilled over into New Mexico, for example, half of the confirmed cases and one potential death involve adults, largely unvaccinated. Last year, too, adults older than 20 accounted for more than a quarter of U.S. measles cases. This is all in keeping with what experts have warn ed: Adults are now susceptible to this childhood disease.

Doctors tend to be unfamiliar with adult measles, because adults used to not get it. In the prevaccine era, the extremely contagious virus blazed through with such frequency that virtually all children were infected with measles before reaching adulthood. Today, vaccine coverage is widespread enough that unvaccinated children can easily live to adulthood without ever encountering the virus, but not uniformly high enough to prevent outbreaks altogether. Vaccinated adults can get occasional breakthrough cases, but the illness tends to be much milder. Unvaccinated adults, however, are a uniquely vulnerable group, because measles only becomes nastier and deadlier with age.

The risk from measles follows a U-shaped curve, Neal Halsey, a measles expert and professor emeritus at Johns Hopkins, told me. On the left are children under 5, whose still-maturing immune systems might struggle to fend off the virus. On the right are adults; the rise in mortality gets steeper and steeper over time, eventually surpassing the mortality in young children. When measles managed to reach isolated villages in the past—such as when a sick sailor brought it to a remote part of Greenland in 1951—outbreaks on “virgin soil” proved especially deadly for adults. Of the 77 people who died in Greenland then, 59 were over the age of 35. Measles may be a classic childhood illness, but it mostly killed adults there.

This age gradient of measles severity persists today. Although the typical symptoms of rash, fever, and cough are the same, adults—even healthy adults in their 20s and 30s—grow more prone to the severe complications that might prove dangerous and even fatal. Pneumonia and encephalitis, or infections of the lungs and brain respectively, are more common. One in four adults with measles will need to be hospitalized, a rate that is roughly two to three times that of school-age children.

Matthew Goetz still has “vivid memories” of adult patients he treated as an infectious-disease doctor during a 1988–90 outbreak in Los Angeles. The first patient wasn’t diagnosed until after a couple of days in the hospital, he recalls, because doctors had little reason to suspect that an adult would have measles. Several more soon showed up. Of the 33 patients eventually admitted to the public hospital where Goetz worked, nine had to be transferred to the ICU. Six developed respiratory failure so severe that they needed a ventilator.

When measles returned to Southern California with the Disneyland outbreak of 2014–15, adults made up more than half of those cases. The two sickest patients of the outbreak, who both needed to be ventilated for pneumonia, were also adults, Kathleen Harriman, an epidemiologist at the California Department of Public Health, told me.

Why measles gets deadlier with age of first contact is still not entirely understood; the adult immune system must somehow be less optimized to fight off the virus. Halsey points out that this pattern is not unique to measles: Chicken pox and hepatitis A are also milder in children than in adults. So is COVID, as we’ve recently seen.

The consequences of measles can linger long after infection too. Measles has a singular ability to induce “immune amnesia,” making survivors potentially susceptible to other diseases they’ve already had or been vaccinated against. This is because the virus attacks immune cells, including memory B cells, which “remember” how to fight known pathogens through antibodies. A 2019 study found that a course of measles infection in unvaccinated children wrecked 11 to 73 percent of their antibody repertoire. This range suggests that immune amnesia’s impact may vary widely from person to person, but the overall trend explains some old and odd observations about postmeasles immune suppression. For example, measles can make autoimmune diseases, in which the immune system mistakenly attacks one’s own body, go into remission. Immune amnesia also explains, at least in part, a long-standing pattern of children becoming more vulnerable to other illnesses after getting measles.

This effect has largely been studied in children, so scientists do not really know how it affects adults. “I would anticipate that it would be very similar—and it also might even be slightly worse,” says Stephen Elledge, a biologist at Harvard and senior author on the 2019 immune-amnesia study. A course of measles tends to last longer and be more severe in adults, he reasons, so the disease may kill off more of their memory cells. He suggests that anyone who gets measles should get revaccinated for other diseases, just in case.

If the measles vaccination rate dips further, adult cases could become even more common. The U.S. eliminated measles in 2000, after many years of achieving a better than 95 percent vaccination rate among kindergartners. This number started slipping in 2020 and is now down to 92.7 percent, which is, importantly, edging toward the measles herd-immunity threshold of 92 to 94 percent. Under this threshold, herd immunity can no longer limit spread enough to protect the unvaccinated. A bigger pool of unvaccinated kindergartners means a greater potential for outbreaks that grow massive enough to threaten unvaccinated adults. And if those unvaccinated kids never get their shots later in life, they will become susceptible adults, growing more vulnerable to measles with age.

For now, the Texas outbreak is already so widespread that the U.S. is likely to lose its measles-elimination status. In the time it will take to get this outbreak under control, more children will certainly get infected, as will more adults.

COVID Broke the Rules of Virus Evolution

2025-02-24T08:00:00-05:00

In the early, uncertain days of the coronavirus pandemic, scientists delivered one comforting pronouncement: The virus that caused COVID mutates rather slowly. If that remained true, the virus would not change much to become more dangerous soon, and any vaccine could provide years of durable protection.

What actually happened was that SARS-CoV-2 began mutating quickly, first to be more transmissible and then to evade our immunity, causing breakthrough infections and reinfections. Five years and an alphanumeric soup of variants later, most of us have gotten COVID at least once. The vaccine is still being updated to match new circulating variants. And the virus itself is still changing.

In truth, scientists were both right and wrong about the speed at which SARS-CoV-2 mutates. The rate of mutations as this virus jumps from person to person is indeed unimpressive. But scientists were not aware of a second, accelerated evolutionary track: When SARS-CoV-2 infects a single immunocompromised patient, it can persist for months, accumulating countless mutations in that time.

And if we are unlucky, that highly mutated virus might spread to others. This is the likely origin of Omicron, which appeared in fall 2021 with more than 50 mutations—an astounding evolutionary leap. Omicron looked like it had achieved four or five years’ worth of expected evolution in just months, Jesse Bloom, who studies viral evolution at the Fred Hutchinson Cancer Center, told me at the time. These mutations enabled Omicron to cause a massive wave of infections even among the vaccinated.

Scientists now believe that chronic infections in immunocompromised patients are a key driver of variants in Omicron and beyond. Even as COVID surveillance has faded in urgency, researchers are watching chronic infections for signs of what’s to come.

In retrospect, clues were there from the beginning. At the start of the pandemic, researchers in New York, including Harm van Bakel, a geneticist at the Icahn School of Medicine at Mount Sinai, began sequencing viruses from cancer patients who tested positive for SARS-CoV-2 in March and April 2020—and then kept testing positive for up to two months. The patients couldn’t clear the virus because their immune systems had been weakened by disease and by cancer treatments they received. The study, published in December 2020, concluded that immunocompromised patients with COVID might need long isolation periods, lest they unwittingly spread the virus. (These chronic infections in people who are immunocompromised are distinct from long COVID, which doesn’t necessarily involve continual shedding of virus.)

That same month, a preprint from a group led by Ravindra Gupta in the U.K. connected more of the dots. Gupta and his colleagues had found an immunocompromised patient with a lingering infection who was treated with antibodies from COVID survivors, only for the virus to acquire curious new mutations. Two mutations in particular gave the virus a slight edge in infectivity and antibody evasion. An immunocompromised host, the authors suggested, could provide the ideal viral training ground: A weakened immune system cannot wipe out the virus but can put up just enough defense for the virus to learn its tricks. In this case, the infused antibodies from COVID survivors likely contributed to whatever defenses the patient himself had, but even together they were not enough to completely clear the infection.

The virus from that particular patient probably didn’t spread far, if at all; most do not. But countless chronic infections all around the world subjecting the virus to similar immune defenses could ultimately lead to the same battle-tested mutations showing up over and over again. Indeed, mutations similar to the two in the U.K. patient soon showed up in variants such as Alpha and Omicron that did sweep around the world, Gupta told me recently. And in 2021, multiple alarming variants were found to have a different mutation that researchers in New York first observed in immunocompromised patients way back at the beginning of the pandemic. (Researchers at Mount Sinai, led by van Bakel and Viviana Simon, did match a minor variant from an immunocompromised patient to other infections in the New York City area, though it didn’t seem to spread much beyond that.)

None of the more notorious COVID variants has been directly traced to a single immunocompromised patient. But indirect evidence has accumulated over time that many variants do develop this way. Chronic infections, scientists have now observed over and over, create a distinct pattern of mutations: an overabundance of changes in the spike protein (which helps penetrate human cells) but not in the rest of the virus. This pattern is clearly found in both BA.1 and BA.2 versions of Omicron, as well as the variant that gave rise to JN.1, which drove last winter’s COVID surge. Bloom now says he has “very high confidence” that these variants came from chronic infections. The evidence is not as clear with other variants, he told me, but they could very well have evolved in the same way.

Long before COVID, Bloom had tracked the evolution of influenza during chronic infections in four immunocompromised patients; some mutations in these patients eventually showed up in the seasonal flu. I wrote about the study when it was published in 2017, intrigued by the possibility that chronic infections could predict changes in flu from year to year. At the time, this was quite a novel idea.

Flu and COVID evolution do differ in important ways, but chronic COVID infections, too, are now being examined as harbingers of the future. “Those will actually teach us a lot about the future tricks SARS-CoV-2 will come up with,” says Simon, a microbiologist at the Icahn School of Medicine at Mount Sinai. To discover what those might be, she and van Bakel are now leading a research project to create better tools for sequencing chronic infections and to better understand which immunocompromised patients are most at risk for carrying them. What they find could be a preview for the future of COVID.

Eat Less Beef. Eat More Ostrich?

2025-01-08T07:30:00-05:00

A few months ago, I found myself in an unexpected conversation with a woman whose husband raises cattle in Missouri. She, however, had recently raised and butchered an ostrich for meat. It’s more sustainable, she told me. Sure, I nodded along, beef is singularly terrible for the planet. And ostrich is a red meat, she added. “I don’t taste any difference between it and beef.” Really? Now I was intrigued, if skeptical—which is, long story short, how my family ended up eating ostrich at this year’s Christmas dinner.

I eat meat, including beef, and I enjoy indulging in a holiday prime rib, but I also feel somewhat conflicted about it. Beef is far worse for the environment than virtually any other protein; pound for pound, it is responsible for more than twice the greenhouse-gas emissions of pork, nearly four times those of chicken, and more than 13 times those of beans. This discrepancy is largely biological: Cows require a lot of land, and they are ruminants, whose digestive systems rely on microbes that produce huge quantities of the potent greenhouse gas methane. A single cow can belch out 220 pounds of methane a year.

The unique awfulness of beef’s climate impact has inspired a cottage industry of takes imploring Americans to consider other proteins in its stead: chicken, fish, pork, beans. These alternatives all have their own drawbacks. When it comes to animal welfare, for example, hundreds of chickens or fish would have to be slaughtered to feed as many people as one cow. Meanwhile, pigs are especially intelligent, and conventional means of farming them are especially cruel. And beans, I’m sorry, simply are not as delicious.

So, ostrich? At first glance, ostrich didn’t seem the most climate-friendly option (beans), the most ethical (beans again), or the tastiest (pork, in my personal opinion). But could ostrich be good enough in all of these categories, an acceptable if surprising solution to Americans’ love of too much red meat? At the very least, I wondered if ostrich might be deserving of more attention than we give to it right now, which is approximately zero.

You probably won’t be shocked to hear that the literature on ostrich meat’s climate impact is rather thin. Still, in South Africa, “the world leader in the production of ostriches,” government economists in 2020 released a report suggesting that greenhouse-gas emissions from ostrich meat were just slightly higher than chicken’s—so, much, much less than beef’s. And in Switzerland, biologists who put ostriches in respiratory chambers confirmed their methane emissions to be on par with those of nonruminant mammals such as pigs—so, again, much, much less than cows’.

But Marcus Clauss, an author of the latter study, who specializes in the digestive physiology of animals at the University of Zurich, cautioned me against focusing exclusively on methane. Methane is a particularly potent greenhouse gas, but it is just one of several. Carbon dioxide is the other big contributor to global warming, and a complete assessment of ostrich meat’s greenhouse-gas footprint needs to include the carbon dioxide released by every input, including the fertilizer, pesticides, and soil additives that went into growing ostrich feed.

This is where the comparisons get more complicated. Cattle—even corn-fed ones—tend to spend much of their life on pasture eating grass, which leads to a lot of methane burps, but growing that grass is not carbon intensive. In contrast, chicken feed is made up of corn and soybeans, whose fertilizer, pesticides, and soil additives all rack up carbon-dioxide emissions. Ostrich feed appears similar, containing alfalfa, wheat, and soybeans. The climate impact of an animal’s feed are important contributions in its total greenhouse-gas emissions, says Ermias Kebreab, an animal scientist at UC Davis who has extensively studied livestock emissions. He hasn’t calculated ostrich emissions specifically—few researchers have—but the more I looked into the emissions associated with ostrich feed, the murkier the story became.

Two other ostrich studies, from northwest Spain and from a province in western Iran, indeed found feed to be a major factor in the meat’s climate impact. But these reports also contradicted others: In Spain, for instance, the global-warming potential from ostrich meat was found to be higher than that of beef or pork—but beef was also essentially no worse than pork.

“Really, none of the [studies] on ostrich look credible to me. They all give odd numbers,” says Joseph Poore, the director of the Oxford Martin Programme on Food Sustainability, which runs the HESTIA platform aimed at standardizing environmental-impact data from food. “Maybe this is something we will do with HESTIA soon,” Poore continued in his email, “but we are not there yet …” (His ellipses suggested to me that ostrich might not be a top priority.)

The truth is, greenhouse-gas emissions from food are sensitive to the exact mode of production, which vary country to country, region to region, and even farm to farm. And any analysis is only as good as the quality of the data that go into it. I couldn’t find any peer-reviewed studies of American farms raising the ostrich meat I could actually buy. Ultimately, my journey down the rabbit hole of ostrich emissions convinced me that parsing the relative virtues of different types of meat might be beside the point. “Just eat whatever meat you want but cut back to 20 percent,” suggests Brian Kateman, a co-founder of the Reducetarian Foundation, which advocates eating, well, less meat. (Other activists, of course, are more absolutist.) Still, “eat less meat” is an adage easier to say than to implement. The challenge, Clauss said, is, “any measure that you would instigate to make meat rarer will make it more of a status symbol than it already is.”

I thought about his words over Christmas dinner, the kind of celebration that many Americans feel is incomplete without a fancy roast. By then, I had, out of curiosity, ordered an ostrich filet (billed as tasting like a lean steak) and an ostrich wing (like a beef rib), which I persuaded my in-laws to put on the table. At more than $25 a pound for the filet, the bird cost as much as a prime cut of beef.

Ostrich has none of the strong or gamey flavors that people can find off-putting, but it is quite lean. I pan-seared the filet with a generous pat of butter, garlic, and thyme. The rosy interior and caramelized crust did perfectly resemble steak. But perhaps because I did not taste the ostrich blind—apologies to the scientific method—I found the flavor still redolent of poultry, if richer and meatier. Not bad, but not exactly beefy. “I wouldn’t think it’s beef,” concluded my brother-in-law, who had been persuaded to smoke the ostrich wing alongside his usual Christmas prime rib. The wing reminded me most of a Renaissance Fair turkey leg; a leftover sandwich I fixed up the next day, though, would have passed as a perfectly acceptable brisket sandwich.

I wouldn’t mind having ostrich again, but the price puts it out of reach for weeknight meals, when I can easily be eating beans anyway. At Christmas, I expect my in-laws will stick with the prime rib, streaked through as it is with warm fat and nostalgia.

The Ozempic Flip-Flop

2024-12-12T10:00:00-05:00

Photographs by Kristian Thacker

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A few years ago, West Virginia, which has the highest obesity rate in the nation, quietly began a small and unusual pilot program that would touch hundreds of lives: It started covering obesity drugs for state employees—even as many other insurers balked at what they considered expensive “vanity” drugs.

The program was, by health measures, a success. Patients shed as much as 120 pounds, their cholesterol dropped, their prediabetes faded, and they cut down on blood-pressure meds. As word began to spread, more patients wanted to join. A school nurse told me her weight loss inspired at least six other teachers and staff to get into the pilot program too.

Then it all came to an abrupt end. In March, the state’s Public Employee Insurance Agency (PEIA) decided it could no longer bear the crushing costs of Wegovy and Zepbound. (These obesity drugs are sometimes better known by the brand names Ozempic and Mounjaro, respectively, which is how they are sold for diabetes.) In the months after, PEIA patients began running out of medication. They rationed their remaining supplies, stretching the weekly injections to 10 days, two weeks, even three weeks. They considered copycat compounded versions. One woman began sharing her diabetic mother’s Ozempic. Those who could no longer get the drugs felt their “food noise,” the constant thoughts about eating that the obesity drugs suppress, return with a vengeance. And they have regained weight.

West Virginia’s pilot program is a microcosm of the dilemma posed by new obesity drugs that are at once effective and shockingly expensive. Patients, doctors, and insurers alike are stuck in an intractable situation. Since the program ended, Laura Davisson, the director of medical weight management at West Virginia University, told me, “there’s a lot of desperation that we’re seeing in our practice.” Her center was one of a handful in the state’s pilot program, which was always small; it enrolled about 1,000 patients at its peak, a tiny fraction of the more than 200,000 West Virginians who rely on PEIA. (About two in five people in West Virginia have obesity.) And these 1,000 patients have since become unwitting subjects in an experiment about what happens when patients are given a life-changing drug—only to have it taken away.

West Virginia University was one of the few health centers that could prescribe obesity drugs in the state’s pilot program. (Kristian Thacker for The Atlantic)

Megan Pigott is what one might call a Wegovy super-responder; she lost 120 pounds, more than a third of her body weight, after starting the drug in 2022. Before that, she had been counting calories since elementary school; she had tried SlimFast shakes, a cabbage-and-green-pepper-soup diet that left her miserable, and an older obesity drug called liraglutide. Nothing worked as well as Wegovy, which WVU prescribed for her as part of a weight-management plan that also included dieting and exercise. The drug is meant to be taken indefinitely, first to help patients lose weight and then to keep it off. Wegovy, Pigott told me, finally gave her hope.

After PEIA cut off coverage, she ran out of Wegovy in July. Half of the weight she lost has already come back. She is now considering a generic version of liraglutide, despite the drug causing vomiting and diarrhea when she previously took it. (Wegovy can cause these side effects, too, but Pigott personally found them milder.) To afford even this cheaper and less effective medication, she plans to drive an hour and half to the nearest Rite Aid, which takes a coupon that reduces the cost to $245 a month. Wegovy’s out-of-pocket price, which is more than double that even with a manufacturer’s coupon, is out of the question. “I felt like a drug seeker,” Pigott told me, going to such lengths for medication to lose weight. She is willing to try because, like other PEIA patients I interviewed, she found that managing her obesity had reversed so much of what ailed her body.

When Cassie Hornbeck Maxwell started Wegovy, she had already been diagnosed with prediabetes, sleep apnea, and polycystic ovarian syndrome, a hormonal disorder that can cause irregular periods—all of which are associated with obesity. “I had given up on myself,” she told me. “I had given up on my health.” With Wegovy, her health problems faded away one by one: Her blood sugar went down, she stopped needing a CPAP machine to sleep, and her periods became regular. Her experience matches growing anecdotal and clinical evidence that obesity drugs can mitigate these associated conditions.

Hilaria Ireland Swisher has cut her use of blood-pressure medication in half. She told me she had cried when she first started on Zepbound, so overwhelmed was she to have—after a lifetime of dieting, dieting, dieting, and regaining the weight anyway—a drug that might finally end her health struggles. Obesity made her everyday life difficult: She used to lose her breath climbing a flight of stairs, and her feet would ache for days after outlet shopping with friends. But the drug-induced weight loss kicked off a virtuous cycle. She can move without pain, so she can be more active and keep healthier habits. Now she goes to the gym twice a week.

This is why patients on PEIA don’t want to lose access to the drugs. Whatever the downsides of the drugs—the long-term side effects are still unknown—patients don’t want to go back. The pilot program has been a bit of a roller coaster for patients, says Bisher Mustafa, a weight-management specialist at Marshall Health, one of the centers in the PEIA pilot program. Davisson at WVU has been advocating for PEIA to keep at least the patients in the pilot program on the drugs. Kicking them off Wegovy and Zepbound now, she argues, would reverse the progress already made: “All that money you just put in, you’re going to throw away.”

Laura Davisson is the director of medical weight management at West Virginia University and sees a lot of desperation in her practice. (Kristian Thacker for The Atlantic)

Around the country, however, other insurers faced with the same costs as PEIA have been largely unswayed by the argument that covering obesity drugs will ultimately save money, by preventing obesity-related conditions such as diabetes and heart attacks down the line. North Carolina also dropped coverage for state employees earlier this year, and private insurance has been cutting patients off too. Wegovy and Zepbound are still new enough that firm evidence of cost savings is hard to come by. A handful of studies and simulations, though, suggest that any future health savings will still be dwarfed by the cost of the drugs, at least at current prices. A simulation from Wegovy’s manufacturer, Novo Nordisk, for example, found a savings of $85 million over five years for 100,000 patients—but the current list price of Wegovy over that same period would run $8 billion, a huge discrepancy even if insurers do not pay full price.

In West Virginia, PEIA says it was struggling with costs: The pilot program for 1,000 patients ran at roughly $15 million a year at its peak. Expanding it to 10,000 patients would require $150 million a year, or 40 percent of the agency’s total prescription-drug budget. “I’ve laid awake at night pretty much since I made the decision,” the agency’s director, Brian Cunningham, said in June. “But I have a fiduciary responsibility, and that’s my No. 1 responsibility.” (PEIA did not respond to The Atlantic’s questions about ending the pilot program.) Shutting down the pilot program puts West Virginia in line with other states: Most never covered the obesity drugs for state employees in the first place. Only about a quarter of Americans, with any sort of insurance, have coverage for these medications, according to Obesity Coverage Nexus.

For the West Virginians who briefly gained and then lost coverage, this talk of numbers can feel rather abstract compared with the change they feel so viscerally in their bodies every day. To insurers, a heart attack averted might be a number in a spreadsheet, but to patients, this is their life. Some have written letters to PEIA and state legislators pleading their case. Angela Young, a retired state employee (who wasn’t part of the pilot but lost coverage when she got on PEIA after a divorce), put it to me most bluntly. She feels the extra weight in the knee she had replaced. She struggles with shortness of breath and heart problems. “I’m assuming,” she said, “this is eventually going to kill me.”

A billboard just outside of Fairmont, West Virginia, advertises for inexpensive semaglutide, a type of GLP-1 drug. (Kristian Thacker for The Atlantic)

Even a short stint on the obesity drugs, PEIA patients told me, changed their lives in ways beyond the physical. “When you’re an overweight person, it’s like you’re invisible,” Lory Osborn said. “Like you’re less than a person,” Randi Bourne, the school nurse with six co-workers in the pilot program, told me. They had always been aware of the fat-shaming, the willful ignoring, the subtle and not-so-subtle disrespect, but losing weight opened their eyes to just how differently society treated people with obesity. Maxwell felt she had lost part of her identity when she was seen first as “the fat person.” Losing weight finally let her be seen as herself—as Cassie—but would regaining it erase a part of her identity again?

The drugs also made Maxwell rethink how she thought about herself and about obesity. Like many, she had long considered obesity a problem of self-discipline and motivation. Being on Wegovy and then Zepbound—feeling the food noise disappear with a tweak in brain chemistry—made her see it as a medical condition. Obesity is more complicated than a simple imbalance of the hormone mimicked by these drugs, but doctors do now generally consider it a chronic disease. Maxwell now sees it that way too.

Lory Osborn felt panic, like the rug was being ripped out from underneath her, when she found out about the pilot program ending. (Kristian Thacker for The Atlantic)

To her, and other patients, that makes PEIA’s decision all the more unjustifiable. “It’s the same thing as giving someone with cancer a cancer drug, or someone with diabetes their insulin,” Swisher said of the obesity drugs. Putting them in a different category, many said, felt like yet another instance of discrimination. Historically, the reluctance of insurance companies to cover obesity medications is born out of a belief that obesity is a personal failing. Medicare is still prohibited by law from covering medications for weight loss; the Biden administration recently proposed a rule to sidestep that law, but the Trump administration would need to approve it.

In the fall, PEIA proposed raising premiums for next year. It even cited the high cost of GLP-1 drugs, the class that includes Wegovy and Zepbound, as a key reason. But PEIA had already canceled the obesity-drugs pilot program. The cost, going forward, would be from funding the drugs prescribed for diabetes. (The pilot program was so small that some 86 percent of the money PEIA had been spending on GLP-1 drugs was still for diabetes treatment. However, about two or three times more people in West Virginia have obesity than diabetes, so expanding the pilot program would make obesity costs much higher.) The agency did not propose eliminating coverage for diabetes.

When Pigott started Wegovy, she was prediabetic. “One of the reasons I took the medicine was to prevent myself from getting diabetes,” she said. And it worked: Her blood-sugar levels went down. Now her premiums are going up, and she still can’t get the drug—not unless, of course, she eventually does develop diabetes. “It doesn’t make sense,” she said. To get help, she would first have to get sicker.

What have you experienced while taking GLP-1 drugs? Share your story with us.

(By writing to us, you are agreeing to let The Atlantic use your response, which we may edit for length or clarity. You are also agreeing that The Atlantic’s reporters may contact you at the address provided to discuss whether you would be willing to be interviewed.)

Here’s How We Know RFK Jr. Is Wrong About Vaccines

2024-11-19T10:20:24-05:00

When I was taking German in college in the early years of this millennium, I once stumbled upon a word that appeared foreign even when translated into English: Diphtherie, or diphtheria. “What’s diphtheria?” I wondered, having never encountered a single soul afflicted by this disease.

Diphtheria, once known as the “strangling angel,” was a leading killer of children into the early 20th century. The bacterial infection destroys the lining of the throat, forming a layer of dead, leathery tissue that can cause death by suffocation. The disease left no corner of society untouched: Diphtheria killed Queen Victoria’s daughter, and the children of Presidents Lincoln, Garfield, and Cleveland. Parents used to speak of their first and second families, an elderly woman in Ottawa recalled, because diphtheria had swept through and all their children died.

Today, diphtheria has been so thoroughly forgotten that someone like me, born some 60 years after the invention of a diphtheria vaccine, might have no inkling of the fear it once inspired. If you have encountered diphtheria outside of the historical context, it’s likely because you have scrutinized a childhood immunization schedule: It is the “D” in the DTaP vaccine.

Vaccine breakthroughs over the past two centuries have cumulatively made the modern world a far more hospitable place to be born. For most of human history, half of all children died before reaching age 15; that number is down to just 4 percent worldwide, and far lower in developed countries, with vaccines one of the major drivers of improved life expectancy. “As a child,” the vaccine scientist Stanley Plotkin, now 92, told me, “I had several infectious diseases that almost killed me.” He ticked them off: pertussis, influenza, pneumococcal pneumonia—all of which children today are routinely vaccinated against.

But the success of vaccines has also allowed for a modern amnesia about the level of past human suffering. In a world where the ravages of polio or measles are remote, the risks of vaccines—whether imagined, or real but minute—are able to loom much larger in the minds of parents. This is the space exploited by Robert F. Kennedy Jr., one of the nation’s foremost anti-vaccine activists and now nominee for secretary of Health and Human Services. It is a stunning reversal of fortune for a man relegated to the fringes of the Democratic Party just last year. And it is also a reversal for Donald Trump, who might have flirted with anti-vaccine rhetoric in the past but also presided over a record-breaking race to create a COVID vaccine. Kennedy has promised that he would not yank vaccines off the market, but his nomination normalizes and emboldens the anti-vaccine movement. The danger now is that diseases confined to the past become diseases of the future.

Walt Orenstein trained as a pediatrician in the 1970s, when he often saw children with meningitis—a dangerous infection of membranes around the brain—that can be caused by a bacterium called Haemophilus influenzae type b or Hib. (Despite the name, it is not related to the influenza virus.) “I remember doing loads of spinal taps,” he told me, to diagnose the disease. The advent of a Hib vaccine in the 1980s virtually wiped these infections out; babies are now routinely vaccinated in the first 15 months of life. “It’s amazing there are people today calling themselves pediatricians who have never seen a case of Hib,” he says. He remembers rotavirus, too, back when it used to cause about half of all hospitalizations for diarrhea in kids under 5. “People used to say, ‘Don’t get the infant ward during diarrhea season,’” Orenstein told me. But in the 2000s, the introduction of rotavirus vaccines for babies six months and younger sharply curtailed hospitalizations.

To Orenstein, it is important that the current rotavirus vaccine has proved effective but also safe. An older rotavirus vaccine was taken off the market in 1999 when regulators learned that it gave babies an up to one-in-10,000 chance of developing a serious but usually treatable bowel obstruction called intussusception. The benefits arguably still outweighed the risks—about one in 50 babies infected with rotavirus need hospitalization—but the United States has a high bar for vaccine safety. Similarly, the U.S. switched from an oral polio vaccine containing live, weakened virus—which had a one in 2.4 million chance of causing paralysis—to a more expensive but safer shot made with inactivated viruses that cannot cause disease. No vaccine is perfect, says Gregory Poland, a vaccinologist and the president of the Atria Academy of Science & Medicine, who himself developed severe tinnitus after getting the COVID vaccine. “There will always be risks,” he told me, and he acknowledges the need to speak candidly about them. But vaccine recommendations are based on benefits that are “overwhelming” compared with their risks, he said.

The success of childhood vaccination has a perverse effect of making the benefits of these vaccines invisible. Let’s put it this way: If everyone around me is vaccinated for diphtheria but I am not, I still have virtually no chance of contracting it. There is simply no one to give it to me. This protection is also known as “herd immunity” or “community protection.” But that logic falls apart when vaccination rates slip, and the bubble of protective immunity dissolves. The impact won’t be immediate. “If we stopped vaccinating today, we wouldn’t get outbreaks tomorrow,” Orenstein said. In time, though, all-but-forgotten diseases could once again find a foothold, sickening those who chose not to be vaccinated but also those who could not be vaccinated, such as people with certain medical conditions and newborns too young for shots. In aggregate, individual decisions to refuse vaccines end up having far-reaching consequences.

Evolutionary biologists have argued that plague and pestilence rose in tandem with human civilization. Before humans built cities, back when we still lived in small bands of hunter-gatherers, a novel virus—say, from a bat—might tear through a group only to reach a dead end once everyone was immune or deceased. With no one else to infect, such a virus will burn itself out. Only when humans started clustering in large cities could certain viruses keep finding new susceptibles—babies or new migrants with no immunity, people with waning immunity—and smolder on and on and on. Infectious disease, you might then say, is a necessary condition of living in a society.

But human ingenuity has handed us a cheat code: Vaccines now allow us to enjoy the benefits of fellow humanity while preventing the constant exchange of deadly pathogens. And vaccines can, through the power of herd immunity, protect even those who are too young or too sick to be effectively vaccinated themselves. When we get vaccinated, or don’t, our decisions ricochet through the lives of others. Vaccines make us responsible for more than ourselves. And is that not what it means to live in a society?

A ‘Crazy’ Idea for Treating Autoimmune Diseases Might Actually Work

2024-11-04T13:36:43-05:00

Lupus, doctors like to say, affects no two patients the same. The disease causes the immune system to go rogue in a way that can strike virtually any organ in the body, but when and where is maddeningly elusive. One patient might have lesions on the face, likened to wolf bites by the 13th-century physician who gave lupus its name. Another patient might have kidney failure. Another, fluid around the lungs. What doctors can say to every patient, though, is that they will have lupus for the rest of their life. The origins of autoimmune diseases like it are often mysterious, and an immune system that sees the body it inhabits as an enemy will never completely relax. Lupus cannot be cured. No autoimmune disease can be cured.

Two years ago, however, a study came out of Germany that rocked all of these assumptions. Five patients with uncontrolled lupus went into complete remission after undergoing a repurposed cancer treatment called CAR-T-cell therapy, which largely wiped out their rogue immune cells. The first treated patient has had no symptoms for almost four years now. “We never dared to think about the cure for our disease,” says Anca Askanase, a rheumatologist at Columbia University’s medical center who specializes in lupus. But these stunning results—remission in every patient—have fueled a new wave of optimism. More than 40 people with lupus worldwide have now undergone CAR-T-cell therapy, and most have gone into drug-free remission. It is too early to declare any of these patients cured for life, but that now seems within the realm of possibility.

Beyond lupus, doctors hope CAR-T portends a bigger breakthrough against autoimmune diseases, whose prevalence has been on a troubling rise. CAR-T has already been used experimentally to treat patients with other autoimmune diseases, including multiple sclerosis, myositis, and myasthenia gravis. And the success of CAR-T has inspired researchers to borrow other—cheaper and simpler—strategies from cancer therapy to kill immune cells gone awry. Not all of these ideas will pan out, but if any do, the next few years could bring an inflection point in treating some of the most frustrating and intractable diseases of our modern era.

CAR-T-cell therapy was originally developed as a way to kill malignant cells in blood cancer. It could, scientists later reasoned, also be used to kill specific white blood cells, called B cells, that go haywire with certain autoimmune diseases. One group tried a CAR-T-like therapy against an autoimmune disease called pemphigus vulgaris, and another CAR-T against lupus. It worked—but these experiments were only in mice.

This was the sum total of available scientific evidence when a 20-year-old woman came to her doctors in Erlangen, Germany, asking to try anything for her severe and uncontrolled lupus. None of the long-term medications typically used to manage lupus were working. Her kidneys, heart, and lungs were all failing, and she could walk only 30 feet by herself. CAR-T was risky, her doctor agreed, but lupus was killing her.

CAR-T-cell therapy could essentially turn her immune system against itself. First, doctors extracted from her blood a class of immune cells, called T cells, which they then engineered into chimeric antigen receptor T (CAR-T) cells that could recognize and destroy the B cells driving her lupus. CAR-T cells can cause dangerous and overwhelming inflammatory responses in cancer patients, and her doctors did worry that CAR-T could do the same for someone with autoimmune disease, whose immune system is already in overdrive. “We take the T cells out, activate them like crazy, and then shoot those massively overactivated T cells in an activated autoimmune disease. So if you think about it, that's kind of crazy to do that, right?” says Fabian Müller, a hematologist-oncologist at the University Hospital of Erlangen and one of the doctors on the German team that pioneered the treatment. But fortunately, the woman with lupus did not have any serious side effects, nor did any of the other patients the German group has since dosed. They are all living their everyday lives, free of lupus symptoms and medications. The woman who could walk a mere 30 feet now runs five times a week, Müller told me. She’s gone back to school and is considering studying for a master’s in immunology.

Müller and his colleagues believe that CAR-T-cell therapy works by wiping out enough B cells to trigger a “deep reset” of the immune system. CAR-T cells are dogged little assassins; they are able to find and destroy even the B cells hiding deep in the body’s tissues. A patient’s B-cell count eventually recovers, but the new ones no longer erroneously attack the body itself. Cancer patients are sometimes considered “cured” after five years of remission, and the first lupus patient to receive CAR-T is not so far off from that milestone. But the therapy cannot erase the genetic predisposition many patients have for the disease, says Donald Thomas, a rheumatologist in Maryland. Whether remission is actually durable enough to be a “cure” will take time to find out.

Still, these extraordinary results have set off a gold rush among biotech companies eager to solve autoimmune diseases. CAR-T start-ups founded to treat cancer are pivoting to target autoimmune diseases. And large pharmaceutical companies such as Bristol Myers Squibb, AstraZeneca, and Novartis are developing their own therapies. Columbia’s Askanase is now an investigator on five separate trials, all using CAR-T or a similar cellular therapy, and she hears from more companies all the time. There’s so much interest, she told me, “I don’t even know there are enough patients” to test new treatments. About 1.5 million Americans have lupus, but only a minority of them—those sick enough to justify experimental treatment but not so sick that they’ve suffered too much irreversible organ damage—are eligible for trials.

For now, CAR-T for lupus and other autoimmune diseases is pretty much only accessible in the U.S. through clinical trials—which, in effect, means it’s inaccessible to almost all lupus patients. Jonathan Greer, a rheumatologist in Florida, works in a seven-doctor practice that treats hundreds of people with lupus; not a single one has received CAR-T. He doesn’t know of a single center in Florida that is up and running to do these studies, so interested patients would have to travel out of state.

Even if it becomes FDA approved for autoimmune diseases, CAR-T is a long and expensive process. Because each patient’s own cells are reengineered, it cannot be easily scaled up. The cost of CAR-T for cancer runs about $500,000. Patients also need chemotherapy to kill existing T cells to make room for CAR-T, which adds risk, and in lupus, they usually need to taper off any medications keeping their disease in check, which can cause flare-ups. All these complications make the current iteration of CAR-T suitable only for lupus patients with severe disease, who have run out of other options.

The practical limitations of CAR-T have dogged the cancer field for a long time now, and researchers have already come up with ideas to get around it. A number of simpler strategies for killing B cells are now making their way from blood cancer to autoimmune disease. They include using donor T cells, a different type of immune cell called natural killer cells, or a molecule that binds a T cell to the B cell it’s meant to destroy. Those molecules, called bispecific T-cell engagers, or BiTEs, are “cheap, fast, uncomplicated,” Müller said, but they may not penetrate as deeply into the tissues where B cells reside. Nevertheless, in September, The New England Journal of Medicine published two successful case reports describing successful treatment in a handful of autoimmune diseases, including lupus, with a BiTE called teclistamab. Similar BiTES on the market could be repurposed for autoimmune disease too.

These simpler therapies may ultimately be “good enough,” Askanase said. And their ease of use could ultimately beat out custom CAR-T therapy, which is unlikely to reach all of the millions of people with lupus worldwide. It’s simply too expensive and too cumbersome, a problem that has held back other cutting-edge therapies that were approved to much initial fanfare. Even if CAR-T itself is never widely adopted for autoimmune diseases, it has opened the door to new ideas that could one day revolutionize their treatment.

Abortion Pills Have Changed the Post-Roe Calculus

2024-10-18T06:30:00-04:00

For all the upheaval that followed the overturn of Roe v. Wade, it did not dramatically change the most basic fact about abortions in America: the number. Since 2022, abortions in the United States have held steady—even increased slightly, based on the best of limited data. One major reason? The rise of abortion pills, which are now used in the majority of abortions in America. Every month, thousands of women in states where abortion is banned have been able to discreetly order the pills by mail and take them at home. Even with abortion bans in place, the availability of these pills makes these rules less absolute than the anti-abortion movement would like.

“Abortion pills pose the single greatest threat to unborn children in a post-Roe world,” according to Project 2025, the Heritage Foundation’s conservative policy playbook. They are “death by mail,” according to Students for Life; Kristan Hawkins, the organization’s president, told me that “it’s a travesty what has unfolded under the Biden-Harris FDA.” And the anti-abortion movement is formulating plans to target the pills through a number of legal and political avenues—some of which could apply regardless of who is elected president next month.

Abortion pills had accounted for a steadily growing share of abortions in the U.S. for years, but in 2021, the FDA made them significantly easier to obtain: The pills are actually two different drugs, mifepristone and misoprostol, and the agency nixed a long-standing requirement to prescribe mifepristone only in person. With that, abortion pills became available by mail. The FDA cited COVID-related risks in its 2021 decision, but anti-abortion advocates immediately decried the move—and the policy has remained in place beyond the pandemic. After the overturning of Roe in 2022, 21 states passed new abortion bans or restrictions, but more than a dozen states, including New York and California, took steps to keep abortion pills available by mail, even in restricted states, by passing “shield laws.” These laws explicitly protect doctors, midwives, and nurse practitioners who use telehealth to prescribe the pills by mail across state lines.

Since then, an average of 6,000 to 7,000 people a month living in states with complete or six-week bans have been able to get abortion pills via telehealth, according to data from the Society for Family Planning, which surveys abortion providers in the United States. This number does not include people who had an abortion outside the formal health-care system, for instance by using pills ordered from overseas. And in states where abortion remains legal, the number of abortions—and the proportion involving abortion pills—also rose from 2020 to 2023, according to Guttmacher Institute data. (The number of women traveling to other states for abortions also doubled in this time, which is another reason abortions have not significantly fallen post-Roe.)

“The anti-abortion movement hasn’t quite figured out what to do with this,” says Greer Donley, a law professor at the University of Pittsburgh, who helped draft the nation’s first shield law. The shield laws have not yet been directly challenged in court. And when anti-abortion groups tried to go after the FDA’s original approval of mifepristone via a lawsuit, the Supreme Court dismissed the case this year for lack of standing.

Still, last week, three states—Missouri, Kansas, and Idaho—sought to revive that case, asking courts to reinstate certain restrictions on mifepristone. And although a President Kamala Harris would be likely to stick to the current FDA policy for abortion pills, a Trump administration could change those policies directly. It could, as my colleague Rose Horowitch has reported, curtail access to mifepristone simply by reinstating the in-person requirement for dispensing the drug—or just pull the FDA’s approval of mifepristone altogether. (In August, Donald Trump expressed openness to cracking down on abortion pills; his running mate, J. D. Vance, walked that position back a few days later.) Anti-abortion activists are hoping that Trump will enforce the long-dormant Comstock Act, a 150-year-old anti-obscenity law that bans the mailing of material “intended for producing abortion, or for any indecent or immoral use.” This could criminalize the mailing of abortion pills, even without the passage of a federal abortion ban, though anti-abortion activists have also suggested that Trump keep quiet about Comstock until he wins. (Trump, for his part, refused to share his views on the Comstock Act for months, before finally saying that he would not enforce it.)

Regardless of who becomes president, the anti-abortion movement is devising ways to restrict abortion pills through state governments too. Shield laws, for example, could be directly challenged if a red-state prosecutor goes after a doctor prescribing the pills from a shield-law state. Linda Prine, a doctor with the nonprofit Aid Access, which sends pills to states with abortion bans, told me she no longer leaves her home state of New York. Providers working under shield laws, she said, are all being “super careful.”

Anti-abortion groups could also test the limits of shield laws in more indirect ways. In Texas, says John Seago, the president of Texas Right to Life, pro-abortion groups have put up billboards advertising abortion pills: “You can go to people putting up the billboard. That’s aiding and abetting.” His group has also encouraged Texas lawmakers to introduce new laws that create liability for internet-service providers or credit-card-processing companies involved in abortion-pill transactions.

In Louisiana, where abortion is already banned, a law went into effect this month further restricting both mifepristone and misoprostol as “controlled dangerous substances.” The law is named after a Louisiana woman whose husband secretly slipped misoprostol into her drinks, and anti-abortion activists have used cases like hers to argue that the pills need more regulation. “A faceless, doctorless process to obtain abortion drugs enables abusers to poison or coerce women and girls,” Emily Davis, the vice president of communications for Susan B. Anthony Pro-Life America, said in a statement. But the law is also affecting routine medical care unrelated to abortion: The two drugs are commonly used in miscarriage and postpartum management, and hospitals in Louisiana have been doing timed drills to make sure staff can quickly access the locked closets where the medications now need to be kept.

Anti-abortion groups are also trying creative approaches to regulating abortion pills—such as through environmental regulations. Hawkins told me that Students for Life will be working with state legislatures next year on laws such as those requiring the disposal of fetal tissue from abortions as medical waste. These laws are designed to put the onus on the provider of abortion pills—presumably a doctor operating under a shield law—and states could then go after the provider for environmental-cleanup fees or fines, Kristi Hamrick, the organization’s vice president of media and policy, told me.

The new prevalence of abortion pills has opened up a new frontier, and the political and legal fights ahead may look quite different from those in the past. “We innovate, and we keep coming back. Our work is definitely just beginning,” Hawkins said. Seago, in Texas, told me he does not expect every attempt to restrict abortion pills to work. In the decades before Roe was overturned, he said, states introduced a number of different restrictions to limit access to abortion. Some worked. Some didn’t. With abortion pills, he told me, “we’re not expecting a silver bullet.” But activists like him are demanding that lawmakers try to stop their use nonetheless.

Another Reason to Hate Ticks

2024-10-07T12:30:00-04:00

When Clark Giles first heard about ticks making people allergic to meat, he found the notion so unbelievable, he considered it “hogwash.” Then, in 2022, it happened to him. Following a spate of tick bites, he ate a hamburger and went into sudden anaphylaxis. His lips became numb, his face swollen, and his skin a “red carpet from my knees to my shoulders,” he says. Eventually, Giles—who raises sheep on a homestead in Oklahoma—had to give up eating not just beef but pork, and, yes, even lamb.

From there, his allergy started to manifest in stranger ways. During lambing season, the smell of afterbirth left him with days of brain fog, fatigue, and joint aches. To touch his sheep, he now needs nitrile gloves. To shovel their manure, he now needs a respirator. And Giles doesn’t even have it the worst of people he knows: A friend with the same allergy was getting so sick, he had to give up his sheep altogether.

This unusual allergy is most often caused by the lone-star tick, whose saliva triggers an immune reaction against a molecule, alpha-gal, found in most mammals besides humans. The allergy is also known as alpha-gal syndrome, or AGS. In recent years, the lone-star tick has been creeping northward and westward from its historical range, in the southeastern United States. (Oklahoma is, in fact, right on the edge; ticks are more prevalent in its east than its west.) Alpha-gal syndrome, too, is suspected to be on the rise. Farmers who spend their days outdoors are particularly exposed to lone-star ticks, and repeated bites may cause more severe reactions. And so, Giles is among a group of farmers who have become, ironically, allergic to the animals that they raise.

There are no official numbers for how many farmers are afflicted with alpha-gal syndrome. But AGS has become prevalent enough, says Charles Green, Virginia’s deputy commissioner of agriculture, that the state farm bureau’s upcoming annual convention is offering an alpha-gal-safe meal option. Green himself developed the allergy after getting tick bites on his family farm. And he isn’t even the only ag commissioner I’ve interviewed with the condition: A couple of years ago, I spoke with the commissioner in North Carolina, a top hog-producing state, who could no longer, as his job usually requires, “eat more barbecue than any human being on the face of the Earth.”

For most people with AGS, just avoiding the meat from mammals is enough. But for those who are more sensitive, anything of mammalian origin is off the table: dairy, wool, gelatin, lanolin, and even more obscure products such as magnesium stearate, a fat derivative often found in pills and drug capsules. And for farmers like Giles, who are extremely sensitive, even the fumes from manure, dander, and amniotic fluid can set off reactions. “It’s so much more far-reaching than just, Don’t eat this. It’s, Don’t touch it. Don’t work with it. Don’t be around it,” says Jenna Olcott, who is no longer able to help out on her family’s small cattle farm in Missouri. Farmers with severe AGS find it difficult, and in some cases impossible, to care for their animals at all.

Sonya Bowes has lost count of the number of tick bites she’s gotten on her tiny farm in rural Kentucky. They’re hard to avoid, she says, when taking care of grazing animals in tall grass. She knew something was wrong when she started experiencing mysterious symptoms around her dairy cows, such as sudden drops in her blood pressure, that turned out to be signs of an allergic reaction. She can no longer milk them without getting sick. When we spoke last week, she had already sold her three cows as well as her rabbits. She’s planning to sell her pigs too, at a probable financial loss, because she cannot care for them anymore. Bowes’s small farm has been her livelihood and her lifelong dream. “It’s just been devastating” to give up on that dream.

Antonia Florence and her husband downsized their cattle farm in Virginia after their allergic reactions became so severe, they lost a calf because they were unable to physically help in the birthing process. “We had to stand back and ask ourselves, ‘Did that calf die because we could not care for it?’” she says. “It wasn’t ethical.” Amniotic fluid from cows is known to contain alpha-gal, and anecdotally, it seems to be a strong trigger of AGS. It is also, however, sometimes simply unavoidable; when a calf gets stuck during birth, a farmer may have to get up to their shoulders inside the mother to help. When Olcott helped her husband pull a stuck calf, she told me, everywhere the fluid splattered on her skin became swollen and red, as if she had been scorched. A case study in Spain has also documented three cattle workers who reacted to touching or even breathing in amniotic fluid.

A second factor in the Florences’ decision was that their cattle were also becoming ill—with a different tick-borne illness called theileriosis. This bovine parasite does not affect humans, but managing it requires farmers to get up close with their cattle, which Florence and her husband could no longer do. Together, she told me, these two tick-borne illnesses are killing their farm. Raising cattle isn’t their only source of income, but the couple had put “every evening, every weekend, and every holiday” into the endeavor. Her husband also grew up on this farm, and some of the animals they raised even traced their lineage back to his grandfather’s cows. Unable to fully give up the animals, he still keeps about 10 cattle, but no more mothers or calves. Florence worries about the toll on his health, getting exposed to animals he’s allergic to all the time. He needed a pacemaker recently, and she wonders if it is related to an increased risk of heart disease with AGS.

Alpha-gal syndrome is forcing affected farmers to ask existential questions—not just about their identity as a farmer but about even the long-term viability of their industry. AGS is still unusual enough that it is likely to be underdiagnosed; a survey published in 2023 found that 42 percent of health-care providers had never heard of the syndrome. But as lone-star ticks continue to spread across the country, more and more Americans may eventually find themselves unable to eat beef and pork. (Of course, those opposed to eating animals on ethical and environmental grounds might find cosmic justice in the spread of alpha-gal syndrome. A bioethicist, inspired by the lone-star tick, once proposed decreasing the world’s red-meat consumption by inducing a human immune intolerance to it.)

A few farmers I spoke with have considered switching to raising poultry for other people with AGS, including chicken as well as more exotic species, such as emu and ostrich. The big, flightless birds have red meat that bears a striking resemblance to beef, and they’ve gained popularity in the AGS community. Olcott, in fact, is raising these birds for herself on her family’s cattle farm. They’ve butchered and eaten an ostrich already—“I don’t taste any difference between it and beef”—and still have four emus. She jokes to her husband about switching the whole farm to emus and ostriches, as more sustainable sources of red meat. He isn’t sold yet. But he is much more careful about ticks these days.

A Simple Lab Ingredient Derailed Science Experiments

2024-09-25T12:17:55-04:00

Last year, in July, Reine Protacio’s experiments suddenly stopped working. Every scientist encounters baffling results from time to time; you chalk it up to error, repeat the experiment, and hope for the best. But in this case, the problem didn’t resolve and in fact spread to other members of the lab: Their yeast, which normally multiplies with such intense fecundity that 500 colonies might bloom across a single laboratory dish, had become stunted. Now they were getting just two colonies, maybe three—lonely white dots in a sea of nothing. It was as if something was poisoning the yeast.

After two straight months of failed experiments, Protacio went looking for a culprit. Her lab once had a faulty water purifier, so she switched the water source. No difference. She systematically replaced the sugar and other nutrients for growing yeast. No difference. The mystery, she eventually learned, ran deeper and wider than she thought. And when she and her colleagues at the University of Arkansas for Medical Sciences started sharing her findings, several scientists around the world reported similar stories of ruined experiments. The cases all pointed to the same suspect: agar.

Agar is and has been a staple of microbiology labs for a century. “We buy it in bulk. We buy kilograms at a time,” Protacio told me. Mixed with water, the seaweed-derived white powder forms a sturdy, transparent gel perfect for growing microbes. In my own brief foray into the laboratory as an undergrad, I poured agar into probably hundreds of petri dishes, a tedious but necessary first step for many experiments. The lab where Protacio works uses agar to grow model organisms called fission yeast, whose chromosomes have striking similarities with ours. The bad agar derailed their experiments for two months. Although the lab could recoup the cost of the agar, she said, “they can’t reimburse us for the lost time and the lost productivity.” So the lab started raising the alarm.

In February, Wayne Wahls, who co-leads the lab where Protacio works, wrote to an email list of fission-yeast scientists asking if anyone else had encountered similar problems. One researcher replied yes, and then another. A biologist in Massachusetts even had this agar problem way back in 2006. The more that Wahls, Protacio, and a growing group of other scientists spoke publicly about the problem—in a preprint paper, then an article in Science—the more stories they started to hear. A few of the scientists joined a study of the agar as collaborators, and the preprint has since been submitted to a journal.

The full pattern of agar failure that emerged is confusing, though. The problems in agar seem to have come and gone not just once but several times, sporadically, over the years—suggesting surprising variability in a standard lab product. They also seem to fade under certain conditions: when petri dishes are kept in the dark, according to one lab, or when yeast are fed a nutrient-rich diet, according to Protacio’s own work. Sunrise Science Products, the company that supplied the seemingly toxic batch to her lab, told me it’s been able to successfully grow fission yeast on the same batch of agar. “Please understand that we are NOT disputing their findings in their experimental situation,” the CEO, Liz Kylin, wrote in an email. Perhaps the problem shows up only in certain batches and under certain conditions, which Sunrise is still trying to understand. “Whatever this issue turns out to be, it is certainly elusive, probably extremely specific,” Kylin wrote.

Scientists have started to wonder if the potential toxicity originated in the seaweed used to make the agar. That could explain the variability from batch to batch: Perhaps certain factors—ecological, meteorological—alter the biochemical makeup of seaweed, the same way a wheat harvest differs from season to season and wine grapes vary from year to year.

Agar is also used in food, particularly in desserts in Asia. (Protacio is from the Philippines, and she originally knew agar as an ingredient in sago at gulaman, a cool, sweet drink that often contains bits of agar jelly.) And laboratory agar actually has its origins in food too: In the 1880s, Fanny Hesse suggested that her microbiologist husband use agar in his work, because she had used it to set fruit and vegetable jellies; her mother had heard about it from friends who had lived in Java. Today, however, culinary and laboratory agar are typically made from different types of seaweed. Agar in food is usually extracted from Gracilaria, which grows readily in large artificial ponds and tanks.

Laboratory agar is a more rarefied product. It comes from Gelidium, a slowly growing wild seaweed that yields a higher-quality agar whose lower gelling temperature is more suitable for lab work. These days, Gelidium is harvested primarily off the coast of Morocco, according to Dennis Seisun and Nesha Zalesny, who run the industry-analysis firm IMR International. The red, frilly seaweed can be collected when it washes ashore, but the finest-quality agar comes from Gelidium gathered from the seabed by professional divers in the summer. “If you can reproduce the waters of Morocco in a pond, the company would do it,” Zalesny told me, but Gelidium has so far resisted attempts at mass cultivation.

The reliance on wild seaweed has caused headaches for labs before. In 2015, a Gelidium shortage caused the wholesale price to nearly triple. But scientists have not, up to this point, been particularly keen to find a replacement for their agar. Seisun and Zalesny used to work for a company that makes gellan gum, an agar alternative that can be manufactured entirely in a factory—no divers needed, no finicky wild seaweed. Yet the product never took off. “Agar still is the king and queen and the gold standard,” Seisun told me. Protacio’s lab ended up switching to a different agar supplier—a cheaper one, actually—and since then everything has been just fine.

‘That’s Something That You Won’t Recover From as a Doctor’

2024-09-12T07:00:00-04:00

Photographs by Bethany Mollenkof

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Kylie Cooper has seen all the ways a pregnancy can go terrifyingly, perilously wrong. She is an obstetrician who manages high-risk patients, also known as a maternal-fetal-medicine specialist, or MFM. The awkward hyphenation highlights the duality of the role. Cooper must care for two patients at once: mother and fetus, mom and baby. On good days, she helps women with complicated pregnancies bring home healthy babies. On bad days, she has to tell families that this will not be possible. Sometimes, they ask her to end the pregnancy; prior to the summer of 2022, she was able to do so.

That summer, Cooper felt a growing sense of dread. Thirteen states—including Idaho, where she practiced—had passed “trigger laws” meant to ban abortion if Roe v. Wade were overturned. When this happened, in June 2022, some of the bans proved so draconian that doctors feared they could be prosecuted for providing medical care once considered standard. Soon enough, stories began to emerge around the country of women denied abortions, even as their health deteriorated.

In Texas, a woman whose water broke at 18 weeks—far too early for her baby to survive outside the womb—was unable to get an abortion until she became septic. She spent three days in the ICU, and one of her fallopian tubes permanently closed from scarring. In Tennessee, a woman lost four pints of blood delivering her dead fetus in a hospital’s holding area. In Oklahoma, a bleeding woman with a nonviable pregnancy was turned away from three separate hospitals. One said she could wait in the parking lot until her condition became life-threatening.

Idaho’s ban was as strict as they came, and Cooper worried about her high-risk patients who would soon be forced to continue pregnancies that were dangerous, nonviable, or both.

She was confronted with this reality just two days after the ban went into effect, when a woman named Kayla Smith walked into Cooper’s office at St. Luke’s Boise Medical Center. (St. Luke’s was founded by an Episcopal bishop but is no longer religiously affiliated.) Smith was just over four months pregnant with her second baby—a boy she and her husband had already decided to name Brooks.

Her first pregnancy had been complicated. At 19 weeks, she’d developed severe preeclampsia, a condition associated with pregnancy that can cause life-threatening high blood pressure. She started seeing spots in her vision, and doctors worried that she would have a stroke. The only cure for preeclampsia is ending the pregnancy—with a delivery or an abortion. But Smith had chosen to stay pregnant, despite the risks, and she was able to eke it out just long enough on IV blood-pressure drugs for her daughter to be born as a preemie, at 33 weeks. The baby ultimately did well after a NICU stay, one of those success stories that MFMs say is the reason they do what they do.

This time, however, Smith’s ultrasound had picked up some worrying fetal anomalies, raising the possibility of Down syndrome. “Okay, that’s fine,” Smith remembers saying. “But is our son going to survive?” The answer, Cooper realized as she peered at his tiny heart on the ultrasound, was almost certainly no. The left half of the heart had barely formed; a pediatric cardiologist later confirmed that the anomaly was too severe to fix with surgery. Meanwhile, Smith’s early-onset preeclampsia in her first pregnancy put her at high risk of developing preeclampsia again. In short, her son would not survive, and staying pregnant would pose a danger to her own health. In the ultrasound room that day, Smith started to cry.

Cooper started to cry too. She was used to conversations like this—delivering what might be the worst news of someone’s life was a regular part of her job—but she was not used to telling her patients that they then had no choice about what to do next. Idaho’s new ban made performing an abortion for any reason a felony. It contained no true exceptions, allowing doctors only to mount an “affirmative defense” in court in cases involving rape or incest, or to prevent the death of the mother. This put the burden on physicians to prove that their illegal actions were justifiable. The punishment for violating the law was at least two years in prison, and up to five. The state also had a Texas-style vigilante law that allowed a family member of a “preborn child” to sue an abortion provider in civil court for at least $20,000.

[From the May 2022 issue: Jessica Bruder on the future of abortion in a post-Roe America]

Because Smith had not yet developed preeclampsia, her own life was not technically in danger, and she could not have an abortion in Idaho. Merely protecting her health was not enough. Lawmakers had made that clear: When asked about the health of the mother, Todd Lakey, one of the legislators who introduced the trigger ban in 2020, had said, “I would say it weighs less, yes, than the life of the child.” The fact that Smith’s baby could not survive didn’t matter; Idaho’s ban had no exception for lethal fetal anomalies.

If she did get preeclampsia, Smith remembers asking, when could her doctors intervene? Cooper wasn’t sure. Idaho’s abortion law was restrictive; it was also vague. All Cooper would say was When you are sick enough. Sick enough that she was actually in danger of dying? That seemed awfully risky; Smith had a two-and-a-half-year-old daughter who needed her mom. She also worried that if she continued her pregnancy, her unborn son would suffer. Would he feel pain, she asked, if he died after birth, as his underdeveloped heart tried in vain to pump blood? Cooper did not have a certain answer for this either.

Kylie Cooper is an obstetrician who manages high-risk patients. (Bethany Mollenkof for The Atlantic)

Smith decided that getting an abortion as soon as possible, before her health was imperiled, would be best, even if that meant traveling to another state. She knew she wanted her abortion to be an early induction of labor—rather than a dilation and evacuation that removed the fetus with medical instruments—because she wanted to hold her son, to say goodbye. She found a hospital in Seattle that could perform an induction abortion and drove with her husband almost eight hours to get there. Unsure how much their insurance would cover, they took out a $16,000 personal loan. Two weeks later, Smith again drove to Seattle and back, this time to pick up her son’s ashes. The logistics kept her so busy, she told me, that “I wasn’t even allowed the space to grieve the loss of my son.”

If Smith had walked into Cooper’s office just a week earlier, none of this would have been necessary. She would have been able to get the abortion right there in Boise. But at least she had not yet been in immediate danger, and she’d made it to Seattle safely. Cooper worried about the next patient, and the next. What if someone came in tomorrow with, say, her water broken at 19 weeks, at risk of bleeding and infection? This happened regularly at her hospital.

As summer turned to fall, Cooper started to feel anxious whenever she was on call. “Every time the phone rang, or my pager went off, just this feeling of impending doom,” she told me. Would this call be the call? The one in which a woman would die on her watch? She began telling patients at risk for certain complications to consider staying with family outside Idaho, if they could, for part of their pregnancy—just in case they needed an emergency abortion.

Cooper described her feelings as a form of “moral distress,” a phrase I heard again and again in interviews with nearly three dozen doctors who are currently practicing or have practiced under post-Roe abortion restrictions. The term was coined in the 1980s to describe the psychological toll on nurses who felt powerless to do the right thing—unable to challenge, for example, doctors ordering painful procedures on patients with no chance of living. The concept gained traction among doctors during the coronavirus pandemic, when overwhelmed hospitals had to ration care, essentially leaving some patients to die.

[From the December 2019 issue: Caitlin Flanagan on the dishonesty of the abortion debate]

In the two-plus years since Roe was overturned, a handful of studies have cataloged the moral distress of doctors across the country. In one, 96 percent of providers who care for pregnant women in states with restrictive laws reported feelings of moral distress that ranged from “uncomfortable” to “intense” to “worst possible.” In a survey of ob-gyns who mostly were not abortion providers, more than 90 percent said the laws had prevented them or their colleagues from providing standard medical care. They described feeling “muzzled,” “handcuffed,” and “straitjacketed.” In another study, ob‑gyn residents reported feeling like “puppets,” a “hypocrite,” or a “robot of the State” under the abortion bans.

The doctors I spoke with had a wide range of personal views on abortion, but they uniformly agreed that the current restrictions are unworkable as medical care. They have watched patients grow incredulous, even angry, upon learning of their limited options. But mostly, their patients are devastated. The bans have added heartbreak on top of heartbreak, forcing women grieving the loss of an unborn child to endure delayed care and unnecessary injury. For some doctors, this has been too much to bear. They have fled to states without bans, leaving behind even fewer doctors to care for patients in places like Idaho.

Cooper had moved to Idaho with her husband and kids in 2018, drawn to the natural beauty and to the idea of practicing in a state underserved by doctors: It ranked 47th in the nation in ob-gyns per capita then, and she was one of just nine MFMs in the state. But in that summer of 2022, she began to fear that she could no longer do right by her patients. What she knew to be medically and ethically correct was now legally wrong. “I could not live with myself if something bad happened to somebody,” she told me. “But I also couldn’t live with myself if I went to prison and left my family and my small children behind.”

At first, Cooper and other doctors distressed by Idaho’s ban hoped that it could be amended. If only lawmakers knew what doctors knew, they figured, surely they would see how the rule was harming women who needed an abortion for medical reasons. Indeed, as doctors began speaking up, publicly in the media and privately with lawmakers, several Idaho legislators admitted that they had not understood the impact of the trigger ban. Some had never thought that Roe would be overturned. The ban wasn’t really meant to become law—except now it had.

Frankly, doctors had been unprepared too. None had shown up to testify before the trigger ban quietly passed in 2020; they just weren’t paying attention. (Almost all public opposition at the time came from anti-abortion activists, who thought the ban was still too lax because it had carve-outs for rape and incest.) Now doctors found themselves taking a crash course in state politics. Lauren Miller, another MFM at St. Luke’s, helped form a coalition to get the Idaho Medical Association to put its full lobbying power in the state legislature behind medical exceptions, both for lethal fetal anomalies and for a mother’s health. Cooper and a fellow ob-gyn, Amelia Huntsberger, met with the governor’s office in their roles as vice chair and chair, respectively, of the Idaho section of the American College of Obstetricians and Gynecologists.

The results of these efforts were disappointing. The lobbying culminated in a bill passed in March 2023 that offered doctors only marginally more breathing room than before. It changed the affirmative-defense statute into an actual exception to “prevent the death of the pregnant woman,” and it clarified that procedures to end ectopic and molar pregnancies—two types of nonviable abnormal pregnancies—were not to be considered abortions. But an exception for lethal fetal anomalies was a nonstarter. And an exception to prevent a life-threatening condition, rather than just preventing the death of the mother, was quashed after the chair of the Idaho Republican Party, Dorothy Moon, lambasted it in a public letter. The previous year, the Idaho GOP had adopted a platform declaring that “abortion is murder from the moment of fertilization” and rejected an exception for the life of the mother; it would reiterate that position in 2024.

[Read: Dobbs’s confounding effect on abortion rates]

Cooper and Huntsberger felt that their meeting with two of the governor’s staffers, in December 2022, had been futile as well. It had taken months to schedule a 20-minute conversation, and one of the staffers left in a hurry partway through. “There was a lot of acknowledgment of Yeah, this is really bad. The laws may not be written ideally,” Huntsberger told me. “There was also no action.”

After the meeting, the two women sat, dejected, in a rental car across from the state capitol, Huntsberger having traveled more than 400 miles from Sandpoint, Idaho, where she was a general ob-gyn in a rural hospital. That was when Cooper turned to her colleague and said she had something to confess: She had just been offered a job in Minnesota, a state where abortion is legal. And she was going to take it. She had reached a point where she just couldn’t do it anymore; she couldn’t keep turning away patients whom she had the skills to help, who needed her help. “There were so many drives home where I would cry,” she later told me.

Huntsberger was heartbroken to lose a colleague in the fight to change Idaho’s law. But she understood. She and her husband, an ER doctor, had also been talking about leaving. “It was once a month, and then once a week, and then every day,” she told me, “and then we weren’t sleeping.” They worried what might happen at work; they worried what it might mean for their three children. Was it time to give up on Idaho? She told Cooper that day, “Do what you need to do to care for yourself.” Cooper and her family moved to Minnesota that spring.

Huntsberger soon found a new job in Oregon, where abortion is also legal. A week later, her rural hospital announced the shutdown of its labor-and-delivery unit, citing Idaho’s “legal and political climate” as one reason. Staffing a 24/7 unit is expensive, and the ban had made recruiting ob-gyns to rural Idaho more difficult than ever. Even jobs in Boise that used to attract 15 or 20 applicants now had only a handful; some jobs have stayed vacant for two years. The three other ob-gyns at Huntsberger’s hospital all ended up finding new positions in states with fewer abortion restrictions.

During Huntsberger’s last month in Idaho, many of her patients scheduled their annual checkups early, so they could see her one last time to say goodbye. Over the years, she had gotten to know all about their children and puppies and gardens. These relationships were why she had become a small-town ob-gyn. She’d never thought she would leave.

Two other labor-and-delivery units have since closed in Idaho. The state lost more than 50 ob-gyns practicing obstetrics, about one-fifth of the total, in the first 15 months of the ban, according to an analysis by the Idaho Physician Well-Being Action Collaborative. Among MFMs, who deal with the most complicated pregnancies, the exodus has been even more dramatic. Of the nine practicing in 2022, Cooper was the first to leave, followed by Lauren Miller. A third MFM also left because of the ban. Then a fourth took a new job in Nevada and a fifth tried to retire, but their hospital was so short-staffed by then that they were both persuaded to stay at least part-time. That left only four other MFMs for the entire state.

After the Supreme Court overturned Roe v. Wade, St. Luke’s Boise Medical Center started airlifting pregnant women with certain complications to other states to receive treatment. (Bethany Mollenkof for The Atlantic)

The departure of so many physicians has strained Idaho’s medical system. After Cooper and others moved away, St. Luke’s had to rely on traveling doctors to fill the gaps; the hospital was eventually able to hire a few new MFMs, but the process took a long time. Meanwhile, ob-gyns—and family doctors, who deliver many of the babies in rural Idaho—had to manage more pregnancies, including high-risk ones, on their own. The overall lack of ob-gyns has also had implications for women who aren’t pregnant, and won’t be: Idaho is an attractive place to retire, and the state’s growing population of older women need gynecological care as they age into menopause and beyond.

Anne Feighner, an ob-gyn at St. Luke’s who has stayed in Boise for now, thinks all the time about her colleagues who have left. Every day, she told me in June, she drove by the house of her neighbor and fellow ob-gyn, Harmony Schroeder, who at the moment was packing up her home of 20 years for a job in Washington State. She, too, was leaving because of the abortion ban. Across the street is the pink house where Cooper used to live and where her daughters used to ride scooters out front.

“I still have a lot of guilt over leaving,” Cooper told me. She had made the decision in order to protect herself and her family. But what about her patients in Idaho, and her colleagues? By leaving, she had made a terrible situation for them even worse.

Sara Thomson works 12-hour shifts as an obstetrician at a Catholic hospital in Idaho; she is Catholic herself. Even before the abortion ban, her hospital terminated pregnancies only for medical reasons, per religious directive. “I had never considered myself a quote-unquote abortion provider, ” Thomson told me—at least not until certain kinds of care provided at her hospital became illegal under Idaho’s ban. It started to change how she thought of, as she put it, “the A-word.”

She told me about women who showed up at her hospital after their water had broken too early—well before the line of viability, around 22 weeks. Before then, a baby has no chance of survival outside the womb. This condition is known as previable PPROM, an acronym for “preterm premature rupture of membranes.”

In the very best scenario, a woman whose water breaks too early is able to stay pregnant for weeks or even months with enough amniotic fluid—the proverbial “water”—for her baby to develop normally. One doctor, Kim Cox, told me about a patient of his whose water broke at 16 weeks; she was able to stay pregnant until 34 weeks, and gave birth to a baby who fared well. Far more likely, though, a woman will naturally go into labor within a week of her water breaking, delivering a fetus that cannot survive. In the worst case, she could develop an infection before delivery. The infection might tip quickly into sepsis, which can cause the loss of limbs, fertility, and organ function—all on top of the tragedy of losing a baby.

In the very worst case, neither mother nor baby survives. In 2012, a 31-year-old woman in Ireland named Savita Halappanavar died after her water broke at 17 weeks. Doctors had refused to end her pregnancy, waiting for the fetus’s heartbeat to stop on its own. When it did, she went into labor, but by then, she had become infected. She died from sepsis three days later. Her death galvanized the abortion-rights movement in Ireland, and the country legalized the procedure in 2018.

[Read: Abortion isn’t about feminism]

Doctors in the United States now worry that abortion bans will cause entirely preventable deaths like Halappanavar’s; the possibility haunts Thomson. “We shouldn’t have to wait for a case like Savita’s in Idaho,” she said.

Previable PPROM is the complication that most troubles doctors practicing under strict abortion bans. These cases fall into the gap between what Idaho law currently allows (averting a mother’s death) and what many doctors want to be able to do (treat complications that could become deadly). The condition is not life-threatening right away, doctors told me, but they offered very different interpretations of when it becomes so—anywhere from the first signs of infection all the way to sepsis.

No surprise, then, that the trigger ban provoked immediate confusion among doctors over how and when to intervene in these cases. Initially, at least, they had more legal leeway to act quickly: The Biden administration had sued Idaho before the trigger ban went into effect, on the grounds that it conflicted with a Reagan-era federal law: the Emergency Medical Treatment and Active Labor Act (EMTALA), which requires ERs to provide stabilizing treatment when a mother’s health, not just her life, is at risk. The Department of Health and Human Services interpreted “stabilizing treatment” to include emergency abortions, and a federal judge issued a partial injunction on Idaho’s ban, temporarily allowing such abortions to take place. But Idaho appealed the decision, and when the U.S. Supreme Court agreed to hear the case in January 2024, it stayed the injunction. With that, any protection that the federal law had granted Idaho doctors evaporated.

Sara Thomson, an obstetrician at a Catholic hospital in Idaho, says the state’s ban has changed how she thinks about “the A-word.” (Bethany Mollenkof for The Atlantic)

Thomson was still working under these severe restrictions when I met her in Boise this past June. She missed the days when her biggest problem at work was persuading her hospital to get a new ultrasound machine. A former military doctor, she struck me as soft-spoken but steely, like the most quietly formidable mom in your PTA. At one point, she pulled out a Trapper Keeper pocket folder of handwritten notes that she had taken after our first phone call.

The cases that most distressed her were ones of previable PPROM where the umbilical cord had prolapsed into the vagina, compressing the cord and exposing the baby and mother to infection. When this happens, Thomson said, a developing fetus cannot survive long: “The loss of the baby is sadly inevitable.”

Previously at her Catholic hospital, she would have offered to do what was best for the mother’s health: terminate the pregnancy before she became infected, so she could go home to recover. Now she told patients that they had no choice but to wait until they went into labor or became infected, or until the fetus’s heart stopped beating, slowly deprived of oxygen from its compressed umbilical cord, sometimes over the course of several days. Thomson did not know that a fetus could take so long to die this way—she was used to intervening much sooner. She found forcing her patients to wait like this “morally disgusting.”

“Every time I take care of a patient in this scenario, it makes me question why I’m staying here,” she told me. It ate at her to put her own legal interests before her patients’ health. She knew that if a zealous prosecutor decided she had acted too hastily, she could lose years of her career and her life defending herself, even if she were ultimately vindicated. But if she made a “self-protective” decision to delay care and a patient died, she wasn’t sure how she could go on. “From a moral perspective, that’s something that you won’t recover from as a doctor.”

At St. Luke’s, the largest hospital in Idaho, doctors started airlifting some patients with complications like previable PPROM out of state after the trigger ban took effect. Rather than delay care to comply with the law, they felt that the better—or, really, less bad—option was to get women care sooner by transferring them to Oregon, Washington, or Utah.

After the Supreme Court stayed the injunction allowing emergency abortions for a mother’s health, in January 2024, Idaho doctors became even more cautious about performing abortions, and the transfers picked up. Over the next three and a half months alone, St. Luke’s airlifted six pregnant women out of state. Smaller hospitals, too, transferred patients they would have previously treated.

One woman described fearing for her life as she was sent away from St. Luke’s last year, after losing a liter of blood when her placenta began detaching inside her. “I couldn’t comprehend,” she later told The New York Times. “I’m standing in front of doctors who know exactly what to do and how to help and they’re refusing to do it.” Another woman whose water broke early went into labor en route to Portland, her doctor told me, and delivered her fetus hundreds of miles from home. Her baby did not survive, and she was left to figure out how to get back to Idaho by herself—a medical transport is only a one-way ride. Another became infected and turned septic in the hours it took her to get to Salt Lake City. She had to go to the ICU, says Lauren Theilen, an MFM at the Utah hospital where she was taken. Other patients were sick when they left Idaho and even sicker when they arrived somewhere else.

Where exactly was that line between a patient who could be transferred versus one who needed care immediately, then and there? “I have sometimes wondered if I’m being selfish,” says Stacy Seyb, a longtime MFM at St. Luke’s, by putting patients through medical transfer to avoid legal sanction. But no doctor works alone in today’s hospitals. When one of the first legally ambiguous cases came up, Seyb saw the unease in the eyes of his team: the nurses, the techs, the anesthesiologists, the residents—all the people who normally assist in an emergency abortion. If he did something legally risky, they would also be exposed. Idaho’s law threatens to revoke the license of any health-care professional who assists in an abortion. He came to feel that there was no good option to protect both his team and his patients, but that an out-of-state transfer was often the least terrible one. In Portland or Seattle or Salt Lake City, health-care providers do not have to weigh their own interests against their patients’.

In April, when the Supreme Court heard the Idaho case, the media seized upon the dramatic image of women being airlifted out of state for emergency abortions. Justice Elena Kagan made a point of asking about it in oral arguments. In a press conference afterward, Idaho’s attorney general, Raúl Labrador, pushed back on the idea that airlifts were happening, citing unnamed doctors who said they didn’t know of any such instances. If women were being airlifted, he said, it was unnecessary, because emergency abortions were already allowed to save the life of the mother. “I would hate to think,” he added, “that St. Luke’s or any other hospital is trying to do something like this just to make a political statement.” (St. Luke’s had filed an amicus brief with the Court in support of the federal government.)

Labrador’s comments echoed accusations from national anti-abortion groups that doctors and others who support abortion rights are sowing confusion in order to “sabotage” the laws. When Moon, the chair of the Idaho Republican Party, had rallied lawmakers against any health exceptions back in 2023, she’d also evoked the specter of “doctors educated in some of the farthest Left academic institutions in our country.” (Neither Labrador nor Moon responded to my requests for an interview.)

It is true that doctors tend to support abortion access. But in Idaho, many of the ob-gyns critical of the ban are not at all pro-abortion. Maria Palmquist grew up speaking at Right to Life rallies, as the eldest of eight in a Catholic family. She still doesn’t believe in “abortion for birth control,” she told me, but medical school had opened her eyes to the tragic ways a pregnancy can go wrong. Lately, she’s been sending articles to family members, to show that some women with dangerous pregnancies need abortions “so they can have future children.”

Kim Cox, the doctor who told me about a patient who had a relatively healthy child after PPROM at 16 weeks, practices in heavily Mormon eastern Idaho. Cox said that “electively terminating” at any point in a pregnancy is “offensive to me and offensive to God.” But he also told me about a recent patient whose water had broken at 19 weeks and who wanted a termination that he was prepared to provide—until he realized it was legally dicey. He thought the dangers of such cases were serious enough that women should be able to decide how much risk they wanted to tolerate. Because, I ventured, they might already have a kid at home? “Or 10 kids at home.”

Anne Feighner, an ob-gyn at St. Luke’s, has decided to stay in Boise for now. (Bethany Mollenkof for The Atlantic)

Megan Kasper, an ob-gyn in Nampa, Idaho, who considers herself pro-life, told me she “never dreamed” that she would live to see Roe v. Wade overturned. But Idaho’s law went too far even for her. If doctors are forced to wait until death is a real possibility for an expecting mother, she said, “there’s going to be a certain number of those that you don’t pull back from the brink.” She thought the law needed an exception for the health of the mother.

In the two-plus years since the end of Roe, no doctor has yet been prosecuted in Idaho or any other state for performing an abortion—but who wants to test the law by being the first? Doctors are risk-averse. They’re rule followers, Kasper told me, a sentiment I heard over and over again: “I want to follow the rules.” “We tend to be rule followers.” “Very good rule followers.” Kasper said she thought that, in some cases, doctors have been more hesitant to treat patients or more willing to transfer them than was necessary. But if the law is not meant to be as restrictive as it reads to doctors, she said, then legislators should simply change it. “Put it in writing.” Make it clear.

She does wonder what it would mean to test the law. Kasper has a somewhat unusual background for a doctor. She was homeschooled, back when it was still illegal in some states, and her parents routinely sent money to legal-defense funds for other homeschoolers. “I grew up in a family whose values were It’s okay to take risks to do the right thing,” she told me. She still believes that. “There’s a little bit of my rebel side that’s like, Cool, Raúl Labrador, you want to throw me in jail? You have at it.” Prosecuting “one of the most pro-life OBs” would prove, wouldn’t it, just how extreme Idaho had become on abortion.

When I visited Boise in June, doctors were on edge; the Supreme Court’s decision on emergency abortions was expected at any moment. On my last day in town, the Court accidentally published the decision early: The case was going to be dismissed, meaning it would return to the lower court. The injunction allowing emergency abortions would, in the meantime, be reinstated.

As the details trickled out, I caught up with Thomson, who was, for the moment, relieved. She had an overnight shift that evening, and the tight coil of tension that had been lodged inside her loosened with the knowledge that EMTALA would soon be back in place, once the Court formally issued its decision. Doctors at St. Luke’s also felt they could stop airlifting patients out of state for emergency abortions.

But Thomson grew frustrated when she realized that this was far from the definitive ruling she had hoped for. The decision was really a nondecision. In dismissing the case, the Court did not actually resolve the conflict between federal and state law, though the Court signaled openness to hearing the case again after another lower-court decision. The dismissal also left in place a separate injunction, from a federal appeals court, that had blocked enforcement of EMTALA in Texas, meaning that women in a far larger and more populous state would still be denied emergency abortions. This case, too, has been appealed to the Supreme Court.

Moreover, the federal emergency-treatment law has teeth only if an administration chooses to enforce it, by fining hospitals or excluding them from Medicare and Medicaid when they fail to comply. The Biden administration has issued guidance that says it may sanction hospitals and doctors refusing to provide emergency abortion care, and as vice president, Kamala Harris has been a particularly vocal advocate for abortion access. A Trump administration could simply decide not to enforce the rule—a proposal that is outlined explicitly in Project 2025, the Heritage Foundation’s blueprint for a second Trump term. If the emergency-treatment law is a mere “Band-Aid,” as multiple doctors put it to me, it is one that can be easily torn off.

EMTALA is also limited in scope. It covers only patients who show up at an ER, and only those with emergency pregnancy complications. It would not apply to women in Idaho whose pregnancies are made more dangerous by a range of serious but not yet urgent conditions (to say nothing of the women who might want to end a pregnancy for any number of nonmedical reasons). It would not apply to the woman carrying triplets who, as an MFM recounted to me, wanted a reduction to twins because the third fetus had no skull and thus could not live. She had to go out of state to have the procedure—tantamount to an abortion for just one fetus—which made the pregnancy safer for her and the remaining babies. And it did not apply when Kayla Smith, already grieving for her unborn son, worried about preeclampsia. Her family ultimately left Idaho for Washington, so she could have another child in a safer state; her younger daughter was born in late 2023.

[From the June 1969 issue: The right of abortion]

Smith has joined a lawsuit filed by the Center for Reproductive Rights challenging the limited scope of exceptions under Idaho’s ban. A group in Idaho is also planning a ballot initiative that will put the question of abortion to voters—but not until 2026. In the meantime, doctors still want Idaho to add medical exceptions to the law. After the disappointingly narrow exceptions the state legislature passed in 2023, it did nothing more in its 2024 session. A hearing that Thomson was slated to speak at this spring got canceled, last minute, by Republicans, who control the legislature.

Still, Thomson told me she was set on staying in Idaho. She and her husband had moved their family here 11 years ago because they wanted their four kids to “feel like they’re from somewhere.” Having grown up in a Navy family, she’d moved every few years during her own childhood before joining the military for medical school and continuing to move every few years as a military doctor. When her son was just 14 months old, she deployed to Iraq. She got her job in Idaho after that. When she and her husband bought their house, she told him this was the house she planned to live in for the rest of her life.

In the past two years, she’d seriously wavered on that decision for the first time. The moral distress of practicing under the ban had sent her to see a counselor. “I was in a war zone,” she told me, “and I didn’t see a counselor.” This past fall, she came up with a backup plan: If she had to, she could stop practicing in Idaho and become a traveling doctor, seeing patients in other states.

But then she thought about all the women in Idaho who couldn’t afford to leave the state for care. And she thought of her kids, especially her three girls, who would soon no longer be girls. The eldest is 20, the same age as a patient whose baby she had recently delivered. “This could be my daughter,” Thomson thought. If everyone like her left, she wondered, who would take care of her daughters?

This article appears in the October 2024 print edition with the headline “What Abortion Bans Do to Doctors.”

A Food-Allergy Fix Hiding in Plain Sight

2024-09-09T11:27:35-04:00

Tami McGraw used to be so allergic to red meat that even fumes from cooking might send her into anaphylactic shock. She couldn’t fry sausages for her family. She couldn’t go to cookouts with friends. Once, she passed out driving home with her son after accidentally inhaling fumes while volunteering at the school cafeteria. “That’s the closest I came to dying,” she told me. Every whiff of sizzling meat, every journey out of the house came spring-loaded with danger.

The episode in the school cafeteria rattled McGraw so much that she brought up with her allergist a then-unorthodox therapy called Xolair. Xolair is a bimonthly or monthly injection originally approved in 2003 for asthma, which McGraw has been diagnosed with. But doctors had long suspected that Xolair could do more, and they had already started noticing an intriguing curious side effect in asthma patients: Their allergic reactions to food were diminished too.

McGraw’s doctor agreed to prescribe her Xolair—officially for asthma but unofficially with the hope of treating her allergy. Soon, she found she could cook red meat in the house again. Then, she could eat it. She had a bite of bacon, a bite of hamburger. All good. McGraw still doesn’t care for red meat—doctors recommend continuing avoidance, and she had developed a distaste after her allergic reactions anyway—but she no longer worries about a cross-contaminated utensil or fumes lingering in the air. “I could go in places without fear,” she said. “I could go out to eat.” Since 2016, she has been living, in other words, a pretty normal life.

Earlier this year—more than 20 years after Xolair first came to market and eight years after it transformed McGraw’s life—Xolair was approved for food allergies. The drug is finally available to the millions of Americans with severe, sometimes-fatal allergic reactions. Rates of food allergies have been rising this entire time, nearly doubling in children since Xolair was initially developed. Though it is not meant to be a cure, the drug provides enough protection against accidental exposure to bring tremendous relief.

“It’s a complete life-changer,” says Robert Wood, a pediatric allergist at Johns Hopkins who co-led the study that recently got Xolair green-lighted for food allergies. And it’s been a long time coming.

Xolair works by intercepting immune molecules called IgE, known to be a trigger in allergic reactions. For this reason, its potential to calm food allergies was apparent from the very beginning, but a frustrating series of events in the 2000s kept drugs like it out of many patients’ reach.

First, a similar drug that was ahead of Xolair in development was unceremoniously shelved in 2004—despite promising results in treating peanut allergy—as the result of a bitter legal battle between its manufacturer and Xolair’s. This cleared the path for Xolair, which suffered a different setback: Its clinical trial for peanut allergy was terminated early in 2006 for safety reasons unrelated to the drug itself. Two children had severe reactions when they were being “challenged” with peanuts to gauge the extent of their allergy. Xolair’s manufacturer deemed the peanut challenges, and therefore the whole trial, too risky. The incomplete results from the study, when they were published, nevertheless looked encouraging.

Throughout this period, Xolair was available to patients with asthma, and in 2014, it was also approved for idiopathic, or unexplained, chronic hives. Both of these conditions tend to involve high levels of IgE, the molecule that Xolair blocks. They often overlap with food allergies, says Scott Commins, an allergist at the University of North Carolina, who is also McGraw’s doctor. This led to a two-tier system: Commins could offer Xolair to food-allergy patients who, like McGraw, also had asthma or chronic hives. Patients who didn’t have multiple conditions were out of luck. They could get Xolair off-label, but few could afford it. Insurance companies do not cover off-label prescriptions, and the list price runs $30,000 to $60,000 a year. “We were definitely not able to use it as much as we wanted,” Commins told me.

To secure FDA approval and insurance coverage of Xolair for food allergies, patients needed more than promising preliminary data and anecdotal stories: They needed a big, definitive clinical trial. In 2019, Wood and other researchers finally secured the funding for such a trial, dubbed OUtMATCH, which was a collaboration between the National Institute of Allergy and Infectious Diseases and Xolair’s manufacturers. The results of the first of its three stages were published this February: After 16 weeks on Xolair, two-thirds of participants allergic to peanuts and at least two other foods (such as milk and eggs) were able to eat the equivalent of two and a half peanuts. A similar proportion could eat their other allergy foods too. This study persuaded the FDA to approve the drug for food allergies.

Xolair is most life-changing for patients with allergies that are difficult to avoid—either because their allergen is rarely labeled or because they react to even trace amounts, or both. That includes people like McGraw, and it includes people like Christine Robinson, whom I interviewed five years ago about her corn allergy. Chemicals derived from corn, it turns out, are hidden just about everywhere in processed food: Robinson would react to bottled water, iced tea, table salt, bagged salads, frozen fish, the wax on apples and oranges. She went out with an armament of Benadryl, Zantac, prednisone, and EpiPens, the last of which delivers a jolt of emergency epinephrine to counteract anaphylaxis. Since we first talked, she has also started Xolair. “It’s amazing, really,” she told me recently. She still doesn’t eat corn, but her reactivity is much lower. “The reactions are not an emergency now; they are an annoyance.” Recently, her EpiPen expired before she had occasion to use it.

Patients with only mild allergies, on the other hand, might not find an injection every two or four weeks worth the trouble. And Xolair did not work as well for one-third of people in the trial. Predicting who will or will not respond to Xolair and understanding why is one of the big remaining questions ahead, says Scott Sicherer, an allergist at Mount Sinai and a principal investigator on the OUtMATCH trial.

Xolair also has the practical advantage of treating multiple food allergies at once, says Stacie Jones, a pediatric allergist at Arkansas Children’s Hospital who is also part of the OUtMATCH study. The only other treatment available, oral immunotherapy, is food specific: Patients ingest a tiny daily amount of their allergy food, gradually upping the dose over time until they reach a maintenance dose. An oral immunotherapy for peanuts called Palforzia is approved, and some allergy doctors now offer custom regimens for a number of foods. But the process can be arduous, and patients with multiple allergies generally need to go through it for each food.

Xolair and oral immunotherapy potentially could be used together. The second of the three stages of the OUtMATCH trial was designed to investigate whether adding Xolair can make oral immunotherapy safer and more effective. The third stage follows participants after they discontinue Xolair, and as some reincorporate allergy foods back into their diet. “What we’re learning in the clinic and in the study is that most people can actually start to eat the food they’re allergic to,” Wood told me, adding that the results would be published in the coming months. The data, if convincing, could dramatically change how Xolair is used—the drug is currently approved only alongside strict avoidance.

In our conversation, Wood also evinced more than a hint of impatience about the two decades needed to make Xolair available for food allergies in the first place. “It’s honestly quite ridiculous that it took this long,” he told me. “But at least we’re here now.”

Why People Are Breaking Open Their Mounjaro Pens

2024-08-15T11:24:34-04:00

Updated at 2:49 p.m. on August 15, 2024

By the time Lisa started breaking open her Mounjaro pens with pliers, she had run out of other ideas. She was 300 pounds. She had already tried bariatric surgery. (It had limited success.) She had tried getting her insurance company to cover Mounjaro. (It stopped after a month.) She had tried a cheaper copycat version from a compounding pharmacy. (It didn’t work as well, and she worried about what she was actually getting.) “I was absolutely desperate to stay on,” she says, but she could not afford the sticker price.

That’s when she learned online about a money-saving loophole: She could split a maximum-strength Mounjaro pen into the smaller doses she needed. (The single-use injection pens come in multiple concentrations that cost the same.) One pen became as many as six. A year of dose-splitting later, she has lost 75 pounds—at a fraction of the original cost.

Lisa is among a small number of patients who have taken to hacking their injection pens. (I’m identifying Lisa and other patients in this story by only their first names to protect their medical privacy.) As new drugs used for weight loss—which go by the brand names Mounjaro, Ozempic, Zepbound, Wegovy—have skyrocketed in popularity, patients have sometimes found that the one-size-fits-all dosing does not, in fact, fit all. Most dose-splitters are trying to save money, but others are managing side effects. They swap tips online. They take risks because they want to stay on a medication that is, by many accounts, utterly life-changing.

Breaking open the pens is risky; it can introduce microbes into the injected drug, which can lead to infection. “We do not condone these practices,”a spokesperson from Novo Nordisk, which makes Ozempic and Wegovy, told me. “People using Mounjaro or Zepbound should never ration,” a spokesperson from their manufacturer, Eli Lilly, reiterated. These drugs are sold in pens of different concentrations because patients need to ramp up gradually from a low dose to minimize side effects, before getting on the highest doses indefinitely for weight maintenance.

Doctors uniformly told me they did not recommend breaking open the injection pens. At the same time, they understood the forces that have pushed patients into doing so: Mounjaro, Ozempic, Zepbound, and Wegovy—which all mimic a natural hormone called GLP-1—are far more effective for weight loss than any obesity medications that came before them. They are so powerful, but so expensive that demand has far outstripped the willingness and ability of insurance to pay.

“There’s a lot of desperation that we’re seeing in our practice, and people looking for all kinds of work-arounds,” says Laura Davisson, the director of medical weight management at West Virginia University Health Sciences, who had many patients lose coverage after the state’s public-employee insurance stopped covering the new drugs. In rural communities especially, such as where Sarah Ro, the director of a weight-management program at the University of North Carolina, practices, obesity rates are high and few patients can afford to pay out of pocket. She’s heard of patients splitting doses to save money. “Oh my goodness,” she told me. “I’m going, What have we created?”

Even putting costs aside, fixed-dose injection pens are not ideal for patients. After Ozempic was approved in 2017—the first of these drugs to be—doctors noticed that the standard regimen of increasing doses in four-week increments did not work for every patient. Some patients had debilitating side effects of nausea, diarrhea, or constipation at even the lowest, 0.25 mg, dose; they might need to start at only half or a quarter of that. Some needed to go up more slowly with in-between doses. And some might be “super responders,” losing weight so quickly that they never need the full dose at all.

Ozempic doses are actually quite easy to adjust, even if patients aren’t technically supposed to. Unlike subsequent drugs, Ozempic is packaged in multidose pens with dials. Only the official dosages are labeled—0.25 mg, 0.5 mg, 1 mg, 2 mg—but people quickly reverse-engineered how many dozens of clicks correspond to one milligram. Novo Nordisk officially cautions users to “not set the dose by counting the number of clicks.” But doctors told me they consider counting clicks to be pretty safe, and some even advised their patients on Ozempic to do so if a dose needs adjusting. “I don’t have a problem with it,” Davisson told me. Novo Nordisk uses the same pen for its insulin, allowing people with diabetes to choose the amount of insulin they need.

Wegovy contains the same active ingredient as Ozempic, semaglutide, but is approved for treating obesity instead of diabetes. (Using Ozempic for weight loss is off-label, and typically never covered by insurance.) Wegovy also comes at a slightly higher maximum dose and is packaged differently, in single-use, single-dose pens. That means patients on Wegovy cannot count clicks to adjust their doses—even though it contains, once again, the exact same drug as Ozempic. “It’s so frustrating,” says Katherine Saunders, an obesity-medicine doctor at Weill Cornell Medicine. Saunders told me she almost never follows the exact ramp-up schedule laid out by drug manufacturers, instead fine-tuning it based on how much weight a patient is losing and how many side effects they’re having. Single-dose fixed pens hamper her ability to personalize the regimen. When I asked if she would prefer flexible dosing as a doctor, she answered, “Yes, oh my gosh, yes, yes.” In Canada and Europe, Wegovy is actually sold in clickable pens. “We would love to have that flexibility,” says Fatima Cody Stanford, an obesity-medicine doctor at Harvard.

In the U.S., Mounjaro and Zepbound are packaged only in nonadjustable single-dose pens. (They both contain the same ingredient, tirzepatide, at the same doses, but Mounjaro is approved for diabetes and Zepbound for obesity.) This is why patients on tirzepatide—which is considered slightly more effective than the semaglutide in Ozempic or Wegovy—have gone to more extreme methods of breaking open these pens. The process is a lot more complicated, requiring sterile medical supplies and math to get the correct dosage.

Nicole started dose-splitting because she had awful vomiting and vertigo the day she increased her dosage from 2.5 mg to 5 mg. “I really was considering going to the emergency room,” she told me. She learned to split her first pen so she could ramp up more slowly with intermediate doses; the cost-saving is nice, too. Another dose-splitter, Phil, told me he has taught several of his friends how to split Mounjaro pens too. “For me, that’s really just a harm-reduction principle,” he said. “There are so many people this drug could be so life-changing for, but it’s just utterly, ruinously expensive.”

For her part, Lisa compared the risks of dose-splitting with the risks of her alternatives: Either going to a compounding pharmacy, whose copycat drugs might be unreliable or impure, or continuing to live with obesity. “I feel like this is an acceptable risk for me versus the risk of carrying an extra 130 pounds,” she said. She has another 55 pounds to go before she gets to that target weight loss of 130. Over time, the dose she needs has gone up, as it typically does. The six doses she got out of one pen became four, three, two, and now just 1.5. Eventually, she’ll probably need to get on the full maximum dose. She’s glad for the money she’s already saved, but dose-splitting can only work for so long. For most people, it’s not a long-term solution for a long-term medication.

What have you experienced while taking GLP-1 drugs? Share your story with us.

(By writing to us, you are agreeing to let The Atlantic use your response, which we may edit for length or clarity. You are also agreeing that The Atlantic’s reporters may contact you at the address provided to discuss whether you would be willing to be interviewed.)

This article originally stated that a patient had bloodshot eyes while taking Mounjaro. In fact, she experienced this side effect with a different drug.

Why I Buy German Toothpaste Now

2024-07-23T11:14:02-04:00

For as long as I can remember, I have bought into the gospel of fluoride, believing that my teeth would surely rot out of my head without its protection. So it felt a little bit illicit, recently, when I purchased a box of German fluoride-free kids’ toothpaste for my daughter. The toothpaste came in blue, understated packaging—no cartoon characters or candy flavors—which I associated with German practicality. And instead of fluoride, it contained an anticavity ingredient called hydroxyapatite, vouched for by several dental researchers I interviewed for this story. Could it be, I wondered as I clicked “Buy,” that toothpaste doesn’t need to contain fluoride after all?

The scientific case for hydroxyapatite toothpaste is actually quite simple: Composed of calcium and phosphate, hydroxyapatite is the very mineral that primarily makes up our bones and teeth. Tooth enamel, the hard protective outer layer, is naturally about 96 percent hydroxyapatite. NASA researchers first patented an idea for repairing teeth with a hydroxyapatite precursor in the 1970s; nothing came of it then, but a Japanese company acquired the patent and eventually created a popular toothpaste called Apagard. Hydroxyapatite toothpaste has been approved for cavity prevention in Japan since 1993. It is also approved in Canada and endorsed by the Canadian Dental Association. And it’s sold in Europe, where the European Commission has deemed the ingredient safe in toothpaste.

In the United States, however, fluoride still reigns supreme. You likely won’t find toothpaste containing hydroxyapatite at your corner drugstore. A few boutique hydroxyapatite-based brands have popped up, but they cannot market themselves for cavity prevention without FDA approval, a long and expensive process that no hydroxyapatite toothpaste has yet gone through. The American Dental Association (ADA), meanwhile, gives its Seal of Acceptance only to toothpastes that contain fluoride.

Fluoride does work remarkably well: It is incorporated into the enamel structure of the tooth itself, forming a mineral crystal that is significantly more resistant to cavity-causing acid than the tooth’s natural material, according to Bernhard Ganss, a scientist at the University of Toronto’s Faculty of Dentistry. “The dogma in dentistry has always been: Fluoride is a good thing.”

The trouble with fluoride is that, at very high levels, it becomes a bad thing. Ingesting too much can lead to a condition called fluorosis, in which teeth become mottled in mild cases or structurally weak in more serious ones. The same can happen to bones. More controversially, high levels of fluoride in drinking water—higher than the level recommended in the U.S., but lower than the current EPA limit—have been linked to lower IQ in children. Toothpaste typically contains more than 1,000 times the fluoride recommended in drinking water. We use much less toothpaste than water, of course, and it’s not meant to be swallowed, but young children do not spit out toothpaste reliably.

Hydroxyapatite is a way to sidestep the fluoride controversy. It offers the anticavity benefits of fluoride, but without the risks. Bennett Amaechi, a dentistry professor at the University of Texas Health Science Center at San Antonio, says he now recommends it to parents who have concerns about fluoride. He has collaborated with toothpaste manufacturers to study hydroxyapatite, but Felicitas Bidlack told me the same thing about its utility. Bidlack is not a dentist, but she is a tooth enamel researcher, recommended to me by the American Dental Association, which one could hardly accuse of being anti-fluoride. Yet for kids under 2 still learning not to swallow toothpaste, she would likely choose hydroxyapatite. “That’s what I would do as a mother,” she told me.

Fluoride toothpaste is in a bit of catch-22, Bidlack added. Sweet candy flavors, bright colors, and glitter can make toothpaste enticing enough for kids to want to brush their teeth, but if it’s too enticing, kids might simply eat it. “If you provide fluoride with this good-tasting goo that they put in their mouths, there is definitely a risk of unintentional ingestion,” says Ganss, who has published papers on hydroxyapatite in collaboration with scientists from the Dr. Wolff Group, a German business that manufactures toothpaste. He went even further: For very young kids, “I would actually really stand up and say no fluoride, period.”

I found these conversations clarifying, as they cut through the contradictory advice I’ve been given about fluoride for my 1-year-old. Toothpaste marketed to kids under 2 in the U.S. does not, in fact, contain fluoride (it usually contains a sugar alcohol called xylitol), and toothpastes that do contain fluoride are labeled as unsuitable for kids younger than 2 unless instructed by a doctor. But the American Academy of Pediatrics, whose guidelines our pediatrician repeated, says to use fluoride toothpaste as soon as the first tooth appears—though only a rice-size smear, which would limit exposure to fluoride. So is fluoride good or not? Is it safe or not? Wouldn’t it be nice not to deal with fluoride at all?

Hydroxyapatite’s track record is not as long as fluoride’s, but the evidence so far looks good: In clinical trials that have followed kids or adults for six months to a year and a half—largely funded by toothpaste manufacturers—hydroxyapatite and fluoride have come out about equally protective against cavities. Hydroxyapatite is chemically not as resistant to cavity-causing acid as the mineral formed by fluoride, but Ganss says that daily brushing might replenish hydroxyapatite often enough that the real-world protection is the same. The mineral may also have some other benefits: In studies, hydroxyapatite has helped reduce tooth sensitivity and the amount of bacteria stuck to teeth. The one thing it cannot do is resolve the controversy over adding fluoride to drinking water, which is done as a public-health measure in most parts of the U.S. to prevent tooth decay. Hydroxyapatite can’t be put into drinking water, because it doesn’t dissolve at a neutral pH. “The tap water would be milky,” Ganss says. “It would probably clog all your pipes within a few days or so.”

The researchers I spoke with thought fluoride still had its uses, particularly in treatments and toothpaste for adults who know not to swallow too much. Amaechi still brushes with the Colgate he’s used all his life, as he sees no reason for him, as an adult, to change his habits. But he does recommend hydroxyapatite in specific situations—for example, patients with dry mouth, he says, may particularly benefit from this formulation.

Age 2 isn't some magic threshold at which the calculus regarding toothpaste in small children suddenly changes, of course. Canada, in fact, recommends holding off on fluoride for most kids until age 3; fluoride-free options for kids are now expanding in the U.S., even without FDA approval of hydroxyapatite. The German children’s toothpaste came only in boring white mint, but I found a number of brands in the U.S. already selling more tempting flavors, such as orange creamsicle and birthday cake.

Ozempic Patients Need an Off-Ramp

2024-05-22T11:09:39-04:00

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When patients start on the latest obesity drugs, they find that their food cravings drop away, and then the pounds do too. But when patients go off the drugs, the gears shift into reverse: The food cravings creep back, and then the pounds do too. Within a year of stopping semaglutide—better known by its brand names Wegovy or Ozempic—people regain, on average, two-thirds of the weight they lost. Tirzepatide, also known as Zepbound or Mounjaro, follows a similar pattern. And so the conventional medical wisdom now holds that these obesity drugs are meant to be taken indefinitely, possibly for a lifetime.

To pharmaceutical companies selling the blockbuster drugs—known collectively as GLP-1 drugs, after the natural hormone they mimic—that might be a pretty good proposition. To patients paying more than $1,000 a month out of pocket, not so much. Most Americans simply cannot afford the cost month after month after month.

This has forced some doctors to get creative, devising regimens to sub in cheaper, if less well-known, alternatives. GLP-1 drugs do work remarkably well, inducing more weight loss more quickly than any other obesity medication on the market, but some doctors now wonder whether patients need to be on GLP-1 drugs, specifically, forever. “What if we do a short-term investment, use it for six months to a year to get 50 pounds off?” asks Sarah Ro, an obesity-medicine doctor and the director of the University of North Carolina Physicians Network Weight Management Program. Then, as she and other doctors are now exploring, patients might transition to older, less expensive alternatives for long-term weight maintenance.

In fact, Ro has already helped patients—she estimates hundreds—make the switch out of financial necessity. Few of her patients in rural North Carolina have insurance that covers the new obesity drugs, and few can afford to continually pay out of pocket. In April, many also lost coverage when North Carolina’s health insurance for state employees abruptly cut off GLP-1 drugs for obesity. Ro switched her patients to older drugs such as topiramate, phentermine, metformin, and bupropion/naltrexone, plus lifestyle counseling. It’s not exactly an ideal solution, as these medications are generally considered less effective—they lead to about half as much weight loss as GLP-1 drugs do—but it is a far less expensive one. When prescribed as generics, Ro told me, a month’s supply of one of these drugs might cost as little as $10.

Jamy Ard, an obesity-medicine doctor at Wake Forest University School of Medicine, has also switched regimens for patients who lost coverage of GLP-1 drugs after retiring and getting on Medicare, which currently does not pay for any drugs to treat obesity. (Like many researchers in the field, Ard has received grants and consulting fees from companies behind obesity drugs.) Doctors I spoke with didn’t know of any studies about switching from GLP-1 drugs to older ones, but Ard says this research is a practical necessity in the United States. With GLP-1 medications exploding in popularity, more and more patients taking them will suddenly lose coverage when they hit retirement age and go on Medicare. “Now I’ve got to figure out, well, how do I treat them?” he told me.

Long-term data on the older drugs themselves are, in fact, pretty sparse, despite the drugs having been available for years and years. Until Ozempic came along, obesity drugs were not a lucrative market, so companies weren’t interested in funding the long and very expensive trials that follow patients for several years. “Studies like that cost a fortune,” Louis Aronne, an obesity-medicine doctor at Weill Cornell Medicine, told me. Some of the longest-term follow-up data about these drugs come from patients at his practice in Manhattan—not a representative population, he admits—which he published in a five-year study funded by the National Institutes of Health. (Aronne has also received grants and consulting fees from the makers of obesity drugs.)

How patients do after switching from GLP-1 to older drugs is entirely anecdotal, but so far outcomes do seem to vary quite a bit. A small minority of patients who stop GLP-1 injections are actually able to maintain their weight on diet and exercise, without any additional medications. Others may find that the older pills are simply not effective for them. In Ro’s experience, about 50 to 60 percent of her patients have so far successfully kept the weight off using one or more older drugs, on top of lifestyle changes such as cutting out fast food and sugary sodas.

The best drug to switch to may also depend on the patient. Each of the older medications works differently, hitting different biological pathways. The combination of naltrexone and bupropion, for example, makes food less pleasurable and seems to work especially well in people with a tendency toward emotional eating, Ard said. Topiramate, meanwhile, makes carbonated drinks unpleasant, which could help patients who drink a lot of soda. The older drugs also have different side effects. Aronne rattled off for me a list of health risks that might rule out a particular drug for a particular patient: seizures for bupropion, or glaucoma for topiramate. Finding the most effective and best-tolerated drug for a patient may take some trial and error.

Doctors are now discovering that some patients can maintain the weight they lost on lower or less frequent doses of GLP-1 drugs. “For the first time in my career, we’re lowering the dose of medicines,” Aronne said. Just reducing the dose doesn’t save money, though, as lower-dose injection pens cost the same as those with higher doses. However, by instead extending the time between doses from the standard seven days to a longer 10-day interval, doctors told me, some patients have been able to stretch their supplies.

But tapering off obesity medications entirely, GLP-1 or otherwise, will probably not be possible for most patients. Weight loss tends to trigger a powerful set of compensatory mechanisms in the body, which evolved long ago to protect us from starvation. The more weight we lose, the more the body fights back. The fight never quite goes away, and most patients will likely require some kind of continued intervention just to stay at a lower weight. Long-term weight maintenance has always been the “holy grail” of obesity treatment, Susan Yanovski, a co-director of the Office of Obesity Research at the National Institutes of Health told me. The best maintenance strategy—whether it involves GLP-1 drugs, and at what dose—may ultimately be pretty individual. What works best and for whom still needs to be studied. “These are really good research questions,” Yanovski said. But they are not necessarily the questions that pharmaceutical companies focused on developing new meds are most keen to answer.

In time, the current crop of GLP-1 drugs will eventually become available as generics, too, and cost may no longer drive patients to seek out cheaper alternatives. But for now, it very much does.

A Dentist Found a Jawbone in a Floor Tile

2024-04-22T16:05:54-04:00

Recently, a man visiting his parents’ newly renovated home recognized an eerily familiar white curve in their tile floor. To the man, a dentist, it looked just like a jawbone. He could even count the teeth—one, two, three, four, five, at least. They seemed much like the ones he stares at all day at work.

The jawbone appeared at once very humanlike and very old, and the dentist took his suspicions to Reddit. Could it be that his parents’ floor tile contains a rare human fossil? Quite possibly. It’s “clearly hominin,” John Hawks, a paleoanthropologist at the University of Wisconsin at Madison who also blogged about the discovery, told me in an email. (Hominin refers to a group including modern humans, archaic humans such as Neanderthals, and all of their ancestors.) It is too soon to say exactly how old the jawbone is or exactly which hominin it belonged to, but signs point to something—or someone—far older than modern humans. “We can see that it is thick and with large teeth,” Amélie Vialet, a paleoanthropologist at the Muséum National d'Histoire Naturelle in Paris, wrote in an excited email to me about the jawbone. “That’s archaic!”

An international team of researchers, including Vialet, is now in contact with the dentist to study the floor tile. (I’m not naming him for privacy reasons.) This thin slice of jawbone has a story to tell—about a life lived long ago, in a world very different from ours. It is in fragments of hominin bone like this one that we begin to understand our past as humans.

How could a hominin bone have ended up in someone’s tiled floor in the first place? Travertine, the type of rock from which this tile was cut, is a popular building material used perhaps most famously by ancient Romans to construct the Colosseum. Today, a good deal of the world’s travertine—including the floor tile with the jawbone, according to the dentist—is quarried in Turkey, from a region where the stone famously forms natural thermal pools that cascade like jewels down the hillside. Travertine tends to be found near hot springs; when mineral-rich water gurgles to the surface, it leaves a thin shell over everything that it touches. In time, the layers accrue into thick, opaque travertine rock. If in the middle of this process a leaf falls in or an animal dies nearby, it too will become entombed in the rock. “Fossils are relatively common in travertine,” says Andrew Leier, a geologist at the University of South Carolina.

Hominin fossils, specifically, are rare, but at least one has been found in Turkish travertine before. In 2002, a Turkish geologist named M. Cihat Alçiçek discovered a slice of human-looking skull sitting on a shelf in a tile factory. He brought the 35-millimeter-thick fragment to John Kappelman, an anthropologist at the University of Texas at Austin, and later also to Vialet in Paris. The skull turned out to belong to Homo erectus, an archaic human species that walked the Earth more than 1 million years ago, long before modern humans. Vialet thinks the newly discovered jawbone could be just as old.

Vialet and her collaborators are now hoping to extract the tile, ideally intact, from the hallway where it’s been cemented in place. (The dentist is soliciting suggestions on Reddit for how to do so without also destroying his parents’ floor.) Then, chemical signatures in the rock can be used to date the fossil. Vialet also hopes to generate a 3-D model of the jawbone with micro-CT scanning, tracing the curve of the mandible and the roots of the teeth to find anatomical clues about its origin.

The teeth could prove to be the real gold mine. Their hard enamel likely contains carbon, oxygen, and nitrogen isotopes whose presence could hint at what the hominin once ate. Shooting high-energy X-rays at the teeth can also reveal how quickly they grew, which is useful because different hominins developed at different rates, Kappelman told me in an email. The spongy insides of teeth also tend to be good sources of ancient DNA. (Given the high temperature of the hot springs where travertine deposits form, Kappelman thinks DNA probably wasn’t well preserved, but extracting it is still worth a try.) Bit by bit, researchers will begin to piece together a portrait of the hominin, who died by a hot spring so many eons ago only to be unearthed and then cut into floor tile for someone’s home.

Paleontologists and quarries, as Hawks wrote in his blog post, exist in an “uneasy symbiosis.” The industrial extraction process unearths far more rock than scientists could ever hope to, but it leaves science at the whim of commercial practice. Alçiçek, the Turkish geologist who spotted the skull in the early 2000s, says far fewer fossils are being found in travertine quarries these days because the technology has changed. Twenty years ago, companies were able to extract only the “uppermost part of the travertine body, which is rich in fossils,” he wrote in an email, but now they can dig deeper, into layers devoid of fossils. Today, he says, discovering a fossil in the travertine quarries is rare.

Industrial quarrying can also damage the fossils it does uncover. That Homo erectus skull, for example, was already chopped up by the time Alçiçek saw it, and the rest has never been found. In 2007, back when the skull discovery was first announced, his collaborator Kappelman mused in a draft of a press release about where other pieces might have ended up. “Turkish travertine is sold all around the world today,” Kappelman said back then. “Some lucky shopper at Home Depot might just be surprised to find a slice of Homo erectus entombed in her kitchen countertop.”

To this day, Kappelman told me, he still goes straight to the travertine-tile section whenever he shops at Home Depot. The rest of this jawbone has to be somewhere.

The Bone-Marrow-Transplant Revolution

2024-04-18T08:23:24-04:00

In the fall of 2021, Gabriel Arias felt like his body was “rotting from the inside.” He was diagnosed with acute myeloid leukemia, a form of blood cancer so aggressive that doctors had him hospitalized the day of his biopsy. In cases like his, the ideal treatment is a transplant. Arias’s cancer-prone blood cells needed to be destroyed and replaced with healthy ones taken from the bone marrow or blood of a donor who matched him biologically. Fortunately, doctors found him a match in the volunteer-donor registries—a man in Poland. Unfortunately, Arias’s single match in the entire world was no longer available to donate.

In the past, the road to transplant might have ended here, but a medical advance had dramatically expanded the pool of donors for patients such as Arias. With the right drug, Arias could now get a transplant from his brother, a partial match, or, as he ultimately chose, he could join a clinical trial in which his donor would be a stranger who shared just eight of 10 markers used in bone-marrow transplants. Under this looser standard, Arias’s registry matches multiplied from one to more than 200. “It really is a game changer,” says Steve Devine, the chief medical officer of the nonprofit NMDP, which runs the U.S. donor registry and has led research into the use of mismatched donors. Today, agonizing searches for a matched donor are largely a thing of the past.

The drug powering this breakthrough is actually very old. Cyclophosphamide was first developed in the 1950s for chemotherapy. Fifty years later, researchers at Johns Hopkins began studying whether it could be repurposed to prevent a common and sometimes deadly complication of bone-marrow transplants called graft-versus-host disease, where the donor’s white blood cells—which form the recipient’s new immune system—attack the rest of the body as foreign. The bigger the mismatch between donor and recipient, the more likely this was to happen. Cyclophosphamide worked stunningly well against graft-versus-host disease: The drug cut rates of acute and severe complications by upwards of 80 percent.

Cyclophosphamide has now enabled more patients than ever to get bone-marrow transplants —more than 7,000 last year, according to NMDP. (Bone-marrow transplant is still used as an umbrella term, though many of these procedures now use cells collected from the blood rather than bone marrow, which can be done without surgery. Both versions are also known, more accurately, as hematopoietic or blood stem-cell transplants.) The field has essentially surmounted the problem of matching donors, a major barrier to transplants, Ephraim Fuchs, an oncologist at Johns Hopkins University, told me. Fuchs couldn’t remember the last time a patient failed to get a blood stem-cell transplant because they couldn’t find a donor.

It wasn’t obvious that cyclophosphamide would work so well. “I’m just going to come clean,” Devine told me. “Back in 2003 and 2005, I thought it was crazy.” Derived from a relative of mustard gas, the drug is known to be highly toxic to a variety of blood cells; in fact, doctors had long used it to kill the diseased bone marrow in patients before transplant. Why would you want to give such a drug after transplant, when the new donor cells are still precious and few? It defied a certain logic.

But as far back as the 1960s, researchers also noticed that high doses of post-transplant cyclophosphamide could prevent graft-versus-host disease in mice, even if they did not know why. Over the next few decades, scientists working away in labs learned that cyclophosphamide isn’t quite carpet-bombing the blood. It actually spares the stem cells most important to successful transplant. (Blood stem cells differentiate into all the types of red and white blood cells that a patient will need.) Why cyclophosphamide works so well against graft-versus-host disease is still unclear, but the drug also seems to selectively kill white blood cells active in the disease while sparing those that quell the immune system.

By the late ’90s, doctors saw a clear need to expand the search for donors. Bone-marrow transplants are most successful when donor and recipient share the same markers, known as HLA, which are protein tags our cells use to distinguish self from nonself. We inherit HLA markers from our parents, so siblings have about a one-in-four chance of being perfectly matched. As families got smaller in the 20th century, though, the likelihood of a sibling match fell. Donor registries such as NMDP were created to fill the gap, however imperfectly.

Doctors soon began coalescing around the idea of using family members who were only haploidentical, or half matched, meaning they shared at least five out of 10 HLA markers. Every child is a half match to their parents, and every parent to their child; siblings also have a 50 percent chance of being half matches. But when doctors first tried these transplants, the “outcomes were horrible,” Leo Luznik, an oncologist at Johns Hopkins, told me. Patients had frighteningly high rates of graft-versus-host disease, and more than half died within three years.

Based on the lab findings, Luznik, Fuchs, and other colleagues at Johns Hopkins wondered if post-transplant cyclophosphamide could help. The pharmaceutical companies that made it were uninterested in funding any research, Luznik said, because “it was an old, very cheap drug." With government grants, however, the team was able to prove that cyclophosphamide got the rate of graft-versus-disease as low as in matched sibling transplants. By the late 2000s, transplants with half-matched family members were becoming routine.

Still, not every patient will have a sibling or parent or child who can donate. Doctors began wondering if cyclophosphamide could work for unrelated donors too. If only eight of the 10 markers have to be matched, then almost everyone would find a donor, even multiple donors. This was especially important for patients of mixed or non-European ancestry, who have a harder time finding unrelated donors, because people of those backgrounds make up a smaller proportion of registry donors and because they can carry a more diverse set of HLA markers. Two-thirds of white people can find a fully matched registry donor, but that number drops to 23 percent for Black Americans and 41 percent for Asians or Pacific Islanders.

Amelia Johnson, who is half Indian and half Black, was one of the first children to get a transplant from a mismatched unrelated donor in a clinical trial in 2022. Her mom, Salome Sookdieopersad, remembers being told, “You guys need to start recruiting bone-marrow donors to help increase your chances.” When that still didn’t turn up an ideal match, Sookdieopersad prepared to donate to her daughter as a half match. But then Amelia was offered a spot in the clinical trial, and they decided to take it. Transplants with mismatched unrelated donors had already been tried in adults—that was Arias’s trial—and they offered other potential benefits. A younger donor, for example, has younger cells, which fare noticeably better than older ones. Amelia did end up with a bout of graft-versus-host disease; cyclophosphamide lowers the risk but not to zero. Still, the transplant was necessary to save her life, and her mom pointed out that some risk was unavoidable, no matter the type of donor: A friend of Amelia’s got graft-versus-host even with a perfectly matched one. Doctors were able to treat Amelia’s complications, and she returned to school last August. The pediatric trial she was part of is ongoing.

In adults, where more data are available, doctors are already moving ahead with mismatched, unrelated donors. Between this and half-matched family members, patients who once might have had zero donors are now finding themselves with multiple possibilities. Doctors can be choosier too: They can select the youngest donor, for example, or match on characteristics such as blood type. The larger pool of donors also prevents situations like Arias’s, in which a single matched donor who signed up years ago is no longer available, which happens with some regularity. Cyclophosphamide is now routinely used in matched transplants too, because it lowers the risk of graft-versus-host disease even further.

Arias’s mismatched unrelated donor in the trial was an anonymous 22-year-old man who lives somewhere in the United States. When Arias and I spoke last month, it had been almost exactly two years since his transplant. He’s cancer free. He and his wife just welcomed a baby girl. None of this would have likely been possible without the transplant, without the donor, without a 70-year-old drug that had been smartly repurposed.

Why a Cognitive Scientist Put a Head Cam on His Baby

2024-04-05T09:47:18-04:00

Updated at 10:03 a.m. on April 16, 2024

When Luna was seven months old, she began wearing, at the behest of her scientist father, a hot-pink helmet topped with a camera that would, for about an hour at a time, capture everything she saw, heard, and said.

Her dad, Brenden Lake, is a cognitive scientist at New York University, where he thinks about better ways to train artificial intelligence. At home, he trains human intelligence, by which I just mean that he’s a dad. On a recent Sunday morning, he held up a robot puppet and asked Luna, who was meting out her wooden toys, “That’s for robot?” “Oh, goodness!” he added in a silly Muppet voice. Luna seemed only half-interested—in the way small children are always sort of on their own planet—but a couple of minutes later, she returned to pick up the puppet. “Robot,” she said. “Robot,” she repeated, dispelling any doubt about her intentions. Her dad turned to me, surprised; he’d never heard her say “robot” before. Had she learned the word just now?

At one and a half years old, Luna has mastered a technique that current AI models still struggle with. Humans are able to learn from very few examples, meaning that even a single encounter can solidify the connection between a silver hand puppet and the phonemes that comprise robot. Artificial intelligence, by contrast, might need dozens or hundreds of examples; large language models such as the one powering ChatGPT are trained on hundreds of billions, if not trillions, of words—an inhuman amount of data. “It would take 1,000 years to hear a word count of that magnitude,” Lake told me. Given that humans require far less time—and far fewer words—to master language, could AI be trained more efficiently? Could it learn more like, say, a toddler?

These questions are what initially motivated Lake to record his daughter’s early life. (He convinced his wife with a more sentimental pitch: They could capture and replay Luna’s baby milestones.) Along with 25 or so other babies, Luna is part of the BabyView study, a project run out of Stanford that aims to capture exactly what young kids see and hear in the crucial period when they’re picking up language at a shocking speed. Lake hopes to one day feed the data from Luna and others back into his own models—to find better ways of training AI, and to find better ways of understanding how children pull off the ubiquitous yet remarkable feat of learning language.

The camera helmet in action (Wai Keen Vong)

Recent technological leaps—in artificial intelligence but also in hardware—have given scientists new tools to study developmental psychology. Cameras and microphones are now small and light enough for infants to wear for longer stretches, including at home. In the early 2010s, Michael Frank, a developmental psychologist at Stanford who now leads the BabyView study, decided along with two colleagues to put head cams on their own babies. They would track their kid’s development from about six months, when babies have enough neck strength not to be bothered by a camera, to around two and a half years, when toddlers really start to protest. Frank’s baby, however, refused to consent from the start; she absolutely loathed having anything on her head. “I didn’t have the fortitude” to continue, he told me, and his daughter dropped out. But the data collected from the two other babies—and later a third—were released in 2021 as a research data set called SAYCam.

Not long after, Frank decided to go bigger and more ambitious with BabyView, which has the same idea but would feature more babies, crisper audio, and higher-resolution video. This resulting data will be shared online, but to protect the privacy of the babies, it’ll be accessible only to institutional researchers, and participants can choose to delete videos well before they are shared.

Lake decided to sign his daughter up for BabyView—fortunately, Luna tolerates a head cam just fine—because he was immediately interested in using the SAYCam corpus to train AI. On a basic level, would it even work? His group at NYU published a much-publicized paper in Science this past winter, which showed that even AI models trained on 61 hours of low-res video, or just 1 percent of the waking hours of one SAYCam baby, could classify images that showed objects including a ball, a cat, and a car. A suite of other studies from his lab has found that AI models trained on SAYCam can form their own categories such as “food,” “vehicle,” and “clothing,” or clusters of words that correspond to nouns or verbs—as you might expect a young toddler to do as they learn about the world.

To be clear, Lake and his colleagues do not claim to have replicated in silico how toddlers actually learn. The models are trained, after all, on snippets of video and text—a poor imitation of the rich sensory experience of being in a physical world. But the studies are most interesting as proof of concept. In the field of language acquisition, for example, experts have long debated the extent to which babies are born with innate knowledge, strategies, and biases that prime them for language. On one extreme, one could posit that babies are born as blank slates. The AI models definitely started as blank slates; if training them with just a small percentage of a baby’s audiovisual experience can get them to classify balls and cats, that shows how a neural network can learn “starting from nothing,” says Wai Keen Vong, a research scientist with Lake at NYU who was the lead author on the paper. By adult-human standards, though, the model might not be that impressive; its overall accuracy was just over 60 percent. Maybe it needs more data, or maybe it needs a different way of learning.

This is so where things could get interesting. Lake would like to equip artificial intelligence with some of the strategies babies seem to display in lab experiments. For example, when young children are presented with a new word—such as kettle—they seem to instinctively know that kettle refers to the entirety of the kettle, not just to its handle or its material or its color. When they are presented with two objects—one familiar and one unfamiliar—they will assume that a new word they hear refers to the new object. These strategies likely help babies sift through the cluttered, chaotic world of their everyday life, and they might help artificial intelligence learn more like a child too, though AI is far, far from actually imitating a child.

That said, AI models could also inspire new ideas about how children learn. Chen Yu, a developmental psychologist at the University of Texas at Austin, told me about a study he conducted with his collaborators, in which parents and children wore head cams as they played with toys in a lab. Curiously, Yu and his collaborators noticed that a computer vision model trained on the child’s POV outperformed one trained on the parents’. What about a child’s perspective is more conducive to learning? They wondered if children were manipulating the toys more thoroughly, turning them back and forth to see the objects from different angles. With these AI-enabled approaches, Yu said, researchers can generate new hypotheses that can then be tested back in the lab. Linda Smith, a frequent collaborator of Yu’s and a longtime researcher of children’s cognitive development at Indiana University, told me that when she got her start, decades ago, “artificial intelligence and human cognition were one field. It was all the same people.” The fields may have since diverged, but the overlap still makes perfect sense.

In his academic career, Lake, who had previously taught an AI model how handwriting works, has also been seeking out ways to create an AI that learns more like a human. This naturally led him to how children learn. “Children are the most impressive learners in the known universe,” he told me. After having kids of his own, he thought parenting might inspire fresh insights for his research. Has it? I probed, curious because I too have a 1-year-old at home, whose intellectual progression is possibly the most remarkable thing I have ever witnessed. Not really, he admitted. Watching children learn is so fascinating, so surprising, so fun. But the process is also so intuitive—if it were that easy for any parent to understand how their child learns, wouldn’t we have figured it out already?

This article originally misidentified Chen Yu's employer as the University of Austin.