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The state of Florida is trying out a new approach to measles control: No one will be forced to not get sick.

Joseph Ladapo, the state’s top health official, announced this week that the six cases of the disease reported among students at an elementary school in Weston, near Fort Lauderdale, do not merit emergency action to prevent unvaccinated students from attending class. Temporary exclusions of that kind while an outbreak is ongoing are part of the normal public-health response to measles clusters, as a means of both protecting susceptible children and preventing further viral spread. But Ladapo is going his own way. “Due to the high immunity rate in the community, as well as the burden on families and educational cost of healthy children missing school,” he said in a letter released on Tuesday, the state’s health department “is deferring to parents or guardians to make decisions about school attendance.”

That decision came off as brazen, even for an administration that has made systematic efforts to lower vaccination rates among its constituents over the past two years. Ladapo’s letter acknowledges the benefits of vaccination, as well as the fact that vulnerable children are “normally recommended” to stay home. Still, it doesn’t bother giving local parents the bare-minimum advice that all kids who are able should get their MMR (measles, mumps, and rubella) shots, Dorit Reiss, a professor and vaccine-policy expert at UC Law San Francisco, told me: “I wouldn’t have expected him, in the middle of a measles outbreak, to be willing to sacrifice children in this way.”

The Florida Department of Health has not responded to a request for comment on Ladapo’s future plans, should this situation worsen. For the moment, though, he has chosen to lower the guardrails from their standard height. It’s an escalation of his, and Florida’s, broader push against established norms in public health, especially as they relate to vaccination. So what happens now?

At least in any immediate sense, Ladapo’s decision may not do much harm. In fact, there’s good reason to believe that its effects will end up being minimal. Parents who have children at the school, Manatee Bay Elementary, have until today to decide whether to pull out those kids for the next three weeks. Many seem to have already done so: About 200 students and six teachers have been absent, according to local news reports. In the meantime, Broward County Public Schools’ superintendent said yesterday that just 33 students out of the school’s nearly 1,100 were still unvaccinated. Given those two facts—some degree of self-imposed isolation, and 97 percent of the community now having some level of immune protection—the virus will have a hard time spreading no matter what the rules for attendance might be.

Disease modeling, too, suggests that the risk of a larger outbreak is low. For a study released in 2019, a team of researchers based at Newcastle University and the University of Pittsburgh simulated thousands of measles outbreaks at schools in Texas, the most populous state to allow nonmedical exemptions from routine vaccine requirements. The researchers looked at the extent to which a policy of sequestering unvaccinated kids would help to reduce the outbreaks’ size. In the median outcome, even without any school-wide interventions, they found that an initial case of measles spreads only to a small handful of people. Adding in the rule that unvaccinated kids must stay at home has no effect on transmission. When the school’s vaccination rates are assumed to be unusually low, the rule reduces the outbreak’s size by one case.

Not all of the modeling outcomes are so rosy. For the very worst-case scenarios, in which a case of measles emerges in a school where unvaccinated kids happen to be clustered, the study found that forced suspensions have dramatic benefits. A major outbreak in the Dallas–Fort Worth area, for example, might end up infecting 477 people in the absence of any interventions, according to the model. When unvaccinated kids are kept from going to school, that number drops by 95 percent.

Hypothetical models can’t tell us what will happen in a real-life school with real-life kids, like the one in Weston, Florida. But given Manatee Bay Elementary’s reported vaccination rate, it’s fair to assume that Ladapo’s policy won’t be catastrophic. Indeed, it may well end up sparing a few dozen families from the fairly serious inconvenience of being out of school without having much effect at all on the outbreak’s final size.

But is the sparing of that inconvenience worth the risks that still remain? (And how should one value the time of a parent who could have vaccinated their child but chose not to?) As Reiss points out, if this policy leads to even one more case in the current outbreak, it will have put one more kid at risk of hospitalization, long-term complications, or even death. Worst-case outbreak scenarios do occur from time to time, as we all know well by now, and the Weston outbreak getting much worse is certainly within the realm of possibility. Any public-health authority would have to weigh these odds in the face of a six-case cluster, and surely almost every statewide health authority would choose to err on the side of caution. In Florida, though, the scale appears to tip the other way: Ladapo has rolled the dice on doing less.

That’s been his way since the very day he was appointed by Governor Ron DeSantis, in September 2021. Just hours after he was introduced, the state ended mandatory quarantines for low-risk students who had been exposed to COVID. The following March, just a few weeks after being confirmed into the job, Ladapo announced that Florida would be “the first state to officially recommend against the COVID-19 vaccines for healthy children.” He continued to scale up from there: That fall, he recommended against the use of mRNA vaccines by any men under the age of 40. A year later, in October 2023, his office warned everyone under the age of 65 about the risks of getting an mRNA-based COVID booster. And then, finally, just last month, Ladapo came out with a warning that mRNA-based COVID vaccines “are not appropriate for use in human beings.”

[Read: The curious case of Florida’s pandemic response]

The man’s commitment to undermining vaccination is truly unparalleled among leading public-health officials. “As a surgeon general he stands alone,” Reiss told me. Yet Ladapo’s policy activism, however grotesque it might seem, has been bizarrely ineffective in practice. Take his March 2022 move to lead the way on not vaccinating young people against COVID. Media coverage of that announcement dwelled on reasonable concerns that this policy would dampen immunization rates; vaccine experts said it was a dangerous and irresponsible move that would “cause more people to die.” In practice, though, it seems to have done almost nothing. At the time of Ladapo’s announcement, 24.2 percent of Florida’s kids and 66.3 percent of its teenagers had received at least one dose of a COVID vaccine. (The corresponding national numbers at the time were somewhat higher.) By the end of the year, and in spite of Ladapo’s contrarian guidance, Florida’s vaccination numbers for these age groups were up by about four and three points, respectively—which is almost exactly the same amount, percentage-wise, as the increases in those numbers seen across the country.

Or compare Florida’s experience to that of Nevada, a state that had very similar child and teen vaccination rates in March 2022: 23.1 percent and 64.0 percent. Through the end of 2022, while Ladapo was discouraging his constituents from getting shots, that state’s Democratic governor was engaged in a large-scale effort to do the opposite. Yet the results were essentially the same: Nevada’s rates increased by pretty much the same amount as Florida’s.

For all of Ladapo’s efforts to dampen his state’s enthusiasm for life-saving interventions, Florida’s age-adjusted rates of death from COVID do not appear to have increased relative to the rest of the country, at least according to reported numbers. In this way, one of the nation’s loudest and most powerful voices of vaccine skepticism seems to be shouting into the wind. His proclamations and decisions to this point have been exquisitely effective at producing outrage, but embarrassingly feeble when it comes to changing outcomes. Even taken on its own terms, as a means of changing public-health behavior, Ladapo’s anti-vaccine activism has been a demonstrable failure.

[Read: The good news about vaccine hesitancy]

Perhaps this week’s decision to relax the rules on fighting measles will mark just one more step along that path: Once again, Florida’s surgeon general will have taken an appalling stance that ends up having no effect. But then again, now could be different. By the time Ladapo got around to undermining COVID shots, more than two-thirds of the state’s population, and 91 percent of its seniors, were already fully vaccinated. The damage he could have done was limited, by definition. But the measles outbreak in Weston is unfolding in real time. More such outbreaks are nearly guaranteed to occur in the U.S. in the months ahead. Reiss worries that Ladapo’s new idea, of choosing not to separate out unvaccinated kids during a school outbreak, could end up spreading into other jurisdictions. “If this becomes a precedent, that becomes a bigger problem,” she told me.

For the first time since taking office, Ladapo may finally have a real opportunity to make a difference through his vaccination policy. That’s a problem.

In my childhood home, an often-repeated phrase was “All disease begins in the gut.” My dad, a health nut, used this mantra to justify his insistence that our family eat rice-heavy meals, at the exact same time every day, to promote regularity and thus overall health. I would roll my eyes, dubious that his enthusiasm for this practice was anything more than fussiness.

Now, to my chagrin, his obsession has become mainstream. Social-media testimonials claim that improving your “gut health” not only helps with stomach issues such as bloating and pain but also leads to benefits beyond the gastrointestinal system (easing problems including, but not limited to, itching, puffy face, slow-growing hair, low energy, acne, weight gain, and anxiety). You can now find a staggering range of products claiming to support digestive health: Joining traditionally gut-friendly fermented foods such as yogurt and sauerkraut are “probiotic” or “prebiotic” teas, cookies, gummies, supplements, powders, and even sodas.

The reality is less straightforward. Maintaining the health of the gastrointestinal tract, like the health of any body part, is always a good idea. But expecting certain foods and products to overhaul gut health is unrealistic, as is believing that they will guarantee greater overall well-being. Those claims are “a little bit premature,” Karen Corbin, an investigator at the Translational Research Institute of Metabolism and Diabetes, told me. Obsessing over it just isn’t worth the trouble, and can even do more harm than good. “Gut health” cookies, after all, are still cookies.

In my dad’s defense, your gut does matter for your health. A massive microbial civilization lives mostly along the large intestine, helping the body get the most out of food. Broadly, a healthy gut is one where the different segments of this population—numerous species of bacteria, fungi, and viruses—live in harmony. An unhealthy one implies a disturbance of the peace: One group may grow too powerful, or an invading microbe may throw things off-balance, leading to problems including gastroenteritis and a compromised immune system.

Diet in particular has a profound impact on the gut—and how it subsequently makes you feel. “Food can have effects on the microbiome, which can then secondarily affect the host,” Purna Kashyap, a gastroenterologist at the Mayo Clinic, told me. The effects of food on a person and their microbes, he added, are generally congruent; fast food, for example, is “bad for both of us.” Neglect to feed your microbiome and the balance of microbes could tip into disarray, resulting in an imbalanced gut and corresponding bloating, stomach pain, and problems with bowel movements.

Fermented foods such as yogurt and kimchi, long considered good for digestive health, are known as “probiotics” because they contain live bacteria that take up residence in your gut. Other foods are considered “prebiotic” because they feed the microbes already in your gut—mostly fiber, because it isn’t digested in the stomach. Getting more fiber improves regularity and supports a more normal GI system, Corbin said.

But the fundamental problem with the gut-health obsession is that “there’s no clear definition of a healthy gut microbiome,” Corbin said. The makeup and balance of people’s microbiomes vary based on numerous factors, including genes, diet, environment, and even pets. This means that a treatment that works to rebalance one gut might not work for another. It also means that a product promoting a healthy gut doesn’t mean anything concrete. The idea that achieving gut health, however it’s defined, can solve stomach-related issues is misguided; many diseases can cause abdominal distress.

Less certain is how much gut health is responsible for benefits beyond the gastrointestinal tract. No doubt the microbiome is connected to other parts of the body; recent research has suggested that it has a role in weight gain, depression, and even cancer, supporting the idea that having a healthy gut could lead to other benefits. But the mechanisms underpinning them are largely unknown. Which microbes are involved? What are they doing? There are “a lot of tall claims based on animal studies that the microbiome influences diabetes or obesity or whatever,” and the translatability of those studies to humans is “really unlikely,” Daniel Freedberg, a gastroenterologist at Columbia University, told me. Until scientists can show definitively that microbe X leads to outcome Y, Corbin said, any relationships between the gut and overall health are “just correlations.”

None of this is to say that paying more attention to your digestive health is a bad idea. Especially for people diagnosed with gastrointestinal problems like IBS or Crohn’s disease, it can be essential. For everyone else, pursuing a healthy gut with food and supplements can be a nonspecific process with poorly defined goals. The food industry has capitalized on interest in probiotics and prebiotics—as well as lesser-known postbiotics and synbiotics—making products such as “insanely probiotic” yogurt, probiotic-fortified chocolate and spaghetti, and prebiotic sodas. Particularly with probiotics, the specifics are lacking. Which bacteria, and how many of them, actually make it past the stomach into the colon isn’t well understood. “A lot of probiotics are unlikely to contain viable bacteria, and probably very few of them are really making it through to the colon,” Freedberg said.

Prebiotics are generally more important, although the source matters. Prebiotic fiber is “one of the most important things that determines what bacteria are there,” Freedberg told me, but getting small amounts from fiber-fortified products isn’t going to make a huge difference. The soda brands Poppi and Olipop largely contain inulin, a type of fiber that’s common in food manufacturing for its slightly sweet taste, Freedberg explained, though it probably doesn’t contain a lot, otherwise it would become “sludgy.” Olipop contains about nine grams of fiber per can, roughly the same amount as one cup of cooked lima beans.

Of course, any product that is inherently unhealthy won’t magically become good for you the moment fiber or live bacteria are added to it. With desserts and salty snacks, no amount of fiber “is going to overcome the issue” that they are full of sugar or salt, Corbin said. Concerns about medium aside, though, gut-health products elicited a shrug from her: Buying foods containing additional prebiotic fiber is a “reasonable approach,” so long as they’re healthy to begin with. If probiotics make a patient feel “fantastic,” Freedberg said, “I’m not going to rock the boat.” Prebiotic and probiotic products may help to a degree, but don’t expect them to overhaul an unhealthy gut one soda at a time. All of the experts I spoke with said that people concerned about their gut health should eat a lot of fruits, vegetables, whole grains, and legumes, and cut out junk that won’t feed their microbiome. In other words, a basic healthy diet is more than enough to achieve good gut health.

My dad’s gut-health mantra was apparently borrowed from Hippocrates, suggesting that people have been obsessing over the digestive system for thousands of years with the belief that it is the key to overall health. The draw of this idea is its simplicity: Proposing that the body’s many ills can be collapsed into a single mega-ailment makes treatment seem refreshingly uncomplicated compared with the medical interventions needed to address individual problems. That the proposed treatments are easy and self-administrable—sipping fibrous soda, popping bacteria-packed pills—adds to the appeal.

But perhaps what is most compelling about the idea is that there is some truth to it. Lately, research on the microbiome has seen some promising advances. A large study published in 2022 showed significantly elevated levels of certain bacteria in people with depressive symptoms. Another study, co-authored by Corbin in 2023, was one of the first to show, in a human clinical trial, that a high-fiber diet shifts the microbiome in a way that could promote weight loss. This moment is especially confusing because we are finally beginning to understand the gut’s connections to the rest of the body, and how eating certain foods can soothe it. Much more is known about the gut than in the days of Hippocrates, but still far less than the gut influencers on social media would have you believe.

This article was originally published by Knowable Magazine.

The stories have become horribly familiar: houses so overrun by bedbugs that the bloodsucking insects pile an inch deep on the floor. An airport shutting down gates for deep cleaning after the parasites were spotted. Fear and loathing during Fashion Week 2023 in Paris, with bedbug-detection dogs working overtime when the insects turned up in movie theaters and trains.

For reasons that almost certainly have to do with global travel and poor pest management, bedbugs have resurfaced with a vengeance in 50 countries since the late 1990s. But recently, the resurgence has brought an added twist: When exterminators swarm out to hunt these pests, they might encounter not just one but two different kinds of bugs.

Besides the common bedbug, Cimex lectularius, which has always made its home in the Northern Hemisphere, there are now sightings of its relative, the tropical bedbug, Cimex hemipterus, in temperate regions. Historically, this species didn’t venture that far from the equator, write the entomologists Stephen Doggett and Chow-Yang Lee in the 2023 issue of the Annual Review of Entomology. But in recent years, tropical bedbugs have turned up in the United States, Sweden, Italy, Norway, Finland, China, Japan, France, Central Europe, Spain—“even in Russia, which would have once been unthinkable,” says Lee, a professor of urban entomology at UC Riverside.

Like the common bedbug, the tropical version has grown resistant to many standard pesticides—to the point where some experts say they wouldn’t bother spraying should their own home become infested. It has been estimated that the fight against bedbugs is costing the world economy billions annually.

This all adds up to a sobering new reality: For many people, bedbugs are becoming a fact of life again, much as they used to be throughout humanity’s history. But as scientists race to find new strategies to combat these pests—everything from microfabricated surfaces that entrap the insects to fungal spores that invade and kill them—they also learn more about the often-bizarre biology of bedbugs, which might one day reveal the parasite’s Achilles’ heel.

Genomics shows that bedbugs emerged 115 million years ago, before the dinosaurs went extinct. When the first humans appeared and moved into caves, the ancestors of today’s bedbugs were ready and waiting. It is thought that these insects initially fed on bats. But bats reduce their blood circulation during their sleeplike torpor state, likely making it harder for the bloodsucking parasite to feed. Presumably, then, at least some bedbug ancestors happily switched to humans.

Since then, the bugs have followed humankind across the globe, tagging along on ancient shipping routes and modern plane rides. Preserved bedbugs were found in the quarters used by workers in ancient Egypt some 3,550 years ago.

Bedbugs can survive a year or more without feeding. About as big as flattened apple seeds, they squeeze into tiny cracks in walls or in the joints of bed frames during the day; they crawl out at night, attracted by a sleeper’s exhaled carbon dioxide and body warmth. At the turn of the 20th century, an estimated 75 percent of homes in the U.K. contained bedbugs. Bizarre prescriptions for remedies have circulated down the years, including a recipe for “cat juice” in a pest-control guide from 1725. The formula called for suffocating and skinning a cat, roasting it on a spit, mixing the drippings with egg yolk and oil, and smearing the concoction into crevices around the bed.

DDT (dichlorodiphenyltrichloroethane) and the pesticides that followed helped bring a few decades’ worth of respite from the 1940s to the 1990s—enough that most people forgot about the insects and didn’t recognize them when they reappeared around the turn of the millennium.

Doggett and Lee hypothesize that the bloodsuckers’ comeback started in areas of Africa, where common and tropical bedbugs naturally coexist, and where DDT (and, later, other insecticides) were sprayed in bedrooms against malaria-carrying mosquitoes. Initially, this would have killed the majority of bed bugs too. But some resistant ones survived and multiplied.

[Read: Animals of the future]

Bedbugs suck up more than three times their body weight in blood. As they do, they also take in any viruses or other infectious agents that might circulate in the body of their prey, such as hepatitis B and HIV. They have never been found to transmit these pathogens in the wild—but this doesn’t mean that the parasites are benign. “Bedbugs produce some of the most irritating bites of all insects,” says Doggett, a medical entomologist at Westmead Hospital, in Sydney, Australia. “If I receive one, I don’t sleep, as I react so badly. If there are lots of bedbugs, the bites are horrendous.” There have been cases where people have accidentally set mattresses on fire in desperate attempts to chase off the bugs, sometimes burning down their home in the process.

Humans aren’t the only ones to react so strongly. The Cimicidae family, to which bedbugs belong, comprises about 100 species. Almost all prefer to bite nonhuman animals, such as birds. Biologists have observed cliff-swallow chicks jumping to their death from heavily infested nests rather than enduring the bites.

Infestations in which hundreds of bugs may descend upon a bed at night can cause a human sleeper to become anemic. Victims can even develop insomnia, anxiety, and depression. They may find themselves shunned by friends, blacklisted by landlords, and—being sleep-deprived—more prone to car accidents and problems at work.

[Read: The psychological toll of bedbugs]

Indirectly, at least, bedbugs may cause human deaths. Doggett has noticed that some people in Africa are giving up the bed nets that protect them from mosquitoes and life-threatening malaria infections because bedbugs hide in them. “In some regions, malaria cases are on the rise, and we think that bedbugs are contributing to this,” he says.

By now, bedbug resistance has been reported against most of the prevalent insecticides, including organochlorines, organophosphates, carbamates, neonicotinoids, aryl pyrroles, and pyrethroids. Some of today’s bedbug strains tolerate pesticide doses that are many thousands of times higher than those that used to consistently kill them. Resistant bedbugs have either developed gene mutations that prevent pesticides from binding effectively to their cells or they produce enzymes that quickly break down the toxins in their body. Others are growing thicker exoskeletons that the poisons can’t easily penetrate.

An investigation some years back into a hospital in Cleveland discovered that new bedbugs showed up in the facility every 2.2 days on average. And tropical bedbugs seem just as happy in our modern indoors as the common variety does. “Heating and air-conditioning have made our living environments more standardized,” Lee says. “If a tropical bedbug happens to be introduced to a house in Norway, it can now survive there even in winter.”

Currently, the only bedbug sprays that still tend to work are certain combination products that blend different classes of pesticides. But it’s only a matter of time before these, too, will fail, experts say: Reports of resistance have already been documented. More and more, exterminators incorporate nonchemical approaches such as heat treatments, in which trained professionals warm up rooms to more than 120 degrees Fahrenheit for several hours. They sometimes sprinkle a floury dust called diatomaceous earth around rooms, which clings to those bugs that hide from the heat in wall cracks or under mattresses. The dust abrades the insect’s exoskeleton, dehydrating it to death.

Such measures—combined with more awareness—have helped plateau, or even partly reverse, the spread of bedbugs in some places. In New York City, for example, bedbug complaints fell by half from 2014 to 2020, from 875 complaints a month to 440, on average. To be sure, that’s still 14 complaints a day.

But although effective, nonchemical methods tend to work slowly. “It’s very common that an elimination takes one to two or even three months,” says Changlu Wang, an entomologist at Rutgers University. Meanwhile, residents must keep living in their infested quarters.

Nonchemical measures may also be expensive, because they can require laborious steps such as sealing cracks in walls and physically removing bugs by vacuuming. Although a quick (but increasingly futile) spraying of pesticides may cost a few hundred dollars, mechanical eradications can run as high as several thousand dollars. This puts effective bedbug control out of many people’s reach, making them vulnerable to entrenched infestations that can spread through communities.

The result is that the epidemic has shifted to the poor, says Michael Levy, an epidemiologist at the University of Pennsylvania: “While many cities now have bedbug policies, very few provide much assistance to those who cannot afford treatment.” A 2016 report on 2,372 low-income apartment units in 43 buildings across four New Jersey cities found that 3.8 percent to 29.5 percent were infested with bedbugs.

The northward spread of tropical bedbugs complicates matters further. Although the two species look alike, tropical bedbugs have more hair on their legs, which allows them to climb out of many of the smooth-walled traps that are used to monitor homes. This means that infestations could stay undetected longer, Lee says. And the larger a population grows, the harder it is to get rid of.

To fight back, researchers find inspiration in traditional wisdom. In the Balkan region, homeowners used to spread the leaves of the bean plant Phaseolus vulgaris L. around their beds. The leaves possess tiny hooks on their surface that trap the bugs. Now scientists at UC Irvine are developing a “physical insecticide” in the shape of a synthetic material sporting sharply curved microstructures that mimic those on the bean leaves. These irreversibly impale the feet of the bedbugs, Catherine Loudon, a biology professor at UC Irvine, wrote in a 2022 paper in Integrative and Comparative Biology: “The bugs are unable to get away once they are pierced.”

Other recent approaches are also rooted in nature. Scientists have found, for example, that essential oils can repel bedbugs. However, the effect is mostly temporary. Certain fungal spores, on the other hand, work permanently. “Basically, the spores go into the body of the bedbug and kill it,” Wang says. At least one product containing the insect-killing fungus Beauveria bassiana is now available in the United States.

[Read: A better bed bug trap]

Researchers continue to be fascinated by the biology of this insect, particularly its sex life. Although female bedbugs possess a normal set of genitalia, the males typically mate by stabbing a needle-sharp penis straight into the female’s abdomen to inject sperm. They usually do this just after a female bedbug has fed, because this makes her too engorged to protect herself.

Having to cope with these frequent injuries has led female bedbugs to evolve the only immunity organ in the insect kingdom, says Klaus Reinhardt, a zoologist at the Dresden University of Technology, in Germany. They have also evolved a remarkably elastic material that covers the parts of their abdomen most likely to be stabbed. “It resembles one of those self-sealing injection bottles that close up again when you pull the needle,” Reinhardt says.

Although this knowledge will likely do little to combat these pests directly, answering another question might: Why don’t bedbugs stay on their host’s body, as lice do? As it turns out, bedbugs don’t like our smell. Certain lipids in human skin repel the bugs, according to a 2021 study in Scientific Reports. This makes them retreat to daytime hiding places, marking their trails with pheromones.

Already, exterminators try to trap bedbugs with fake trail markings. And one day, we might deter the insects from spreading by treating suitcases with smells they despise.

But for now, caution remains the best approach. Experts advise that travelers check accommodations for bedbug-defecation stains: on mattress seams and furniture, and behind headboards. (The insects poop as frequently as a few dozen times after every blood meal, often right next to their victims.) Suitcases should be kept in the hotel bathtub or wrapped in a plastic bag. Upon arrival back home, the luggage’s contents should be put into the clothes dryer for at least 30 minutes at the highest setting, or into a very cold freezer for several days.

If bedbugs do invade a home, “the biggest mistake is to try and get rid of them on one’s own,” Doggett says. “The average person doesn’t appreciate how challenging it is to control bedbugs and will use supermarket insecticides that are labeled for bedbugs but don’t work. The infestation will spread, and the costs escalate.”

No medication in the history of modern weight loss has inspired as much awe as the latest class of obesity drugs. Wegovy and Zepbound are so effective that they are often likened to “magic” and “miracles.” Indeed, the weekly injections, which belong to a broader class known as GLP-1s, can lead to weight loss of 20 percent or more, fueling hype about a future in which many more millions of Americans take them. Major food companies including Nestlé and Conagra are considering tailoring their products to suit GLP-1 users. Underlying all this excitement is a huge assumption: They work for everyone.

But for a lot of people, they just don’t. Anita, who lives in Arizona, told me she “took it for granted” that she would lose weight on a GLP-1 drug because “the people around me who were on it were just dropping weight like mad.” Instead, she didn’t shed any pounds. Likewise, Kathryn, from Florida, hasn’t lost any weight since starting the medication in October. “I was really hoping this was something that would be a game changer for me, but it feels like it was just a lot of wasted money,” she told me. (I’m identifying both Anita and Kathryn by their first name only to allow them to speak openly about their health issues.)

Some people can’t tolerate the side effects of the drugs and have to stop taking them. Others simply don’t respond. For some, the strength of the dose, or length of the treatment, does not seem to make a difference. Appetites might remain robust; the “food chatter” in the brain may stay noisy. Together, both groups of less successful GLP-1 users account for a not-insignificant share of patients on these drugs—potentially up to a third. “We don’t really know why it happens, [but] we know it does happen,” Louis Aronne, an obesity-medicine specialist at Weill Cornell Medical College, told me. Despite the promise of a so-called Ozempic revolution, lots of “No-zempics” have been left behind.

Of the two biggest reasons some people don’t lose weight on GLP-1 drugs—side effects and nonresponse—the former is much more straightforward. The GLP-1 drugs Wegovy and Zepbound (which contain the active ingredients semaglutide and tirzepatide, respectively), are known for causing potentially gnarly gastrointestinal symptoms, such as nausea and vomiting, although most people’s reactions are mild and temporary. Yet some have it far worse. Severe, albeit uncommon, side effects include pancreatitis, severe gastrointestinal distress, low blood sugar, and even hair loss, which “can push people off” the drugs, Steven Heymsfield, a professor who studies obesity at Louisiana State University, told me. In one of the biggest studies of semaglutide, encompassing more than 17,000 people over about five years, nearly 17 percent of patients discontinued the medication because of side effects.

Far more mysterious are the people who tolerate the drugs but respond weakly to them—or sometimes not at all. Researchers have known this might happen since these drugs were in early clinical trials. About 14 percent of people who took semaglutide for obesity saw minimal impacts of less than 5 percent weight loss in one study, as did 9 to 15 percent of people who took tirzepatide in a similar one. In her own experience working with patients, “somewhere between a quarter and a third” are nonresponders, Fatima Cody Stanford, an obesity-medicine specialist at Harvard, told me, adding that it can take up to three months to determine whether the drug is working or not. That the same medication at the same dosage can lead to dramatic weight loss in one person and hardly any in another “remains confounding,” Aronne told me.

The broad explanation is that it has something to do with genetics. The drugs work by masquerading as the appetite-suppressing hormone GLP-1 and binding to its receptor, like a key fitting into a lock. Although the lock’s overall shape is generally consistent from person to person, its nooks and crannies can vary because of genetic differences. “For some people, that key just won’t fit right,” Eduardo Grunvald, an obesity-medicine doctor at UC San Diego Health, told me. In other cases, genes may limit the effects of these drugs after they bind to GLP-1 receptors. One possibility is that people metabolize the drugs differently: Some patients may break them down too quickly for them to take effect; others may process them too slowly, potentially building up such high levels of the medications that they become toxic, Heymsfield said.

For No-zempic patients, perhaps the most consequential impact of individual variation is on the propensity for obesity itself. “We are all very different from a genetic standpoint, in terms of our risk of weight gain,” Grunvald said. Numerous factors can drive obesity, including diet, environment, stress, and—most pertinent to GLP-1 drugs—altered brain function.

GLP-1 drugs target a pathway that regulates appetite and insulin levels. Some cases of obesity can be caused by a disruption in that particular mechanism, in which case GLP-1s can indeed be wondrous. But “not everyone has dysfunction in this particular pathway,” Stanford said. When that is the case, the drugs won’t be very effective. A different pathway, for example, controls the absorption of fat from food; another increases energy expenditure. In these people, GLP-1s might tamp down appetite to a degree, maybe leading to some weight loss, but a different drug may be required to treat obesity at its root. “It is not all about food intake,” Stanford said.

That’s not to say that No-zempics are out of options. They might have better success switching from one GLP-1 to the other, or even stacking them, Heymsfield said. Some patients who don’t respond to GLP-1s at all can get better results with older drugs that work on different obesity pathways, Aronne said. One, called Qysmia, a combination of the decades-old drugs phentermine and topiramate, can lead to an average weight loss of 14 percent body weight at its highest dose. If medications don’t work, bariatric surgery remains a powerful option, one that may even be growing in popularity. Last year, the number of bariatric surgeries performed in the U.S. grew despite the boom in GLP-1 usage, a trend that some expect to continue, because so many people don’t tolerate the drugs.

The intense hype around the game-changing nature of GLP-1s makes it easy to forget that they are, in fact, just drugs. “Every drug that’s ever been made” works in some people and not in others, Heymsfield said; there’s no reason to think GLP-1s would be any different. Remembering that they are in an early stage of development has a sobering effect. Eventually, obesity drugs may leave fewer people behind. The category is expanding rapidly: By one count, more than 90 new drug candidates are in development.

They are evolving to attack obesity from multiple fronts, which, at least in theory, widens their net of potential users. In an early study on an experimental candidate named retatrutide—called a triple agonist because it acts on GLP-1 as well as two other targets involved in obesity, GIP and glucagon receptors—100 percent of people on the highest dose lost 5 percent or more of their body weight. New candidates are also expected to have fewer side effects. They have to, Heymsfield said, because the competition is so steep that any new drug has to be “as good with less side effects, or better.”

But no matter how good these drugs get, it’s unrealistic to think that they’ll become a one-size-fits-all treatment for everyone with obesity. The disease is simply too complex, with too many drivers, for a single type of medication to treat it. More than 200 different drugs exist for treating high blood pressure alone; in comparison, Aronne said, regulating weight is “far more complicated.” The future, rife with options, holds promise that No-zempics may find a way forward. Yet considering all the unknowns about obesity and what causes it, that may not be enough to guarantee that they will see the results they want.

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Imagine an older man goes in to see his doctor. He’s 72 years old and moderately overweight: 5-foot-10, 190 pounds. His blood tests show high levels of triglycerides. Given his BMI—27.3—the man qualifies for taking semaglutide or tirzepatide, two of the wildly popular injectable drugs for diabetes and obesity that have produced dramatic weight loss in clinical trials. So he asks for a prescription, because his 50th college reunion is approaching and he’d like to get back to his freshman-year weight.

He certainly could use these drugs to lose weight, says Thomas Wadden, a clinical psychologist and obesity researcher at the University of Pennsylvania, who recently laid out this hypothetical in an academic paper. But should he? And what about the tens of millions of Americans 65 and older who aren’t simply trying to slim down for a cocktail party, but live with diagnosable obesity? Should they be on Wegovy or Zepbound?

Already, seniors make up 26.6 percent of the people who have been prescribed these and other GLP-1 agonists, including Ozempic, since 2018, according to a report from Truveta, which draws data from a large network of health-care systems. In the coming years, that proportion could rise even higher: The bipartisan Treat and Reduce Obesity Act, introduced in Congress last July, would allow Medicare to cover drug treatments for obesity among its roughly 50 million Part D enrollees above the age of 65; in principle, about two-fifths of that number would qualify as patients. Even if this law doesn’t pass (and it’s been introduced half a dozen times since 2012), America’s retirees will continue to be prescribed these drugs for diabetes in enormous numbers, and they’ll be losing weight on them as well. One way or another, the Boomers will be giving shape to our Ozempic Age.

Economists say the cost to Medicare of giving new drugs for obesity to just a fraction of this aging generation would be staggering—$13.6 billion a year, according to an estimate published in The New England Journal of Medicine last March. But the health effects of such a program might also be unsettling. Until recently, the very notion of prescribing any form of weight loss whatsoever to an elderly patient—i.e., someone 65 or older—was considered suspect, even dangerous. “Advising weight loss in obese older adults is still shunned in the medical community,” the geriatric endocrinologist Dennis Villareal and his co-authors wrote in a 2013 “review of the controversy” for a medical journal. More than a decade later, clinicians are still struggling to reach consensus on safety, Villareal told me.

Ample research shows that interventions for seniors with obesity can resolve associated complications. Wadden helped run a years-long, randomized trial of dramatic calorie reduction—using liquid meal replacements, in part—and stringent exercise advice for thousands of overweight adults with type 2 diabetes. “Clearly the people who were older did have benefits in terms of improved glycemic control and blood-pressure control,” he told me. Other, smaller studies led by Villareal find that older people who succeed at losing weight through diet and exercise end up feeling more robust.

Such outcomes are significant on their own terms, says John Batsis, who treats and studies geriatric obesity at the UNC School of Medicine. “When we talk about older adults, we really need to be thinking about what’s important to older adults,” he told me. “It’s for them to be able to get on the floor and play with their grandchildren, or to be able to walk down the hallway without being completely exhausted.” But weight loss can also have adverse effects. When a person addresses their obesity through dieting alone, as much as 25 percent of the weight they lose derives from loss of muscle, bone, and other fat-free tissue. For seniors who, through natural aging, are already near the threshold of developing a functional impairment, a sudden drop like this could be enfeebling. Wadden’s trial found that, among the people who were on the weight-loss program for more than a decade, their risk of fracture to the hip, shoulder, upper arm, or pelvis increased by 39 percent. An analogous increase has turned up in studies of patients who undergo bariatric surgery, Batsis told me.

[Read: Ozempic makes you lose more than fat]

The effect of dieting on muscle and bone can be attenuated, but not prevented, through resistance training. And obesity itself—which is associated with higher bone density, but perhaps also reduced bone quality—may pose its own fracture risks, Batsis said. But even when a weight-loss treatment benefits an older patient, what happens when it ends? People tend to regain fat, but they don’t recover bone and muscle, Debra Waters, the director of gerontology research at the University of Otago, in New Zealand, told me. That makes the long-term effects of these interventions for older adults very murky. “What happens when they’re 80? Are they going to have really poor bone quality, and be at higher risk of fracture? We don’t know,” Waters said. “It’s a pretty big gamble to take, in my opinion.”

Villareal told me that doctors should apply “the general principle of starting slow and going slow” when their older patients are trying to lose weight. But that approach doesn’t necessarily square with the rapid and remarkable weight loss seen in patients who are taking semaglutide or tirzepatide, which may produce a greater proportional loss of muscle and bone. (For semaglutide, it appears to be about 40 percent.)

Then again, when given to laboratory animals, GLP-1 drugs seem to tamp down inflammation in the brain; and they’re now in clinical trials to see whether they might slow the progression of Alzheimer’s disease and dementia. Their multiple established benefits could also help seniors address several chronic problems—diabetes, obesity, fatty liver disease, and kidney disease, for instance—all at once. “Such a ‘one-stop shop’ approach can lead to reduction of medication burden, adverse drug events, hypoglycemic episodes, medication costs, and treatment nonadherence,” one team of geriatricians proposed in 2019.

Overall, Batsis remains optimistic. “As a clinician, I’m very excited about these medications,” he told me. As a scientist, though, he’s inclined to wait and see. It’s surely true that some degree of weight loss is a great idea for some older patients. “But the million-dollar question is: What’s the sweet spot? How much weight is really enough? Is it 5 to 10 percent? Or is it 25 percent? We don’t know.” Waters said that if Medicare is going to pay for people’s Wegovy, then it should also cover scans of their body composition, to help predict how weight loss might affect their muscles and bones. Wadden said he thinks that treatments should be limited to people who have specific, weight-related complications. For everyone else—as for the hypothetical 72-year-old man who is prepping for his college reunion—he counsels prudence.

To some extent, such advice is beside the point. Older people are already on Ozempic, and they’re already on Trulicity, and some of them are already taking GLP-1 drugs as a treatment for obesity. Truveta reported that the patients in its member health-care systems who are over 65 have received 281,000 prescriptions for GLP-1 drugs across the past five years. Given the network’s size, one can assume that at least 1 million seniors, overall, have already tried these medications. Millions more will try them in the years to come. If we still have questions about their use, mass experience will start providing answers.

GoFundMe started as a crowdfunding site for underwriting “ideas and dreams,” and, as GoFundMe’s co-founders, Andrew Ballester and Brad Damphousse, once put it, “for life’s important moments.” In the early years, it funded honeymoon trips, graduation gifts, and church missions to overseas hospitals in need. Now GoFundMe has become a go-to for patients trying to escape medical-billing nightmares.

One study found that, in 2020, the number of U.S. campaigns related to medical causes—about 200,000—was 25 times higher than the number of such campaigns on the site in 2011. More than 500 campaigns are currently dedicated to asking for financial help for treating people, mostly kids, with spinal muscular atrophy, a neurodegenerative genetic condition. The recently approved gene therapy for young children with the condition, by the drugmaker Novartis, costs about $2.1 million for the single-dose treatment.

Perhaps the most damning aspect of all this is that paying for expensive care with crowdfunding is no longer seen as unusual; instead, it is being normalized as part of the health system, like getting blood work done or waiting on hold for an appointment. Need a heart transplant? Start a GoFundMe in order to get on the waiting list. Resorting to GoFundMe when faced with bills has become so accepted that in some cases, patient advocates and hospital financial-aid officers recommend crowdfunding as an alternative to being sent to collections. My inbox and the Bill of the Month project (run by KFF Health News, where I am the senior contributing editor, and NPR) have become a kind of complaint desk for people who can’t afford their medical bills, and I’m gobsmacked every time a patient tells me they’ve been advised that GoFundMe is their best option.

GoFundMe itself acknowledges the reliance of patients on the company’s platform. Ari Romio, a spokesperson for the company, said that “medical expenses” is the most common category of fundraiser it hosts. But she declined to say what proportion of campaigns are medically related, because people starting a campaign self-select the purpose of the fundraiser. They might choose the family or travel category, she said, if a child needs to go to a different state for treatment, for example. So although the company has estimated in the past that a third of the funds raised on the site are medical-related, that could be an undercount.  

Andrea Coy of Fort Collins, Colorado, turned to GoFundMe in 2021 as a last resort after an air-ambulance bill tipped her family’s finances over the edge. Her son Sebastian, then a year old, had been admitted with pneumonia to a local hospital and then transferred urgently by helicopter to Children’s Hospital Colorado in Denver when his oxygen levels dropped. REACH, the air-ambulance transport company that contracted with the hospital, was out-of-network, and billed the family nearly $65,000 for the ride—more than $28,000 of which Coy’s insurer, UnitedHealthcare, paid. Even so, REACH continued sending Coy’s family bills for the remaining balance, and later began regularly calling Coy to try to collect, enough that she felt the company was harassing her, she told me.

Coy made multiple calls to her company’s human-resources department, REACH, and UnitedHealthcare for help in resolving the case. She applied to various patient groups for financial assistance and was rejected again and again. Eventually, she got the outstanding balance knocked down to $5,000, but even that was more than she could afford on top of the $12,000 the family owed out-of-pocket for Sebastian’s actual treatment.

That’s when a hospital financial-aid officer suggested she try GoFundMe. But, as Coy said, “I’m not an influencer or anything like that,” so the appeal “offered only a bit of temporary relief—we’ve hit a wall.” They have gone deep into debt and hope to climb out of it.

In an emailed response, a spokesperson for REACH noted that they could not comment on a specific case because of patient-privacy laws, but that, if the ride occurred before the federal No Surprises Act went into effect, the bill was legal. (That act protects patients from such air-ambulance bills and has been in force since January 1, 2022.) But the spokesperson added, “If a patient is experiencing a financial hardship, we work with them to find equitable solutions.” What is “equitable”—and whether that includes seeking an additional $5,000, beyond a $28,000 insurance payment, for transporting a sick child—is subjective, of course.  

In many respects, research shows, GoFundMe tends to perpetuate socioeconomic disparities that already affect medical bills and debt. If you are famous or part of a circle of friends who have money, your crowdfunding campaign is much more likely to succeed than if you are middle-class or poor. When the family of the former Olympic gymnast Mary Lou Retton started a fundraiser on another platform, *spotfund, for her recent ICU stay at a time when she was uninsured, nearly $460,000 in donations quickly poured in. (Although Retton said she could not get affordable insurance because of her preexisting condition—dozens of orthopedic surgeries—the Affordable Care Act prohibits insurers from refusing to cover people because of their prior medical histories, or charging them abnormally high rates.)

And given the price of American health care, even the most robust fundraising can feel inadequate. If you’re looking for help to pay for a $2 million drug, even tens of thousands is a drop in the bucket.

Rob Solomon, the CEO of the platform from 2015 to March 2020, who was named one of Time magazine’s 50 most influential people in health care, has said that he “would love nothing more than for ‘medical’ to not be a category on GoFundMe.” He told KFF Health News that “the system is terrible. It needs to be rethought and retooled. Politicians are failing us. Health-care companies are failing us. Those are realities.”

But despite the noble ambitions of its original vision, GoFundMe is a privately held for-profit company. In 2015, the founders sold a majority stake to a venture-capital investor group led by Accel Partners and Technology Crossover Ventures. And when I asked about medical bills being the most common reason for GoFundMe campaigns, the company’s current CEO, Tim Cadogan, sounded less critical than his predecessor of the health system, whose high prices and financial cruelty have arguably made his company famous.

“Our mission is to help people help each other,” he said. “We are not, and cannot, be the solution to complex, systemic problems that are best solved with meaningful public policy.”

And that’s true. Despite the site’s hopeful vibe, most campaigns generate only a small fraction of the money owed. Almost all of the medical-expense campaigns in the U.S. fell short of their goal, and some raised little or no money, a 2017 study from the University of Washington found. The average campaign made it to just about 40 percent of the target amount, and there is evidence that yields—measured as a percent of their target—have gotten worse over time.  

Carol Justice, a recently retired civil servant and a longtime union member in Portland, Oregon, turned to GoFundMe after she faced a mammoth unexpected bill for bariatric surgery at Oregon Health & Science University.

She had expected to pay about $1,000, the amount left in her deductible, after her health insurer paid the $15,000 cap on the surgery. She didn’t understand that a cap meant she would have to pay the difference if the hospital, which was in-network, charged more.

And it did, leaving her with a bill of $18,000, to be paid all at once or in monthly $1,400 increments. “That’s more than my mortgage,” she told me. “I was facing filing for bankruptcy or losing my car and my house.” She made numerous calls to the hospital’s financial-aid office, many unanswered, and received only unfulfilled promises that “we’ll get back to you” about whether she qualified for help.

So, Justice said, her health coach—provided by the city of Portland—suggested starting a GoFundMe. The campaign yielded about $1,400, just one monthly payment, including $200 from the health coach and $100 from an aunt. She dutifully sent each donation directly to the hospital.

In an emailed response, the hospital system said that it couldn’t discuss individual cases, but that “financial assistance information is readily available for patients, and can be accessed at any point in a patient’s journey with OHSU. Starting in early 2019, OHSU worked to remove barriers for patients most in need by providing a quick screening for financial assistance that, if a certain threshold is met, awards financial assistance without requiring an application process.”

This particular tale has a happy-ish ending. In desperation, Justice went to the hospital and planted herself in the financial-aid office, where she had a tearful meeting with a hospital representative who determined that—given her finances—she wouldn’t have to pay the bill.

“I’d been through the gamut and just cried,” she said. She told me that she would like to repay the people who donated to her GoFundMe. But so far, the hospital won’t give the $1,400 back.

About four years ago, a new patient came to see me for a psychiatric consultation because he felt stuck. He’d been in therapy for 15 years, despite the fact that the depression and anxiety that first drove him to seek help had long ago faded. Instead of working on problems related to his symptoms, he and his therapist chatted about his vacations, house renovations, and office gripes. His therapist had become, in effect, an expensive and especially supportive friend. And yet, when I asked if he was considering quitting treatment, he grew hesitant, even anxious. “It’s just baked into my life,” he told me.

Among those who can afford it, regular psychotherapy is often viewed as a lifelong project, like working out or going to the dentist. Studies suggest that most therapy clients can measure their treatments in months instead of years, but a solid chunk of current and former patients expect therapy to last indefinitely. Therapists and clients alike, along with celebrities and media outlets, have endorsed the idea of going to therapy for extended stretches, or when you’re feeling fine. I’ve seen this myself with friends who are basically healthy and think of having a therapist as somewhat like having a physical trainer. The problem is, some of the most commonly sought versions of psychotherapy are simply not designed for long-term use.

Therapy comes in many varieties, but they all share a common goal: to eventually end treatment because you feel and function well enough to thrive on your own. Stopping doesn’t even need to be permanent. If you’ve been going to therapy for a long time, and you’re no longer in acute distress, and you have few symptoms that bother you, consider taking a break. You might be pleasantly surprised by how much you learn about yourself.

Therapy, in both the short and long term, can be life-altering. Short-term therapy tends to be focused on a particular problem, such as a depressed mood or social anxiety. In cognitive behavioral therapy, usually used for depressive and anxiety disorders, a clinician helps a client relieve negative feelings by correcting the distorted beliefs that he has about himself. In dialectical behavior therapy, commonly used to treat borderline personality disorder, patients learn skills to manage powerful emotions, which helps improve their mood and relationships. Both treatments typically last less than a year. If you start to get rusty or feel especially challenged by life events that come your way, you simply return for another brief stint. Termination is expected and normal.

[Read: What’s the smallest amount of therapy that’s still effective?]

Some types of therapy, such as psychodynamic therapy and psychoanalysis, are designed to last for several years—but not forever. The main goal of these therapies is much more ambitious than symptom relief; they aim to uncover the unconscious causes of suffering and to change a client’s fundamental character. At least one well-regarded study found that long-term therapy is both highly effective and superior to briefer treatment for people diagnosed with a clinically significant psychiatric illness; other papers have shown less conclusive evidence for long-term therapy. And few studies compare short and extended treatment for clients with milder symptoms.

In fact, there’s reason to believe that talk therapy in the absence of acute symptoms may sometimes cause harm. Excessive self-focus—easily facilitated in a setting in which you’re literally paying to talk about your feelings—can increase your anxiety, especially when it substitutes for tangible actions. If your neurotic or depressive symptoms are relatively mild (meaning they don’t really interfere with your daily functioning), you might be better served by spending less time in a therapist’s office and more time connecting with friends, pursuing a hobby, or volunteering. Therapists are trained to use the tools they’ve learned for certain types of problems, and many of the stress-inducing minutiae of daily life are not among them. For example, if you mention to your therapist that you’re having trouble being efficient at work, he might decide to teach you a stress-reduction technique, but your colleagues or boss might provide more specific strategies for improving your performance.

One of my childhood friends, whose parents were both psychoanalysts, went to weekly therapy appointments while we were growing up. He was a happy, energetic kid, but his parents wanted him and his sister to be better acquainted with their inner lives, to help them deal with whatever adversity came their way. My friend and his sister both grew up to be successful adults, but also highly anxious and neurotic ones. I imagine their parents would say the kids would have been worse without the therapy—after all, mental illness ran in their family. But I can find no substantial clinical evidence supporting this kind of “preventive” psychotherapy.

[Read: What it’s like to visit an existential therapist]

Beginning therapy in the first place is, to be clear, a privilege. Therapy is not covered by many insurance plans, and a very large number of people who could benefit from it can’t afford it for any duration. Only 47 percent of Americans with a psychiatric illness received any form of treatment in 2021; in fact, federal estimates suggest that the United States is several thousand mental-health professionals short, a gap that is likely to grow in the coming years. Stopping therapy when you’re ready opens up space for others who might need this scarce service more than you do.

I do not mean to suggest that a therapy vacation should be considered lightly, or that it’s for everyone. If you have a serious mental-health disorder, such as major depression or bipolar disorder, you should discuss with your mental-health provider whether ending therapy is appropriate for your individual situation. (Keep in mind that your therapist might not be ready to quit when you are. Aside from a financial incentive to continue treatment, parting with a charming, low-maintenance patient is not so easy.) My rule of thumb is that you should have minimal to no symptoms of your illness for six months or so before even considering a pause. Should you and your therapist agree that stopping is reasonable, a temporary break with a clear expiration date is ideal. At any time, if you’re feeling worse, you can always go back.

Psychiatrists do something similar with psychiatric meds: For example, when I prescribe a depressed patient an antidepressant, and then they remain stable and free of symptoms for several years, I usually consider tapering the medication to determine whether it’s still necessary for the patient’s well-being. I would do this only for patients who are at a low risk of relapse—for example, people who’ve had just one or two episodes, rather than many over a lifetime. Pausing therapy should be even less risky: The beautiful thing about therapy is that, unlike a drug, it equips you with new knowledge and skills, which you carry with you when you leave.

[Read: The quick therapy that actually works]

About a year after my patient and I first talked about ending therapy, I ran into him in a café. He told me that stopping had taken him six months, but now he was thriving. Maybe you, like my patient, are daunted by the idea of quitting cold turkey. If so, consider taking a vacation from treatment instead. It might be the perfect way to see how far you’ve really come.

In Arnold Monto’s ideal vision of this fall, the United States’ flu vaccines would be slated for some serious change—booting a major ingredient that they’ve consistently included since 2013. The component isn’t dangerous. And it made sense to use before. But to include it again now, Monto, an epidemiologist and a flu expert at the University of Michigan, told me, would mean vaccinating people “against something that doesn’t exist.”

That probably nonexistent something is Yamagata, a lineage of influenza B viruses that hasn’t been spotted by global surveyors since March of 2020, shortly after COVID mitigations plummeted flu transmission to record lows. “And it isn’t for lack of looking,” Kanta Subbarao, the director of the WHO’s Collaborating Centre for Reference and Research on Influenza, told me. In a last-ditch attempt to find the missing pathogen, a worldwide network of monitoring centers tested nearly 16,000 influenza B virus samples collected from February to August of last year. Not a single one of them came up Yamagata. “The consensus is that it’s gone,” Cheryl Cohen, the head of South Africa’s Centre for Respiratory Diseases and Meningitis, told me. Officially removing an ingredient from flu vaccines will codify that sentiment, effectively publishing Yamagata’s obituary.

[Read: The flu may never be the same]

Last year around this time, Subbarao told me, the WHO was already gently suggesting that the world might want to drop Yamagata from vaccines; by September, the agency had grown insistent, describing the ingredient as “no longer warranted” and urging that “every effort should be made to exclude it as soon as possible.” The following month, an advisory committee to the FDA unanimously voted to speedily adopt that same change.

But the switch from a four-flu vaccine to a trivalent one, guarding against only three, isn’t as simple as ordering the usual, please, just hold the Yams. Trivalent vaccines require their own licensure, which some manufacturers may have allowed to lapse—or never had at all; manufacturers must also adhere to the regulatory pipelines specific to each country. “People think, ‘They change the strains every season; this should be no big deal,’” Paula Barbosa, the associate director of vaccine policy at the International Federation of Pharmaceutical Manufacturers and Associations, which represents vaccine manufacturers, told me. This situation is not so simple: “They need to change their whole manufacturing process.” At the FDA advisory-committee meeting in October, an industry representative cautioned that companies might need until the 2025–26 season to fully transition to trivalents in the Northern Hemisphere, a timeline that Barbosa, too, considers realistic. The South could take until 2026.

In the U.S., though, where experts such as Monto have been pushing for expedient change, a Yamagata-less flu vaccine could be coming this fall. When I reached out to CSL Seqirus and GSK, two of the world’s major flu-vaccine producers, a spokesperson from each company told me that their firm was on track to deliver trivalent vaccines to the U.S. in time for the 2024–25 flu season, should the relevant agencies recommend and request it. (The WHO’s annual meeting to recommend the composition of the Northern Hemisphere’s flu vaccine isn’t scheduled until the end of February; an FDA advisory meeting on the same topic will follow shortly after.) Sanofi, another vaccine producer, was less definitive, but told me that, with sufficient notice from health authorities, its plans would allow for trivalent vaccines this year, “if there is a definitive switch.” AstraZeneca, which makes the FluMist nasal-spray vaccine, told me that it was “engaging with the appropriate regulatory bodies” to coordinate the shift to a trivalent vaccine “as soon as possible.”

Quadrivalent flu vaccines are relatively new. Just over a decade ago, the world relied on immunizations that included two flu A strains (H1N1 and H3N2), plus one B: either Victoria or Yamagata, whichever scientists predicted might be the bigger scourge in the coming flu season. “Sometimes the world got it wrong,” Mark Jit, an epidemiologist at the London School of Hygiene & Tropical Medicine, told me. To hedge their bets, experts eventually began to recommend simply sticking in both. But quadrivalent vaccines typically cost more to manufacture, experts told me. And although several countries, including the U.S., quickly transitioned to the heftier shots, many nations—especially those with fewer resources—never did.

Now “the extra component is a waste,” Vijay Dhanasekaran, a virologist at the University of Hong Kong, told me. It’s pointless to ask people’s bodies to mount a defense against an enemy that will never attack. Trimming Yamagata out of flu-vaccine recipes should also make them cheaper, Dhanasekaran said, which could improve global access. Plus, continuing to manufacture Yamagata-focused vaccines raises the small but serious risk that the lineage could be inadvertently reintroduced to the world, Subbarao told me, as companies grow gobs of the virus for their production pipeline. (Some vaccines, such as FluMist, also immunize people with live-but-weakened versions of flu viruses.)

Some of the researchers I spoke with for this article weren’t ready to rule out the possibility—however slim—that Yamagata is still biding its time somewhere. (Victoria, a close cousin of Yamagata, and the other B lineage that pesters people, once went mostly quiet for about a decade, before roaring back in the early aughts.) But most experts, at this point, are quite convinced. The last couple of flu seasons have been heavy enough to offer even a rather rare lineage the chance to reappear. “If it had been circulating in any community, I’m pretty sure that global influenza surveillance would have detected it by now,” Dhanasekaran said. Plus, even before the pandemic began, Yamagata had been the wimpiest of the flu bunch, Jit told me: slow to evolve, crummy at transmitting, and already dipping in prevalence. When responses to the pandemic starved all flu viruses of hosts, he said, this lineage was the likeliest to be lost.

[Read: The pandemic broke the flu]

Eventually, companies may return to including four types of flu in their products, swapping in, say, another strain of H3N2, the most severe and fastest-evolving of the bunch—a change that Subbarao and Monto both told me might actually be preferable. But incorporating a second H3N2 is even more of a headache than returning to a trivalent vaccine: Researchers would likely first need to run clinical trials, experts told me, to ensure that the new components played nicely with each other and conferred additional benefits.

For the moment, a slimmed-down vaccine is the quickest way to keep up with the flu’s current antics. And in doing so, those vaccines will also reflect the strange reality of this new, COVID-modified world. “A whole lineage of flu has probably been eliminated through changes in human behavior,” Jit told me. Humanity may not have intended it. But our actions against one virus may have forever altered the course of another.

The newest and much-hyped obesity drugs are, at their core, powerful appetite suppressants. When you eat fewer calories than you burn, the body starts scavenging itself, breaking down fat, of course, but also muscle. About a quarter to a third of the weight shed is lean body mass, and most of that is muscle.

Muscle loss is not inherently bad. As people lose fat, they need less muscle to support the weight of their body. And the muscle that goes first tends to be low quality and streaked with fat. Doctors grow concerned when people start to feel weak in everyday life—while picking up the grandkids, for example, or shoveling the driveway. Taken further, the progressive loss of muscle can make patients, especially elderly ones who already have less muscle to spare, frail and vulnerable to falls. People trying to slim down from an already healthy weight, who have less fat to spare, may also be prone to losing muscle. “You have to pull calories from somewhere,” says Robert Kushner, an obesity-medicine doctor at Northwestern University, who was also an investigator in a key trial for one of these drugs.

Kushner worries about patients who start with low muscle mass and go on to become super responders to the drugs, losing significantly more than the average 15 to 20 percent of their body weight. The more these patients lose, the more likely their body is breaking down muscle. “I watch them very carefully,” he told me. The impacts of losing muscle may go beyond losing just strength. Muscle cells are major consumers of energy; they influence insulin sensitivity and absorb some 80 percent of the glucose flooding into blood after a meal. Extreme loss might alter these metabolic functions of muscle too.

Exactly how all of this will affect people on Wegovy and Zepbound, which are still relatively novel obesity drugs, is too early to say. (You may have heard these same two drugs referred to as Ozempic and Mounjaro, respectively, which are their names when sold for diabetes.) These drugs cause a proportion of muscle loss higher than diet and exercise alone, though roughly on par with bariatric surgery. Lifestyle changes can blunt the loss, but pharmaceutical companies are on the hunt for new drug combinations that could build muscle while burning fat.

The arrival of powerful weight-loss drugs has moved the field beyond simple weight loss, Melanie Haines, an endocrinologist at Massachusetts General Hospital, told me. That challenge is largely solved. Instead of fixating on the number of pounds lost, researchers, doctors, and ultimately patients can focus on where those pounds are coming from.

Doctors currently offer two pieces of standard and unsurprising advice to protect people taking obesity drugs against muscle loss: Eat a high-protein diet, and do resistance training. These recommendations are perfectly logical, but their effectiveness against these drugs specifically is unclear, John Jakicic, a professor of physical activity and weight management at the University of Kansas Medical Center, told me. He is now surveying patients to understand their real-world behavior on these drugs.

Fatigue, for example, is a common side effect. “When you’re tired, and you’re fatigued, do you really feel like exercising?” he said. Haines wonders the same about eating enough protein. The drugs are so good at suppressing appetite, she said, that some people might not be able to stomach enough food to get adequate protein. (Food companies have started pitching high-protein snacks and shakes to people on obesity drugs.)

[Read: The Ozempic plateau]

If patients stop taking Wegovy and Zepbound—and about half of patients do stop within a year, at least in real-world studies of people taking this class of drugs for diabetes—the weight regained comes back as fat more than muscle, says Tom Yates, a physical-activity professor at the University of Leicester. Muscle mass tends not to entirely recover. It’s “almost as if you’re better off staying where you are than going through cycles of weight loss,” he told me.

Yet, he pointed out, the U.K. recommends Wegovy for a maximum of two years. In the U.S., patients who can’t afford the steep out-of-pocket price have been forced to stop when insurance companies abruptly cut off coverage or a manufacturer’s discount coupon expires. These policies are likely to trigger cycles of weight loss and gain that lead, ultimately, to net muscle loss.

Meanwhile, drug companies are already thinking about the next generation of weight-loss therapies. “Wouldn’t it be great to have another mechanism that’s moving away from just appetite regulation?” Haines said. Companies are testing ways to preserve—perhaps even enhance—muscle during weight loss by combining Wegovy or Zepbound with a second muscle-boosting drug. Such a combination could, in theory, allow patients to lose fat and gain muscle at the same time.

Years ago, scientists first became interested in potential muscle-enhancing drugs that mimic mutations found in certain breeds of almost comically ripped dogs and cattle. At the time, they hoped to treat muscle-wasting diseases. The drugs never quite worked for that purpose, but the trial for one such drug, an antibody called bimagrumab, found that patients also lost fat in addition to gaining lean mass. A start-up acquired the drug and began testing it for weight loss in combination with semaglutide, the active ingredient in Wegovy, or Ozempic. And last year, Eli Lilly, the maker of Zepbound, snapped up that company for up to $1.9 billion—in hopes of making its own combination therapy.

[Read: Are you sure you want an Ozempic pill? ]

Pairing bimagrumab with an existing obesity drug could potentially maximize the weight loss from both. Losing weight tends to get harder over time; as you lose muscle, your body burns fewer calories. A drug that minimizes that muscle loss—or even flips it into muscle gain—could help patients boost the amount of energy their body expends, while Wegovy or Zepbound suppresses calories consumed. The mechanisms of how this might actually work in the body still need to be understood, though. Previous studies of bimagrumab found that patients grew more muscle, but they didn’t necessarily become faster or stronger. Haines, who is planning a small study of her own with bimagrumab, is most interested in how the combination affects not the structural but the metabolic functions of muscle.

Bimagrumab is the furthest along of several drugs that tinker with the same pathway for muscle growth. The biotech company Regeneron recently published promising data on two of its muscle-enhancing antibodies paired with semaglutide in primates; a trial in humans is due to begin later this year. The start-up Scholar Rock is testing another antibody called apitegromab. Other companies are interested in combining the obesity drugs with different potential muscle boosters that work by mimicking certain hormones such as apelin or testosterone. If they succeed, the next generation of drugs could help sculpt a more muscular body, not just a smaller one. Eating less can only do so much to better your health.

Scott Napper, a biochemist and vaccinologist at the University of Saskatchewan, can easily envision humanity’s ultimate doomsday disease. The scourge would spread fast, but the progression of illness would be slow and subtle. With no immunity, treatments, or vaccines to halt its progress, the disease would eventually find just about every single one of us, spreading via all manner of body fluids. In time, it would kill everyone it infected. Even our food and drink would not be safe, because the infectious agent would be hardy enough to survive common disinfectants and the heat of cooking; it would be pervasive enough to infest our livestock and our crops. “Imagine if consuming a plant could cause a fatal, untreatable neurodegenerative disorder,” Napper told me. “Any food grown within North America would be potentially deadly to humans.”

This nightmare illness doesn’t yet exist. But for inspiration, Napper needs to look only at the very real contagion in his own lab: chronic wasting disease (CWD), a highly lethal, highly contagious neurodegenerative disease that is devastating North America’s deer, elk, and other cervids.

[Read: An incurable disease is coming for deer]

In the half century since it was discovered in a captive deer colony in Colorado, CWD has worked its way into more than 30 U.S. states and four Canadian provinces, as well as South Korea and several countries in Europe. In some captive herds, the disease has been detected in more than 90 percent of individuals; in the wild, Debbie McKenzie, a biologist at the University of Alberta, told me, “we have areas now where more than 50 percent of the bucks are infected.” And CWD kills indiscriminately, gnawing away at deer’s brains until the tissue is riddled with holes. “The disease is out of control,” Dalia Abdelaziz, a biochemist at the University of Calgary, told me.

What makes CWD so formidable is its cause: infectious misfolded proteins called prions. Prion diseases, which include mad cow disease, have long been known as terrifying and poorly understood threats. And CWD is, in many ways, “the most difficult” among them to contend with—more transmissible and widespread than any other known, Marcelo Jorge, a wildlife biologist at the University of Georgia, told me. Scientists are quite certain that CWD will be impossible to eradicate; even limiting its damage will be a challenge, especially if it spills into other species, which could include us. CWD is already a perfect example of how dangerous a prion disease can be. And it has not yet hit the ceiling of its destructive potential.

Among the world’s known infectious agents, prions are an anomaly, more like zombies than living entities. Unlike standard-issue microbes—viruses, bacteria, parasites, fungi—prions are just improperly folded proteins, devoid of genetic material, unable to build more of themselves from scratch, or cleave themselves in two. To reproduce, they simply find properly formed proteins that share their base composition and convert those to their aberrant shape, through mostly mysterious means. And because prions are slightly malformed versions of molecules that our bodies naturally make, they’re difficult to defend against. The immune system codes them as benign and ignores them, even as disease rapidly unfolds. “This is an entirely new paradigm of infectious disease,” Napper told me. “It’s a part of your own body that’s turning against you.”

And yet, we’ve managed to keep many prion diseases in check. Kuru, once common in the highlands of Papua New Guinea, was transmitted through local rituals of funerary cannibalism; the disease fizzled out after people stopped those practices. Mad cow disease (more formally known as bovine spongiform encephalopathy) was contained by culling infected animals and eliminating the suspected source, cow feed made with infected tissues. Even scrapie, a highly contagious prion disease of sheep and goats, is limited to livestock, making it feasible to pare down infected populations, or breed them toward genetic resistance.

[Read: Insomnia that kills]

CWD, meanwhile, is a fixture of wild animals, many of them migratory. And whereas most other prion diseases primarily keep quarters in the central nervous system, CWD “gets in pretty much every part of the body,” Jorge told me. Deer then pass on the molecules, often through direct contact; they’ll shed prions in their saliva, urine, feces, reproductive fluids, and even antler velvet long before they start to show symptoms. Candace Mathiason, a pathobiologist at Colorado State University, and her colleagues have found that as little as 100 nanograms of saliva can seed an infection. Her studies suggest that deer can also pass prions in utero from doe to growing fawn.

Deer also ingest prions from their environment, where the molecules can linger in soil, on trees, and on hunting bait for years or decades. A team led by Sandra Pritzkow, a biochemist at UTHealth Houston, has found that plants can take up prions from the soil, too. And unlike the multitude of microbes that are easily done in by UV, alcohol, heat, or low humidity, prions are so structurally sound that they can survive nearly any standard environmental assault. In laboratories, scientists must blast their equipment with temperatures of about 275 degrees Fahrenheit for 60 to 90 minutes, under extreme pressure, to rid it of prions—or drench their workspaces with bleach or sodium hydroxide, at concentrations high enough to rapidly corrode flesh.

Infected deer are also frustratingly difficult to detect. The disease typically takes years to fully manifest, while the prions infiltrate the brain and steadily destroy neural tissue. The molecules kill insidiously: “This isn’t the kind of disease where you might get a group of deer that are all dead around this watering hole,” Jorge told me. Deer drift away from the herd; they forage at odd times. They become braver around us. They drool and urinate more, stumble about, and begin to lose weight. Eventually, a predator picks them off, or a cold snap freezes them, or they simply starve; in all cases, though, the disease is fatal. Because of CWD, deer populations in many parts of North America are declining; “there is definitely some concern that local populations will disappear,” McKenzie told me. Researchers worry the disease will soon overwhelm caribou in Canada, imperiling the Indigenous communities who rely on them for food. Hunters and farmers, too, are losing vital income. Deer are unlikely to go extinct, but the disease is depriving their habitats of key grazers, and their predators of food.

[Read: America needs hunting more than it knows]

In laboratory experiments, CWD has proved capable of infecting rodents, sheep, goats, cattle, raccoons, ferrets, and primates. But so far, jumps into non-cervid species don’t seem to be happening in the wild—and although people eat an estimated 10,000 CWD-infected cervids each year, no human cases have been documented. Still, lab experiments indicate that human proteins, at least when expressed by mice, could be susceptible to CWD too, Sabine Gilch, a molecular biologist at the University of Calgary, told me.  

And the more prions transmit, and the more hosts they find themselves in, the more opportunities they may have to infect creatures in new ways. Prions don’t seem to evolve as quickly as many viruses or bacteria, Gilch told me. But “they’re not as static as we would like them to be.” She, McKenzie, and other researchers have detected a multitude of CWD strains bopping around in the wild—each with its own propensity for interspecies spread. With transmission so unchecked, and hosts so numerous, “this is kind of like a ticking time bomb,” Surachai Supattapone, a biochemist at Dartmouth, told me.

The world is unlikely to ever be fully rid of CWD; even the options to slow its advance are so far limited. Efforts to survey for infection depend on funding and researchers’ time, or the generosity of local hunters for samples; environmental decontamination is still largely experimental and tricky to do at scale; treatments—which don’t yet exist—would be nearly impossible to administer en masse. And culling campaigns, although sometimes quite effective, especially at the edges of the disease’s reach, often spark public backlash.

Deer that carry certain genetic variants do seem less susceptible to prions, and progress more slowly to full-blown disease and death. But because none so far seems able to fully block infection, or completely curb shedding, prolonging life may simply prolong transmission. “Once an animal gets infected,” Abdelaziz told me, there’s almost a “hope it dies right away.” Even if sturdier prion resistance is someday found, “it’s probably just a matter of time until prions start to adapt to that as well,” Gilch said.

Vaccines, in theory, could help, and in recent years, several research groups—including Napper’s and Abdelaziz’s—have made breakthroughs in overcoming the immune system’s inertia in attacking proteins that look like the body’s own. Some strategies try to target the problematic, invasive prions only; others are going after both the prion and the native, properly folded protein, so that the vaccine can do double duty, waylaying the infectious invader and starving it of reproductive fodder. (So far, lab animals seem to do mostly fine even when they’re bred to lack the native prion protein, whose function is still mostly mysterious.) In early trials, both teams’ vaccines have produced promising immune responses in cervids. But neither team yet fully knows how effective their vaccines are at cutting down on shedding, how long that protection might last, or whether these strategies will work across cervid species. One of Napper’s vaccine candidates, for instance, seemed to hasten the progression of disease in elk.

Vaccines for wildlife are also tough to deliver, especially the multiple doses likely needed in this case. “It’s not like you can just run around injecting every elk and deer,” Napper told me. Instead, he and other researchers plan to compound their formula with a salty apple-cider slurry that he hopes wild cervids might eat with some regularity. “The deer absolutely love it,” he said.

Should any CWD vaccines come to market, though, they will almost certainly be the first prion vaccines that clear the experimental stage. That could be a boon for more than just deer. Another prion disease may spill over from one species to another; others may arise spontaneously. CWD is not, and may never be, the prion disease that most directly affects us. But it is, for now, the most urgent—and the one from which we have the most to lose, and maybe gain.

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