Publisher Health

Caroline Mazel-Carlton began hearing voices when she was in day care. Mornings, by the time she was in middle school, a bowl of oatmeal awaited her for breakfast next to a white saucer of colorful pills. Her voices remained vibrant. They weren’t within her head; they spoke and screamed from outside her skull. They belonged to beings she could not see.The voice who had been with her longest warned of catastrophes coming for her family in Zionsville, a town north of Indianapolis, calamities tied in some unspecified way to TV images from the gulf war: fighter planes, flashes in the sky, explosions on the ground, luminous and all-consuming. A woman’s voice castigated her at school, telling her that her clothes smelled and that she had better keep her hand down, no matter that she knew the answers to the teacher’s questions. Another voice tracked her every move, its tone faintly mocking. “She’s getting out of bed now; oh, she’s walking down the hall now.”Her mix of psychotropic pills shifted, expanded: antipsychotics, mood stabilizers, an antidepressant, a benzodiazepine for anxiety, a stimulant for attention deficit. The pileup of drugs was typical; people hearing voices or having other hallucinations rarely wind up on just one medication. Multiple chemicals are prescribed, often more than one similar antipsychotic simultaneously, in an attempt to quell the psyche.At most, for Mazel-Carlton, the antipsychotics sometimes succeeded in reducing her voices to a wall of sound. This could feel more assaultive than hearing them separately. The antipsychotics caused obesity — 50 pounds of new weight — and the feeling that she was losing control of her forearms and her neck. Her hands quivered and seemed to want to flap-paddle the air. To the isolation caused by the difference of her mind, the drugs added isolation from severe side effects. Her agitation and self-disgust, her terror of being barely human, drove her to twist clusters of her hair around her fingers, to yank hard. Patches of bare scalp crept into view. Classmates taunted, asking why she shook and was going bald, calling her “fat-ass” and “crackhead.”In high school, she supplemented her prescriptions with street drugs — weed, Valium, heroin — in a quest to escape. Though her grades were dismal, she received a perfect score on the verbal section of her SATs. For years she had found partial release in literature: in “Hamlet,” in “Ethan Frome,” with the “delirious descent” of its attempted suicide, which she read aloud to herself over and over. She also read books aloud to her two little sisters. They adored the way she changed her voice during the dialogue and when the narration switched between characters. This talent drew from the voices she heard. It wasn’t that she gave those voices to the characters in the books but more that her mind was well tuned to the nuances of speech, because she heard speech so intimately and ceaselessly. And for her, reading aloud, whether to her sisters or herself, partly quieted the people who existed neither within the books nor within the reality that her family and other human beings inhabited.Her perfect score was enough to get her into Indiana University Bloomington, where she signed up for a neuroscience seminar, figuring, she said, “I’ll learn why I’m crazy.” Though answers weren’t forthcoming, she loved the course. But she was also bartering sex for drugs. It was blurrier than prostitution but no softer: men in states of addiction and states of rage; she absorbing their anger, their brutality; a man battering her in the shower; she waking up in a costume of florid bruises.After an abortion, a voice told her he would remove her fingers “one by one by one.” She was arrested more than once. She tussled with cops; she raved and slammed her head against the wall of a solitary-confinement cell. Her third arrest was for stealing electronics to trade for drugs. It may only have been the wherewithal of her parents, both lawyers, that spared her a criminal sentence. She was sent to a high-end locked ward in the outskirts of Houston and then to a psychiatric farm in the foothills of the Appalachian Mountains, where, after dutifully earning the privilege of not taking her pills under the vigilant eye of a nurse, she decided to quit all her medications. The choice was impulsive but not irrational. She felt calmer at the farm, shoveling out sheep stalls and ministering to the chapped hooves of a runt donkey. And she could no longer bear the drugs’ futility and harm. She did no tapering. She flushed the drugs down the toilet morning by morning and evening by evening, careful that if anyone checked her med case they would find the right number of pills remaining.She shed pounds. Her hair grew back. Her voices seemed to be in retreat though hardly in surrender. She graduated to a group home in Asheville, N.C., where a staff member took the residents on an outing to a flat-track roller-derby bout. Mazel-Carlton expected to be repelled by a crowd of men titillated by skaters in skimpy outfits, but she sat rapt among families watching women of all builds competing in a violent sport that resembled rugby without a ball. She bought skates the next day. She practiced on her own, talked her way into drilling with the local team and soon was in the foreground on billboards around the city: pint-size, with a helmet low above her dark eyes, one of the team’s key scorers. She felt she was starting to manage her turmoil and convert it to determination, and she credited roller derby, where mayhem had to be marshaled and deployed.Around that time, in the late 2000s, when Mazel-Carlton was in her mid-20s, a new position arose in mental health: peer-support specialist, someone with what’s known as lived experience who works alongside practitioners. The idea is that peers can better win the trust of people who are struggling. For Mazel-Carlton, a series of these low-paying roles took her, in 2012, to Holyoke, Mass., once home to more than 25 paper mills, now one of the poorest places in the state. There, she went to work for a fledgling peer-run organization that is now called the Wildflower Alliance, with a three-room headquarters above a desolate downtown street and a goal of transforming the way our society understands and treats extreme mental distress.She began leading Hearing Voices Network support groups — which are somewhat akin to Alcoholics Anonymous meetings — for people with auditory and visual hallucinations. The groups, with no clinicians in the room, gathered on secondhand chairs and sofas in humble spaces rented by the alliance. What psychiatry terms psychosis, the Hearing Voices Movement refers to as nonconsensus realities, and a bedrock faith of the movement is that filling a room with talk of phantasms will not infuse them with more vivid life or grant them more unshakable power. Instead, partly by lifting the pressure of secrecy and diminishing the feeling of deviance, the talk will loosen the hold of hallucinations and, crucially, the grip of isolation.Mazel-Carlton also worked as a sometime staff member at Afiya house, a temporary residence run by the alliance as an alternative to locked wards. The people who stay at Afiya are in dire need; many are not only in mental disarray but also homeless. Many are suicidal. There are no clinicians on staff, no security personnel, only people who know such desperation firsthand. In the living room, a homemade banner declares: “Holding multiple truths. Knowing that everyone has their own accurate view of the way things are.”Afiya house in Western Massachusetts.Danna Singer for The New York TimesA decade after her arrival in Holyoke, Mazel-Carlton and the Wildflower Alliance are now leaders in a growing effort to thoroughly reform how the field of mental health approaches severe psychiatric conditions. Their views remain marginal to the medical establishment. The conventional mode emphasizes risk management, especially when it comes to psychosis; mainstream providers maintain that antipsychotic drugs, despite their downsides, can reduce the long-term odds of mental disintegration, suicide and — however low the odds to begin with — violent eruptions.Yet the evidence that the medications improve outcomes is murky. And it is countered by other studies suggesting that maintenance on the drugs may actually worsen outcomes and even cause brain atrophy, though these findings have been debated. The area is devoid of conclusive science, a failure that is a prominent part of a wider problem in biomedical psychiatry: its lack of progress in treating serious conditions, or even precisely diagnosing and comprehending them. “Something has gone wrong in contemporary academic and clinical psychiatry,” a 2019 lead opinion piece in The New England Journal of Medicine stated. “We are facing the stark limitations of biologic treatments,” it argued. “There is no comprehensive biologic understanding of either the causes or the treatments of psychiatric disorders.”Last June, the World Health Organization published a 300-page directive on the human rights of mental-health clients — and despite the mammoth bureaucracy from which it emerged, it is a revolutionary manifesto on the subject of severe psychiatric disorders. It challenges biological psychiatry’s authority, its expertise and insight about the psyche. And it calls for an end to all involuntary or coercive treatment and to the dominance of the pharmaceutical approach that is foremost in mental health care across conditions, including psychosis, bipolar disorder, depression and a host of other diagnoses. Psychiatry’s problematic drugs, the W.H.O. maintains, must no longer be an unquestioned mainstay.To back its position, the W.H.O. highlights stark words from Thomas R. Insel, who from 2002 to 2015 was head of the National Institute of Mental Health, the largest funder of mental-health research in the world: “I spent 13 years at N.I.M.H. really pushing on the neuroscience and genetics of mental disorders, and when I look back on that, I realize that while I think I succeeded at getting lots of really cool papers published by cool scientists at fairly large costs — I think $20 billion — I don’t think we moved the needle in reducing suicide, reducing hospitalizations, improving recovery for the tens of millions of people who have mental illness.”Better outcomes, the W.H.O. predicts, “will depend on a re-evaluation of many of the assumptions, norms and practices that currently operate, including a different perspective on what ‘expertise’ means when it comes to mental health.” Michelle Funk, a former clinician and researcher who is leading the W.H.O’s work on mental-health policy, law and human rights and is the primary author of the report, spoke to me about the need for a radical change in prevailing clinical presumptions: “Practitioners cannot put their expertise above the expertise and experience of those they’re trying to support.” Present methods can do damage and undermine outcomes not only through psychotropic side effects, and not only through the power imbalances of locked wards and court-ordered outpatient care and even seemingly benign practitioner-patient relationships, but also through a singular focus on reducing symptoms, a professional mind-set that leaves people feeling that they are seen as checklists of diagnostic criteria, not as human beings. “The widespread belief by many in the health sector that people with a mental-health condition have a brain defect or disorder of the brain,” Funk added, “so easily leads to overwhelming disempowerment, loss of identity, loss of hope, self-stigma and isolation.”In demanding a “fundamental paradigm shift” in the field of mental health, the W.H.O. is calling for a close to half a century of psychiatric history. In the early 1960s, weeks before his assassination, President John F. Kennedy signed a mental-health bill into law and declared that “under present conditions of scientific achievement, it will be possible for a nation as rich in human and material resources as ours to make the remote reaches of the mind accessible.” American science, he pledged, would not just land a man on the moon but would triumph over mental illness.This confidence stemmed from psychiatry’s first pharmaceutical breakthrough a decade earlier, the discovery of chlorpromazine (marketed in the United States as Thorazine), the original antipsychotic. The drug brought on debilitating side effects — a shuffling gait, facial rigidity, persistent tics, stupor — but it becalmed difficult behavior and seemed to curtail aberrant beliefs. The Times hailed the drug’s “humanitarian and social significance,” and Time magazine compared Thorazine to the “germ-killing sulfas,” groundbreaking drugs developed in the 1930s and 1940s to fight off bacterial infections. But patients didn’t seem persuaded that the benefits outweighed the harm; they frequently abandoned their medication.Thorazine was followed by Haldol, a more potent antipsychotic whose side effects were no kinder. Yet each drug contributed to a sweeping release of residents from psychiatric asylums, and by the 1970s, crude concepts emerged about how these medications work. Overactive systems of dopamine, a neurotransmitter, were thought to be the culprit in psychosis, and antipsychotics inhibited these systems. The problem was that they impaired dopamine networks all over the brain, including in ways that led to movement disorders and torpor.By the 1980s, though, biological psychiatrists believed that they would solve this flaw by creating more finely tuned antipsychotics. Joseph Coyle, then a professor of psychiatry and neuroscience at the Johns Hopkins School of Medicine, was quoted in a 1984 Pulitzer Prize-winning Baltimore Sun series that heralded new brain research and deftly targeted antipsychotics and other psychotropics on the horizon: “We’ve gone from ignorance to almost a surfeit of knowledge in only 10 years.” A protégé of Coyle’s, Donald Goff, now a psychiatry professor at New York University’s Grossman School of Medicine and for decades one of the country’s pre-eminent researchers into psychosis, told me, about the end of the 1980s, “Those were heady years.” Every day, as he neared a Boston clinic he directed, he saw the marks of Haldol in some of the people he passed on the sidewalk: “As you approached, there were the patients from the clinic with their strange movements, their bent-over bodies, their tremors. Not only was the illness debilitating; the medications were leaving them physically so miserable.” Yet he sensed, he said, “the possibility of limitless progress.”What were christened the “second-generation antipsychotics” — among them Risperdal, Seroquel and Zyprexa — came on the market mostly in the 1990s. In addition to their assault on dopamine, they seemed to act, in lesser ways, on other neurotransmitters, and they appeared to have fewer side effects. “There was so much optimism,” Goff remembered. “We were sure we were improving people’s lives.” But quickly worries arose, and eventually Eli Lilly and Johnson & Johnson, makers of Zyprexa and Risperdal, would pay out several billions of dollars — a fraction of the drugs’ profits — in lawsuits over illegal marketing and the drugs’ effects on users’ metabolisms. Zyprexa caused a greatly heightened risk of diabetes and severe weight gain (Eli Lilly concealed internal data showing that 16 percent of patients gained over 66 pounds on Zyprexa). Some boys and young men who took Risperdal were affected by gynecomastia; they grew pendulous breasts. In 2005, the N.I.M.H. published a study with 1,460 subjects looking at whether the new antipsychotics were in fact better, in efficacy or safety, than one of the first-generation drugs. The answer was no. “It was a resounding disappointment,” Goff said, though he advocates long-term and probably lifelong medication as, on balance, the best way to guard against psychiatric devastation.“If you look at the treatments we have right now,” Coyle, Goff’s mentor, told me, “in terms of their fundamental mechanisms” — the drugs’ disruption of dopamine pathways — “they’re no different than they were almost 70 years ago with the discovery of chlorpromazine. That’s pretty scary.”The W.H.O.’s directive points to 22 examples from around the world, from Norway to Myanmar, of the kind of care it hopes will ultimately displace mainstream psychiatric thinking. The report features Afiya house, along with the other work of the alliance, as well as the type of Hearing Voices groups that Mazel-Carlton is leading — and seeding across the country. Priorities common to the 22 are combating alienation, moving “beyond the biomedical model” that puts “psychotropic drugs at the center” and replacing “the language of diagnoses” with an emphatic embrace of “human diversity.” In a sense, the W.H.O. and Mazel-Carlton are aligned with the neurodiversity movement that has begun to change society’s perceptions of autism. Mazel-Carlton takes care not to diminish the suffering of people like herself and speaks of expanding “the options for healing.” Yet she sees her wish as analogous to not just the mainstreaming of autism but the nascent acceptance of new forms of gender identity. “Our society needs to expand its view of what it means to be human,” she says. “To expand what is affirmed and honored.”Two years into her work with the alliance, in 2014, Mazel-Carlton was overtaken by despair. It wasn’t the first time. Before she left Asheville for Holyoke, her voices grew louder and more lacerating, and she planned out a suicide. This time her reeling began on the forensic psych ward of a decrepit state hospital where the alliance had a peer contract. One day a man with curly blond hair, who was around Mazel-Carlton’s age, was forced down and strapped to the bed in an isolation room. She went in alone without consulting anyone on staff. She had always refused staff offers to review patient charts. She didn’t want assessments; she wanted to know the people, to talk with them as they paced the low-ceilinged halls. She sat on the floor below the bound man. “He was remorseful, tearful,” she remembered. “He was, ‘I’m never going to get out of here now.’ I think he’d been injected; typically, they would give a shot,” she said, referring to the involuntary injection of antipsychotics. “He wasn’t trying to free himself from the restraints, but one of the staff pulled me out of the room, saying that I didn’t understand the danger. Most of them saw me as a crazy person with keys.”The incident wasn’t unusual, but her voices surged, filling her car on her drive home. Her oldest insisted, “They’re going to kill us.” She obeyed his order to barricade her bedroom door with a dresser. “We have to kill them,” he commanded.She had no idea what to do. If she went into the alliance’s office to work, colleagues would figure out what was happening to her mind. If she didn’t go in, they would know just the same. She decided to ask her boss at the alliance whether she could stay at Afiya, not as a staff member but as someone in terrible crisis.“Afiya was where I was no longer hiding,” Mazel-Carlton said, recalling her time there. The house, two towns up the road from Holyoke, is a compact four-bedroom home of gray clapboard, with a chain-link fence bordering one side of a little yard and some low-end rental units across the way. When she was on the psych ward in Houston in her early 20s, or at the Appalachian farm or the Asheville group home, Mazel-Carlton concealed her voices, and until then at the alliance she hadn’t confided their intensity. But somehow Afiya inspired sharing, though the house had no group sessions and no formal methods. An atmosphere without judgment pulled people into revealing conversations. In a basement den, by the hovering blues and golds of a large fish tank, she talked with a gender-nonbinary person about how they each longed to be completely open about themselves, and yearned to live as examples for other people, but also “about how much that can cost, about how there’s a lot of cruelty in the world.”In a bright living room, with a guitar and tambourines mounted between windows, a staff member asked Mazel-Carlton what would help her. As she related this moment to me, the memory of the simple, genuine question moved her to tears, because she felt fully entrusted with knowing what she needed, something that seldom happens with those engulfed in their own realities; their perception is presumed to be too warped. “Some of my voices have their own tastes,” she told me. “I don’t know if I personally like Lynyrd Skynyrd, but my oldest voice does” — the one who impelled her to barricade herself. She told the staff person that she needed him to play “Free Bird.” “He is a serious guitarist; he toured Europe.” He took the guitar from the wall. “Before he even got to the solo where the guitar goes wild, I felt this peace come over that voice.”She stayed seven nights, the official limit. It’s all that is feasible given the demand for Afiya’s bedrooms, with residents coming via mental-health agencies and word of mouth. Fleeting as a week is, it’s not all that different from a typical stay on a psych ward, to which Afiya sees itself as a better alternative. The W.H.O. estimates that Afiya is one of three dozen comparable places, known as peer-run respite houses, across the country.Ephraim, the director of Afiya house.Danna Singer for The New York TimesIn March, Mazel-Carlton, whom I first met in 2019, took me to Afiya and introduced me to its director, Ephraim, who asked that only his first name be used to protect his privacy. That afternoon, over his slender frame, he was wearing a black sweatshirt emblazoned with “Spiritbox,” the name of one of his favorite metal bands. Guests, he explained, are free to come and go at any hour. Then he shared: “I feel like I want to die every day. It’s one of the first things I think about when I wake up. That is normal for me. Many people act like it isn’t normal. Here, we have people express that they want to harm someone. These are all normal thoughts. But people train themselves to believe that they’re not. Giving space to express these things, to have these conversations, that’s the healing thing, that’s the magic here. When we don’t allow that space, things get bigger.”“For some people,” Ephraim said, “staying here is only a slight beginning. There’s power in feeling able to talk and feeling truly heard, in not feeling alone. But for other people, it’s transformative.”For several years now, from her cramped alliance office with a bit of roller derby memorabilia on a shelf above her computer, Mazel-Carlton has been a leader in running Hearing Voices Network groups and training others to do the same around the country, from Augusta, Maine, to Eureka, Calif. H.V.N. originated in the mid-’80s after a Dutch psychiatrist, Marius Romme, worked with a client, Patsy Hage, who was hallucinating and suicidal. Hage insisted that Romme pay attention to the content of her voices instead of dismissing what they said as meaningless. Romme went on to study hundreds of people like Hage, and in a 1989 paper in Schizophrenia Bulletin, he argued that practitioners should “accept the patient’s experience of the voices”; that “biological psychiatry” may not be “very helpful in coping with the voices because it, too, places the phenomenon beyond one’s grasp”; that practitioners should “stimulate the patient to meet other people with similar experiences”; and that patients benefited when they could “attribute some meaning to the voices.” Romme’s paper was mostly ignored, but Hearing Voices support groups cropped up, especially in Britain and across Europe. In the United States, it took much longer; some of the first were started by the alliance around 2008, four years before Mazel-Carlton began working there.For Mazel-Carlton, one of the groups’ most essential tenets is that there must be no disabusing anyone of a personal reality. Unlike on a psych ward or in many a psychiatrist’s office, unusual beliefs are not monitored, corrected, constrained. Mazel-Carlton’s motto is, “If I’m controlling, I’m not connecting” — and connection, for her, is everything. It defines hope.Ideally the groups meet in person, but with the pandemic, the movement has turned to Zoom, and one day in March, I joined a virtual group that Mazel-Carlton helps to conduct. The session drew seven people spanning from North Carolina to Washington State. This particular group focuses on the spiritual, a common theme for people with voices and visions. At the outset, Mazel-Carlton invited everyone to open up by reminding: “This is where I can go if I have direct experiences of the divine. It’s a place I can go, if I’m someone with a psychiatric label, to talk about spirituality without having my experience pathologized. We validate one another here.”A man described being rocked and comforted by “an upside-down angel” when he was growing up. Mazel-Carlton modeled an H.V.N. principle that prizes curiosity about other realities by asking the man for more about his experience. In reply to another participant, she said, “I’m so sorry that people are refusing to honor your soul’s identity.” Then a woman talked about visiting her grandmother in a nursing home during Covid and seeing her grandmother’s “glowing pink orb rising from her chest” and everything as “sparkling and glowing and timeless.”The woman said, “Everything was connected; there was this pulse, this flow” — and there was a fight with a nurse when the woman, feeling that she was God, took off her mask. A psychiatrist labeled her psychotic, “so I couldn’t keep telling him my experiences, because he was telling me I’m sick, and I’m not sick.” In this, according to the mainstream view, she was confirming her illness; denial of one’s diagnosis, termed anosognosia, is seen as a glaring symptom of psychotic disorder.“The first time I came to this group,” the woman went on, “and said something about what happened that day with my grandma, I looked at the screen and people were nodding their heads, and I thought, holy [expletive], people get what I’m talking about. And when people talked about feeling like they’re Jesus Christ, I was like, Oh, my God, I’m not the only one? In group, I don’t feel alone, and feeling alone is like something crushing my chest.” She began to cry minimally. “Group is a place to be vulnerable,” she said. “In my everyday life, I don’t feel safe. I have to put on my armor.”On a wall next to Mazel-Carlton’s desk, there’s a map of the United States dotted with colored pins. Blue pins mark places where she and alliance colleagues have led or arranged for an H.V.N. facilitator training. “I sometimes feel like a general mapping the revolution,” she said. Through her zeal, the network had grown from a handful of U.S. groups to 120, though after two years of the pandemic, the number is closer to 100. Zoom sessions can’t match the reassurance and resonance of in-person gatherings.On the map, red pins represent another campaign. They stand for cities and towns where Mazel-Carlton and the alliance have conducted trainings in their approach to suicide prevention. The workshops are for prospective founders of support groups — and within the groups, as at H.V.N. meetings, clinicians tend to be barred from the room — but they are also for practitioners and family members who want a new way to talk with those contemplating suicide.A slide within the training protocol Mazel-Carlton has designed teaches that the mission is “to stay present” and not “to prevent them from doing that.” “Stay away from fix-it mode, from savior mode,” Mazel-Carlton tells trainees. “With our capes on, we can’t listen.” A first principle is that people must be allowed to talk freely about all that is preying on them, including the wish to take their own lives, and in the groups, a foundational pact is that no one will be reported, not to any hotline, not to the police or any practitioner, no matter what he or she expresses an intent to do. To comprehend how thoroughly this defies dominant practice, take the policy of the country’s most-called — and heavily federally funded — suicide hotline. It advertises confidentiality but covertly scores risk and, each year, without permission, dispatches police cars and ambulances to the doors of thousands. From hotline to psych hospital, the focus is on risk management. It is on exerting control. By contrast, the core idea of the alliance’s program is that as long as you are talking about killing yourself, and feel you are being listened to and understood, you are much less prone to end your life. There’s little research that assesses these approaches or compares them. A 2020 study in the journal Suicide and Life-Threatening Behavior links a person’s perception of being coercively hospitalized with an increased risk of attempted suicide after hospitalization; there is little research that looks at the approach favored by the alliance.Under Mazel-Carlton, the groups have grown to almost 30 from three, from Boston to Denver, despite the obstacles of the pandemic. At least as important, countless U.S. practitioners have learned new ways to listen to the desperate. And a Brazilian mental-health organization, CENAT, has brought Mazel-Carlton to that country, where she has spoken on suicide to clinicians, along with clergy, law enforcement and the diagnosed in São Paulo, Vitória and Salvador. MercyCare, an Australian community-services nonprofit, has flown her in to speak in Sydney, Melbourne and Perth. Over the past two years, in the United States, she has given dozens of talks on suicide and the Hearing Voices movement to audiences of several hundred at conferences, to social-work graduate students, to staff at psych hospitals on grand rounds. In early May, she was in Indianapolis, teaching a roomful of clinicians not far from her childhood home.‘We must also combat the notion that people with mental illness are to be feared.’In addition to leading groups and organizing trainings, Mazel-Carlton packs her days, late into the evenings, with one-on-one sessions — with a grandmother desperate to hear that her grandson’s voices will not destroy his life, with a young man who is certain that his house is under surveillance and who winds up confiding in Mazel-Carlton the sources of his shame. One woman, a mother, told Mazel-Carlton that a voice was commanding that she cut off her hand; if she didn’t, the voice would harm her child. Mazel-Carlton listened and eventually wondered aloud to the woman what the voice might be straining to communicate beneath its horrifying terms. She drew her into thinking about the voice’s underlying meaning, that it could be expressing something about the pressures and conflicts of motherhood, especially during Covid, how caring for a child sometimes feels like a commandment to give up too much of oneself.“As human beings,” Mazel-Carlton said later, “we are drawn to meaning; it gives us a sense of power. But to get there, you can’t feel only that the voice is scary. And to do this work, you have to get past your own fears.”The work, for her, is “a spiritual practice.” But she can be overwhelmed by all that people bring to her, along with her own voices, which are sometimes loud enough that she asks me to repeat a question. The only medication she uses is to help her sleep: trazodone, which at her low dose is prescribed for insomnia. It often fails.Mazel-Carlton knows that the alliance’s methods are not always successful. A year ago, a close friend of hers killed herself, someone who had stayed at Afiya and participated in the alliance’s groups. “When she died, there were people in our community who talked about how they should have done more,” Mazel-Carlton said. “But here’s the reality. As long as our wider world is deeply marginalizing of neurodiversity, we are going to lose people.”The W.H.O. report features another innovative approach, temporary residences called Soteria Houses. In Israel, Pesach Lichtenberg has founded two of a handful of such houses now operating around the world. At the outset of his career, Lichtenberg was taken with the promise of psychopharmacology. In the mid-1980s, he moved from New York City to Israel for his psychiatric training, and one day, as he made rounds with a senior colleague, a patient spoke “about demons and the messiah and so forth,” he told me. “I was fascinated. I’ve always had the problem of being intrigued. But as we walked away from this person, the senior psychiatrist said: ‘That’s not him. That’s his dopamine talking.’ It struck me as such a wonderful insight.” Lichtenberg laughed at himself almost bitterly. “Today I’m ashamed that I could think this way.”For 25 years, Lichtenberg ran the psych ward at a Jerusalem hospital. He described his patients as sodden with medication. “Half the dose was to calm the patient, and the rest was to assuage the anxiety of the staff,” he said. Then, in 2016, utterly disillusioned, he opened his first Soteria House in Jerusalem. He was inspired by a book about the Soteria origin story by Loren Mosher, a former head of schizophrenia research at the N.I.M.H., who was appalled by psychiatry’s heavy reliance on antipsychotics. He established a pair of treatment houses in the Bay Area in the 1970s that minimized medication and prioritized two words, “being with,” as the main treatment philosophy.Mosher’s Soterias eventually closed for lack of funds; two decades later, Lichtenberg picked up where Mosher left off. Lichtenberg’s two Soteria facilities, with two others in the works, can house up to 10 people; the average stay is five weeks. Clinicians are present but sidelined, hierarchies of knowledge are banished, medication is a secondary option, mostly to be avoided unless residents arrive already on drug regimens, and “being with” is carried out above all by melavim, companions — paid interns whose ameliorative mission is simply to be engaged, empathetic and curious, to leave residents feeling less alien, less alone.While visiting Lichtenberg’s houses in 2019, I sat with three residents and two melavim, who talked in an internal courtyard. One resident said that Descartes was the source of his trouble, that while at a job one night, passing the hours playing video games, he had wandered onto a website that included Descartes’s dictum “I think, therefore I am.” “It is stuck in my head like glue,” the young man said, eyes in anguish below his bangs. Before that night, he had had issues with obsessional thoughts. Since, everything outside him was unreal. The melavim, the other residents, the courtyard’s walls and benches, none of it existed. He knew his mind was awry but couldn’t set it right. The melavim asked him about his experience, listening openly, no more, no less.As I spent time with Lichtenberg, I asked about one of the pressing fears with psychosis — eruptions of violence. What he recounted was akin to what I heard at Afiya, where I was told there was just one incident in 10 years, when a staff member suffered two black eyes and was threatened with a pair of scissors. Lichtenberg said that chairs have been broken and plates smashed but that threats against other residents, melavim or staff members are rare. With the exception of one broken nose, the situations have ended with hardly more than a scratch, though one melaveh was put in a headlock before being released without injury. “If someone becomes intimidating,” Lichtenberg said, “I’ll sometimes put my hands behind my back, look him in the eyes and tell him, ‘If you want to attack me, it’s going to be so easy for you.’”Occasionally the Israeli Soterias will insist on medication if a resident becomes too belligerent, but the drug is almost as often an anti-anxiety pill as an antipsychotic, and the dose may then be tapered down, sometimes to nothing. The houses refuse to take a small fraction of applicants because of a recent history of violence, but they have also knowingly accepted residents who, a few months or only weeks before their arrival, put a parent in the hospital, for example, or assaulted a government security officer.Avraham Friedlander, a former director of Lichtenberg’s first house, told me about a resident who, on the man’s first day, interrupted a group meeting in the living room. He splintered a darbuka, a Middle Eastern drum, and began to dance aggressively. In response, Friedlander joined him in the middle of the group, dancing wildly. “Everybody made a drumbeat with their feet, stomping, and we fought in a choreographed way, a dance-fight,” Friedlander said. “He grabbed me; he put me on the floor; but I wasn’t hurt; and later we talked. He was asking what was happening to his mind. He was crying. I slept near him that night, and when he woke with nightmares, I sang him songs and gave him tea.”Soteria’s methods may seem romantic and naïve, but Lichtenberg has won the support of Israel’s Health Ministry, and two of Israel’s four public insurance carriers as well as the Defense Ministry’s insurance system will pay for a stay in Soteria as an alternative to hospitalization. Since Lichtenberg got started in 2016, 17 houses with practices similar to Soteria’s have opened throughout Israel. This year, at the invitation of one of Jerusalem’s major psychiatric institutions, Kfar Shaul Psychiatric Hospital, Lichtenberg has taken over its locked ward and begun to turn it into a Soteria facility.In the United States, the mainstream mental-health establishment has been slower to embrace these alternative approaches, but that might be changing. I asked Ashwin Vasan, the new commissioner of New York City’s Department of Health and Mental Hygiene, whose most recent work has been in mental health, about how cities like New York and San Francisco should respond to a spike in violence and overall lawlessness attributed to the mentally ill and those who don’t have housing. His email reply focused on preventing crises not only by adherence to medication but also by “breaking extreme isolation.” As part of this effort, he added, “We must also combat the notion that people with mental illness are to be feared.”The data does much to support Vasan, suggesting that while those with hallucinations and delusions are probably disproportionately prone to violence, this pattern largely disappears when researchers control for factors like poverty, homelessness and substance abuse. Those may be the more relevant drivers. Data also indicates that people diagnosed with psychosis are less likely to be perpetrators of violence than they are to be its victims.Chacku Mathai, a Hearing Voices Network facilitator, in Rochester, N.Y.Danna Singer for The New York TimesChacku Mathai, whose Indian family immigrated to the United States when he was a child, works as a project director with a large New York State-funded program, OnTrackNY, which combines an emphasis on medication with the inclusion of client perspectives about their care. And he facilitates Hearing Voices groups. During one of our many conversations, Mathai told me a parable about a traveler in a foreign land coming across a bird he has never seen before, a peacock. Thinking that such a freakish creature will never survive, the traveler cuts off its feathers to correct nature’s error.Mathai, who hears voices and has visions and was hospitalized after a suicide attempt as a teenager, is something like the peacock, except that he rejects medication that would shear away his difference. By immersing himself in yogic practices, he gives his mind a measure of rest. Still, voices stalk him, suspicious of people and full of foreboding. Sometimes, he told me, he thinks about whether, if the perfect antipsychotic existed, he would take it. “My experience is so rich,” he said, “I wouldn’t trade it for anything.” He spoke of having a keen empathy for the singularity and solitude of others, a sensitivity that can bring a feeling of being universally joined.Beth, who asked that I use only her first name and who has led H.V.N. groups in Western Massachusetts, pointed out that though the Hearing Voices movement wrestles against conventional psychiatry, it isn’t anti-psychiatry. A former music teacher and cellist, Beth used to take medications that left her with terrible tremors and a torturous physical restlessness called akathisia, deepening the agony of a teaching career lost to her struggles. But after an odyssey of working with inflexible psychiatrists, she found one willing to chart a path of mutual understanding and compromise. She continues to have unsettling visions, but a religious practice along with a calibrated mix of drugs helps somewhat to make her life more manageable while inflicting only mild tremors, and she is playing her cello for the first time in 20 years.Beth, who has led Hearing Voices Network groups in Western Massachusetts.Danna Singer for The New York Times“It’s like an ecosystem of dreams,” Dmitriy Gutkovich said, describing his voices to me over Zoom from Foster City, Calif. Some threaten his family; others speak philosophically on entropy. He takes an almost negligible dose of an antipsychotic, an amount bordering on a placebo. More relevant, he explained, is that H.V.N. groups helped him to realize that coexistence with voices is possible. It is, he said, “about understanding them and their intentions, so that we can live in harmony; it’s about relationship management.” A decade ago, in his early 20s, he was “not in a period of perfect functioning,” he said wryly. “The professional assessment was doom and gloom.” He is now married and a new father. On the screen, he smiled beatifically about this. He is a marketing director at a magazine and oversees an eight-person team.Sometimes, at the end of a conversation with Mazel-Carlton, a mother will ask: “When can we talk again? When?” There is nothing like the panic of a parent whose son or daughter knows another reality. In her office, late one afternoon in March, with the overhead light off and the light from the lone window getting dim, she counseled a mother for the second time by Zoom. The woman’s grown son believed he was taking directions from God. In the recent past, he had been hospitalized, suicidal, homeless. “He thinks he’s kind of like a savior,” she told Mazel-Carlton. His ever-changing plans terrified her. “I need to know how to talk to him. I don’t want to say the wrong thing. I’m trying to just be there, to be empathetic.”She knew Mazel-Carlton’s lessons well, and quietly, Mazel-Carlton echoed and encouraged her.“But I don’t know how to get him to understand that I’m on his side. He’s very turned off to the mental-health system. He told me I put him in the hospital. I said it wasn’t me, it was the psychiatrist. I know he’s going to do what he’s going to do, I know I can’t prevent it, but he says he was comfortable being homeless, because no one could tell him anything — and now what if he becomes homeless again? He could be killed, God forbid.”“I’m not putting this on you,” Mazel-Carlton said, “but it sounds like he’s had some institutional trauma. So what I might avoid is bringing things up from a mental-health lens.”“I think about the M-word,” she said, talking about medication. “But I don’t say it.”“I think that’s wise.”“I can’t help it.”“I think it’s good that you don’t go there,” Mazel-Carlton said. “Pharmaceuticals are easily accessible — he knows that. He knows he can make that choice anytime. When a mom brings up medication, it can sound like, I don’t like the way you are. Like, the way you are makes me uncomfortable.”“I’m freaking out.”“As adults, the moments when we feel that our parents trust us — that’s the lottery-like feeling,” Mazel-Carlton said.“To let him be who he is,” the mother said. “Not to get in his face. I’m really working on it.”“I know you are.”Daniel Bergner is a contributing writer for the magazine. This article is adapted from his book “The Mind and the Moon: My Brother’s Story, the Science of Our Brains, and the Search for Our Psyches,” published this month by Ecco. Danna Singer is a photographer based in Philadelphia as well as a lecturer at Yale School of Art and Princeton. In 2020, she was named a Guggenheim fellow.

Meet Shawn Siepler, the founder of Clean the World. The nonprofit recycles partially used soap left behind from hotel guests for those in need.When hotel or motel guests check into their rooms, they expect at the very least to be greeted with a clean space, a made-up bed and in the bathroom, soap.But what happens when you leave that soap behind?They typically end up in the trash, said Shawn Siepler, the founder of Clean the World, a nonprofit founded in 2009 that recycles bar soap from over 8,000 hospitality partners, including Marriott International and Walt Disney Resorts, for those in need. By collecting, melting, reforming and packaging partially used soap left behind by hotel guests, the nonprofit has distributed nearly 70 million bars of soap in more than 120 countries, including Romania, where many Ukrainian refugees have arrived.Clean the World currently focuses on repurposing bar soap in seven warehouses worldwide. Companies can enroll in the program online and receive boxes to collect discarded products at their properties. Full boxes are shipped to the nonprofit’s warehouses.The organization now has approximately 60 employees, but its beginning was far more humble, with Mr. Siepler and a small group of family and acquaintances scraping used soap by hand with potato peelers in a garage in Orlando.“The first time that the police came by the garage, they wanted to see what all of us Puerto Ricans were cooking. So I gave them a tour,” Mr. Siepler said during a video interview.The conversation has been edited for length and clarity.Before starting Clean the World, you traveled a lot as a sales executive. How did your job lead you to the nonprofit?I was traveling — New York on Monday, Chicago on Tuesday, St. Louis on Wednesday, Los Angeles, Thursday and back — and two clients that I personally managed were Target and Best Buy, both headquartered in Minneapolis. I was in Minneapolis in a hotel room when I came up with the concept of Clean the World.In Minneapolis, my alcohol consumption had to be increased to stay warm. So it was one of those nights that I’m like, “What happens to the soap?” and called the front desk to ask. And they said it was thrown away — they actually told me to have another cocktail.I was doing very well, but had an itch of wanting to do something on my own and thinking about sustainability and green technology as an entrepreneur. And that led to me ask, “What happens to the soap?” I was looking for items that could be recycled.The company started in your cousin’s single-car garage — tell me what those early days were like.I’m an original born-and-raised South Floridian, and we were collecting soap from hotels around the Orlando airport area in my cousin’s garage. We’d all sit around on upside-down pickle buckets with potato peelers, and we would scrape the outside of the bars of soap to surface clean it.My other cousin was on the meat grinder, and he would grind it down. And then we had these Kenmore cookers, and you would cook the soap. All the impurities would bubble up, and you’d wipe those off, and it would turn into this paste.Then we made big wood soap molds, and the paste would dry the next day. We’d wire-cut the bars, take them out and put them on racks.We had to have music on — salsa and merengue. Of course, we couldn’t get the power right when the meat grinder was on, so the power would cut out every 30 minutes.How did Clean the World become the operation it is today?We launched in the garage February 2009.We were distributing just to local charities in Orlando, and then we had an opportunity to go to Haiti in July of 2009. We take 2,000 bars of soap and go into a church that has 10,000 people in it. I remember just saying, “We’re gonna come back. We’re gonna bring more soap. I promise.”When we did that trip, our local Fox affiliate went with us and documented our work. When it ran in New York, it just so happened that Katie Couric was doing CBS Evening News and a senior producer called us in late August or September 2009 and said, “We want to do a piece on you.”Travel Trends That Will Define 2022Card 1 of 7Looking ahead.

After reaching historic lows more than a decade ago, rates are on the rise again.Last month, the Centers for Disease Control and Prevention released its latest data on cases of sexually transmitted infections during the first year of the pandemic. In the early months of 2020, the number of people diagnosed with gonorrhea and syphilis declined, as you might expect — it was, after all, a time of extreme isolation for many. Subsequently, though, infection rates surged so much that by the end of the year, the case counts were 10 percent and 7 percent higher than in 2019. In total, there were some 134,000 reports of syphilis and 678,000 reports of gonorrhea. These were “stunning” increases, says Hilary Reno, an associate professor at the Washington University School of Medicine and medical director of the St. Louis County Sexual Health Clinic. “I can’t tell you how many primary-care physicians have called me recently and said, ‘I just saw my first-ever case of syphilis this year.’”Indeed, syphilis was nearly eradicated in the United States around 2000; gonorrhea reached its lowest rates of infection in 2009. Many doctors who began practicing during that period haven’t had experience diagnosing these S.T.I.s, particularly in their female patients. According to Ina Park, a professor of family and community medicine at the University of California, San Francisco, “There’s an entire generation of physicians and clinicians who had never seen syphilis in women and babies before.”This is a significant problem: S.T.I.s can irrevocably damage the reproductive system. At least 20,000 women are rendered infertile by untreated S.T.I.s in the United States each year. Syphilis can cause sores and rashes and, if untreated for decades, fatal damage to the brain, heart and other organs. Gonorrhea can be painful and may result in pelvic inflammatory disease in women. Each condition is caused by bacteria and can be cured with antibiotics (though drug-resistant strains of the bacterium that causes gonorrhea are on the rise). Unfortunately, they are often asymptomatic, especially in women, and for them it can be harder to see signs of infection and easier to mistake some of those signs as normal discharge or yeast infections.The ease with which S.T.I.s spread undetected makes it crucial to screen for them regularly. Yet that is not happening. “The pandemic made S.T.I.s worse in America — for the first year, people all but stopped getting testing and treatment,” says David C. Harvey, executive director of the National Coalition of S.T.D. Directors, a trade association for state and local S.T.I. Health Department programs that collected its own data during the pandemic. (The C.D.C. data comes from a national surveillance system that includes mandatory lab reporting and sample surveys.) Moreover, contact tracers, assigned to notify sexual partners of exposure, were redeployed to focus on Covid.Historically, the highest rates of syphilis have been among gay and bisexual men, then among heterosexual men. And while that is still true, cases among gay and bisexual men have risen more slowly in recent years and even declined slightly in 2020. Cases among heterosexual women, on the other hand, increased 30 percent from 2018 to 2019 and 21 percent from 2019 to 2020, jumps that experts attribute in part to the increasing prevalence of opioid and methamphetamine abuse, which makes risky sexual behavior — transactional sex, condomless sex — more likely among all genders.Illustration by Ori ToorThis trend among women has fueled a corresponding surge in syphilis among newborns. In 2020, there was a nearly 15 percent increase in congenital syphilis — amounting to a 235 percent increase from 2016. Congenital syphilis can lead to severe lifelong health complications and stillbirth; of 2,148 infants who contracted syphilis in 2020, 149 did not survive. When women who are engaging in substance abuse become pregnant, they frequently avoid prenatal care for fear of being drug-tested and potentially losing custody of the child. That means many of them aren’t tested for syphilis and don’t receive the treatment that would prevent their baby from getting it. The C.D.C. recommends testing for the infection at the first prenatal visit and, for women who test positive or are at increased risk, early in the third trimester as well as at delivery. (Most states require doctors to perform the initial test, but only 19 also require screening in the third trimester.)Perhaps the simplest explanation for the overall rise in S.T.I.s between the 2000s and now is that lawmakers reallocated funding to other problems deemed more dire. Many S.T.I. clinics that provided free or low-cost testing and treatment closed or scaled back hours. Other factors contributed to the problem. The growth of online dating expanded sexual networks. The ability to prevent H.I.V. infection with prophylactic medication reduced the inhibitions against having sex without a condom. And most states still do not provide comprehensive sex education. If they did, more people would know that it’s important to treat S.T.I.s and not wait, says Whitney Irie, a lecturer in population medicine at Harvard Medical School. As it is, a popular impression is that S.T.I.s are “essentially obsolete,” she says. “I don’t think there’s a clear understanding, especially among people with a uterus, of the long-term impact on your reproductive organs. There’s this casualness about it that lends itself to being casual about preventive measures.”Reducing the burden of S.T.I.s will require outreach, particularly for marginalized groups, including women, people in the L.G.B.T.Q. community, Native Americans and Alaskan Natives and people of color, all of whom suffer disproportionately high rates largely because the health care system has neglected them. Black women, for example, have rates of syphilis, gonorrhea and chlamydia that are as much as seven times that of white women, and they face additional hurdles to receiving sexual health care. Black women, Irie says, must also contend with the “perceived stigma and perceived shame from their community” that receiving sexual health care means you don’t share its values, such as female monogamy. That’s a stereotype applied to women across many demographics.To reach those who have been disenfranchised, providers need to be trained to offer sexual health care to patients who have experienced historical trauma and sexual trauma, including assault and abuse. “If they’re met with a system that doesn’t use open terminology or doesn’t recognize their trauma, their experience can be horrible,” Reno says. “We can retraumatize them, and they don’t come back ever.”Public-health initiatives have also succeeded by partnering with local institutions people trust. In St. Louis, which has some of the nation’s highest rates of S.T.I.s, many barbershops and beauty salons offer testing information and free condoms; elsewhere, projects in partnership with churches have been able to increase mammograms and H.I.V. testing among Black women. Half of all new S.T.I. infections are among 15-to-24-year-olds, but school-based health centers that offer comprehensive health services on campus have been shown to improve attendance and graduation rates and decrease urgent-care visits.The pandemic has interrupted countless health services. But it also generated solutions. For example, in March 2020, a program called TakeMeHome began mailing out free H.I.V. self-test kits, with a focus on reaching gay and bisexual men. Half the recipients had not been tested within the previous year, and more than a third of them had never been tested at all; after using the kit, more than 10 percent reported accessing other sexual-health services. “You have to make it as easy for people as possible,” Park says.If you’re sexually active, you will inevitably be exposed to pathogens, just as you are by shaking hands with or breathing the same air as others. “Your clothes are off,” Park says. “That’s the only difference.” S.T.I.s “are not a personal failing,” Reno says. “This is a systemic societal challenge.” Thus, talking openly about sexual health care stands to benefit everyone. Park recommends pressing your provider for testing; ideally, S.T.I. screening would be treated like a trip to the dentist. “Put it in your routine as something you do regularly.”Kim Tingley is a contributing writer for the magazine.

New treatments aim for a gene variant causing the illness in people of sub-Saharan African descent. Some experts worry that focus will neglect other factors.In a Zoom call this spring with 19 leaders of A.M.E. Zion church congregations in North Carolina, Dr. Opeyemi Olabisi, a kidney specialist at Duke University, asked a personal question: How many of you know someone — a friend, a relative, a family member — who has had kidney disease?The anguished replies tumbled out from the assembled pastors:A childhood friend died, leaving a daughter behind.A father and sister felled by the disease.Uncles and sons lost.Three cousins and a brother-in-law on dialysis.None of this surprised Dr. Olabisi, who disclosed that he, too, had lost family members to the disease. His best friend, who had taught him to ride a bike in his native Nigeria, died of kidney failure in his early 30s.Kidney specialists have long known that Black Americans are disproportionately affected by kidney disease. While Black people make up about 12 percent of the U.S. population, they comprise 35 percent of Americans with kidney failure. Black patients tend to contract kidney disease at younger ages, and damage to their organs often progresses faster.Social disparities and systemic racism contribute to this burden, but there is also a genetic factor. Many with sub-Saharan ancestry have a copy of a variant of the gene APOL1 inherited from each parent, which puts them at high risk. Researchers have known for a decade that APOL1 is one of the most powerful genes underlying a common human disease.But there is hope now that much of this suffering can be alleviated. As many as 10 companies are working on drugs to target the APOL1 variants. And Dr. Olabisi has a federal grant to test whether baricitinib, a drug that treats rheumatoid arthritis, can help kidney patients with the variants.Yet the promise of treatments comes with difficult questions.Should genetic testing be offered and, if so, to whom? Although the variants increase risk, they do not preordain kidney disease. If someone knows that they have the variants, will they live in fear of kidney failure?There are as yet no proven ways to reduce the risk of kidney disease in those with two copies of the variants. Rigorous control of blood pressure — a major risk factor for progression of kidney disease — can be difficult to achieve in those who have the variants.“Now we know that the reason you can’t get your blood pressure down is because you have APOL1 kidney disease that is ferociously raising your blood pressure,” said Dr. Jeffrey Kopp, a kidney researcher at the National Institutes of Health. “It’s not your fault.”Despite their elation at the progress being made, some experts like Dr. Olabisi say that a laser focus on variants may let policymakers ignore the social and economic disparities underlying the disease.But, he added, “we don’t want to pretend that the biology doesn’t exist.” That, he said, “would not be doing the community any good.”Dr. Opeyemi Olabisi in the Duke Molecular Physiology Institute in Durham, N.C. He has lost friends and family members to kidney disease.Cornell Watson for The New York TimesA Farmer Provides a ClueWhile it has long been known that kidney failure occurs in African Americans five times as much in as it does in white Americans, “We had never been able to understand all the reasons,” said Dr. Neil Powe, a professor of medicine and an epidemiologist at the University of California, San Francisco.Researchers began looking for a genetic cause. Finally, a little more than a decade ago, a Havard team led by Giulio Genovese, Dr. David Friedman and Dr. Martin Pollak found it: variants of APOL1 that ramped up the gene’s activity.Understand Sickle Cell DiseaseThe rare blood disorder, which can cause debilitating pain, strokes and organ failure, affects 100,000 Americans and millions of people globally, mostly in Africa.The Global Epicenter: In Nigeria, where 150,000 babies are born each year with sickle cell disease, the effects of the condition are pervasive and devastating. On the Edge of Fear: A cure for the disease, which in the United States mostly affects Black people, seems near. For some, it may come too late.Preventing Complications: A legacy of neglect toward Americans with sickle cell means that patients may not receive the treatments needed to stave off the disease’s risks. A Haunting Memory: The Times reporter Gina Kolata shares her experience reporting on the inequities in access to medical advances in the treatment of the disease.It was a complete surprise. APOL1 is part of the immune system and can destroy trypanosomes — protozoa that can cause illnesses. But no one expected it to have anything to do with the kidneys.It turns out that the variants rose to a high frequency among people in sub-Saharan Africa because they offer powerful protection against deadly African sleeping sickness, a disease caused by trypanosomes. It is reminiscent of another gene variant that protects against malaria but causes sickle cell disease in those who inherit two copies. That variant became prominent in parts of Africa and other areas of the world where malaria is common, but sickle cell variants are much less common than APOL1 risk variants.About 39 percent of Black Americans have one copy of the gene’s risk variants; another 13 percent, or nearly 5.5 million, have two copies. Those with two copies are at increased risk for fast progressing kidney disease that often starts in young adulthood. Approximately 15 percent to 20 percent of those with two copies develop kidney disease in their lifetime.In contrast, 7.7 percent of Americans with African ancestry have one copy of the sickle cell variant, and 0.3 percent have two copies.“What nature gave with one hand, it took away with the other,” Dr. Olabisi said.One way to treat kidney disease might be using medicines that block the gene and its variants from acting in the body. But researchers had to find out if APOL1 was necessary for kidney function. If it was, drugs that blocked it might do more harm than good.Researchers found an answer: A farmer in India had no APOL1 gene. His kidneys were totally healthy.Often, in drug development, Dr. Friedman says, the drug dose has to be fine tuned — too much is dangerous and too little is useless. The discovery of the farmer, he said, “tells you you can probably drive the level of the APOL1 protein very low.”But ethical issues have tempered some experts’ enthusiasm about the genetic discoveries.Harriet A. Washington, a lecturer in ethics at Columbia University and author of the book “Medical Apartheid,” worries that knowledge of the role of APOL1 variants can drive the medical establishment toward “a blame-the-victim approach signaling an inherent flaw in African Americans.”The implication, she said: “This is something happening in nature, so what can we do about it?” Such an attitude, she added, “invites futility and absolves health care from treating sufferers.”Joseph L. Graves, Jr., a professor of biological sciences at North Carolina Agricultural and Technical State University, raised another issue. “We don’t want to fall into the myth of the genetically sick African,” he said.“All populations have genetic variants, but the action of those variants is determined by the environment in which those people live,” Dr. Graves explained. “People want to find simple explanations for complex phenomena. Find a genetic variant and make the story simple, but that’s not how it works. Environmental effects are really important.”He added that for Black Americans, profound environmental effects rise from structural racism — inequitable effects of law and policies — which can lead to a lack of access to health care, including preventive care to ward off chronic illness.Erika Blacksher, an ethicist at the nonprofit Center for Practical Bioethics in Kansas City, Mo., added that while finding “a treatment that might counteract the effect of the genetic variant is good news,” she worried that social inequities could not be disentangled from the high rate of kidney disease among those with sub-Saharan African ancestry, not all of whom have the APOL1 variant. Emphasizing the variants, she said, “deflects from our social responsibility to actually change the conditions that contribute to the onset of chronic kidney disease.”Making a PlanMalcolm, left, and Martin Lewis, 26, have lupus, an autoimmune disease that attacks the body’s tissues and organs.Amir Hamja for The New York TimesMartin and Malcolm Lewis, 26-year-old identical twins, have lupus, an autoimmune disease that can ravage the body’s organs. So when Martin developed kidney disease at age 10, his doctors said lupus was to blame.In July 2020, Martin, an actor who lives in Brooklyn, was visiting Malcolm, a data analyst who was hospitalized at Duke with a lupus flare-up. There, the brothers met Dr. Olabisi, who told them about APOL1.They discussed his research project, which involves testing Black Americans and enrolling those with the variant and with kidney disease in a study of the arthritis drug. He invited them to participate and asked if they wanted to know if they had APOL1 variants.“I was all for it,” Malcolm said. So was Martin.When they were tested, the brothers learned they had the variants and that the variants, not lupus, most likely were damaging their kidneys. They hardly knew how to react.“I am still trying to grapple with it,” Malcolm said.But Dr. Olabisi was not surprised. Researchers think the variants cause kidney disease only when there is a secondary factor. A leading candidate is the body’s own antiviral response, interferon, which is produced in abundance in people with lupus.High levels of interferon also occur in people with untreated H.I.V. As happens in people with Covid-19, they can suffer an unusual and catastrophic collapse of their kidneys if they have the variants. Other viral infections, including some that may go unnoticed, can elicit surges of interferon that could set off the APOL1 variants. Interferon is also used as a drug to treat some diseases including cancer and was tested as a treatment for Covid patients.For now, there is little Malcolm and Martin can do except take medications to control their lupus.Martin said he understands all that, but he’s glad he learned he has the variants. Now, he knows what he might be facing.“I’m the kind of person who likes to plan,” he said. “It does make a difference.”From a Gene to DrugsWhile Dr. Olabisi is waiting to start his study, a drug company, Vertex, has forged ahead with its own research. But there was no agreement on how APOL1 variants caused kidney disease, so it was not clear what a drug was supposed to block.“If you don’t understand the mechanism, that means you can’t measure effects in a lab,” said Dr. David Altshuler, chief scientific officer at Vertex. “And if you can’t measure effects in the lab, that means you can’t correct them.”It was known how the APOL1 protein protected against sleeping sickness — it punched holes in the disease-causing trypanosomes, making them swell with fluid and burst.Vertex researchers hypothesized that the variants spurred APOL1 proteins to punch holes not just in trypanosomes but also in kidney cells.What followed was years of work in lab studies and in animals given genes for human APOL1 variants and then screening about a million compounds that might block APOL1.Finally, the researchers settled on a drug that worked in animal models.Vertex tested the experimental drug in a 13-week study in patients with advanced kidney disease. The drug reduced the amount of protein in their urine by 47.6 percent, a sign of improved kidney function.In late March, the company announced it would take the next step — a clinical trial that would enroll approximately 66 patients in the first phase, to find the best dose, and 400 in the next phase, to see if the drug could improve kidney functions in patients with the risk variants and kidney damage and protect them from developing kidney failure or dying.Other companies began later and have revealed less about their plans and progress. AstraZeneca, for example, would only say that it was in the early stages of testing a drug that could bind to APOL1 mRNA, the messenger that carries instructions from the gene to cells’ protein making machinery.MAZE, a small biotech company, is pursuing a strategy similar to the Vertex one, said Dr. Sekar Kathiresan, a co-founder and board member.“I’m optimistic this can move quickly,” Dr. Kathiresan said.Using Their PulpitsAt the meeting with the pastors in North Carolina, Dr. Olabisi said he hoped to test 5,000 Black members of the community for kidney disease with a simple urine test and to use a saliva test to detect APOL1 variants. Testing of the arthritis drug would follow.“I’m in,” said the Rev. Dr. Daran Mitchell, the pastor of Trinity A.M.E. Zion Church in Greensboro, N.C.He and the other pastors were enthusiastic. It would be a community effort, led by people in the community and promoted on social media. Subjects could be tested in churches or in community centers or in their homes. And it was a way to advance the day when a treatment would be available.Dr. Olabisi smiled.“This gives me energy and a lot of hope,” he said.

Kidneys from Black donors are automatically downgraded in transplant assessments, but studying a gene variant could help change that.Transplant specialists, when evaluating kidneys that come from donors, try to work out how likely it is that the kidney will fail after being transplanted into a recipient. Their risk calculations consider factors including the donor’s age, height, weight and history of diabetes. And, to the dismay of some researchers, it also includes the donor’s race.Kidneys from Black donors, living or dead, are automatically downgraded as higher risk.Some experts are now asking if there is a better way of evaluating kidneys from Black donors, one that can rely more on genetic screening rather than race to assess the risk of failure.The proposed genetic screening would check whether donors carry two copies of variants in a gene, APOL1, that are strongly associated with kidney disease. Because most Black donors do not have those genetic variants, the experts argue, their kidneys should not be automatically downgraded.But before instituting that change, researchers say they have to determine if, in fact, kidneys from donors that have the risk variants of APOL1 are more likely to fail.The first hint came from a study by Dr. Barry Freedman, of Wake Forest University in North Carolina involving 1,153 deceased donor kidney transplants performed at 113 different transplant programs. It found that kidneys from deceased donors with two risk variants were twice as likely to fail rapidly compared with kidneys from donors who have one gene variant or none.But that finding will need to be replicated in a bigger research effort. It is getting underway with APOLLO, a large study sponsored by the National Institutes of Health, to assess living and deceased donors. Study researchers are testing kidney donors for APOL1 and following the fate of thousands of transplant patients who have received kidneys from Black American donors at more than 97 transplant programs.In the study, living donors can decide if they want to learn the result of their genetic test and if they want the recipient of their kidney to know the result as well. Medical privacy regulations forbid doctors from telling kidney transplant candidates if a living donor has the variants without the donor’s consent.Dr. Freedman said that whatever results come from the research, more transplant centers are broaching the idea of genetic testing people who want to donate kidneys.Until recently, he added, “many transplant centers said they don’t want to talk about it.”

Thousands of Indians are reeling under a brutal heatwave that has swept through the country.Some areas of the capital, Delhi, have recorded temperatures of 49C.But life has become hardest for the working poor – vast swathes of people employed in the country’s unorganised sector – who are struggling to cope with the soaring temperatures. With no other means of livelihood, they toil through the day in soaring temperatures to ensure they and their families don’t go hungry.Video edited by Anshul Verma

Just as it’s hard to understand a conversation without knowing its context, it can be difficult for biologists to grasp the significance of gene expression without knowing a cell’s environment. To solve that problem, researchers at Princeton Engineering have developed a method to elucidate a cell’s surroundings so that biologists can make more meaning of gene expression information.
The researchers, led by Professor of Computer Science Ben Raphael, hope the new system will open the door to identifying rare cell types and choosing cancer treatment options with new precision. Raphael is the senior author of a paper describing the method published May 16 in Nature Methods.
The basic technique of linking gene expression with a cell’s environment, called spatial transcriptomics (ST), has been around for several years. Scientists break down tissue samples onto a microscale grid and link each spot on the grid with information about gene expression. The problem is that current computational tools can only analyze spatial patterns of gene expression in two dimensions. Experiments that use multiple slices from a single tissue sample — such as a region of a brain, heart or tumor — are difficult to synthesize into a complete picture of the cell types in the tissue.
The Princeton researchers’ method, called PASTE (for Probabilistic Alignment of ST Experiments), integrates information from multiple slices taken from the same tissue sample, providing a three-dimensional view of gene expression within a tumor or a developing organ. When sequence coverage in an experiment is limited due to technical or cost issues, PASTE can also merge information from multiple tissue slices into a single two-dimensional consensus slice with richer gene expression information.
“Our method was motivated by the observation that oftentimes biologists will perform multiple experiments from the same tissue,” said Raphael. “Now, these replicate experiments are not exactly the same cells, but they’re from the same tissue and therefore should be highly similar.”
The team’s technique can align multiple slices from a single tissue sample, categorizing cells based on their gene expression profiles while preserving the physical location of the cells within the tissue.

A research team supported by the National Institutes of Health has identified characteristics of people with long COVID and those likely to have it. Scientists, using machine learning techniques, analyzed an unprecedented collection of electronic health records (EHRs) available for COVID-19 research to better identify who has long COVID. Exploring de-identified EHR data in the National COVID Cohort Collaborative (N3C), a national, centralized public database led by NIH’s National Center for Advancing Translational Sciences (NCATS), the team used the data to find more than 100,000 likely long COVID cases as of October 2021 (as of May 2022, the count is more than 200,000). The findings appeared May 16 in The Lancet Digital Health.
Long COVID is marked by wide-ranging symptoms, including shortness of breath, fatigue, fever, headaches, “brain fog” and other neurological problems. Such symptoms can last for many months or longer after an initial COVID-19 diagnosis. One reason long COVID is difficult to identify is that many of its symptoms are similar to those of other diseases and conditions. A better characterization of long COVID could lead to improved diagnoses and new therapeutic approaches.
“It made sense to take advantage of modern data analysis tools and a unique big data resource like N3C, where many features of long COVID can be represented,” said co-author Emily Pfaff, Ph.D., a clinical informaticist at the University of North Carolina at Chapel Hill.
The N3C data enclave currently includes information representing more than 13 million people nationwide, including nearly 5 million COVID-19-positive cases. The resource enables rapid research on emerging questions about COVID-19 vaccines, therapies, risk factors and health outcomes.
The new research is part of a related, larger trans-NIH initiative, Researching COVID to Enhance Recovery (RECOVER), which aims to improve the understanding of the long-term effects of COVID-19, called post-acute sequelae of SARS-CoV-2 infection (PASC). RECOVER will accurately identify people with PASC and develop approaches for its prevention and treatment. The program also will answer critical research questions about the long-term effects of COVID through clinical trials, longitudinal observational studies, and more.
In the Lancet study, Pfaff, Melissa Haendel, Ph.D., at the University of Colorado Anschutz Medical Campus, and their colleagues examined patient demographics, health care use, diagnoses and medications in the health records of 97,995 adult COVID-19 patients in the N3C. They used this information, along with data on nearly 600 long COVID patients from three long COVID clinics, to create three machine learning models to identify long COVID patients.
In machine learning, scientists “train” computational methods to rapidly sift through large amounts of data to reveal new insights — in this case, about long COVID. The models looked for patterns in the data that could help researchers both understand patient characteristics and better identify individuals with the condition.
The models focused on identifying potential long COVID patients among three groups in the N3C database: All COVID-19 patients, patients hospitalized with COVID-19, and patients who had COVID-19 but were not hospitalized. The models proved to be accurate, as people identified as at risk for long COVID were similar to patients seen at long COVID clinics. The machine learning systems classified approximately 100,000 patients in the N3C database whose profiles were close matches to those with long COVID.
“Once you’re able to determine who has long COVID in a large database of people, you can begin to ask questions about those people,” said Josh Fessel, M.D., Ph.D., senior clinical advisor at NCATS and a scientific program lead in RECOVER. “Was there something different about those people before they developed long COVID? Did they have certain risk factors? Was there something about how they were treated during acute COVID that might have increased or decreased their risk for long COVID?”
The models searched for common features, including new medications, doctor visits and new symptoms, in patients with a positive COVID diagnosis who were at least 90 days out from their acute infection. The models identified patients as having long COVID if they went to a long COVID clinic or demonstrated long COVID symptoms and likely had the condition but hadn’t been diagnosed.
“We want to incorporate the new patterns we’re seeing with the diagnosis code for COVID and include it in our models to try to improve their performance,” said the University of Colorado’s Haendel. “The models can learn from a greater variety of patients and become more accurate. We hope we can use our long COVID patient classifier for clinical trial recruitment.”
This study was funded by NCATS, which contributed to the design, maintenance and security of the N3C Enclave, and the NIH RECOVER Initiative, supported by NIH OT2HL161847. RECOVER is coordinating, among others, the participant recruitment protocol to which this work contributes. The analyses were conducted with data and tools accessed through the NCATS N3C Data Enclave and supported by NCATS U24TR002306.

Instead of relying on the cell’s repair mechanisms, the vaccinia virus MacGyvers a tool for DNA repair from one that it already uses to copy DNA, reports a team of researchers at the Medical University of South Carolina (MUSC) in the Journal of Virology. Blocking that tool — an enzyme known as polymerase — at once disrupts the virus’s ability to copy and to repair DNA, exposing an Achilles’ heel that could be targeted with a therapeutic.
“For vaccinia virus, polymerase is a Sawzall — a tool that you can use for everything” said Paula Traktman, Ph.D., senior author of the article and dean of the College of Graduate Studies at MUSC, who has studied the virus for decades. “Viruses have smaller chromosomes, and so they’ve evolved to be able to use their tools for different things.”
“It’s like the virus’s Swiss Army knife,” said Conor Templeton, Ph.D. lead author of the article, who was a predoctoral candidate in the Traktman laboratory during the study and has since completed his doctorate. “It’s a protein that’s involved in replicating or copying DNA, but it also seems to be involved in repair.”
Such detailed basic science findings about the way viruses copy and repair their DNA have paved the way for breakthrough antiviral therapies in the past 20 years, said Traktman.
“HIV antiretroviral drugs were made by really painstaking analysis of which proteins in the virus are essential, leading to drugs that now have made it a chronic disease,” she said. “A curative treatment for hepatitis C was made possible by painstaking analysis of which proteins are essential for the virus. The more we know about the enemies, the better the weapons we can develop against them.”
Better therapies for pox viruses are certainly needed. The vaccinia virus is a close relative of the virus causing smallpox and was used in the vaccine that successfully eradicated it in the late 20th century. Although smallpox no longer naturally occurs, the threat that it might be used as a bioweapon remains, and currently, there is only one approved antiviral agent against it. Other pox viruses, most notably monkeypox, continue to afflict humans and can be lethal.

Ultra-powerful 7T MRI scanners could be used to help identify those patients with Parkinson’s disease and similar conditions most likely to benefit from new treatments for previously-untreatable symptoms, say scientists.
Both Parkinson’s disease and a related disorder, progressive supranuclear palsy (PSP), are progressive brain diseases that not only affect movement but also damage motivation and cognition. These latter symptoms can have a major impact on a patient’s outcome, affecting their survival and general wellbeing, as well as the stress and costs for families.
To understand the causes of these cognitive symptoms, researchers at the University of Cambridge used a new ultra-high strength ‘7T’ MRI scanner at the Wolfson Brain Imaging Centre to measure changes in the brains of people with Parkinson’s disease, PSP, or in good health. 7T refers to the strength of the magnetic field; most MRI scanners tend to be 3T or below.
The results are published today in the journal Movement Disorders.
Patients with Parkinson’s disease and PSP are often treated with drugs such as L-DOPA, which compensate for the severe loss of dopamine. But, dopamine treatment does little for many of the non-motor symptoms. That is why scientists have begun to turn their attention to noradrenaline, a chemical that plays a critical role in brain functions including attention and arousal, thinking and motivation.
Professor James Rowe from the Department of Clinical Neurosciences at the University of Cambridge, who led the study, said: “Noradrenaline is very important for brain function. All of our brain’s supply comes from a tiny region at the back of the brain called the locus coeruleus — which means ‘the blue spot’. It’s a bit like two short sticks of spaghetti half an inch long: it’s thin, it’s small, and it’s tucked away at the very base of the brain in the brain stem.”
A study last year from Professor Rowe’s team, examining brains donated to the Cambridge Brain Bank, found that some people with PSP had lost as much as 90% of the noradrenaline-producing locus coeruleus.