An ‘Impossible’ Disease Outbreak in the Alps
In one tiny town, more than a dozen people were diagnosed with the rare neurodegenerative disease ALS. Why?
Photographs by Elliott VerdierIn March 2009, after a long night on duty at the hospital, Emmeline Lagrange took a deep breath and prepared to place a devastating phone call. Lagrange, a neurologist, had diagnosed a 42-year-old woman with amyotrophic lateral sclerosis, or ALS. The woman lived in a small village in the French Alps, an hour and a half drive away from Lagrange’s office in Grenoble Alpes University Hospital. Because ALS is rare, Lagrange expected that the patient’s general practitioner, Valerie Foucault, had never seen a case before.Snow fell outside Lagrange’s window as she got ready to describe how ALS inevitably paralyzes and kills its victims. But to her surprise, as soon as she shared the diagnosis, Foucault responded, “I know this disease very well, because she is the fourth in my village.”ALS, also known as Lou Gehrig’s disease, occurs in roughly two to three people out of every 100,000 in Europe. (The rate is slightly higher in the United States.) But every so often, hot spots emerge. Elevated ALS rates have been observed around a lagoon in France, surrounding a lake in New Hampshire, within a single apartment building in Montreal, and on the eastern—but not western—flank of Italy’s Mount Etna. Such patterns have confounded scientists, who have spent 150 years searching for what causes the disease. Much of the recent research has focused on the genetics of ALS, but clusters provocatively suggest that environmental factors have a leading role. And each new cluster offers scientists a rare chance to clarify what those environmental influences may be—if they can study it fast enough. Many clusters fade away as mysteriously as they once appeared.After the call, Lagrange was uneasy; she had a hunch about how much work lay ahead of her. For the next decade, she and a team of scientists investigated the cluster in the Alps, which eventually grew to include 16 people—a total 10 times higher than the area’s small population should have produced. Even during that first call, when Lagrange knew about only four cases of ALS, she felt dazed by the implications, and by Foucault’s desperate plea for help. If something in the village was behind the disturbing numbers, Foucault had no idea what it was. “She was really upset,” Lagrange remembers. “She said to me, ‘This is impossible; you must stop this.’”For some people, the trouble begins in the throat. As their muscles waste, swallowing liquids becomes a strenuous activity. Others may first notice difficulty moving an arm or a leg. “Every day, we see that they lose something,” Foucault said of her patients. “You lose a finger, or you lose your laugh.” Eventually, enough motor neurons in the brain or spinal cord die that people simply cannot breathe. Lou Gehrig died two years after his diagnosis, when he was just 37. Stephen Hawking, an anomaly, lived with ALS until he was 76.Five to 10 percent of people with ALS have a family member with the disease. In the 2000s, advancements in DNA sequencing led to a swell of genetic research that found that about two-thirds of those familial cases are connected to a handful of genetic mutations. But only one in 10 cases of ALS in which patients have no family history of the disease can be connected to genetic abnormalities. “What we have to then explain is how, in the absence of genetic mutation, you get to the same destination,” Neil Schneider, the director of Columbia’s Eleanor and Lou Gehrig ALS Center, told me.Scientists have come up with several hypotheses for how ALS develops, each more complicated and harder to study than genetics alone. One suggests that ALS is caused by a combination of genetic disposition and environmental exposures throughout a lifetime. Another suggests that the disease develops after one person receives six cumulative “hits,” which can be genetic mutations, exposures to toxins, and perhaps even lifestyle factors such as smoking.Elliott Verdier for The AtlanticEmmeline Lagrange stands in her office at Grenoble University Hospital.Each time a cluster appears, researchers have tried to pin down the exact environmental hazards, professions, and activities that might be linked to it. After World War II, a neurodegenerative disease that looked just like ALS—though some patients also showed features of Parkinson’s and dementia—surged in Guam, predominantly among the native Chamorro people. “Imagine walking into a village where 25 percent of the people are dying from ALS,” says Paul Alan Cox, an ethnobotanist who studied the outbreak. “It was like an Agatha Christie novel: Who’s the murderer?”Early research tried to pin the deaths on an unlikely culprit: the highly toxic cycad plant and its seeds, which locals ground into flour to make tortillas. Cox and his colleagues hypothesize that human cells mistake a compound called BMAA found in the plant for another amino acid, leading to misfolded proteins in the brain. Peter Spencer, an environmental neuroscientist at Oregon Health & Science University, has argued for a different explanation: The body converts cycasin, a compound also found in the plant’s seeds, into a toxic chemical that can cause DNA damage and, eventually, neurodegeneration. Each theory faced its own criticism, and a consensus was never reached—except for perhaps an overarching tacit agreement that the environment was somehow integral to the story. By the end of the 20th century, the Guam cluster had all but vanished.Genetic mutations are precise; the world is messy. This is partly why ALS research still focuses on genes, Evelyn Talbott, an environmental epidemiologist at the University of Pittsburgh, told me. It’s also why clusters, muddled as they might be, are so valuable: They give scientists the chance to find what’s lurking in the mess.Montchavin was a mining town until 1886, when the mine closed, leaving the village largely deserted. In 1973, it was connected to a larger network of winter-tourism destinations in the Alps. On a sunny December afternoon, the week before ski season officially began, I met Foucault outside of the church in the center of Bellentre, a town of 900 whose borders include Montchavin and neighboring villages. The mountains loomed over us, not yet capped with much snow, as she greeted me in a puffer coat. She led me briskly up a steep hill, chatting in a mix of French and English, until we arrived at her home, which she occasionally uses as an office to see patients.Foucault made us a pot of black tea, then set down a notepad of scrawled diagnoses and death dates on the table beside her. The first person Foucault knew with ALS lived a stone’s throw from where we were sitting, in a house down the hill; he had been diagnosed in 1991. The second case was a ski instructor, Daniel, who lived in Montchavin and had a chalet near Les Coches, a ski village five minutes up a switchback road by car. Daniel, whose family requested that I use only his first name for medical privacy, had told Foucault in 2000 that he was having trouble speaking, so she’d sent him to a larynx specialist. When the specialist found nothing wrong with his throat, Daniel was referred to a neurologist in Grenoble, who diagnosed him with ALS.In 2005, after Foucault heard that the husband of one of her general-medicine patients had been diagnosed with ALS, she called her father, a heart doctor in Normandy. “It’s not normal,” he told her. A few years later, she saw one of her patients, the 42-year-old woman, in the village center with her arm hanging limp from her body. Even before the woman received her ALS diagnosis from Lagrange, Foucault suspected the worst.Elliott Verdier for The AtlanticValerie Foucault stands in her backyard in Bellentre.After her call with Foucault, Lagrange assembled a team of neurologists and collaborators from the French government to search for an environmental spark that might have set off the cluster in Montchavin. They tested for heavy metals in the drinking water, toxins in the soil, and pollutants in the air. When the village was turned into a ski destination in the 1970s, builders had repurposed wood from old train cars to build garden beds—so the team checked the environment for creosote, a chemical used in the manufacture of those train cars. They screened for compounds from an artificial snow used in the ’80s. They checked gardens, wells, and even the brain of one deceased ALS patient. Years passed, and nothing significant was found.The day after I had tea with Foucault, I visited Lagrange at the hospital. Her voice faltered as she ruffled through the piles of papers from their investigation on her desk. She’d cared for most of Montchavin’s ALS patients from their diagnosis to death. She worked in Montchavin on the weekends and took her family vacations there. “I felt responsible for them,” she said. “People were telling me, This is genetic. They all live together; they must be cousins. I knew it was not so.” Lagrange’s team had tested the genomes of 12 people in the Montchavin cluster, and none had mutations that were associated with ALS. Nor did any of the patients have parents, grandparents, or great-grandparents with ALS.But their lives did overlap in other meaningful ways. The first Montchavin cases worked together as ski instructors and had chalets in a wooded patch of land called L’Orgère, up the mountain. Many of them hiked together; others simply enjoyed spending time in nature. “We thought they must have something in common, something that they would eat or drink,” Lagrange told me, sitting in her desk chair in a white lab coat and thick brown-framed glasses. She handed me a daunting packet: a questionnaire she’d developed for the ALS patients, their families, and hundreds of people without the disease who lived in the area. The survey, which took about three hours to complete, asked about lifestyle, eating habits, hobbies, jobs, everywhere they had lived, and more. It revealed that the ALS patients consistently ate three foods that the controls didn’t: game, dandelion greens, and wild mushrooms.Lagrange’s team didn’t immediately suspect the mushrooms. But Spencer, the environmental neuroscientist in Oregon, did after he saw one of Lagrange’s colleagues present on the Montchavin cluster at a 2017 conference. Having researched the role of the cycad seed in the Guam cluster, Spencer knew that some mushrooms contain toxins that can powerfully affect the nervous system.Spencer joined the research group, and in 2018, he accompanied Lagrange to Montchavin to distribute more surveys and conduct in-person interviews about the victims’ and other locals’ diets— the pair had particular interest in people’s mushroom consumption. From the responses, the team learned that the ALS patients were not the only mushroom foragers in town, but they shared an affinity for a particular species that local interviewees without ALS said they never touched: the false morel.Elliott Verdier for The AtlanticThe streets of Montchavin are quiet before ski season begins.A false morel looks like a brain that has been left out in the sun. Its cap is a shriveled mass of brown folds, darker than the caramel hue of the true morel. One species, Gyromitra esculenta, grew around Montchavin and was especially abundant near the ski chalets in spring if enough snow had fallen the preceding winter. France has a rich foraging culture, and the false morel was just one of many species mushroom enthusiasts in Montchavin might pick up to sauté with butter and herbs. The false morel contains gyromitrin, a toxin that sickens some number of foragers around the world every year; half of the ALS victims in Montchavin reported a time when they had acute mushroom poisoning. And according to Spencer, the human body may also metabolize gyromitrin into a compound that, over time, might lead to similar DNA damage as cycad seeds.No one can yet say that the false morel caused ALS in Montchavin; Lagrange plans to test the mushroom or its toxin in animal models to help establish whether it leads to neurodegeneration. Nevertheless, Spencer feels that the connection between Montchavin and Guam is profound—that the cluster in the Alps is another indication that environmental triggers can be strongly associated with neurodegenerative disease.Once you start looking, the sheer variety of potential environmental catalysts for ALS becomes overwhelming: pesticides, heavy metals, air pollution, bodies of water with cyanobacteria blooms. Military service is associated with higher ALS risk, as is being a professional football player, a painter, a farmer, or a mechanic. Because of how wide-ranging these findings are, some researchers doubt the utility of environmental research for people with ALS. Maybe the causes are too varied to add up to a meaningful story about ALS, and each leads to clusters in a different way. Or perhaps, Jeffrey Rothstein, a Johns Hopkins University School of Medicine neurologist, told me, a cluster means nothing; it’s simply a rare statistical aberration. “Patients are always looking for some reason why they have such a terrible disease,” he said. “There’s been plenty of blips like this over time in ALS, and each one has its own little thought of what’s causing it, and they’ve all gone nowhere.”“A lot of people look askew to the idea that there are clusters,” Eva Feldman, a neurologist at the University of Michigan, told me. But she sees evidence of clusters all the time in her practice. Once, she saw three women with ALS who’d grown up within blocks of one another in the Grand Rapids area. Her research has shown an association between ALS and organic pollutants, particularly pesticides. Feldman thinks that the importance and scope of environmental triggers for ALS can be pinpointed only by investigating clusters more thoroughly. To start, she told me, doctors should be required to disclose every case of ALS to state officials. Feldman is also planning what she says is the first-ever prospective study on ALS in the U.S., following 4,000 healthy production workers in Michigan. She believes that clusters have significance and that because doctors can’t do much to stop ALS once it starts, “we would be naive to throw out any new ideas” about how to prevent it from occurring in the first place.Even for the people whose lives were upended by the Montchavin cluster, the idea that mushrooms could be linked to such suffering can be difficult to accept. Those who ate them knew the mushrooms could cause unpleasant side effects, but they believed that cooking them removed most of the danger. When I asked Claude Houbart, whose father, Gilles, died in 2019, about his mushroom habits, she called her mother and put her on speakerphone. Claude’s mother said she knew Gilles ate false morels, but she never cooked them for herself or the family—simply because she didn’t want to risk upset stomachs.Daniel, Foucault’s second ALS patient, also kept his foraging hobby out of the home. He never ate false morels in front of his wife, Brigitte, though she knew he picked wild mushrooms with friends. “I am a bit reluctant when it comes to mushrooms; I would have never cooked them,” Brigitte told me, sitting at her kitchen table in Montchavin, surrounded by photos of Daniel and their now-adult children. After Daniel died in 2008, Brigitte and her family spread his ashes in the woods where he’d spent so much of his time. “He didn’t want a tomb like everyone else,” she said. “When we walk in the forest, we think about him.”Elliott Verdier for The AtlanticBrigitte sits in her home in Montchavin.Hervé Fino, a retired vacation-company manager who has lived in the Alps for 41 years, learned to forage in Montchavin. Bundled in a plaid overcoat inside a wood-paneled rental chalet, Fino recalled local foragers telling him that false morels were edible as long as they were well cooked, but he never ate the mushrooms himself, fearing their digestive effects. Fino told me about one of his friends who regularly gathered false morels, and once made himself a false-morel omelet when his wife was out of town. “He was sick for two days, very ill,” Fino said. Later, that same friend was diagnosed with ALS. He died by suicide.In a gruff voice, Fino speculated about what besides the mushroom might have caused the disease. His friend fell into an icy-cold brook two days before he was diagnosed—“Perhaps the shock triggered the disease?” Another woman owned a failing restaurant next to the cable car—maybe the stress had something to do with it. He shrugged his shoulders. Those events didn’t seem right either, not momentous enough to so dramatically alter someone’s fate. Maybe no single explanation ever will. Claude told me she understands why people are skeptical. “Eating a mushroom and then dying in that way?” she said. “Come on.”Before leaving Montchavin, I walked through L’Orgère, the area where the first ALS patients had their ski cabins. The windows were dark, and below, the village of Montchavin was mostly empty before the tourist season began. Clumps of snow started to fall, hopefully enough to satisfy the skiers. Recent winters in the French Alps have been warm and dry—not the right conditions for false morels. “There are no more Gyromitra in Montchavin,” Lagrange said. In her view, Montchavin has joined the ranks of ALS clusters come and gone; no one has been diagnosed there since 2019, and it’s been longer since Lagrange’s team has turned up a fresh false-morel specimen.Even so, on my walk, I couldn’t help but scan for mushrooms, nor could I shake the feeling that my surroundings were not as benign as I’d once believed. Fino said he still keeps an eye out for false morels too. He would never pluck them from the ground to bring home, and yet, he hasn’t stopped looking. One day in 2023, after he parked his car near a ski lift, his gaze caught on a lumpy spot near his feet. Two dark-brown mushrooms stuck out of the damp soil.Elliott Verdier for The AtlanticHervé Fino walks in the snow near Montchavin.
