Paul Alan Cox arrived alone on the remote Samoan island of Savaii when he was all of 19 years old. A devout Mormon sent by the church on a mission, he settled in Fatuvalu, a traditional village on the northern coast with fewer than 200 people. One day, a high chief named Aumalosi came to visit from nearby Letui village. The chief, who didn’t speak English, sat down in Paul’s hut and began uttering what seemed like strange noises, breaking down the Samoan language syllable by syllable and gesturing for Paul to repeat them. The chief came back day after day, month after month, walking the 4 miles each way, and the syllables turned into long passages. Paul learned that Aumalosi was reciting local proverbs and excerpts of speeches from high chiefs.
One afternoon when Aumalosi arrived at Paul’s hut, the young American was prone on his mat, very sick. By then, Paul could speak enough Samoan to apologize for being unable to do the lesson.
“I did not come for the lesson,” Aumalosi replied. He emptied the contents of a woven coconut-leaf basket onto the mat: condensed milk, tinned peaches, gingersnap cookies, and other imported delicacies. “Perhaps you are sick because you are not used to our food,” he said. Aumalosi had gone to the local district store and spent all his money on food the American could eat.
“I have spent much of the last 40 years trying to pay back the contents of that coconut basket,” Paul, now 63, says. The unorthodox path inspired by this quest includes—incongruously—establishing a national park, launching a cosmetics line, and earning international acclaim for his contributions to medicine.
Paul left Samoa after two years and returned to his studies at Brigham Young University, graduating valedictorian with a degree in philosophy and botany. He went on to earn degrees in ecology and biology at the University of Wales and Harvard (where he also twice won the Bowdoin Prize for essay writing, a feat earlier accomplished by Ralph Waldo Emerson). While at Harvard, a professor recognized Paul’s unusual background and encouraged him to pursue ethnobotany, a field that requires expertise in plant science, anthropology, and languages (along with the faith that people who have lived off the same land for thousands of years must know something about their environment). Quickly becoming a star in the field, he taught for 14 years at BYU, until the king of Sweden appointed him to a prestigious chair at Uppsala University.
Today he makes his home in Jackson, Wyoming, where he and his team at the Institute for EthnoMedicine conduct groundbreaking research in an unassuming residential cabin. When I visited in April, I watched Paul speak snippets of Mandarin to a pair of Taiwanese tourists, and Spanish to a Mexican waiter. He interpreted an unreleased Swedish documentary film and explained the Samoan concept of time using snatches of Samoan phrases. When I asked how many languages he speaks, he lost count past a dozen or so, and then he told a story.
He was working with the Minangkabau hill tribes in Indonesia, trying to learn their language, when a group took him to the place where their ancestral queen lived. In his best Minangkabauan he told them, “Surely your queen had a beautiful palace.” Suddenly, everybody was laughing; one guy was hyperventilating. It turns out he had complimented the ancient queen on her private parts. “No matter what language it is, I always screw up,” he says. When visiting indigenous people for the first time, Paul believes, you should assume the role of a puppy that just made a mess on the rug. “The second we walk into a village we’re messing up their culture. We just don’t understand it. But people don’t kill the puppy that soiled the carpet. They teach it.”
Paul (center) and his team at their cabin in Jackson, Wyoming. From left: James Metcalf, Rachael Dunlop, Sandra Banack, and James Powell.
In 1985, back in Samoa doing research, Paul watched as a healer brewed a tea from the bark of the mamala tree and used it to treat hepatitis. Paul sent the tea to researchers at the National Cancer Institute, who found that its powerful antiviral qualities could relieve the infection in T-cells. It became one of the leading drugs used to treat HIV/AIDS, and Paul negotiated a deal to ensure that part of the profits go to the Samoan people. He then worked with the U.S. Congress and the government of American Samoa to create the United States’ 50th national park.
Later, he brought his wife and four young children to Samoa. They stayed for a year, living without plumbing or electricity in a fale, or thatch hut. They were supposed to blend in, but while they were there the villagers faced a terrible dilemma: The government required the island to build a new school, whose construction would cost $50,000. The only way to pay for the school was to sell their 30,000-acre forest to loggers. Paul convinced the chiefs to halt the logging while he made a quick trip back to the States to raise the money. The school was built, the forest preserved.
Much to his dismay, the grateful people of Savaii declared him a chief, a title that comes with the name Nafanua, after a goddess who first saved the island’s forests. Objective ethnobotanists aren’t supposed to get themselves declared chiefs, any more than faithful Mormons are supposed to be given the names of goddesses. But Paul has defied convention at every turn.
In 1997, the Nafanua published a page-turning book about the experience titled, appropriately, Nafanua. That same year he was awarded the Goldman Environmental Prize, known as the “Green Nobel,” and TIME named him one of its 11 “Heroes of Medicine.”
Still, the biggest challenge of his career lay ahead.
The Poison That Gave Us Air
For decades, researchers had been flummoxed by a deadly illness suffered by as many as a quarter of the Chamorro people of Guam. Shortly after World War II, doctors began reporting that the people were coming down with a strange combination of Alzheimer’s, Parkinson’s, and ALS (or Lou Gehrig’s disease). The Chamorros themselves called it lytico-bodig, “listless paralysis.” They were suffering at a rate up to a hundred times higher than the rate of ALS elsewhere. Neurologists tried for five decades to identify the cause, ruling out genetics.
When Paul learned of the disease, he immediately thought of a possible trigger: flying foxes, giant fruit bats with wing spans reaching up to 5 feet. (Paul had studied their role in pollinating rain forests for his doctoral dissertation at Harvard.) He knew that they inhabited the island of Guam; that the bats eat vast quantities of seeds from cycads, a tropical plant that dates back to the dinosaurs; and that natives of the Pacific islands have been eating these bats for millennia. Perhaps a toxin in those seeds was bioaccumulating, building up in the bats the way pesticides do in the environment.
Neurologists hadn’t explored this relationship, so Paul did what comes naturally: He and two other scientists, Sandra Banack and Susan Murch, flew to Guam and talked to the Chamorros themselves. They wrote the names of local foods on 3-by-5 cards, and then asked the interviewees to sort the cards in order of their favorites. Flying foxes consistently landed at the top of the pile. Not only did the people eat bats, they said they were delicious.
For centuries, the bats had been a sustainable food, until Americans came to Guam after the war, bringing guns. Since the bats have no natural predators, they simply circled their home tree when startled by gunfire, making them easy to pick off. The Chamorros started consuming them in such numbers that soon the bats began to disappear.
Paul and his colleagues suspected that the flying foxes themselves weren’t to blame for the high rates of disease. The real source, they thought, lay in what the bats were eating. Cycad seeds contain high concentrations of an amino acid called BMAA, produced by cyanobacteria within the plant’s roots. Also known as blue-green algae, cyanobacteria have been around 3.5 billion years, growing in deserts, oceans, lakes, and even in some car radiators and air conditioning filters. They’re probably the chief reason our atmosphere changed two billion years ago, in what scientists grandly call the Great Oxygenation Event, enabling the evolution of oxygen-breathing species like flying foxes and humans.
But BMAA is also a potent neurotoxin; if taken in massive amounts, it can cause paralysis or death, while the more insidious effects happen slowly. To begin at the beginning of the food chain, it goes like this: The cycads live in synergy with cyanobacteria in the roots. Cyanobacteria produce BMAA, which gets taken up in the cycad seeds. Bats eat the seeds, concentrating the BMAA. Chamorros eat the bats.
Still: How could BMAA cause lytico-bodig?
As the bats vanished from Guam, the Chamorros began importing them from other islands. These imported bats, they confided to Sandra Banack, didn’t taste as good—nor did they contain high levels of BMAA. A decade or two after the native bats began declining, so did the disease.
Paul and Sandra reasoned that BMAA was causing a slow breakdown in the proteins of the central nervous system. Analysis of victims’ brain and nerve tissues had revealed the exact same defects as victims of ALS, Alzheimer’s, and Parkinson’s, including tangled-up proteins. (Medical researchers call them “tangle diseases,” and they’re related to a host of incurable neuronal ailments, including Lewy body dementia, Pick’s disease, and supranuclear palsy.) If the scientists could isolate the process behind lytico-bodig, then they just might find a hint at a remedy for one of them.
Possibly even all of them.
The Dancing Centenarians
As a boy, Paul grew up hiking and climbing in the wilds of the American West. His grandfather was a lifelong conservationist; his mother a fisheries biologist and administrator for the U.S. Fish and Wildlife Service; his father a U.S. Fish and Wildlife agent, national park ranger, and state park superintendent. Paul was so taken by the wilderness that his childhood hero was Glenn Exum, the legendary climber who pioneered a route—now called the Exum Ridge—up part of the Grand Teton in Wyoming. One of Paul’s favorite stories: While charting a course through the mountains, Exum reached a spot where he couldn’t descend safely, and where the only move he could make was a leap to an uncertain hold. In other words, a leap of faith. “It’s a trope I think of a lot,” Paul says today. “I work with a low-percent odds of success.”
Following the revelations in Guam, Paul and his colleagues collaborated with Australian researchers and discovered that BMAA displaces a key amino acid, L-serine, in nerve proteins. Paul wondered if L-serine—a natural component of sweet potatoes, tofu, and even bacon—could offer some sort of clue. So he traveled to a place that was free of tangle diseases and met directly with the people.
The villagers of Ogimi, on the Japanese island of Okinawa, boast a higher percentage of centenarians than anywhere else in the world. (“Hundred-year-old women walking as gracefully as ballerinas,” Paul says.) He learned that their diet, based on tofu and seaweed, contained extraordinary doses of L-serine. He seemed to be on the right track, but lithe centenarians don’t actually prove anything.
Cue the monkeys.
Outnumbering people on the Caribbean island of St. Kitts, vervet monkeys were introduced from Africa by slavers several centuries ago. A biomedical facility on the island maintains monkeys for research, and Paul’s team organized a study to examine the effects of BMAA and L-serine. For 44 days, a group of vervets received bananas after their regular meal. Some of the fruit contained BMAA, some L-serine, some BMAA with L-serine, and some contained rice flour as a control.
In our culture, doctors think of the body as a machine. But what if the illness is the machine?
After 140 days, tissue samples from the monkeys’ brains and central nervous systems got sent to the Brain Endowment Bank at the University of Miami’s School of Medicine. Sure enough, the tissues with the BMAA-fed monkeys revealed brain tangles and beta-amyloid plaques, sticky gunk formed from the membranes around destroyed nerve cells—classic hallmarks of Alzheimer’s. “I was speechless,” Paul says. What’s more, the vervets given L-serine and BMAA showed just half the symptoms of the monkeys given BMAA alone. The team repeated the experiment with twice the monkeys and got the same result. What they saw in the slides looked exactly like the brain tissue of the Chamorro patients.
“Our sense was that this disease might represent a neurological Rosetta Stone,” Paul says. “And if we could figure out what was going on in this village, you might get a deep understanding of the diseases.” All of the tangle diseases are characterized by “misfolding” proteins in the nerve cells—the proteins tau and amyloid for Alzheimer’s, and other proteins for each of the other neuronal diseases. So in other words, by figuring out just one disease—learning what caused the protein to misfold—they might learn the mechanism behind the misfolding proteins in the other diseases. Thus, the vervet slides showing misfolded tau—a sure sign of Alzheimer’s—was their Rosetta Stone. They could see it on the molecular level. BMAA was homing in on the proteins, swapping itself for one of the 20 amino acids and killing the nerve cells. And that amino acid is L-serine.
Why L-serine in the diets of vervets and Okinawans seems to slow or stop the misfolding remains a mystery. (Fruit flies given BMAA become paralyzed, while they’re more likely to remain normal if given L-serine.) One possibility is a flooding-the-field hypothesis: Plentiful L-serine in the blood increases the odds that that amino acid, rather than BMAA, will get inserted into the protein.
Paul thinks another phenomenon may be at play: L-serine somehow sends up an alert, serving as a kind of vaccine.
Your Body May Not Be a Google Car
Different people have different paradigms for illness, Paul says. And our own paradigms tend to change. In Fiji, you may be sick because you failed to respect your ancestors. In Samoa, maybe you’re not getting along with your family, or maybe you’re angry about something and it’s affecting your health. In our culture, doctors and researchers like to think about the body as a machine. A disease is a kind of malfunction of that machine, so you cure the disease by fixing the machine.
This paradigm may help explain medical science’s focus on genetics. Our genes are considered our software, our DNA like the programming in a highly advanced Google car. Understand the code and you can understand a problem with the machine. But what if our body isn’t a machine?
A real machine is relatively predictable. Take one that makes gummy bears in a candy factory. It bangs out one identical gummy bear after another; the manufacturer can predict even the tiniest variability in size and weight. Our bodies are not like that. We’re unpredictable. Besides, Paul says, “Other cultures don’t have this reductionist view of our souls being separate from our bodies.” He believes the soul is not a line of code.
“So,” he says, “I decided that neurodegenerative illnesses are not malfunctions of the machine. They are the machine.” After all, each disease tends to do exactly the same thing to the protein in nerve cells, over and over. Then he thought: What if we could disrupt those machines?
He points out that most researchers believe that Alzheimer’s is caused by beta amyloid, the main ingredient in the plaques that form in patients’ brains. A minority say that the disease is caused by tau, the protein that collapses into tangles. “What if they’re both wrong?” Paul asks. “What if this neuropathology is not the cause, but the symptom?” In other words, what if the tangle diseases involved a gene-environment interaction that caused a switch to be turned on or off? Imagine, say, BMAA turning the switch on, causing a cascade of disruptions in the nerve protein, and L-serine turns the switch off. Imagine if a lifetime diet of L-serine, like that of the Ogimi residents in Okinawa, caused the switch to stick permanently in the off position, and you never get the disease?
Paul, however, doesn’t present this notion as science just yet. “It’s just total baloney by me.”
The Lake Effect
After Paul’s group began publishing their findings, he heard from a leading ALS researcher at Dartmouth College’s Geisel School of Medicine. Elijah Stommel had discovered that a disproportionate number of patients lived on a New Hampshire lake that, like many bodies of water around the world, contained blooms of blue-green algae—cyanobacteria. Other researchers began reporting clusters in Biscayne Bay, off Miami, and among oyster farmers in France.
In one scene from the Swedish documentary film that Paul showed me in Jackson, he stands in the stark white desert of Qatar with a canteen. He pours some water onto the ground and—voila!—a blue-green circle of BMAA-packed cyanobacteria appears. As the Earth’s climate changes, scientists say warmth-loving blue-green algal blooms are becoming increasingly common. Pollution and fertilizer run-off also cause the blooms, fuzzy clumps you can pull out of the water. And as the blooms increase, so do the rates of neuronal diseases. Evidence is mounting that patients’ genes are interacting with the environment to trigger these diseases.
Each of us has a genetic makeup that helps predict the diseases we may suffer from, so most research gets directed at determining which of those genes are involved in which diseases. Several individual genes have already been implicated in ALS. The problem is, genes aren’t the only factor. In fact, 90 percent of ALS patients have no family connection to the disease.
Besides, genes are not fate. Elements in the environment can turn genes on and off. The ALS genes discovered so far, for example, only affect a tiny fraction of ALS patients. What’s more, their discovery only moves researchers a very little way toward a remedy.
Environmental factors are hard to pin down, though, especially with tangle diseases. “We’re saying there’s a 10-, maybe 30-year window from when you’re exposed to when the disease pops up,” Sandra Banack says. “How do you study an environment toxin for 10 to 30 years before you get sick? Epidemiologically, it’s a very difficult problem to study environmental triggers. So it’s just easier to work with genetics.”
In other words, focusing almost exclusively on genetic research follows the same protocol as the drunk looking for his car keys under the street light: That’s the only place he can see. Paul and his team are trying to shine a light in a different direction.
The Untangled Diet
I was sitting at the conference table with Paul in his Jackson lab when he received an email from the Miami brain bank. It was big news: The tissues of the vervet monkeys fed BMAA revealed the second piece of the Rosetta Stone. Besides showing the tangles and plaques of Alzheimer’s, they also displayed microglial activation in the central nervous system—a precursor to ALS. Here was further proof that the tangle diseases were being triggered by the same environmental factors.
Skeptical ALS researchers had told Paul’s team that their theories about BMAA and L-serine were well and good, but what about the spinal cord, the part of the nervous system where ALS does its worst work? Here was clear evidence for the first time.
Sandra Banack walked in, and when Paul told her the news, she sprinted over and hugged him. “This is it!” she shouted. “This is proof!”
Will the critics be convinced? “I could have the angel Gabriel come in and they still won’t be convinced,” Paul replied.
Still, the proof-gathering continues. The Food and Drug Administration approved a human trial in 2012 to test the safety of L-serine for ALS patients. (The FDA saw little risk since L-serine has been a part of the human diet for millennia—one of the key advantages of ethnobotany.) Next will come a phase two trial to determine whether L-serine relieves symptoms in early-onset ALS patients. If that works (and there is no guarantee), then Paul will ask the FDA to recommend L-serine as a supplement for patients. After that: a trial with hundreds of patients, “and probably some pharmaceutical company will license the patent,” he says. Meanwhile, you can buy L-serine on Amazon.
I asked Sandra whether their team takes it, and she walked me back to an alcove with a sink, a stove, and a large tub of sparkling white powder. Heating up a teakettle, she stirred a spoonful of L-serine into a coffee cup and handed it over. It tasted a little like aspartame. “We’re all taking it,” she said.
The Fluorescent Spider
Late one night, Paul invited me to have ice cream at his home atop a butte overlooking the Tetons, the same mountains where his childhood hero took a literal leap of faith and managed to find a hold. Paul began another story, which, when you listen to enough of them, you realize they tend to begin and end with the sacred.
“An anthropologist asked me, ‘How can you be a Mormon and be objective among indigenous people?’ I say I have a spot in my life for the sacred, and so when people tell me the frigate bird is sacred, I get that.”
He continued with what at first seemed like a non sequitur: “I was on the coast of Guadalcanal with people who worship the waki mani mani, which is a boy with the head of a fish who walks on the water. This was my Albert Schweitzer phase. He wrote that he wouldn’t even brush the ants off his arms, because they had the right to be there and he didn’t.
“So I’m climbing this big tree, and I had a local guy from the village with me. This great big fluorescent spider drops on my arm; it’s orange, like safety yellow orange, and I’m in my Schweitzer phase so I won’t brush him off. I say to my buddy from the village, ‘What do you call this?’ And he looks at it and he says, ‘Well, in my language we call it … death.’” He laughed and dished out a generous bowl of ice cream.
“After a couple days the villagers say, ‘Why don’t you come with us?’ So we hike and we hike, and we swim this river and then we climb this mountain, and as we get near to the top, everybody falls silent. We get up there, and it’s a graveyard. They had taken cement and carried it on their backs, and they had stuck metal cups and forks and knives in the cement to mark the graves. Nobody’s talking. We just stood there for a bit. This is important to these people. They had taken me to this special place, and I was really moved.”
He didn’t have to tell the moral. It has to do with understanding that the truth lies somewhere between science and story, listening and laboratory, body and soul.
