THE TANGLE.(progressive supranuclear palsy)

Billy Borja grew up in Sinajana, a hilltop village near the center of the island of Guam. As a teen-ager in the nineteen-fifties, he liked to hunt, and a few times a month he would take his shotgun down into the "boonies," which was what locals called the jungle that surrounded Sinajana. He almost always came back with a deer, a wild pig, or a dozen flying foxes--fruit bats with wingspans of three feet, which were a delicacy on Guam and on Rota, its nearest neighbor in the Mariana archipelago, and on many other islands in Oceania. Borja's mother boiled the bats in coconut milk and served them in the native Chamorro way: heads, wings, hair, and all.

In 1965, when Borja was twenty-three and just married, he left his young wife, Cecilia, and went to California, where he got a job picking apples in the Salinas Valley. From there, he joined the U.S. Navy, and Cecilia came to live with him at the base at Long Beach. When Borja retired from the Navy, in 1985, he and Cecilia decided to return to Guam. He had not been back in twenty years. The Borjas settled on Billy's old family farm in Sinajana with the three youngest of their five children. Cecilia got a job as a government clerk, Billy hunted and fished, and they tended a flower garden together. Guam had changed while the Borjas were away. Even before they went to California, most of the thatched huts had been replaced with concrete houses, which would not blow down in the typhoons. Now there were gas stations and shopping centers in Sinajana. The boonies had been invaded by brown tree snakes. All the birds were gone, because the snakes had eaten them. The fruit bats were almost all gone, too, overhunted by the Chamorros and the snakes.

One day in October of 2002, Borja, a thin, fit man of fifty-nine, was out cutting brush on the farm. Suddenly, for no apparent reason, he stumbled and fell to the ground. In the next few months, he fell several more times. His wife noticed that he was walking oddly; although his right arm swung freely, his left hung limp. Early in 2003, he developed a shuffling gait and a strange, fixed stare. Borja went to see a doctor at the Guam naval hospital, who referred him to a neurologist named John Steele. "The most striking immediate feature of his appearance is a staring quality of his gaze," Steele wrote in his examination notes. "He blinks very infrequently and when he does, the eyelids close slowly and are slow to open." Borja was able to swivel his eyes to the left and the right but not up or down. Steele had seen that stare before. As a young resident in a hospital in Toronto in the early nineteen-sixties, he and two senior colleagues had identified a rare neurological disease called progressive supranuclear palsy, or P.S.P.; the disease is often called Steele-Richardson-Olszewski syndrome, after the doctors who discovered it. In 1983, Steele moved to Guam, where he still lives; over the years, he has encountered dozens of patients with the fixed gaze that is characteristic of P.S.P. victims.

Steele recommended for Borja a drug usually prescribed for Parkinson's disease, but he was not optimistic. At this point, he suspected that Borja had P.S.P., which is untreatable and implacable. Borja's speech began to slur; he tired easily. He grew weak, and could stand only if two of his sons held him up, one on each side. Cecilia quit her job to take care of him, and when he could no longer walk she and the children drove him wherever he wanted to go. Borja told them that he was frightened. Often, he couldn't sleep, for fear that he might never wake up. One night last August, he grew very agitated. "Why're you whining like a baby?" his wife scolded him gently, although by then he couldn't speak. She reproaches herself now for not taking the moment more seriously--she was in denial, she says. The next morning, while she was feeding him breakfast in bed, he grabbed her arm and pulled it to his chest, something he had never done before. Their youngest son was getting ready for work, and she hurried out of the bedroom for a minute to help him. When she went back in, Borja was dead.

For more than a hundred and fifty years, Chamorros on Guam and on Rota have suffered from a strange neurological disease, which they call lytico-bodig--"lytico" from the Spanish word for paralytic and "bodig" from a Chamorro word for listlessness. The symptoms are polymorphous: some cases present like Alzheimer's disease; others like Parkinson's or amyotrophic lateral sclerosis (A.L.S.); still others like P.S.P. These diseases all have in common a peculiar pattern of neurofibrillary tangles in the brain, and for this reason some neurologists call them the tangle diseases. At the height of the epidemic on Guam, in the nineteen-fifties, the incidence rate was as much as a hundred times as high as the global average for A.L.S. In the worst-hit village, Umatac, a small, remote place where Magellan is said to have landed in 1521, during his voyage around the world, a Chamorro lay sick in almost every hut.

In the nineteen-fifties and sixties, scientists from around the world travelled to Guam and Rota, hoping that if they could figure out what was happening in the islands they would have a clue to the cause of some of the world's most poorly understood diseases. In 1956, the National Institutes of Health established a research station on Guam, to look into the cluster of tangle diseases in the Marianas. Clusters of these diseases are usually small; most are statistical flukes. This cluster was by far the biggest on record. It was so pronounced and so geographically isolated that many neurologists assumed the answer would be easy to find. And the reward would be huge: a scientist who managed to unravel the mystery could help save innumerable lives and would very likely win a Nobel Prize and millions of dollars of funding for research. But by the early nineteen-eighties, when Steele arrived on Guam, the epidemic was already beginning to recede, the research station had closed, and there was still no explanation for the disease, much less a cure. Since then, there has been a dramatic drop in the number of new diagnoses; the only people at risk seem to be those who, like Borja, lived on Guam before 1950 or so. Whatever triggered the disease seems to have disappeared with the Chamorro way of life.

By the turn of the century, the case had gone cold. Fifty years of research seemed to have accomplished almost nothing. On Guam, Steele and a few others still treated and studied the epidemic's last surviving victims. Elsewhere in the world, scientists remembered Guam as a sort of fable of neurology and its difficulties. Then, three years ago, a newcomer to the problem ventured a guess in the journal Neurology, provoking the curiosity and skepticism of nearly every specialist who read it. The author, Paul Cox, was an ethnobotanist; as the director of the National Tropical Botanical Garden on the Hawaiian island of Kauai, and an expert on Pacific fruit bats, he was a complete outsider to neurology. But Cox was convinced that he had succeeded where generations of more qualified scientists had failed.