More than 50 years ago, US Navy doctors stationed on the Pacific island of Guam found a shocking rate of an unknown neurodegenerative disease with the fatal progressive paralysis of Lou Gehrig's disease, the tremors of Parkinson's, and the forgetfulness of dementia.
Guam's indigenous Chamorro people were 50 times to 100 times more likely to suffer the symptoms of amyotrophic lateral sclerosis, also known as Lou Gehrig's disease and ALS, than populations just about anyplace else on the planet. In one village, more than a quarter of the adults who died between 1944 and 1953 were the victims of this mysterious combination of brain illnesses.
Hundreds of research papers since have investigated and dismissed a variety of suspected causes, including microbes, genes, mineral deficiencies and nerve toxins.
Now, a Hawaii-based research team thinks the answer may lie in the Chamorro's favorite entree: Flying fox bats boiled in coconut cream.
This month, researchers led by enthnobotanist Paul Alan Cox, reported finding a toxin they believe works its way up the food chain from the seeds of an ancient palmlike tree that the bats eat, to the nerve cells of the Chamorros, who have devoured the flying foxes nearly into extinction.
To their surprise, Cox and his team also found the same toxin in the brain tissues of people in their control group of Canadians living thousands of miles away -- making the researchers wonder if they had stumbled onto a common thread among neurodegenerative diseases worldwide.
Because of the combination of illnesses, scientists have long thought that unlocking the mystery of the Guam cases was crucial to understanding Alzheimer's, Parkinson's and Lou Gehrig's disease.
"Solve Guam and you have the road map to solve all other gene and environmental interactions leading to neurodegenerative disease," said John Q. Trojanowski, director of the Alzheimer's Disease Center at the University of Pennsylvania School of Medicine.
The new research is provocative, Trojanowski said, but still far from proving a causal connection between dinner and disease.
Cox's work, published in the Proceedings of the National Academy of Sciences, targets bacteria that grow inside the roots of the cycad trees and produce a substance called BMAA that is toxic to nerves. The trees are unusually common on Guam, but cycad species are found all over the world's tropics, including parts of Florida.
Two years ago, Cox teamed up with neurologist Oliver Sacks -- who wrote the book upon which the movie "Awakenings" was based -- to propose that the Chamorros unwittingly ingested large quantities of cycad neurotoxins by eating flying foxes, which feed on cycad seeds. Since then, Cox has been making his case, paper by paper.
His new study reports huge concentrations of BMAA in flying fox specimens. Cox and his team also found BMAA in the brain tissue of six Chamorros who died from the island's neurodegenerative disease, known locally as lytico-bodig and internationally as ALS-PDC -- and in the only two samples that came from Canadians who died from Alzheimer's. The other 13 Canadian brain tissue samples, taken from people without Alzheimer's, showed no measurable levels of BMAA.
"As a Canadian myself, it was a difficult day," said coauthor Susan Murch, a plant neurochemist at University of Guelph in Canada. "It gave the findings a bigger potential implication outside Guam, but our study was not designed to look at Alzheimer's in Canada. At this point, it's only an indication that the bacteria might exist in other ecosystems and we need to look at what's going on there to understand what these findings mean."
Twice before, researchers have suggested cycad toxins as the cause of lytico-bodig -- and twice, their theories have been shot down.
In the 1950s, a nutritionist blamed cycad nuts, which the Chamorros ground into flour.
During the Japanese occupation of Guam during World War II, many Chamorro fled into the forests and may have eaten more cycad flour than usual. But two similar clusters of neurodegenerative disease were found in remote indigenous populations in Japan and Papua New Guinea, neither of whom seemed to eat cycad nuts. So, scientists decided the nuts couldn't be the common thread leading to disease.
Then in the late 1980s, BMAA was found in cycad seeds, and a research group headed by neuroscientist Peter Spencer at Oregon Health and Science University showed that high doses produced neurological problems in monkeys. It seemed even more plausible when Spencer found on a subsequent expedition that cycad seeds were used for healing skin wounds or other medical reasons in the two afflicted communities in Japan and New Guinea.
But the idea of a cycad-disease link was again defeated by follow-up experiments in mice that suggested the Chamorros would need to be exposed to unrealistically huge amounts of cycad flour to accumulate enough BMAA to make them sick, especially since they take pains to wash the cycad seeds before grinding them.
Flying foxes, Cox said, seem to be able to deliver the fatal doses.
He is now looking for ways that BMAA might work its way up the food chain to cause disease in Japan and New Guinea. It is also possible, Cox said, that BMAA may not have anything to do with the disease, but may be a marker of other disease-causing toxins getting into the brain the same way.
For now, the cause of lytico-bodig, which has been steadily declining for 30 years -- perhaps following the decline in the bat population -- remains a mystery.
"It's like an Agatha Christie novel," Cox said. "Here's the cast of characters: Who's the murderer?"