Copyright 2005 Knight Ridder/Tribune News Service
Knight Ridder/Tribune News Service
Copyright 2005 The Miami Herald
The Miami Herald
May 10, 2005, Tuesday
SECTION: DOMESTIC NEWS
KR-ACC-NO: K1399
LENGTH: 1063 words
BYLINE: By Georgia Tasker

MIAMI _ In an unusual scientific journey, an ethnobotanist is tracking a toxin he believes could be a cause of Alzheimer's, Parkinson's, Lou Gehrig's and other baffling neurological diseases.

Doing research ordinarily done by other types of scientists, Paul Alan Cox thinks he may have made a significant discovery: that the toxin is produced by blue-green algae, the oldest and most pervasive organism on the planet.

Cox and his nine collaborators found that 97 percent of all blue-green algae, more commonly known as cyanobacteria, produce the neurotoxin, according to their paper in the Proceedings of the National Academy of Sciences. This "suggests a potential for widespread human exposure," they wrote.

Cyanobacteria occur naturally in oceans, lakes and estuaries. The Red Sea is named for a reddish cyanobacteria. When conditions are right, the cyanobacteria explode into blooms, concentrating the toxins they give off.

Much more investigation remains before anyone can say definitively the cyanobacteria cause neurological disease and, if they do, how the bacteria get from the algae into human brains.

No one knows exactly what causes neurodegenerative diseases; research is focused on genetics and environment.

Some scientists are skeptical of Cox's theories.

"He's run with this hypothesis when the likelihood is that nobody can replicate the data," said Dr. Daniel Perl, director of neuropathology at Mount Sinai Medical Center in New York. "I don't know what the hell he's measuring."

But the findings excite others, including Dr. Walter Bradley, head of the department of neurology at the University of Miami. The university is examining brain tissues to see if they contain the toxin.

"I believe if what Paul has found turns out to be correct, he is likely to get the Nobel Prize. It may be the answer or one of the answers to neurodegeneration," Bradley said.

Deborah Mash, who heads the brain endowment bank at the University of Miami, said the testing began within the last four or five months. While hundreds of tests must be done, Mash said the researchers detected the toxin in brains of deceased people who had Alzheimer's and ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig's disease).

"We're confident our data are real. We think they're promising and supportive of what Cox is saying."

The story of Cox's research begins on the Pacific island of Guam, where an extraordinarily high number of indigenous Chamorros suffered degenerative symptoms: paralysis, impaired speech, eyes that saw straight ahead but not up or down, weakness and dementia.

When Oliver Sacks wrote "Island of the Color Blind" (Knopf, $24) in 1996, he devoted half of the book to the Guam story of neurological disorders. In 2002, Sacks co-authored a paper with Cox about the Chamorros eating bats in which the neurotoxin had magnified 10,000-fold.

Cox entered neurology as an outsider, with a doctorate in biology from Harvard University and years of research as an ethnobotanist, studying plants that indigenous people use in daily life, particularly for medicine.

He began pursuing his research in the mid-1990s, when it was known only that Chamorros used flour made from cycads that had small amounts of the cyanobacteria in their roots and seeds, but not enough toxin to harm the people.

Cox went village to village to see what else the villagers ate besides the cycad flour. He discovered the Chamorros considered bats a delicacy. They ate them with such gusto that they caused one species to go extinct and put a second on the endangered species list, after which the neurodegenerative diseases began to diminish in the 1950s. No Chamorros have developed the symptoms since 1960.

Dried museum remains of some of the Guam bats collected in the 1950s were tested and found to have prodigious amounts of the toxin, Cox said.

Cox and other scientists next analyzed the brain tissue of the islanders who died of the degenerative diseases and brain tissue of 15 Canadians as a control group. While the brain tissue of the islanders tested positive, the surprising result was that two Canadian samples turned up with the toxin, both in brains of people who died of Alzheimer's disease.

A second small study was done on Canadian brain tissue from seven Alzheimer's patients and one non-Alzheimer's control. Again the toxin appeared, in six of the seven Alzheimer samples.

The toxin is a non-protein amino acid, BMAA or B-N-methylamino-L-alanine, identified in 1967. "There are only 20 amino acids that make up the proteins in everything from daisies to elephants to people," Cox explained. BMAA is not one of the 20 amino acids that make up proteins, but it has been discovered both as a free amino acid in the body and bound to proteins.

"If a protein is a pearl necklace, and amino acids are individual pearls, BMAA gets stuck in there as a square pearl," Cox said.

Cox hypothesizes that BMAA enters the food chain, eventually accumulating in proteins, then is gradually released as proteins are metabolized. Some BMAA ends up in the brain, free to damage the neurons.

"This is certainly very interesting science, and we are keeping our eye on it," said Niles Frantz, at the Alzheimer's Association in Chicago. "At the same time, it is very preliminary research, and the connection to Alzheimer's disease has not been proven."

Perl, who was the neuropathologist for scientists preceding Cox in the Guam work, has a brain bank of Chamorro samples. "I've been working on this for 25 years, and I'd love to find the answer," he said, noting there could be "a number of things he could be seeing."

John Hardy, chief of the laboratory of neurogenetics for the National Institutes of Health in Bethesda, Md., also is skeptical. "There is no trail of evidence to say BMAA can cause tangle diseases. It's just an idea, in my view."

The Institute for Ethnomedicine, affiliated with the National Tropical Botanical Garden, has funded Cox's research. He is on leave as director of the National Tropical Botanical Garden. He previewed his latest findings at The Kampong in Coconut Grove, Fla., in January.

"We're afraid all people could be exposed to low levels of BMAA," he said. "What once was believed to occur only on Guam might be more widespread."