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Medical Mystery: Does Cyanobacteria play a role in brain diseases like Alzheimer's?

Cyanobacteria, the blue-green algae known as pond scum, produce a toxin called BMAA. Does it play a role in brain diseases like Alzheimer's? [Photo: iStockphoto]

Act 1 - Batty in the South Pacific

After World War II, the native Chamorro people on the island of Guam were struck by a strange neurological disease, a devastating complex of Lou Gehrig's disease with Parkinson's symptoms and an Alzheimer's-like dementia. It killed a quarter of adult Chamorros.

Ethnobotanist Paul Cox found a link between the BMAA neurotoxin and brain disease. Florida scientists advanced his hypothesis while Florida private donors supported the research and created the Institute for Ethnomedicine in Jackson Hole, Wyo., for him to continue his studies. "Florida has been the major incubator of the thing, the major funder and the major intellectual driver." [Photo: Paul Alan Cox]
Scientists knew that those brain diseases are caused by unknown environmental factors working on genetically susceptible people. They quickly came to view the outbreak on Guam as a Rosetta Stone for solving the whole raft of neurodegenerative illnesses — find the cause there, the thinking went, and you'll find the cause everywhere.
The National Institutes of Health opened a research station, and researchers began focusing on the seed of a primitive, chemical-rich plant called the cycad. In the cycad's roots, cyanobacteria, the blue-green algae that most of us know as pond scum, produced a toxin called BMAA that damages nerve cells and was taken up into the cycad's seeds.

Researchers knew Chamorros ate flour that was ground from cycad seed but dropped that line of investigation after determining that the concentrations of BMAA in the flour were so small that the Chamorros would have to eat truckloads of it to get sick.

That was until 2002, when two researchers published a paper proposing an answer to the riddle. One was Oliver Sacks, the scientist on whom the movie Awakenings was based. The other was Paul Cox, an ethnobotanist — someone who studies the relationships between indigenous people and the plants around them. Cox also was a former Mormon missionary named by Time magazine as one of its "Heroes of Medicine" in 1997.

Cox and Sacks argued that fruit bats on Guam ate the cycad seeds and thereby "biomagnified" — concentrated — the neurotoxin in their bodies. The Chamorros cooked the bats whole in coconut milk and ate them as a delicacy and so ended up getting a whopping dose of BMAA big enough to cause brain disease, the two suggested. Cox also observed that the epidemic had dwindled as the bats went nearly extinct.

Fruit bats in Guam feasted on cycad seeds, magnifying the neurotoxin BMAA. The Chamorro people in turn ate the bats as a delicacy. [Photo: Paul Alan Cox]

Act 2 - The Florida Breakthrough

Deborah Mash
Deborah Mash, a UM neurology scientist, wants government and private donors to fund research into a link between BMAA and Alzheimer's. "They better fund this research. People better get in the game. Our research is on the downswing. Without more money, we'll probably close the BMAA project in the next six months." [Photo: Daniel Portnoy]
Cox's theory found many detractors, but he plowed onward. In 2004, he gave a lecture at the University of Miami. In the audience was Deborah Mash, a top-flight UM neuroscientist who researches addiction and neuro diseases. Mash, who founded the school's "brain bank" — a repository for donated tissue samples from healthy and diseased brains — intitially wondered only why the Chamorros would eat bats in the first place.

"The toenails, the hair, in coconut milk, the fur. Come on, man, who the hell eats that? Unless, of course — da-ta-da-dah — there's a buzz factor," Mash says. "For the Guam people it was almost like cocaine."

Aside from the "buzz factor" observation, Mash avoided the BMAA issue. She was focused on other research and knew how controversial the BMAA hypothesis was — "some very fine careers went up and down on this." But Cox and Walter Bradley, then UM's world-renowned neurology department chair, were persuasive, and Mash conducted a blind study using tissue samples from her brain bank.

In 2009, Mash published results of a study that detected BMAA in the brains from 25 Alzheimer's and ALS donors but in only two of 25 samples from healthy donors. Mash's study was "an important piece of the puzzle," Bradley says — indicating that BMAA from algae might be an omnipresent environmental hazard not confined to bats on Guam but perhaps in food, in the water, in the air near water, everyplace cyanobacteria exists, which is just about everywhere.

Act 3 - Dolphins and Dementia

Larry Brand
Larry Brand of UM's Rosenstiel school of marine science: "We now know that the cyanobacterias as a group produce well over 1,000 different, weird compounds. The vast majority we haven't investigated so we don't even know what effects they may be having on us." [Photo: Daniel Portnoy]
Obviously, Americans and other victims of neurodegenerative diseases weren't gobbling up fruit bats, so how would they be ingesting big doses of BMAA? Back in Miami, marine biologist Larry Brand, of UM's Rosenstiel School of Marine and Atmospheric Science on Virginia Key, explored sources.

A laid-back Texan with a doctorate from Woods Hole Oceanographic Institution and MIT and 30 years at UM, Brand is an algae guru. He didn't know Mash but read her paper. "Here I am working on cyanobacteria blooms here in Florida and, hmmm, that's a possibility" — maybe Americans were consuming it in fish and crustaceans that had ingested it from algae in lakes, ponds, rivers and seas, he thought.

Brand studied fish caught near algae blooms and was shocked by the results. Some samples showed nothing. But others were chock full of BMAA. Pink shrimp from Florida Bay and fish from the Caloosahatchee River had concentrations almost as high as the Guam fruit bats. One blue crab from Biscayne Bay had levels twice that of the Guam bats.

Brand also got startling results after studying brains from the carcasses of bottlenose dolphins — apex predators in which the effects of a biotoxin were most likely to be magnified. "All but one of them had high levels of BMAA similar to what you see in Alzheimer's patients. The one that had essentially no BMAA was hit by a boat," he says.
Standing in the Rosenstiel school library, Brand bends over a map showing algae bloom occurrences in Florida. He says people are creating big increases in blooms by dumping more and more nutrients into local waters. Toxins from algae can make us sick from eating tainted fish and breathing tainted air. "Undoubtedly, it's going to be causing increasing human health problems," he says.

bottlenosed dolphin
[Photo: iStockphoto]

The Culprits
People — and their fertilizers, sewage and domestic animal waste — are making the world a friendlier place for toxin-producing algae. Limiting fertilizer use in Florida to stop blooms is a contentious issue, however. Proposed EPA limits on fertilizer, manure and sewage in Florida waterways prompted state officials, agriculture companies and other businesses to file legal challenges, saying the limits will cause great harm to government, whose treatment plants will have to comply, and to the economy. A federal appeals court in August rejected the challenge.


Act 4 - Don't Go Near the Water?

Walter Bradley
UM neurology department chairman emeritus Walter Bradley gave botanist Paul Cox's hypothesis a boost after he became interested in Cox's idea that a toxin from algae causes neurodiseases. The Oxford-educated scientist is the author of the primary neurology textbook used in medical schools and, for lay readers, "Treating the Brain — What the Best Doctors Know" and "Gib's Odyssey: A Tale of Faith and Hope on the Intracoastal Waterway," about a patient who made a solo voyage from Key West to New York and back. Bradley has spent 40 years studying Lou Gehrig's disease. He says it's too early to worry people about eating seafood or living near algae waters. "It's a matter of dosage and susceptibility. Everything in moderation." [Photo: Alan Diaz/Miami Herald]

Supporters of the BMAA hypothesis this month will hold their annual symposium in Miami to discuss their work. Much more research needs to be done, but getting funding for controversial ideas such as the BMAA hypothesis is difficult. Mash exhorts government and private donors to come forward. Some 590,000 Floridians are expected to have Alzheimer's by 2025.

"Our laboratories need to come up to speed, and the naysayers need to get out of the way," Mash says. "Our state is unique. We're surrounded by water. Let's go! Let's go!"
But the naysayers aren't getting out of the way. They scoff at the notion that BMAA in our food or air downwind from an algae bloom is causing neurodisease. One vocal critic of the theory, Christopher A. Shaw, of the University of British Columbia neuroscience department, e-mails, "You do know that the entire story is b.s. from beginning to end?" In an interview, Shaw, whose focus is on a different cycad compound for Guam, gives a point-by-point, scientific knockdown of the BMAA hypothesis, starting with the flaws he sees in Cox's original study.

David Morgan, a University of South Florida medical school professor and coordinator of its Alzheimer Research Laboratory, praises the quality of the methods and researchers on Mash's brain tissue study but questions the conclusions being drawn from it. BMAA may just coincide with some other agent that actually causes Alzheimer's or may be one contributing factor, just as small strokes are, for a disease that likely has many causes.
"The possibility that it causes it is feasible. The likelihood that it is a major cause is low," Morgan says.

Even researchers such as Cox, Bradley and Mash who are hot on the BMAA trail say it's not time to give up eating fish or worry about inhaling every time there's an algae bloom offshore. Clearly, some people are more genetically susceptible to brain diseases than others.

At a BMAA conference a few years back, Bradley's wife had planned the menu for the event at their home and then was horrified, Bradley says, to hear Brand relate his findings of BMAA in fish and crustaceans. "Guess what we fed them?" Bradley says. "Crab cakes and shrimp."