Brand is attempting to understand that risk by tracking how BMAA moves through the food chain in Florida waters where regular cyanobacteria blooms occur. Many of the fish and shellfish specimens he sent to Mash’s lab contained no BMAA, but quite a few did. Bottom-feeders registered notably high, perhaps because cyanobacteria accumulate not only on the ocean surface but also along the seafloor. Compared with the amount of BMAA found in the fruit bats of Guam, the levels of the toxin Brand found in Florida oysters and mussels were moderate. But pink shrimp, largemouth bass, and blue crabs—all eaten by humans—contained levels comparable to or even exceeding those in the bats. One blue crab topped the charts with 7,000 parts per million of BMAA, twice as much toxin as found in a Guam bat.
“That was a shocker,” Brand says. He wondered if it was a fluke, but blue crabs collected by his team from bloom areas in the Chesapeake Bay had similarly high levels of BMAA. Last year Swedish researchers also found the neurotoxin in bottom-feeding fish living in the Baltic Sea, a hotbed for cyanobacteria blooms, although at lower levels than seen in the Chesapeake Bay and along the Florida coast.
The correlations between BMAA and neurological disease seem strong—but as skeptics point out, correlation does not prove causation. And that is just one problem they have with Cox’s theory.
The field has been dogged by clashing findings, leading some critics to question whether BMAA truly is a potent neurotoxin. “You can stuff mice with as much BMAA as you like and you simply don’t see it in the brain,” says Christopher Shaw, a neuroscientist at the University of British Columbia in Vancouver. Furthermore, he says, no known mechanism can explain how an amino acid that is alien to human biology could travel across the blood-brain barrier, get incorporated into proteins, and then trickle out to cause disease.
Raising further doubt, a team led by Douglas Galasko, director of the Alzheimer’s Disease Research Center at the University of California, San Diego, twice tried to find BMAA in Chamorros and North Americans who died of brain disease—and both times came up empty-handed, though using a different method of chemical identification than the one employed by Cox and the Miami team.
David Thurman, a neurologist and epidemiologist at the Centers for Disease Control and Prevention in Atlanta, adds that even if BMAA is doing what Cox believes it is, it appears unlikely to be a major factor behind neurological disorders like ALS and Alzheimer’s. Most experts, he notes, think these brain afflictions have multiple causes, including genes, poor diet, lack of exercise, and a variety of environmental agents, including pathogens and pesticides.
Surprisingly, Cox agrees that the overall risk from BMAA is probably low. In fact, he eats shrimp and crab with relish. “ALS is very rare, and only a few people are genetically at risk,” he says. “Even if BMAA causes common disorders like Alzheimer’s and Parkinson’s, that still doesn’t mean we should shun seafood.” Commercial fishermen generally are not working in areas heavily contaminated with cyanobacteria, he notes, so the danger of exposure in the United States and Canada should be modest for those who eat typical store-bought or homegrown food and avoid drinking—as Cox puts it—“green, smelly” water.
Nevertheless, Cox and his colleagues press on, for the same reasons that researchers flocked to Guam in the 1950s: If BMAA exposure accounts for at least some of the most devastating neurological disorders, learning more about this obscure compound could have huge implications for understanding the underlying disease. Recently, Cox and colleagues have been studying ALS clusters on the Kii Peninsula in southeastern Japan, and he has joined forces with University of Miami neurologist Bradley to study a heightened incidence of the disease among American veterans of the first Gulf War.
In conjunction with Elijah Stommel, the ALS specialist at Dartmouth, Cox is also investigating the peculiar clusters of cases in New England. As word about their work has spread, more doctors have come forward to report cases in the region, with the number of ALS victims jumping from the 200 in Stommel’s original database to 800 today. Sometimes a disease can be more prevalent in one spot than another due to random fluctuations, so the two researchers are working with epidemiologists who are using geographic software programs to distinguish true clusters from artifacts.
The data suggest that ALS is 2.5 times more common than average within one-half mile of a lake or pond where cyanobacteria have bloomed. Stommel hypothesizes that people living around the lakes may have breathed in BMAA from the air, eaten fish contaminated with it, or accidentally swallowed it
while swimming. He and Cox are conducting tests of brain bank tissue to see if the ALS patients in these regions do in fact have elevated levels of BMAA.
While the evidence mounts, Cox is already thinking about ways to detect toxic exposure before it causes disease. He recalls the intriguing case of a woman who died of an ALS-like illness called progressive supranuclear palsy. For decades before her death, she had a habit of cutting her hair, dating it, and putting it in her diary. Since virtually everything consumed leaves a trace residue in hair, Cox and biochemist Murch realized they had an opportunity to see if the woman had been exposed to BMAA. Her hair, they discovered, had been accumulating the toxin as early as 1939, with the level creeping upward over the next two decades. By 1957 the neurotoxin had reached the kind of abundance that Cox had measured in Alzheimer’s patients. The amount peaked around 1962 and then began to decrease, with none detectable at the time of the woman’s death.
“If we had a time machine,” Cox reflects, “we could have gone back in 1957, taken a hair sample, and told her, ‘You are accumulating a very weird neurotoxin.’ We would have found out how she was getting exposed and might have prevented her disease.”
In the future, doctors might routinely test for BMAA overload. They might even be able to counteract its effects. Before health officials are likely to consider limiting environmental exposure to BMAA, however, they will need stronger proof of harm. To that end, Mash would like to see the compound tested again in primates. “The one monkey trial ever done was certainly very provocative,” she says. To her frustration, funding agencies have been reluctant to spend money on a theory so contentious.
For now, Mash and Cox grasp at each clue hoping it will prove the clincher. Researchers in France and Sweden have, over the past couple of years, shown that when BMAA is injected into rodents it gets incorporated into their eyes (pdf), where it could build up and potentially cause damage to cells in the retina. Almost half of the Chamorros who died of lytico-bodig showed damage to retinal cells. Most experts attribute that damage to a parasite, not BMAA. But John Steele, a neurologist at Guam Memorial Hospital who led some of the key research on the disease, adds a detail that sounds. . .fishy: Despite intensive research, no one has yet identified what the parasite could have been.