Was Lou Gehrig's ALS Caused by Drinking Water?
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One of the major discoveries made by Cox and his colleagues, published in 2004, was that 50 to 100 times as much BMAA is bound within proteins than exists as free amino acids, which are not bound together into chains but float in the cellular or intercellular fluid. Cells build proteins by stringing together amino acids using a process called translation.
“At the time Cox first published his hypothesis,” says Walter Bradley, a neurologist and ALS expert at University of Miami Miller School of Medicine, “the scientific world thought translation was so accurate that no amino acid other than the 20 that normally make up our proteins could be incorporated into them.” Since amino acids dissolve in water, most scientists also didn’t think BMAA could biomagnify.
Cox’s ability to see solutions where others see obstacles has earned rave reviews from some of his peers. Bradley, who collaborates with Cox, calls him a polymath, a Renaissance man. A former graduate student, Renee Richer — who helped connect higher rates of ALS in Gulf War veterans with inhalation of desert crusts containing cyanobacteria — describes him as “one of those rare minds that comes along only once in a while.”
But along with the kudos are still some criticisms. A handful of scientists were skeptical of the BMAA hypothesis, before and after Cox came along. These included Douglas Galasko, director of the Alzheimer’s Disease Research Center at the University of California, San Diego; Tom Montine, a professor at the University of Washington; and Daniel Perl of the Uniformed Services University of the Health Sciences in Bethesda, Maryland. The three published two separate studies, in 2005 and 2009, that failed to find BMAA in human brains. In the first study they had looked only for free, unbound BMAA, not BMAA in protein chains in tissues. “If BMAA is incorporated into proteins, leading to protein dysfunction or an immune reaction, this would be a remarkable and novel mechanism of toxicity,” Montine and his colleagues wrote in the journal Neurology in 2005.
As well as questioning biomagnification and sample size, they asked if Cox could have been detecting an isomer, a compound with the same molecular formula as BMAA but a different structural formula.
In response, Cox and Banack published two papers, in 2010 and 2011, detailing a method for differentiating BMAA from its isomers and suggesting that other scientists standardize their research techniques so that results could be more accurately compared. In 2009, Deborah Mash, a professor of neurology at the University of Miami Miller School of Medicine, replicated Cox’s brain study, finding BMAA in the brains of ALS, Parkinson’s, and Alzheimer’s victims but not in the brains of people who’d died from Huntington’s, a neurodegenerative disease that’s linked to a specific gene. She also verified that BMAA crosses the blood-brain barrier in laboratory rats.
A 2006 paper coauthored by Susan L. Ackerman of the Jackson Laboratory in Maine, published in Nature, revealed that insertion of the wrong amino acid into a protein chain, known as misincorporation, can cause neurodegenerative disease. And research by Ken Rodgers and Rachael Dunlop in Sydney, Australia, which at press time was scheduled to be unveiled at the International Symposium on ALS/MND (motor neuron disease) in December, found that BMAA can be incorporated into protein chains within human neurons, causing proteins to “misfold” and form aggregates within the cells.
Many proteins have a highly specific three-dimensional structure in which the water-loving (hydrophilic) parts stay on the outside, and the water-repelling (hydrophobic) parts stay on the inside. “If proteins are damaged or contain a nonprotein amino acid such as BMAA, the structure of the protein can be altered so that the hydrophobic parts become exposed, and the damaged proteins can then stick together and form aggregates,” Rodgers says. What’s more, he found that the higher the concentration of BMAA, the more likely that it would be incorporated into a protein chain. When proteins misfold and stick together within nerve cells, it is thought to lead to neurofibrillary tangles, a telltale sign of neurodegenerative disease.