Parkinson's: The Pesticide Link

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Since the British physician James Parkinson first described the "shaking palsy" in 1817, Parkinson's disease has been linked to a variety of possible environmental causes, both natural and artificial. It has been linked, too, to genetic factors, dating back to the beginning of the twentieth century, when early-onset Parkinson's was first found to run in a few scattered, unlucky families. Those who study the connection between Parkinson's and the environment suggest that it's probably the combined result of having a genetic predisposition to the disease and a dangerous exposure to some sort of neurotoxin. A favorite expression of people in this field is that "genetics loads the gun and environment pulls the trigger."

In the 1950s, scientists noticed that a large proportion of the Chamorro people, who live on the Pacific island of Guam, were gripped by a syndrome that rendered them stiff and immobile by middle age. It looked a lot like Parkinson's disease. What made the situation so fascinating (and so perplexing) was that in some patients the symptoms were closer to two other neurodegenerative diseases -- Alzheimer's and amyotrophic lateral sclerosis (Lou Gehrig's disease). After decades of research, scientists discovered that the culprit was a local dietary staple: the Mariana fruit bat. The bat drank nectar from the cycad tree, from which it received a concentrated dose of a brain toxin, the amino acid beta-methylamino-L-alanine (BMAA). When people ate the meat of the fruit bat, they ingested huge amounts of BMAA. The story was told in 2002, when the journal Neurology published an article about the fruit bats and their "biomagnification" of BMAA. The findings are still the subject of some debate, but they were consistent with the accumulating picture: that at least some environmental agents might account for at least some forms of parkinsonism.

In 1982, six young people showed up in emergency rooms in northern California unable to move, speak, or eat on their own. This time the detective work was accomplished much more rapidly. It took only a few weeks for William Langston, then a neurologist at the Santa Clara Valley Medical Center in San Jose, to put the story together. The patients were all heroin users, and they had all used a batch of garage-concocted heroin that was contaminated with the chemical compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, or MPTP. "At the molecular level, very little separated a toxic chemical from a harmless one," Langston and John Palfreman wrote in their book, The Case of the Frozen Addicts. But that small chemical change was enough to turn the designer heroin into one of the most potent known neurotoxins, virtually wiping out all the cells of the substantia nigra, which produces dopamine. MPTP has a molecular structure very much like the herbicide Paraquat. So the "frozen addicts" were taken as further evidence that both pesticide exposure and MPTP could be related to the same kind of dramatic brain damage.

The tragedy of the addicts (who recovered some function with L-dopa treatments) had a silver lining. MPTP turned out to be an excellent way to create parkinsonian symptoms in experimental animals -- a necessary first step in the search for a cure.

Scientists also observed these symptoms in groups of people exposed to unrelated compounds, such as heavy metals. One in particular, manganese, was implicated in a 2006 study of residents of the steelmaking town of Hamilton, Ontario, who had a higher-than-expected rate of Parkinson's disease. Investigators attributed this to the manganese content of particulate air pollution from factory emissions. It turns out that manganese is an ingredient in the widely used fungicide Maneb.

But pesticides remain the clearest culprit. One study found that in the brains of people who had died of Parkinson's disease, the substantia nigra had higher levels of Dieldrin (an organochlorine pesticide no longer approved for use in the United States) and of lindane (an insecticide occasionally still used to treat scabies and lice) than did the brains of people who had died of other causes. Laboratory studies have also provided important clues to the connection between pesticides and brain damage. When human brain cells are grown in culture and exposed to a variety of chemicals, several widely used pesticides -- in particular, Paraquat and Rotenone, a natural pesticide approved for use in organic foods -- have been shown to cause increased levels of alpha-synuclein, a protein in the substantia nigra, similar to the levels that are seen in people with Parkinson's disease.

Editor's note: The original version of this article incorrectly identified the Mariana fruit bat as a rodent. Bats are not rodents. We regret the error.