Research bolsters link of pesticides to Parkinson's

MERCED, Calif. — A thousand acres stretched before him as Gary Rieke walked briskly behind a harvester, the parched, yellow stalks of rice sweeping against his knees. Stopping to adjust a bolt on the machine, Rieke struggled to maneuver a wrench with his trembling fingers.

It was 1988, and Rieke was in his mid-40s, too young and too fit to feel his body betraying him. For two decades, he had farmed in the San Joaquin Valley, and he knew what he wanted his hand to do. But for some frustrating reason, it refused to obey.

Unbeknownst to Rieke, by the time he noticed the slightest tremor, about 400,000 of his brain cells had been wiped out. Like an estimated 1 million other Americans, most over 55, he had Parkinson's disease, and his thoughts could no longer control his movements. In time, he would struggle to walk and talk.

Rieke, who was exposed to weedkillers and other toxic compounds all his life, has long suspected that they were somehow responsible for his disease.

Now many experts are increasingly confident that Rieke's hunch is correct. Scientists have amassed a growing body of evidence that long-term exposure to toxic compounds, particularly pesticides, can destroy neurons and trigger Parkinson's in some people.

So far, they have implicated several pesticides that cause Parkinson's symptoms in animals. But hundreds of agricultural and industrial chemicals probably play a role, they believe.

Researchers don't use the word "cause" when linking environmental exposures to a disease. Instead, epidemiologists look for clusters and patterns in people, and neurobiologists test theories in animals. If their findings are repeatedly consistent, that is as close to proving cause and effect as they get.

Now, with Parkinson's, this medical detective work has edged closer to proving the case than with almost any other human ailment. In most patients, scientists say, Parkinson's is a disease with environmental origins.

For almost two centuries, since English physician James Parkinson described a "shaking palsy" in 1817, doctors have been baffled by the condition.

In most people, a bean-size sliver at the base of the brain, called the substantia nigra, is crammed with more than half a million neurons that produce dopamine, a chemical messenger that controls the body's movements. But in Parkinson's patients, more than two-thirds of those neurons have died.

After decades of work, researchers are still struggling with many unanswered questions, such as which chemicals may kill dopamine neurons, who is vulnerable and how much exposure is risky.

Scientists caught the trail of pesticides in 1982, when neurologist Dr. Bill Langston treated a man who had a virtually overnight onset of Parkinson's symptoms. He and fellow doctors found the source to be a botched batch of synthetic heroin that contained MPTP, a compound that targeted the same neurons missing in Parkinson's patients. A chemist told Langston the formula for the heroin compound "looks just like paraquat." Paraquat has been one of the world's most popular weedkillers for decades.

Since that discovery, scientists have conducted hundreds of animal experiments, at least 40 studies of human patients, and three of human brain tissue. They have found "a relatively consistent relationship between pesticide exposure and Parkinson's," British researchers reported online in September in the journal Environmental Health Perspectives.

To pinpoint which environmental exposures are most important, scientists are trying to unravel how genes and toxic chemicals interact to destroy brain cells. One leading theory is that pesticides cause overexpression of a gene that floods the brain with a neuron-killing protein.

More than 1 billion pounds of herbicides, insecticides and other pest-killing chemicals are used on U.S. farms and gardens and in households. Nearly all adults and children tested have traces of multiple pesticides in their bodies.

So far, animal tests have implicated the pesticides paraquat, rotenone, dieldrin and maneb — alone or in combination — as well as industrial compounds called PCBs, or polychlorinated biphenyls.

Pesticide-industry representatives stress that there are many risk factors and insufficient evidence implicating any specific pesticide. Scientists agree that they cannot specify an individual culprit.

A connection to rural living or farming has turned up worldwide. Scientists first observed a high rate of Parkinson's in rural areas in the early 1980s in Saskatchewan. Since then a dozen published studies have reported an increase of 60 percent to 600 percent among people exposed to pesticides, according to the British scientists' review.

Still, the science of epidemiology has inherent weaknesses. Most of the human studies, for example, relied on patients' memories — most of which cannot be validated — to report their pesticide exposures.

"You need to be cautious in drawing conclusions when you know there are flaws in these studies," said Pamela Mink, an epidemiologist who evaluated the human studies in a peer-reviewed report partly funded by the pesticide industry.

For Rieke, it is impossible to determine which chemicals may have played a role in his disease. He owned two dry-cleaner shops — handling industrial solvents for seven years — and for 25 years he mixed and applied at least a dozen herbicides and insecticides on his Merced farm.