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Researchers see link between Parkinson’s, toxins
December 11, 2005
By Marla Cone

Gary Rieke, who has Parkinson’s disease, at home with his wife, Linda

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, he struggled to handle a wrench with his trembling fingers.

When he was in his mid-40s, back in 1988, Rieke was seemingly too young and too fit to be betrayed by his body.

Having farmed for two decades in the heart of the San Joaquin Valley, he knew what his hand needed to do.

It refused to obey.

Unknown to Rieke, by the time he noticed the slightest tremor, about 400,000 of his brain cells had been wiped out.

Like about 1 million other Americans, most older than 55, he has Parkinson’s disease.

Rieke, who was exposed to weedkillers and other toxins all his life, has long suspected that such substances lie behind his ailment.

Today, many experts are confident that his hunch is correct.

Scientists have amassed evidence that long-term exposure to toxic compounds, particularly pesticides, destroys neurons and triggers Parkinson’s in some people.

They have implicated several pesticides that cause Parkinson’s symptoms in animals.

Yet hundreds of agricultural and industrial chemicals probably play a role, they think.

Researchers don’t use the word cause when linking environmental exposure to a disease. Instead, epidemiologists seek clusters and patterns in humans, and neurobiologists test theories in animals.

A set of consistent findings is as close as they get to cause and effect.

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 blackened, bean-sized sliver at the base of the brain — called the substantia nigra — is crammed with more than a half-million neurons that produce dopamine, a 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 questions, such as which chemicals might kill dopamine neurons, who is vulnerable and how much exposure is risky.

There is a substantial and rapidly growing body of evidence concerning insecticides, many scientists say.

Scientists caught the trail of pesticides in 1982, when neurologist Bill Langston treated a man who had a virtually overnight onset of Parkinson’s symptoms.

Langston 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 that 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.

More than 1 billion pounds of herbicides, insecticides and other pest-killing chemicals is used on U.S. farms and gardens and in households. Almost all adults and children tested have traces of 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.

"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 paid for in part by the pesticide industry.

Most patients probably were exposed decades before their illness was diagnosed. There is no national registry for Parkinson’s. No one knows whether rates are high in places such as the San Joaquin Valley.

Among those trying to obtain more definitive answers, environmental epidemiologist Beate Ritz of the University of California, Los Angeles, has contacted almost 300 Parkinson’s patients and 250 healthy people in California’s Tulare, Fresno and Kern counties.

She is pinpointing their pesticide exposures down to the day, the pound and the street corner by overlaying their addresses with California’s agricultural database, which details pesticide use on farms since the 1970s.

Also, 52,000 farmers and other pesticide applicators have been tracked by federal researchers since the mid-1990s, and one goal is to document their exposure and see how many wind up with Parkinson’s.

Animal studies provide more evidence but also have weaknesses. Mink and toxicologist Abby Li, who co-wrote the report financed partly by the pesticide industry, concluded that the data "do not provide sufficient evidence" to prove pesticides cause Parkinson’s.

Neurotoxicologist Deborah Cory-Slechta has presented the most compelling evidence on how everyday environmental factors can play a role in Parkinson’s disease. Her theory was that testing one chemical at a time for its effect on the brain was misguided.

She injected mice with paraquat and the fungicide maneb. Use of the two sometimes overlaps on farms. Alone, paraquat and maneb did not harm mice in her laboratory.

But "When we put them together, we were astounded," Cory-Slechta said.

The most dramatic damage was in mice exposed to maneb as fetuses and then to paraquat as adults. Their motor activity declined 90 percent, and their dopamine levels plummeted 80 percent.

The amounts used in those tests "are not high levels of exposure. These are very, very low doses," said Cory-Slechta, who now directs Rutgers University’s Environmental and Occupational Health Sciences Institute in New Jersey.

Paraquat and maneb are unlikely to be the only combination with such a devastating effect. Yet the U.S. Environmental Protection Agency considers only single exposures when approving pesticides, an approach that "doesn’t mimic environmental reality," Cory-Slechta said.

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

At 59, Rieke had to sell the farm and retire. Now 64, he seems 10 years older despite taking seven medications daily.

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