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 heart of 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, some 400,000 of his brain cells had been wiped out. Like an estimated other 1 million 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.
Scientists are "definitely there, beyond a doubt, in showing that environmental toxicants have to be involved" in some cases of Parkinson's disease, said Freya Kamel, an epidemiologist with the National Institute of Environmental Health Sciences who has documented a high rate of neurological problems in farmers who use pesticides.
"It's not one nasty thing that is causing this disease. I think it's exposure to a combination of many environmental chemicals over a lifetime. We just don't know what those chemicals are yet, but we certainly have our suspicions."
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-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 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.
Expressed in legal terms, pesticides are not guilty beyond a reasonable doubt -- but there is a substantial, and rapidly growing, body of evidence, many scientists say.
Clues and breakthroughs are emerging from an odd menagerie of laboratory flies, mice, rats and monkeys, from bits of human brain, and from farmers like Rieke.
And it all started with a junkie named George.
It was July 1982, and a 42-year-old patient named George Carrillo had lingered in Santa Clara emergency rooms and psychiatric units for more than two weeks. He seemed catatonic, unable to move or speak. Dr. Bill Langston, who ran a neurology department, was brought in to try to figure out what was wrong.
Langston gently lifted the man's elbow. His arm was stiff, moving like a gearshift. Langston had seen this odd, rigid movement many times before, in patients with Parkinson's disease.
But this was no ordinary Parkinson's patient. His symptoms had developed virtually overnight.
The doctors soon tracked the source: a botched batch of synthetic heroin that contained MPTP, a compound that acted like an assassin, targeting the same neurons missing in Parkinson's patients.
Langston had stumbled across a powerful chemical that unleashed an immediate, severe form of Parkinson's.
Still, it was obvious that synthetic heroin wasn't the culprit for most Parkinson's patients. People are exposed to some 70,000 chemicals in their environment. Which others could cause the disease?
A few days later, a chemist contacted Langston. The formula for the heroin compound, the chemist said, "looks just like paraquat." Paraquat has been one of the world's most popular weedkillers for decades. It was a good place to start.