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The Pesticide Connection: Timeline

Trail Of Clues: How Parkinson’s and pesticides got linked

by Lauren K. Wolf
November 25, 2013 | APPEARED IN VOLUME 91, ISSUE 47

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1976 Obscure case
University of Maryland grad student makes and shoots up a bad batch of drugs, gives himself Parkinson's-like symptoms (Psych. Res. 1976, 1, 249)

1982 Medical mystery
Six heroin addicts land in California medical facilities with signs of advanced Parkinson’s after injecting a poorly made designer drug

1983 Discovery disseminated
Neurologist J. William Langston (shown) and coworkers report in Science that the addicts' illness was most likely caused by MPTP

1983 Primate proof
Scientists at the National Institute of Mental Health inject monkeys with MPTP, creating an animal model of Parkinson's




1984 Culprit cornered
Scientists learn that MPTP itself is not a neurotoxin but that its metabolite MPP+ kills neurons in the brain

1984 Weed killer
MPP+ is identified as a once-promising herbicide called cyperquat (Nature 1984, DOI: 10.1038/311464a0)

1986 Epidemiology begins
Neurologist Ali H. Rajput and team report a correlation between rural living and Parkinson's for patients in Saskatchewan

1989 Surgical relief
Two of the addicts, George Carillo and Juanita Lopez, receive fetal stem cell transplants to repair the damage in their brains

"Not only George but Juanita was making steady progress. It seemed as if the grafts had established themselves and were making a functional difference to both patients’ lives.” - from “The Case of the Frozen Addicts”

1995 Tale telling
“The Case of the Frozen Addicts” by Langston and Jon Palfreman is published




1999 Pesticide testing
Researchers inject paraquat into mice, see a loss of dopamine-producing nerve cells in the substantia nigra (Brain Res. 1999, DOI: 10.1016/ S0006-8993(98) 01192-5)

2000 Animal model
J. Timothy Greenamyre and team demonstrate that rotenone produces Parkinson’s-like symptoms in rats

2007 Toxicity recognized
U.S. voluntarily restricts use of rotenone to nuisance fish




2007 Zero tolerance
The European Union bans the use of paraquat

2011 Pinpointing pesticides
FAME study reports that risk of having Parkinson’s is two to three times higher for pesticide users who have worked with paraquat or rotenone



To calculate pesticide exposure for residents of California’s Central Valley over a 25-year period, Ritz and coworkers pulled data from the state’s Pesticides Use Reporting program. As shown for the town of Shafter in 1988, the researchers first located all fields being sprayed with a particular pesticide and determined the compound’s application rate. Then, the team drew a 500-meter-radius circle around a person’s residence (bottom). If a sprayed field fell within the circle, the resident—either a Parkinson’s patient or a control subject—was counted as being exposed. This procedure was carried out for each year of the study period.
Credit: Courtesy of Beate Ritz

2011 Public health
Beate Ritz and coworkers study California residents, find increased risk for people working near fields sprayed with a combo of paraquat, maneb, and ziram

2013 Synopsis study
Meta-analysis of 104 epidemiology studies finds that people exposed to pesticides in general and paraquat in particular are two times more likely to have Parkinson’s (Neurology 2013, DOI: 10.1212/WNL.0b01 3e318294b3c8)

"From a preventive perspective, we observed that the route of exposure … and the method of toxin application … has never been investigated. Risk appears to increase as the duration of exposure increases.”

2013 Contradictory results
Syngenta Crop Protection conducts experiment showing that paraquat doesn’t kill nerve cells when injected into mice

“What is clear is that the use of [paraquat] to provoke a statistically significant reduction in … neurons in the [substantia nigra] of the mouse brain is a more fragile process than is currently characterized in the published literature.”

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