Hot on Parkinson's Trail

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http://www.truthout.org/issues_05/112805HA.shtml

 

 

 

Hot on Parkinson's Trail

By Marla Cone

The Los Angeles Times

 

Sunday 27 November 2005

 

Scientists have amassed evidence that long-term exposure to toxic

compounds, especially pesticides, can trigger the neurological disease.

 

Merced, California - 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.

 

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.

 

The work has revolutionized the thinking about Parkinson's,

shifting the decades-long debate about whether its roots are genetic

or environmental. Among the research leaders are UCLA, the Parkinson's

Institute in Sunnyvale, Calif., which Langston founded and now

directs, and Atlanta's Emory University, each named national centers

for Parkinson's research in 2001 and given a total of $20 million in

federal grants.

 

Head trauma contributes to some cases of Parkinson's, and it

probably explains why boxer Muhammad Ali was stricken. But why does it

afflict others with seemingly nothing in common, such as the late Pope

John Paul II and actor Michael J. Fox?

 

A couple of genes seem to play a role in early onset of

Parkinson's in the small percentage of people who are afflicted at a

young age. But for 90% of people who get the disease, a broad array of

environmental factors are believed responsible. In fact, when

Parkinson's patients have identical twins who carry the exact same

genes, most of the twins do not contract the disease.

 

" All told, the forms of Parkinson's with a known or presumed

genetic cause account for a small fraction of the disease, likely 5%

or less, " epidemiologists Dr. Caroline Tanner of the Parkinson's

Institute and Lorene Nelson of Stanford University reported in 2003.

 

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 over-expression of a gene that floods the brain with a

neuron-killing protein.

 

Exposure to chemicals early in life, followed by toxic exposures

in adulthood, may be especially important, triggering a slow death of

neurons that debilitates people decades later.

 

Compounds with little in common, such as a fungicide and an

insecticide, apparently can team up to administer a one-two punch,

decimating brain cells.

 

" Pesticides and related industrial chemicals, those classes of

compounds, clearly are associated with some cases of Parkinson's, "

said Gary Miller, a toxicologist and associate professor at Emory

University's Rollins School of Public Health. " The question is, how

many? 5%, 10%, 50%? In a chemical-free society, people would still get

Parkinson's disease. It would just occur later in life and at a lower

incidence. "

 

Even 5% would involve 50,000 Americans alive today.

 

More than 1 billion pounds of herbicides, insecticides and other

pest-killing chemicals are used on US 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.

 

" We know for sure that if you expose animals to certain

pesticides, it will kill the same neurons as Parkinson's disease.

That's a fact. In humans, there is high suspicion, but there is no

definite proof, " said Dr. Marie-Francoise Chesselet, director of the

UCLA Center for Gene-Environment Studies in Parkinson's Disease.

 

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, Canada. Since then a dozen published

studies have reported an increase of 60% to 600% 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.

 

Most patients probably were exposed decades before their

diagnosis. Because there is no national registry for Parkinson's, as

there is for cancer, no one knows whether rates are high in places

such as the San Joaquin Valley.

 

Among those trying to obtain more definitive answers, UCLA

environmental epidemiologist Dr. Beate Ritz has contacted nearly 300

Parkinson's patients and 250 healthy people in 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 extensive 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 industry, concluded that the human and animal data " do not provide

sufficient evidence " to prove pesticides cause Parkinson's.

 

Scientists first tested paraquat in rodents, but the findings were

inconclusive. Neurologist Tim Greenamyre showed that rotenone, a

pesticide, could kill rats' dopamine neurons and cause Parkinson's

symptoms. But since rotenone is a natural plant compound that is not

used much on farms, it was not a likely source of the human disease.

 

Neurotoxicologist Deborah Cory-Slechta has presented the most

compelling evidence yet 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 impact on the brain was misguided.

 

" It's not how humans are exposed, " she said. " You don't get a

single dose of a pesticide. You get chronic, low-level exposure. "

 

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% and

their dopamine levels plummeted 80%.

 

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.

 

Paraquat and maneb are unlikely to be the only combination with

such a devastating effect. Yet the US Environmental Protection Agency

considers only single exposures when approving pesticides, an approach

that " doesn't mimic environmental reality, " Cory-Slechta said.

 

" There may be hundreds, if not thousands, of other compounds that

are silent killers of dopamine neurons, " said Dr. Donato Di Monte,

director of basic research at the Parkinson's Institute.

 

" Each of these risk factors, they kill 10, 20 or 30% of your

neurons. It's like eroding a house on a cliff, and the house finally

falls over.

 

With so much emerging human and animal data, Chesselet predicts

that " in two years, we will have a preponderance of evidence " against

some classes of chemicals. Kamel thinks specific pesticides will be

pinned down within five years.

 

For Rieke, it is impossible to determine which chemicals may 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 Merced farm.

 

At 59, Rieke had to sell the farm and retire. Now 64, he seems 10

years older despite taking seven medications daily.

 

" Every year, there are things that we all take for granted that my

dad can no longer do, " said his son, Greg. " There's no cure, and it

never gets better. There's not a lot of hope, if you will. "

 

Though it's too late for Rieke, scientists are confident they'll

soon be able to predict who is vulnerable to environmental assaults on

their brains.

 

" That would be the Holy Grail for us, " Miller said. " To actually

pinpoint people at risk of this disease and protect them. "

 

Parkinson's and Pesticides

 

Scientists now believe that exposure to toxic substances,

particularly pesticides, could explain some brain cell degeneration

that leads to Parkinson's disease, a disorder that affects body

movement and coordination.

 

Neurons

 

Neurons or brain cells in the mid-brain produce dopamine, one of

two neurotransmitters that help the brain and body communicate to

produce smooth muscle movements and body coordination.

 

People with Parkinson's disease lose 60% to 80% of their

dopamine-producing neurons in a part of the mid-brain called the

substantia nigra, hindering communication between the mind and body.

Scientists think some pesticides may kill neurons in the substantia nigra.

 

When Dopamine Is Present

 

In a normal mid-brain, the substantia nigra has cells that are

pigmented, or colored black, a byproduct of dopamine production.

 

Absence of Dopamine

 

Parkinson's patients lack this pigmentation because they've lost

so many neurons.

 

Source: Medline Plus.

 

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