Hot on Parkinson's Trail
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
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
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
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
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
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
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
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.
While Parkinsons's Disease is a serious threat, and contrary to the article's suggestions, it IS treatable. The first issue is removing any toxic chemicals or heavy metals that have accumulated in the system. In combination with this is a sound nutritional protocol for allowing the body to heal. Brain cells, according to research DO regenerate to some degree, so there is always hope, especially if preventive steps are taken, or treatment is begun early.