The Possible Assuage of Parkinson’s
Disease Risk, due to Pesticide Exposure, with Genetic Modification
of Crops
Monica
Siegenthaler
Bio
361, Davidson College
Attempts at controlling pests have been made
for hundreds of years. Farmers
have, in the past, made use
of the natural processes of genetic selection to provide some resistant
to weeds. The chemical use
of
toxins in preventing the proliferation of pests was first documented
200 years ago. It was not
until 1945
and 1946, however, that the first commercial selective broadleaf weed
herbicides, 2.4-D and MCPA,
respectively, came onto the market.
Since then, the industry has experienced continual growth,
having a
market value of $31 billion in 1998 (Cobb and Kirkwood, 2002).
Herbicides are the most widely
used class of pesticides in the world accounting for 44% of all sales
in
1988. More than 90%
of the total mass of pesticides applied each year in the U.S. is herbicides
(Cobb and
Kirkwood, 2002). It is estimated
that without herbicide use, agricultural yield would drop by 30 to
50%
(Palmiera, 1999). Even with
the use of herbicides, weeds currently cause more than an estimated
$40
billion in annual global agricultural losses (Cobb and Kirkwood, 2002).
Unfortunately, pesticides are
known to cause detrimental effects on the environment and animal health.
Pesticides can easily contaminate the soil, air, and water.
Detection of pesticide residues has even been
found in drinking water. The
US Geological Survey, for example, detected the herbicide atrazine
in each
of 146 water samples collected at 8 locations throughout the Mississippi
drainage basin. Over 74% of the
samples also contained alachlor, metachlor, or cyanazine.
Atrazine concentration exceeded the EPA
maximum contaminant level for several weeks in rivers as large as
the Missouri and Mississippi. The
central US rivers supply drinking water to 18 million people and many
herbicides are not removed from
drinking water by conventional filtration and treatment (Liebman et
al, 1993).
The presence of pesticides
in the environment result in adverse health effects.
One debated effect is the
link between herbicides and cancer.
Some research shows significant results for a link, while others
discard the idea. Schreinemachers (2000), for example, demonstrated
an increase in cancer mortality in
four northern wheat-producing states. The study compared rare cancer cases in different counties that
are
above and below the median of wheat acreage per county. The findings verified increased mortality for
cancer of the nose and eye in men and women, brain and leukemia for
boys and girls, and all cancers in
boys (Schreinemachers, 2000). Another study, conducted in North Carolina,
suggests that children
under14 have four times the normal risk of contracting cancer, namely
soft tissue sarcoma, if their gardens
are treated with pesticides of herbicides (“Garden”, 1995).
Other studies linking herbicides to child
cancer include one in which agent orange causes a form of leukemia
in Vietnam veteran’s children (“Agent
Orange Linked”, 2001). Moreover,
three Swedish case-control studies suggest that exposure to 2,4,5-T
and 2,4-D and similar compounds results in a six-fold increase in
risk for soft tissue sarcoma. Similar
survey conducted in New Zealand, however, found these associations
weak (Coggon, 1987).
Aside from cancer, pesticides
have also been associated with the disruption of biological pathways,
such
as the production of ATP. For instance, three herbicides, paraquat, dinoseb, and 2,4-D, have
been shown
to affect mitochondrial bioenergetics. Each herbicide causes the effects by different
mechanisms. Their
effects lead to the disruption of cellular energetic and metabolism
(Palmeira, 1999). Interestingly,
one
neurological disease in which neuronal mitochondria are unable to
produce ATP has an unknown etiology,
but has recently been studied in the light of the industrial chemicals
that have contaminated the
environment.
Parkinson’s disease (PD) is characterized by tremor, rigidity,
shuffling gait, decreased muscular activity
(hypokinesia), slowness of movement (bradykinesia), and difficulty
initiating voluntary movement
(Veldman et al, 1998; King, 2002).
Such characteristics are a result of significant loss of substantia
nigra
dopamine neurons. For comparison, there is a 4.7-6.0% loss of
nigral cell loss as one ages from their 5th
decade to their 9th decade of life, but such loss does
not cause parkinsonian features (Veldman et al,
1998). In order for the symptoms
of Parkinson’s disease to appear, there must be an 80% loss of the
nigral
dopamine neurons (King, 2002).
The cause of such substantial loss is unknown.
Research has shown, however, that relatives of PD
patients are two to five times more likely to have PD than the relatives
of controls, suggesting the role of
inheritance. Some research
has found that certain genes, such as the dopamine receptor gene D2,
may be
genetic determinants of PD. There
are, however, certain environmental trends, that undermine a solely
genetic cause in the manifestation of PD (Veldman et al, 1998).
Parkinson’s disease tends to be more prevalent in industrialized
countries than in underdeveloped
countries. The frequency of PD, for example, in China
(57 per 100,000) is less than in the US (347 per
100,000). Further, there is a difference between the
occurrences of PD in genetically homogenous
populations living in different locations.
Parkinson’s disease, for instance, is much lower in Nigeria
that it
is among the Afro- American population in the US.
The prevalence of PD among Afro-Americans in the
US, in fact, is about the same as that for white people in the US.
The incidence of PD in Japanese or
people of Okinawan ancestry living in the US is similar as well to
that of the white people in the US, but is
much higher than the incidence among Asians living in an Asian country
(Veldman et al, 1998).
Another trend, as described in by Rajput
in 1984 is the relation between PD and rural living, which in this
case is an industrialized for of rural living.
Rural living, for example in industrialized countries makes
use
of many industrial products, such as tractors and pesticides, whereas
rural living in underdeveloped
countries makes use of oxen and tilling instead. Rajput’s initial findings that rural living
significantly
increases the risk of PD has since been supported by several studies
(Tanner et al, 1987; Rajput et al,
1987; Ho et al, 1989; Tanner et al, 1990; Won et al, 1991; Stern et
al, 1991; Vieregge et al, 1992;
Butterfield et al, 1993; Svenson et al, 1993; De Michele et al, 1996;
Liou et al, 1997). Although there are
studies that did not find this relationship, they are few in comparison
to those that do support rural living
as a risk factor of PD (Veldman et al, 1998).
The relation between farming and PD may be
explained by studies, such as that of Semchuck et al (1992),
in which occupational herbicide use was a significant predictor of
PD risk. This association was made by
interviewing 130 Calgary residents with neurologist confirmed PD and
260 randomly selected age- and
sex-matched community controls (Semchuck et al, 1992).
A similar sort of study, conducted in Detroit,
suggests that PD is linked with occupational exposure to pesticides
(Gorell et al, 1998).
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
is a toxic molecule belonging to the bipyridyl chemical group (Veldman
et al, 1998; IPCS Inchem, 2002). Research has shown that MPTP is converted to
MPP+, a highly neurotoxic metabolite, in the brain by monoamine oxidase
(MAO). It has been suggested
that MPP+ causes the selective neuronal degeneration by binding to
neuromelanin, a pigment molecule of the substantia nigra.
Once bound to the pigment, MPP+ is accidentally taken up by
mitochondria, where it inhibits complex I, resulting in mitochondrial
respiratory chain dysfunction. The
production of energy is ultimately diminished, leading to calcium
release and cell death (Kopin et al, 1987; Velderman et al, 1998;
King, 2002). The resulting cell death often gives rise to
parkinsonism, which is a term used to describe “any of a group of
nervous disorders similar to Parkinson's disease, marked by muscular
rigidity, tremor, and impaired motor control and often having a specific
cause, such as the use of certain drugs or frequent exposure to toxic
chemicals” (Dictionary.com, 2002).
Therefore, victims of parkinsonism experience the same symptoms
as Parkinson’s patients.
It is believed that pesticides
that are structurally similar to MPP+, such as paraquat, may cause
the same degenerative effects. In one study, Liou et al (1997) discovered that Taiwanese farmers
using paraquat in conjunction with other pesticides had a 4.74 fold
increased risk for PD, whereas the farmers that used pesticides other
than paraquat had a 2.17 fold increased risk (Liou et al, 1997).
Syngenta currently sells paraquat in over
one hundred countries. This
non-selective, broad-leaf herbicide
is extensively used on plantations of bananas, cocoa, coffee, cotton,
palm oil, pineapple, rubber and sugar
cane (“Time”, 2002; “Paraquat”, 1996).
Paraquat is often applied to destroy weeds in preparing the
land
for planting, and to desiccate and defoliate crops in preparation
for field burning. The use of paraquat is
currently restricted in the US so that it can be purchased and used
only by certified applicators. Some
countries, however, such as the UK, do not have any regulatory measures
against the use of paraquat
(“Paraquat”, 1996).
Due to the strictly regulated use of paraquat, the high prevalence
of PD in the US then cannot be explained
solely by the use of paraquat. Associations
between PD and pesticides in general, however, have been
suggested in several studies (Veldman et al, 1998).
Nelson reported at the 2000 American Academy of
Neurology annual meeting that exposure to home pesticides is linked
to increase risk of PD. Exposure
to
herbicides, for example, increased the risk for PD by 30% with a low-level
of exposure (less than 30
days total) and 70% with a high-level of exposure (average of 160
days total). Garden insecticides
increased the risk of PD, and in-home use of insecticides, with an
average exposure of 77days, increased
showed a 70% increased risk. The
specific kinds of pesticides used are unknown, however, because
studies relating PD to pesticide exposure often consist of interviews
in which the participants are asked
about their past exposure to pesticides in general, rather than exposure
to specific pesticides. Parkinson’s
disease expert William Koller, MD, PhD explains, “the whole concept
is tantalizing, but there’s never
been a single agent or even a class of agents that have been identified
as a risk factor.” Nelson
and her
colleges, however, hope to re-interview the participants of the original
study to determine any trends in the
brands or type of pesticides used (Stevenson, 2000).
If exposure to pesticides really is a risk
factor for PD, biotechnology may hold a key to reducing the use of
pesticides, and in turn reducing the overall incidence of PD.
The discovery, isolation, and manipulation of
genes have flourished over the past few decades, leading up to the
advent of herbicide-tolerant crops
(Marshall, 1998). The most
common of these transgenic crops are Bt crops and Roundup-ready
crops. Roundup-ready crops contain a transgene, derived
from a petunia, that produces large quantities of
the phenylalanine-producing enzyme, EPSP synthase (Kleiner, 1998).
Glyphosate, also known as
Roundup, is a broad-spectrum herbicide that Monsanto introduced in
1974 (Mendelson, 1998). It
works
by inhibiting the production of EPSP synthase, which results in the
absence of the amino acid
phenylalanine, leading to plant death (Kliener, 1998; Wade, 1999).
The idea behind the Roundup-ready
crops is that the inserted gene produces an amount of EPSP synthase
that is overwhelming for glysophate.
In the past, farmers used caution when spraying
Roundup, so as not to spray too much and cause damage to
the crop in addition to the targeted species.
Roundup-ready crops, however, allow the farmer to spray
without worries of killing the crop.
Currently, Roundup-ready soybeans, canola, cotton, and corn
exist,
covering over 33 million acres worldwide.
Monsanto plans to add sugar beets, wheat, and potatoes to the
Roundup-ready line (Kliener, 1998).
Bt crops, another line of transgenic plants,
contain a gene gun-inserted gene that produces the Bacillus
thuringiensis (Bt) toxin (Levidow, 1999).
Bt has been used as an insecticide in the US since 1958.
The
toxin is used on fruits, vegetables, and other cash crops including
corn, potatoes, and cotton for the
effective control of beetle larvae, moth and butterfly caterpillars,
mosquito and blackfly larvae, mites,
flatworms, and nematodes (Swadener, 1994).
The toxin works by being activated within
the insect’s digestive system. The
delta- endotoxin, which is
the toxic constituent of the bacterium, binds to specific receptors
on the intestinal lining of the insect. The
binding causes a conformational change in the intestinal membrane,
resulting in the formation of pores.
The pores cause the intrinsic balance of ions to be disrupted,
and leads to the cessation of feeding and the
eventual death by starvation (Levidow, 1999).
Thus, the insertion of the Bt gene in plants
results in the constituent release of Bt. Therefore, the farmer
does not need to spray in order to control for such pests.
These crops, such as Bt cotton, BT corn, and Bt
potatoes are widely grown in countries such as the United States,
Spain, Canada, Argentina, South Africa,
and France (Levidow, 1999).
Although there is much debate concerning
the adverse effects of such genetically altered crops on the
environment, Monsanto advertises these crops with the claim that they
will significantly reduce the volume
of pesticides used, which is an obvious favorable effect on the environment. GMO opposition has
expressed their thoughts on the pesticide use issue and argues that
Roundup-ready crops and Bt crops will
increase the use of pesticides since farmers will not worry about
the detrimental effects on the crops.
Published data, however, shows that pesticide use on Bt cotton
in Australia has decreased by 50%, and
insecticides used on Bt corn in the US has decreased by 30% (Levidow,
1999). In addition, the volume
of
herbicides used by US farmers has decreased by 50% since the introduction
of Roundup-ready crops
(Barton and Dracup, 2000).
The associations found between exposure to
pesticides and increased risk of PD suggests that a decrease
in the use of pesticides, due to the advent and use of Bt crops and
Roundup-ready crops, may lessen the
occurrence of PD. Even if
such correlations do not exist, biotechnology can be applied for medicinal
purposes. Pargyline, a MAO-blocking
drug prevents MPTP-induced parkinsonism and inhibits cell death
in substantia nigra (King, 2002).
Insertion of the pargyline gene in plants, such as tobacco,
can produce a
medicinal product for the cautionary prevention of Parkinson’s deleterious
effects. Smoking the medicinal
tobacco, moreover, would provide further measures in the prevention
of the disease. The risk of PD has
been shown to have an inverse relation with smoking.
A proposed explanation of this association asserts
that cigarette smoke contains MAO inhibitors, and actually reduces
the amount of MAO in the brain by
40%. Furthermore, nicotine
has been shown to stimulate the release of dopamine, which is the
deficient
chemical in PD patients (Veldman, 1998).
Therefore, genetic modification of plants,
whether directed to the improvement of health or not, may
greatly reduce current health risks, such as that of PD.
Although opposition object to the current trends of
genetic modification in biotechnology, the delineated benefits certainly
outweigh the postulated minute
adverse effects that genetic modification may have on the environment.
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