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” (, 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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