Anencephaly is a nightmarish neural tube defect in which the fetus does not develop a forebrain, and the rest of the brain is not covered by skin or bone. Most anencephalic children die in the womb or within hours of birth.  A study published in the October 2006 issue of Occupational and Environmental Medicine now confirms a suspected epidemiological link between parents' occupation and this defect.

 

The study took place in Mexico between 2000 and 2001. Mexico has the highest occurrence of anencephaly in the world, with 8.05 cases per 10,000 live births in 2002, according to the International Clearinghouse for Birth Defects Monitoring System.

 

A review of fetal and infant death certificates identified cases of anencephaly of at least 20 weeks' gestation. Of these, 157 cases were paired with 151 malformation-free cases. The mothers and fathers of the children answered questions on their age, occupation, reproductive history, food and vitamin intake, cooking methods, geographic location, and on-the-job exposure to pesticides. Principal investigator Marina Lacasaña, a professor at the University of Granada Andalusian School of Public Health, and colleagues at the Mexican National Institute of Public Health divided parental exposures into the acute risk period (from three months before the mother's last menstruation before pregnancy through one month after) and the nonacute risk period (the time before the acute risk period).

 

The results showed a nearly fivefold increase in risk of anencephaly for mothers exposed to pesticides while working in agriculture during the acute risk period. Fathers who were exposed to pesticides at any time while working in agriculture had twice the risk of having an anencephalic child.  Some of the more heavily used pesticides reported by the parents, including chlorpyrifos and methyl parathion, have been previously linked with possible reproductive effects.

 

Rudy Rull, a research scientist at the Northern California Cancer Center who has researched birth defects and pesticides exposure, believes the study has some strong points. "One of the strengths of the study is that in the exposure section they focus in on timing, which is a really sensitive issue for neural tube defects . . . especially the months before and after conception."

 

However, the challenge for this and other studies will be to identify what pesticides are causing the defect. Many studies have shown that working in agriculture increases the risk of neural tube defects, says Rull, "but there's a lot you can be exposed to [in any given farm field]. We need to know which pesticides increase the risk."

 

The authors also noted there were few cases where workers wore adequate protective clothing. They hope their research will have policy implications; as they concluded in their paper, "Women involved in agricultural work, or who are living with men who work in agriculture, should be protected from direct and indirect pesticide exposure, especially during the periconceptional period, if they are planning to have a child."

 

 

The organophosphate and carbamate pesticides used today act by blocking acetylcholinesterase (AChE), an enzyme needed for proper functioning of the nervous system in insects, humans, and other animals. These pesticides, which contaminate air, water, soil, and food, are toxic not only to insects, but also to people and other animals. Now Yuan-Ping Pang, director of the Mayo Clinic's Computer-Aided Molecular Design Laboratory, has discovered an insect-specific region on AChE that could presage a new generation of better-targeted pesticides.

 

 

Bug-specific breakthrough. A model shows two active sites (C289 and R339) where mosquito-specific pesticides may bind with the AChE enzyme. These two sites are found only in insects and thus may lead to pesticides that are safer for humans.

 

 

Current pesticides bind the amino acid serine at the active site of AChE.  In work described in the 1 January 2007 issue of Bioorganic & Medicinal Chemistry Letters, Pang created three-dimensional computer models based on genomic information of AChEs obtained for the greenbug (Schizaphis graminum) and the English grain aphid (Sitobion avenae), which decimate wheat, barley, and sorghum worldwide. Models of the active site revealed that the amino acid cysteine occurs at a particular location (dubbed C289) in the two insects, but not in people. "We inspected the entire active site of the human enzyme and couldn't find one cysteine residue," says Pang. A sequence analysis of AChEs from 68 species obtained from GenBank also detected C289 in cockroaches, lancelets, rice beetles, bollworms, silkworms, honey bees, moths, and armyworms.

 

Because C289 is located at the entrance to the active site of AChE, it potentially could react with chemical pesticides designed to target that enzyme. Some early experiments in Pang's laboratory have shown that the lone cysteine can snag reactive chemicals and damage the enzyme. "For the first time, we have a blueprint to make a new generation of pesticides that are toxic only to pests," Pang notes.

 

Next Pang created a computer model of AChEs in the malaria-carrying Anopheles mosquito. In addition to the insect-specific C289 detected in the first study, he identified an insect-specific arginine, R339, at another location of the active site. The discovery of these two targets makes it possible to "create an effective new pesticide that specifically kills mosquitoes," says Pang, "and potentially revolutionize the way we control mosquito-caused diseases." The discovery of other such combinations could yield any number of new pesticides that target particular pests while sparing beneficial species such as honey bees. The mosquito study appears in the December 2006 inaugural issue of the online journal PLoS ONE.  AChE is one of the most important targets for the chemical control of many agricultural and medical insect pests, according to entomologist Kun Yan Zhu at Kansas State University, whose laboratory first sequenced the cDNA that encodes AChE in the greenbug. The discovery of insect-specific AChE regions "could potentially lead to the development of novel pesticides that would be expected to be toxic to insects but nontoxic or less toxic to humans," Zhu says.