As U.S. and allied soldiers in Iraq face the constant danger of chemical and biological weapons, scientists are still trying to figure out why some veterans of the last gulf war returned home with mysterious symptoms and brain damage.

This ScienCentral News video reports that neuroscientists are studying a gene that could make some people more susceptible to chemical agents.

A Genetic Link

A new Gulf War means renewed concern about exposure to nerve gas, which is thought to contribute to Gulf War Syndrome, a loosely defined collection of symptoms, including chronic fatigue, diarrhea, migraines, dizziness, memory problems, loss of muscle control, and loss of balance.

Now scientists think they have found a genetic link between certain pesticides and chemical weaponry to a number of neurological disorders, including Gulf War Syndrome. During the Gulf War, thousands of soldiers could have been exposed to toxic nerve gases. At the same time, pesticides were widely used to ward off insect-borne diseases, a leading killer of servicemen in previous wars.

Some scientists used to attribute the symptoms to stress, because not all Gulf War veterans exhibited symptoms of the syndrome. “The cause of Gulf War Syndrome is a little bit controversial,” says Dr. Carrolee Barlow, professor at the Salk Institute for Biological Studies and molecular neuroscience director at the pharmaceutical company Merck. “It’s thought to be due to a combination of exposure to chemicals that are in some of the pesticides, or in some of the nerve gas that they could have been exposed to.”

Now there appears to be a genetic reason why some soldiers got sicker than others. The research team at the Salk Institute, headed by post-doctoral researcher Christopher Winrow, studied organophosphates, the toxic components of nerve agents and pesticides. They looked at the effects of these components on mice with either one, two or no copies of a gene called NTE.

Both mice and humans can have up to two copies of this gene, one from the mother and one from the father. The research team engineered mice to lack either one or both copies of the gene. The mice without the gene did not survive. The mice with only one copy of the gene survived, but reacted more strongly to the organophosphates than mice with two copies of the gene. “When we looked at mice that had one copy of the gene disrupted and exposed those to the chemicals, we found that these mice were much more sensitive to the toxic effects of the chemical,” says Winrow.

The NTE gene encodes for an enzyme called neuropathy target esterase, that can give nerve cells some protection against nerve agents. Researchers found that fewer copies of the gene led to less enzyme and more susceptibility to organophosphates. Over time this led to neurological problems, echoing symptoms similar to the Gulf War Syndrome. These findings, which will be published in the journal Nature Genetics on April 1st, are the first to demonstrate a clear genetic link between neurological disorders and exposure to organophosphate chemicals, which include household pesticides as well as nerve agents like sarin gas.

“What our study suggests is that if you inherit even one bad copy or one modified copy from either one of your parents, you’d be at increased risk if you are exposed to pesticides or nerve gas,” says Barlow. People who have lower levels of NTE because of genetic variations might be at greater risk of damage from nerve gas toxins. They could be screened in advance, and take greater precautions.

Gulf War Syndrome was first noted after operations Desert Storm and Desert Shield in 1991. The Pentagon has identified about 130,000 troops it believes were exposed to low levels of sarin in 1991 when U.S. forces destroyed a weapons depot at Khamisiyah in southern Iraq. However some veterans, like Major Denise Nichols, a retired U.S. Air Force flight nurse who was stationed on the border of Iraq and Saudi Arabia during the last Gulf War, believe other nerve agent exposures occurred during that war.

Nichols, who suffers from Gulf War Syndrome, says that although she appreciates the efforts of scientists looking at the genetic aspect of the syndrome, the defense department should take more precautions to protect all soldiers against exposure to toxic chemicals. “Toxic overload to the body could be the reason. It’s not one thing; it’s the totality of all the things that the troops have experienced,” she says. “We also need to look at how much the human body can take.”

The research was supported by a grant from the U.S. Department of Defense.