Low-dose sarin nerve gas may have long-term effects

WASHINGTON -- Low levels of sarin nerve gas affected behavior and organ functions in laboratory animals at least a month after exposure, suggests new research that may provide clues to the mysterious illnesses of Persian Gulf War veterans.

In separate Army-sponsored studies, scientists observed behavioral problems, brain changes and immune system suppression in the animals many days after exposure to doses that caused no immediate effects, such as convulsions or pupil constriction.

Both studies involved rodents, and "that's a big leap to human beings," said Melinda Roberson, a behavioral neuroscientist involved in a study still under way.

The studies provide new information in an area where a lack of research has made it impossible to conclude whether Gulf veterans' illnesses are linked to low-level sarin gas exposure.

"They are pushing back the frontiers of biological effects of low levels of sarin. The evidence is building," said Dr. Francis O'Donnell, a medical consultant for the Defense Department who helps track Gulf War illness research.

Suffering from illnesses

Veterans of the 1991 war have suffered from various illnesses they believe linked to their service in the Gulf. Symptoms include chronic fatigue, diarrhea, migraines, dizziness, memory problems, loss of muscle control and loss of balance.

Most scientists have blamed stress. Some veterans attribute the health problems to toxic substances they encountered in the Gulf, including sarin, a toxic chemical weapon that is lethal at high levels. Others suggest it may be a combination of the factors.

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. Some veterans believe other sarin exposures occurred.

On its Web site, the Pentagon tells veterans that "current medical evidence indicates that long-term health problems are not likely."

Dr. Robert Haley, an epidemiologist at University of Texas Southwestern Medical Center at Dallas, has published almost two dozen studies suggesting that some Gulf War veterans' illnesses are linked to brain damage resulting from exposure to toxins such as sarin.

The Pentagon criticized those studies, in part because veterans Haley studied were not downwind of Khamisiyah when the depot was destroyed. Haley said the new research gives "biological plausibility" to his suggestion of a link to sarin gas exposure.

The study on guinea pigs is under way at the Army Medical Research Institute for Chemical Defense at Aberdeen Proving Ground, Md. Its preliminary findings were presented in November at the Society for Neuroscience's annual meeting in Washington.

In that study, guinea pigs were injected with nerve gas five days a week for two weeks. Some were injected with 20 percent of the dose required to kill half the animals and others with 40 percent of that dose.

Researcher Jim McDonough, a physiological psychologist, said that would be much higher than the level that the Pentagon says veterans were exposed to from the Khamisiyah depot destruction. Some veterans' groups question the accuracy of the Pentagon's exposure estimates, insisting they were much higher. Other researchers say there is no way to calculate the exposure levels for sure.

Although veterans were not injected with sarin, McDonough said the biochemical effects on the brain are the same for either exposure method. He likened the exposures to nicotine's effects on the brain whether the nicotine is smoked, chewed or delivered through a skin patch.

The exposed animals were examined after two hours, then at three days, 10 days, a month and 100 days. There were no changes in some physical signs the scientists monitored, such as weight gain and temperature.

But researchers said they found significant increases in certain behaviors.

For example, 100 days after exposure, animals in the 40 percent dose group spent significantly more time in the center of their activity chambers and traveled greater distances in the chambers, McDonough said. Guinea pigs in both dosage level groups also reared up on their hind legs significantly more often at 100 days.

Roberson said researchers saw a reduction in activity by the enzyme acetylcholinesterase, a key to controlling electrical impulses in the brain. She said that could affect behavior. Researchers are exposing another group of animals to verify the results.

Separately, researchers at Lovelace Respiratory Research Institute in Albuquerque, N.M., known for its tobacco studies, exposed mice to low-level doses of sarin in a three-part Army-funded study. The study, begun in 1998, was finished last year.

The mice inhaled sarin doses an hour a day for five days and an hour a day for 10 days. The levels were one-tenth and one-twentieth the concentrations required to kill a human. The mice were examined a day and a month after exposure.

Researchers found that the exposures, particularly when combined with heat stress, caused both decreases and increases in the numbers of receptor sites in areas of the brain critical for cognition and memory, "things that might be associated with Gulf War syndrome," said Rogene Henderson, Lovelace senior scientist.

Receptor sites are essentially docking stations for brain signals. In some cases the changes did not appear until a month after exposure, Henderson said.

Researchers found that the exposure also suppressed the immune system, the body's defense mechanism against infection and disease. Researcher Mohan Sopori, an immunologist, said that indicates something happened to the autonomic nervous system, which is responsible for the body's automatic functions such as sleeping and bowel movements.

------

On the Net: U.S. Army Medical Research Institute for Chemical Defense: http://chemdef.apgea.army.mil/

Lovelace Respiratory Research Institute: http://www.lrri.org/

Veterans Affairs Department background: http://www.va.gov/gulfwar/