October 19, 1999
Web posted at: 7:17 p.m. EDT (2317 GMT)

In this story: Drug is protection against nerve gas How PB works Variations in reactions $20 million in studies planned Pentagon: Would use PB again RELATED STORIES, SITES

WASHINGTON (CNN) -- For the first time since beginning research into Gulf War Syndrome, the Pentagon said Tuesday that it could not rule out a particular drug as the cause of a wide range of ailments in Gulf War veterans.

Officials cautioned that this did not prove that the drug did harm the troops, just that it cannot be discounted as a possible causative agent.

MESSAGE BOARD The U.S. Military

Previous studies have ruled out oil well fires, depleted uranium shells and stress as probable causes.

Drug is protection against nerve gas

The drug in question in the latest report is pyriostigmine bromide -- or PB -- which was given to an estimated 250,000 U.S. troops as a way to increase the effectiveness of treatments against a particular nerve agent known as soman.

"Iraq was known to have nerve agents available and militarized, and had used them against Iran and the Kurds," Dr. Beatrice Golomb, the study's primary author said, adding that it was also known that the Soviets had soman and may have made it available to Iraq.

The Pentagon financed the review of scientific literature on PB that resulted in the 358-page report by the RAND Corp., a California think tank.

"RAND reviewed a wide variety of sources, including medical and pharmacological investigations, basic science research related to this nerve-signaling chemical, and also declassified government documents, including a number of documents declassified by the British late in this review," said Golomb.

PB had been approved by the Food and Drug Administration for decades in treating an autoimmune condition known as myasthenia gravis, according to Golomb. But the drug has not been approved as a nerve agent pre-treatment.

The drug binds temporarily to an enzyme that controls a nerve-signaling chemical known as acetylcholine. If the nerve gas soman is present, the drug prevents soman from binding to the enzyme permanently, which would lead to uncontrollable symptoms.

Acetylcholine is vitally involved in regulation of muscle action, pain, memory and other cognitive function, mood and sleep. Those are the same physical areas that most often show up in the complaints of sickened Gulf War veterans.

Golomb said her review found a wide variety in the way different people processed the drug. There was also a wide variation in the effectiveness of the drug. So the same dose could produce in different people up to a 25-fold difference in its inhibition of the enzyme.

A second area of the review focused on something called the "blood brain barrier" that was supposed to prevent PB from reaching the brain.

Golomb said post-Gulf War research on animals found stress, perhaps heat -- and certain chemical combinations -- could allow quite a bit of PB to pass into the brain.

"One study suggests that PB itself may enable access to the brain of substances that are normally excluded, such as infectious viruses," said Golomb.

A third theory, the report said, was that PB lead to changes in how a person's body regulates the nerve-signaling chemical. The resulting excess of acetylcholine would trigger the body to react in ways to suppress production and receptivity of the enzyme. And Golomb said that effect has lasted as long as some studies were running.

The Pentagon has earmarked about $20 million, of $133 million spent researching Gulf War Syndrome, specifically to study the effects of the drug.

"Most of the ongoing studies to date reveal no definitive results to link PB to illnesses seen in our Gulf veterans," said Dr. Sue Bailey, assistant secretary of defense for health affairs.

According to the report, areas for further study include:

• Whether individual people react differently to PB

• Whether people who have a negative initial reaction are more likely to suffer negative long-term effects

• Whether stress can change the way the drug enters the brain

• Whether environmental factors in the Persian Gulf caused the U.S. supply of PB to become toxic

• Whether PB was administered in proper dosages

• Whether a person's weight might be a factor to assure proper dosage

Pentagon: Would use PB again

Bernard Rostker, the Pentagon's special assistant for Gulf War illnesses, told reporters that in the future the Pentagon would undertake careful consideration before using PB again.

Bailey said PB is still considered an invaluable tool against the poison gas soman and will continue to be used.

"It is life and death versus the possibility of some long-term side effects," she said.

Correspondent Mike Boettcher and The Associated Press contributed to this report.