The use of the drug pyridostigmine bromide (PB) by 250,000 soldiers during the Persian Gulf War "cannot be ruled out" as a cause of lingering illnesses in some veterans, according to a new report prepared for the Defense Department.
Numerous hypotheses of how the drug--which was given to protect against the nerve gas soman--might produce lingering symptoms years after exposure are "scientifically viable," wrote the author. "This does not imply that it is necessarily a causal factor, only that the possibility cannot be dismissed," said Beatrice Alexandra Golomb of Rand Corp., a California think tank.
The 385-page review of the scientific literature on PB will be presented today at a press conference at the Pentagon. It is the latest development in an arduous search for causes of numerous ill-defined ailments collectively known as "Gulf War syndrome" afflicting some veterans. About 697,000 men and women served in the Gulf in 1990 or 1991. The number with chronic symptoms since then is unknown.
The Rand study reviewed about 1,000 published studies on the drug, which was taken in varying doses--often not more than a few times--during the Gulf War. Compared to reviews done previously, it gives somewhat more credence to the hypothesis that PB could cause chronic illness.
The drug increases the activity of acetylcholine, a neurotransmitter involved in muscle activity, cognition and various functions of the respiratory and digestive systems. It's been used for decades, at much higher doses than those given to soldiers, to treat the neurological disease myasthenia gravis. Neither people with that ailment, nor healthy volunteers who've taken PB experimentally, are known to suffer Gulf War syndrome-like symptoms.
Among the issues the Rand report said are worth studying further are these:
* Were there conditions present in the Gulf War that might have made PB toxic? An Israeli study concluded that in times of psychological stress, more of the drug enters the brain than usual.
* Do individuals respond differently to the drug? One study found that people who recalled having a strong, immediate reaction to PB were more likely to have chronic symptoms.
* Were there unusual interactions between PB and other chemicals, such as insect repellants and insecticides? Studies with lower animals have found synergistic effects. However, the report noted that in a study that showed nervous system damage, hens were exposed to the equivalent of 467 PB pills, 1,667 cans of the insecticide permethrin, and 76 tubes of the repellant DEET. Future studies should use more "physiologically plausible" doses.
* The myriad mood, sleep and cognitive complaints of some veterans "could be manifestations of prolonged dysregulation" of the acetylcholine system--if PB can cause such dysregulation. The answer is unknown and urgently needed, the report said.
The Defense Department has spent $100 million on Gulf War health research since 1994, and has about $17 million worth of studies on PB underway. "We are confident that as we move forward with this funded research, we will address these concerns," said Bernard Rostker, head of the Pentagon's office on Gulf War illnesses. He and Sue Bailey, assistant secretary of defense for health affairs, said unanswered questions about PB shouldn't necessarily exclude it from future use.
"PB at the moment is the best protection against soman, which is particularly deadly, very fast-acting and not susceptible to conventional treatment," said Bailey. "I feel no hesitancy to use any drug that would protect our troops against a deadly threat."