MYSTERIOUS symptoms suffered by thousands of troops who served in the
Gulf War might be explained by exposure to a combination of an anti-nerve gas
agent and two pesticides. The chemicals could account for many of the cases of
“Gulf War syndrome”, a debilitating collection of ailments reported by many Gulf
Researchers at Duke University in Durham, North Carolina, and the University
of Texas Southwestern Medical Center in Dallas suggest that an anti-nerve gas
pill taken by many of the troops may have interfered with the body’s natural
defences against the toxic effects of an insecticide and an insect repellent
they routinely used to protect against disease-carrying flies and
A year ago, the researchers reported that chickens exposed to relatively low
levels of all three chemicals developed nerve damage (This Week, 22 April 1995,
p 5). Last week, at a meeting of the Federation of American Societies for
Experimental Biology in Washington DC, the researchers outlined a possible
mechanism behind the damage.
“The chemicals were used with good intent, to protect the troops from
diseases like malaria and leishmaniasis,” says Mohamed Abou-Donia, professor of
pharmacology and neurobiology at Duke University. “They did the job. These other
effects were unforeseen.” Because of fears of nerve gas attacks, American troops
were issued with pills containing pyridostigmine bromide. If their officers
thought there was danger of a gas attack they would order the troops to take the
pills. The drug is designed to protect the peripheral nervous system from nerve
agents long enough to allow soldiers to take a stronger antidote.
To deter insects, soldiers applied the commonly used repellent DEET directly
to their skin. The insecticide permethrin was sprayed on clothes, sleeping bags
and tents. Individually, each chemical is harmless in the doses soldiers were
exposed to. But together, says the team, they could have caused nerve damage
that would account for the fatigue, headache, poor concentration and other
symptoms many veterans report.
About 700 000 American troops served in the Gulf between August 1990 and
March 1991. Some 30 000 have sought medical attention for unexplained illness.
In their study, the researchers exposed chickens to amounts of the chemicals
which by themselves are harmless. But when exposed to a combination of two or
three of the chemicals, the chickens began to stumble and shake, and show other
signs of nerve damage. At postmortem, nerve damage was visible under the
microscope. Another clue was that in the sick chickens the activity of a blood
enzyme called plasma butyrylcholinesterase (BuChE), which helps to neutralise
toxins, was lower than normal.
BuChE is a “scavenger enzyme” which breaks down toxic substances. Normally,
it would break down any DEET or permethrin that gets into the body. Abou-Donia
says the pyridostigmine may have interfered with BuChE and stopped it from
mopping up stray molecules of pesticide.
Pyridostigmine protects nerve cells by binding temporarily to
acetylcholinesterase (AChE), the enzyme which normally breaks down the
neurotransmitter acetylcholine, preventing nerve cells from firing
uncontrollably. Nerve agents destroy this enzyme and the nervous system goes
But pyridostigmine also binds to BuChE in the blood, preventing it from going
to work on stray molecules of DEET and permethrin. What would otherwise be safe
levels of the chemicals then become harmful, damaging the peripheral and central
nervous systems, and possibly also crossing into the brain and causing damage
Diagram). About four people in every hundred have naturally low
levels of BuChE, and this could make them particularly vulnerable to damage from
the mix of chemicals.FIG-20270201.jpg
That is the theory. But Abou-Donia says more research is needed before he and
his colleagues can be sure that this is the mechanism. They are testing blood
samples from Gulf War veterans to see whether those suffering the worst symptoms
have unusually low levels of BuChE.
The US Department of Defense says its officials will meet Robert Haley, the
epidemiologist heading the study at Southwestern Medical Center. The Pentagon is
continuing to study veterans’ illnesses, but says there is no evidence so far of
a “syndrome” resulting from a single cause.
According to one member of an expert committee investigating Gulf War
syndrome, the problem with this explanation is that although veterans seem to be
suffering nervous symptoms they show no sign of damage to the nervous system.
“The study’s relevance to the Gulf veterans remains to be demonstrated,” says
Howard Kipen of the Robert Wood Johnson Medical School in New Jersey. “No one
has yet demonstrated an excess of nervous system disease in the veterans.”