By Debora MacKenzie
Exclusive from New Scientist Print Edition
A week into the invasion of Iraq and news networks are beaming home images of American and British soldiers donning gas masks and body suits to protect themselves from potential chemical weapons attack.
The troops have practised the drills, and are carrying the best high-tech chemical detectors an army can buy. The US marines even have a brand new piece of kit: pigeons, which act like canaries in a 19th-century coal mine. The birds are so sensitive to nerve agents such as sarin and VX that they fall ill at a whiff of danger.
What the soldiers have not been told is that about one in 10 of them are almost as sensitive to nerve agents as the pigeons. There is now mounting evidence that exposure to minuscule amounts of these chemicals can cause permanent brain damage in susceptible people, and that is exactly what happened 12 years ago when thousands of troops returning from Kuwait started to complain of debilitating symptoms.
Repeated surveys find 30 per cent more sick people among Gulf veterans than in comparable groups who did not serve. But the official position in Britain, Canada and the US is that Gulf war syndrome is not a specific medical condition.
All accept something is wrong with the 1991 veterans, but official research has focused on post-traumatic stress. The US has paid disability compensation to more than 110,000 of the 696,000 troops who fought in that war.
Then in October 2002, the US Department of Defense admitted there is “increasing evidence” that neural damage is affecting the ex-soldiers. It doubled research funding, including work on protective treatments. Veterans called it a “stunning reversal”.
Part of the problem has been that veterans report a variety of symptoms which, though serious and chronic, are often vaguely defined. But in September 2002, researchers at the Gulf War Illnesses Research Unit at King’s College in London showed that stress cannot explain symptoms displayed by British veterans.
At the same time, a medical team in the US identified three distinct syndromes among US Gulf war veterans. Han Kang and his team at the US Department of Veterans Affairs used a statistical technique called factor analysis that reveals unusual clusters of symptoms. They found syndromes that matched those seen in a smaller group by Robert Haley of the University of Texas Southwestern Medical Center in Dallas, who pioneered the investigation.
Syndrome 1 involves symptoms such as sleep and memory disturbance, while people with syndrome 3 have joint and muscle pain. The most serious is syndrome 2, whose symptoms include confusion and dizziness.
When Haley’s team used magnetic resonance spectroscopy (MRS) to study veterans with syndrome 2 they found that they had lost nerve cells in the basal ganglia, structures involved in the brain functions disturbed in those with the syndrome. Veterans with other syndromes had also lost neurons in brain areas that fitted their symptoms. The finding was confirmed in another group by MRS expert Michael Weiner at the University of California at San Francisco.
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Chemical weapons alerts
But what caused the damage? Haley found that syndrome 2 veterans are eight times as likely as healthy veterans to have been present when chemical weapons alarms sounded in the Gulf: for example, in January 1991, when Czech experts using sensitive Russian-made equipment detected nerve agent near a US army camp in Saudi Arabia.
Military authorities have denied that any soldiers were damaged by chemical weapons during Desert Storm, as none ever showed symptoms of acute nerve gas poisoning. But Jonathan Tucker of the US Institute of Peace, a congressionally funded think tank in Washington DC, has found dozens of reports of low levels of chemical weapons being detected near troops. These could have been released when allied forces bombed Iraqi arms depots or factories.
Syndrome 2 veterans were also around eight times as likely as healthy comrades to have reacted badly to pyridostigmine, a drug given to soldiers in the Gulf, then and now, to protect against nerve agent attacks. In troops who were both exposed to nerve agent and showed side effects to the drug, the risk of long-term ill effects was five times the risk conferred by each factor separately.
The link, says Haley, is that chemical weapons, and the drug that protects against them, affect the same physiological pathway. Nerve gas sends muscles into fatal spasm by blocking an enzyme that destroys acetylcholine, the neurotransmitter that makes muscles contract. In theory, pyridostigmine protects by blocking the enzyme for a short time, keeping nerve agents from binding to it permanently.
But some people may not be able to cope with having the enzyme blocked at all. Animal experiments show that exposure to enzyme blockers at levels too low to produce acute toxic effects can subtly change acetylcholine activity in the brain, and the animals’ long-term behaviour.
Memory and cognition
Rogene Henderson of the University of New Mexico reported in 2002 that low doses of sarin change the distribution of acetylcholine receptors in rats’ brains. Affected regions include those used for memory and cognition – which are the functions disturbed in Gulf war veterans.
The effect is more marked in stressed animals, which may explain why soldiers who saw combat show more severe symptoms. Other groups have also shown that nerve agents cause basal ganglion damage in animals.
Why are all soldiers not equally affected by the exposure to nerve agents? Pigeons make good detectors because they do not produce the enzyme paraoxonase which destroys nerve gas. Haley has found that syndrome 2 victims have very low levels of the form of human paraoxonase that is most effective against nerve agents, an observation repeated by Department of Veterans Affairs researchers in New Jersey in a study yet to be published.
In Britain, Bharti Mackness and her team at the Manchester Royal Infirmary have found that British veterans with Gulf war syndrome have half the paraoxonase activity of healthy colleagues.
Evidence that this kind of physical damage underlies Gulf war syndrome has been mounting since 1997. But the US government did not begin to take it seriously until the Department of Veteran’s Affairs appointed a new Research Advisory Committee on Gulf war veterans last year.
The Department is now planning a national survey of Gulf veterans based on the newly defined syndromes, while Haley is building a more powerful MRS lab to observe brain damage more precisely. “We will then turn to finding treatments,” he says. He has already shown that mice induced to make more paraoxonase are protected from a chemical similar to sarin.
Such progress promises to shed more light on why so many Gulf veterans are sick, and stop it from happening again. But it has come too late to help soldiers exposed to chemical weapons during the current conflict.