Unraveling a mystery

Dr. Robert Haley, chief of epidemiology at the University of Texas Southwestern Medical Center, sounds as exuberant as a schoolboy winning his first science fair when he talks about all the media attention garnered by his team's latest study on Gulf War Syndrome -- results of which unequivocally point to brain damage caused by exposure to toxic chemicals as the cause of the veterans' myriad mysterious ills.

"It made the front page of The New York Times national section and the Wall Street Journal and every paper in the country," he says. "Dan Rather reported it on the CBS Evening News, and CNN had it on for 24 hours. It was completely unanticipated."

What Haley means is that the medical center never sent out a press release or called a news conference -- not that that always guarantees media coverage. His colleague Dr. James Fleckenstein, a professor of radiology at the medical center, simply reported the results at the Radiological Society of North America meeting in late November -- -before the research paper was even peer reviewed and published -- and the media went wild. Not only did Haley's work get national and international coverage, but the press, for the most part, also was positive, with numerous editorials calling for the federal government to fund more of Haley's research.

But that's not the only positive feedback the Southwestern team has received recently. In mid-October, the Pentagon released the results of a study supporting Haley's earlier work, which pointed to an experimental drug given to American troops during the war to protect against a nerve gas as one possible culprit behind the chronic illnesses suffered by thousands of Gulf War vets. The Pentagon study sharply contradicted two earlier government studies -- by a presidential committee and by the Institute of Medicine -- that ruled out the drug as a cause.

It wasn't long ago -- just two years ago, in fact -- that Haley was the Rodney Dangerfield of the medical research field. He and his research team didn't get any respect. Naysayers in the Pentagon, Veterans Affairs Administration, and the media doubted such a thing as Gulf War Syndrome existed, much less gave credence to theories on what caused it. When the respected PBS news show Frontline devoted an hour-long segment to the subject in the fall of 1997, Haley and the Southwestern Medical Center team's work was glossed over and relegated to the category of fringe theories.

"There's a whole sea change occurring," Haley says. "When meaningful research gets done, the research causes changes in thinking. That's the beauty of science. It's not like politics. Here it really does change if you do good work in respected publications."

The latest study builds on the group's earlier work ("The war over Gulf War Syndrome," March 5, 1998), in which the doctors hypothesized that the veterans' symptoms -- chronic fatigue, sleeplessness, motor coordination problems, memory loss, and muscle pain -- stemmed from damage in the brain stem and basal ganglia caused by low level exposure to a combination of neurotoxic chemicals, including nerve gas, an experimental nerve-gas antidote, and pesticides.

What the recent study showed was that a group of sick vets had substantial brain damage compared with a control group of healthy vets. Haley's team had previously done magnetic resonant imaging of veterans' brains and discovered that structurally their brains were normal -- that is, they did not suffer a loss of brain cells. So this time, convinced that their brain-damage theory was right, they tested the actual chemical component of the existing brain cells with a relatively new technique called magnetic resonant spectroscopy.

"This is way out in the frontier," Haley says.

MRS scans of 22 veterans who complained of illness indicated they had 10 to 25 percent less of the chemical NAA, or N-acetyl-aspartate, in their brain stems and basal ganglia compared with 18 healthy vets. Scientists conducting the readings did not know which samples belonged to the ill veterans. The same results turned up on a second test of six other Gulf War veterans.

"That's a significant loss," Haley says. "Even a 5 percent loss would be significant."

Scientists are not sure exactly what the chemical NAA does, Haley says. "But the way to think about it is that if a brain cell is sick, it can't make much of it. So it's a perfect measure of neurotoxicity."

Developed in the last five years, MRS has helped unravel other medical mysteries such as epilepsy. MRS scans show that people who suffer from epilepsy have a reduction of NAA in the temporal lobe. Schizophrenics also have an abnormal NAA level in the left basal ganglia.

The group's earlier work also helped answer another puzzling question about the illness -- why some vets are sick and others are not. The doctors knew that certain people have a genetic predisposition to neurotoxicity: They lack significant quantities of a certain enzyme that breaks down the chemical agents in the body. Haley's group tested the sick veterans for a specific enzyme that protects against the nerve gas sarin. Compared with the healthy veterans, the sick veterans had a low or nonexistent level of the enzyme called PON-Q that can effectively combat low levels of sarin.

Shortly after the war started, U.S. troops bombed Iraqi warehouses that stored sarin gas. Clouds containing low levels of the gas blew over the troops. "The gene study explains why one guy would get sick and another wouldn't," Haley says. "If he had a low amount of the PON-Q enzyme, the gas would go right to his brain. They told us we'd never be able to prove what the soldiers were exposed to, but we proved it was sarin."

Scientists who claim the sample size is too small to be significant have met the study with some caution. That's a criticism that was lodged at the early studies into another controversial disease -- AIDS. "The following five and six studies of the AIDS epidemic all confirmed what the first showed," Haley says. "With an epidemic, you don't get a difference in outcome by just increasing the sample size. This is also more cost-effective. Anyone can design a study with 1,000 people. But this is the most efficient way to solve a problem. The government did a random sampling on all 700,000 vets, and they found out nothing after spending millions."

The Southwestern doctors have proposed doing a big random-sample survey of Gulf War veterans, but the Veteran Affairs central office, he says, has been the holdout. "They've been extremely negative about our work," Haley says. "They've done everything to thwart our efforts."

Haley has intensely studied 250 members of a mobile construction battalion that traveled across the war zone, and he feels certain his group's work has pinpointed why they're sick and how it happened. Now the question is, How common are the findings to the other vets who are complaining? The Southwestern doctors have been turned down twice for a random-selection study, but Haley thinks the third time might be the charm.

"Our timing is better, and we've developed support for our theory," he says. "There's a general consensus now in the science world that we're right, but it hasn't been proved to their satisfaction or mine. It doesn't feel good yet, because we haven't made anyone well yet." Southwestern is testing five medications to see whether any make a difference on the vets' symptoms.

As for the hard knocks he and his colleagues have endured along the way, Haley is philosophical. "That's the way science is. We're all skeptical about any new finding until it's proved. It's very cruel to people with new ideas, and it ought to be. It keeps science from being trivial and haphazard."

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