Gulf War Syndrome (continued)
This is why the government has funded a great deal more research, to try to resolve some of these uncertainties," says Joyce Lashoff, PhD, retired dean of the School of Public Health at Berkeley and former chair of the Presidential Advisory Committee on Gulf War Veterans' Illnesses. "We recommended further research, and I think we have to wait for those results before we can be more definitive."
UMDNJ researchers are playing a leadership role in the federally funded investigations. In 1994, Benjamin Natelson, MD, professor of neurosciences at UMDNJ-New Jersey Medical School (NJMS), was named to head one of three nationwide centers chosen by the Department of Veterans Affairs to investigate Gulf War illnesses. His center, based at the Veterans Administration Hospital in East Orange, received a five-year, $2.5 million grant to focus on a possible link between Gulf War veterans' ills, chronic fatigue syndrome and multiple chemical sensitivity.
This past November, another large grant was awarded by the Centers for Disease Control and Prevention to UMDNJ-Robert Wood Johnson Medical School (RWJMS). The three-year, $1.8 million grant was given to the Environmental and Occupational Health Sciences Institute (EOHSI), a joint program of UMDNJ and Rutgers, to see if it can develop a sufficiently distinct definition of Gulf War illness that would separate it from any other known physical or psychological illnesses.
A possible link between the veterans' ills and exposure to Iraqi nerve gas should be "of particular concern" as the United States prepared for a possible second war with Iraq, warned a letter to President Clinton sent in February. The letter was written by Marguerite Knox, clinical assistant professor at the University of South Carolina College of Nursing, and a former member of the Presidential Advisory Committee chaired by Lashoff. Five of the 11 other former members of the committee co-signed it.
"I'm a veteran and was there during the war," said Knox. "It's very difficult for me emotionally to see my fellow veterans suffer and not to be able to help them. It's seeing those individuals, and hearing their pleas, that you cannot wipe out of your mind."
It's unlikely, however, that nerve gas or any other single agent will turn out to be the missing link in what afflicts Gulf War veterans, says Howard Kipen, MD, who directs the EOHSI study to define Gulf War illness.
"The data we have don't indicate there was anything about being exposed to a certain toxin that caused it," says Kipen, associate professor of environmental medicine at RWJMS. "Those data say that just being there was enough. The people who went there feel sicker than the people who didn't."
Seeking Clues in History
Kipen goes so far as to say that the mere fact of going to war-not necessarily
to the Gulf War, but to any war-makes people sicker on average than their
non-combatant counterparts. "I would make the case that this is not
unique to the Gulf," he says.
In the grant application for his current study, Kipen cites historical medical research dating back over 100 years, to the Civil War, to which he gives the generic term "war syndrome." After the Civil War, the condition was known as "soldier's heart." After World War I it became known as "Effort Syndrome" in Britain and as "neurocirculatory asthenia" in the United States. Whatever the war, the unexplained illnesses were characterized primarily by shortness of breath, palpitations, chest pain, fatigue, dizziness, confusion, concentration problems, forgetfulness and nightmares.
Historically, some of the war syndromes have been considered primarily physiologic in nature, others primarily psychological. Following the Vietnam war, for instance, some soldiers' illnesses were blamed on the defoliant Agent Orange. Others were classified as suffering from what was first dubbed post-Vietnam Syndrome, now more generally known as post-traumatic stress syndrome.
"However," Kipen writes in his grant application, "it isn't clear where one begins and the other ends, as shared symptoms in both groups include fatigue, shortness of breath, headaches, sleep disturbances, impaired concentration and forgetfulness."
In the aftermath of the Persian Gulf war, much effort has gone into identifying precise, physical causes of the veterans' illnesses. Potential hazards included smoke from oil well fires, diesel fuels and their combustion products, pyridostigmine bromide tablets (given to troops to protect against potential poison gas exposure), anthrax and botulinum toxoid vaccines, depleted uranium used in artillery shells, infectious diseases, chemical or biological warfare agents, and even such commonplace pesticides as DEET.
The "final" report of the President's Advisory Committee concluded in late 1996 that none of these physical causes appeared to be a likely culprit, but that prudence dictated that more research needed to be conducted. By then, new facts were already emerging: The Pentagon had finally admitted that shortly after the war's end, US troops had blown up an Iraqi ammunitions dump at Khamisiyah, including rockets filled with nerve gas. Research showed that very low levels of the gas might have passed over as many as 100,000 troops.
The president asked the advisory committee to provide oversight as research into the Khamisiyah event continued. Last November, the committee reported that it still looked as though the nerve gas had little to do with the troops' illnesses. But as of this February, enough controversy remained that the President appointed a new panel to examine the nerve gas connection yet again.
Few of those who've spent time examining the evidence expect the new panel to find a smoking gun. "If you ask me what caused Gulf War illness, I'm ready to say I don't know and I don't think anyone will ever know," says Arthur L. Caplan, PhD, a former member of the Presidential Advisory Committee and a professor of bioethics at the University of Pennsylvania. "I'm skeptical that more studies are going to find the answer to this riddle. It's very difficult and almost impossible to figure out why people got sick, because we didn't do good weapons monitoring, and we didn't do good pre- and post-deployment physicals." Just the same, he adds, "While we don't know what made people sick there, we do know they got sick."
Defining the Problem
If causes are elusive, Kipen hopes at least to develop a distinct definition
of Gulf War illness and its symptoms.
"The problem is, nobody has a definition of what constitutes Gulf War illness," he says. "We're trying to come up with a definition, to be able to say, okay, here's a person who has Gulf War illness-he doesn't have asthma, he doesn't have cancer, he doesn't have anything else known to medicine."
"While we don't know what made people sick there, we do know they got sick"
One of the defining factors appears to be the breadth of the veterans' symptoms: They don't hurt in one particular place, but all over.
"They don't have just stomach complaints, or just back aches," says Kipen. "There's not much parsimony to what they're complaining of. They seem to be characterized by symptoms in a number of different organ systems."
While Kipen seeks to develop a definition specific to the Gulf veterans, Natelson's $2.5 million grant from the VA is exploring links to other illnesses that also remain unexplained but have been far better studied: chronic fatigue syndrome and multiple chemical sensitivity.
"Our hypothesis is that serving in the Gulf was a trigger for chronic fatigue syndrome or chemical sensitivity," says Natelson.
Last year, at the annual meeting of the American Psychological Association, Gudrun Lange, PhD, assistant professor in the department of psychiatry and radiology at NJMS and one of Natelson's research colleagues, presented some preliminary results of his work. The study involved 42 healthy veterans and 53 suffering from severe fatigue with no other known medical illness. In an attempt to determine if any other psychiatric illness is causing the fatigue, the Gulf War research group conducted extensive psychiatric examinations. About half were found to have no other diagnosable mental illness.
"That would mean that at least for some veterans, we can't say their fatigue is due to the fact of having depression, post-traumatic stress or any diagnosable psychiatric illness," Natelson says.
Searching for Causes
What's causing the fatigue? "That's the $64,000 question," says
Natelson.
The "hurts all over" nature of the veterans' symptoms suggests to Kipen either a powerful physiologic explanation yet to be identified, or a powerful psychological one. Kipen, Natelson and their colleagues are studying the possibility that damage to the neuroendocrine system, or to immune-regulating cytokines, might play a role.
In another study, Natelson's group has been performing magnetic resonance imaging tests on the brains of veterans to see if changes consistent with low-dose exposure to nerve gas are seen.
Another investigation, just getting underway, will be led by Nancy Fiedler, PhD, associate professor of environmental and community medicine at RWJMS. Fiedler will expose a number of veterans to low levels of diesel fumes, the kind that soldiers were exposed to around military vehicles and which have no known toxicity.
"The hypothesis is that we will see a difference in reaction between the healthy veterans and those with fatiguing illness. The fatigued ones will be more symptomatic and their cognitive performance will be worse," says Fiedler. "And we expect those with emotional distress to find the fumes more noxious."
Since diesel fumes-the mere smell of them-have no physically toxic effect, wouldn't a heightened reaction among the fatigued veterans suggest that their condition is purely psychological in origin? Fiedler insists that such questions miss the point.
"It's very difficult for me emotionally to see my fellow veterans suffer and not to be able to help them"
"This experiment involves a complex interaction among stress, emotional factors and chemical exposures," she says. "All of those factors are in play, and all affect the health status of humans. To say it's psychological or physical doesn't even make sense. The mind-body dualism that's going on in the press about Gulf War illness I find to be insulting."
Fiedler's statements go to the heart of the controversy: Is a disorder caused by the harrowing effects of war "merely" psychological, or could it be that the severe stresses involved in combat cause permanent physical changes in the brain that result in a myriad of bodily symptoms? As Kipen puts it, "All psychiatric illnesses are biochemical underneath, especially the ones we can treat well. Physical causes of the veterans' unexplained illnesses have not been demonstrated to date, but we know something happened. The people who went to the Gulf have more symptoms than people who didn't go. The question is: where's the lesion?"
Although precise answers on the Gulf War have not surfaced, Natelson does believe that his work has already produced useful implications for preventing similar disabilities following the next armed conflict.
"We think it's unwise for the military to not screen potential combatants for underlying psychiatric disease," he says. "We found that some of our Gulf warriors had diagnosable psychiatric illnesses that preceded their going to the Gulf. So one of the things we're hoping to do is to convince the military that people who are vulnerable to stress should not be deployed. If they're going to activate weekend warriors from the reserves, fly them across the world, put them in harm's way, and then return them home to their job as a mechanic, it's just common sense that they not send someone who's particularly vulnerable to the stresses of deployment and battle."
Following Natelson's advice might be the Pentagon's best hope for launching a pre-emptive strike against the next outbreak of an unexplained war syndrome.