Researchers Think They've Found the Cause of Gulf War Illness

After nearly 30 years of trying to prove a theory -- that an environmental toxin was responsible for sickening roughly 250,000 U.S. troops who served in the 1990-91 Persian Gulf War -- Dr. Robert Haley says new research confirms that sarin nerve gas caused Gulf War Illness.

Following the Gulf War, nearly one-third of all who deployed reported unexplained chronic symptoms such as rashes, fatigue, gastrointestinal and digestive issues, brain "fog," neuropathy, and muscle and joint pain. Federal agencies spent years broadly dismissing the idea that troops may have been suffering from exposure to chemical agents, with many veterans experiencing symptoms sent to mental health providers.

But a study published last week in the journal Environmental Health Perspectives used genetic research and survey data to determine that U.S. service members exposed to sarin were more likely to develop Gulf War Illness, and those who were exposed and had a weaker variant of a gene that helps digest pesticides were nine times more likely to have symptoms.

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"Quite simply, our findings prove that Gulf War illness was caused by sarin, which was released when we bombed Iraqi chemical weapons storage and production facilities," said Haley, director of the Division of Epidemiology in the Internal Medicine Department at University of Texas Southwestern Medical Center.

"There are still more than 100,000 Gulf War veterans who are not getting help for this illness and our hope is that these findings will accelerate the search for better treatment," Haley said.

Originally developed as a pesticide, the chemical weapon sarin was known to have been stockpiled by Iraqi President Saddam Hussein prior to and after the 1990-91 Persian Gulf War. The synthetic nerve agent attacks the central nervous system and brain, killing victims by triggering an overreaction of neurotransmitters that causes convulsions and asphyxiation.

Thousands of coalition troops likely were exposed to sarin and cyclosarin, an organic phosphate also used as a chemical weapon, when the U.S. destroyed a bunker housing chemical weapons at the Khamisiyah Ammunition Storage Depot in southern Iraq, sending a plume of contaminants that spread across a 25-mile radius. Others may have been subjected to low levels of contaminants, as troops frequently reported that chemical weapons alarms went off in the absence of any apparent attack.

In the years following the war, veterans who sought medical help at the Department of Veterans Affairs were greeted with skepticism and sent to psychiatrists for mental health treatment. Health surveys conducted by the VA in the early 2010s of Gulf War veterans focused mainly on questions about psychological and psychiatric symptoms.

And in 2013, veterans' suspicions of the lack of concern at the VA were confirmed when VA whistleblower and epidemiologist Steven Coughlin came forward to say that the department buried or obscured research findings that would link physical ailments to military service -- a concerted effort to deny veterans health care and benefits.

Coughlin's charges were later confirmed by an email sent to staff from former Undersecretary for Benefits Allison Hickey expressing concern that changing what the VA still calls "chronic multisymptom illness" to "Gulf War illness" might "imply a causal link between service in the Gulf and poor health which could necessitate legislation for disability compensation for veterans who served in the Gulf."

Research Confirms Earlier, Smaller Studies

For the new study into sarin, Haley and colleagues randomly selected 1,116 veterans who completed a U.S. Military Health Survey, including 508 who deployed and developed Gulf War Illness and 508 veterans who went but never developed symptoms. They collected blood and DNA samples from each participant and asked the veterans whether they heard nerve gas alarms during their deployment, and if so, how often.

The researchers also tested for variants of a gene that helps the body metabolize pesticides, called PON1. Some people have variants of this gene that are more effective in breaking down sarin while others have a variant that helps process chemicals like pesticides but is less efficient against sarin.

The study found that those who reported hearing nerve agent alarms and who also had the least robust form of the gene had a nine-fold chance of having Gulf War Illness. Those with a genotype that is a mix of the two variants had more than four times the chance of having Gulf War Illness, while those who just heard nerve agent alarms, which the researchers used as a proxy for exposure, raised the chance of developing the condition by nearly four times, although to a lesser degree of those who have a mix of genes.

According to the researchers, the data "leads to a high degree of confidence that sarin is a causative agent for Gulf War Illness."

"Our hypothesis was, if you have the strong form of the gene, then when you're exposed to low-level sarin, that gene makes a strong isoenzyme that destroys sarin in your blood. If you have the weak form of the gene, the enzyme that it makes is not very strong, so it goes through your blood into your brain and you get sick," Haley said in an interview with Military.com. "You've heard the expression 'correlation does not equal causation,' right? That's true, unless you are dealing with a gene-environment interaction."

A Mysterious Malady

The mysterious symptoms experienced by thousands of service members, which came to be known as Gulf War Syndrome and, later, Gulf War Illness, generated hypotheses of the possible cause, including an additive in anthrax vaccines, preventive medicines given to troops such as the anti-nerve agent pyridostigmine bromide, ciprofloxacin, depleted uranium, and exposure to nerve gas, pesticides or smoke from oil well fires.

A congressional investigation in 1997 concluded that the Departments of Defense and Veterans Affairs had very little interest in finding a cause and blamed the symptoms as related to stress or other mental health disorders.

In its report, the Committee on Government Reform and Oversight found that the DoD and VA were "plagued by arrogant incuriosity and a pervasive myopia that sees a lack of evidence as proof" that the illness didn't exist.

"Sadly, when it comes to diagnosis, treatment and research for Gulf War veterans, we find the Federal Government too often has a tin ear, a cold heart and a closed mind," the report noted.

As Congress investigated the issue, Haley was studying possible causes, funded by Ross Perot, the Texas billionaire and Navy veteran known for donating to veterans' charities and resources, including efforts to help U.S. prisoners of war in Vietnam.

Haley's early work pointed to sarin as a possible cause, but other scientists, including the medical body of the National Academies of Sciences, Engineering and Medicine, found his studies to be insufficient in size and suffering from selection or "recall bias," meaning that vets may or may not remember whether they heard nerve gas alarms and how often.

Haley said the new research links veterans with Gulf War Illness with their genotype and "cannot be explained away by errors in recalling the environmental exposure or other biases in the data."

Others now concur. In an editorial accompanying the study, Marc Weisskopf, a professor of environmental epidemiology and psychology at the Harvard T.H. Chan School of Public Health, and Kimberly Sullivan, a research associate professor with Boston University School of Public Health, said the study makes a strong case for a causal link and explains, to some extent, why some troops got sick and some did not.

"The authors' exploration of a gene-environment interaction between presumed nerve agent exposure and the PON1 gene offers some strong arguments that there is a true causal effect at work," they wrote in their opinion piece.

The VA has established service connection for Gulf War veterans with certain chronic, unexplained symptoms, which the department calls "chronic multisymptom illness" or "undiagnosed illness."

Those who have certain symptoms, such as chronic fatigue syndrome, fibromyalgia and some gastrointestinal disorders, and served in the 1990-1991 conflict do not have to prove service connection and are eligible for benefits including a health exam, health care and disability compensation.

Historically, however, the VA has been strict in determining service connection. A 2017 Government Accountability Office report found the VA denied 83% of 102,000 claims filed for Gulf War Illness between 1994 and 2015.

New Hope

Haley said the research could pave the way for more veterans to access health care and benefits and open up research into possible treatments. He said that the symptoms are caused by brain inflammation, which may be treatable once scientists figure out exactly how sarin works.

"Once we know, we could come up with treatments to reverse it," Haley said. "I really believe this is optimistic and that it means this is not brain damage. This is not loss of neurons and like a stroke or something that you're never going to recover from."

Among the veterans excited about the new study is Paul Sullivan, a Persian Gulf War veteran who works as director of veteran outreach at the law firm Bergmann & Moore and deployed to Iraq as an Army cavalry scout with the 1st Armored Division in 1991.

He said the results provide evidence that affected veterans need to access care from the VA.

"This landmark study provides a clear path for VA to presume sarin exposure for all 1991 Gulf War veterans," Sullivan said Thursday. "The study provides a compelling missing scientific link for treatment research for my fellow Gulf War Veterans disabled since our exposures during Desert Storm."

Haley said he has received letters from veterans asking if they could get tested for the different types of the PON1 gene and whether it would be helpful. Routine genetic testing does not include PON1, but further research may lead to a diagnostic test that would provide peace of mind to veterans, he said.

The research was conducted in collaboration with a survey research team from North Carolina-based RTI International and funded by the DoD and VA, both of which have funded thousands of studies on Gulf War Illness despite long-standing skepticism.

"This is the scientific process. Nobody's bad. Nobody's good. People have their theories. Skepticism is the name of the game. That is what makes it fun," Haley said.

-- Patricia Kime can be reached at Patricia.Kime@Military.com. Follow her on Twitter @patriciakime.

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