After 30 years, researchers believe they finally have definitive evidence of the primary cause of Gulf War syndrome: exposure to low levels of the nerve gas sarin.
Gulf War syndrome is blamed for leaving a quarter million veterans of the 1991 conflict with a disabling array of long-term symptoms. They range from respiratory disorders, profound fatigue and foggy memory, to chronic digestive problems and widespread joint and muscle pain.
Rick Rhodenbaugh, 58, is one of them.
Soon after returning home from his 1991 deployment, Rhodenbaugh was having persistent breathing difficulties, along with chronic diarrhea (that was initially diagnosed as irritable bowel syndrome). Over the years, his symptoms have included debilitating fatigue, body aches, complete loss of smell, and wavering between hypersensitivity and insensitivity to pain.
"There are a lot of days where it's like having the flu, but without a fever," said the Kansas resident.
There have been many theories as to the cause, given that troops were exposed to multiple chemicals and pollutants during the war - including burning oil wells, pesticides and anti-nerve gas medications.
Now the new study offers what experts called the strongest evidence yet that the main culprit was sarin - a nerve gas released into the air when Iraqi munitions facilities were bombed.
Researchers found that veterans who carry a "weak" form of a gene that detoxifies the body from nerve gas exposure were especially vulnerable to becoming ill. That, they say, not only implicates sarin as the cause, but can explain why only some exposed veterans fell ill while others did not.
"We take the position that this is evidence of causality," said lead researcher Dr. Robert Haley, who has been studying Gulf War syndrome for 28 years.
Linking specific genes to the risk of the illness is critical because genes are "randomly assigned" and "can't be biased," said Haley, a professor at the University of Texas Southwestern Medical Center in Dallas.
Marc Weisskopf, a professor at the Harvard School of Public Health in Boston, agreed that the study overcomes longstanding challenges in pinpointing the culprit behind Gulf War syndrome.
"One of the great difficulties has been understanding exactly what people were exposed to," said Weisskopf, co-author of an editorial published online May 11 with the study in Environmental Health Perspectives.
Researchers have had to rely on Gulf veterans' recollection of their exposures. That always comes with the risk of bias, Weisskopf said, because a person with symptoms is more likely to remember a potentially hazardous exposure.
Alarms went off
In the case of sarin - an odorless, colorless gas - researchers have had to use a proxy for veterans' exposure: whether they heard nerve-agent alarms go off during their deployment. But while studies have linked that self-reported exposure to a higher risk of Gulf War syndrome, that does not prove a cause-and-effect relationship, or explain why only some exposed veterans became ill.
So for the new study, Haley's team looked at the interaction between exposure to nerve-gas alarms and veterans' genes - specifically a gene called PON1.
PON1 has two forms: Q, which makes an enzyme that efficiently breaks down nerve agents like sarin; and R, whose enzyme breaks down other chemicals but has weak effects on nerve agents.
The researchers found that Gulf War veterans who'd heard nerve gas alarms during deployment were at increased risk of becoming ill. But the effect was much greater among those who carried two copies of the "weak" R variant of PON1.
In that "RR" group, veterans who'd heard alarms were about nine times more likely to develop Gulf War syndrome. Alarm exposure raised the odds of illness among vets with two copies of the "strong" gene variant, too - but by 3.7 times.
Weisskopf said the findings offer a "strong argument" for sarin as the primary cause of Gulf War syndrome - though other exposures, like pesticides, could have contributed, too.
Not 'in their heads'
Anthony Hardie, director of the advocacy group Veterans for Common Sense, said the findings have major implications.
Even today, he said, some veterans are told their symptoms are "all in their heads," and this study provides further proof Gulf War illness is real.
Beyond that, Hardie said, it might help more veterans with the illness get compensation from the Department of Veterans Affairs (VA).
"Right now, most veterans who file a claim with the VA are denied," he noted.
"I think this landmark study offers a clear path for the VA to definitively presume sarin exposure for all 1991 Gulf War veterans, and to stop denying all these claims," Hardie said.
The findings are based on a sampling of just over 1,000 Gulf War veterans, half of whom have the syndrome.
Like other veterans, Rhodenbaugh had his disability claims denied for years before finally having all of his health problems declared service-related in 2019. He credits a letter written by Haley, describing his situation in detail.
Rhodenbaugh said he hopes this research helps others like him get compensation. He noted that even among veterans who were in his unit in the Gulf, some have questioned why only some of them fell ill when they all had the same exposures.
"Understanding the DNA part explains that," Rhodenbaugh said.
It has long been difficult, Weisskopf said, to get evidence on the cause of Gulf War syndrome that rises to the level needed to convince "a variety" of parties.
"Hopefully, this will turn the tide," he said.
Johns Hopkins University has more on Gulf War syndrome.
SOURCES: Robert Haley, MD, professor, internal medicine, University of Texas Southwestern Medical Center, Dallas; Marc Weisskopf, PhD, ScD, professor, environmental epidemiology and physiology, Harvard T.H. Chan School of Public Health, Boston; Anthony Hardie, national chair and director, Veterans for Common Sense, Washington, D.C.; Richard Rhodenbaugh, Gulf War veteran, Kansas; Environmental Health Perspectives, May 11, 2022, online