It's been 25 years, and Chad Donovan still wonders which toxic hazard in the Gulf War might have caused the fatigue, stomach problems and rashes he has suffered ever since.

Maybe it was the nerve gas pills, which his unit took in Saudi Arabia while standing in formation so nobody refused.

Maybe one of the "false alarms" after a missile attack really did signal the presence of chemical weapons.

Maybe the mushroom-cloud detonation of unused Iraqi ordnance whooshed toxins into the air.

And then there were the sand fleas, pesticides, burning oil wells, dust storms and uranium-depleted bullets that made the Gulf War one of the most toxic conflicts in history.

Today, researchers at the Minneapolis VA Medical Center are leading a wave of studies to solve the mystery of Gulf War Illness, a cluster of unexplained symptoms reported by 25 to 65 percent of the 700,000 soldiers deployed to the Gulf in 1990 and 1991. They have identified genetic markers that could improve tests and treatment, one of the most significant advances in years, and started a clinical trial on a promising prescription drug.

But 25 years later, many Gulf War vets remain like Donovan — sick, sore and exhausted by the lack of answers.

"Everyone I'm still in contact with has had issues," said Donovan, who served with the Army's 82nd Airborne Division that deployed days after Iraq invaded Kuwait. "Insomnia, the achy joints, stomach issues. I still have stomach issues, and nobody knows what's causing them."

More than $500 million in research hasn't found causes or cures for the illness, which the U.S. Department of Veterans Affairs classifies as "unexplained illness" or "chronic multisymptom illness."

The consequence isn't just scant treatment of the illness, which typically produces joint pain, chronic fatigue or digestive problems. With limited diagnostic criteria, many veterans can't prove their illnesses stem from Gulf War service and can't qualify for VA disability benefits.

And while federal policy is to presume that any Gulf War vets with symptoms qualify for VA coverage, the reality is different. Eighty percent of Gulf War Illness-related claims were denied in 2015, according to federal data presented to Congress this year.

"So many veterans can't get these presumptive illnesses service-connected," said James Bunker, who directs the National Gulf War Resource Center in Kansas. "So they're being denied the care they should be getting."

A 'big mushroom cloud'

Americans were primed for the worst when the Gulf War started, based on reports that Iraq had stockpiled chemical weapons; and they were subsequently relieved when they watched the so-called surgical war of precision bombs and lightning-quick attacks play out on cable TV.

But that relief might have fueled disbelief when soldiers came home reporting fatigue and pain. Many soldiers were told it was "in their heads," said Brian Engdahl, a psychologist and Gulf War researcher at the Minneapolis VA.

"The live coverage of 'shock and awe,' the way we blew Saddam back to Baghdad, got people thinking that this was the perfect war," Engdahl said.

Blaming psychological causes also led research astray, said Roberta White, a Boston University expert on environmental toxins who evaluates Gulf War research proposals for the U.S. Department of Defense. "The VA wasted millions of dollars on stress as the predictor," she said.

Donovan was in the third planeload of American soldiers to arrive in Saudi Arabia in 1990 as part of Operation Desert Shield. Cocky and 20 years old, he picked scorpions out of the desert and labeled them with whiteout to fight those that other soldiers found.

"You're young and you're bored," he recalled.

Now 46 and living in Rochester, Donovan says environmental hazards were everywhere. A pesticide burned his arms. Oil wells set ablaze by Iraqi forces darkened the skies and covered him in soot.

And then there was the explosion. After his unit swept into Iraq during Desert Storm and secured the Tallil airfield, Donovan was assigned to chart unused munitions. He found warheads with what appeared to be chemical markings in a bunker that was detonated.

"It went off like a big boom, big earthquake, big mushroom cloud," he said. "We don't know what happened to all those munitions."

Problems emerged once he got back home. Discharged in 1992, Donovan took a manufacturing job in the Twin Cities and played softball. The routine grew oddly exhausting. Stomach pains repeatedly forced him to the hospital.

Donovan had stayed away from the VA, but his symptoms confounded his doctor. After meeting a veteran services officer at a recent motorcycle rally, he decided to apply for VA disability benefits. With four kids ages 21 to 12, Donovan said his poor health combined with post-traumatic stress disorder have made him an inconsistent husband and father.

"I get angry really easy," he said. "It just happens randomly, like the stomach issues."

His first request was denied, but he is appealing. He isn't alone. The number of Gulf War veterans reporting symptoms and filing claims has increased — along with the denial rate.

Officials for the VA's benefits division did not respond to questions about the rising number of claims and denials.

Now, however, research at the Minneapolis VA could give vets more satisfying answers. Teaming with Dr. Apostolos Georgopoulos at the hospital, Engdahl found that six genetic markers in blood predicted Gulf War Illness with 84 percent accuracy.

Effects of 'toxic stew'

Using a unique brain scanner based on anti-submarine technology, the researchers also are studying brain activity in 1,000 veterans to identify patterns of dysfunction in those with Gulf War Illness. Already, their research has shown that the cerebellum is smaller in the brains of sickened Gulf War vets.

"To individual veterans, that is reassuring," Engdahl said. "They say, 'Aha … you can see it in my scans.' It's not just in their heads, figuratively."

Skeptics are suspicious over the spike in veterans claiming illnesses, since they haven't been exposed to Gulf War toxins for decades. But it makes sense to some researchers.

Dr. Beatrice Golomb of the University of California, San Diego, was the first chairwoman of the VA's research committee on Gulf War Illness and is one of the leading researchers on the topic. She believes the "toxic stew" of vaccines, pesticides, chemical agents and other Gulf War hazards disrupted a brain chemical that regulates acetylcholine, a neurotransmitter responsible for muscle and digestive functions in the body. The disruption also damages the mitochondria that control energy levels in cells, and worsens with age.

White, the Boston researcher, said confirming such "biomarkers" of Gulf War Illness could soon make a difference: "We're going to have what we need to say 'This person is a real case.' "

Some research delays were inevitable because scientists knew less about genetics, the human brain and immune systems in the 1990s. But veterans believe the effect of the delays has been severe.

Brian Zimmermann of Sandstone, Minn., was in the Army's First Infantry, which swept across southern Iraq during Desert Storm and trapped Iraqi soldiers on the infamous "highway of death." Memories of a child bleeding to death and grisly fatalities haunt Zimmermann, who has post-traumatic stress disorder. But he also developed joint pains that still send him to the hospital numerous times each year. His disability claim was denied for Gulf War Illness but approved for PTSD.

Several veterans from his unit have recently died by suicide, and he attributes it to their physical suffering. "It's not the PTSD that is killing us," he said. "It's the pain and being told you're not hurt, that it's in your head."

Experts doubt Gulf War Illness will ever be linked to a single cause, like the defoliant Agent Orange that sickened Vietnam vets. Chemical tests have drawn links to pesticides and the pyridostigmine bromide pills soldiers took to protect against nerve gas. Detonations of Iraqi weapons caches also have been scrutinized.

Vaccinations for common diseases and germ warfare agents such as anthrax might have played a role. "When they gave those shots, you wouldn't believe the amount of guys that were sick, me included," Zimmermann said. "We couldn't have fought anybody."

Some veterans who developed symptoms received shots but never were deployed to the Gulf — supporting the vaccine theory. On the other hand, few received the anthrax and botulism shots that have raised the most suspicions.

Treatment, not causes

Some believe the search for a cause is unproductive. An advisory group with the National Academy of Sciences recommended this year that studies on Gulf War Illness should focus more on treatments and less on causes.

Treatment studies are underway. Golomb's mitochondria research led to a test of CoQ10, a dietary supplement that supports energy production in cells. A larger second trial at five VA medical centers, including the Minneapolis hospital, is pending.

Ronald Bach, a protein chemist at the Minneapolis VA, has another promising lead. Unimpressed by neurological studies of Gulf War Illness, Bach instead examined its effects on blood and the immune system. He found biomarkers in blood indicating that people with Gulf War Illness have overactive immune systems that were triggered by all of the toxins.

"The body was traumatized and [the immune system] remained activated," he said. "The trick is trying to figure out a way to turn it off."

In a trial now underway, Bach seeks to use a steroid, prednisone, to tamp down the overactive immune systems.

Current federal treatment guidelines — based on reported associations between Gulf War Illness and depression and anxiety — recommend behavioral therapy first, and then pain pills, acupuncture or antidepressants to manage symptoms, but not cure them.

White hopes chemical and biological research will yield treatments that are more on point; she is particularly troubled by the use of antidepressants, which have never been studied for this illness.

"We're on the crux of really … being able to at least treat it, if not cure it," she said.

Gulf War vets have been eager to help. Engdahl has recruited 100 so far for his brain study, including William Brownell, 72, of St. Paul.

Serving in the Army's 54 Bravo unit during the war, Brownell took air samples after missile attacks and checked Iraqi prisoners for hazardous agents. He's been plagued ever since by breathing troubles, which he attributes to the burning oil wells. He hopes volunteering will find a cure for younger vets.

"If I can help," he said, "they may find out what is going on."

Jeremy Olson • 612-673-7744