Harold C. Sox Jr., MD
Chairman, Institute of Medicine Committee on Health Effects Associated with Exposures during the Gulf War
Professor and Chair, Department of Medicine,
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire
Subcommittee on Labor, Health and Human Services, and Education
Committee on Appropriations
October 12, 2000
Good morning, Mr. Chairman and members of the committee. My name is Harold Sox. I am a professor and chair of the Department of Medicine at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. I chaired the Institute of Medicine Committee on Health Effects Associated with Exposures During the Gulf War, which released its report on Thursday,
September 7th. I appreciate the opportunity to provide testimony to you today based on the findings of this report. I am accompanied by Dr. Samuel Potolicchio, a member of the IOM committee and Professor in the Department of Neurology at George Washington University Medical Center.
The genesis of the report was a request from the Department of Veterans Affairs, asking the Institute of Medicine to study the available scientific evidence on potentially harmful agents to which Gulf War veterans may have been exposed. Congress subsequently mandated a similar study listing 33 specific agents for study. Thousands of Gulf War veterans have experienced chronic, unexplained health problems, and are asking whether these agents might be responsible.
It is important to clarify the scope of the committee’s work. The committee was charged with assessing the scientific literature regarding potential health effects of chemical and biological agents present in the Gulf War. The findings of the report will be used by the Department of Veterans Affairs as a scientific basis for developing a compensation program for Gulf War veterans. The committee was not asked to examine whether a unique Gulf War syndrome exists or to review or evaluate the literature on Gulf War syndrome or illnesses. Additionally, it was not asked to make judgments regarding the veterans’ levels of exposure to the putative agents as there is a presumption of exposure for Gulf War veterans. For the first study of the series, the Institute of Medicine chose to study the agents of most concern to the veterans: sarin, pyridostigmine bromide (PB), depleted uranium, and the vaccines to prevent anthrax and botulism.
Because of the limited studies in Gulf War veterans, most of the studies that we examined involved exposures in occupational, clinical, and healthy-volunteer settings. We carefully assessed each study's quality, limitations, and applicability.
When it comes to the long-term health effects of these substances, the bottom line is we simply don't know enough to say whether there is a connection between exposure to these agents or combinations of agents and specific health outcomes that remain long after the exposure. At most, we found some very limited evidence that might suggest a possible connection with the nerve agent sarin. These effects, if they truly exist, occur in individuals whose dose was large enough to cause acute symptoms immediately after the exposure. It will take further research to explore this relationship.
Let's begin with the nerve agent sarin. It is so potent that as little as 100 milligrams — about two drops — can cause convulsions and death. As a gas, roughly 50 milligrams can be fatal. Lower doses can cause overstimulation of nerves and muscles within seconds or hours, creating symptoms such as severe cramping, difficulty breathing, twitching, and heavy sweating. In the more severe cases, these symptoms are widespread and affect many parts of the body.
All of these short-term effects are well-documented, and we ranked the evidence as sufficient to establish causality, the highest level of evidence. In part, this means many studies have strongly, repeatedly, and consistently linked these acute health effects and exposure to sarin, and that the greater the exposure, the greater the effect. But the long-term effects of sarin are a very different story. The evidence is far more limited and much weaker. Studies describing three different populations — two involving victims of terrorist attacks in Japan and one involving industrial accidents in the United States — linked neurological and psychological symptoms that persisted for six months or longer. In one of these studies, some symptoms persisted for up to three years, the longest that any of the subjects were followed. In all three study populations however, the doses of sarin were high enough to trigger an immediate, intense, widespread, and acute reaction. Among the conditions that persisted over the long term were fatigue, headaches, blurred vision, and symptoms of post-traumatic stress disorder. In other words, people who had long-term symptoms were the ones who had experienced intense symptoms immediately.
Because we are dealing with studies of only three populations here, and because we could not rule out other explanations for the effects, the committee categorized these findings as limited or suggestive of an association — well shy of the evidence needed to establish a possible link, but warranting further investigation. In this case, we recommend research to track the health of the victims of sarin attacks in Japan, since they provide the best opportunity for conducting controlled studies.
Based on available research, we could not form a conclusion about an association between long-term health effects and exposure to lower doses of sarin — low enough so that there were no immediate signs or symptoms. Yet, research with nonhuman primates gives a hint that low doses of sarin over long periods may create delayed, neurological reactions. More research is needed to substantiate this finding. We recommend that such studies be pursued.
The second agent we considered was the drug pyridostigmine bromide. It is routinely used to treat patients with myasthenia gravis, a disease that causes weakening of the muscles. PB does have side effects. It is known to cause mild, tolerable, and transient gastrointestinal and muscular symptoms. In the Gulf War, troops were given packets of PB tablets to take in advance of a chemical weapons attack in order to blunt the effects of nerve agents. The recommended doses were lower than those commonly used by doctors to treat patients with myasthenia gravis.
There have been many studies of the short-term effects of PB, and the committee judged this evidence to be sufficiently strong to demonstrate an association between exposure and the immediate onset of mild, transient symptoms. Many studies have repeatedly and consistently supported this linkage. Long-term side effects of PB are another story. There simply was not enough evidence to draw any conclusion about PB's long-term effects. In other words, we don't know if they occur, and we can't be certain that they don't occur. One series of studies has suggested that PB, either alone or in combination with other chemicals, may be related to some chronic changes in nerve function reported by Gulf War veterans. However, weaknesses in the design of these studies, which include uncertainties about exposures and a small sample, made it impossible for us to decide if exposure to PB is associated with long-term nerve damage. We recommend further investigation using an improved design.
The third agent that we considered was depleted uranium. During the Gulf War, some tanks and munitions containing depleted uranium caught fire or exploded. As a result, a number of soldiers are likely to have inhaled or ingested uranium dust, although the intensity of the exposure is unknown. Flying fragments containing depleted uranium injured others, leaving fragments embedded in tissue.
In its depleted form, uranium is 40 percent less radioactive than in its natural state. Health effects of natural uranium have been widely investigated, mostly in occupational settings. While these studies have either shown no effect or a small effect as a result of uranium exposure, our committee found weaknesses in many of these studies. We could not draw conclusions about exposure to uranium and death from a number of diseases, including lymphatic or bone cancer, nonmalignant respiratory illness, and diseases of the liver and gastrointestinal tract.
But we were able to arrive at more certain conclusions regarding kidney disease and lung cancer. We concluded that there is limited evidence of no association between kidney disease and exposure to uranium. We based this conclusion on several adequate, consistent studies that showed good kidney function despite continuous exposure to uranium as it dissolved from uranium fragments embedded in body tissues. Similarly, at low levels of exposure, we found limited evidence of no association with death from lung cancer. At higher levels of exposure, though, the evidence did not permit any conclusion about the relationship to lung cancer. We recommend follow-up research on veterans with embedded fragments of depleted uranium and other long-term studies.
Finally, our committee considered the vaccines given to prevent anthrax and botulism. More than 150,000 U.S. troops received injections of these vaccines to protect them in the event of biological warfare. Based on our review of the scientific literature, we concluded that the evidence is sufficient to demonstrate an association between these vaccines and subsequent short-term local and systemic effects. The symptoms include redness and swelling at the site of injection, similar to those associated with any vaccination. But when it came to evaluating more lasting effects, we didn't find any published, peer-reviewed studies that systematically followed subjects over the long term. This situation is not unusual, as few vaccines have been monitored for adverse effects over long periods of time.
Since troops usually received several vaccines, often within a short span of time, some have questioned whether several vaccines in combination may have created a cumulative effect when any single injection did not cause a reaction. Although we did find some research on cumulative effects of vaccines, the shortcomings in these studies made it impossible for us to form a strong conclusion. We did decide that this evidence was inadequate to determine whether an association exists.
This is a brief overview of the report’s findings. The IOM is beginning the second phase of this study, and it will examine the literature on the health effects of pesticides and solvents. This study will be completed in 2002 as there is a large body of literature on these compounds. Plans for future IOM studies include completion of the remaining agents from those listed in the legislation. Additionally, the IOM will conduct updates of the literature as new studies become available.
Thank you for your attention. My colleague and I will be happy to answer your questions.