STATEMENT OF
JOHN R. FEUSSNER, M.D.
CHIEF RESEARCH AND DEVELOPMENT OFFICER
VETERANS HEALTH ADMINISTRATION
DEPARTMENT OF VETERANS AFFAIRS
BEFORE THE NATIONAL SECURITY, VETERANS AFFAIRS AND
INTERNATIONAL RELATIONS SUBCOMMITTEE
COMMITTEE ON GOVERNMENT REFORM
U. S. HOUSE OF REPRESENTATIVES
REGARDING
RESEARCH AND TREATMENT OF GULF WAR VETERANS' ILLNESSES

January 24, 2002

Mr. Chairman and members of the Subcommittee, thank you for providing VA this opportunity to discuss the current status of the federal research program on Gulf War veterans' illnesses. I serve as the Department of Veterans Affairs' ( VA) Chief Research and Development Officer and the Chairperson of the Research Working Group ( RWG) of the Military and Veterans Health Coordinating Board ( MVHCB). I am accompanied today by Dr. Mark Brown, Director, Environmental Agents Service, and Dr. Han Kang, Director, Environmental Epidemiology Service.

In your invitation letter, you indicated that the purpose of the hearing was to assess the status of research and treatment of Gulf War veterans' illnesses among U.S. and coalition forces. You also requested follow-up of the recent General Accounting Office (GAO) report, Coalition Warfare: Gulf War Allies Differed in Chemical and Biological Threats Identified and in Use of Defensive Measures.

As you know, the United States deployed nearly 700,000 military personnel during the Gulf War from August 1990 to the cease-fire on February 28, 1991. Within months of their return, some Gulf War veterans reported various symptoms and illnesses that they believed were related to their service. Veterans, their families, and the VA have been concerned about possible health effects from exposures during the Gulf War.

Overview of the Research Portfolio on Gulf War Veterans' Illnesses

To date, the Federal government is projecting cumulative expenditures of $174 million for research related to Gulf War veterans from FY 1994 through FY 2001. There are 193 projects at various stages of completion in the research portfolio on these veterans' illnesses. In FY 1999 and FY 2000, 43 new projects were added to this portfolio. Research projects have been funded in the categories of basic research and applied research, such as clinical epidemiology and population-based epidemiologic research. To date, 116 federally funded projects have been completed. All projects and their focus areas are described in detail in annual reports to Congress.

An important role of the RWG is programmatic review and recommendations to funding agencies on research proposals that have been competitively and scientifically reviewed. The RWG continues to work diligently to foster the highest standards of competition and scientific merit review for all research on illnesses in Gulf War veterans.

Mr. Chairman, I will highlight the following topics in my testimony today: 1) an update on the status of several major research and treatment initiatives; 2) the status of two major Institute of Medicine studies; and 3) a brief description of our collaboration on research and other initiatives with our Gulf War coalition partners.

Status Report on Research and Treatment of Gulf War Veterans' Illnesses

We know that combat casualties do not always result in visible wounds, and that historically after all conflicts, some veterans have returned with debilitating health problems. VA recognizes its responsibility for developing effective treatments and prevention strategies for service-related diseases. Studies clearly show that some Gulf War veterans report a variety of chronic and ill-defined symptoms including fatigue, cognitive problems, and musculoskeletal problems, at significantly higher rates than the rates reported by non-deployed veterans.

Four National Research and Treatment Initiatives on Illnesses in Gulf War Veterans

Highlights of the ongoing research efforts include Phase III of the VA National Health Survey of Gulf War Era Veterans and Their Families, an epidemiological study of amyotrophic lateral sclerosis ( ALS) in Gulf War veterans, and two major treatment trials.

The VA National Health Survey of Gulf War Veterans and Their Families began in 1995 when health surveys were mailed to 15,000 Gulf War veterans and 15,000 non-deployed veterans. The self-reported survey results have been published and provided to the Subcommittee. Results from the initial two phases of this study show that Gulf War veterans are reporting significantly higher rates of diverse symptoms, including joint, muscle, respiratory, gastrointestinal, and skin problems. This population also reports higher rates of chronic fatigue and symptoms of post-traumatic stress disorder (PTSD).

In 1998, the third phase of this study began, which was designed to perform medical evaluations on a randomly selected subgroup of the veterans who completed the earlier mailed surveys. Phase III included 1,061 Gulf War veterans and their spouses and children, and 1,128 non-deployed veterans and their spouses and children. Veterans and spouses were examined for illnesses that had frequently been reported by Gulf War veterans in previous studies, namely, chronic fatigue syndrome, fibromyalgia, post-traumatic stress disorder, neurological abnormalities (including cognitive dysfunction and peripheral neuropathy), arthritis, hypertension, asthma, and chronic bronchitis. Children were examined for birth defects, which were diagnosed through pediatric examinations.

Each individual received a complete physical examination, including a neurological exam. In addition, veterans received several blood tests, neuropsychological testing, nerve conduction velocity tests, and pulmonary function tests. The preliminary results show that Gulf War veterans demonstrated significantly increased rates of two disorders, compared to non-deployed veterans. These were chronic fatigue syndrome (1.6% vs. 0.4%) and post-traumatic stress disorder (10.1% vs. 3.2%). There were no observed differences in veterans in the rates of fibromyalgia, cognitive dysfunction, peripheral neuropathy, arthritis, hypertension, asthma, and chronic bronchitis. There were no observed differences in the rates of the primary or secondary outcomes among the spouses of Gulf War veterans and non-deployed veterans.

Gulf War veterans have voiced concerns about a possible association between ALS and service in the war. This fatal neurological disease is also called Lou Gehrig's disease. Neither a cause nor an effective treatment for ALS is known. Preliminary data suggested that the age distribution of cases of ALS in Gulf War veterans appeared to be younger than the age distribution of cases of ALS in the general U.S. population. Accordingly, in March 2000, VA began a research effort to identify all cases of ALS, occurring among Gulf War veterans deployed to the Gulf during Operations Desert Shield/Desert Storm and non-deployed veterans. VA collaborated with the Department of Defense ( DoD), and the Centers for Disease Control and Prevention ( CDC), university experts, and the ALS Association to determine the veterans' health status and to describe their exposures to potential risk factors for ALS, based on clinical examinations at centers of excellence in neurological diseases. The case-finding and medical confirmation of cases was recently completed.

The preliminary results show that Gulf War veterans deployed to Operations Desert Storm and Desert Shield had almost a two-fold increased rate of ALS, compared to non-deployed veterans. There were 40 cases of ALS diagnosed among almost 700,000 Gulf War veterans. There were 67 cases among almost 1.8 million non-deployed veterans. The next step in this investigation will involve careful evaluation of possible risk factors in the veterans, including family history, military occupation, injuries and trauma, and exposures to hazardous chemicals.

As a result of the study, the Secretary of Veterans Affairs decided to take steps to compensate veterans with ALS who were deployed to the Gulf region during Operations Desert Shield/Desert Storm. VA has contacted the Gulf War veterans identified in the study to help them file new claims or to expedite existing claims.

In 1998, the VA Cooperative Studies Program initiated planning for two treatment trials, known as the "ABT" (antibiotic treatment) and "EBT" (exercise-behavioral therapy) trials. Patient characteristics for entry into both trials were similar. All veterans who served in the Gulf War between August 1990 and August 1991 were eligible for the studies. Patients were eligible if they had at least two of three symptoms (fatigue, musculoskeletal pain, and cognitive dysfunction) that began after August 1990. In addition, patients had to be symptomatic when the study began with symptoms that had lasted for more than six months.

The ABT trial initiated its enrollment of 491 Gulf War veterans in May 1999 at 26 VA sites and 2 DoD sites. The primary hypothesis of the study was that antibiotic treatment, with doxycycline for 12 months, would improve the health status of patients with chronic symptoms who tested positive for Mycoplasma infection at baseline. The secondary hypotheses were that doxycycline treatment would reduce symptoms of fatigue, pain, and memory problems; and that doxycycline treatment would convert patients who were Mycoplasma positive to Mycoplasma negative. The trial was completed in December 2001, when patient follow-up was finished.

Of the patients enrolled in the ABT study, 84% exhibited all three symptoms of fatigue, pain, and neurocognitive difficulties. The preliminary results show that doxycycline was not an effective treatment. The antibiotic did not lead to an improvement of physical function or to reductions in fatigue, pain, or memory problems. In addition, this study does not support a possible relationship between chronic symptoms experienced by some Gulf War veterans and persistent Mycoplasma infections.

The EBT trial initiated enrollment of 1,092 Gulf War veterans in April 1999 at 18 VA sites and 2 DoD sites. The primary hypotheses of the study were that both aerobic exercise and cognitive behavioral therapy ( CBT) would significantly improve physical function in veterans, and that the combination of exercise and CBT would be more beneficial than either treatment alone. The secondary hypotheses were that treatment would lead to improvement in mental health function, and to improvement in symptoms of fatigue, pain, and memory problems. The EBT trial was completed in December 2001.

After 12 months of treatment, the functional status and symptoms of each individual were compared to his or her baseline. The preliminary results show that exercise and/or CBT did not improve physical function. However, exercise, CBT, or the combination did lead to significant improvements in mental health function. In addition, exercise, with or without CBT, lead to significant improvements in symptoms of fatigue and memory problems. Aerobic exercise appears to be a promising treatment for Gulf War veterans who have chronic symptoms of fatigue and memory problems.

Longitudinal Studies to Determine the Long-Term Health of Gulf War Veterans

The Research Working Group determined that continuing longitudinal studies that evaluate the health status of Gulf War veterans are a high priority, to determine whether their health is getting better or worse over time. There are five ongoing studies, which are supported by VA, DoD, and CDC. The five studies in Boston, New Orleans, New Jersey, Iowa, and the United Kingdom are following approximately 18,000 veterans, altogether. Each of these studies has included questionnaires on physical symptoms, psychological symptoms, and exposures during the Gulf War. The New Jersey, Iowa, and U.K. studies have also included comprehensive medical histories and physical examinations. The Boston and New Orleans scientists have evaluated their cohorts at four time points, beginning soon after service personnel returned from the war. The British scientists have evaluated their cohort at three time points, and the New Jersey and Iowa scientists have evaluated their cohorts at two time points. The RWG continues to be committed to facilitating the long-term monitoring of the health of Gulf War veterans. To aid in such an assessment, the VA Office of Research and Development released a Request for Proposals in 2000. Multiple proposals were submitted in response to this solicitation in 2001. DoD funding has recently been approved to perform a longitudinal study of the participants of the VA National Health Survey of Gulf War Era Veterans and Their Families.

In addition to the follow-up of the health of Gulf War veterans, the RWG has made a commitment to monitor the health of service members after future deployments. The Millennium Cohort Study is a prospective study of U.S. military forces, which was designed to collect population-based demographic and health data systematically to evaluate the health of service personnel throughout their military careers and after leaving military service. This study is a cross-sectional sample of 100,000 military personnel who will be followed prospectively by mail surveys every three years over a 21-year period, starting in 2001. In 2004 and 2007, 20,000 new personnel will be added to the cohort. The total of 140,000 veterans will be followed until 2022. The principal objective of the study is to evaluate the impact of military deployments on various measures of health over time, including chronic diseases such as cancer, heart disease, and diabetes. This ambitious study requires the collaboration of DoD and VA scientists over an extended period of time.

Other Research Initiatives on Illnesses in Gulf War Veterans

VA recently established two new Centers for the Study of War-Related Illnesses at the VA Medical Centers in East Orange, New Jersey and Washington, D.C. These new Centers will assist VA in the development of appropriate preventive strategies to minimize illness following future conflicts, including both combat and peacekeeping operations, and to develop new approaches for improving the treatment of active-duty and veteran patients with war-related illnesses. Each Center will focus on medical care and risk communication for veterans, education for health care providers, and center-initiated research.

In September 2001, CDC funded two research projects designed to develop and implement more effective methods of risk communication for active-duty service members, veterans, and their health care providers. The project at Rutgers University is entitled "Improving Health Risk Communications to Prevent Unexplained Illnesses Related to Military Deployments." The project at the Jackson Foundation and Walter Reed Army Medical Center is entitled "Health-e VOICE: Optimized Implementation of a Stepped Clinical Risk Communications Guideline." These two projects will be funded for three years.

In 2000, DoD published three Broad Agency Announcements to announce the availability of research funding. The review of projects and awarding of funds were completed in 2001. The number of new projects funded in each area is:

• Toxicity of heavy metals that are relevant to the military, including depleted uranium and tungsten (5 projects);
• Biomarkers to assess toxic chemical exposures and health effects (7 projects); and
• Consequences of deployment stress on health and performance (6 projects).

A study at the University of California at San Francisco and the San Francisco VA Medical Center, which DoD recently funded for five years, will focus on neuroimaging of veterans with symptoms of central nervous system dysfunction. A preliminary study of 12 ill Gulf War veterans in Texas suggested that these individuals showed normal brain anatomy on magnetic resonance imaging (MRI), but showed biochemical abnormalities on magnetic resonance spectroscopy (MRS). This study was limited because of the small sample size and because there was no control for alcoholism, depression, PTSD, or drug treatments. The San Francisco study will carefully evaluate 200 Gulf War veterans and 200 non-deployed veterans, through neurological exams and neuropsychological testing. Then, MRI and MRS will be performed to detect anatomical and biochemical abnormalities, while controlling for the effects of other concurrent illnesses.

Institute of Medicine Studies Related to Gulf War Veterans' Illnesses

In 1998, VA contracted with the Institute of Medicine (IOM) to perform periodic reviews of the scientific and medical literature regarding adverse health effects associated with the exposures experienced during the Gulf War. The first phase of this study focused on pyridostigmine bromide, depleted uranium, sarin, cyclosarin, and the anthrax and botulinum toxoid vaccines. This first phase was funded for 27 months, and a report on this first phase was published in September 2000, entitled Gulf War and Health: Volume I. Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines.

The IOM has already begun its next two-year review, focusing on health effects from pesticides and solvents used during the Gulf War. That report is expected to be completed in August 2002.

In 1999, VA requested the IOM to perform a study to identify effective treatments for health problems in Gulf War veterans. The IOM Committee's charge was as follows:

1. Identify and describe approaches for assessing treatment effectiveness.
2. Identify illnesses and conditions common among Gulf War veterans, including medically unexplained symptoms, using data obtained from the VA and DoD Gulf War registries, as well as information in published articles.
3. Identify validated models of treatment for these identified conditions and illnesses; or identify new approaches, theories, or research on the care of patients with these conditions, if validated treatment models are not available.

In July 2001, IOM published the results of this study, entitled Gulf War Veterans: Treating Symptoms and Syndromes. IOM stated that difficult-to-diagnose symptoms experienced by some Gulf War veterans have a large overlap with the following seven diagnoses: chronic fatigue syndrome, depression, fibromyalgia, headache, irritable bowel syndrome, panic disorder, and PTSD. A major focus of the report was the evaluation of proven treatments for these recognized diagnoses, and IOM provided recommendations for improving health care for patients with these disorders. It concluded that available studies of proven therapies for persons with these disorders are a valuable resource for deriving effective treatments for undiagnosed illnesses. VA has already implemented many of IOM recommendations. For example, VA is developing clinical practice guidelines for chronic fatigue syndrome, fibromyalgia, and depression.

Collaboration on Research and Other Initiatives with Gulf War Coalition Partners

There has been extensive international coordination and collaboration on research between the United States and its Gulf War coalition partners. For example, there have been three research conferences that were organized by the Persian Gulf Veterans Coordinating Board (now called the Military and Veterans Health Coordinating Board, or MVHCB). British scientists have provided presentations at all 3 conferences in 1998, 1999, and 2001. The 2001 Conference had extensive international participation. The participants included 400 scientists and clinicians from Great Britain, France, Canada, Australia, the Netherlands, Denmark, and Israel.

Research scientists from the U.S. and the UK are in continual communication. DoD funded the first large British study of Gulf War veterans in 1996, which has been directed by Dr. Simon Wessely. DoD is now funding a joint research project on the health of Gulf War veterans in Iowa and Great Britain, which includes the cohort studied by Dr. Wessely. Dr. Wessely, who is an expert in cognitive behavioral therapy, is on the Data Safety Monitoring Board of the EBT study. Since 1998, a British medical officer from the Ministry of Defence has been based at the office of the MVHCB. In addition, another British medical officer is an ex officio member of the Research Working Group of the MVHCB. Research scientists from the U.S. and Canada are also in frequent communication, particularly in regard to the potential health effects of exposure to depleted uranium. In addition, scientists working for the Canadian Department of National Defence adopted the questionnaire developed by Iowa scientists for a survey of all Canadian Gulf War veterans, which was published in 1998.

As the Chair of the Research Working Group, I was asked to brief a French scientific delegation on April 4, 2001. Several of the issues discussed at that briefing were related to the findings in an 135-page report on illnesses in Gulf War veterans that was published a few weeks later. This French report was entitled: Mission Report from the Working Group responsible for analyzing health data relating to French veterans of the Gulf War. This report reviewed 350 American and British studies of illnesses in Gulf War veterans. The conclusions of this exhaustive review by the French Working Group were as follows:

• "None of the articles reported mortality excess among members deployed during the Gulf War as regards to members who were not deployed, except for mortality excess due to road accidents."
• "No life-threatening effects on offspring have been reported."
• "No known diseases were found in excess among members deployed in the Gulf."
• "Hospitalizations were slightly more frequent among personnel deployed in the Gulf War compared to a monitored control group of members who were not deployed during that same period of time. This slight increase relates to "non-focused signs and symptoms" that could be explained by providing routine medical check-up to members deployed in the Gulf."
• "Various signs and symptoms, functional in most cases, were found in all the studies and obviously the frequency was higher among the members involved in the Gulf War compared to the control group members. These signs and symptoms often reflect chronic fatigue, depressive symptomatology, and also arthralgia, mood or memory disorders."
• "The identification of these signs does not clearly show a specific Gulf War syndrome concept. Consequently, an analysis of the data or factorial analysis was carried out by several authors; it shows a 'construct' of these signs depending on the factors that could have these syndromes in common. These factors are also found (though in lower quantity) among members not deployed during the Gulf War. This led to the rebuttal of a specific Gulf War syndrome concept by four out of five authors."
• "No unique cause could be distinctly attributed to the excess of detected signs and symptoms."
• "No specific link found by the authors as far as depleted uranium, fumes from burning oil wells or nerve agent sarin are concerned."
• "No publication established a link between pyridostigmine and the detected signs and symptoms, even though the assumption of a causal relation cannot be totally dismissed."
• "There are uncertainties and controversies on the possible long-term effects of low dose exposures to organophosphorous insecticides, predominantly when they are related to other factors such as stress, heat, etc."
• "The various vaccinations used during deployment and mainly those used to protect against bacteriological weapons (such as anthrax, botulism and plague etc.) seem to be responsible for an excess of some of the signs and symptoms observed."

The French Working Group concluded, "The medical data pertaining to French Veterans are not accessible. Thus, it prevents us from upholding or overturning the findings drawn from the international [American and British] literature. . . The questions that are being asked about the Gulf War have revealed, or confirmed, to the members of the Working Group that epidemiological monitoring in France for war veterans is totally inadequate."

The recommendations for a health study of French Gulf War veterans were: "In order to bring reliable and clear answers to questions raised by public debate and to concerns expressed by soldiers deployed in the Gulf, we are adamant in proposing several projects that we have classified as epidemiological studies, other research and mid-term and long-term monitoring. We feel it is essential to carry out an in-depth study using a questionnaire for all the veterans who participated in the Gulf War."

A comprehensive epidemiological study will begin with the evaluations of approximately 25,000 French Gulf War veterans in February 2002, and is planned to take two years. Dr. Roger Salamon, a professor at the University of Bordeaux, is directing the study, which will include a comprehensive questionnaire covering a full range of health effects, and a medical examination in a civilian or military medical facility.

Mr. Chairman, you also requested follow-up of the recent General Accounting Office (GAO) report, Coalition Warfare: Gulf War Allies Differed in Chemical and Biological Threats Identified and in Use of Defensive Measures. This report summarized the experience of troops from the U.S., UK, and France during the Gulf War. It outlined each country's approach to "chemical, biological, and radiological defense, including their use of protective gear and specific drugs and vaccines." One of GAO's major conclusions was that "owing to the number of differences in the experience of the three sets of veterans, they do not point unambiguously to any single cause for the reported illnesses." The GAO report drew "no conclusions regarding the cause or causes of health problems reported by veterans of the Gulf War." GAO also stated that they could "not preclude the possibility that additional time or more thorough examination could yield additional reports of health problems among French veterans." Indeed, plans for a "more thorough examination" of the 25,000 French Gulf War veterans are being implemented.

Summary of Major Research Findings To Date

The Federal research program has yielded several important results, as follows:

• Gulf War veterans have consistently reported increased rates of self-reported symptoms related to a wide variety of organ systems, compared to non-deployed veterans. Several large epidemiological studies in the US, UK, and Canada have shown increased rates of self-reported illnesses in Gulf War veterans, including chronic fatigue, memory problems, posttraumatic stress disorder, major depression, musculoskeletal problems, and asthma.
• Several large epidemiological studies have shown that Gulf War veterans do not suffer from a unique, previously unrecognized "Gulf War syndrome." Five controlled studies have been published, that used a statistical technique, factor analysis, to identify patterns of symptoms. Thousands of Gulf War veterans and non-deployed veterans have been evaluated in three American and two British studies. In all five studies, the patterns of symptoms reported by Gulf War veterans were similar to the patterns reported by non-deployed veterans. These five large studies are consistent with the conclusions of an Institute of Medicine report, published in 2000: "Thus far, there is insufficient evidence to classify veterans' symptoms as a new syndrome. . . All Gulf War veterans do not experience the same array of symptoms. Thus, the nature of the symptoms suffered by many Gulf War veterans does not point to an obvious diagnosis, etiology, or standard treatment." The General Accounting Office was the most recent oversight group to perform a general evaluation of illnesses in Gulf War veterans. Their report, which was dated July 31, 2001, concluded, "Seven expert panels have concluded that no unique Gulf War syndrome exists. . . No one diagnosis predominates; diagnoses include all types of injuries and illnesses."
• There are few differences in the rates and causes of hospitalizations among Gulf War veterans and non-deployed veterans, when all 697,000 Gulf War veterans were compared with an equal number of non-deployed veterans. Hospitalizations for fractures and soft-tissue injuries were more frequent in Gulf War veterans in military hospitals nationwide and in civilian hospitals in the state of California. In VA hospitals nationwide, hospitalizations for respiratory system and digestive system diagnoses were more frequent in Gulf War veterans.
• Phase III of the VA National Health Survey of Gulf War Veterans and Their Families has recently been completed and the analyses of the data have just begun. The preliminary results suggest significant increases in the rates of chronic fatigue syndrome and post-traumatic stress syndrome in Gulf War veterans, compared to non-deployed veterans. There were no differences in the rates of several other diseases, such as fibromyalgia, cognitive dysfunction, and peripheral neuropathy. Because there are few published data on the results of medical evaluations of patients, three other large studies continue to evaluate objective medical diagnoses, in Portland, Iowa, and the UK.
• Mortality rates in both Gulf War veterans and non-deployed veterans are about 40% of the mortality rates in the general U.S. population, which means that veterans are much healthier. This has been referred to as a "healthy warrior effect." In both the U.S. and the UK, Gulf War veterans have had a significantly higher mortality rate due to unintentional injuries, mostly motor vehicle injuries, compared to non-deployed veterans. This is the only difference in mortality rates, to date. In the U.S. study, the rate of motor vehicle fatalities has recently declined in Gulf War veterans, so that it is now equal to the rate in the non-deployed veterans.
• Two very large, population-based studies of hospital records have demonstrated that the rates of birth defects were the same in the offspring of Gulf War veterans and non-deployed veterans. These studies were performed by the Walter Reed Army Institute of Research in Washington, DC, and the Naval Health Research Center in San Diego, respectively. In addition, the preliminary results of the VA National Health Survey of Gulf War Veterans and Their Families seem to be consistent with these earlier findings. This study relied on the most valid method of determination of birth defects, which is a medical examination by a pediatrician. There seem to be no significant differences between the rates of birth defects in offspring of Gulf War veterans and non-deployed veterans.
• Neurological examinations have been performed in several populations of Gulf War veterans, and these studies have shown mixed results. The preliminary results of the study of amyotrophic lateral sclerosis (ALS) demonstrated 40 cases of ALS among 700,000 Gulf War veterans and 67 cases of ALS among 1.8 million non-deployed veterans. There was almost a two-fold increase in the ALS rate in Gulf War veterans.
• In contrast, other studies have shown that Gulf War veterans do not demonstrate objective evidence of neurological diseases at higher rates than non-deployed veterans. The rates of hospitalization for neurological diseases were low in military hospitals nationwide, and the rates were the same among Gulf War veterans and non-deployed veterans. In VA hospitals nationwide and in civilian hospitals in California, the rates of neurological diseases were low, and the rates were significantly lower among Gulf War veterans, compared to non-deployed veterans. In the VA National Health Survey, neurological examinations, neuropsychological testing, and nerve conduction velocity tests were performed. There were no significant differences in the rates of cognitive dysfunction and peripheral neuropathy between Gulf War veterans and non-deployed veterans. Large population-based studies in Portland, Iowa, and the UK are using similar methods to evaluate the central and peripheral nervous systems, and these studies will be completed in 2002. Also, eight studies are performing neuroimaging in Gulf War veterans and non-deployed veterans, including conventional magnetic resonance imaging (MRI), functional MRI, magnetic resonance spectroscopy, and single-photo emission computed tomography.
• Studies of several populations of Gulf War veterans and non-deployed veterans have demonstrated consistent results on neuropsychological testing, including the VA National Health Survey. Self-reports of memory and concentration problems have often been more common among groups of Gulf War veterans than among control subjects. However, on objective neuropsychological testing, overall performance has been similar on most tests in Gulf War veterans and control subjects. In a small proportion of tests, such as attention or response speed, Gulf War veterans have performed significantly more poorly than controls.
• In many studies, Gulf War veterans have been diagnosed with significantly higher rates of PTSD and major depression than non-deployed veterans. These higher rates have been demonstrated through structured psychiatric interviews, as well as through self-administered questionnaires. The VA National Health Survey is the largest population-based study that used structured psychiatric interviews, which are the most valid method of diagnosing diseases such as PTSD. The rates of PTSD appear to be significantly higher in Gulf War veterans (10.1%) than in non-deployed veterans (3.2%)
• Four studies have shown that the rates of infectious diseases have been low in Gulf War veterans, and significantly lower than the rates in non-deployed veterans. Two studies have demonstrated no differences in the rates of infection with Mycoplasma fermentans in Gulf War veterans, compared to non-deployed veterans, either before or after the war. The Antibiotic Treatment Trial was a national clinical trial designed to determine whether long-term treatment with doxycycline would lead to improvement in Mycoplasma-positive Gulf War veterans. The preliminary results of the ABT suggest that doxycycline does not lead to an improvement of physical functioning or chronic debilitating symptoms. The study also shows no relationship between the presence of chronic symptoms, changes in clinical health status, and the results of Mycoplasma blood tests.
• US soldiers destroyed many of the chemical rockets at Khamisiyah, Iraq, on March 10, 1991. DoD assessed that some US troops were likely exposed to very low levels of sarin and cyclosarin from the demolitions. This is the only known event during the Gulf War that may have exposed large numbers of troops to chemical warfare agents, even at low concentrations. There are 6 research projects that focus on the possible long-term effects of exposures due to the demolitions at Khamisiyah, two of which have been published. One study demonstrated no differences in the rates or causes of hospitalizations among veterans who may have had low-level exposure due to Khamisiyah, compared to veterans who had no exposure. A second study showed no differences in the rates or causes of mortality among veterans with possible low-level exposure, compared to veterans with no exposure. The Institute of Medicine is performing one of the ongoing studies, which will finish in 2002. This study is comparing the rates of mortality, hospitalization, and self-reported symptoms in Gulf War veterans with possible low-level exposure due to Khamisiyah, with the rates in Gulf War veterans with no exposure.
• Several studies have been published recently that focused on the potential health effects of pyridostigmine bromide (PB) and pesticides, alone or in combination. The key research question is whether PB can cross the blood-brain barrier. Several studies have evaluated whether other chemicals, such as pesticides, or stressful stimuli, such as heat stress or swimming stress, can increase the permeability of the blood-brain barrier, and can therefore enhance penetration of PB into the brain. All these recent studies have reached the same conclusion, that other chemicals or stressful stimuli do not increase the permeability of the blood-brain barrier to PB, and that PB does not penetrate the brain, even at very high doses. If PB does not cross into the brain, it is unlikely to cause changes in brain function.
• The available scientific and medical evidence to date does not support concerns that depleted uranium (DU) has caused or is causing illnesses in Gulf War veterans. No Gulf War veterans experienced intakes high enough to cause adverse health effects. A total of 104 individuals were exposed to DU in friendly fire incidents, some of whom have retained metallic fragments. While there has been no clinical evidence of illness associated with DU exposure to date, the veterans involved in friendly fire incidents will remain under medical surveillance indefinitely.
• During the Gulf War, about 150,000 service members received the anthrax vaccine. There is inadequate evidence to determine if this vaccine can cause long-term adverse effects, because studies of this vaccine have not used active surveillance to systematically evaluate long-term health outcomes. DoD and CDC are performing several studies to evaluate the potential long-term effects of the anthrax vaccine. These new studies focus on safety in humans and lab animals and studies of efficacy in non-human primates. They will also follow-up the health status of military and non-military populations who received the anthrax vaccine during the 1960s to 1990s.

Conclusion

As the federal research program continues to provide more results, we will substantially increase our understanding of Gulf War veterans' illnesses, which, in turn, will enhance our ability to diagnose and treat them. In addition, this newly gained knowledge may enhance prevention and intervention in illnesses in participants of future deployments.

Mr. Chairman, thank you again for providing this opportunity to summarize our work to date to understand the health problems of Gulf War veterans. You have my assurance that we will continue this effort to resolve or ameliorate health problems in this population to the greatest extent possible. Mr. Chairman, this concludes my testimony. My colleagues and I are ready to answer any questions that you, the other subcommittee members, or the distinguished guests may have.