On August 2, 1990, Iraqi armed forces invaded Kuwait; within 5 days the United States began to deploy troops to Southwest Asia (SWA)1 in Operation Desert Shield. Intense air attacks against the Iraqi armed forces began on January 16, 1991, and opened a phase of the conflict known as Operation Desert Storm. Oil-well fires became visible by satellite images as early as February 9, 1991; the ground war began on February 24, and by February 28, 1991, the war was over. The oil fires were extinguished by November 1991. The last troops to participate in the ground war returned home on June 13, 1991. In all, approximately 697,000 U.S. troops had been deployed to the Persian Gulf area during the conflict.
Although considered an extraordinarily successful military operation with few battle casualties and deaths, veterans soon began reporting numerous health problems that they attributed to their participation in the Gulf War. Although the majority of men and women who served in the Gulf War returned to normal activities, a large number of veterans have had a range of unexplained illnesses including chronic fatigue, muscle and joint pain, loss of concentration, forgetfulness, headache, and rash (Chapter 2).
The men and women who served in the Persian Gulf region were potentially exposed to a wide range of biological and chemical agents including sand, smoke from oil-well fires, paints, solvents, insecticides, petroleum fuels and their combustion products, organophosphate nerve agents, pyridostigmine bromide (PB), depleted uranium (DU), anthrax and botulinum toxoid vaccinations,
and infectious diseases, in addition to psychological and physiological stress. Veterans have become increasingly concerned that their ill health may be related to exposure to these agents and circumstances.
In response to the veterans’ concerns, the Department of Veterans Affairs (VA) approached the National Academy of Sciences and requested that the Institute of Medicine (IOM) conduct a study to extensively review the literature and summarize the strength of the scientific evidence concerning the association between health effects and the chemical and biological compounds that were likely present during the Gulf War.
To carry out the charge as requested by the VA, the IOM formed the Committee on Health Effects Associated with Exposures During the Gulf War. As the committee began its deliberations in January 1999, one of its first tasks was to determine the initial group of compounds for study. The committee decided that the compounds of most concern to the veterans should be selected for initial review. Following meetings with leaders of different veterans’ organizations, the committee decided it would begin this first phase by studying the following compounds: depleted uranium, chemical warfare agents (sarin and cyclosarin), pyridostigmine bromide, and vaccines (anthrax and botulinum toxoid). Subsequent studies will examine the remaining agents.
Subsequent to the VA–IOM contract, two public laws were passed: the Veterans Programs Enhancement Act of 1998 (Public Law 105-368) and the Persian Gulf War Veterans Act of 1998 (Public Law 105-277). Each law mandated studies similar to the study already agreed upon by the VA and IOM. These laws detail several comprehensive studies on veterans’ health and specify numerous biological and chemical hazards that may potentially be associated with the health of Gulf War veterans.
It should be noted that the charge to the IOM committee was not to determine whether a unique Gulf War syndrome exists, nor was it to make judgments regarding levels of exposure of veterans to the putative agents. Additionally, the committee’s charge was not to focus on broader issues, such as the potential costs of compensation for veterans or policy regarding such compensation. These decisions remain the responsibility of the Secretary of Veterans Affairs (VA). This report does, however, provide an assessment of the scientific evidence regarding health effects that may be associated with exposures to specific agents that were present in the Gulf War. The Secretary may consider these health effects as the VA develops a compensation program for Gulf War veterans.
ADDRESSING GULF WAR HEALTH ISSUES
Past and Current Efforts
In the years since the Gulf War, a number of federal and private sector efforts have explored the causes of and treatments for the illnesses of Gulf War veterans. Initial efforts focused on concerns about potential health effects of the Kuwait oil-well fires. Subsequently, concern has broadened to encompass possi-
ble health effects of other agents and treatments for the veterans’ health problems. Extensive research and policy efforts continue. In addition to the panels identified in Box 1.1, there are ongoing efforts by individual veterans, veteran service organizations, academia, Congress, federal agencies, private sector organizations, and others. These efforts focus on the spectrum of work needed to fulfill the goal of improving the health of Gulf War veterans who are ill and preventing illnesses in future deployments. This work includes clinical research on the effectiveness of potential treatments, improving exposure models, epidemiologic research on the health status of Gulf War veterans, research on the nature of the veterans’ illnesses, and studies on the potential adverse health effects of the agents that were likely present in the Gulf War.
Complexities in Resolving Gulf War Health Issues
Investigations of the health effects of past wars have often focused on narrowly defined hazards or health outcomes, such as infectious diseases (e.g., typhoid, malaria) during the Civil War, specific chemical hazards (e.g., mustard gas in World War I, Agent Orange and other herbicides in Vietnam), and combat injuries. A discussion of the possible health effects of the Gulf War, however, involves many complex issues, some of which are explored below. These include exposure to multiple biological and chemical agents, limited exposure information, individual variability factors, and illnesses that are often nonspecific and lack defined medical diagnoses or treatment protocols. While, the committee was not tasked with addressing these issues it presents them in this introductory chapter to acknowledge the difficulties faced by veterans, researchers, policymakers, and others in reaching an understanding about the veterans’ ill health.
Multiple Exposures and Chemical Interactions
Although Operation Desert Shield/Desert Storm was relatively short in duration, military personnel were potentially exposed to numerous agents. Many of the exposures are not unique to the Gulf War, however, the number of agents and the combination of agents to which the veterans may have been exposed make it difficult to determine whether any one agent, or combination of agents, is the cause of Gulf War veterans’ illnesses. These include preventive measures (e.g., PB, vaccines, pesticides, insecticides), hazards of the natural environment (e.g., sand, endemic diseases), job-specific exposures (e.g., paints, solvents, diesel fumes), war-related exposures (e.g., smoke from burning oil-well fires, DU), and hazards from cleanup operations (e.g., sarin and cyclosarin). Thus, military personnel may have been exposed to a variety of agents, at varying doses, and lengths of time. The literature on the agents, however, is quite limited with regard to combinations of biological and chemical agents and their interactions.
Limitations of Exposure Information
Determining whether or not Gulf War veterans face an increased risk of illness because of their exposures during the Gulf War requires extensive information about each exposure (e.g., the actual agent(s), duration of exposure, route of entry, internal dose) and documentation of adverse reactions. Unfortunately, very little is known about most Gulf War exposures. After the ground war, an environmental monitoring effort was initiated primarily because of concerns related to smoke from oil-well fires rather than for the other agents to which the troops may have been exposed. Consequently, exposure data for other agents are lacking or are limited.
While a variety of exposure assessment tools are being used in ongoing research to fill gaps in exposure information there are limitations to accurate reconstruction of past exposure events. For example, surveys of veterans are used to obtain recollections about agents to which they may have been exposed, although survey results may be limited by recall bias (see Chapter 3). Models are being refined to estimate exposures to sarin and cyclosarin, however, it is difficult to accurately incorporate intelligence information, meteorological data, transport and dispersion data and troop unit location information. Extensive efforts are under way to model and obtain information on potential exposures to depleted uranium, smoke from oil-well fires, and other agents. Although modeling efforts are important for discerning the details of the exposures of Gulf War veterans, these efforts are not yet complete and will require external review and validation. Further, even if there were accurate troop locations, the location of individual soldiers would be very uncertain. Because of the limitations in the exposure data, it is difficult to determine the likelihood of increased risk for disease or other adverse health effects in Gulf War veterans.
Differences among individuals in their genetic, biological, psychological, and social vulnerabilities add to the complexities in determining health outcomes related to specific agents. Sensitive individuals will exhibit different responses to the same agents than members of the population without the susceptibility. For example, an individual may be a poor metabolizer of a particular substance, depending on his or her genetic makeup. Such an individual may be at higher or lower risk for specific health effects due to exposure to certain agents. Researchers are investigating the genotypes coding for two forms of an enzyme that differ in the rate at which they hydrolyze certain organophosphates (including sarin). Lower hydrolyzing activity would mean that despite identical exposure to sarin, more sarin would be bioavailable in those individuals resulting in increased anticholinesterase effects (see Chapter 5).
Many Gulf War veterans suffer from an array of health problems and symptoms (e.g., fatigue, muscle and joint pain, memory loss, rash) that are not specific to any one disease and are not easily classified by standard diagnostic coding systems. Population-based studies have found higher prevalence of self-reported symptoms in Gulf War veterans compared to nondeployed Gulf War era veterans or other control groups (see Chapter 2; Iowa Persian Gulf Study Group, 1997; Goss Gilroy, 1998; Unwin et al., 1999). All Gulf War veterans do not experience the same array of symptoms, which has complicated ongoing efforts to determine if there is a unique Gulf War syndrome or if there is overlap with other symptom-based disorders. Thus, the nature of the symptoms suffered by many Gulf War veterans does not point to an obvious diagnosis, etiology, or standard treatment (see Chapter 2).
THE GULF WAR SETTING
Although the committee’s charge was to review the scientific evidence on the possible health effects of various agents to which Gulf War veterans were exposed, the committee realized at the onset that it needed to have as complete an understanding of the Gulf War experience as possible. The committee sought to understand the Gulf War setting and veterans’ experiences. For that reason, the committee met with representatives of veterans’ groups and opened its meetings whenever possible to hear from veterans, researchers, and other members of the interested public (see Appendixes A and B).
The following information provides a context for the many scientific articles that the committee reviewed and provides an appreciation (albeit limited) of the collective experiences of Gulf War veterans. This information is compiled from many sources including presentations by veterans and other speakers at the committee’s public meetings (see Appendix B) (Gunby, 1991; NIH, 1994; Hyams et al., 1995; IOM, 1995, 1996, 1999; Persian Gulf Veterans Coordinating Board, 1995; Ursano and Norwood, 1996; PAC, 1996, 1997; Lawler et al., 1997; Joellenbeck et al., 1998; U.S. Department of Veterans Affairs, 1998).
The pace of the buildup for the war was unprecedented. Within 5 days after Iraq invaded Kuwait, the United States and other coalition countries began moving troops into the region. By September 15, 1990, the number of American service members reached 150,000 and included nearly 50,000 reservists. Within the next month, another 60,000 troops arrived in Southwest Asia, and in November an additional 135,000 reservists and guard members were called up. By February 24, 1991, more than 500,000 U.S. troops had been deployed to the Persian Gulf region.
The Gulf War reflected many changes from previous wars in the demographic composition of military personnel and uncertain conditions for many reservists. Of the nearly 700,000 U.S. troops who fought in Operation Desert Shield/Desert Storm, almost 7 percent were women and about 17 percent were from National Guard and reserve units. Additionally, military personnel were, overall, older than those who had participated in previous wars. Rapid mobilization exerted substantial pressures on those who were deployed, disrupting lives, separating families, and for reserve and guard units, creating uncertainty about whether jobs would be available when they returned to civilian life.
Combat troops were crowded together in warehouses and tents upon arrival and then often moved to isolated desert locations. Most troops lived in tents and slept on cots lined up side by side, affording virtually no privacy or quiet. Sanitation was often primitive, with strains on latrines and communal washing facilities; feminine hygiene products were initially in short supply. Hot showers were infrequent, the time interval between laundering of uniforms was sometimes long, and desert flies were a constant nuisance, as were scorpions and snakes. Additionally, military personnel worked long hours and had restricted outlets for relaxation. Troops were ordered not to fraternize with local people, and alcohol was prohibited in deference to religious beliefs in the host countries. A mild, traveler’s type of diarrhea affected more than 50 percent of the troops in some units. Fresh fruits and vegetables from neighboring countries were identified as the risk factor and were removed from the diet. Thereafter, the diet consisted mostly of prepackaged foods and bottled water.
For the first two months of troop deployment (August and September) the weather was extremely hot and humid, with air temperatures as high as 115°F and temperatures of the sand reaching 150°F. Except for coastal regions, the relative humidity was less than 40 percent. Troops had to drink large quantities of water to prevent dehydration. While the summers were hot and dry, temperatures in winter (December through March) were cold, with wind chill temperatures at night dropping well below freezing. Wind and blowing sand made protection of skin and eyes imperative. Individuals were not allowed to wear contact lenses, except in air-conditioned areas that were protected from sand. Goggles and sunglasses helped somewhat, but visibility was often poor.
Environmental and Chemical Exposures
Certainly the most visually dramatic environmental event of the Gulf War was the smoke from more than 750 oil-well fires. Smoke plumes rose and combined to form giant plumes that could be seen for hundreds of kilometers. In addition to oil-well fires, there were other potential sources of exposure to petroleum-based products. Kerosene, diesel, and leaded gasoline were used in un-
vented tent heaters, cooking stoves, and portable generators. Petroleum products, including diesel fuels, were used to suppress sand and dust. Additionally, petroleum fuels were used for burning waste and trash.
Pesticides, including dog flea collars, were widely used by troops in the Gulf to combat the region’s ubiquitous insect and rodent populations. Pesticides used included methyl carbamates, organophosphates, pyrethroids, and chlorinated hydrocarbons. Although guidelines for use were strict, there were many reports of misuse.
There were many possible exposures related to particular occupational activities in the Gulf War. The majority of occupational chemical exposures appear to have been related to repair and maintenance activities including battery repair (corrosive liquids), cleaning or degreasing (solvents, including chlorinated hydrocarbons), sandblasting (abrasive particulates), vehicle repair (asbestos, carbon monoxide, organic solvents), weapon repair (lead particulates), and welding or cutting (chromates, nitrogen dioxide, heated metal fumes). Additionally, troops painted vehicles and equipment used in the Gulf with chemical agent-resistant coating (CARC) either before being shipped to the Gulf or at ports in Saudi Arabia. Because working conditions in the field were not ideal, recommended occupational hygiene standards may not have been followed at all times.
Exposure of U.S. personnel to depleted uranium occurred as the result of friendly fire incidents, cleanup operations, and accidents (including fires). Others may have inhaled DU dust through contact with DU-contaminated tanks or munitions (see Chapter 4).
Threat of Chemical and Biological Warfare
When U.S. troops first arrived in the Gulf, they had no way of knowing if they would be exposed to biological and chemical weapons. Iraq had used such weapons in fighting Iran and in attacks on the Kurdish minority in Iraq. Military leaders feared that the use of such weapons in the Gulf could result in the deaths of tens of thousands of Americans. Therefore, in addition to the standard vaccinations given prior to military deployment, about 150,000 troops received anthrax vaccine and about 8,000 received botulinum toxoid vaccine (see Chapter 7). Additionally, troops were given blister packs of 21 tablets of pyridostigmine bromide to protect against possible chemical warfare. Troops were to take PB upon the orders of a commanding officer when chemical warfare attack was believed to be imminent (see Chapter 6).
Chemical sensors and alarms were distributed throughout the region to warn of such attacks. The alarms were extremely sensitive and could be triggered by many substances including some organic solvents, vehicle exhaust fumes, and insecticides. Although follow-up analysis by the Department of Defense (DoD) found no evidence of the use of chemical warfare agents, the alarms sounded frequently, and troops responded by donning the confining protective gear and ingesting PB as an antidote to the effects of nerve gas. In addition to the alarms, there were widespread reports of dead sheep, goats, and camels, which troops
were taught could be an indication of the use of chemical or biological weapons. The sounding of these alarms, and the reports of dead animals, plus rumors that other units had been hit by chemical warfare agents, caused the troops to be concerned that they would be or had been exposed to these agents.
Despite the small numbers of U.S. personnel injured or killed during combat in the Gulf War, the troops, as in any war, faced the fear of death, injury, or capture by the enemy. They witnessed the many horrors of war, including dead bodies.
After the war, there was the potential for other exposures, including U.S. demolition of a munitions storage complex at Khamisiyah, Iraq, which—unbeknownst to demolition troops at the time—contained stores of sarin and cyclosarin (see Chapter 5).
It has been documented from the Civil War to the Gulf War that a variety of physical and psychological stressors placed military personnel at high risk for adverse health effects (Hyams et al., 1996). In addition to the threat or experience of combat, the Gulf War involved rapid and unexpected deployment, harsh living conditions, continuous anticipation of exposure to chemical and biological agents, environmental pollution from burning oil fires, and family disruption and financial strain.
SCOPE OF THE REPORT
The committee was charged with conducting a review of the scientific literature on the possible health effects of agents to which Gulf War veterans may have been exposed. The breadth of this review included all relevant toxicological, animal, and human studies. Because only a few studies related directly to veterans’ exposures, the committee reviewed studies of any human populations—including veterans—that had been exposed to the agents of concern at any dose. These studies come primarily from occupational, clinical, and healthy volunteer settings.
By examining the full range of evidence for health outcomes in different populations, the committee addressed the question, Could exposure to a given agent be associated with a specific health outcome? As discussed in Chapter 3, an association between a specific agent and a health outcome does not mean that exposure to the agent invariably results in the health outcome or that all cases of the health outcome are related to exposure to the specific agent. Such complete correspondence between exposure and disease is the exception in the study of disease in large populations (IOM, 1994).
The committee began its task by hearing from many veterans’ organizations, because the committee realized that it could not conduct a credible scientific review without an understanding of veterans’ experiences and perspectives. Thus, to supplement the scientific process, the committee opened several of its meetings to veterans and other interested individuals. The committee held a scientific workshop (see Appendix A) and two public meetings (Appendix B). They also received information in written form from veterans’ organizations,
veterans, and other interested persons who made the committee aware of their experiences or their health status and provided information about research. This information helped the committee by providing details on the Gulf War experience, in identifying particular agents and health issues of concern, and in providing a context for the committee’s work.
The committee and staff reviewed more than 10,000 abstracts of scientific and medical articles related to the agents selected for study. The full text of more than 1,000 peer-reviewed journal articles, many of which are described in this report, were carefully reviewed by the committee (see Appendix C for a complete description of the committee’s literature review strategy).
ORGANIZATION OF THE REPORT
Chapter 2 provides an overview of major studies that have been conducted on the health of Gulf War veterans. It highlights the complexity of efforts to understand the nature of the veterans’ illnesses, reviews some of the many studies that have provided data on the symptomatology of illnesses in Gulf War veterans, and discusses the limitations of these studies. Chapter 3 outlines the methods used by the committee to review the literature, the issues it debated while considering the evidence, and its criteria for reaching conclusions about the strength of the evidence for or against associations between adverse health effects and specific agents.
The next four chapters review the scientific literature on each of the agents chosen for study: depleted uranium (Chapter 4), sarin and cyclosarin (Chapter 5), pyridostigmine bromide (Chapter 6), and the anthrax and botulinum toxoid vaccines (Chapter 7). Each of these chapters explains the use of the agent during the Gulf War, contains an overview of the toxicology of the agent, describes the results of animal studies, and provides detailed descriptions of human studies. Further, when evidence was available on combinations of chemicals or other agents, the committee includes that information in its discussion. The committee provides conclusions in each of the chapters about the strength of the relationship between the agent and the possibility of adverse health outcomes. Finally, where there are gaps in the information, the committee makes recommendations for future research efforts in those areas (Chapter 8).
Goss Gilroy Inc. 1998. Health Study of Canadian Forces Personnel Involved in the 1991 Conflict in the Persian Gulf, Vol. 1. Ottawa, Ontario: Goss Gilroy Inc. Prepared for the Department of National Defence.
Gunby P. 1991. Physicians provide continuum of care for Desert Storm fighting forces. JAMA 265(5):557–558.
Hyams KC, Hanson K, Wignall FS, Escamilla J, Oldfield EC III. 1995. The impact of infectious diseases on the health of US troops deployed to the Persian Gulf during Operations Desert Shield and Desert Storm. Clin Infect Dis 20:1497–1504.
Hyams KC, Wignall S, Roswell R. 1996. War syndromes and their evaluation: From the U.S. Civil War to the Persian Gulf War. Ann Intern Med 125(5):398–405.
IOM (Institute of Medicine). 1994. Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam. Washington, DC: National Academy Press.
IOM (Institute of Medicine). 1995. Health Consequences of Service During the Persian Gulf War: Initial Findings and Recommendations for Immediate Action. Washington, DC: National Academy Press.
IOM (Institute of Medicine). 1996. Health Consequences of Service During the Persian Gulf War: Recommendations for Research and Information Systems. Washington, DC: National Academy Press.
IOM (Institute of Medicine). 1999. Gulf War Veterans: Measuring Health. Washington, DC: National Academy Press.
Iowa Persian Gulf Study Group. 1997. Self-reported illness and health status among Gulf War veterans: A population-based study. JAMA 277(3):238–245.
Joellenbeck LM, Landrigan PJ, Larson EL. 1998. Gulf War veterans’ illnesses: A case study in causal inference. Environ Res 79(2):71–81.
Lawler MK, Flori DE, Volk RJ, Davis AB. 1997. Family health status of National Guard personnel deployed during the Persian Gulf War. Families, Systems, Health 15(1): 65–73.
NIH (National Institutes of Health) Technology Assessment Workshop Panel. 1994. The Persian Gulf experience and health. JAMA 272(5):391–396.
PAC (Presidential Advisory Committee on Gulf War Veterans’ Illnesses). 1996. Presidential Advisory Committee on Gulf War Veterans’ Illnesses: Final Report. Washington, DC: U.S. Government Printing Office.
PAC (Presidential Advisory Committee on Gulf War Veterans’ Illnesses). 1997. Special Report. Washington, DC: U.S. Government Printing Office.
Persian Gulf Veterans Coordinating Board. 1995. Unexplained illnesses among Desert Storm veterans: A search for causes, treatment, and cooperation. Arch Intern Med 155:262–268.
Unwin C, Blatchley N, Coker W, Ferry S, Hotopf M, Hull L, Ismail K, Palmer I, David A, Wessely S. 1999. Health of UK servicemen who served in the Persian Gulf War. Lancet 353(9148):169–178.
Ursano RJ, Norwood AE, eds. 1996. Emotional Aftermath of the Persian Gulf War: Veterans, Families, Communities, and Nations. Washington, DC: American Psychiatric Press.
U.S. Department of Veterans Affairs. 1998. Consolidation and Combined Analysis of the Databases of the Department of Veterans Affairs Persian Gulf Health Registry and the Department of Defense Comprehensive Clinical Evaluation Program. Washington, DC: Environmental Epidemiology Service, Department of Veterans Affairs.