U.S. service members who deploy outside the United States may encounter chemical, biological, physiological, radiological, and psychological exposures they may never have experienced during military service in the United States or as civilians. These potential exposures include chemical warfare agents, vaccines for anthrax, vector-borne diseases such as malaria, extreme heat and cold, and the stresses of being in a war zone. Some of the exposures may be to chemicals that are, or were, used in civilian life, such pesticides and fuels, but the duration or frequency of those exposures may be different in deployment situations. Veterans who served in the Vietnam, 1990–1991 Gulf War, and Post-9/11 conflicts have a variety of health effects that are associated with their deployment exposures. In some cases, those health effects can be long-lasting and affect reproductive functions. Veterans are understandably concerned that their exposures during their deployments might have caused or might be the cause of adverse health effects in their children and possibly their grandchildren.
The National Academies of Sciences, Engineering, and Medicine’s (the National Academies’) Veterans and Agent Orange: Update 2014 highlighted some of the areas of research that might shed light on the biological mechanisms associated with generational effects and also addressed issues related to the feasibility of research designed to investigate these concerns (NASEM, 2016a). Specifically, the report recommended that the Department of Veterans Affairs (VA) encourage the investigation of epigenetic1 changes in somatic tissues, germ cells, and epigenetic changes that take place during gestation. The report also supports research to identify specific markers of environmentally induced epigenetic activity. Such research efforts may help elucidate the mechanisms responsible for adverse health effects in exposed individuals or their offspring. In part, the present report provides guidance to VA on how to address those research recommendations.
This Gulf War and Health, Volume 11 report examines the long-term health consequences of military service in the Gulf War. While the previous 10 volumes focused on the health of Gulf War veterans, this
1Epigenetics is most commonly taken to refer to heritable changes in gene expression that do not result from change in actual gene sequences. (“Heritable” here can refer to inheritance not only between parents and offspring but also between parent and daughter cells.)
volume includes an assessment of reproductive effects related to exposures that may have occurred during the Post-9/11 conflicts as well as any effects on the health of any children born after both Gulf War and Post-9/11 exposures. This report also examines the mechanisms, methods, and feasibility issues of potential investigations intended to help determine if there are health effects in children or grandchildren of veterans, of any era, related to their parents’ or grandparents’ deployment exposures.
In response to the invasion of Kuwait by Iraq in August 1990, the United States led a coalition of 34 countries, including the United Kingdom, Australia, Canada, France, and Denmark, in a buildup of forces in the Persian Gulf called Operation Desert Shield. This multinational effort was followed by Operation Desert Storm, which began in January 1991 and was over by the end of February. Over the course of the buildup and war, almost 700,000 U.S. troops were deployed to the Persian Gulf region, although by June 1991 only about 50,000 U.S. troops remained in the area. Although brief, with relatively few injuries and deaths among the coalition forces, the legacy of the war has been a large contingent of veterans who suffer from a number of health problems, particularly Gulf War illness,2 which have persisted for more than 25 years (NASEM, 2016).
The U.S. military engaged in further conflicts in the Middle East following the terrorist attacks of September 11, 2001. Operation Enduring Freedom (OEF) began in October 2001, with troops stationed in and around Afghanistan for military and humanitarian purposes. Operation Iraqi Freedom (OIF) began in March 2003 as American-led coalition forces invaded Iraq, and it officially ended on August 31, 2010. Operation New Dawn (OND) was initiated on September 1, 2010, to reflect the changing mission of and reduction in U.S. military personnel in Iraq, and it officially ended on December 15, 2011. The U.S. military mission in Iraq ended in 2011; the U.S. mission in Afghanistan continues.
The operation of the 1990–1991 Gulf War reflected a number of changes from previous wars, particularly in the demographic composition of military personnel. Military personnel were, overall, men who were older than those who had participated in previous wars, with a mean age of 28 years (Joseph, 1997). There were also more women (almost 7%), parents, and activated members of the reserves and National Guard (about 17%, or 106,000), who were temporarily uprooted from their civilian lives (VA, 2011). As of 2014, more than 2.6 million service members have served in Iraq and Afghanistan, and almost half have deployed to the region more than once (VA, 2015). As of 2010, 15.5% of all military personnel and nearly one-fourth of Army reserves were women (Reynolds and Shendruk, 2018).
During the Gulf War and Post-9/11 conflicts, service members who were deployed to the theater of conflict were potentially exposed to hazardous agents and situations, both known and unknown, many of which were unique to those conflicts. Because Iraq had been known to use chemical and possibly biological agents against its own people and others, many Gulf War service members received mandatory vaccines to prevent anthrax and botulism. Pyridostigmine bromide (PB) was first used as a prophylaxis against potential nerve agent exposure in the Gulf War. Both the Gulf War and Post-9/11 conflicts included exposures to depleted uranium in munitions. Gulf War service members were also exposed to oil-well-fire smoke from the burning oil wells in Kuwait. Veterans of both the Gulf War and Post-9/11 conflicts were exposed to dust, dust storms, excessive heat, pesticides, chemical-agent-resistant coating paint, and diesel fuels, among other exposures. Military field operations also generated large quantities of waste; it has been estimated that 8–10 pounds of solid waste per person per day were generated
2 Gulf War illness is characterized by persistent symptoms of fatigue, mood and cognition problems, musculoskeletal pain, sleep disturbance, and neurologic, respiratory, skin, and gastrointestinal problems (NASEM, 2016).
at the military bases in Iraq and Afghanistan, although this number varied depending on the base and its population (Faulkner, 2011). A wide variety of refuse was burned, from food and human waste to packaging and equipment, as well as materials abandoned by the enemy. Thus, the characterization of exposures and their associated health effects is complicated by the possible exposure to multiple chemical and biologic agents, repeated exposures to those agents, a dearth of environmental sampling data, and individual variability. While some of these exposures were documented in medical records or via air sampling, many were not.
In response to the growing concerns of Gulf War veterans about their health, Congress passed two laws in 1998: P.L. 105-277, the Persian Gulf War Veterans Act, and P.L. 105-368, the Veterans Programs Enhancement Act. The goals of these laws were to identify what health outcomes might be expected from the environmental agents to which veterans had been exposed during their deployments and to require VA to treat those health outcomes (see Box 1-1 for a list of the toxicants of concern). The laws directed the Secretary of Veterans Affairs to enter into a contract with the National Academy of Sciences (NAS, now part of the National Academies) to review and evaluate the scientific and medical literature regarding associations between illness and exposure to toxic agents, environmental or wartime hazards, or preventive medicines or vaccines associated with Gulf War service and to consider the NAS conclusions when making decisions about compensation.
The Persian Gulf War legislation directs the National Academies to study diverse biologic, radiologic, chemical, and physical agents. Exposures to some Gulf War agents have been extensively studied and characterized, primarily in occupational settings (for example, exposure to pesticides, solvents, and fuels). However, exposures to other agents have not been studied or characterized in human populations (for example, exposure to nerve agents or oil-well-fire smoke) (NASEM, 2016b).
In December 2016, Congress passed P.L. 114-315, also known as the Jeff Miller and Richard Blumenthal Veterans Health Care and Benefits Improvement Act of 2016; section 632 of that law again called on VA to contract with the National Academies to examine the “scientific research regarding the descendants of individuals and veterans with toxic exposure.” The law requests that the National Academies conduct a review of the toxicologic and epidemiologic literature and areas needing further study relating to descendants of veterans with toxic exposures. It further asks for details regarding the scope, methodology, and feasibility of any future study and other agencies suited to conduct such research.
The National Academies has previously prepared numerous studies on the health of Gulf War and other veterans, including Vietnam veterans. As a result of 1998 legislation, the National Academies has conducted more than 10 studies and updates in the Gulf War and Health series on veterans’ exposures and the health effects associated with those exposures:
- Volume 1: Depleted Uranium, Pyridostigmine Bromide, Sarin, and Vaccines (IOM, 2000)
- Volume 2: Insecticides and Solvents (IOM, 2003)
- Updated Literature Review of Sarin (IOM, 2004)
- Volume 3: Fuels, Combustion Products, and Propellants (IOM, 2005)
- Amyotrophic Lateral Sclerosis in Veterans: Review of the Scientific Literature (IOM, 2006a)
- Volume 4: Health Effects of Serving in the Gulf War (IOM, 2006b)
- Volume 5: Infectious Diseases (IOM, 2007)
- Updated Literature Review of Depleted Uranium (IOM, 2008a)
- Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress (IOM, 2008b)
- Volume 7: Long-Term Consequences of Traumatic Brain Injury (IOM, 2009)
- Volume 8: Update of Health Effects of Serving in the Gulf War (IOM, 2010)
- Volume 9: Long-Term Effects of Blast Exposures (IOM, 2014)
- Volume 10: Update of Health Effects of Serving in the Gulf War, 2016 (NASEM, 2016b)
Beginning with volume 1 of the Gulf War and Health series, National Academies’ committees developed a process for assessing the evidence for each study and reaching conclusions regarding the weight of the evidence for each exposure or environmental agent and possible health outcomes (see
Chapter 2). Because each committee was composed of different experts and the exposures to be assessed varied for each report, each committee made slight modifications to the assessment process. Although the first three volumes of the Gulf War and Health series dealt with specific environmental agents, in 2005, VA requested that the National Academies appoint a committee to review the medical literature and to summarize what was known then about the current status of Gulf War veterans’ health. The resulting report, volume 4, and two subsequent updates, volumes 8 and 10, summarized the overall health effects in veterans and noted which health outcomes were more evident in veterans who had deployed to the Persian Gulf region than in their nondeployed counterparts, irrespective of the specific exposures experienced by the deployed veterans. Volumes 6, 7, and 9 deviated from the rest of the series with a broader scope to include Post-9/11 veterans; volume 6 also included and addressed Vietnam veterans. All these efforts assessed reproductive effects in veterans and developmental effects in their children based on the evidence available at that time.
The National Academies has also produced other reports of relevance to this report beginning with four reports published after the 1990–1991 Gulf War, but prior to the Post-9/11 conflicts in Afghanistan and Iraq: Health Consequences of Service During the Persian Gulf War: Recommendations for Research and Information Systems (IOM, 1996); Strategies to Protect the Health of Deployed U.S. Forces: Medical Surveillance, Record Keeping, and Risk Reduction (IOM, 1999); Strategies to Protect the Health of Deployed U.S. Forces: Analytical Framework for Assessing Risks (NRC, 2000a); and Strategies to Protect the Health of Deployed U.S. Forces: Assessing Health Risks to Deployed U.S. Forces, Workshop Proceedings (NRC, 2000b). These studies provide a roadmap for DoD to identify and assess the potential health effects from the toxicants to which U.S. service members may be exposed during any deployment, including the use of environmental and biological sampling. In response to veterans’ concerns about exposure to burn pits, The Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan report was released (IOM, 2011); this study built on the earlier Review of the Department of Defense Enhanced Particulate Matter Surveillance Program Report (NRC, 2010). Health effects for the several toxicants of concern—particularly trichloroethylene, tetrachloroethylene, and benzene—were also evaluated in Contaminated Water Supplies at Camp Lejeune: Assessing Potential Health Effects (NRC, 2009).
In response to veterans’ concerns about the health of their children and grandchildren as legislated in P.L. 114-315, VA asked the National Academies to examine the potential health effects of deployment-related exposures on veterans and on their children and grandchildren and to provide guidance on a path forward for research in this area. The committee’s full statement of task is given in Box 1-2. The committee organized its approach to its statement into two tasks. Task 1 is an update of prior Gulf War and Health reports, but with a focus on the reproductive and developmental effects that might occur in, respectively, veterans and their offspring following exposure to the many agents listed in Box 1-1. Task 2 is the development of a framework for a health monitoring program as well as an approach to designing epidemiologic studies to identify any reproductive or developmental studies in veterans and their descendants. Task 2 also includes an in-depth discussion of potential cellular and animal pathophysiological studies that might provide important information to address the many data gaps identified throughout both tasks 1 and 2. The committee’s approach to its statement of task is discussed in more detail in Chapter 2.
Chapter 2 explains the committee’s approach to the statement of task given in Box 1-2. It provides an overview of how the committee assessed exposures that might have been experienced by Gulf War and Post-9/11 veterans and how it evaluated the literature and came to its conclusions, along with a description of the categories of association that are used to determine the strength of an association between an exposure and a reproductive or developmental health effect. Chapter 3 provides background information on how environmental exposures can affect the genome and epigenome, explains how those changes may be transmitted to descendants, and gives context for this new and evolving field of research. Chapters 4 through 7 are updates of what is known about the reproductive and developmental effects that are associated with exposures to many of the toxicants listed in Box 1-1. Specifically, Chapter 4 examines deployment-related exposures, such as to chemical warfare agents and vaccines, as well as new studies comparing deployed versus nondeployed veterans; Chapter 5 focuses on exposures to
pesticides, such as organophosphates and pyrethroids; Chapter 6 examines exposures to combustion products, such as particulate matter and dioxins, and fuels, including diesel and JP-8; and Chapter 7 focuses on exposures to solvents, such as benzene, trichloroethylene, and tetrachloroethylene. The committee’s conclusions concerning the health effects of those exposures, which are based on the strength of the evidence described in these chapters, are summarized in Chapter 8, which also includes a brief discussion of epigenetics and what is being learned from human and animal studies in this area. Chapter 9 addresses the committee’s second task of providing VA with a framework for a health monitoring research program to identify any health effects in the descendants of veterans that may be related to the veterans’ deployment exposures. Chapter 10 describes the various basic research studies that might
be conducted to elucidate the underlying genetic and epigenetic mechanisms of these health effects as well as other biological repercussions that are passed down from generation to generation. Chapter 11 provides a context and path forward to help VA and veterans identify and understand whether exposures experienced by veterans during their deployments may be affecting the health of their children, grandchildren, and future generations. Finally, short biographical sketches of the committee members may be found in Appendix A, while Appendix B provides a glossary of the technical terms used in this report.
Faulkner, W.M. 2011. Exposure to toxins produced by burn pits: Congressional data request and studies. Memorandum for the Assistant Secretary of Defense for Health Affairs. Washington, DC: Joint Staff. March 28, 2011. Enclosure: ASD (HA) Memorandum, February 17, 2011. Response to ASD (HA) Request for Information.
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. 1999. Strategies to protect the health of deployed U.S. forces: Medical surveillance, record keeping, and risk reduction. Washington, DC: National Academy Press.
IOM. 2000. Gulf War and health, volume 1: Depleted uranium, pyridostigmine bromide, sarin, vaccines. Washington, DC: National Academy Press.
IOM. 2003. Gulf War and health, volume 2: Insecticides and solvents. Washington, DC: The National Academies Press.
IOM. 2004. Gulf War and health: Updated literature review of sarin. Washington, DC: The National Academies Press.
IOM. 2005. Gulf War and health, volume 3: Fuels, combustion products, and propellants. Washington, DC: The National Academies Press.
IOM. 2006a. Amyotrophic lateral sclerosis in veterans: Review of the scientific literature. Washington, DC: The National Academies Press.
IOM. 2006b. Gulf War and health, volume 4: Health effects of serving in the Gulf War. Washington, DC: The National Academies Press.
IOM. 2007. Gulf War and health, volume 5: Infectious diseases. Washington, DC: The National Academies Press.
IOM. 2008a. Gulf War and health: Updated literature review of depleted uranium. Washington, DC: The National Academies Press.
IOM. 2008b. Gulf War and health, volume 6. Physiologic, psychologic, and psychosocial effects of deployment-related stress. Washington, DC: The National Academies Press.
IOM. 2009. Gulf War and health, volume 7: Long-term consequences of traumatic brain injury. Washington, DC: The National Academies Press.
IOM. 2010. Gulf War and health, volume 8: Update of health effects of serving in the Gulf War. Washington, DC: The National Academies Press.
IOM. 2011. The long-term health consequences of exposure to burn pits in Iraq and Afghanistan. Washington, DC: The National Academies Press.
IOM. 2014. Gulf War and health, volume 9: Long-term effects of blast exposures. Washington, DC: The National Academies Press.
Joseph, S.C. 1997. A comprehensive clinical evaluation of 20,000 Persian Gulf War veterans. Military Medicine 162(3):149–155.
NASEM (National Academies of Sciences, Engineering, and Medicine). 2016a. Veterans and Agent Orange: Update 2014. Washington, DC: The National Academies Press.
NASEM. 2016b. Gulf War and health, volume 10: Update of health effects of serving in the Gulf War. Washington, DC: The National Academies Press.
NRC (National Research Council). 2000a. Strategies to protect the health of deployed U.S. forces: Analytical framework for assessing risks. Washington, DC: National Academy Press.
NRC. 2000b. Strategies to protect the health of deployed U.S. forces: Assessing health risks to deployed U.S. forces, workshop proceedings. Washington, DC: National Academy Press.
NRC. 2009. Contaminated water supplies at Camp Lejeune: Assessing potential health effects. Washington, DC: The National Academies Press.
NRC. 2010. Review of the Department of Defense Enhanced Particulate Matter Surveillance Program report. Washington, DC: The National Academies Press.
Reynolds, G.M., and A. Shendruk. 2018. Demographics of the U.S. Military. Washington, DC: Council on Foreign Relations. April 24. https://www.cfr.org/article/demographics-US-military (accessed July 27, 2018).
VA (Department of Veterans Affairs). 2011. Caring for Gulf War I veterans. Veterans Health Administration. http://www.publichealth.va.gov/docs/vhi/caring-for-gulf-war-veterans-vhi.pdf (accessed October 20, 2018).
VA. 2015. The scent of war: VA studies a legacy of dust, smoke, and burn pits and what it means for veterans. VA Research Currents, February 18. https://www.research.va.gov/currents/winter2015/winter2015-18.cfm (accessed July 27, 2018).
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