STATEMENT OF
LAWRENCE DEYTON, MSPH, MD
CHIEF PUBLIC HEALTH AND ENVIRONMENTAL HAZARDS OFFICER
VETERANS HEALTH ADMINISTRATION
DEPARTMENT OF VETERANS AFFAIRS
BEFORE THE
SUBCOMMITTEE ON HEALTH
HOUSE COMMITTEE ON VETERANS AFFAIRS
HOUSE OF REPRESENTATIVES
GULF WAR EXPOSURES

July 26, 2007

Mr. Chairman and members of the Subcommittee, thank you for providing the Department of Veterans Affairs ( VA) this opportunity to discuss VA's response to the health care and other needs of veterans who have served in combat in Southwest Asia. With me today is

• Mark Brown, PhD, Director, Environmental Agents Service, Office of Public Health and Environmental Hazards
• Timothy O'Leary, Director, Biomedical Laboratory Research and Development Service, Director, Clinical Science Research and Development Service, Office of Research and Development and
• Eugene Oddone, MD, MHSc, Director, Center for Health Services Research in Primary Care and Principal Investigator, National Registry of Veterans with ALS

BACKGROUND

The United States deployed nearly 700,000 military personnel to the Kuwaiti Theater of Operations during Operations Desert Shield and Desert Storm (August 2, 1990, through July 31, 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 VA subsequently became concerned about the possible adverse health effects from various environmental exposures during Operations Desert Shield and Desert Storm.

Of particular concern have been the symptoms and illnesses that, to date, have eluded specific diagnosis. More than 130,000 Gulf War veterans have participated in the two health registries that VA and the Department of Defense ( DoD) maintain. In addition, more than 335,000 have been seen at least once as patients by VA. Although the majority of veterans seeking VA health care had readily diagnosable health conditions, we remain very concerned about the veterans whose symptoms could not be diagnosed.

I would like to provide a brief description of some of the programs and initiatives VA developed in response to health concerns of veterans of the 1991 Gulf War. I will also focus on how these new programs have benefited the veterans who are now returning from the current conflicts in Southwest Asia, specifically veterans from Operation Enduring Freedom ( OEF) and Operation Iraqi Freedom ( OIF) and their families.

VA INITIATIVES FOR SOUTHWEST ASIA COMBAT VETERANS

The VA Gulf War Veteran Health Registry. Even before the 1991 Gulf War cease-fire VA had concerns that returning veterans might have certain unique health problems including respiratory effects from exposure to the intense oil fire smoke.

In response, VA quickly established a clinical registry to screen for this possibility. The new voluntary health registry examination also helped encourage new combat veterans to take advantage of VA health care programs. VA has long maintained health registries on other at-risk populations, including veterans exposed to radiation, and Vietnam veterans exposed to Agent Orange.

Formally established by law in 1992, VA's Gulf War Veterans' Health Examination Registry is still available to all Gulf War veterans, including veterans of the current conflict in Iraq. It offers a comprehensive physical examination, and collects data from participating veterans about their symptoms, diagnoses, and self reported Gulf War hazardous exposures. As of June 2007, this program evaluated over 100,000 Gulf War veterans, or about 1 in 7 veterans.

The program has also seen nearly 7,000 veterans who served in the current conflict in Iraq, who as Gulf War veterans themselves, are eligible for this program.

After 15 years, the principal finding from VA's systematic clinical registry examination of about 14 percent of 1991 Gulf War veterans is that they are suffering from a wide variety of common, recognized illnesses. However, no new or unique syndrome has been identified. Registry data has significant limitations. VA recognizes that in the long run, establishing high quality epidemiological research studies is the best approach for evaluating the health impacts of service in the 1991 Gulf War (or in any deployment). VA has adopted that approach.

New Compensation for Undiagnosed Illnesses. Many new Gulf War veterans encountered problems when they tried to prove that their difficult-to-diagnose or undiagnosed illnesses were connected to their military service. This affected their access to disability compensation. In response, VA asked Congress for authority, granted under Public Law 103-446, to provide compensation benefits to Gulf War veterans who are chronically disabled by undiagnosed illnesses when certain conditions are met. This statute as amended authorizes VA to pay compensation for disabilities that cannot be diagnosed as a specific disease or injury, or for certain illnesses with unknown cause including chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome.

Symptoms potentially covered include 1) fatigue; 2) skin signs or symptoms, including hair loss; 3) headache; 4) muscle pain; 5) joint pain; 6) neurologic signs or symptoms; 7) neuropsychological signs and symptoms, including memory loss; 8) signs or symptoms involving the respiratory system ; 9) sleep disturbances; 10) gastrointestinal signs or symptoms; 11) cardiovascular signs and symptoms; 12) abnormal weight loss; and 13) menstrual disorders. This is a unique benefit for Gulf War veterans, and more than 3,300 have received service connection for their undiagnosed or difficult to diagnose illnesses under this authority. Veterans from the current conflict in Iraq are also eligible for this special benefit.

Epidemiological Research on Gulf War Veterans. Despite the value of VA's Gulf War Health Registry program, additional epidemiological research is required to properly characterize any possible long-term health effects of Gulf War 1 service to the average Gulf War veteran. This is because the registry participants are self-selected, and therefore do not represent the average veteran. Registry findings demonstrate that Gulf War veterans are not showing up with any unique health problems; however, these findings do not tell us if veterans are suffering from any diagnoses at rates different from expected. That requires population-based epidemiological and related research studies, which VA has carried out.

VA Gulf War Veteran Mortality Study. VA researchers have been continuously monitoring the cause-specific mortality of all Gulf War veterans in comparison to their non-deployed peers. In post-war monitoring, Gulf War veteran mortality from most causes is not significantly different in comparison to non-deployed peer as controls. Moreover, the mortality for both groups is less than half that of matched civilian controls. This is almost certainly because people who choose to go into the military are healthier to begin with.

Initially, Gulf War veterans have shown an increased risk of death from accidents, especially motor vehicle accidents. VA's data shows that this is a temporary effect, and by 6 years post-war this difference has disappeared. This overall pattern is very consistent with earlier mortality data from Vietnam veterans.

New Clinical Guidelines for Combat Veteran Health Care. Early on, VA recognized the need to assure training of our health care providers to allow them to best respond to the specific health care needs of Gulf War veterans with difficult-to-diagnose illnesses. With that in mind, and in collaboration with the Department of Defense ( DoD), VA developed two Clinical Practice Guidelines on combat veteran health issues. This included a general guideline on post combat deployment health, and a second dealing with diagnosis of unexplained pain and fatigue. These clinical guidelines give VA health care providers access to the best medical evidence for diagnoses and treatment. Developed in response to veterans of the 1991 Gulf War, today VA highly recommends these for the evaluation and care of all returning combat veterans, including veterans from OEF and OIF. (also available on line at www.va.gov/EnvironAgents)

New VA "War-Related Illness & Injury Study Centers:" Specialized Health Care for Combat Veterans. In 2001, as part of VA's overall health response for veterans returning from the 1991 Gulf War, VA established two War Related Illness and Injury Study Centers (WRIISCs), at the Washington, DC, and East Orange, NJ VA Medical Centers (VAMCs) Today, these two centers are providing specialized health care for combat veterans from all deployments who experience difficult to diagnose or undiagnosed but disabling illnesses. VA now anticipates concerns about unexplained illness after virtually all deployments including OEF and OIF, and we are building on our understanding of such illnesses.

Currently, VA is expanding on this program to better meet the health care needs of new combat veterans suffering from mild to moderate traumatic brain injury. To that end, VA is establishing a third WRIISC at the Palo Alto VA Health Care System. This will take advantage of their unique assets including a Polytrauma Unit, interdisciplinary program on blast injuries which integrates the medical, psychological, rehabilitation, prosthetic needs of injured service members, their programs in traumatic brain injury, spinal cord injury, blind rehabilitation post traumatic stress disorder, and research into new and emerging areas of combat injuries and illnesses. This is a critical development because combat injuries we see today among OEF and OIF veterans are much more likely, compared to previous wars, to involve some degree of traumatic brain injury. This has been the result of the types of weapons commonly used to attack our troops, including improvised explosive devices, blasts from landmines, artillery and mortar attacks, and the resulting shrapnel produced from such devices. Many of the long-term chronic health effects from traumatic brain injury appear similar to the difficult-to-diagnose and treat illnesses currently being treated by the WRIISC programs today.

Expanded Education on Combat Health Care for VA Providers. In response to health problems faced by veterans of the 1991 Gulf War, VA developed the Veterans Health Initiative ( VHI) Independent Study Guides for health care providers titled, "A Guide to Gulf War Veterans Health." Although originally focusing on health care for combat veterans from the 1991 Gulf War, this study guide remains highly relevant for treating OEF and OIF combat veterans, since many of the hazardous deployment-related exposures are the same for both conflicts.

VA also developed several additional VHI Independent Study Guides and other materials relevant to veterans returning from Iraq and Afghanistan. These include the Under Secretary for Health Information Letter "Preparing for the Return of Women Veterans from Combat Theater," ( IL 10-2003-011), which provides guidance on the special care needs for women OEF and OIF combat veterans.

Another VHI independent study guide in this series, "Endemic Infectious Diseases of Southwest Asia," provides guidance to health care providers about the infectious disease risks in Southwest Asia, particularly in Afghanistan and Iraq. The emphasis is on diseases not typically seen in North America.

Similarly, "Health Effects from Chemical, Biological and Radiological Weapons" was developed to improve recognition of health issues related to chemical, biological, and radiological weapons and agents.

The guideline, "Military Sexual Trauma," was developed to improve recognition and treatment of health problems related to military sexual trauma, including sexual assault and harassment.

Similarly, "Post-Traumatic Stress Disorder: Implications for Primary Care" is an introduction to PTSD diagnosis, treatment, referrals, support and education, as well as awareness and understanding of veterans who suffer from this illness.

"Traumatic Amputation and Prosthetics" includes information about patients who experience traumatic amputation during military service, their rehabilitation, primary and long-term care, and prosthetic clinical and administrative issues.

Finally, "Traumatic Brain Injury" presents an overview of Traumatic Brain Injury issues that primary care practitioners may encounter when providing care to veterans and active duty military personnel. All are available in print, C.D. R.O.M. and on the web at www.va.gov/VHI.

VA National Training on Health Care for New Combat Veterans. Based on our experience treating veterans from the 1991 Gulf War, VA recognized the need to quickly familiarize all VA health care providers on the unique health concerns of new combat veterans returning from Iraq and Afghanistan. VA has sponsored multiple regional education conferences and a three-day National Conference on "Providing Health Care for a New Generation of Combat Veterans Returning from OEF and OIF," in April 2007.

The conference objective was to sharpen the response of VA providers to new and transitioning combat veterans coming to us today, and to the new physical and behavioral health care challenges that these returning veterans bring with them. The meeting included plenary sessions featuring VA and DoD leadership, and breakout presentations from national and international experts describing their clinical and research experiences with new combat veterans.

Approximately 1,400 people attended this event, from throughout all of VHA. The target audience was VA primary care providers from around the country, including social workers, psychologists and mental health professionals, physicians, physician assistants, nurses, and others who provide direct care to new combat veterans returning from Iraq and Afghanistan.

National subject matter experts from VA, DoD, and academia, presented their recent experiences responding to the health care needs of new combat veterans. The goal was to give VA healthcare professionals the tools they will need to respond to the unique and sometimes complex healthcare needs of returning combat veterans, and to develop the necessary competencies to provide optimal care. The deliberately multidisciplinary approach also helped providers to focus on more integrated health care delivery, foster networking. and share best practices, all of which should enable us collectively to improve outcomes for returning wounded service members.

Breakout session topics covered Polytrauma; Pain Management; Behavioral Health; Diversity Issues; Prosthetics; and Special Topics for New Combat Veterans.

Outreach to Combat Veterans and their Families. VA has many programs designed to help returning combat veterans and their families. To help veterans of the 1991 Gulf War and their families be more aware of VA's health care and other benefits that are available for them, and of new research results on Gulf War veterans' health, VA initiated the "Gulf War Review" newsletter, which is regularly mailed out to over 400,000 veterans from that conflict.

VA has developed many new outreach and information products for new combat veterans and their families. The Secretary sends a letter to every newly separated OEF and OIF veteran, based on records for these veterans provided to VA by DoD. The letter thanks the veteran for their service, welcomes them home, and provides basic information about health care and other benefits provided by VA.

Similarly, in collaboration with DoD, VA published a new short brochure called "A Summary of VA Benefits for National Guard and Reservists Personnel." To date, over one million copies have been distributed. The new brochure summarizes health care and other benefits available to this special population of combat veterans upon their return to civilian life (also available online at www.va.gov/EnvironAgents). "Health Care and Assistance for U.S. Veterans of Operation Iraqi Freedom" is a new brochure on basic health issues for that deployment (also available online at www.va.gov/EnvironAgents).

Finally, VA started the " OEF and OIF Review," which is mailed to all separated OEF and OIF veterans (over 700,000 individuals as of July 2007) and their families, on VA health care and assistance programs for these newest veterans (also available online at www.va.gov/EnvironAgents).

Combat-Theater Veterans' Enhanced Access to VA Health Care. VA provides combat veterans enhanced enrollment placement and cost-free health care services and nursing home care for conditions possibly related to their service in a theater of combat operations after November 11, 1998 for a 2-year period beginning on the date of their separation from active military service. These veterans are placed into enrollment Priority Group 6 if not otherwise qualified for a higher enrollment Priority Group assignment and have full access to VA's Medical Benefit Package.

Veterans, including activated Reservists and members of the National Guard, are eligible if they served on active duty in a theater of combat operations during a period of war after the Gulf War or; were in combat against a hostile force during a period of "hostilities" after November 11, 1998 and, have been discharged under other than dishonorable conditions.

Veterans who enroll with VA under this authority retain enrollment eligibility even after their 2-year post discharge period ends under current enrollment policies. At the end of this 2-year period VA will reassess the combat veteran's information (including all applicable eligibility factors existing at this time) and make, as appropriate, a new Priority Group assignment.

Special Depleted Uranium ( DU) Surveillance Program. Special armor piercing munitions and tank armor made from depleted uranium ( DU) was used with great effect by US forces during the 1991 Gulf War, as well as more recently during the initial phases of OEF and OIF. However, some veterans returning from these conflicts have had concerns that DU may have affected their health. In response, in 1993, VA established the DU Follow-up Program at the Baltimore VA Medical Center to monitor the health of veterans who had retained DU fragments in wounds - typically from "friendly fire" incidents in 1991 Gulf War. The program provides ongoing and thorough detailed physical examinations for affected veterans, including a broad array of testing of the blood, immune, reproductive, and central nervous systems, and of kidney and liver function.

In 1998, in response to increasing concerns among Gulf War veterans, this program was expanded to offer DU screening for any veteran concerned about possible DU exposure, and not just those with possible retained DU fragments or with other types of high exposure risks. The program is also open for veterans who served in OEF and OIF.

Researchers with VA's DU Follow-up Program have not identified any clinically significant uranium-related health effects among veterans from exposure from inhalation or from retained DU fragments. There are however some concerns about certain physical changes that have been noted in imbedded DU fragments, and indications for surgical removal of fragments are currently under review by this group.

VA and DoD will continue to monitor health effects in this population, which includes both 1991 Gulf War veterans and veterans from the current conflict in Iraq.

New VA Toxic Embedded Fragments Surveillance Center. In response to health concerns for new OEF and OIF combat veterans suffering from retained embedded fragments composed of a wide range of metals and other materials as a result of blast injuries from improvised explosive devices, VA is establishing the Toxic Embedded Fragments Surveillance Center at the Baltimore VA Medical Center. New studies indicate that some metals, such as certain tungsten alloy fragments, are highly carcinogenic in rats and may pose a health hazard in veterans. Some metals are also known or presumed to be human reproductive hazards, including lead, cadmium, nickel, and copper.

The Baltimore VA DU Surveillance Program has shown us that retained DU fragments and other materials are not necessarily inert in the body, and may change over time to produce potential toxic health effects. Such effects may be minimized and managed through careful ongoing medical surveillance.

New Combat Veteran Health Surveillance. The long-term epidemiological studies supported by VA assessing the health effects of the 1991 Gulf War on veterans who were deployed to Southwest Asia took a considerable amount of time. Today, we appreciate the importance of rapidly monitoring the health status of new combat veterans and have initiated surveillance and studies to more rapidly identify any health effects that may occur from this current conflict. This has been made possible via VA's electronic inpatient and outpatient medical records, which summarizes every single visit by a combat veteran including all medical diagnoses. For example, according to VA's July 2007 update "Analysis of VA Health Care Utilization among Southwest Asian War Veterans," since fiscal year (FY) 2002 over 700,000 OEF and OIF veterans have left active duty and become eligible for VA health care. About 35 percent of these new veterans (over 250,000) have received VA health care at least once since 2002.

This simple surveillance shows that new OEF and OIF veterans are coming to VA with a wide range of medical and psychological conditions. No special conditions stand out, and therefore these new combat veterans are being assessed individually to identify all their outstanding health problems. VA will continue to monitor the health status of recent OEF and OIF veterans using updated deployment lists provided by DoD to ensure that VA tailors its health care and disability programs to meet the needs of this newest generation of war veterans. Also using this new combat veteran roster, VA has developed a new clinical reminder in the electronic health record to assist VA primary care clinicians in providing timely and appropriate care to new combat veterans.

INDEPENDENT REVIEWS ON GULF WAR VETERANS' HEALTH
VA has sought advice on the health of combat veterans serving in Southwest Asia from a wide range of external advisory groups. For example, VA has long relied upon the independent scientific advice of the National Academy of Sciences ( NAS) Institute of Medicine ( IOM) to help evaluate potential associations between environmental hazards encountered during various military deployments and specific health effects. This external review process has resulted, for example, in VA recognizing about a dozen diseases as presumed to be connected to exposure to Agent Orange and other herbicides used during the Vietnam War, and to the dioxin impurity some contained.

The National Academy of Sciences was established in 1863 with the signature of President Abraham Lincoln, to "investigate, examine, experiment, and report upon any subject of science or art" for agencies in the federal government. In 1970, the NAS created the IOM to provide independent, objective, authoritative, credible and timely scientific analyses on medical and health issues.

The US Congress, through US government agencies, regularly seeks the IOM's unique scientific advice on a broad range of health-policy issues. Their studies are conducted by independent committees of volunteer scientists composed of leading nationally and internationally recognized experts, selected by the IOM based on their expertise, good judgment and freedom from conflict of interests. The IOM requires that a committee's formal findings and recommendations are evidence-based whenever possible and noted as only expert opinion when that is not possible. Each IOM report undergoes extensive formal internal and peer review by external experts who are anonymous to the committee, and whose names are revealed only once the study is published.

Congressionally Mandated NAS/ IOM Veterans' Health Reviews. The NAS/ IOM's highly developed formal review process has proven invaluable to VA for establishing fair, scientifically based disability policies for veterans. Their reputation for objectivity, scientific integrity, and independence means that their reports stand as authoritative even when their findings fail to please all stakeholders. Since 1991, IOM has completed nineteen independent reviews of Gulf War health issues (see attachment). For evaluation of Gulf War-related health effects, Congress directed (in Public Laws 105-277 and 105-368) the NAS to "identify the biological, chemical, or other toxic agents, environmental or wartime hazards, or preventive medicines or vaccines to which members of the Armed Forces who served in the Southwest Asia theater of operations during the Persian Gulf War may have been exposed by reason of such service." Public Law 105-277 further required the NAS, for each substance or hazard considered, to determine, to the extent feasible, (1) whether a statistical association exists between exposure to the substance or hazard and the occurrence of illnesses, (2) the increased risk of the illness among exposed human or animal populations, and (3) whether a plausible biological mechanism or other evidence of a causal relationship between the exposure and illness exists.

VA RESPONSE TO PREVIOUS NAS COMMITTEE "GULF WAR & HEALTH" REPORTS

The 2000 Report. The initial 2000 NAS committee report in this series, "Gulf War & Health Volume 1," reviewed health effects from exposure to the four potential hazardous exposures related to the 1991 Gulf War. These included sarin, depleted uranium, vaccinations, and pyridostigmine bromide ("P.B.," a nerve agent protecting drug used by DoD). The report contained 13 findings, of which four indicated a positive association between some health outcome and the reviewed general risk factors. Many were obvious, such as an association between a large exposure to the military nerve agent sarin and severe health effects including death. Others were related to common side effects of drugs and vaccines seen among civilians or military personnel using these agents to protect their health.

Following review by a VA Task Force, VA determined that establishing new presumptions of service connection for any diseases based on the report findings was not necessary. This was primarily because the types and degree of exposures associated with long-term health effects described in the NAS committee report had either not occurred during the 1991 Gulf War (for example, severe, life-threatening and immediate nerve agent poisoning), or that the related health effects were transitory and short-lived (for example, a normal sore arm following a vaccination). Those findings were published in the Federal Register, as required by the relevant statutes that established this process.

The 2002 NAS Report. The second 2002 NAS committee report, "Gulf War & Health Volume 2," reviewed health effects from exposure to pesticides and solvents used during the 1991 Gulf War. An important issue was that virtually all the pesticides and solvents used during that conflict were in common approved use throughout the civilian and military at that time. The report contained 77 findings, of which 21 indicated a positive association between a pesticide or a solvent and some general health outcome. These were primarily for various cancers and serious hematological disorders (e.g., leukemias, non-Hodgkin's lymphoma, multiple myeloma and aplastic anemia), subtle general neurological effects detected via neurobehavioral tests, and other health effects (e.g., reactive airway dysfunction syndrome, and allergic contact dermatitis).

Following review by a VA Task Force, VA determined that it was not necessary to establish new presumptions of service connection for any diseases based on the report findings. This was in part because the NAS committee findings were generally limited to long-term, chronic occupational exposures that do not directly correlate to potential hazards of service or exposure scenarios for the 1991 Gulf War. Furthermore, individuals who were chronically exposed to relatively high levels of these environmental hazards as part of their military occupation, whether or not during service in that war, may qualify under existing VA service connection policies for benefits for diseases resulting from such exposures. It should be pointed out that VA's decision to not establish any new presumptions does not alter existing claim procedures, nor does it prevent any veteran from establishing service connection for any disease that could be related to their service in the 1991 Gulf War. Rather, it merely means that each case must be decided on its facts and merits, as is currently the case for veterans from any era.

The 2004 NAS Sarin Update Report. In 2004, at the request of the Secretary of Veterans Affairs, a new NAS committee completed a special update on long-term health effects from exposure to the nerve agent sarin. The initial 2000 NAS committee report described above had concluded that available scientific evidence could not show an association between trace sarin exposure and subsequent long-term adverse health effects. In response, the Secretary of Veterans Affairs determined that there was not an adequate basis to support establishing presumptive service connection for any long-term health problems resulting from low-level sarin exposure.

After the completion of the 2000 NAS committee report, several new studies on sarin effects in laboratory animals were published that were not available to the NAS committee when they conducted their initial review, and which some saw as requiring a new look by the NAS committee. The new NAS committee reviewed 19 epidemiological studies of sarin health effects published since the earlier 2000 report, including studies of U.S. and U.K. veterans of the 1991 Gulf War potentially exposed at Khamisiyah, Iraq in 1991, of civilians exposed during the Japan sarin terrorist attacks in 1994 and 1995, and all the studies used in the earlier 2000 NAS committee report. They also reviewed over 100 animal studies.

The August 2004 NAS Sarin Update came to the same conclusions as the earlier 2000 report. In other words, and consistent with their earlier findings, the NAS committee was not able to find a scientific basis to associate any disease with exposure to low levels of sarin, based upon their exhaustive review of the relevant scientific literature.

The 2004 NAS Report. The third full NAS committee report, "Gulf War & Health Volume 3: Fuels, Combustion Products, and Propellants," contained nine positive findings on long-term health effects related to exposure to the reviewed agents. These included associations between exposure to combustion products (e.g., smog) and lung cancer, cancers of nasal cavity and nasopharynx, cancers of the oral cavity and oropharynx, laryngeal cancer, bladder cancer, low birth weight/intrauterine growth retardation and exposure during pregnancy, preterm birth and exposure during pregnancy, and incident asthma. They also reported an association between exposure to hydrazine rocket fuels and lung cancer. As with previous reports, an important point is that most of the agents considered were in common use throughout the civilian and military at the time of the 1991 Gulf War.

The NAS committee considered over 33,000 potentially relevant references, and focused on about 800 epidemiological studies on persistent health outcomes associated with exposure to oil-fire products, diesel-heater fumes, hydrogen sulfide (a specific combustion product), hydrazines and red fuming nitric acid (as rocket propellants), and gasoline and jet fuel. The committee pointed out that fuels and related combustion products are common pollutants with an abundant scientific health literature available for their review. Combustion products included ambient air pollution "smog," combustion products from motor vehicles, and fumes from stoves and heaters using a wide variety of fuels. Fuels included gasoline, kerosene, diesel and military fuels including JP-4, JP-5 and JP-8. Finally, to ensure a focus on information that would be the most relevant to veterans of the 1991 Gulf War, the committee emphasized studies of long-term rather than short-term health effects. A VA Task Force reviewing the new NAS committee report determined that new presumptive service connections were not warranted because none of the specific hazardous agents reviewed, or the exposure levels experienced by most Gulf War service members, were significantly different compared to U.S. civilians or to troops not deployed to the Gulf War.

The 2006 NAS Report "Volume 4: Health Effects of Serving in the Gulf War." The September 2006 fourth full NAS report reviewed peer-reviewed scientific literature on the health status of veterans of the 1991 Gulf War. The report was intended to inform VA about illnesses and clinical issues including possible relevant treatments, which might have been overlooked among this population, regardless of the specific underlying cause. It documented increased rates of certain illnesses among Gulf War veterans, based on a review of 850 epidemiological and other studies of this group, which they selected from among over 4,000 potentially relevant reports. They concluded that " VA and DoD have expended enormous effort and resources in attempts to address the numerous health issues related to the Gulf War veterans. The information obtained from those efforts, however, has not been sufficient to determine conclusively the origins, extent, and potential long-term implications of health problems potentially associated with veterans' participation in the Gulf War."

The NAS committee identified numerous serious limitations in existing epidemiological studies of Gulf War veterans, in large part due to the lack of veteran exposure data. However, they did "not recommend that more such studies be undertaken for the Gulf War veterans." Rather, the committee recommended "continued surveillance to determine whether there is actually a higher risk in Gulf War veterans" for illnesses that current research has identified as possibly appearing at higher rates among Gulf War veterans, specifically, brain and testicular cancer, ALS, birth defects, and post-deployment psychiatric conditions.

The NAS committee also concluded, "Every study reviewed by this committee found that veterans of the Gulf War report higher rates of nearly all symptoms examined than their nondeployed counterparts." Not surprisingly, they reported that symptom-defined "unexplained illnesses," consistent with Chronic Fatigue Syndrome, Fibromyalgia, Irritable Bowel Syndrome and Multiple Chemical Sensitivity, were the most common health problem reported in studies of Gulf War veterans. However, they concluded that "the results of that research indicate that although deployed veterans report more symptoms and more severe symptoms than their nondeployed counterparts, there is not a unique symptom complex (or syndrome) in deployed Gulf war veterans."

They also found that "Gulf War veterans consistently have been found to suffer from a variety of psychiatric conditions," including PTSD, anxiety, depression and substance abuse. Similarly, they found that available studies have "not demonstrated differences in cognitive and motor measures" in deployed versus non-deployed veterans, and show no apparent increase in risk of peripheral neuropathy, cardiovascular disease or diabetes. Finally, they reported difficulties in interpreting data on birth defects, and found little data supporting objective respiratory illnesses among Gulf War veterans. A VA Task Force reviewing the new NAS committee report determined that new presumptive service connections were not warranted because existing VA policies and procedures for disability compensation effectively cover veterans with these health problems. These include, for example, VA policies recognizing service connection for PTSD, and for service connection for difficult to diagnose or undiagnosed illnesses.

The 2006 Report "Infectious Diseases." The October 2006 fifth NAS report in this series, "Gulf War and Health Vol. 5: Infectious Diseases," reviewed published, peer-reviewed scientific and medical literature on long-term health effects from infectious diseases associated with Southwest Asia, including those diseases relevant to the 1991 Gulf War and to Operations Iraqi Freedom and Enduring Freedom ( OIF/ OEF). They identified over 20,000 potentially relevant scientific reports, and focused on 1,200 that had the necessary scientific quality.

They focused on nine infectious diseases that were 1) prevalent in Southwest Asia, 2) diagnosed among U.S. or other troops serving there, and 3) known to cause long-term health problems. They also focused upon those infectious diseases that appeared to be of special concern to veterans who served in Southwest Asia. These were Brucella (causing brucellosis); Campylobacter; Salmonella and Shigella (causing diarrheal disease); Coxiella burnetii (causing Q fever); Leishmania (causing leishmaniasis); Mycobacterium tuberculosis (causing tuberculosis); Plasmodia (spp) (causing malaria) and West Nile Virus (causing West Nile fever). They selected these from among about 100 naturally occurring pathogens that potentially could have infected U.S. troops in the 1991 Gulf War, or in OIF/ OEF. The NAS committee identified 34 different long-term health effects in their report that might appear weeks to years after initial infection, associated with these nine infectious diseases. Most if not all identified long-term health effects are well-known to be associated with the initial acute infection. A VA Task Force is currently reviewing the new NAS committee report to determine if new presumptive service connections are warranted.

OTHER REVIEWS ON GULF WAR VETERANS' HEALTH

• Armed Forces Epidemiological Board. U.S. Department of Defense, 1996, 1999, 2000, 2000.
• Goss Gilroy Inc. Canadian Epidemiological Study of Gulf War Veterans. 1998.
• The Rt Hon The Lord Lloyd of Berwick. Independent Public Inquiry on Gulf War Illnesses. 2004.
• U. S. Department of Veterans Affairs, Research Advisory Committee on Gulf War Veterans Illnesses, James Binns, Chair. Scientific Progress in Understanding Gulf War Veterans' Illnesses: Report and Recommendations, 2004.
• U.S. Department of Defense Special Oversight Board for Department of Defense Investigations of Gulf War Chemical and Biological Incidents. Final Report, 2000.
• U.S. Department of Defense. Report of the Defense Science Board Task Force on Persian Gulf War Health Effects, 1994.
• U.S. Department of Health & Human Services, National Institutes of Health Technology Assessment Workshop Panel. The Persian Gulf Experience and Health. 1994
• U.S. Government Accountability Office. Gulf War Illnesses: DOD's Conclusions About U.S. Troops' Exposure Cannot Be Adequately Supported. 2004.
• U.S. Presidential Advisory Committee on Gulf War Veterans' Illnesses: Interim Report. 1996.
• U.S. Presidential Advisory Committee on Gulf War Veterans' Illnesses: Final Report. 1996.
• U.S. Presidential Advisory Committee on Gulf War Veterans' Illnesses: Special Report, 1997.
• United Kingdom Parliamentary Office of Science and Technology. Gulf war illnesses: Dealing with the Uncertainties. 1997.
• United States Senate, Committee on Veterans' Affairs, Report of the Special Investigation Unit on Gulf War illnesses. 1998.

Collaboration with the VA Gulf War Veterans Research Advisory Committee. One of the most recent advisory groups on Gulf War veteran health issues has been the VA Research Advisory Committee ( RAC) on Gulf War Veterans Illnesses, chaired by Mr. James Binns. VA has been pleased with recent efforts with the RAC to lay the groundwork for improved research on Gulf War veterans' health. VA and the RAC have agreed to several important steps to improve the quality of VA's Gulf War research portfolio. The RAC has recommended scientific experts to serve as research review panel members of a new scientific merit review board. In addition, VA consults with the RAC regarding the relevancy of proposals that have been identified as being fundable. VA and the RAC will also work together to identify researchers who can partner with VA investigators.

VA RESEARCH ON GULF WAR VETERANS' HEALTH
VA's Office of Research and Development ( ORD) early on recognized that while there were few visible casualties associated with the 1991 Gulf War, many individuals returned from this conflict with unexplained medical symptoms and illnesses. To date, VA, DoD and the Department of Health and Human Services ( HHS) have funded a total of 330 projects pertaining to the health consequences of military service in the Gulf War, as described in Annual Reports to Congress on Federally Sponsored Research on Gulf War Veterans' Illnesses. Although the causes and successful treatment of GWVI remain illusive VA's ORD has committed to continued funding of relevant research in this area.

In addition, the Institute of Medicine recently announced (in a report described in more detail later) that Gulf War and other combat veterans may be at increased risk for amyotrophic lateral sclerosis ( ALS, also known as Lou Gehrig's disease) as a result of their service. Accordingly, VA's ORD is supporting a research portfolio composed of studies dedicated to understanding chronic multi-symptom illnesses, long-term health effects of potentially hazardous substances to which Gulf War veterans may have been exposed to during deployment and conditions and/or symptoms that may be occurring with higher prevalence in Gulf War veterans, such as ALS, multiple sclerosis and brain cancer.

While VA, DoD and HHS funds its Gulf War research independently, each closely coordinates its efforts with the others to avoid duplication of effort and to foster the highest standards of competition and scientific merit review for all research on illnesses in Gulf War veterans. The Research Subcommittee of the Deployment Health Work Group, which is a component of the VA/ DoD Health Executive Council, currently conducts this coordination. HHS participates in both the Deployment Health Work Group and its Research Subcommittee.

ALS is a rare, progressive and nearly always fatal disease of the nervous system. About 5 to 10 percent of cases appear to be inherited but the cause of the remaining 90 to 95 percent of cases is not known. Although certain environmental exposures have been considered as potential causes of ALS, none have been clearly tied to this disease.

In December 2001, based on pre-publication announcements from two studies suggesting that Gulf War veterans were at greater risk for ALS, VA announced that it would explore options for compensating veterans who served in the Gulf War and who subsequently develop amyotrophic lateral sclerosis ( ALS). VA in 2001 implemented a policy of referring all Gulf War ALS claims to VA's Central Office for special review.

More recent scientific publications suggest that all veterans may be at greater risk of developing ALS. A 2005 study published in the journal Neurology (Weisskopf et al.) evaluated ALS risk among veterans from World War 2, and the Korean and Vietnam Wars, and reported as a group these veterans were at significantly greater risk for ALS compared to civilians. The two studies that supported VA's ALS policy for Gulf War veterans were published in 2003, and also suggested that veterans from the 1991 Gulf War were at similarly greater risk for ALS (Horner et al., Haley).

In response to the suggestion that all veterans might be at an increased risk of ALS, in May 2005, VA contracted with the NAS/IOM to evaluate the scientific basis of all relevant studies. In their November 10, 2006, report the IOM committee concluded that although there are significant limitations to these studies, there is "limited and suggestive evidence of an association between military service and later development of ALS."

What the IOM Found. Following a thorough review of relevant scientific literature, the IOM committee in their November 2006, report identified one "high-quality cohort study that adequately controlled for confounding factors and reported a relationship between serving in the military and later developments of ALS" (the Weisskopf study). They also found "three related studies [that] supported the association" but which were of variable quality (which included the Gulf War veteran studies).

They concluded, "On the basis of its evaluation of the literature, the committee concludes that there is limited and suggestive evidence of an association between military service and later development of ALS." This is the IOM's weakest positive category of association for a health effect. However, the committee concluded, "[a]lthough the study has some limitations . . . overall it was a well-designed and well conducted study. It adequately controlled for confounding factors (age, cigarette use, alcohol consumption, education, self-reported exposure to pesticides and herbicides, and several main lifetime occupations)."

A VA Task Force consisting of the Under Secretaries for Health and for Benefits, the OGC, and the DAS for Policy and Planning was established to review the new IOM report.

VA Research on ALS. Although presently, there is no effective treatment for ALS, ORD currently supports a broad research portfolio dedicated to understanding the cause(s) and treatment for this devastating disease. Recent advances in neurological research may allow for the development of strategies to promote the restoration of nerve function. The development of novel strategies and technologies for the development and delivery of therapeutics for ALS patients remains an important goal in ALS research. ORD-funded projects are directed towards improving our understanding of the continuum of the development, progression, treatment and prevention of ALS."

Several VA investigators are conducting research on ALS as it relates to military service during the first Gulf War. This work includes identification of biological markers to identify cases of ALS, examination of the effects of pesticides and insecticides used during the Gulf War on the progression of ALS and examination of the prevalence of ALS in Gulf War veterans. One project is examining the overall and cause-specific mortality risk of ALS, multiple sclerosis or brain cancer in a group of more than 620,000 Gulf War veterans and assessing the demographic, military and in-theater exposure characteristics associated with the risk of deaths from these diseases.

VA researchers are also studying new ways to selectively increase the ability of therapeutic agents to enter the brain and spinal cord without compromising the blood brain barrier. While this barrier protects the central nervous system from harmful agents, it also limits the ability of many therapeutic agents to enter the brain.

VA investigators have ongoing research projects studying the use of stem cell transplants as a means to restore lost function following the loss of neurons associated with ALS, Alzheimer's disease, Parkinson's disease, spinal cord injury and stroke. Stem cells derived from neurons, as well as from hematopoietic (blood) cells, are being studied. It is hoped that these stem cells will mature into adult neurons and replace damaged neurons. In addition, VA investigators are examining gene therapy to deliver growth factors and other small molecules needed for regeneration and/or protection of the brain and spinal cord.

VA investigators are also examining the use of a neuromotor prosthesis to enhance communication and increase independence for veterans suffering from ALS. A neuromotor prosthesis is a brain-computer interface that uses an electrode that picks up brain signals and sends them to a computer for decoding. The brain signals are translated into commands to power electronic or robotic devices, or to communicate via word processing, e-mail or the internet. VA researchers have already demonstrated the potential usefulness of this technology in an ALS patient and are developing multi-site studies designed to improve this technology and improve the lives of individuals suffering from this disease and their families.

ORD also supports a national registry of veterans with ALS to identify, as completely as possible, all veterans with ALS and to collect data for studies examining the causes of ALS. The registry is designed to track the health status, collect DNA samples and clinical information and provide a mechanism for VA to inform veterans with ALS about research studies for which they may be eligible to participate. The registry will provide VA with a valuable mechanism for involving veterans in clinical trials and other studies that may yield improved outcomes for ALS. In addition, data gathered as part of the registry has the potential to benefit not only veterans, but also the larger community of individuals with ALS.

Other exciting ALS projects supported by ORD include a 15-site clinical trial to determine the tolerability and efficacy of sodium phenylbutyrate as a new therapy for ALS, and a study examining a compound that has been shown to delay the onset of ALS symptoms in animal models of the disease. Finally, ORD supports a cooperative effort to collect and store high-quality biological specimens donated by veterans diagnosed with ALS for use in biomedical research.

Anthrax Vaccine Research. ORD supports a study utilizing state of the art technology to investigate and characterize the response of human cells to anthrax vaccination and other agents. This study represents a novel approach to identifying underlying mechanisms operating in specific cell populations which are influenced in response to exposure to anthrax vaccination. It is hoped that this study will disclose biological processes that may improve our understanding of the illnesses affecting Gulf War veterans.

LESSONS LEARNED
VA developed a wide range of health care and research programs to benefit veterans of the 1991 Gulf War. Lessons learned from this process have provided significant benefits to new combat veterans returning today from Southwest Asia. Both groups of combat veterans - those who served in the 1991 Gulf War and those who are serving in OEF and OIF, remain a high priority for VA. This issue of a possible increased risk for being diagnosed with ALS for all service members remains a large concern for VA. In response, VA has initiated new research on this possibility, and is considering how to respond to findings of the recent IOM report on this issue.