Executive Summary
More than seventeen years have
passed since the United States and its
international allies liberated
Kuwait from the grip of Saddam
Hussein's Iraqi military forces in the 1990-1991
Gulf War. Despite the
swift and decisive victory
achieved in Operation Desert Storm, at least one
fourth of the nearly 700,000
U.S. military personnel who
served in the war have experienced a complex of
difficult and persistent
health problems since their
return home. Illness profiles typically include
some combination of chronic
headaches, cognitive
difficulties, widespread pain, unexplained
fatigue, chronic diarrhea, skin rashes,
respiratory problems, and other
abnormalities. This symptom complex, now
commonly referred to as
Gulf War illness, is not
explained by routine medical evaluations or by
psychiatric diagnoses, and has
persisted, for many veterans, for
17 years. While specific symptoms can vary
between individuals, a
remarkably consistent illness
profile has emerged from hundreds of reports and
studies of different Gulf
War veteran populations from
different regions of the U.S., and from allied
countries.
For many years, diverse views
about the cause or causes of Gulf war illness
have been put forward and
vigorously debated. Hundreds of
burning oil well fires that turned the Kuwaiti
sky black with smoke,
dramatic reports of
uranium-tipped munitions, sandstorms, secret
vaccines, and frequent chemical alarms,
along with the government's
acknowledgment of nerve agent releases in
theater, led many to believe that
veterans were suffering from
effects of hazardous exposures that occurred
during their deployment.
Government officials and special
committee reports maintained that there was
little evidence that this was
the case, and noted that veterans
returning from other wars have often experienced
chronic health
problems related to the stressful
circumstances of serving in a war zone. All
sides called for research to
better understand the problem.
Multiple official investigations were launched
and hundreds of research
studies funded.
In 1998, the U.S. Congress
mandated the appointment of a public advisory
panel of independent scientists
and veterans to advise on federal
research studies and programs to address the
health consequences of the
Gulf War. The Research Advisory
Committee on Gulf War Veterans' Illnesses was
appointed by the
Secretary of Veterans Affairs in
2002 and directed to evaluate the effectiveness
of government research in
addressing central questions on
the nature, causes, and treatments of Gulf
War-related illnesses.
According to its charter, the
guiding principle for the Committee's work is
the premise that the
fundamental goal of all Gulf
War-related government research is to improve
the health of Gulf War
veterans, and the choice and
success of federal Gulf War research should be
judged accordingly.
The Committee has convened public
meetings on a regular basis to consider the
broad spectrum of
scientific research,
investigative reports, and government research
activities related to the health of Gulf
War veterans. In addition to
annual reports on Committee meetings and
activities, it has periodically
issued formal scientific
recommendations and reports. The Committee's
last extended report,
Scientific
Progress in Understanding Gulf
War Veterans' Illnesses
, issued in 2004, provided findings
and
recommendations on topics the
Committee had considered up to that time. The
present report provides a
comprehensive review of
information and evidence on topics reviewed by
the Committee since that time,
as well as additional information
on topics considered in the 2004 report.
The central focus of this report
is Gulf War illness, the multisymptom condition
that affects veterans of
the 1990-1991 Gulf War at
significantly elevated rates. Despite
considerable government, scientific, and
media attention, little was
clearly understood about Gulf War illness for
many years. Now, 17 years after
the war, the extensive body of
scientific research and government
investigations that is currently available
provides the basis for an
evidence-based assessment of the nature and
causes of Gulf War illness. As
described throughout the report,
scientific evidence leaves no question that Gulf
War illness is a real
condition with real causes and
serious consequences for affected veterans.
Research has also shown that
this pattern of illness does not
occur after every war and cannot be attributed
to psychological stressors
during the Gulf War.
Although Gulf War illness is the
most prominent and widespread issue related to
the health of Gulf War
veterans, it is not the only one.
Additional issues of importance include
diagnosed medical and
psychiatric conditions affecting
Gulf War veterans, and questions related to the
health of veterans' family
members.
Section 1 of this report provides
an overview of information related to the
prevalence and
characteristics of Gulf War
illness, and other health issues, from the large
body of Gulf War
epidemiologic research.
Section 2 addresses evidence
related to the causes of Gulf War illness,
including
what has been learned about
effects of psychological stressors, oil well
fires, depleted uranium, and other
exposures of possible concern,
and compares the weight of evidence related to
each exposure as a cause
or contributor to Gulf War
illness.
Section 3 addresses the nature of
Gulf War illness, reviewing research
on biological findings associated
with Gulf War illness and its relationship with
multisymptom conditions
found in the general population.
Section 4 reviews research
programs sponsored by federal agencies to
address Gulf War-related health
issues. Research recommendations provided in
relation to topics
considered in each section are
summarized and prioritized in Section 5 of the
report.
Gulf War research has posed a
complex scientific challenge for researchers.
Most obviously, Gulf War
illness does not fit neatly into
well-established categories of disease. The
underlying pathophysiology of
Gulf War illness is not apparent
from routine clinical tests, and the illness
appears not to be the result of a
single cause producing a
well-known effect. There are relatively few
sources of objectively measured
data for studying Gulf War
illness or its association with events and
exposures in the Gulf War. Some
observers have suggested that
these complexities pose too difficult a
challenge, and that it is unlikely that
the nature and causes of Gulf War
illness can ever be known. On the contrary, the
Committee has found
that the extensive scientific
research and other diverse sources of
information related to the health of Gulf
War veterans paint a cohesive
picture that yields important answers to basic
questions about both the
nature and causes of Gulf War
illness. These, in turn, provide direction for
future research that is urgently
needed to improve the health of
Gulf War veterans.
Epidemiologic Research: What is
Gulf War Illness and How Many Veterans Are
Affected?
Gulf War illness refers to the
complex of symptoms that affects veterans of the
1990-1991 Gulf War at
significantly excess rates. It is
characterized by multiple diverse symptoms not
explained by established
medical diagnoses or standard
laboratory tests, symptoms that typically
include a combination of memory
and concentration problems,
persistent headache, unexplained fatigue, and
widespread pain, and can also
include chronic digestive
difficulties, respiratory symptoms, and skin
rashes. A similar profile of excess
symptoms has been described in
every study of U.S. Gulf War veterans from
different regions and units,
and in Gulf War veterans from the
United Kingdom and other allied countries.
Gulf War illness is not the only
health condition related to Gulf War service,
but it is by far the most
common. Gulf War illness
prevalence estimates vary with the specific case
definition used. Studies
consistently indicate, however,
that an excess of 25 to 32 percent of veterans
who served in the 1990-
1991 Gulf War are affected by a
complex of multiple symptoms, variously defined,
over and above rates
in contemporary military
personnel who did not deploy to the Gulf War.
That means that between
175,000 and 210,000 of the nearly
700,000 U.S. veterans who served in the
1990-1991 Gulf War suffer
from this persistent pattern of
symptoms as a result of their wartime service.
Research has not supported early
speculation that Gulf War illness is a
stress-related condition. Large
population-based studies of Gulf
War veterans consistently indicate that Gulf War
illness is not the result
of combat or other deployment
stressors, and that rates of posttraumatic
stress disorder (PTSD) and other
psychiatric conditions are
relatively low in Gulf War veterans. Gulf War
illness differs fundamentally
from trauma and stress-related
syndromes that have been described after other
wars. No Gulf War
illness-type problem, that is, no
widespread symptomatic illness not explained by
medical or psychiatric
diagnoses, has been reported in
veterans who served in Bosnia in the 1990s or in
current conflicts in Iraq
and Afghanistan.
Epidemiologic studies indicate
that rates of Gulf War illness vary in different
subgroups of Gulf War
veterans. Gulf War illness
affects veterans who served in the Army and
Marines at higher rates than
those in the Navy and Air Force,
and enlisted personnel more than officers.
Studies also indicate that
Gulf War illness rates differ
according to where veterans were located during
deployment, with highest
rates among troops who served in
forward areas. More specifically, studies
consistently show that the
rate of Gulf War illness is
associated with particular exposures that
veterans encountered during
deployment.
Identified links between
veteran-reported exposures and Gulf War illness
have raised a great deal of
interest, but have also been the
source of considerable confusion. The use of
self-reported exposure
information raises a number of
concerns, most obviously in relation to recall
bias. These concerns
emphasize the importance of
assessing findings across a broad spectrum of
studies, rather than relying on
results from individual studies,
and of evaluating the impact of recall and other
information bias on study
results where possible.
The Committee identified an
additional problem that has had a profound
effect on epidemiologic study
results and their interpretation.
Exposures assessed in Gulf War studies are
highly correlated, that is,
veterans who had one type of
exposure also usually had many others. In
analyzing the effects of any
single exposure during the war,
it is essential that effects of other exposures
be considered and adjusted
for, to avoid the well-known
problem of "confounding," or confusing the
effects of multiple exposures
with one another. Many Gulf War
epidemiologic studies failed to control for
confounding effects,
yielding illogical results that
made it appear as if all, or nearly all, wartime
exposures caused Gulf War
illness. In contrast, adjusted
results―that is, those that controlled for
effects of other exposures in
theater―consistently identified a
very limited number of significant risk factors
for Gulf War illness.
The Urgent Need for Effective
Treatments for Gulf War Illness
Gulf War illness has persisted
for a very long time for most ill veterans―over
seventeen years for many.
Studies indicate that few
veterans with Gulf War illness have recovered
over time and only a small
minority have substantially
improved. The federal Gulf War research effort
has yet to provide tangible
results in achieving its ultimate
objective, that is, to improve the health of
Gulf War veterans. Few
treatments have been studied and
none have been shown to provide significant
benefit for a substantial
number of ill veterans.
Treatments that are effective in
improving the health of veterans with Gulf War
illness are urgently
needed. In recent years,
Congressional actions have led to promising
initiatives in this effort at both the
Department of Defense (DOD) and
the Department of Veterans Affairs (VA). At DOD,
the Office of
Congressionally Directed Medical
Research Programs has developed an innovative
program aimed at
identifying treatments and
diagnostic tests for Gulf War illness. The
program funded a limited number of
new treatment studies in 2007 and
has invited proposals for additional studies to
be funded in 2009. In
addition, VA has sponsored a
center of excellence for Gulf War research at
the University of Texas
Southwestern, focused on
identifying specific biological abnormalities
that underlie Gulf War illness that
can be targeted for treatment.
Research to identify effective treatments for
Gulf War illness has been
given highest priority by the
Committee and requires expanded federal support.
Other Health Issues Affecting
Gulf War Veterans
Although Gulf War illness has
been the most prominent health issue associated
with military service in
the 1990-1991 Gulf War, a number
of other health issues are extremely important.
Studies have indicated
that veterans of the 1990-1991
Gulf War have developed amyotrophic lateral
sclerosis (ALS) at twice the
rate of nondeployed veterans of
the same era. Gulf War veterans who were
downwind from nerve agent
releases resulting from weapons
demolitions at Khamisiyah, Iraq, in March of
1991, have also been found
to have twice the rate of death
due to brain cancer as other veterans in
theater. Recent studies have
suggested that excess cases of
ALS have declined in recent years, but the
seriousness of both ALS and
brain cancer are clear causes for
concern and require continued monitoring for the
foreseeable future.
These findings also highlight the
need for information on rates of other diagnosed
diseases, particularly
neurological diseases and
cancers, which have only minimally been assessed
in Gulf War veterans.
Multiple studies have reported
that rates of PTSD and other psychiatric
disorders are higher in Gulf War
veterans than in nondeployed era
veterans but are, overall, substantially lower
than in veterans of other
wars.
Hospitalization and mortality
studies have identified only limited differences
between Gulf War and
nondeployed era veterans. Early
U.S. mortality studies indicated that Gulf War
veterans had higher death
rates due to accidents, and
somewhat lower disease-related mortality rates.
Although identified
differences appeared to diminish
in the years after the war, the most recent year
for which comprehensive
mortality information has been
reported for U.S. Gulf War veterans is 1997.
Given concerns about
diseases of longer latency, it is
extremely important that current
disease-specific mortality rates for U.S.
Gulf War veterans be made
publicly available, and reported on a regular
basis.
For many years, concerns have
been raised about rates of birth defects in Gulf
War veterans' children and
anomalous health problems in
their family members. Large population-based
studies in the U.S. and the
U.K. have provided some evidence
of excess rates of several types of birth
defects among children born
to Gulf War veterans, in
comparison to nondeployed era veterans. The
specific types of birth defects
identified have differed in
different studies, however, and rates, overall,
have been in the normal range
expected in the general
population. Phase III of VA's large U.S.
National Survey of Gulf War Era
Veterans and their Families
included clinical evaluations of veterans'
spouses and children. On clinical
evaluation, no notable
differences were identified between spouses of
Gulf War and nondeployed
veterans. Findings from clinical
evaluations of veterans' children have not been
reported from this study,
however. Further, no studies have
provided comprehensive information on the health
of Gulf War
veterans' children, including
rates of diagnosed conditions, symptomatic
illness, and learning and
behavioral disorders.
What Caused Gulf War Illness?
Review of Evidence Relating Gulf War Illness to
Experiences and Exposures
During Deployment
In addition to the many physical
and psychological challenges common to other
wartime deployments,
military personnel who served in
the 1990-1991 Gulf War were exposed to a long
list of potentially
hazardous substances. Many
possible "causes" of Gulf War illness have been
suggested and even
promoted in different quarters
since the war. Understanding the causes of Gulf
War illness has been
particularly challenging because
of the lack of hard data on individual exposures
in theater. Efforts by
early government and scientific
panels to address this issue were also limited
by the sparsity of scientific
research information on the
health of Gulf War veterans for the first 10
years after the war.
This is no longer the case today,
as a result of the extensive number of
government investigations and
scientific studies conducted to
better understand events of the Gulf War and
their association with Gulf
War illness. Government reports
have provided important insights into the types
and patterns of
exposures encountered by Gulf War
military personnel. The large number of
epidemiologic and clinical
studies of Gulf War veterans also
allow assessment of associations between Gulf
War experiences and
chronic health problems across a
broad spectrum of veteran groups and research
designs. In addition,
toxicological studies conducted
in recent years have provided extensive
information on biological effects
of Gulf War-related exposures
that were previously unknown. The Committee
found that epidemiologic
research on Gulf War veterans,
assessed across diverse study designs and
populations, provided clearer
and more consistent findings than
had previously been assumed. When combined with
what has been
learned about patterns of
exposures in theater and findings from
toxicological research, a coherent picture
emerges about the most likely
causes of Gulf War illness.
The Committee used a standardized
approach for evaluating available evidence
related to psychological
stressors in theater and each of
the other deployment-related hazards of possible
concern. Three major
categories of evidence were
considered. First, the Committee reviewed what
is known about the extent
and patterns of veterans'
exposure to each potential hazard. Second, the
Committee reviewed the broad
spectrum of available scientific
research to determine what is known, in general,
about health effects of
each exposure. This included
consideration of epidemiologic and clinical
studies of human populations,
and laboratory studies conducted
in animal models. Third, the Committee reviewed,
in detail, results
from the many studies of Gulf War
veterans that assessed associations between
symptom complexes and
the exposure in question.
Individually, single studies or
types of information might suggest that a
specific exposure
could
have
caused Gulf War illness. But it
is important to consider evidence of all types
and studies from all sources
to determine what the evidence
most clearly indicates
did
cause Gulf War
illness. Of the many
experiences and exposures
associated with Gulf War service, studies of
Gulf War veterans consistently
implicate only two wartime
exposures as significant risk factors for Gulf
War illness: use of
pyridostigmine bromide (PB) pills
as a nerve agent protective measure, and use of
pesticides during
deployment. This is consistent
with what is known about the extent and patterns
of these exposures in
theater, and with general
information from other human and animal studies.
Studies of Gulf War
veterans have also consistently
indicated that psychological stressors during
deployment are
not
significantly associated with
Gulf War illness. For several other deployment
exposures an association
with Gulf War illness cannot be
ruled out, due to inconsistencies or limitations
of available information.
Remaining exposures appear
unlikely, from available evidence, to have
caused Gulf War illness for the
majority of affected veterans.
Psychological stress.
Studies of Gulf War veterans
consistently indicate that serving in combat and
other psychological stressors
during the war are not significantly associated
with Gulf War illness, after
adjusting for effects of other
wartime exposures. Time-limited biological
effects of psychological
stressors have long been
described in human studies, and more extreme
psychological stressors and
trauma can lead to chronic
psychiatric disorders such as PTSD. Combat and
extreme psychological
stressors were less widespread
and less sustained in the Gulf War than in other
wars, including current
Middle East deployments, and PTSD
rates are lower in Gulf War veterans than in
veterans of other wars.
Population-based studies
generally indicate that between three and six
percent of Gulf War veterans are
diagnosed with PTSD and that the
large majority of veterans with Gulf War illness
have no psychiatric
disorders. Serving in combat and
other wartime stressors are associated with
higher rates of PTSD in
Gulf War veterans, but not with
higher rates of Gulf War illness.
Kuwaiti oil well fires.
Widespread exposure to smoke from the
Kuwaiti oil well fires was unique to
military service in the 1991 Gulf
War, and most prominently affected ground troops
in forward locations.
Epidemiologic findings relating
oil well fire smoke exposure to Gulf War illness
have been mixed,
although a dose-response effect
has been identified by several studies. There is
little information from
human or animal research to
indicate whether intense exposure to petroleum
smoke or vapors can lead to
persistent multisymptom illness.
Although studies of Gulf War veterans do not
provide consistent
evidence that exposure to oil
fire smoke is a risk factor for Gulf War illness
for most veterans, questions
remain about effects for
personnel located in close proximity to the
burning wells for an extended period.
Limited findings from
epidemiologic studies indicate that higher-level
exposures to smoke from the
Kuwaiti oil well fires may be
associated with increased rates of asthma in
Gulf War veterans, and that an
association with Gulf War illness
cannot be ruled out.
Depleted uranium (DU).
Low-level exposure to spent DU
munitions and dust is thought to have been
widespread during the Gulf War
and was most prominent among ground troops in
forward locations.
Recent animal studies have
demonstrated acute effects of soluble forms of
DU on the brain and behavior,
but persistent effects of short
term, low-dose exposures like those encountered
by the majority of Gulf
War veterans have only minimally
been assessed. There is little information from
Gulf War or other
human studies concerning chronic
symptomatic illness in relation to DU or uranium
exposure. Exposure
to DU in post-Gulf War
deployments, including current conflicts in the
Middle East, has not been
associated with widespread
multisymptom illness. This suggests that
exposure to DU munitions is not
likely a primary cause of Gulf
War illness. Questions remain about long-term
health effects of higherdose
exposures to DU, however,
particularly in relation to other health
outcomes.
Vaccines.
Receipt of multiple vaccines over
a brief time period is a common feature of
overseas
military deployments. About
150,000 Gulf War veterans are believed to have
received one or two
anthrax shots, most commonly
troops who were in fixed support locations
during the war. Although
recent studies have demonstrated
that the anthrax vaccine is highly reactogenic,
there is no clear evidence
from Gulf War studies that links
the anthrax vaccine to Gulf War illness. Taken
together, limited findings
from Gulf War epidemiologic
studies, the preferred administration to troops
in support locations, and the
lack of widespread multisymptom
illness resulting from current deployments,
combine to indicate that the
anthrax vaccine is not a likely
cause of Gulf War illness for most ill veterans.
However, limited evidence
from both animal research and
Gulf War epidemiologic studies indicates that an
association between Gulf
War illness and receipt of a
large number of vaccines cannot be ruled out.
Pyridostigmine bromide (PB).
Widespread use of PB as a protective
measure in the event of nerve
gas exposure was unique to the
1990-1991 Gulf War. Pyridostigmine bromide is
one of only two
exposures consistently identified
by Gulf War epidemiologic studies to be
significantly associated with
Gulf War illness. About half of
Gulf War personnel are believed to have taken PB
tablets during
deployment, with greatest use
among ground troops and those in forward
locations. Several studies have
identified dose-response effects,
indicating that veterans who took PB for longer
periods of time have
higher illness rates than
veterans who took less PB. In addition, clinical
studies have identified
significant associations between
PB use during the Gulf War and neurocognitive
and neuroendocrine
alterations identified many years
after the war. Taken together, these diverse
types and sources of
evidence provide a consistent and
persuasive case that use of PB during the Gulf
War is causally
associated with Gulf War illness.
Pesticides.
The widespread use of multiple types
of pesticides and insect repellants in the Gulf War
theater is credited with keeping
rates of pest-borne diseases low. Pesticide use,
assessed in different
ways, is one of only two
exposures consistently identified by Gulf War
epidemiologic studies to be
significantly associated with
Gulf War illness. Multisymptom illness profiles
similar to Gulf War illness
have also been associated with
low-level pesticide exposures in other human
populations. In addition,
Gulf War studies have identified
dose-response effects, indicating that greater
pesticide use is more
strongly associated with Gulf War
illness than more limited use. Pesticide use
during the Gulf War has
also been associated with
neurocognitive deficits and neuroendocrine
alterations in Gulf War veterans in
clinical studies conducted many
years after the war. Taken together, all
available sources of evidence
combine to support a consistent
and compelling case that pesticide use during
the Gulf War is causally
associated with Gulf War illness.
Nerve agents
.
There have been no reports that
U.S. forces encountered large-scale, high-dose
exposures to chemical weapons
during the Gulf War, but concerns have emerged
related to possible longterm
effects of low-dose nerve agent
exposures. Recent animal studies have identified
brain, autonomic,
behavioral, neuroendocrine, and
immune effects of low-level sarin exposure that
were previously
unknown. Studies of individuals
exposed to symptomatic but sublethal doses of
sarin in Japanese
terrorist incidents in the 1990s
have identified central nervous system effects
that have persisted for many
years. The extent of low-level
exposure to nerve agents during the Gulf War,
however, is unclear.
Monitoring equipment used by U.S.
forces had little capacity to detect nerve
agents at levels that did not
cause immediate symptoms. The
Department of Defense estimates that about
100,000 U.S. troops may
have been exposed to low levels
of nerve agents following weapons demolitions in
March of 1991 at
Khamisiyah, Iraq, but questions
have been raised about the models used to
determine who was exposed,
and at what levels. It is also
unclear whether additional low-level exposures
may have occurred in other
locations. Veterans'
self-reported experiences concerning low-level
nerve agent exposure in the Gulf
War are particularly uncertain,
and findings from epidemiologic studies linking
chemical agents with Gulf
War illness are inconsistent.
Studies of Gulf War veterans have identified
increased rates of brain cancer
and measurable differences in
brain structure and function that relate, in a
dose-response manner, to
modeled nerve agent exposure
levels resulting from the Khamisiyah
demolitions. Findings from Gulf
War clinical studies, and from
other human and animal research, suggest that an
association between Gulf
War illness and low-level nerve
agent exposure cannot be ruled out, for whatever
subgroups of veterans
were exposed.
Infectious disease.
A substantial proportion of Gulf War
military personnel contracted acute
gastrointestinal and respiratory
infections during deployment, but there is
little information concerning
patterns of infection in theater
and no evidence of widespread chronic illness
resulting from those
infections. Atypical leishmania
infections were identified in a limited number
of veterans who served in
the 1990-1991 Gulf War, and a
much larger number of leishmaniasis cases have
been reported in
personnel serving in the current
Iraq War. Several studies have identified DNA
indicators of mycoplasma
infection in about 40 percent of
symptomatic Gulf War veterans, but questions
about testing methods
have not been adequately
addressed. Taken together, there is little clear
evidence implicating infectious
diseases as prominent causes of
Gulf War illness. Questions remain, however,
concerning the possibility
that some individuals with Gulf
War illness have undetected chronic leishmania
and mycoplasma
infections.
Other exposures in theater.
A number of other potentially
hazardous exposures in theater have been
suggested as causing or
contributing to Gulf War illness. These include
fine sand and airborne
particulates, exhaust from tent
heaters, other fuel exposures, solvents, and
freshly-applied CARC
(chemical agent resistant
coating) paint. For most, there is limited
evidence of the types considered for
other exposures. Available
information, however, suggests that these
exposures are not likely to have
caused Gulf War illness for most
affected veterans. Epidemiologic studies have
provided little clear
information linking any of these
exposures to Gulf War illness and most were not
most prevalent among
ground troops who were forward
deployed. Some, like sand, solvents, and fuel
exposures, have also been
widely encountered by personnel
in current Middle East deployments. Information
from human and
animal studies indicates that
fuel and solvent exposures can have neurological
effects compatible with
symptoms of Gulf War illness, but
neither has been associated with Gulf War
illness in studies of Gulf
War veterans.
Combinations of exposures.
Compared to the diverse types of
evidence available related to effects
of individual exposures, research
on effects of combinations of Gulf War-related
exposures is limited.
Gulf War studies consistently
indicate that exposures in theater were highly
correlated―that is, that
personnel most often experienced
individual exposures in connection with multiple
other exposures. This
includes correlations between use
of PB and pesticides and among different types
of pesticides. Animal
studies have identified
significant effects of exposure to combinations
of PB, pesticides and insect
repellants, sarin, and stress, at
dosage levels comparable to those experienced by
veterans during the Gulf
War. Diverse findings have been
reported in relation to chemical absorption,
metabolism, and biological
effects of mixtures of
neurotoxicants, which differ from those of
individual exposures. There is little
information from human studies,
however, including the many epidemiologic
studies of Gulf War
veterans, concerning combined
effects of Gulf War exposures.
A persuasive theoretical case can
be made that exposure to mixtures of neurotoxic
compounds in theater
are likely contributors to Gulf
War illness. Such a case would draw on the
consistency of evidence from
all sources indicating that both
PB and pesticides are significantly associated
with Gulf War illness, the
high correlation between troops'
use of PB and pesticides during deployment, and
synergistic effects
between these exposures
demonstrated by animal studies. Many of the
pesticides used in the Gulf War,
as well as PB and nerve agents,
exert toxic effects on the brain and nervous
system by altering levels of
acetylcholine, an important nerve
signaling chemical. Although such a case is
compelling, little evidence
is available from studies of Gulf
War veterans to indicate whether or not Gulf War
illness is associated
with combinations of these
exposures. This important possibility can and
should be fully evaluated in
Gulf War studies. Pending such
assessments, it is not possible to definitively
determine the extent to
which mixtures of cholinergic and
other neurotoxicant exposures during deployment
contributed to Gulf
War illness. Based on evidence
from toxicological research in animals and what
is known about patterns
of exposures during the Gulf War,
an association between Gulf War illness and
combined effects of
neurotoxicant exposures cannot be
ruled out.
There is almost no research to
indicate if other wartime exposures interact
synergistically with these
neurotoxic compounds or with one
another. That is, the biological effects of
different combinations of
PB, multiple pesticides,
low-level nerve agents, oil and dense smoke from
burning wells, DU dust, fuel
vapors, exhaust from tent
heaters, CARC paint, airborne particulates,
infectious agents, and receipt of
multiple vaccines, experienced
concurrently or over a brief time period, are
unknown. Many have
suggested that unknown and
difficult-to- characterize effects may have been
precipitated by an "exposure
cocktail" or "toxic soup" effect
during Gulf War deployment. While such a theory
is intriguing, there is
currently little evidence to
indicate whether or not such effects actually
occurred, and the extent to which
they may have contributed to Gulf
War illness.
What the Weight of Evidence Tells
Us About the Causes of Gulf War Illness
Seventeen years after the Gulf
War, answers to the question of what caused Gulf
War illness remain
vitally important. An extensive
amount of available information now permits an
evidence-based
assessment of the relationship of
Gulf War illness to the many experiences and
exposures encountered by
military personnel during the
Gulf War. The strongest and most consistent
evidence from Gulf War
epidemiologic studies indicates
that use of pyridostigmine bromide (PB) pills
and pesticides are
significant risk factors for Gulf
War illness. The consistency of epidemiologic
evidence linking these
exposures to Gulf War illness,
identified dose-response effects, findings from
Gulf War clinical studies,
additional research supporting
biological plausibility, and the compatibility
of these findings with known
patterns of exposure during
deployment, combine to provide a persuasive case
that use of PB pills and
pesticides during the 1990-1991
Gulf War are causally associated with Gulf War
illness. Gulf War
studies also consistently
indicate that psychological stressors during
deployment are
not
significantly
associated with Gulf War illness.
Evidence related to other
deployment-related exposures is not as abundant
or consistent as evidence
related to PB, pesticides, and
psychological stressors. For several wartime
exposures, there is some
evidence supporting a possible
association with Gulf War illness, but that
evidence is inconsistent or
limited in important ways.
Clinical studies of Gulf War veterans, studies
of other populations exposed to
sarin, and findings from animal
studies all suggest that low-level nerve agent
exposure can produce
persistent neurological effects
that may be compatible with symptoms of Gulf War
illness. Therefore, an
association between Gulf War
illness and low-level nerve agents cannot be
ruled out for those veterans
who were exposed. However,
inconsistencies in epidemiologic studies and
unreliable exposure
information preclude a clear
evaluation of the extent to which such exposures
occurred and may have
contributed to Gulf War illness.
Limited evidence from several sources also
suggests that an association
with Gulf War illness cannot be
ruled out in relation to combined effects of
neurotoxicant exposures,
receipt of multiple vaccines, and
exposure to the Kuwaiti oil fires, particularly
for personnel in close
proximity to the burning wells
for an extended period.
There is little reliable
information from Gulf War studies concerning an
association of DU or anthrax
vaccine to Gulf War illness. The
prominence of both exposures in more recent
deployments, in the
absence of widespread unexplained
illness, suggests these exposures are unlikely
to have been major
causes of Gulf War illness for
the majority of affected veterans. Fine blowing
sand, solvents, and fuel
exposures were also widely
encountered in both the 1990-1991 Gulf War and
in the current Iraq War and
results from studies of Gulf War
veterans have not supported an association
between these exposures and
Gulf War illness. All of the
exposures described can be hazardous in some
circumstances, however, and
some veterans may have
experienced adverse effects on a more limited
basis.
The Nature of Gulf War Illness:
Biological and Clinical Findings
in Gulf War Veterans
Although veterans' symptoms are
the most obvious and consistent indicators of
Gulf War illness, dozens
of research studies conducted by
multiple investigators have identified objective
measures that
significantly distinguish
veterans with Gulf War illness from healthy
controls. Identified differences
relate to structure and function
of the brain, function of the autonomic nervous
system, neuroendocrine
and immune alterations, and
variability in enzymes that protect the body
from neurotoxic chemicals.
These findings provide indicators
of diverse biological differences associated
with Gulf War illness, but
have not, as yet, provided
measures that can be used as diagnostic tests.
While scientific progress has
been made in understanding the
biological nature of Gulf War illness, important
work remains in
characterizing the specific
pathophysiological processes that underlie
veterans' symptoms. The
Committee reviewed the broad
spectrum of studies that have evaluated
biological and clinical parameters
in Gulf War veterans, focusing
most specifically on Gulf War illness.
Identified effects on the brain
and central nervous system
.
Multiple lines of research have
supported early indications that
service in the Gulf War, for some veterans,
resulted in long term effects
on the central nervous system.
Population-based studies of Gulf War veterans
have consistently
identified significantly excess
rates of symptom complexes suggestive of central
nervous system
abnormalities. Studies have also
indicated that Gulf War veterans developed
amyotrophic lateral sclerosis
(ALS) at twice the rate of
nondeployed era veterans, and that veterans
downwind from the Khamisiyah
munitions demolitions have died
from brain cancer at twice the rate of other
Gulf War veterans. Earlier
reports suggesting that Gulf War
illness is not associated with neurological
abnormalities generally
referred to the lack of
significant findings identified with standard
clinical evaluations and peripheral
nerve function testing. It is
important to distinguish the lack of findings in
these areas from the diverse
central nervous system effects
identified using specialized brain imaging
scans, neuropsychological
testing, and measures of balance
and audiovestibular function.
Neuroimaging studies.
Three research teams have identified
significant differences between veterans
with Gulf War illness and
controls using proton magnetic resonance
spectroscopy (MRS) scans of the
brain. Findings indicate that
symptomatic veterans have significantly reduced
functioning brain cell mass
in the brainstem, basal ganglia,
and hippocampus. Reduced neuronal function in
the left basal ganglia
was correlated with increased
central dopamine activity in one study.
Symptomatic Gulf War veterans
have also been reported to
exhibit alterations in overall and regional
cerebral blood flow, using
specialized SPECT scan analyses.
In addition, a significant correlation has been
reported between
reduced white matter volume in
Gulf War veterans and levels of nerve agent
exposures resulting from the
Khamisiyah weapons demolitions.
Preliminary results from three unpublished
federal Gulf War research
projects are also of great
interest, and will be reviewed in final form as
they become available. These
include early results from a
larger MRS study that appear not to support
earlier findings of reduced
neuronal function in the
brainstem and basal ganglia of symptomatic Gulf
War veterans. Preliminary
findings from an additional SPECT
study suggest that symptomatic Gulf War veterans
differ from healthy
controls in cerebral blood flow
responses to cholinergic challenge. Early
results from a third study
indicate that symptomatic Gulf
War veterans have significantly reduced total
white matter volume
compared to healthy controls. In
contrast to the diverse findings reported from
studies using specialized
brain imaging methods, few
abnormalities have been identified in
symptomatic veterans using
electroencephalogra ms (EEG),
computed tomography (CT) scans, or standard
magnetic resonance
imaging (MRI) of the brain.
Overall, of the seven identified
Gulf War research projects that evaluated brain
structure and function
using proton MRS, specialized
SPECT scans, and specialized MRI assessments,
six have identified
significant differences between
veterans with Gulf War illness and healthy
controls, and one identified no
case/control differences. An
additional study has identified significant
brain volume differences in Gulf
War veterans in relation to
modeled nerve agent exposures during the Gulf
War. These findings have
been important in documenting
brain alterations in Gulf War veterans, but have
often come from
relatively small studies that
assessed different types of abnormalities in
different areas. Additional
research is needed to determine
if these findings can be replicated and/or
further extended in larger
samples.
Neuropsychological studies.
Neuropsychological studies provide
objective measures of brain function
and have been used for many years
to quantify neurocognitive deficits resulting
from chemical exposures.
They constitute the largest body
of research on central nervous system function
in Gulf War veterans. A
wide variety of specialized tests
are used to assess cognitive domains that
include attention, executive
system functioning, motor skills,
visuospatial functioning, memory, and mood.
Changes in affect and
emotional functioning can be
symptoms of brain injury, and so are important
to measure in
neuropsychological tests. But
PTSD and other psychiatric conditions can
themselves affect
neurocognitive function, and so
must be appropriately controlled for when
analyzing test outcomes.
Research studies have
consistently identified significant differences
in neurocognitive function between
symptomatic Gulf War veterans and
healthy controls. These include differences on
tests of attention and
executive system functioning,
memory, visuospatial skills, psychomotor skills,
and mood and emotional
functioning. Some studies
indicate that symptomatic veterans display a
slowing of response speed that
affects their mental flexibility
across multiple cognitive domains. Identified
differences have generally
been modest, but have
consistently been significant and remained
significant after adjustments for
emotional functioning and
psychiatric disorders. Studies also indicate
that many symptomatic veterans
who report cognitive difficulties
do not have objectively measurable
neurocognitive deficits. Two studies
have identified subgroups of
symptomatic Gulf War veterans with more marked
neurocognitive
impairment on measures of memory,
attention, and response time, suggesting this
subgroup should be the
focus of additional study.
Studies have also evaluated
veterans' neurocognitive function in relation to
exposures during the Gulf
War. Significantly poorer
performance on tests of memory, attention, and
mood have been identified in
relation to self-reported
exposure to pesticides, PB, and chemical
weapons. Neurocognitive effects have
also been identified in relation
to modeled nerve agent exposures resulting from
the Khamisiyah weapons
demolitions. Department of
Defense-modeled nerve agent exposure levels were
significantly correlated
with slower performance on
psychomotor and visuospatial tasks in a
dose-response pattern―that is,
greater exposure was associated
with worse neurocognitive performance.
Autonomic nervous system
dysfunction
.
The autonomic nervous system
(ANS) is the part of the
nervous system that regulates
involuntary, or "automatic" physiological
activities. Autonomic pathology
can be associated with diverse
symptoms such as dizziness, weakness, digestive
abnormalities, and sexual
dysfunction. Autonomic function
is often assessed by determining effects of
physiological challenges on
ANS regulation of heart rate and
blood pressure. The Committee reviewed results
from seven published
studies and two additional
federal projects that assessed ANS function in
symptomatic Gulf War veterans.
Eight of nine projects identified
significant ANS differences between veterans
with Gulf War illness and
healthy controls. Several studies
demonstrated blunted autonomic responsivity to
physiological
challenges, for example, reduced
cardiovascular compensation in response to
orthostatic challenge on tilt
table testing. Studies have also
identified a general reduction in heart rate
variability in the high
frequency range among veterans
with Gulf War illness, observed over a 24-hour
period in one study and
during nighttime hours in
another. Although ANS differences have
consistently been reported in veterans
with Gulf War illness, specific
ANS alterations identified by different studies
have varied, as a result of
differences in study
characteristics and testing methods. Additional
comprehensive research is needed to
provide a clear characterization
of Gulf War illness-related autonomic
dysfunction.
Neuromuscular and sensory
findings
.
Symptoms reported by Gulf War
veterans frequently
include muscle pain and weakness,
or numbness and tingling sensations in the
extremities. Such
symptoms potentially indicate
abnormalities in peripheral nerve function
related to sensation and motor
function. Nine studies have
assessed peripheral sensory and neuromuscular
function in Gulf War
veterans. Overall, based on
standard clinical examination, electromyography,
and nerve conduction tests,
these studies have provided
little indication that veterans with Gulf War
illness are affected by
generalized polyneuropathies or
abnormal neuromuscular transmission. Three of
four studies that
evaluated sensory threshold
measures identified significantly higher (that
is, less sensitive) thresholds in
symptomatic compared to healthy
veterans, however. Two identified higher cold
sensory thresholds, and
one reported a higher threshold
for detecting light touch, suggesting that some
Gulf War veterans may
have subtle small sensory fiber
neuropathies. Consistent findings that Gulf War
veterans are not affected
by more generalized
polyneuropathies or neuromuscular abnormalities
indicate that veterans'
neuromuscular symptoms are not
attributable to overt muscle damage or
peripheral nerve pathology.
Neuroendocrine alterations.
A series of recent studies have
provided detailed evaluation of
hypothalamic- pituitary- adrenal
(HPA) axis functioning in Gulf War veterans.
Studies indicated that Gulf
War veterans are similar to
nondeployed veterans on baseline measures of
cortisol and ACTH
(adrenocorticotropi c hormone),
but had significantly greater suppression of
both hormones in response to
dexamethasone challenge. These
responses were significantly associated with
veterans' symptoms, most
prominently their musculoskeletal
symptoms, but were unrelated to combat exposure
or whether veterans
had PTSD. Cortisol suppression
was most pronounced in veterans who reported
using PB during
deployment. In addition, 24-hour
ACTH levels were significantly reduced among
Gulf War veterans who
did
not
have PTSD, and were
associated with veterans' use of pesticides and PB.
No HPA alterations
were associated with combat
stress, with other self-reported exposures
during deployment, or with PTSD
in Gulf War veterans. Overall,
these studies suggest that Gulf War service and
symptoms of Gulf War
illness are associated with a
unique profile of HPA alterations many years
after the war, effects that differ
from HPA findings associated with
other conditions, including PTSD. Identified
effects were
independent of combat stress, but
significantly associated with veterans' use of
PB and/or pesticides.
Vulnerability to neurotoxicants
.
A question often asked about Gulf
War illness is why some Gulf
War military personnel developed
chronic symptoms during and after deployment,
while others who
served along side them remained
well. It is well established that some people
are more vulnerable to
adverse effects of certain
chemicals than others, due to variability in
biological processes that neutralize
those chemicals, and clear them
from the body. The enzyme paraoxonase (PON1)
circulates in the blood
and hydrolyzes organophosphate
compounds such as pesticides and nerve agents,
converting them to
relatively harmless chemicals
that are then excreted. Individuals who produce
different types and
amounts of PON1 differ, sometimes
dramatically, in their ability to neutralize
different organophosphate
compounds. The Committee reviewed
results from four published studies and two
additional federal
projects that have assessed PON1
measures in Gulf War veterans. Five of the six
projects identified
significant PON1 differences that
were associated with Gulf War illness or, more
generally, with Gulf
War service. Specific findings
from these studies varied, however, reflecting
different types of data that
addressed different research
questions. Additional research is needed to
better characterize the precise
nature of the PON1-Gulf War
illness relationship. It is unknown if Gulf War
illness is linked to
biological variability in other
enzymes that protect the body from neurotoxic
exposures. Limited and
preliminary information from
three studies suggest a possible link between
Gulf War illness and
butyrylcholinestera se (BChE)
that may involve the subset of veterans who have
very low BChE activity
and also experienced specific
exposures during the war.
Immune parameters.
There has been little indication that
Gulf War service, overall, is associated with
increased rates of diagnosable
immune conditions, including autoimmune diseases
and allergies, or with
increased susceptibility to
infectious disease. A well-known hypothesis,
suggesting that Gulf War illness
is related to a systemic shift
favoring Th-2 type immunity, has not been
supported by studies of Gulf War
veterans. Veterans with Gulf War
illness have been shown to differ from healthy
controls on a number of
immune parameters, however. A
variety of specific differences have been
identified by individual
studies, and a number of
consistent findings have emerged. Results from
two studies, using different
methods in different groups of
symptomatic veterans, indicate that Gulf War
illness is associated with a
low-level, persistent immune
activation, reflected in elevated levels of the
cytokines IL-2, IFN-
γ and
IL-
10. Several studies have also
reported that NK cell numbers and/or cytotoxic
activity are significantly
reduced in veterans with Gulf War
illness. A fuller understanding of immune
function in ill Gulf War
veterans is needed, particularly
in veteran subgroups with different clinical
characteristics and exposure
histories.
Additional research and clinical
findings in Gulf War veterans.
Additional information
pertaining to biological and
clinical characteristics of symptomatic Gulf War
veterans is available from a
variety of clinical reports and
studies. Individual clinical studies have
provided several findings of
interest, such as increased
sensitivity to pain and elevated rates of
fibromyalgia in veterans with
musculoskeletal symptoms,
dyspepsia and persistent diarrhea similar to
irritable bowel syndrome in
veterans with gastrointestinal
symptoms, abnormal pulmonary function in a
subset of veterans with
respiratory symptoms, and
verification of rashes and other skin anomalies
in veterans with dermatological
symptoms. But overall, objective
indicators of disease are often not identified
in symptomatic Gulf War
veterans who are referred for
specialty evaluations. Clinical reports have
also not provided explanations
for identified problems, such as
the causes of veterans' persistent diarrhea or
rashes. One study evaluated
Gulf War veteran males and their
sexual partners who experienced a painful
burning reaction to the
veterans' seminal fluid, a
problem reported by about seven percent of Gulf
War veterans. Evaluations
indicated that about 40 percent
of the women had a hypersensitivity reaction to
the veterans' seminal
fluid, but provided no
explanation for the phenomenon, overall. In
general, very limited information is
available on health problems
specific to women veterans. Single studies have
reported that Gulf War
veteran women report elevated
rates of yeast and bladder infections and breast
lumps or cysts, but no
results are available from
medical evaluations.
Single studies have identified
additional significant differences between
symptomatic veterans and
controls on a number of specific
laboratory tests. These include elevated rates
of coagulation
abnormalities in symptomatic
veterans, an elevated proportion of symptomatic
veterans with
insertion/deletion polymorphisms
in the gene encoding for angiotensin- converting
enzyme, and
identification of atypical
circulating polyribonucleotides potentially
indicative of chromosome
alterations.
Future directions in identifying
physiological mechanisms that underlie Gulf War
illness.
To advance efforts to identify
effective treatments and diagnostic tests for
Gulf War illness, the
Committee has recently expanded
its work to review areas of research that may
contribute to a better
understanding of the specific
pathophysiological mechanisms that underlie
veterans' symptoms. This has
included preliminary discussions
in several areas, including biological processes
associated with
neuroplasticity, disordered
sensory processing and neuroendocrine
dysregulation, and mitochondrial
insufficiency. The Committee has
also reviewed, in greater detail, diverse
scientific findings that suggest
a potential role for central
nervous system inflammatory processes in the
pathophysiology of Gulf War
illness, and has identified this
as a promising area for future research. The
research considered indicates
that neurotoxic Gulf War
exposures may activate inflammatory processes in
the brain and that increased
brain levels of proinflammatory
cytokines can produce a complex of multiple
symptoms similar to Gulf
War illness. Additional research
suggests that these processes can become
dysregulated by mechanisms
that include repeated cycles of
brain cell injury and glial activation, as well
as autonomic and
neuroendocrine disruption.
Research in this area is especially warranted
because of its possible clinical
implications. Imaging methods are
available that can potentially identify these
processes in the brain and
a variety of therapeutic agents
are being studied for their effectiveness in
treating dysregulated central
inflammatory processes.
Gulf War Illness in Relation to
Other Multisymptom Conditions
Parallels are commonly drawn
between Gulf War illness and symptom-defined
conditions such as chronic
fatigue syndrome (CFS),
fibromyalgia (FM), and multiple chemical
sensitivity (MCS) found in the
general population. The
prevalence of CFS in Gulf War veterans is
unique, and dramatically higher than
CFS rates found in nondeployed
veterans and in the general population. Rates of
FM and MCS are also
elevated in Gulf War veterans,
but to a lesser degree. It is clear from
multiple studies, however, that case
definitions for CFS, FM, and MCS
do not adequately describe the chronic symptom
complex that affects
Gulf War veterans at excess
rates, and that only a fraction of veterans with
Gulf War illness can be
diagnosed with any of these
conditions. Overall, research studies have
identified both similarities and
differences between Gulf War
illness and other multisymptom conditions.
General similarities are
reflected in indicators of
autonomic dysregulation and neurocognitive
impairment in Gulf War illness,
FM, and CFS, and by indications
that Gulf War illness and MCS are linked to PON1
variability. In
contrast, the epidemiologic
profile of Gulf War illness significantly
differs from multisymptom conditions
in the general population.
Studies have also identified immune parameters
and a number of other
measures that differ in veterans
with Gulf War illness, compared to patients with
CFS or FM. Many
objective measures associated
with these conditions have not been evaluated in
veterans with Gulf War
illness, however. Additional
research in these areas can potentially provide
useful insights into biological
mechanisms that underlie Gulf War
illness and contribute to identifying beneficial
treatments.
Federal Gulf War Research
Programs
In addition to scientific studies
and government reports, the Committee is charged
with reviewing federal
research programs established to
address health consequences of the 1991 Gulf
War. Since 1994, the
U.S. government has reported
expenditures of $340 million, over $440 million
if indirect costs are
considered, for hundreds of
studies identified as Gulf War research in
interagency reports to Congress.
This research has been funded
primarily by the Department of Defense (DOD) and
the Department of
Veterans Affairs (VA). Many
federally-funded studies have provided valuable
insights regarding the
health of Gulf War veterans, as
detailed throughout this report. But much of the
federally funded research
has not advanced understanding of
Gulf War illness or other Gulf War-related
health problems.
Consequently, federal Gulf War
research programs have not, as yet, succeeded in
achieving the primary
objective of Gulf War research,
that is, to improve the health of Gulf War
veterans.
The Committee identified major
problems related to the historical use of
research funds identified as
"Gulf War research" expenditures
by federal agencies. Historically, the large
majority of Gulf War
research funding was provided by
DOD. In recent years, DOD has dramatically cut
funding for projects
identified as Gulf War research
from nearly $30 million annually in 2001 to
under $5 million in 2006.
More troubling, many studies
identified as "Gulf War research" at DOD over
that period had little or no
relevance to Gulf War illness or
the health of Gulf War veterans. The DOD "Gulf
War" portfolio
consisted largely of costly
projects that addressed broad questions related
to current deployments and
other health issues unrelated to
the Gulf War. By 2006, less than 10 percent of
the $4.7 million identified
as DOD funding for "Gulf War
research" supported studies that related to Gulf
War illness or other health
problems associated with Gulf War
service.
The Department of Veterans
Affairs had historically funded a smaller
proportion of federal Gulf War
research, but increased funding
in recent years from a low of $4 million
annually in 2002 to nearly $13
million in 2006. VA also
historically identified a large number of
studies as "Gulf War research" that had
little relevance to Gulf War
health issues. Until 2004, this included
substantial funding for research on
stress and psychiatric illness.
By 2006, a larger number of studies had been
funded that were related to
Gulf War illness and effects of
Gulf War exposures. Still, the largest amount of
funding in VA's Gulf
War research portfolio, nearly 40
percent of the $13 million in 2006, supported
projects focused on
amyotrophic lateral sclerosis
(ALS), few of which included Gulf War veterans
or research issues related
to the development of ALS in Gulf
War veterans.
A number of important changes
have taken place in federal Gulf War research
programs in recent years.
Beginning in 2006, Congressional
actions brought about major changes in Gulf War
research at both VA
and DOD. Congress allocated an
additional $15 million annually for Gulf War
research at VA, and
directed that it be used to
support a center of excellence for Gulf War
research at the University of Texas
Southwestern (UTSW) in Dallas.
The VA/UTSW program is focused on identifying
biological
abnormalities associated with
Gulf War illness that can be targeted to develop
diagnostic tests and
treatments. Congress also
appropriated $5 million in 2006 and $10 million
in 2008 to support an
innovative Gulf War research
program managed by DOD's Office of
Congressionally Directed Medical
Research Programs. The new DOD
Gulf War research program is focused on
identifying treatments for
Gulf War illness and objective
measures that distinguish ill from healthy
veterans. Early indications
suggest that developments at both
VA and DOD represent promising new directions in
the federal Gulf
War research effort. The overall
federal funding commitment for Gulf War
research, however, remains
substantially below historical
funding levels and far below that warranted by
the scope of the problem.
Research Priorities and
Recommendations
The Committee is charged with
determining what has been learned about the
nature, causes, and
treatments for Gulf War illness
and advising on federal research, with the
primary goal of improving the
health of Gulf War veterans. In
reviewing information on the broad variety of
topics related to the health
of Gulf War veterans, the
Committee identified many scientific issues for
which additional research was
needed. Specific research
recommendations have been provided in relation
to each topic considered, and
are compiled and prioritized in
the final section of the report.
The Committee recommends that
highest priority be given to research directed
at identifying beneficial
treatments for Gulf War illness.
This includes clinical studies that
systematically evaluate the
effectiveness of currently
available treatments, as well as research to
identify specific pathophysiological
mechanisms associated with Gulf
War illness that can be targeted for treatment.
The Committee also
gives high priority to research
aimed at identifying objective biological
markers associated with Gulf War
illness, especially those that
advance efforts to improve diagnostic testing.
Recommended research
includes studies that expand on
existing biological findings in Gulf War
veterans―comprehensi ve
research on brain structure and
function, autonomic function, neuroendocrine and
immune alterations, and
processes associated with
biological vulnerability to neurotoxicants― as
well as studies that investigate
neuroinflammatory processes and
utilize genomic and related technologies to
identify biological
characteristics of Gulf War
illness. Additional research priority areas
include studies that characterize
effects of neurotoxic exposures
associated with Gulf War illness, and
epidemiologic studies to assess
rates of neurological diseases in
Gulf War veterans.
The Committee identified
additional areas of research needed to address
other important Gulf War health
issues. These include
epidemiologic studies to identify mortality and
cancer rates in Gulf War veterans,
evaluation of health problems in
veterans' children, and improved
characterization of Gulf War-related
health problems in relation to
exposures in theater. Recommendations are also
provided for improving
clinical and epidemiologic
research on Gulf War veterans, and emphasize the
importance of evaluating
outcomes in subgroups of Gulf War
veterans identified by illness characteristics
and exposures in theater.
The Committee recognizes the
vital importance of Congressional support,
agency commitment and
leadership, and adequate federal
funding for achieving critical scientific
objectives related to the health of
Gulf War veterans and preventing
similar problems in future deployments. It
therefore recommends that
the Administration request and
that Congress allocate not less than $60 million
annually in the federal
budget for Gulf War research, an
amount commensurate with the scope of the
problem, and compatible
with funding levels between 1999
and 2001. The Committee also recommends that
this funding be
specifically directed to research
most capable of improving the health of Gulf War
veterans, as outlined in
this report.
Conclusions
Veterans of the 1990-1991 Gulf
War had the distinction of serving their country
in a military operation
that was a tremendous success,
achieved in short order. But many had the
misfortune of developing
lasting health consequences that
were poorly understood and, for too long, denied
or trivialized. The
extensive body of scientific
research now available consistently indicates
that Gulf War illness is real, that
it is the result of neurotoxic
exposures during Gulf War deployment, and that
few veterans have recovered
or substantially improved with
time. Addressing the serious and persistent
health problems affecting
175,000 Gulf War veterans remains
the obligation of the federal government and all
who are indebted to
the military men and women who
risked their lives in Iraq, Kuwait, and Saudi
Arabia 17 years ago. This
obligation is made more urgent by
the length of time Gulf War veterans have waited
for answers and
assistance.