Research Advisory Committee on

Gulf War Veterans' Illnesses

Minutes of Meeting

June 25, 2002

0730-1600

American Legion Building

1608 K Street NW

Washington, DC

Greetings by James Binns, Chairperson, who then introduced Secretary
Anthony Principi and Deputy Secretary, Leo Mackay.

[Secretary Principi remarks:]{.underline}

The Secretary emphasized that the work of the committee is very
important to the Department and expressed his thanks to the Committee.
He stated that Gulf War (GW) veterans have waited too long to get
answers to questions about their health. Environmental hazards are not
as easily diagnosed as battle wounds. They are difficult to define, and
they cannot be seen.

[Opening comments of Lea Steele, PhD:]{.underline}

Dr. Steele stressed the following:

-   Gulf War Veterans are ill.

-   Their illnesses are not adequately explained by stress or
    psychiatric illness.

-   The illnesses are linked to experiences in the Gulf War.

-   A substantial number of veterans are affected.

Dr. Steele noted that studies have generally not found Gulf veterans to
have experienced an excess of disease-related deaths. However, studies
have consistently found that Gulf veterans experience a wide range of
symptoms at significantly higher rates than non-Gulf veterans. Further,
the pattern of symptoms reported by groups of Gulf veterans differs from
those of non-Gulf veterans, in terms of frequency, severity, and the
occurrence of multiple symptom types together.

Gulf veterans also report an excess of some types of diagnosed
conditions, compared to non-Gulf veterans. Conditions such as heart
disease, cancer, and diabetes have not generally been found to be
elevated among Gulf War veterans. But studies have found increased rates
of respiratory conditions, migraines, skin conditions, digestive
disorders, and some psychiatric conditions.

Dr. Steele pointed out that these unexplained conditions cannot be
adequately explained by stress or by psychiatric conditions. The Gulf
War was brief, and the vast majority of deployed personnel were not in
battlefield areas and did not witness any deaths or serious injuries.
The rate of PTSD was reported to be less than 5% among veterans enrolled
in VA's Gulf War Registry, a lower proportion than in veterans of prior
wars.

Government officials have suggested that these unexplained illnesses are
not the result of events specific to the Gulf War, but are part of a
generalized phenomenon that occurs after every war. However, several
lines of evidence indicate that these conditions are associated with
experiences in the Persian Gulf theater. Numerous studies have found
strong associations between illness and self-reported exposures
encountered in theater. In addition, a study of Kansas veterans found
that illness rates are strongly linked to the locations and time periods
in which veterans served during the war. Specifically, lowest illness
rates (21%) were found among veterans who served primarily on board
ship, intermediate rates (31%) among those who served on land in support
areas, and highest rates (42%) were found among veterans who entered
Iraq or Kuwait.

Dr. Steele's last key point related to the proportion of Gulf veterans
who are affected by these unexplained conditions. Studies of different
veteran groups have found that Gulf veterans report experiencing a
complex of multiple symptom types at rates 26-30% higher than are
reported by nondeployed era veterans. The consistency of these findings
indicates that 26-30% of Gulf veterans are affected by a complex of
multiple symptoms that results from their service in the war.

[Questions posed by Secretary Principi:]{.underline}

Do these symptoms abate over time or remain constant (noting that a
significant number of deployed veterans remain on active duty)?

> Dr. Steele noted that follow-up studies are needed, but that
> preliminary data suggest that many veterans have not improved over
> time.

Do the studies only target veterans or include those that remain on
active duty?

> Dr. Steele stated that studies have included veterans who are no
> longer in service, as well as those remaining on active duty. She also
> noted that some active duty personnel may be reluctant to report
> health problems.

How did those aboard ships (21 percent) exhibit symptoms when they could
have been hundreds to a thousand miles away from the conflict?

> Dr. Steele noted that these personnel may have experienced some of the
> exposures being investigated, such as smoke from oil well fires and
> vaccines.

Is it true that by all reports, the French report much lower rates of
symptoms?

> Dr. Steele acknowledged that the French are generally believed to have
> fewer problems. The French were positioned far from the battlefield in
> Iraq, are not thought to have generally taken pyridostigmine bromide,
> and did not receive the same vaccines as American troops.

[Opening comments of Dr. Haley:]{.underline}

Dr. Haley first summarized the findings that are widely agreed on: 1)
Gulf War syndrome is an epidemic because tens of thousands of deployed
soldiers became sick with similar symptoms within a 4-6 month period
during and right after deployment. 2) All large population surveys show
that GW veterans have higher rates of symptoms and mortality from motor
vehicle accidents than the nondeployed. 3) GW veterans have a rate of
service-connected disability than veterans of any previous war.

Dr. Haley then listed the common symptoms of Gulf War syndrome and
stated that the only anatomical location where a lesion could explain
all the symptoms is the brain. There are well understood degenerative
diseases of deep brain structures, such as basal ganglia and brainstem,
that in the early stages produce symptoms closely resembling those of
Gulf War syndrome. Parkinson's, Huntington's, Wilson's and Fahr's
diseases. While these diseases are relentlessly progressive primary
diseases of basal ganglia and brainstem. In the early stages they
closely resemble Gulf War syndrome, but Gulf War syndrome does not
appear to be progressive like those conditions. So it is as if Gulf War
veterans suffered minor damage to those same deep brain structures,
which progressed for a few months and then stopped progressing. If so,
studies of the cellular integrity of the deep brain structures should be
undertaken to test this idea.

Dr. Haley then summarized research done at his university to test this
theory. First they surveyed a Naval Reserve battalion, deriving a case
definition, and selecting cases and controls for detailed clinical
research. Bringing the ill veterans meeting the case definition and
matched controls to the General Clinical Research Center at the
University of Texas Southwestern Medical Center in Dallas, his group
performed brain scans, genetic tests, neurotransmitter assays,
neurophysiologic, autonomic and quantitative sensory studies, with the
researchers blinded to case- and control-group status. These studies
confirmed that the ill Gulf War veterans have a brain cellular
abnormality of the basal ganglia and brainstem, a genetic predisposition
to injury by chemical nerve agents, a disorder of vestibular
(equilibrium) function, subtle autonomic disturbance, and an abnormality
of temperature sensation. All of these findings point to damage to the
deep brain structures, including the basal ganglia, brainstem and
probably the thalamus.

Dr. Haley's research group is planning additional studies to extend
these findings. The objective is to define further the nature of the
brain injury, develop a cost-effective battery of tests that can
diagnose the brain injury, and new ideas for treatment. He suggested
that the committee should consider recommending a wide array of studies
testing objective tests (biomarkers) that would further the
understanding of the physical nature of the brain injury that underlies
Gulf War syndrome.

[Questions posed by Secretary Principi to Dr. Haley:]{.underline}

Could genetics play a predisposition role?

-   Dr. Haley responded that genetics could indeed be a factor. He
    pointed out that the paraoxonase (PON) enzyme, which protects the
    brain from chemical nerve gas, has been found to be lower from birth
    in the sick Gulf War veterans than in the control veterans. This
    indicates a genetic predisposition to nerve gas injury, the probable
    etiology of Gulf War syndrome.

Could vaccines elevate the enzyme that was noted in Dr. Haley's report?

-   Dr. Haley stated "not this particular enzyme, which remains the same
    throughout life and is not affected by environmental exposures,"
    although he noted that vaccines may have affected other enzymes,
    such as cytokines and inflammatory factors that are under study as
    further contributors to Gulf War syndrome.

[Opening comments of Dr. Golomb:]{.underline}

Dr. Golomb spoke of findings supporting a connection between
acetylcholinesterase inhibitors (such as pyridostigmine bromide pills,
pesticides, and perhaps low level nerve agent exposure) and illness in
GW veterans. Among the more compelling findings, ill GW veterans have
lower activity levels for enzymes specifically involved in detoxifying
some acetylcholinesterase inhibitors (e.g. paraoxonase or PON), and some
studies suggest they may be more likely to have poor metabolizing
genotypes of such enzymes. These findings are difficult to explain in
other than a causal fashion, and appear to confirm a link between
acetylcholinesterase exposure and illness in some ill GW veterans. This
need not exclude a contribution to illness by other exposures in some
veterans. Regarding anthrax vaccination, several lots of anthrax vaccine
were evaluated and shown to have low levels of squalene, which was not a
stipulated vaccine constituent. Some GW veterans that are sick have been
shown to have high levels of squalene antibodies. Squalene is a
precursor to cholesterol, and cholesterol antibodies have been shown to
produce effects, including adverse effects, of lowered cholesterol,
which parallel health problems seen in GW veterans. Additionally,
quality control in anthrax vaccine production was highly problematic,
with persistent near-failing site visit reports by the FDA culminating
in two threats to revoke licensure; specific potential for contamination
was cited, which can have implications to health effects, for instance
through adjuvant effects.

[Question posed by Secretary Principi to Dr. Golomb:]{.underline}

Has research looked at other settings in which there were exposures to
similar chemicals, outside of the Gulf War; and how does that
information fit in?

> Dr. Golomb noted that such studies are limited, but appear to accord
> with the findings in ill GW veterans. For instance, work by Dr. Cherry
> showed that British sheep farmers attributing chronic ill health to
> diazinon (organophosphate, acetylcholinesterase inhibiting) sheep dip
> were more likely to have the poor-metabolizing genotype of paraoxonase
> (PON) and lower PON enzyme activity levels than control sheep farmers,
> directly analogous to the findings in ill veterans, and providing
> triangulating evidence suggesting a link between acetylcholinesterase
> inhibitors, particularly in susceptible subsets, and ill health.

At this point, the Secretary expressed his appreciation to the committee
for the time afforded to bring him up to date, apologized for his
limited time, and departed for the airport.

[Mr. James Binns:]{.underline}

Mr. Binns summarized the findings in the Committee report.

-   GW deployed veterans are ill. Epidemiological studies consistently
    show 25-30% of the veterans are ill over and above the control
    population, and well beyond what can be explained by stress or other
    psychiatric diagnosis.

-   Objective measures have demonstrated that an important category of
    Gulf War illness is neurological in nature.

-   Risk factors found in the Gulf War in 1991 are still present today
    in the war on terrorism, both overseas and at home.

Mr. Binns summarized the recommendations in the Committee report:

-   Use all available methods to identify and evaluate treatments that
    may hold promise for the unexplained illnesses experienced by Gulf
    War veterans.

-   Enlist the expertise of specialists in neurobiology and neurological
    illness.

-   Designate as a research priority the investigation of neurological
    mechanisms, including acetylcholine dysregulation and other
    acetylcholinesterase inhibitor-induced pathology, that potentially
    explain the disease process (in an important subset of ill veterans)
    and may lead to the development of treatments.

-   Establish a research program to identify objective markers in ill
    veterans or subsets of ill veterans, and to investigate linkages
    between markers, exposures, and health status.

-   Make full use of existing data on veterans' health and treatments,
    merging relevant DoD, VA and other federal databases.

-   Manage for results.

-   Increase funding to \$150 million per year for the next 3 years --
    not all from VA but the entire federal government.

Mr. Binns stated the following justifications which support the funding
recommendations:

-   A breakthrough has occurred in identifying objective markers of
    neurological dysfunction.

-   This research/treatment is not just for GW veterans; it will also
    provide benefits in terms of prevention and treatment measures in
    the war on terrorism.

[Comments of Dr. McKay:]{.underline}

The Deputy Secretary thanked the committee for their interim report,
which will be used to support further research efforts. He noted the
report will be transmitted to DoD and that it is important to take into
account the applicability to the war on terrorism. Dr. McKay stated that
this report is a good first step and how much he personally appreciates
the work of the committee.

[Mr. Binns:]{.underline}

Mr. Binns opened this portion with the following remarks and proposed
committee action:

-   Secretary Principi and Deputy Secretary Mackey's participation
    demonstrated the support of VA leadership for the Committee's work.

-   Nine members and one consultant were present with 2 missing from
    today's meeting.

-   He requested concurrence of the previous meeting minutes and
    received no comments. The minutes were approved as drafted, with the
    understanding that Mr. Binns gave the committee till July 1, 2002 to
    send additional comments to Ms. Laura O'Shea.

[Opening comments of Dr. Jack Melling:]{.underline}

Dr. Melling noted that:

-   Multiple vaccines given during deployment are associated with an
    increased level of multi-symptoms syndrome (Hotopf, et al 2000).

-   GW veterans had increased prevalence of functional impairment,
    healthcare utilization and symptoms (Kang et al 2000).

In view of these findings the hypothesis that vaccines may have
contributed to GWI should be explored.

Dr. Melling was posed (by unidentified committee member) with the
question of epidemiology - was the anthrax vaccine a significant factor?
Dr. Melling cited that the prevalence rates of symptoms among GW
veterans were two to three times higher among those who received the
anthrax vaccine (Kang et al, unpublished) than those who did not.

Dr. Melling also noted:

-   Reaction rates to AVA (local and systemic) have been higher than
    identified on the original product insert and noted the insert was
    revised in 2002.

-   Two studies have shown women had higher reaction to AVA than men, at
    least two times as high.

Dr. Melling suggested the following mechanisms for studying the
vaccine/GW association:

-   Study of the combination of vaccines with exposure to: nerve agents,
    pyridostigmine, stress, and environmental toxicants.

-   Research the TH1/TH2 imbalance (vaccines used induce TH2 as opposed
    to TH1 responses. Most vaccines given produced T helper 2 vs. T1
    responses).

-   Establishment of animal models.

> He also noted a guinea pig model that used multiple vaccines and PB
> pretreatment that observed:

-   Weight loss.

-   Temperature rise.

-   Humoral immune responses.

-   Animals stayed healthy.

## However no detailed immunological or molecular pathological studies were done. 

Dr. Melling stated at least one common factor of vaccines given here and
in England was that they both contain a protective antigen. The amount
of protective antigen has not been determined.

The following are further comments/references made by members of the
committee during this open discussion period:

*Dr. Haley: The strength of the vaccine theory is the epidemiological
connection - several studies seem to show it. We know that an imbalance
of the Th2 cells of the immune system can cause symptoms possibly
resembling Gulf War syndrome. This imbalance has been linked to
excessive morbidity and mortality from dengue fever, and certain drugs
like antidepressants can partially mimic this change, but such an
imbalance has not been shown in GW veterans. An imbalance toward Th1
cells is suspected of causing a different spectrum of illness. Those are
the only studies he is aware of linking any disease to Th1/Th2 cell
imbalance. He believes the weakness of this theory is connecting
immunological deficiency diseases to GW syndrome. We do not see
excessive rates of diseases like pneumonias, opportunistic infections,
etc. at a higher ratse in GW veterans. He is not convinced that
immunologic deficiencies are causing the disease. Again this theory
needs to be tested with objective markers in carefully designed
case-control studies utilizing a case definition of Gulf War syndrome.*

*Dr. Melling: There is a U.K. group that has developed a mycobacterial
vaccine that seems to be helping symptoms similar to some of those
involved in GW illness.*

*Dr. Haley: The theory is that there is a T helper antigen in your body
that may differentiate into a T1 or a T2, for example, giving many
vaccines close together may cause you to produce an overabundance of T2
cells. Mycobacterial vaccination could produce more T1 cells, correcting
the imbalance and making you better or not. However, perhaps we should
try to turn off the production of T2 cells instead. But all this
presupposes that the Th1/Th2 imbalance has been associated with a case
definition of Gulf War syndrome, and this has not been done.*

*Dr. Golomb: She does not think one should jump to the conclusion that
this does not affect ill GW veterans.*

*Steve Robinson: We must consider both deployed and non-deployed groups
who receive the vaccine.*

*Dr. Steele: Is it not possible that vaccines caused neurological
diseases?*

*Dr. Haley: Long-term analysis says no.*

*Dr. Golomb: There are some conditions that have been tied to
neurological illness.*

*Dr. Steele: Clinical practice guidelines for post deployment - VA has
made a huge effort with this and with treatment trials. On top of
clinical treatments, the highest form of evidence is trials. As the
committee considers different treatment records, they should conduct
small studies that might tell us what works in treating GW veterans. The
committee should recommend that VA help clinicians find out what is
working by using the mass of clinical data and taking multiple
approaches. They (VA) must develop data for "promising"* *treatments. VA
should further evaluate possibilities for treatments that may work. We
should look at treatments that counteract current problems and
symptoms.*

*Dr. Golomb: It is important to select the group most likely to get
benefit from certain treatments.*

*Dr. Steele: Some of the things VA could do immediately would be to
apply outcome measures to existing GW clinics.*

*Dr. Haley: VA should have a major focus on treatment for raising and
testing hypotheses about what works. Hold off on expensive trials until
they have identified promising results in clinical surveillance
experience.*

*Dr. Steele: We should systematically survey large groups of veterans
what treatments they had and what affects those treatments had.
Something that can be done cheaply and immediately.*

*Mr. Binns: We should define "all available methods" in our
recommendation.*

*William Meggs: We should ask veterans what works.*

*Dr. Steele: It is important to have a systemic method of study.*

Dr. Golomb: Can initially just ask veterans to get feedback on
alternative treatments and drugs they may have had outside known
treatment courses.

*- VA can only give treatments that are "safe and effective" or FDA
approved which limits potential studies. Veterans who are not at
VA/government centers are more open to other therapies.*

*- Could do a preliminary hypothesis generating survey.*

*Mr. Binns: Committee should check and see what type of survey could
easily fit with VA practices.*

*Dr. Golomb: Could conduct a hypothesis generating survey leading to a
small scale study and then large scale trials.*

*Steve Robinson: We must ask what treatments work for veterans. Veterans
have waited long enough for treatment.*

*Dr. Melling: If we have an illness of unknown origin, how do we
determine what treatments are safe and effective? Therefore, it may be
entirely ethical for VA to approach this problem by giving low dose
treatments of drugs to see what works. This could be done to evaluate
new treatments or to evaluate existing medicines that have previously
been applied to other diseases.*

*Dr. Haley: Ten years have already elapsed and no progress has been made
in finding treatments for these sick veterans. The committee should be
very direct toward encouraging treatment strategy in VA. Two VA medical
centers in Texas wrote a research proposal to establish a Gulf War
syndrome treatment clinic, elicit the most troublesome symptoms of Gulf
War veterans, try various medications for each different symptoms to
explore for what might work, and record the experience for analysis. The
results were to identify promising medications for referral to formal
clinical trials. This is way the problem should be approached, but this
approach was rejected in favor of large clinical trials that were
possibly premature.*

*Dr. Haley: The strong inclination of VA up to now has been not to try
exploratory treatments.*

*Mr. Binns: The committee can make suggestions, it is VA's choice to
reject or accept them.*

*Dr. Golomb: For treatments, we must recommend a design because one
treatment may interfere with others.*

At this point, Mr. Binns requested the individual committee members to
report on the studies that they have reviewed.

# Dr. Steele:

Dr. Steele discussed two studies that she reviewed and noted:

-   The emphasis was on treatment trials (VA sponsored).

-   Also, on clinical practice guidelines.

-   Expressed concerns that basically the studies focused only on expert
    guidelines (which is felt to be the low standard) to the much larger
    randomized trials.

-   Noted that VA conducted a large trial that she felt to be of little
    use due to its inability to either prove or disprove protocol.

-   Stressed the intense review of each step of any multiyear study was
    critical and felt these studies (she reviewed) may have fallen short
    of this effort.

Dr. Steel recommends pulling out all "stops". Many physicians claim they
can help but have little funding available. She felt the VA should
expand the scope from just expert based or the large randomized trials.
Dr. Steel also discussed coordination of efforts with VA's centers of
excellence and wants outcome measurements to be instituted immediately
throughout the VA.

At this point, Dr Haley wanted to know if a second interim report could
be issued to help VA identify promising treatments to clarify original
recommendation of "using all available methods". He also wants to
recommend a survey of veterans to respond to what treatment they have
had (in relation to potential treatment of GW-related symptoms), what
worked, or did not and where the treatment was received.

A discussion centered on veterans receiving experimental treatments
outside the VA due to VA's stance on the approval process for these
types of treatment with criticism of VA's Research office surfacing. The
committee suggested issuing Directives for the Secretary's approval that
would provide guidance on the issuance of treatment plans.

# Mr. Steve Robinson:

Mr. Robinson discussed the articles and studies he reviewed and made the
following comments:

-   Brought up concerns of unavailable reports that DoD may have and
    expressed displeasure of existing reports (e.g. Anthrax safety
    study) that did not take into account the effect on GW veterans.

-   Brought up Bronze Anvil, which was explained to be a public
    relations (PR) strategy for the GW and suggested many feel the PR
    strategy is being used to downplay GW illnesses.

-   Review of DoD report-53 showed low level exposure to the nerve agent
    sarin may have long- term health effects.

-   Wants one-site repository of GW information for federally and
    non-federally funded research.

-   Stressed that capability (biological warfare) of Saddam Hussein is
    totally underreported.

-   Stated the United States detection capability (of
    chemical/biological exposure) is no better now than back in 1991.

-   Noted that the Presidential Special Oversight Board recommended a
    stoppage of research due to uncertainty of whether Iraq used
    biological weapons.

-   Claims public, or committee for that matter, has not yet had a full
    accounting of incidents of exposures (in the GW arena) even though
    information may be available though not accessible.

-   Wanted to know if committee can obtain a detail of all engagements
    (detonations of munitions) -- especially those that have not been
    modeled (so that they may have a chance to be modeled).

-   Brought up concern there may be a conscious effort to spread
    misinformation.

There was a discussion headed by Dr. Haley of pushing for the exposure
of those responsible for misinformation and/or withholding of
information. Mr. Binns pointed out the charge of the committee did not
include this purpose.

# Mr. Steve Smithson:

Mr. Smithson discussed the recent mortality study by VA concerning
veterans who served near the Iraqi munitions dump at Khamisiyah that
demonstrated no substantial increase in deaths nor any unusual causes of
death.  He cited that this study began after another VA report suggested
a dramatic increase in deaths among a group of about 35,000 veterans
serving in the Gulf area during the war.

Mr. Smithson then spoke of VSO's interest of the committee's study and
how it impacts health and future compensation for GW illnesses/injuries.
He brought up a book entitled "Gulf War and Health" that looked at four
exposures to agents and stated VA subsequently used this data to issue
presumptives in July of 2001. He once again reminded the committee of
the impact that studies have in providing service connected ratings for
veterans which in turn increases the veterans opportunities to access VA
healthcare.

Dr. Haley explained that the controversy surrounding the release of VA
data on GW mortality needs a better accounting or formal investigation.
From the patterns of numerical discrepancies he has seen in the
published reports and scientific papers, he felt that there had either
been terribly negligent mistakes or purposeful scientific misconduct. If
the latter were found, he expressed that charges should be considered,
and certainly the errors should be corrected and proper analyses and
conclusions about the association of Khamisiyah exposure to mortality
published.

# Dr. William Meggs:

Dr. Meggs discussed his reviews and noted that in toxicology and
environmental health specific agents cause specific illness. There are
also mechanisms for non-specific toxicity, in which toxic substances
cause illness independent of their class.

The Generalized Adaptation Syndrome is a response to sub-lethal
exposures to chemicals that was described by Hans Selye in the 1930's.
With chronic exposure, chronic illnesses may develop but there is no
acute reactivity to exposures. If the subject is removed from the
chronic exposure, the chronic illness improves but there is acute
reactivity to chemicals. Re-exposures can cause violent and even lethal
reactions which Selye termed 'shock reactions.' The stages of reactivity
to chemicals progresses through four stages, the normal stage with no
signs of biological changes, a stage of sensory hyperreactivity and pain
from exposures, a stage of inflammation, and finally a stage with tissue
damage.

Airway studies show that long-term irritation/inflammation can lead to
permanent, chronic damage as well as persistent reactivity to irritants.
Permanent changes to the airway and ongoing inflammation and irritation
to due to chemicals can occur.

Nerve fibers have receptors to chemicals called chemoreceptors. These
receptors react to respiratory irritants and trigger the release of
inflammatory mediators such as substance P. Extra-airway manifestations
of airway inflammation include headaches and myalgias. Some aspects of
GW illness may be related to adverse reactions to the complex mixtures
of chemicals troops were exposed to, through these non-specific
mechanisms.

In summary Dr. Meggs stated, "Exposure to chemicals leads to
inflammation and ongoing exposures maintains inflammation. Subsequent
pathological changes to the airway occur if the exposure continues.
Other organ systems may also be affected."

Dr. Meggs suggested the following treatment for affected GW veterans:

-   Environmental control - take people away from chemical exposures,
    daily allergens etc. (avoid exposure), to see the extent to which
    chronic symptoms resolve.

-   Clinical trials of Substance P inhibitors for some aspects of GW
    illness when these compounds become available.

[Dr. Robert Haley:]{.underline}

Dr. Haley covered articles concerning "Is there a GW syndrome." He
demonstrated that the various studies had used different methods and had
measured different types of symptoms. Studies that had prejudged the
problem as a psychiatric problem had measured the symptoms of
psychiatric illnesses. When they did factor analysis to look for
psychiatric diseases, they found some because every human population has
people with some levels of depression, anxiety, compulsive symptoms,
etc.

On the other hand, studies that based the symptom questionnaires on
preliminary interviews with sick GW veterans, used symptoms more
representative of those that GW veterans really complain of. The studies
in this category have generally agreed on certain symptom complexes to
the extent that they measured the symptoms of each complex.

The Haley et al. study (JAMA 1997) and the Kang et al. study (Arch
Environ Health 2002) had the most complete sets of typical GW veteran
symptoms, and they agreed that there are six factors in the data, and
the first three syndrome factors were very similar. In both studies, the
second syndrome factor identified what appeared to be a "neurologic
syndrome." The Kang et al. study found that this second syndrome was
found only in the deployed population but not in the nondeployed
population, thus suggesting that it is a "unique Gulf War syndrome."
This study involved random samples of approximately 10,000 deployed and
10,000 nondeployed veterans, giving it strong power.

Of great interest was the fact that both the Haley et al. and the Kang
et al. studies found that their second syndrome factor was very strongly
associated with perceived exposure to chemical nerve gas during the war.
The relative risk for this association was 7.8 in the Haley study and
6.8 in the Kang study. In both studies, chemical nerve gas exposure was
by far the most strongly associated risk factor for syndrome 2 and in
both studies it was highly statistically significant at p \< 0.0001.

Dr. Haley suggested that the Kang study and others should have used a
Structural Equation Model (SEM) to test whether the factor syndromes
identified in the deployed population was or was not present in the
nondeployed population. The use of Exploratory Factor Analysis to answer
this question is not valid and would not be condoned by experts in
factor analysis. Dr. Haley's research group has performed an SEM
analysis and found the three syndrome factors to be present in a
different group of deployed Gulf War veterans. He is presently designing
a new random sample survey to apply SEM verification in both deployed
and nondeployed populations.

He then went over other studies that examined similar and/or differing
factors and noted:

-   The bottom line was that there are 3 similar factors in most of the
    studies.

-   The Fukuda study, which did not measure neurologic problems as the
    Haley and Kang studies did, still had a high correlation with the
    Haley factors 1 and 3 and with Kang's factors 1 and 3. Since
    Fukuda's group did not measure neurologic symptoms they did not find
    syndrome 2, which is neurologic.

-   Suggested the GW veterans classified as in the neurologic group
    (syndrome 2) were seven times as likely to recall exposure to nerve
    agents; whereas, those with syndromes 1 and 3 were not associated
    with recalled nerve gas exposure.

-   He recommended further research is needed into neurologic
    conditions, because this appears to be the most severe form of Gulf
    War syndrome.

# Mr. Joel Graves:

Mr. Graves discussed a GW study concerning sarin and co-exposures in
relationship to stress. He further noted:

-   The need to identify the most relevant combinations (of exposures to
    chemicals) to receive more money for research.

-   Suggested taking results of these studies and building a case study.

-   Proposed these case studies be built around multiple definitions.

# Dr. Nicola Cherry:

Dr. Cherry discussed the mortality studies carried out in the US and UK.
She noted that in both countries GW veterans were more likely than those
not deployed to die from accidents but that, to date, there was no
overall excess in mortality. However, with the passage of time, any
Healthy Warrior effect would be expected to disappear, and we have
reached the point where mortality figures may start to be meaningful. In
addition, long term effects of exposure on diseases (particularly
cancer) with an expected latency of at least 10 years will only now be
available for study. As a result, while mortality studies to this point
have not been very informative, this is the moment when we should put
consistent efforts into these data, with repeated analyses to look for
trends.

Dr. Cherry made the following recommendations:

-   Continue to produce analyses of US data by time intervals (including
    immediate analysis of 3 periods of 18 months back to January 1^st^
    1998).

-   Produce data for a wider range of diagnostic codes (preferably for
    all ICD categories).

-   Compare/combine data from Allies.

-   Analysis of mortality data by location/function while in the Gulf
    War.

-   If suspicious increases in deaths are noted, instigate increased
    surveillance and screening to determine new cases while there is
    still the possibility of treatment.

She noted that there is concern that suicides may be misclassified as
accidental deaths.

A question was posed whether there was any progress toward combining
Allied and US data and coordinating research efforts. The answer
provided indicated that this coordination has not evolved.

At the conclusion, Dr. Haley strongly recommended further study on
mortality data.

# Dr. Golomb:

Dr. Golomb discussed enzyme studies that showed the variations that
break down ACHE. She also discussed exposures, chemical/biological, PB,
and insect repellant studies.

# Mr. Binns:

Mr. Binns discussed studies most relevant to "What research has most to
do with health of ill veterans". He discussed Colonel Donnelly, an ill
Gulf War veteran who was subsequently exposed to pesticides and
developed ALS. Mr. Binns requested the committee consider recommending
VA follow up with those (GW) veterans with ALS to see if there were
subsequent pesticide exposures and to consider issuing a warning to
avoid pesticides.

Mr. Binns noted that whether birth defects is linked to GW illness needs
more research.

Mr. Binns also spoke of the work by Dr Soreq in Israel. She is the only
researcher of whom he is aware to have both identified a neurological
mechanism and developed a possible drug treatment. He stated clinical
trials of this genetic drug had recently commenced and recommended the
committee follow her work. He then brought up the work of Dr. Buccafusco
at the Medical College of Georgia on impaired cognitive function and
possible treatment directions related to organophosphate injury. He
suggested the committee contact these and other researchers
(particularly those whose last reports were a couple of years old) to
follow up on progress and solicit future research ideas.

A discussion ensued to determine how best to seek out all studies
regarding GW (even if not labeled as such) and aggregate them into one
data bank.

[Mr. Binns:]{.underline}

Mr. Binns then addressed the committee with the following question,
Where to go from here? The committee made the following comments
regarding challenges and potential strategies:

-   How to reach out.

-   Dr. Golomb has sent out packages requesting certain information to
    neurology specialists and is expecting responses within 2 weeks.

-   Should seek out experts outside US borders.

-   Need to go beyond what is on the table.

-   Staff needs to review current studies for applicability.

-   Must define role of staff (Dr. Golomb brought out that each
    additional task for staff members will delay or deter ongoing work).

-   Should urge VA to search database to look for difference within
    deployed versus non deployed veterans over time.

-   Recognized that DoD has much more research than VA.

-   Should develop specific criteria, not just objectives, for staff
    work.

-   Talked of importance in the use of objective markers.

-   How to guide VA in conducting treatment studies.

The discussion centered on putting out another interim report or, absent
this, taking a measured approach for the December reporting requirement.
No definitive decision was reached though it was mentioned the use of
email would be used to follow-up on this discussion. The committee did
agree on the importance of bio-markers.

A very brief discussion ensued regarding the meetings conducted by some
members of the committee with the National Institute of Health, Veterans
Service Organizations' representatives, and the Environmental Protection
Agency, with all expressing interest in the committee's work. Also, the
committee wishes to construct a website, and the general consensus
seemed to be not use a VA hosted site due to complexity of compliance.

-   Dr. Golomb offered binders (containing reviewed reports) to the
    public as well as the committee members.

-   The Stenographer left for the day (3:30 p.m.).

[Public Comment Period:]{.underline}

# Ms. Denise Nichols:

-   Suggested expansion of Alert System as pointed out by the CDC.

-   Pointed out that Dr. Bill Baumzweiger recommended deployed GW
    veterans to stay out of sunlight due to risk of seizures, heart
    incidences, etc.

-   Suggested that original registry tests be updated and VA mandated to
    follow revised guideline.

-   Recommended those firefighters and police who worked the World Trade
    Center, who are also GW veterans, should be aggressively contacted
    and monitored due to additional exposure of environmental hazards.

-   Suggested that all VA policies and directives concerning GW be
    forwarded to this committee for review.

-   Based on her personal test results, she believes study on usage of
    vitamins could be useful.

-   Recommended review of Steven Johnson Syndrome.

-   Wants to see autopsy data aggressively pursued as well as the
    preservation of tissue samples.

[Ms. Venus Hammack:]{.underline}

-   Suggested a feedback tool, survey or other means of gathering
    information from GW veterans be immediately developed.

-   Make places in VA's libraries available for veterans to give their
    feedback via computer

-   Send letter to all VSO's, not just the top five, and ask them to
    post a notice to draw veteran feedback.

-   There are veterans who would be glad to assist the committee in
    getting a website up and running.

-   Wants to ensure GW tissues, as a result of autopsies, are being
    catalogued for researchers.

-   Noted a problem with Red Cross turning away Gulf War veterans who
    wish to donate blood.

-   Requests a centralized database with GW information to be put in
    place that is accessible to the public such as the website.

-   Request the committee to review the 1994 Reagle Report, which she
    will make available to the committee.

-   Can committee members accept outside help?

> \-

[Vietnam Veterans Association comments:]{.underline}

-   Suggest interim reports are provided immediately to Presidential
    Task Force (also found at wwww.presidentshealthcare.org, Attn: Dr.
    Paul Tibbets).

-   Recommended the committee to ask VA for statistics of GW veterans
    unique visits.

-   Wanted committee to recommend to the Secretary to work with DoD to
    ban from the use of PB.

Dr. Golomb noted that, based on her report, DoD changed its policy so
that PB would not be used -- subject to Presidential waiver.