Gulf War Illnesses: DOD's Conclusions About U.S. Troops' Exposure
Cannot Be Adequately Supported (01-JUN-04, GAO-04-821T).	 
                                                                 
Since the end of the Gulf War in 1991, many of the approximately 
700,000 U.S. veterans have experienced undiagnosed illnesses.	 
They attribute these illnesses to exposure to chemical warfare	 
(CW) agents in plumes--clouds released from bombing of Iraqi	 
sites. But in 2000, the Department of Defense (DOD) estimated	 
that of the 700,000 veterans, 101,752 troops were potentially	 
exposed. GAO was asked to evaluate the validity of DOD, the	 
Department of Veterans Affairs (VA), and British Ministry of	 
Defense (MOD) conclusions about troops' exposure.		 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-04-821T					        
    ACCNO:   A10350						        
  TITLE:     Gulf War Illnesses: DOD's Conclusions About U.S. Troops' 
Exposure Cannot Be Adequately Supported 			 
     DATE:   06/01/2004 
  SUBJECT:   Chemical and biological agents			 
	     Chemical warfare					 
	     Data collection					 
	     Data integrity					 
	     Health hazards					 
	     Health statistics					 
	     Military personnel 				 
	     Statistical data					 
	     Veterans						 
	     Iraq						 
	     Persian Gulf War					 

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GAO-04-821T

United States General Accounting Office

GAO Testimony

Before the Subcommittee on National Security, Emerging Threats, and
International Relations, Committee on Government Reform, House of
Representatives

For Release on Delivery

Expected at 1:00 p.m. EDT GULF WAR ILLNESSES

Tuesday, June 1, 2004

  DOD's Conclusions About U.S. Troops' Exposure Cannot Be Adequately Supported

Statement of Keith Rhodes, Chief Technologist
Center for Technology and Engineering, Applied Research
and Methods

On 8/6/04 this testimony was reissued because, beginning on page 15, the
support for "Some Studies Suggest an Association between Chemical Warfare
Exposure and Gulf War Illnesses" was inadvertently omitted.

GAO-04-821T

Highlights of GAO-04-821T, a report to Subcommittee on National Security,
Emerging Threats, and International Relations, Committee on Government
Reform, House of Representatives

Since the end of the Gulf War in 1991, many of the approximately 700,000
U.S. veterans have experienced undiagnosed illnesses. They attribute these
illnesses to exposure to chemical warfare (CW) agents in plumes-clouds
released from bombing of Iraqi sites. But in 2000, the Department of
Defense (DOD) estimated that of the 700,000 veterans, 101,752 troops were
potentially exposed. GAO was asked to evaluate the validity of DOD, the
Department of Veterans Affairs (VA), and British Ministry of Defense (MOD)
conclusions about troops' exposure.

This testimony summarizes a report GAO is issuing today.

GAO is recommending that the Secretary of Defense and the Secretary of
Veterans Affairs not use the plume-modeling data for any other
epidemiological studies of the 1991 Gulf War. VA concurred with our
recommendation. DOD did not concur but we have clarified the
recommendation to address DOD's concerns as we understand them. GAO also
recommends that the Secretary of Defense require no additional plume
modeling of Khamisiyah and other sites. DOD concurred with our
recommendation.

The Central Intelligence Agency (CIA) did not concur with our report,
stating it could not review the draft report in the time allotted.

June 2004

GULF WAR ILLNESSES

DOD's Conclusions about U.S. Troops' Exposure Cannot Be Adequately Supported

DOD's and MOD's conclusion about troops' exposure to CW agents, based on
DOD and CIA plume modeling, cannot be adequately supported. The models
were not fully developed for analyzing long-range dispersion of CW agents
as an environmental hazard. The modeling assumptions as to source term
data-quantity and purity of the agent-were inaccurate because they were
uncertain, incomplete, and nonvalidated.

The plume heights used in the modeling were underestimated and so were the
hazard area. Postwar field testing used to estimate the source term did
not realistically simulate the actual conditions of bombings or
demolitions. Finally, the results of all models-DOD and non-DOD
models-showed wide divergences as to the plume size and path.

DOD's and VA's conclusion about no association between exposure to CW
agents and rates of hospitalization and mortality, based on two
epidemiological studies conducted and funded by DOD and VA, also cannot be
adequately supported because of study weaknesses. In both studies, flawed
criteria-DOD's plume model and DOD's estimation of potentially exposed
troops based on this model-were used to determine exposure. This may have
resulted in large-scale misclassification.

Troops under the path of the plume were classified as exposed; those not
under the path, as nonexposed. But troops classified as not exposed under
one DOD model could be classified as exposed under another DOD model.
Under non-DOD models, however, a larger number of troops could be
classified as exposed. Finally, as an outcome measure, hospitalization
rate failed to capture the types of chronic illnesses that Gulf War
veterans report but that typically do not lead to hospitalization.

www.gao.gov/cgi-bin/getrpt?GAO-04-821T.

To view the full product, including the scope and methodology, click on
the link above. For more information, contact Keith Rhodes at (202)
512-6412 or [email protected].

June 1, 2004

Mr. Chairman and Members of the Subcommittee:

We are pleased to participate in this international hearing by presenting
our assessment of the plume modeling, conducted by the Department of
Defense (DOD) and the Central Intelligence Agency (CIA), to determine the
number of U.S. troops that might have been exposed to the release of
chemical warfare agents during the Gulf War in 1990. We presented our
preliminary results to you in our testimony on June 2, 2003.1 My statement
today is based on our final report, entitled Gulf War Illnesses: DOD's
Conclusions about U.S. Troops' Exposure Are Unsupported, which is being
issued today.2

As you know, many of the approximately 700,000 veterans of the Persian
Gulf War have experienced undiagnosed illnesses since the war's end in
1991. Some fear they are suffering from chronic disabling conditions
because of wartime exposures to vaccines, as well as chemical warfare
agents, pesticides, and other hazardous substances with known or suspected
adverse health effects. When the issue of the possible exposure of troops
to low levels of chemical warfare agents was first raised, during the
summer of 1993, DOD and the CIA concluded that no U.S. troops were exposed
because (1) there were no forward-deployed Iraqi chemical warfare agent
munitions and (2) the plumes-clouds of chemical warfare agents-from the
bombing that destroyed the Iraqi chemical facilities could not have
reached the troops.

This position was maintained until 1996, when DOD publicly disclosed that
U.S. troops destroyed a stockpile of chemical warfare agent munitions
after the Gulf War in 1991, at a forward-deployed site, Khamisiyah, in
Iraq. Consequently, DOD and the CIA conducted several analyses using
computer modeling, in an effort to estimate the number of troops that
might have been exposed to chemical warfare agents. Recognizing that
actual data on the source term-such as the quantity and purity

1U.S. General Accounting Office, Gulf War Illnesses: Preliminary
Assessment of DOD Plume Modeling for U.S. Troops' Exposure to Chemical
Agents, GAO-03-883T (Washington, D.C.: June 2, 2003). www.gao.gov.

2U.S. General Accounting Office, Gulf War Illnesses: DOD's Conclusions
about U.S. Troops Exposure Cannot Be Adequately Supported, GAO-04-159
(Washington, D.C.: June 1, 2004). www.gao.gov.

(concentration) of the agent-and the meteorological conditions-such as the
wind and the weather patterns-were not available,3 in 1996 and 1997, DOD
and the CIA conducted field-testing and modeling of the demolition of
Khamisiyah, to determine the size and path of the plume, as well as the
number of U.S. troops exposed to chemical warfare agents within the area
of the modeled plume's path. During these initial modeling efforts, DOD
also asked the Department of Energy's (DOE) Lawrence Livermore National
Laboratories (LLNL) to conduct modeling. In 1997, DOD and the CIA also
combined the results of five different meteorological and dispersion
models into a composite simulation of the plume area. They conducted
additional simulations, using meteorological and dispersal models, to
estimate the path of exposure from plumes during the bombings of sites
other than Khamisiyah-Al Muthanna, Muhammadiyat, and Ukhaydir. In 2000,
DOD revised its modeling estimates for the destruction of chemical warfare
agents at Khamisiyah, and estimated that 101,752 U.S. troops had
potentially been exposed.

In response to your request, we evaluated how well conclusions-about the
extent of exposure of U.S. troops and the association between CW exposure
and troops' hospitalization and mortality rates-are supported by available
evidence. Specifically, we have assessed the following:

1. 	How valid is the DOD and MOD conclusion---based on CIA and DOD
plume-modeling results-about U.S. and British troops' exposure to CW
agents?

2. 	What were the costs for the CIA's and DOD's various plume modeling
efforts?

3. 	How valid are the DOD and Department of Veterans Affairs (VA)
conclusions from epidemiological studies, based on DOD's plume modeling
results, that there was no association between CW exposure at Khamisiyah
and the troops' hospitalization and mortality rates?

3Observations were few because Iraq stopped reporting weather station
measurement information to the World Meteorological Organization in 1981.
As a result, data on the meteorological conditions during the Gulf War
were sparse. The only data that were available were for the surface wind
observation site, 80 to 90 kilometers away, and the upper atmospheric
site, about 200 kilometers away.

  Scope and Methodology

To determine the validity of DOD's conclusion-that U.S. troops' exposures
to chemical warfare agents were as DOD estimates suggested- based on its
plume-modeling analysis, we examined the meteorological and dispersion
models DOD used to model chemical warfare agent releases from the U.S.
demolition of Khamisiyah and Coalition bombings of Al Muthanna,
Muhammadiyat, and other sites in Iraq during the Gulf War deployment
period. We evaluated the basis for the technical and operational
assumptions DOD made in (1) conducting the modeling for the bombing and
demolition of Iraqi sites and (2) estimating the specific data and
information used in the modeling, relating to source term, meteorological
conditions, and other key parameters. We also evaluated the efforts of the
CIA and DOD to collect and develop data on source term and other key
parameters used in the modeling efforts.

We interviewed DOD and CIA modelers and officials involved with the
modeling and obtained documents and reports from DOD's Deployment Health
Support Directorate. We also interviewed and received documents from DOE
officials who were involved with the modeling at LLNL. In addition, we
interviewed officials and obtained documents from the Institute for
Defense Analyses (IDA) concerning the IDA expert panel assessment of CIA's
modeling of Khamisiyah. We also interviewed U.S. Army officials at Dugway
Proving Ground, Utah, to determine how chemical warfare agents might have
been released during the Khamisiyah pit area demolitions. Finally, we
interviewed officials at the U.S. Army Center for Health Promotion and
Preventive Medicine, to determine how specific troop unit exposures were
identified, and officials of the United Nations Monitoring, Verification,
and Inspection Commission (UNMOVIC), to obtain information on source term
data from the United Nations Special Commission's (UNSCOM) analyses and
inspections of the Khamisiyah, Al Muthanna, Muhammadiyat, and other sites.

To determine the validity of DOD's and the Department of Veterans Affairs'
(VA) conclusions-based on epidemiological studies-that there was no
association between Khamisiyah exposure and the rates of hospitalization
or mortality, we reviewed published epidemiological studies in which
hospitalization and mortality among exposed and nonexposed U.S. troops
were analyzed. We also interviewed the study authors and researchers and
examined the Gulf War population databases provided to the researchers by
DOD in support of these studies. We interviewed Veterans Benefits
Administration officials and obtained documents and reports on their
analyses of DOD's population databases.

We did not examine whether plume modeling data were being used by VA to
determine eligibility for treatment or compensation.

In an effort to identify the total costs associated with modeling and
related analyses of chemical warfare agent releases during the Gulf War;
we interviewed relevant officials and collected cost data from various DOD
agencies and DOD contractors who supported the modeling efforts.

To determine the extent of British troops' exposure to chemical warfare
agent-related releases during the Gulf War, we interviewed British
Ministry of Defense (MOD) officials in London and at Porton Down, and
reviewed U.K. Ministry of Defense reports concerning the potential effects
of exposure to chemical warfare agent-related releases on British forces.

We conducted our work from May 2002 through May 2004 in accordance with
generally accepted government auditing standards.

                                Results in Brief

DOD and MOD's conclusions, based on DOD's plume-modeling efforts regarding
the extent of U.S. and British troops' exposures to chemical warfare
agents, cannot be adequately supported. Given the inherent weaknesses
associated with the specific models DOD used and the lack of accurate and
appropriate meteorological and source term data in support of DOD's
analyses, we found five major reasons to question DOD and MOD's
conclusions. First, the models were not fully developed for analyzing
long-range dispersion of chemical warfare agents as an environmental
hazard. Second, assumptions regarding source term data used in the
modeling-such as the quantity and purity of the agent-were inaccurate,
since they were based on (1) uncertain and incomplete information and (2)
data that were not validated. Third, the plume heights from the Gulf War
bombings were underestimated in DOD's models. Fourth, postwar field
testing at the U.S. Army Dugway Proving Ground, to estimate the source
term data, did not reliably simulate the actual conditions of either the
bombings or the demolition at Khamisiyah. Fifth, there is a wide
divergence in results among the individual models DOD selected, as well as
in the unselected DOD and non-DOD models, with regard to the size and path
of the plume and the extent to which troops were exposed. Given these
inherent weaknesses, DOD and MOD cannot know which troops were and which
troops were not exposed.

The total costs for the various plume-modeling efforts to analyze the
potential exposure of U.S. troops-from the demolition at Khamisiyah and
the bombing of several other sites in Iraq-cannot be estimated. DOD

organizations and other entities involved with the plume-modeling efforts
could provide only direct costs (that is, contractors' costs), which
totaled about $13.7 million. However, this amount does not include an
estimate of the considerable indirect costs associated with the salaries
of DOD, VA, and contractors' staff or costs of facilities, travel, and
equipment. We requested, but DOD could not provide, this estimate. In
addition, the CIA would not provide direct and indirect costs for Gulf War
plume modeling because, in its view, our request constituted oversight of
an intelligence matter, beyond the scope of GAO authority. The CIA's
contractor, the Science Applications International Corporation (SAIC),
also did not respond to our request for cost data.

DOD's and VA's conclusions-that there is no association between exposures
to chemical warfare agents from demolitions at Khamisiyah and rates of
hospitalization and mortality among U.S. troops-also cannot be adequately
supported. DOD and VA based these conclusions on two government-funded
epidemiological studies, one conducted by DOD researchers, the other by VA
researchers.4 In each of these studies, flawed criteria were used to
determine which troops were exposed. For example, in each study, the
criteria used were based on (1) DOD plume modeling of exposures from
postwar demolition of the Khamisiyah munitions depot and (2) DOD's
estimates, using this modeling, of which troops were under the path of the
plume. Troops under the path of the plume were classified as exposed,
those not under the path as nonexposed. However, troops classified as
nonexposed under one DOD model could be classified as exposed under
another DOD model, thereby confounding the results. In the DOD models, a
small area was identified as being under the path of the plume, resulting
in a small number of troops identified as exposed. But in other modeling
not selected for consideration, such as that performed at the LLNL, for
example, a much larger, as well as different area, was identified as under
the path of the plume, resulting in the potential classification of a
larger number of troops as having been exposed. In addition, these exposed
troops included different troops from those in the DOD models-that is,
troops classified as exposed in the DOD selected models would have been
classified as nonexposed in the other models, even though the area of
coverage was much greater.

4G. C. Gray and others, "The Postwar Hospitalization Experience of Gulf
War Veterans Possibly Exposed to Chemical Munitions Destruction at
Khamisiyah, Iraq," American Journal of Epidemiology 150 (1999); H. K. Kang
and T.A. Bullman, "Mortality Among U.S. Veterans of the Persian Gulf War:
7 Year Follow-up," American Journal of Epidemiology 154 (2001): 399-409.

These flaws may have resulted in large-scale misclassification of the
exposure groups-that is, a number of exposed veterans may have been
classified as nonexposed, and a number of nonexposed veterans may have
been misclassified as exposed. In addition, in the hospitalization study,
the outcome measure-number of hospitalizations-would not capture the
chronic illnesses that Gulf War veterans commonly report, but which
typically do not lead to hospitalization. Several published scientific
studies of exposure involving Gulf War suggest an association between
low-level exposure to chemical warfare agents and chronic illnesses.

In our report, we are recommending that the Secretary of Defense and the
Secretary of Veterans Affairs not use the plume-modeling data for future
epidemiological studies of the 1991 Gulf War, since VA and DOD cannot know
from the flawed plume modeling who was and who was not exposed.

We are also recommending that the Secretary of Defense require no further
plume-modeling of Khamisiyah and the other sites bombed during the 1991
Gulf War in order to determine troops' exposure. Given the uncertainties
in the source term and meteorological data, additional modeling of the
various sites bombed would most likely result in additional costs, while
still not providing any definitive data on who was or was not exposed.

We obtained comments our draft of this report from VA, DOD, and CIA. VA
concurred with recommendation that VA and DOD not use the plumemodeling
data for future epidemiological studies, since VA and DOD cannot know from
the flawed plume modeling who was and who was not exposed. DOD did not
concur with the recommendation, indicating that to them it called for a
blanket prohibition of plume modeling in the future. The intent of our
recommendation is only directed at epidemiological studies involving the
DOD and CIA plume modeling data from the 1991 Gulf War and not a blanket
prohibition of plume modeling in future. We have clarified the
recommendation along these lines. DOD concurred with our second
recommendation, indicating that despite enhancements in the models,
uncertainties will remain. CIA did not concur with our report, indicating
that it could not complete its review in the time allotted.

Background 	According to the CIA, modeling is the art and science of using
interconnected mathematical equations to predict the activities of an
actual event. In this case, modeling was used to determine the direction

and extent of the plume from chemical warfare agents. In environmental
hazard modeling, simulations recreate or predict the size and path (that
is, the direction) of the plume, including the potential hazard area, and
potential exposure levels are generated.

                            Information for Modeling

In addition to identifying the appropriate event to model, modeling
requires several components of accurate information:

o  	the characteristics or properties of the material that was released
and its rate of release (for example, quantity and purity; the vapor
pressure; the temperature at which the material burns; particle size; and
persistency and toxicity); temporal information (for example, whether
chemical agent was initially released during daylight hours, when it might
rapidly disperse into the surface air, or at night, when a different set
of breakdown and dispersion characteristics would pertain, depending on
terrain, plume height, and rate of agent degradation);

o  	data that drive meteorological models during the modeled period (for
example, temperature, humidity, barometric pressure, dew point, wind
velocity and direction at varying altitudes, and other related measures of
weather conditions);

o  	data from global weather models, to simulate large-scale weather
patterns, and from regional and local weather models, to simulate the
weather in the area of the chemical agent release and throughout the area
of dispersion; and

o  	information on the potentially exposed populations, animals, crops,
and other assets that may be affected by the agent's release.

Types of Models Used 	Various plumes during the 1991 Gulf War were
estimated using globalscale meteorological models, such as the National
Centers for Environmental Prediction Global Data Assimilation System
(GDAS) and the Naval Operational Global Atmospheric Prediction System
(NOGAPS). Regional and local weather models were also used, including the
Coupled Ocean-Atmosphere Mesoscale Prediction System (COAMPS), the
Operational Multiscale Environmental Model with Grid Adaptivity (OMEGA),
and the Mesoscale Model Version 5 (MM5).

  DOD's Conclusion about U.S. Troops' Exposure to Chemical Warfare Agents Cannot
  Be Adequately Supported

Transport and diffusion models were also used during the 1991 Persian Gulf
War plume simulation efforts.5 These models estimate both the path of a
plume and the degree of potential hazard posed by the chemical warfare
agents. Dispersion models used during the Gulf War included the Hazard
Prediction and Assessment Capability (HPAC) along with its component, the
Second-order Closure Integrated Puff (SCIPUFF) model; the Vapor, Liquid,
and Solid Tracking (VLSTRACK) model; the Non-Uniform Simple Surface
Evaporation (NUSSE) model; and the Atmospheric Dispersion by
Particle-in-Cell (ADPIC) model.

DOD's conclusion about the extent of U.S. troops' exposure to chemical
warfare agents during and immediately after the Gulf War, based upon DOD
and CIA plume model estimates, cannot be adequately supported. This is
because of uncertainty associated with the source term data and
meteorological data. Further, the models themselves are neither
sufficiently certain nor precise to draw reasonable conclusions about the
size or path (that is, the direction) of the plumes.

In particular, we found five reasons to question DOD's conclusion. First,
the models DOD and the CIA selected were in house models not fully
developed for analyzing long-range dispersion of chemical warfare agents
as environmental hazards. DOD and CIA officials selected several in-house
models to run plume simulations. For Khamisiyah and the other Iraqi sites
selected for examination, DOD selected the COAMPS and OMEGA meteorological
models and the HPAC/SCIPUFF and VLSTRACK dispersion models. However, these
models were not at the time fully developed for modeling long-range
environmental hazards.

Second, the assumptions about the source term data used in the models are
inaccurate. The source term data DOD used in the modeling for sites at
Khamisiyah, as well as Al Muthanna and Muhammadiyat, contain significant
unreliable assumptions. DOD and the CIA based assumptions on field
testing, intelligence information, imagery, UNSCOM inspections, and Iraqi
declarations to UNSCOM. However, these assumptions were based on limited,
nonvalidated, and unconfirmed data concerning (1) the nature of the
Khamisiyah pit demolition, (2) meteorology, (3) agent purity, (4) amount
of agent released, and (5) other chemical warfare agent data. In addition,
DOD and the CIA excluded from their modeling efforts many

5We use dispersion in this report to refer to both transport and diffusion
models.

other sites and potential hazards associated with the destruction of
binary chemical weapons, vast stores of chemical warfare agent precursor
materials, and the potential release of toxic byproducts and chemical
warfare agents from other sites.6

Third, in most of the modeling performed, the plume heights were
significantly underestimated. Actual plume height would have been
significantly higher than the height DOD estimated in its modeling of
demolition operations and bombings. The plume height estimates that the
CIA provided for demolition operations at the Khamisiyah pit were 0 to 100
meters. However, neither DOD nor the CIA conducted testing to support
estimated plume height associated with the bombings of Al Muthanna,
Muhammadiyat, or Ukhaydir. According to DOD modelers, neither plume height
nor any other heat or blast effects associated with these bombings were
calculated from the models; instead, these data were taken from DOD's
Office of the Special Assistant for Gulf War Illnesses. In addition,
according to a principal Defense Threat Reduction Agency modeler, DOD's
data on plume height were inconsistent with other test data for the types
of facilities bombed.

Fourth, postwar field testing at the U.S. Army Dugway Proving Ground, in
Utah, to estimate the source term data did not realistically simulate the
actual conditions of the demolition operations at Khamisiyah or the
effects of the bombings at any of the other sites in Iraq. For field
testing to be effective, conditions have to be as close to the actual
event as possible, but these tests did not provide more definitive data
for DOD and CIA's models. The tests did not realistically simulate the
conditions of the demolition of 122 mm chemical-filled rockets in
Khamisiyah. The simulations took place under conditions that were not
comparable with those at Khamisiyah. There were differences in
meteorological and soil conditions; the construction material of munitions
crates; rocket construction (including the use of concrete-filled pipes as
rocket replacements to provide inert filler to simulate larger stacks);
and the number of rockets, with far fewer rockets and, therefore, less
explosive materials. In addition, in the tests, the agent stimulant used
had physical properties different from those of the actual agent.

6A binary weapon mixes two less-toxic materials to create a toxic nerve
agent within the weapon when it is fired or dropped.

Finally, there are wide divergences-with regard to the size and path of
the plume and the extent to which troops were exposed-among the individual
models DOD selected. The models DOD used to predict the fallout from
Khamisiyah and the other sites showed great divergence, even with the same
source term data. While the models' divergences included plume size and
paths, DOD made no effort to reconcile them. The IDA expert panel observed
that the results were so divergent that it would not be possible to choose
the most exposed areas or which U.S. troops might potentially have been
exposed. IDA therefore recommended a composite model, which DOD adopted.7
However, this approach only masked differences in individual model
projections with respect to divergences in plume size and path. In
addition, DOD chose not to include in the composite model the results of
the LLNL simulation, performed at the IDA expert panel's request. The LLNL
simulation estimated a larger plume size and different path from DOD's
models. The IDA panel regarded the LLNL model as less capable than other
models because it modeled atmospheric phenomena with less fidelity. A
modeling simulation done by the Air Force Technical Applications Center
(AFTAC) also showed significant divergences from DOD's composite model.

According to British officials, the MOD did not collect any source term or
meteorological data during the 1991 Persian Gulf War. It also did not
independently model the plume from Khamisiyah, relying instead on the 1997
DOD and CIA modeling of Khamisiyah. However, according to British MOD
officials, they were reassessing the extent of British troops' exposure,
based on DOD's revised 2000 remodeling of Khamisiyah. We requested from
the British MOD, but did not receive, information on the findings from
this reassessment.

The MOD also determined that a number of British troops were within the
boundary of the plume in the DOD and CIA composite model. The MOD
estimated that the total number of British troops potentially exposed was
about 9,000 and the total number of troops as "definitely" within the path
of the plume, however, was about 3,800. In addition, of 53,500 British
troops deployed, at least 44,000 were estimated as "definitely not" within
the path of the plume. However, since the MOD relied exclusively on DOD's
modeling and since we found that DOD could not know who was

  MOD Relied on U.S. Plume Modeling to Determine Their Troops' Exposure to
  Chemical Warfare Agents

7The composite approach DOD used is also known as the ensemble approach.

  Total U.S. Plume-Modeling Costs

and who was not exposed, the MOD cannot know the extent of British troops'
exposure.

The DOD and CIA were the primary agencies involved in the modeling and
analysis of U.S. troops' exposure from the demolition at Khamisiyah and
bombing of chemical facilities at Al Muthanna, Muhammadiyat, and Ukhaydir,
but several other agencies and contractors also participated. Funding to
support the modeling efforts was provided to various DOD agencies and
organizations, the military services, and non-DOD agencies and
contractors. We collected data on the direct costs these agencies incurred
or funds they spent. As shown in table 1, direct costs to the United
States for modeling the Gulf War were about $13.7 million.

Table 1: U.S. Direct Costs for Modeling Gulf War Illnesses

                  Agency or contractor Direct costsa Work done

BAHR Inc. $11,796 	Reviewed (1) processes and technology used to produce
estimates of U.S. forces potentially exposed and (2) draft reports on
Khamisiyah

                                       b

             Central Intelligence Agency Computer-modeling analysis

Chemical Biological Defense 140,000 Wood-surface evaporative modeling and
environmental data support efforts
Command, Aberdeen Proving
Ground

Defense Threat Reduction Agency 870,000 	Computer-modeling analyses with
HPAC/SCIPUFF dispersion and OMEGA weather models

Institute for Defense Analyses 149,429 Convened a panel of experts to
review Khamisiyah pit modeling analyses

Lawrence Livermore National 60,000 Computer-modeling analyses with ADPIC
dispersion and MATHEW Laboratory weather models

National Center for Atmospheric 308,000 Computer-modeling simulations
using MM5 weather model Research

Naval Research Laboratory 1,090,000 	Meteorological analysis to identify
downwind hazard assessment with NOGAPS and COAMPS weather models.

Naval Surface Warfare Center 522,000 	Computer-modeling analyses with
VLSTRACK dispersion and COAMPS weather models

Office of the Special Assistant to the 7,980,000 Internal costs for
producing case narratives for Al Muthanna, Khamisiyah, Deputy Secretary of
Defense for Gulf War Illnesses

                           Muhammadiyat, and Ukhaydir

                                       c

Science Applications International Computer-modeling analysis Corporation

U.S. Army Center for Health 731,000 Exposure assessment and environmental
modeling to determine U.S.

Promotion and Preventative Medicine 	troops' exposed to chemical releases
from multiple incidents during the Gulf War

    U.S. Army Dugway    1,861,950   Field trials and laboratory testing using 
     Proving Ground                           122 mm chemical-simulant filled 
                                    rockets to develop source term data for   
                                                    modeling                  
White Sands Missile    2,600      Missiles for testing at Dugway Proving   
          Range                                      Ground                   
          Total        $13,726,775 

Sources: Agency and contractor responses provided to GAO regarding their
modeling and analysis costs.

aDirect costs for agencies includes funding for contracts provided by the
Office of the Special Assistant to the Deputy Secretary of Defense for
Gulf War Illnesses.

bThe CIA denied our request for its costs for modeling chemical releases
from Khamisiyah, as well as Al Muthanna, Muhammadiyat, and Ukhaydir.

cSAIC did not respond to our requests for information.

  DOD's and VA's Epidemiology-Based Conclusions on Chemical Warfare Exposure and
  Rates for Hospitalization and Mortality Cannot Be Adequately Supported

DOD and VA each funded an epidemiological study on chemical warfare agent
exposure-DOD's on hospitalization rates and VA's on mortality rates. From
the hospitalization study, conducted by DOD researchers, and the mortality
study, conducted by VA researchers, on exposed and nonexposed troops, DOD
concluded that there was no significant difference in the rates of
hospitalization and VA concluded no significant difference in the rates of
mortality. These conclusions, however, cannot be supported by the
available evidence. These studies contained two inherent weaknesses: (1)
flawed criteria for classifying exposure, resulting in classification
bias, and (2) an insensitive outcome measure, resulting in outcome bias.
In addition, in several other published studies of 1991 Persian Gulf War
veterans, suggest an associations between chemical warfare exposure and
illnesses and symptoms have been established.

DOD and VA Used Flawed Criteria for Determining Troops' Exposure

In the two epidemiological studies, DOD and VA researchers used DOD's 1997
plume model for determining which troops were under the path of the
plume-who were estimated to be exposed-and which troops were not-those who
were estimated to be nonexposed. However, this classification is flawed,
given the inappropriate criteria for inclusion and exclusion.

In the hospitalization study, the DOD researchers included 349,291 Army
troops "coded" as being in the Army on February 21, 1991. However, the
researchers did not report cutoff dates for inclusion in the study-that
is, they did not indicate whether these troops were in the Persian Gulf
between January 17, 1991, and March 13, 1991, the period during which the
bombings and the Khamisiyah demolition took place. Although we requested
this information, DOD researchers failed to provide it. Finally, the total
number of 349,291 troops is misleading because many troops left the
service soon after returning from the Persian Gulf and therefore would not
have been hospitalized after the war in a military hospital-another
criterion for inclusion in the study. Moreover, the researchers did not
conduct any analyses to determine what number or percentage of those who
left active duty were in the exposed or nonexposed group (including
uncertain low-dose exposure or estimated subclinical exposure). Given all
the methodological problems in this study, it is not possible to
accurately estimate the total size or makeup of the exposed and nonexposed
population that may have sought or may have been eligible for care leading
to military hospitalization.

In the mortality study, the VA researchers included 621,902 Gulf War
veterans who arrived in the Persian Gulf before March 1, 1991. Troops

who left before January 17, 1991-the beginning of the bombing of Iraqi
research, production, and storage facilities for chemical warfare agents-
were included in the study. This group was not likely to have been
exposed. Therefore, including them resulted in VA's overestimation of the
nonexposed group.

Troops who came after March 1, 1991-the period during which Khamisiyah
demolition took place-were excluded from the VA study. The Defense
Manpower Data Center (DMDC) identified 696,000 troops deployed to the
Persian Gulf, but the mortality study included only the 621,902 troops
deployed there before March 1, 1991. This decision excluded more than
74,000 troops, approximately 11 percent of the total deployed. In
addition, 693 troops who were in the exposed group were excluded because
identifying data, such as Social Security numbers, did not match the DMDC
database. VA researchers did not conduct follow-up analysis to determine
whether those who were excluded differed from those who were included in
ways that would affect the classification.

DOD and VA Used an Insensitive Outcome Measure for Determining
Hospitalization Rates

Hospitalization rates-the outcome measure used in the hospitalization
study-were insensitive because they failed to capture the chronic
illnesses that 1991 Persian Gulf War veterans commonly report, but that
typically do not lead to hospitalization. Studies that rely on this type
of outcome as an end point are predetermined to overlook any association
between exposure and illness.

Based on DOD's 1997 plume model, DOD's hospitalization study compared the
rates for 1991 Persian Gulf War veterans who were exposed with the rates
for those who were nonexposed. This study included 349,291 active duty
Army troops who were deployed to the Persian Gulf. However, DOD
researchers did not determine the resulting bias in their analyses,
because they did not account for those who left the service.

The Institute of Medicine noted that the hospitalization study was limited
to Army troops remaining on active duty and to events occurring in
military hospitals. Conceivably, those who suffered from Gulf War-related
symptoms might leave active duty voluntarily or might take a medical
discharge. Hospitalization for this group would be reflected in VA or
private sector databases, but not in DOD databases. The health or other
characteristics of active duty troops could differ from those of troops
who

left active duty and were treated in nonmilitary hospitals. Moreover,
economic and other factors not related to health are likely to affect the
use of nonmilitary hospitals and health care services.8

This limiting of the study to troops remaining on active duty produced a
type of selection bias known as the healthy warrior effect.9 It strongly
biased the study toward finding no excess hospitalization among the active
duty Army troops compared with those who left the service after the war.

Some Studies Suggest an Association between Chemical Warfare Exposure and
Gulf War Illnesses

Gulf War Veterans Studies

We found some studies that suggest an association between chemical warfare
agent exposure and Gulf War illnesses. Each of these studies has both
strengths and limitations.

In a privately funded study, Haley and colleagues reported an association
between a syndromic case definition of Gulf War illnesses, developed to
model the ill veterans' symptomatic complaints, with exposure to CW
agents.10 In this study, the authors developed questionnaires on symptoms
and environmental exposure identified in pilot studies of ill Gulf War
veterans, similar to epidemic investigations by the Centers for Disease
Control and Prevention (CDC).11 These questionnaires were given to 249
troops from a U.S. Navy Mobile Construction Battalion that participated in
the Gulf War. Factor analysis of the data on symptoms was used to derive

8Institute of Medicine, Gulf War Veterans: Measuring Health (Washington,
D.C.: National Academy Press, 1999), p. 36.

9R. W. Haley, "Point: Bias from the `Healthy-Warrior Effect' and Unequal
Follow-Up in Three Government Studies of Health Effects of the Gulf War,"
American Journal of Epidemiology 148 (1998): 315-38.

10R. W. Haley and T. L. Kurt, "Self-Reported Exposure to Neurotoxic
Chemical Combinations in the Gulf War," JAMA 277 (1997): 231-37.

11See Michael B. Gregg, ed., Field Epidemiology, 2nd ed. (New York: Oxford
University Press, 2002).

a case definition identifying six syndrome factors.12 Three syndrome
factor variants found to be the most significant were (1) impaired
cognition, (2) confusion-ataxia, and (3) arthro-myo-neuropathy.

Impaired cognition (syndrome 1) was associated with troops' having worn
flea collars that contained chlorpyrifos.13 Confusion-ataxia (syndrome 2),
the most severe clinically, was associated with three risk factors.14 The
first was likely CW exposure; the second was the geographic location near
the Saudi-Kuwaiti border around the fourth day of the air war, conducted
January 18-23, 1991, when Czech chemical detection units detected sarin
and mustard in ambient air near the Saudi-Kuwaiti border; and the third
was side effects experienced after taking pyridostigmine. There was also a
significant synergistic association between likely exposure to CW agents
and the number of side effects from pyridostigmine.15 Arthro-myoneuropathy
(syndrome 3) was associated with the amount of exposure to 95 percent DEET
in ethanol insect repellent and with the number of side effects of
pyridostigmine.16

12R. W. Haley and others, "Is There a Gulf War Syndrome? Searching for
Syndromes by Factor Analysis of Symptoms," JAMA 277 (1997): 215-22. The
six syndrome factors were impaired cognition, confusion-ataxia,
arthro-myo-neuropathy, phobia-apraxia, feveradenopathy, and
weakness-incontinence.

13Impaired cognition is characterized by problems with attention, memory,
and reasoning, as well as insomnia, depression, daytime sleepiness, and
headache. (Study results showed relative risk 8.2, 95 percent, CI
2.9-23.5, p = 0.001.)

14Confusion-ataxia is characterized by problems with thinking,
disorientation, balance disturbances, vertigo, and impotence.

15(1) CW exposure, relative risk 7.8, 95 percent, CI 2.3-25.9, p < 0.0001;
(2) geographic location, relative risk 4.3, 95 percent, CI 1.9-10.0, p =
0.004; (3) pyridostigmine side effects, dose-response trend up to relative
risk 32.4, 95 percent, CI 7.8-135.0, p < 0.0001; (4) synergistic
association, Rothman synergy statistic 5.3, 95 percent, CI 1.04-26.7, p <
0.05. See Jonathan B. Tucker, "Evidence Iraq Used Chemical Weapons during
the 1991 Persian Gulf War," The Nonproliferation Review 4:3 (Spring-Summer
1997): 114-22. Center for Nonproliferation Studies, Monterey Institute of
International Studies, http://cns.miis.edu/pubs (Apr. 28, 2004); and U.S.
Department of Defense, Office of the Special Assistant for Gulf War
Illnesses, Coalition Chemical Detections and Health of Coalition Troops in
Detection Area (Washington, D.C.: Aug. 5, 1996).
http://www.gulflink.osd.mil/czech_french/czfr_refs/n08en011/coalitn.html
(Apr. 28, 2004).

16Arthro-myo-neuropathy is characterized by joint and muscle pains, muscle
fatigue, difficulty lifting, and paresthesias of the extremities. (Results
showed for exposure, doseresponse effect to relative risk 7.8, 95 percent,
CI 2.4-24.7, p < 0.0001; for side effects, doseresponse effect to relative
risk 3.9, 95 percent, CI 1.3-12.1, p < 0.0001.)

The inference that these risk-factor associations represent causal effects
is supported by (1) the large, highly significant relative risks; (2) the
doseresponse effects; and (3) the synergistic effect of the risk factor
associations with the syndromic case definition. Risk factors found not to
be significantly associated with the case definition include environmental
pesticides, pesticides in uniforms, antibiotic or antimalarial
prophylaxis, multiple immunizations, smoke from oil well fires, fumes from
jet fuel, fumes from burning jet fuel in tents, petroleum in drinking
water, depleted uranium munitions, smoking, alcohol use, and combat
exposure.

Another study of Gulf War veterans by Nisenbaum and colleagues, funded by
CDC, examined the risk factors in 1,002 Air Force reservists.17 They
found, first, that the case definition of Fukuda and colleagues of
"multisymptom illness" was strongly associated with at least one of the
three chronic symptom groups fatigue, mood/cognition, and musculoskeletal
pain. And, next, they found that reported exposure to CW agents was most
strongly associated with the "severe illness" case definition of Fukuda
and colleagues and less strongly associated with their "mild-moderate
illness" case definition.18

Both case definitions were less strongly associated with the use of insect
repellent (p = 0.006), the use of pyridostigmine (p = 0.01), and having an
injury requiring medical attention (p = 0.03). But neither case definition
was associated with smoke from oil well fires, coming under attack, seeing
casualties, or having adverse health events in the family. The findings
were attributed to the effects of stress but offered no empirical support
for the explanation.

In a study that VA funded, Proctor and colleagues compared the exposure
histories of 186 Gulf War veterans from Fort Devens, Massachusetts, and 66
from New Orleans, including 48 who deployed only to Germany. Collectively,
the 252 veterans are known as the Massachusetts-New

17R. Nisenbaum and others, "Deployment Stressors and a Chronic
Multisymptom Illness among Gulf War Veterans," Journal of Nervous and
Mental Disease 188 (2000): 259-66.

18Association with "severe illness," adjusted OR 3.46, 95 percent, CI
1.73-6.91, p < 0.0001; association with "mild-moderate illness," adjusted
OR 2.25, 95 percent, CI 1.54-3.27, p < 0.0001. See K. Fukuda and others,
"A Chronic Multisymptom Illness Affecting Air Force Veterans of the
Persian Gulf War," JAMA 280 (1998): 981-88.

Orleans cohort.19 The case definition was a set of eight body-system
symptom scores (BSS, distributed from 0 to 4), each constructed by summing
the 5-point frequency-of-occurrence scales (0 = occurs never, 4 = occurs
almost every day) for three symptoms typical of a particular body system.
The eight body systems were cardiac, dermatological, gastrointestinal,
musculoskeletal, neurological, neuropsychological, psychological, and
pulmonary. Post-traumatic stress disorder (PTSD) was diagnosed with the
structural clinical interviews, Clinician Administered Posttraumatic
Stress (CAPS) disorder scale, or a Mississippi Scale score of >89. The
symptoms were obtained from the 52-item Expanded Health Symptom Checklist,
the exposure measures from an environmental exposure questionnaire and an
Expanded Combat Exposure Scale (CES) questionnaire. Multiple regression
analysis-controlling for age, sex, education, study site, Expanded CES
score, and PTSD status-was used to develop a risk-factor model for each
BSS scale.

Exposure to CW agents and debris from SCUD missiles was associated with
four BSS scales; exposure to smoke from tent heaters, with three BSS
scales; exposure to pesticides, vehicle exhaust, and burning human waste,
with two BSS scales; the Expanded CES, with only one BSS scale; and
exposure to pyridostigmine bromide (antinerve gas pills) and smoke from
oil well fires, with no BSS scale. Controlling for depression scores and
excluding veterans diagnosed with PTSD did not substantially affect the
associations.

Three additional studies conducted with VA and DOD funding extended the
risk-factor research for the Massachusetts-New Orleans cohort. The
association of self-reported CW agent (nerve agent) exposure was tested
with different formulations of the case definition. White and colleagues
used psychological and neuropsychological tests to define illness. They
found that exposure to CW agents was associated with abnormal measures of
mood, memory, and attention or executive function.20 Associations remained
significant after controlling for age, sex, race, years of education,
repeated grade in school, head injury, medication use, diagnosis of
current

19S. P. Proctor and others, "Health Status of Persian Gulf War Veterans:
Self-Reported Symptoms, Environmental Exposures, and the Effect of
Stress," International Journal of Epidemiology 27 (1998): 1000-10.

20R. F. White and others, "Neuropsychological Function in Gulf War
Veterans: Relationships to Self-Reported Toxicant Exposures," American
Journal of Industrial Medicine 40 (2001): 42-54.

PTSD (by CAPS), diagnosis of current depression (by structural clinical
interviews), active duty versus Reserve or Guard status, seeking
disability rating, and Vietnam service.

Lindem and colleagues developed multiple regression models for
neuropsychological test measures as case definitions of Gulf War
illnesses.21 Chemical warfare agent exposure was found to be associated
with attention and executive function (continuous performance test),
delayed verbal recall (California Verbal Learning Test and Visual
Reproduction Test), and confusion and fatigue (Profile of Mood States).
These associations remained significant when controlling for age,
education, and PTSD diagnosis (by CAPS).

Wolfe and colleagues, studying 945 troops from the Massachusetts-New
Orleans cohort, found that the CDC case definition of multisymptom illness
was most strongly associated with having smelled a chemical odor, having
taken up to 21 antinerve gas pills, or having experienced up to 10 formal
alerts for CW agent attack.22

Kang and colleagues conducted a random sample mail survey that VA funded.
Obtaining responses from 11,441 Gulf War veterans and 9,476 nondeployed
Gulf War era veterans, they developed a case definition by factor analysis
of symptoms measured by their questionnaire.23 The first three syndrome
factors closely resembled those that Haley and others derived (noted
earlier). Finding that syndrome 2 was unique to the sample that had been
deployed in the Gulf War (found in the deployed, but not the nondeployed,
sample) and that the component symptoms were neurological in character,
the researchers termed their syndrome 2 a possible unique Gulf War
neurological syndrome. Four symptoms- blurred vision, loss of balance or
dizziness, tremor or shaking, and speech difficulties-were associated with
syndrome 2 only in the deployed sample. Consequently, Kang and colleagues
established their case

21K. Lindem and others, "Neuropsychological Performance in Gulf War Era
Veterans: Traumatic Stress Symptomatology and Exposure to
Chemical-Biological Warfare Agents, Journal of Psychopathology and
Behavioral Assessment 25:2 (2003): 105-19.

22Chemical odor, OR = 6.2, 95 percent, CI 3.9-9.9; antinerve gas pills, OR
= 3.7, 95 percent, CI 2.4-5.6; formal alerts for CW attack, OR = 2.7, 95
percent, CI 2.0-3.7. See J. Wolfe and others, "Risk Factors for
Multisymptom Illness in U.S. Army Veterans of the Gulf War," Journal of
Occupational and Environmental Medicine 44:3 (2002): 271-81.

23H. K. Kang and others, "Evidence for a Deployment-Related Gulf War
Syndrome by Factor Analysis," Archives of Environmental Health 57:1
(2002): 61-68.

definition as having all four of these symptoms. In the deployed sample,
277 met the case definition and 6,730 who had none of the four symptoms
constituted the control group. Of a large number of risk factors analyzed,
only nine were associated with the case definition, with an odds ratio
greater than 3.0. Of these, perceived exposure to nerve agent had the
strongest association (odds ratio 15.1, 95 percent, CI 11.5-19.9, p <
0.000001). This finding-a neurological syndrome appearing as the second
factor in a factor analysis and being the most strongly associated risk
factor, 15 times more common in ill veterans meeting the case definition
than in controls-closely parallels the findings of Haley and colleagues.
The finding received little notice, however, because the VA-funded mail
survey did not (1) provide the odds ratio values in the table reporting
the risk factor analysis results and (2) describe the finding in the text
or abstract of the paper. When we noticed the finding, we manually
calculated the odds ratios from the raw data in the table.

Smith and colleagues showed that hospitalization rates for several ICD-9
diagnoses were higher in veterans categorized in the Khamisiyah 2000 plume
than in those not in the plume, and the association for cardiac
arrhythmias was statistically significant. However, this study suffers
from the same deficiencies as the earlier study that we cited: use,
inappropriately, of hospitalization outcome measures rather than measures
of Gulf War illness, which usually do not result in hospitalization, and
use of plume modeling based on flawed data.24

The 2002 Kang and Bullman study has not been published in a peerreviewed
journal and therefore should not have been included in a review of the
scientific epidemiologic literature. The DOD studies were invalid for two
reasons: (1) Hospitalization and mortality were inappropriate outcomes
because they do not measure Gulf War illnesses, which often do not lead to
hospitalization, and (2) The DOD studies, no matter how powerful their
techniques, could not control for the selection bias that resulted from
the disproportionate early discharge of the ill Gulf War veterans soon
after the Gulf War. Including only DOD hospital records of service members
remaining on active duty resulted in the exclusion of veterans who left
service for poor health. No amount of sophisticated

24T. C. Smith and others, "Gulf War Veterans and Iraqi Nerve Agents at
Khamisiyah: Postwar Hospitalization Data Revisited," American Journal of
Epidemiology 158 (2003): 457-67.

Genetics Studies

techniques can correct for this selection bias toward finding no

25

difference.

In one genetics study, Haley and colleagues found an association between
the case definition of Gulf War illnesses in U.S. Gulf War veterans and
low blood levels of the Q-type isoenzyme of the paraoxonase/arylesterase
enzyme group (PON).26 The PON group of enzymes is a potentially important
predisposing factor in Gulf War illnesses because one of its major
functions in normal body physiology is to protect the nervous system from
organophosphate chemical toxins, such as pesticides and nerve agents. This
finding was remarkable because the only function of Q type of the PON
enzyme group is to protect the nervous system from nerve agents sarin,
soman, tabun, and VX. The R-type isoenzyme has as its main function
protection from organophosphate pesticides, such as diazinon, malathion,
and parathion. Thus, an association between Gulf War illnesses and blood
levels of only the Q-type isoenzyme of PON points specifically to nerve
agent exposure. In addition, the total PON level-that is, the sum of the Q
and R isoenzyme levels-was not associated with the illnesses. And the
genotype (QQ, QR, or RR) was only marginally associated with them, as
expected, because the level of the Q-type isoenzyme is a more important
determinant of susceptibility to nerve agents than the genotype.

In another genetics study, Mackness and colleagues reported lower blood
levels of total PON in ill British Gulf War veterans than in civilian
controls in a previously published study; however, they did not measure
the blood levels of the Q and R isoenzymes of PON, needed for a definitive
study of Haley's hypothesis.27 This finding could indicate that ill
British Gulf War veterans represented a mixture of some with low Q-type
PON and others with low R-type PON. In some veterans, the illness would be
associated with exposure to nerve agents; in others, with exposure to
pesticides. Alternatively, the difference in total PON levels may have
resulted from differences in the assays or in the veterans, since (1) the
enzyme assays in

25H. K. Kang and T. A. Bullman, Mortality among U.S. Gulf War Veterans Who
Were Potentially Exposed to Nerve Gas at Khamisiyah, Iraq (Washington, DC:
Department of Veterans Affairs, May 2002).

26R. W. Haley and others, "Association of Low PON1 Type Q (Type A)
Arylesterase Activity with Neurologic Symptom Complexes in Gulf War
Veterans," Toxicology and Applied Pharmacology 157 (1999): 227-33.

27B. Mackness and others, "Low Paraoxonase in Persian Gulf War Veterans
Self-Reporting Gulf War Syndrome," Biochemical and Biophysical Research
Communications 276 (2000): 729-33.

the controls were performed years before those for the ill veterans and
(2) the controls were civilians studied in an entirely different setting.

In yet a third genetics study, Hotopf and colleagues reported results of
tests for total PON levels in blood samples-obtained in a study by Unwin
and colleagues-for four groups of British troops: (1) ill veterans of the
Gulf War, (2) well veterans of the Gulf War, (3) ill nondeployed veterans
of the Gulf War era, and (4) ill veterans of the Bosnian conflict.28 The
case definition of illness was a score below 72.2 on the SF-36 Physical
Status questionnaire. Again, the researchers did not measure the levels of
the Q and R isoenzymes of PON, making the findings difficult to interpret.
The researchers found a low mean level of total PON in both ill and well
groups deployed to the Gulf War and higher levels in the Gulf War era and
ill Bosnian groups.

The depressing of the total PON level, the researchers suggested, might be
the result of some deployment-related exposures. However, instead of
looking at exposure to CW agents, the researchers investigated the
possible effect of multiple immunizations on total PON levels and found no
evidence for it. An alternative explanation is that total PON level in
both ill and well deployed veterans was the result of misclassification of
veterans by the case definition. A score of 72.2 on the SF-36 scale is not
a very low score, particularly in ill Gulf War veterans, and it is a
nonspecific measure of illness, given that a low score indicates illness
from any cause.29 Consequently, many veterans ill from causes unrelated to
the war would be misclassified as cases of Gulf War illness and,
conversely, many ill from the war but with less disability would be
misclassified as controls. This conclusion is supported by a
nonsignificant trend showing that ill veterans who had been deployed to
the Gulf War had a lower median total PON level than well veterans who had
also been deployed to the Gulf War.

The many flaws of design and methodology in both British studies of PON
levels do not contribute to an understanding of the PON hypothesis and
leave the finding of Haley and colleagues in need of better replication.

28See Matthew Hotopf and others, "Paraoxonase in Persian Gulf War
Veterans," Journal of Occupational and Environmental Medicine 45 (2003):
668-75, and C. Unwin and others, "Health of UK Servicemen Who Served in
the Persian Gulf War," Lancet 353 (1999): 169-78.

29R. W. Haley and others, "Severely Reduced Functional Status in Veterans
Fitting a Case Definition of Gulf War Syndrome," American Journal of
Public Health 92 (2002): 46-47.

Animal Studies

A series of laboratory studies with animals have established the
biological plausibility that brain cell damage results from low-level
exposure to sarin. Husain and colleagues demonstrated in two studies at
the Division of Pharmacology and Toxicology at the Defense Research and
Development Establishment in Gwalior, India, that repetitive
administration of low-dose sarin (approximately 0.25 LD50) daily for 10
days caused delayed onset damage to neurons in the spinal cords and brains
of mice exposed by inhalation and of hens exposed by subcutaneous
injection.30

Privately funded studies by Abou-Donia and colleagues demonstrated that
combinations of organophosphates and similar cholinesterase-inhibiting
chemicals in hens produce greater neurotoxic effect on brain and nerve
tissue than any of the agents alone.31 Abou-Donia's subsequent work,
funded by DOD, extended the findings to synergistic combinations involving
sarin at moderate concentrations (0.5 LD50).32 A similar study by Husain
and Somani, also funded by DOD, on the delayed brain effects of low-dose
sarin (0.05 LD50) in combination with pyridostigmine and exercise,
confirmed these findings. In particular, it demonstrated that the neuronal
damage from very low doses of sarin affected primarily the basal ganglia
region of the brain (striatum).33

A study by Henderson and colleagues, with DOD funding, found that repeated
inhalation exposure to low-level sarin at subsymptomatic doses

30K. Husain and others, "Delayed Neurotoxic Effect of Sarin in Mice after
Repeated Inhalation Exposure," Journal of Applied Toxicology 13 (1993):
143-45, and "A Comparative Study of Delayed Neurotoxicity in Hens
Following Repeated Administration of Organophosphorus Compounds," Indian
Journal of Physiology and Pharmacology 39 (1995): 47-50.

31Mohamed B. Abou-Donia and others, "Neurotoxicity Resulting from
Coexposure to Pyridostigmine Bromide, DEET, and Permethrin," Journal of
Toxicology and Environmental Health 48 (1996): 35-56, and "Increased
Neurotoxicity Following Concurrent Exposure to Pyridostigmine Bromide,
DEET, and Chlorpyrifos," Fundamentals of Applied Toxicology 34 (1996):
201-22.

32Mohamed B. Abou-Donia and others, "Combined Exposure to Sarin and
Pyridostigmine Bromide Increased Levels of Rat Urinary 3-Nitrotyrosine and
8-Hydroxy-2'-Deoxyguanosine, Biomarkers of Oxidative Stress," Toxicology
Letters 123 (2001): 51-58; "Disruption of the Blood-Brain Barrier and
Neuronal Cell Death in Cingulate Cortex, Dentate Gyrus, Thalamus, and
Hypothalamus in a Rat Model of Gulf-War Syndrome," Neurobiology of Disease
10 (2002): 306-26; and "Sarin: Health Effects, Metabolism, and Methods of
Analysis," Food and Chemical Toxicology 40 (2002): 1327-33.

33K. Husain and S. Somani, "Delayed Toxic Effects of Nerve Gas Sarin and
Pyridostigmine under Physical Stress in Mice," Journal of Burns and
Surgical Wound Care 2 (2003): 2-19.

(0.1 LCt50) for 5 or 10 days, with or without heat stress, produced no
immediate effects.34 But at 30 days after exposure to sarin, damage was
produced to cholinergic receptors in several brain regions, including the
basal ganglia. In the same study, Henderson and colleagues identified
evidence of an autonomic nervous system injury affecting the function of
T-cells in the immune system as well.35 In addition, chronic abnormalities
of neuronal metabolism in the basal ganglia have been implicated in ill
Gulf War veterans by several investigators through the use of magnetic

36

resonance spectroscopy.

Two recent laboratory studies at the U.S. Army Medical Research Institute
of Chemical Defense, Aberdeen Proving Ground, support the animal studies.
Scremin and colleagues demonstrated that moderate doses of sarin (0.5
LD50) in combination with pyridostigmine bromide produced prolonged
elevations in rats' cerebral blood flow but that neither agent alone had a
prolonged effect on cerebral blood flow.37 A companion study, by Roberson
and colleagues, demonstrated that repeated administration of sarin to
guinea pigs in doses of 0.2 or 0.4 LD50 produced no immediate ill effects
on behavior, weight, body temperature, flinch threshold, or EEG brain wave
activity. But at 100 days postdosing, abnormal brain function was found,
indicating neurochemical or pathological brain cell changes

38

that affect behavior.

34R. F. Henderson and others, "Response of F344 Rats to Inhalation of
Subclinical Levels of Sarin: Exploring Potential Causes of Gulf War
Illness," Journal of Toxicology and Industrial Health 17 (2001): 294-97
and 18:1 (2002): 48.

35See Henderson and others, "Response of Rats to Low Levels of Sarin," and
"Subclinical Doses of the Nerve Gas Sarin Impair T Cell Responses through
the Autonomic Nervous System," Journal of Toxicology and Applied
Pharmacology 184 (2002): 82-87.

36See R. W. Haley and others, "Brain Abnormalities in Gulf War Syndrome:
Evaluation by 1H Magnetic Resonance Spectroscopy," Radiology 215 (2000):
807-17, and "Effect of Basal Ganglia Injury on Central Dopamine Activity
in Gulf War Syndrome: Correlation of Proton Magnetic Resonance
Spectroscopy and Plasma Homovanillic Acid," Archives of Neurology 57
(2000): 1280-85, as well as D. J. Meyerhoff and others, "Reduced
N-Acetylaspartate in the Right Basal Ganglia of Ill Gulf War Veterans by
Magnetic Resonance Spectroscopy," Proceedings of the International Society
of Magnetic Resonance Medicine 9 (2001): 994.

37O. U. Scremin and others, "Effects of Chronic Exposure to Low Levels of
Cholinesterase Inhibitors on Cerebral Blood Flow," paper for the Society
for Neuroscience Meeting, Orlando, Florida, 2002.

38Melinda Roberson and others, "Depression of Cholinesterase Activity by
Low-Dose Sarin Exposure May Lead to Persistent Changes That Influence
Behavior," Society for Neuroscience, Washington, D.C., Program no. 205.3
(Abstract, 2002).

Conclusions

In evaluating the plume models used, the results from the DOD and CIA
modeling can never be definitive. Plume models can allow only estimates of
what happens when chemical warfare agents are released in the environment.
Such estimates are based on mathematical equations, which are used to
predict an actual event-in this case, the direction and extent of the
plume. However, in order to predict precisely what happens, one needs to
have accurate data on relative to both source term and meteorological
conditions. DOD had neither of these.

Given the unreliability of the input data, the lack of individual troop
location information, and the widely divergent results of the simulations
conducted based on varying models, DOD's analyses cannot adequately
estimate the extent of U.S. troops' exposure to chemical warfare agents
and other related releases. In particular, the models selected were not
fully developed for projecting long-range environmental fallout, and the
assumptions used to provide the source term data were inaccurate or
flawed. Even when models with the same source term data were used, the
results diverged. In addition, the models did not include many potential
exposure events and exposures to some key materials-for example, binary
chemical weapons, mustard agent combustion by-products, and chemical
warfare agent precursor materials. It is likely that if models were more
fully developed and more credible data for source term and meteorological
conditions were included in them, particularly with respect to plume
height as well as level and duration of exposure, the hazard area would be
much larger and most likely would cover most of the areas where U.S.
troops and Coalition forces were deployed. However, given the lack of
verifiable data for analyses, it is unlikely that any further modeling
efforts would be more accurate or helpful.

The results of DOD's modeling efforts were, nonetheless, used in
epidemiological studies to determine the troops' chemical warfare agent
exposure classification-i.e., exposed versus nonexposed. As we noted in
1997, to ascertain the causes of veterans' illnesses, it is imperative
that investigators have valid and reliable data on exposure, especially
for lowlevel or intermittent exposures to chemical warfare agents.39 To
the extent that veterans are misclassified as to exposure, relationships
will be obscured and conclusions misleading. In addition, DOD combined the

39U.S. General Accounting Office, Gulf War Illnesses: Improved Monitoring
of Clinical Progress and Reexamination of Research Emphasis Are Needed,
GAO/NSIAD-97-163 (Washington, D.C.: June 23, 1997).

  Recommendations for Executive Action

results of individual models that showed smaller plume size and ignored
the results of the LLNL which showed much larger plume size and divergent
plume path. Given the uncertainties in source term data and divergences in
model results, DOD cannot determine or estimate-with any degree of
certainty-the size and path of the plumes or who was or who was not
exposed.

In our report, we are recommending that the Secretary of Defense and the
Secretary of Veterans Affairs not use the plume-modeling data for future
epidemiological studies of the 1991 Gulf War, since VA and DOD cannot know
from the flawed plume modeling who was and who was not exposed.

We are also recommending that the Secretary of Defense require no further
plume-modeling of Khamisiyah and the other sites bombed during the 1991
Persian Gulf War in order to determine troops' exposure. Given the
uncertainties in the source term and meteorological data, additional
modeling of the various sites bombed would most likely result in
additional cost, while still not providing DOD with any definitive data on
estimating who was or was not exposed.

We obtained comments on a draft of this report from VA, DOD, and CIA. VA
concurred with the recommendation that VA and DOD not use the
plume-modeling data for future epidemiological studies, since VA and DOD
cannot know from the flawed plume modeling who was and who was not
exposed. DOD did not concur with the recommendation, indicating that to
them it called for a blanket prohibition of plume modeling in the future,
where the limitations of the 1991 Gulf War may not apply. The intent of
our recommendation is only directed at epidemiological studies involving
the DOD and CIA plume modeling data from the 1991 Gulf War and not a
blanket prohibition of plume modeling in the future. We have clarified the
recommendation along these lines. DOD concurred with our second
recommendation, indicating that despite enhancements in the models,
uncertainties will remain. CIA did not concur with our report, indicating
that it could not complete its review in the time allotted.

If you or your staff have any questions about this testimony or would like
additional information, please contact me at (202) 512-6412 or Sushil
Sharma, Ph.D., Dr.PH., at (202) 512-3460. We can also be reached by e-mail
at [email protected] and [email protected]. Individuals who made key
contributions to this testimony were Venkareddy Chennareddy, Susan Conlon,
Neil Doherty, Jason Fong, Penny Pickett, Laurel Rabin, and Katherine
Raheb. James J. Tuite III, a GAO consultant, provided technical expertise.

Keith Rhodes, Chief Technologist Center for Technology and Engineering

Applied Research and Methods

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