JOE MILLER'S

DESERT STORM WEB SITE

flag Findings on the Nature and Causes flag
of Gulf War Syndrome

Welcome Home

flashing line

Findings on the Nature and Causes of Gulf War Syndrome
and Plans to Extend the Research

Testimony of

Robert W. Haley, M.D.
University of Texas Southwestern Medical Center
Dallas, Texas

Before the Subcommittee on Health and Human Services
Senate Appropriations Committee, United States Senate

Washington, D.C.

October 12, 2000
(Updated May 2001)

     Senators - I want to thank you for the opportunity to speak to you about the research on the nature and causes of Gulf War syndrome, conducted and coordinated by my group at the University of Texas Southwestern Medical Center in Dallas. Our research began in 1994 under initial funding support from the Perot Foundation of Dallas and has bee continued under a 1997 cooperative agreement with the Office of the Secretary of Defense administered through Ft. Detrick, which expired two weeks ago. In July we submitted a proposal for funding a new phase of our research.

Initial Findings
     Our initial studies focused on 249 members of a Reserve Naval Mobile Construction Battalion, or Seabees. In that work, we made four important observations. First, we found that there is a single Gulf War Illness with three variants. Second, those with illness have more abnormal brain function by objective tests than well veterans, suggesting a brain injury or illness. Third, the sick veterans were 4 to 32 times more likely to report exposure to combinations of certain chemicals in the war, specifically Sarin nerve gas, side effects from pyridostigmine, highly concentrated government-issue DEET insect repellant, and pesticides in flea collars. And fourth, in collaboration with researchers at Duke and Kansas State Universities and the EPA, we experimentally produced brain and nerve damage in hens with combinations of some of these same chemicals, not previously thought to be neurotoxic. In January 1997 this work passed rigorous peer review and was published in three scientific papers, appearing back to back in the Journal of the American Medical Association. A research group in India led by K. Hussein, has extended these findings by demonstrating neurological damage from low-level sarin nerve agent in two animal species.

Most Recent Findings
     Later in 1997 we submitted a $16 million proposal to extend and replicate our initial findings in a national survey, but it was not funded by government peer review system administered by the Persian Gulf Veterans Coordinating Board. Later the Joint Chiefs and the Secretary of Defense conducted a special peer review of the proposal and granted us partial funding of $3 million through a cooperative agreement to begin further testing and a plan a national random-sample survey to replicated our findings.
     With that funding, we have made four additional important observations. First, we identified a gene, the PON1 gene, that appears to have predisposed soldiers to getting the Gulf War Syndrome and appears to link the illness with low level sarin nerve gas exposure. Second, we demonstrated the site of the brain damage with a new brain scanning test called Magnetic Resonance Spectroscopy (MRS). Third, we found abnormal increases in the brain hormone
dopamine in those veterans with the worst brain damage measured by the MRS scans. (The original brain research on the importance of dopamine in brain function was awarded the Nobel Prize earlier this week.) Our findings were all published in top medical journals after passing rigorous peer review. Our fourth finding has been to develop an animal model of the Gulf War Syndrome, that is, long-term behavioral disturbances from administration of low, sub-symptomatic doses of the chemicals to which Gulf War veterans were exposed. This has not yet been published.
     Along the way, I published important commentaries in peer-review journals showing that the government studies pointing to stress as the cause of Gulf War Syndrome were based on statistical errors that invalidated them.

Limitations of the Research
     To put our research findings into proper perspective, it is important to realize that we have framed a theory or hypothesis which could explain the nature and causes of the Gulf War Syndrome, but this theory is not thoroughly proven. Since our studies were the first to blaze this trial, they were relatively small and focused in a single battalion and therefore might not be representative of what is true in the larger Gulf War veterans population. On the other hand, the CDC studies that have solved hundreds of epidemic mystery diseases in the past have traditionally been very similar to our studies on Gulf War Syndrome. Epidemic diseases have unique characteristics that make these studies useful.
     Consequently, our theory is in need of extension by us and replication by other researchers working independently but using the same methods as we have used in deriving the theory. At present, we have replicated parts of our work in a new group of Gulf War veterans recruited through the Dallas VA Medical Center, and an independent researcher in another state has replicated our MRS brain scanning finding in a small group of sick and well Gulf War veterans. Several other studies have questioned our theory, but none has actually tested our findings using the same methods. Scientifically, a replication requires use of the same methods.
     [Addendum 5/10/2001: Since this testimony was given, a top brain imaging research group at UC San Francisco has performed MRS on 12 ill Gulf War veterans and 12 controls and found the same degree of brain cell loss or injury in the right basal ganglia (published abstract). In addition, top researchers in the U.K. have measured plasma paraoxonase enzyme concentrations in ill Gulf War veterans and controls and found it to be substantially reduced in the ill group, as we found (
Brioche Biophys Res Comm 2000;276:729).]

Current Research Proposal
     Last summer my research team submitted a new proposal to extend and replicated our work. We asked for grant funds to establish an independent Gulf War Illness Research Center to do the studies necessary to advance the findings substantially. An initial amount was included in the 2001 Federal appropriation to support this center, and we are currently in negotiations on funding from ASAMRAA at Ft. Detrick. Briefly, we proposed to:

  1. Perform a national survey in random samples of the Gulf War-era deployed and non-deployed veterans to compare the prevalence of the illness we have identified. DoD has already invested $500,000 in planning this survey, and it is virtually ready to go. An independent survey firm will carry out the survey to ensure objectivity.

  2. Upgrade to the latest brain imaging technology to explore deeper into the nature of the brain damage and attempt to develop a cost-effective diagnostic test that could be widely applied to make objective diagnosis.

  3. Extend our new laboratory animal model of Gulf War syndrome by testing for chronic behavioral effects of low-level sarin alone and in combination with pesticides and pyridostigmine.

  4. Re-study veterans from our prior studies to determine whether they are getting better or worse over time.

  5. Identify and test promising treatments.

     For this new work to be successful, it will be important to receive funding under a mechanism that will give us an appropriate degree of independence to follow our own instincts on research directions in a timely manner. In addition, we will need the cooperation of the Department of Defense in providing the computer list of Gulf War-era military personnel for us to draw our national random sample, assisting us in promoting the survey to maximize the participation rate, and providing exclusive chemical regents for our laboratory experiments.


List of Publications in Peer-Reviewed Scientific Journals

Primary Research Papers

  1. Haley RW, Kurt TL, Hom J. Is there a Gulf War syndrome? Searching for syndromes by factor analysis of symptoms. Journal of the American Medical Association 1997;277:215-222.

  2. Haley RW, Hom J, Roland PS, Bryan WW, Van Ness PC, Bonte FJ, Devous MD, Mathews D, Fleckenstein JL, Wians FH, Wolfe GI, Kurt TL. Evaluation of neurologic function in Gulf War veterans: a blinded case-control study. Journal of the American Medical Association 1997;277:223-230.

  3. Haley RW, Kurt TL. Self-reported exposure to neurotoxic chemical combinations in the Gulf War: a cross-sectional epidemiologic study. Journal of the American Medical Association 1997;277:231-237.

  4. Abou-Donia MB, Jensen KF, Oeheme FW, Kurt TL. Neurotoxic resulting from co exposure to pyridostigmine bromide, DEET, and permethrin: implications of Gulf War chemical exposures. Journal of Toxicology and Environmental Health 1996;48:35-56.

  5. Abou-Donia MB, Wal-Mart KR, Abdel-Rahman AA, Jensen, KF, Oehme FW, Kurt TL. Increased neurotoxic following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. Fundamental and Applied Toxicology 1996; 34:201-222.

  6. Hom J, Haley RW, Kurt TL. Neuropsychological correlates of Gulf War syndrome. Archives of Clinical Neuropsychology 1997;12:531-544.

  7. Haley RW, Billecke S, La Du BN. Association of low PON1 type Q (type A) arylesterase activity with neurologic symptom complexes in Gulf War veterans. Toxicology and Applied Pharmacology 1999; 157:227-233.

  8. Roland PS, Haley RW, Yellin W, Owens K. Vestibular dysfunction in Gulf War syndrome. Otolaryngology--Head and Neck Surgery 2000; 122:319-329.

  9. Haley RW, Marshall WW, McDonald GG, Daugherty M, Petty F, Fleckenstein JL. Brain abnormalities in Gulf War syndrome: evaluation by 1H magnetic resonance spectroscopy. Radiology 2000;215:807-817.

  10. Sinton CM, Fitch TE, Petty F, Haley RW. Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the rat. Toxicology and Applied Pharmacology 2000;165:99-105.

  11. Haley RW, Fleckenstein JL, Marshall WW, McDonald GG, Kramer GL, Petty F. Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome. Archives of Neurology 2000;57:1280-1285.

  12. La Du BN, Billecke S, Haley RW, Broomfield CA. Serum paraoxonase (PON1) isohyets: the quantitative analysis of isohyets affecting individual sensitivity to environmental chemicals. drug Metabolism and Disposition. 2001; 29:566-569.

  13. Cowan J, Sinton CM, Varley AW, Wians FH, Haley RW, Munford RS. Gene therapy to prevent organophosphate intoxication. Toxicology and Applied Pharmacology 2001;173:1-6.

  14. Haley RW, Luk GE, Petty F. Use of structural equation modeling to test the construct validity of a case definition of Gulf War syndrome: invariance over developmental and validation samples, service branches and publicity. Psychiatry Research 2001; 102:175-200.

  15. Haley RW, Maddrey AM, Gershenfeld HK. Severely reduced functional status in veterans fitting a case definition of Gulf War Syndrome. American Journal of Public Health 2001 (in press)

REVIEW ARTICLES AND META-ANALYSES

  1. Haley RW. Is Gulf War syndrome due to stress? The evidence reexamined. American Journal of Epidemiology 1997;146:693-703.

  2. Haley RW. 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 1998;148:315-323. (With counterpoint replies by three government authors and a counter counterpoint rejoinder by Dr. Haley).

  3. Kurt TL. Epidemiological association in US veterans between Gulf War illness and exposures to anticholinesterases. Toxicology Letters 1998;102-103:523-6.

  4. Marshal WW, Haley RW. Use of a secure Internet Web site to collect data in collaborative medical research. Journal of the American Medical Association 2000;284:1843-1849.

SCIENTIFIC LETTERS

  1. Haley RW, Kurt TL, Bryan WW, et al. The authors reply [Letter]. Journal of the American Medical Association 1997;277:385-386.

  2. Haley RW. Is the Gulf War syndrome due to stress? The evidence reexamined, the author replies [Letter]. American Journal of Epidemiology 1998:148:405-406.

  3. Haley RW. Re: Chronic multi-system illness in Gulf War veterans [Letter]. Journal of the American Medical Association 1999; 327:328-329.

  4. Haley RW. The Gulf War syndrome controversy: Dr. Haley replies [Letter]. American Journal of Epidemiology 1999;150:216-7.

  5. Haley RW. Re: Is there a Gulf War syndrome? [Letter]. The Lancet 1999;354:1645-6.

  6. Haley RW. PON1 and low-Dose sarin in marmosets [Letter]. Journal of Psychopharmacology 2000;14:87-88.

  7. Haley RW. Gulf War syndrome: another side of the debate [Letter]. Mayo Clinic Proceedings 2000;75:1221-1222.

  8. Haley RW. Re: "Factor analysis of self-reported symptoms: does it identify a Gulf War syndrome?" [Letter]. American Journal of Epidemiology 2000; 152:1204-1206.

  9. Haley RW. Will we solve the Gulf War syndrome puzzle by population surveys or clinical research? [Letter]. American Journal of Medicine 2000; 109:744-745.

flashing line

home icon

LSnet logo CEnet logo

2001 by CEnet
Questions about this site? Send e-mail to the
webmaster

mailbox

joe@1ce.net

Valid HTML 4.0!