WRITTEN TESTIMONY OF 
Dr. GARTH L. NICOLSON and Dr. NANCY L. NICOLSON
COMMITTEE ON GOVERNMENT REFORM AND OVERSIGHT
Subcommittee on Human Resource and Intergovernmental Relations
UNITED STATES HOUSE OF REPRESENTATIVES
April 2, 1996

Dr. Garth Nicolson is the David Bruton Jr. Chair in Cancer Research and Professor at the University of Texas M. D. Anderson Cancer Center in Houston and Professor of Internal Medicine and Professor of Pathology and Laboratory Medicine at the University of Texas Medical School at Houston.  Among the most cited scientists in the world, having published over 400 medical and scientific papers, edited 13 books, served on the Editorial Boards of 12 medical and scientific journals and currently serving as Editor of two (Clinical & Experimental Metastasis  and the Journal of Cellular Biochemistry), Professor Nicolson has active peer-reviewed research grants from the U.S. Army, National Cancer Institute, American Cancer Society and National Foundation for Cancer Research.  Dr. Nancy Nicolson is trained in molecular biophysics and is the President of the Rhodon Foundation for Biomedical Research of Kingwood, Texas.  She has published over 25 medical and scientific papers and has delivered over 60 international and national scientific presentations. 

Our step-daughter returned from service with the U.S. Army's 101st Airborne Division (Air Assault) during Operation Desert Storm in 1991 and came down with an illness that has unusual signs and symptoms and is called Desert Storm Illness or Gulf War Syndrome (GWS).  We are a Persian Gulf War family; everyone in our family has suffered from GWS.  Since we are medical researchers, we have been involved in conducting a research effort on identifying possible causes and developing treatments for GWS.  Our research into GWS and the laboratory tests for GWS that we have developed have been done completely without compensation or funding from the U.S. Government or other sources.  Nor do we charge veterans or their family members for our assistance.

Approximately 100,000 veterans of Operation Desert Storm and in many cases their immediate family members with GWS have been experiencing a variety of chronic signs and symptoms characterized by disabling fatigue, intermittent fever, joint and muscle pain, impairments in short-term memory, headaches, skin rashes and a collection of additional symptoms that has defied a clinical case definition.2  Although the Department of Defense contends that the mortality rates in the 6 months after Desert Storm were similar in military personnel deployed or not to the Persian Gulf and Operation Desert Storm,3 there are now thousands of U.S. Desert Storm veterans dead from a variety of illnesses.4  Many veterans had delayed onset of GWS signs and symptoms and began to present with this illness between 6 months to one year or more after the end of Operation Desert Storm (Figure 1). 

In their clinical evaluation program on the effects of Operation Desert Storm, the Department of Defense has claimed that Gulf War veterans do not show higher incidence of health problems than the U.S. population as a whole.  What they fail to mention is that every person that served in Operation Desert Storm received a health clearance before deploying to the Persian Gulf, and yet many returned with illnesses that cannot be explained.  Recently National Guard and Air Force Reserve units were studied by the Center for Disease Control (CDC) in Atlanta for evidence of chronic health problems associated with deployment to the Persian Gulf during Operation Desert Storm.  From this CDC study it is clear that the Persian Gulf deployed soldiers have much higher frequencies (from 2.5-times to 13.5-times higher) of chronic health conditions (> 6 months duration) than those who were not deployed to the Persian Gulf Theater of Operations.5  

Although it is now generally agreed that many Desert Storm veterans do have medical problems, it has also been argued that the signs and symptoms of GWS are not well established as criteria for particular illnesses, and they do not readily fit into common military and VA diagnosis categories, often resulting in unknown or psychological diagnoses, such as Post Traumatic Stress Disorder (PTSD).  The concept of a distinct syndrome associated with the Gulf War (GWS) has been advanced, but it has not been proven,2 and we think it is unlikely.6  When we studied 650 veterans of Operation Desert Storm and their immediate family members who suffer from GWS, we found that they have multiple chronic signs and symptoms that are almost identical to myalpic encepthalomyelitis (ME) or Chronic Fatigue-Immune Dysfunction Syndrome (CFIDS).6   In addition, the fact that many of their immediate family members have also presented with similar ME/CFIDS signs and symptoms indicates that diagnoses biased on psychiatric considerations may be an oversimplification of the condition.6 

The variable incubation time of GWS, ranging from many months to years after presumed exposure in Operation Desert Storm, the cyclic nature of the relapsing fevers and the other signs and symptoms are consistent with a disease caused by biological and/or chemical agent(s).7  We suggested that the GWS signs and symptoms could be explained by exposure to various chemicals and/or chronic pathogenic infections.7  We set out to confirm or eliminate the possibility that chronic infections were an important underlying factor in GWS by examining a variety of biological agents that can cause chronic infections as well as the overlapping system-wide signs and symptoms of GWS.  The most common infection found in our studies thus far was an unusual microorganism, Mycoplasma fermentans (incognitus strain), in the blood of GWS patients.  This microorganism is similar to a bacterium, and it is very rarely found in humans.8  Our detection of this mycoplasmal infection deep inside the blood leukocytes (a form of white blood cell) of approximately one-half of the GWS patients examined, including 2 out of 2 British Desert Storm veterans with GWS,9 indicated that this is not a benign infection.  Dr. Steven Joseph, Assistant Secretary of Defense, has stated in letters to Congress that this type of infection is commonly found, not dangerous and is not even listed as a human pathogen.  These statements could not be further from the truth.  The Uniformed Services University of the Health Sciences, the U.S. military's medical school, has been teaching for years that this type of infection, although rare in the U.S. population, is very dangerous and can colonize major organs and can lead to system-wide organ failure and death (see attachments).

In our studies a large portion of the GWS patients that we have tested have an unusual mycoplasmal infection in their blood, but we have found that this infection can be successfully treated with multiple courses of specific antibiotics, such as doxycycline (200 mg/day for 6 weeks per cycle), ciprofloxacin (1500 mg/day for 6 weeks per cycle) or azithromycin (500 mg/day for 6 weeks per cycle).  Multiple treatment cycles are required, and patients relapse often after the first few cycles, but subsequent relapses are milder and they eventually recover their health.9  In our published study approximately one-half of a small random group of GWS patients were mycoplasma-positive (14/30), and most (11/14) recovered after multiple cycles of antibiotics, and a few (3/14) are continuing antibiotic therapy.  None of 21 healthy controls were mycoplasma-positive.9  In our earlier study on 73 Desert Storm veterans and their immediate family members who had the GWS-CFIDS signs and symptoms, 55 had good responses with doxycycline (100-200 mg/day for 4-6 weeks per cycle), and after multiple courses of antibiotic eventually recovered.7  The frequency of recovery increases with each cycle of antibiotic therapy (Figure 2).  Although the numbers of patients in these studies are limited, the studies were conducted without any support whatsoever from the Department of Defense or Veterans Administration.

In his testimony to this Subcommittee on March 28, 1996 Dr. Howard Urnovitz stated that our suggested therapy with antibiotics "appears to abate many of the symptoms associated with Gulf War Syndrome.  Usually the therapy takes longer than ordinary treatments (i.e., 6-9 weeks instead of less than 3 weeks) and in many cases the symptoms return when the therapy is discontinued.  It is not clear whether this response is directly due to the control of some antibiotic-sensitive microorganisms or a direct action on an inflammatory or neurologic process or some placebo effect."  We hypothesize that the therapy takes longer because the type of microorganism involved (a mycoplasma) is slow growing and is inside cells, a more difficult location for antibiotics to achieve proper concentrations for therapeutic effect.  As stated above, multiple cycles of therapy usually result in eventual recovery.  Although anti-inflammatory drugs can alleviate a few of the symptoms, the GWS signs and symptoms appear to quickly return after discontinuing their use.  If the effect was due to an anti-inflammatory action of the antibiotics, then the antibiotics would have to be continuously applied and they would be expected to eliminate only a few of the signs and symptoms of GWS.  In addition, not all antibiotics, even those that can have anti-inflammatory effects, appear to work.  Only the types of antibiotics that are known to be effective against mycoplasmas are effective, most have no effect at all on the signs and symptoms of GWS, and some antibiotics make the condition worse.  Thus the antibiotic therapy does not appear to be a placebo effect, because only a very few types of antibiotics are effective and some, like the penicillins, make the condition worse.  We also believe that this type of infection is immune-suppressing and can lead to other opportunistic infections by viruses and other microorganisms.

We consider it quite likely that many of the Desert Storm veterans suffering from the GWS-CFIDS symptoms may have been infected with slowly proliferating microorganisms, including pathogenic mycoplasmas and quite possibly other bacteria, and such infections, although not usually fatal, can produce various CFIDS signs and symptoms long after exposure.  This would also explain the apparent contagious nature of GWS-CFIDS in veterans and the appearance of similar symptoms in their immediate family members.  Fortunately, these infections can be successfully treated by multiple cycles of specific antibiotics.  

There were several potential sources of chronic biologic agents in the Persian Gulf.  First, deployed soldiers were given multiple inoculations of sometimes questionable vaccines in unproven immunization schemes such as those that were given all at once.  Some of these vaccines could have been contaminated with small amounts of slow growing microorganisms.  Second, the Iraqis were known to have extensive stockpiles of "weaponized" biological agents and the potential to deliver these agents offensively, even at long range in modified SCUD-B (SS-1) missiles.  Third, many of the storage and factory facilities where chemical and biological agents were housed were bombed immediately up to and during the Desert Storm ground offensive, possibly releasing plumes containing these agents high in the atmosphere to be carried downwind to our lines (Figure 3).  These and other possible routes of potential exposure must be carefully examined, not categorically dismissed by high level Defense Department personnel in Washington with little first hand knowledge of the conditions on the ground in the Persian Gulf Theater of Operations.

Finally, are all forms of GWS caused by mycoplasmal, bacterial and/or viral chronic infections?  The answer to this is likely to be no.  GWS is not one disease; it appears to be a collection of various disorders and illnesses that produce complex signs and symptoms.  In addition, Desert Storm veterans were exposed to a variety of toxic agents in the Persian Gulf, and many GWS patients now have multiple sensitivities to various chemicals, and these chemicals can cause toxicological effects and produce many but not all of the signs and symptoms of GWS.  Future efforts should be directed at determining the types of infections in GWS patients and the effects of various chemical agent exposures on such infections and how these could alter the course of chronic diseases.  Controlled clinical trials will have to be designed and initiated, and the necessary resources to conduct and evaluate these trials will have to be allociated.  We have been criticized for not conducting large, controlled clinical trials; however, we have never had the funds to conduct such trials and have had to rely solely on private physicians who believed in our work to conduct the clinical evaluations.  

We believe that Congress holds the key to the solution of GWS.  This and associated disorders (CFIDS) must be studied and solutions found using the peer-reviewed grant award system, such as that used by NIH.  GWS cannot be left to the Department of Defense or the Department of Veterans Affairs, because they have not shown themselves to be especially effective or responsive to the health problems of our Gulf War veterans.

References

1. Boaz Milner I, Axelrod BN, Pasquantonia J, Silanpaa M.  Is there a Gulf War Syndrome?  J Amer Med Assoc (JAMA) 1994; 271:661.

2. NIH Technology Assessment Workshop Panel. The Persian Gulf Experience and Health. J Amer Med Assoc (JAMA) 1994; 272:391-396.

3. Writer JV, DeFraites RF, Brundage, JF.  Comparative mortality among US military personnel in the Persian Gulf region and worldwide during Operations Desert Shield and Desert Storm.  J Amer Med Assoc (JAMA) 1996; 275:118-121.

4.  Nicolson GL, Hyman E, Korényi-Both A, Lopez DA, Nicolson NL, Rea W, Urnovitz H.  Progress on Persian Gulf War Illnesses: reality and hypotheses.   Intern J Occup Med Tox  1995; 4:365-370.

5. Kizer KW, Joseph S, Rankin JT. Unexplained illness among Persian Gulf War vetrans in an Air National Guard unit: preliminary report--August 1990-March 1995.  Morb Mort Week Rep  1995; 44:443-447.

6. Nicolson GL, Nicolson NL.  Chronic Fatigue Illness and Operation Desert Storm.  J Occup Environ Med  1996; 38:14-16.

7. Nicolson GL, Nicolson NL.   Doxycycline treatment and Desert Storm.  J Amer Med Assoc (JAMA) 1995; 273:618-619.

8. Cassell GH, Cole BC.  Mycoplasmas as agents of human disease.  New Eng J Med  1981; 304:80-89.

9. Nicolson GL, Nicolson NL.   Diagnosis and treatment of mycoplasmal infections in Gulf War Illness-CFIDS patients. Intern J Occup Med Immunol Tox   1996; 5:69-78.

Under penalty of perjury, I swear that the statements above are true and correct to the best of my knowledge, information and belief.  [signed Garth L. Nicolson]

Figure 2.

Figure 3.