Toxic Chemicals Blamed for Gulf War Illness

By Steven Reinberg
HealthDay Reporter
Monday, November 17, 2008; 12:00 AM

MONDAY, Nov. 17 (HealthDay News) -- Gulf War illness, dismissed by some as a psychosomatic disorder, is a very real illness that affects at least 25 percent of the 700,000 U.S. veterans who took part in the 1991 Gulf War.

Its likely cause was exposure to toxic chemicals that included pesticides that were often overused during the war, as well as a drug given to U.S. troops to protect them from nerve gas, a frequent weapon of choice of former Iraqi leader Saddam Hussein.

And no effective treatments have been devised for the disorder.

Those are three key conclusions of a Congressionally mandated landmark report released Monday by a federal panel of scientific experts and veterans.

"It is very clear that Gulf War illness is a real condition that was not caused by combat stress or other psychological factors," said Lea Steele, scientific director of the Research Advisory Committee on Gulf War Veterans' Illnesses, which issued the report, and an associate professor at Kansas State University.

"This is something we need to take seriously," Steele said. "These folks were injured in wartime service, much as people who were shot with bullets or hit with bombs."

The committee presented the 450-page report to Secretary of Veterans Affairs James Peake.

Gulf War illness is frequently described as a collection of symptoms that includes memory and concentration problems, chronic headaches, fatigue and widespread pain. Other symptoms can include persistent digestive problems, respiratory symptoms and skin rashes.

The panel also said Gulf War veterans have much higher rates of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's Disease) than other veterans, and soldiers who were downwind from large-scale munitions demolitions in 1991 have died from brain cancer at twice the rate of other Gulf War veterans.

In reaching its conclusions, the panel reviewed evidence about a wide range of possible environmental exposures that could cause Gulf War illness. That review included hundreds of studies of Gulf War veterans, research in other groups of populations, animal studies of toxic exposures, and government investigations about events and exposures during the Gulf War, which began after Hussein invaded Kuwait.

Speculation about the causes of Gulf War illness has included exposure to depleted uranium munitions, vaccines, nerve agents and oil well fires.

The new report says the illness was caused by soldiers' exposure to certain chemicals, Steele said.

"When you put all the evidence together there are two chemicals that jump out as the main causes," she said. One is a drug called pyridostigmine bromide, which is a cholinesterase inhibitor that was given to the troops to protect them against nerve gas.

"It turns out that people who took those pills have a higher rate of Gulf War illness," Steele said. "And people who took more pills have even higher rates of Gulf War illness."

In addition, soldiers were exposed to pesticides that were also cholinesterase inhibitors, Steele said. "The strongest evidence points to pyridostigmine bromide and pesticides as causal factors," she said. "This type of illness has not been seen after other wars."

While pyridostigmine bromide is still in use, its use is more limited than it was in the first Gulf War. It's currently being used against one type of nerve agent, but is not being given out on a widespread basis, Steele said.

"The Gulf War was the only time a lot of people used this drug," she said.

Steele added that the U.S. military has also cut back on its use of pesticides since the 1991 war.

There are other factors that, while not likely causes of Gulf War illness, can't be ruled out, Steele said. These include exposure to nerve agents, exposure to smoke from oil well fires, and vaccines given to the troops. The panel ruled out depleted uranium and anthrax vaccine as causes.

The panel also found government research and funding into Gulf War illness wanting. "There has not been sufficient attention given to Gulf War illness. It's a real problem," Steele said.

"In recent years, both the Department of Defense and the Department of Veterans Affairs have reported a lot of studies that weren't Gulf War illness as Gulf War research," Steele added. "Some of the money was misused."

The panel noted that overall federal funding for Gulf War research has declined substantially in recent years; the group urged lawmakers to devote $60 million annually to such programs.

When veterans with Gulf War illness go to Veterans Administration hospitals for treatment, their problems often aren't taken seriously, Steele said. "VA docs often know nothing about it and aren't able to help them. Sometimes they treat them as if they are head cases or malingering," she said.

James Binns is chairman of the U.S. Department of Veterans Affairs' Research Advisory Committee on Gulf War Veterans' Illnesses.

"We have no treatments that work," said Binns, a Vietnam veteran and former Pentagon official. "I would like to see the new administration take this more seriously. When you look at all the studies, it's as clear as the nose on your face that this [Gulf War illness] is real."

It took 20 years to admit that Agent Orange, a defoliant used in the Vietnam war, caused illness, Binns said. "It's now coming up to 17 years on Gulf War illness," he said. "Troop exposures [to these chemicals] were a serious but honest mistake. Covering it up rather than trying to help them has been unconscionable."

More information

Learn more about Gulf War illness from the University of Chicago Medical Center.

SOURCES: Lea Steele, Ph.D., associate professor, Kansas State University, Manhattan, and scientific director, Research Advisory Committee on Gulf War Veterans' Illnesses; James Binns, chairman, U.S. Department of Veterans Affairs' Research Advisory Committee on Gulf War Veterans' Illnesses

© 2008 Scout News LLC. All rights reserved.

Report to Congress: Gulf War Syndrome is Real

A scientific panel chartered by Congress cites nerve gas drug and pesticides used during the conflict as being associated with veterans' neurological problems.
by Mary Engel and Thomas H. Maugh II
Published on Tuesday, November 18, 2008 by The Los Angeles Times

A congressionally mandated scientific panel has concluded that Gulf War syndrome is real and still afflicts nearly a quarter of the 700,000 U.S. troops who served in the 1991 conflict, according to a report released Monday.

The report broke with most earlier studies by concluding that two chemical exposures were direct causes of the disorder: the drug pyridostigmine bromide, given to troops to protect against nerve gas, and pesticides that were widely used -- and often overused -- to protect against sand flies and other pests.

"The extensive body of scientific research now available consistently indicates that Gulf War illness is real, that it is a result of neurotoxic exposures during Gulf War deployment, and that few veterans have recovered or substantially improved with time," according to the 450-page report presented to Secretary of Veterans Affairs James Peake.

The report bolstered the hopes of thousands of U.S. and allied veterans who have struggled to have their varied neurological symptoms, including memory loss, concentration problems, rashes and widespread pain, recognized by the government.

"I've had vets go to the VA and be turned away and told that this is something that doesn't exist," said John Schwertfager, vice president of the National Gulf War Resource Center, a veterans advocacy group.

But some scientists were not convinced that the new report had found the long-sought smoking gun.

"Even though we know that the Department of Defense did ship pesticides, it doesn't mean that the people who were exposed to them were the ones who ended up having symptoms," said Dr. Lynn Goldman, a professor of environmental health sciences at Johns Hopkins University in Baltimore who has worked on previous reports on the illness. "We felt that there needed to be better records of where people were, what they were exposed to and their prior health status going in."

The new report is the product of the Research Advisory Committee on Gulf War Veterans' Illnesses, which was chartered by Congress because many members thought that veterans were not receiving adequate care. On the 15-member committee appointed in 2002, scientists made up about two-thirds and the rest were veterans.

Several reports had already been issued by the prestigious Institute of Medicine, an arm of the National Academy of Sciences, blaming stress and other unknown causes for the soldiers' symptoms.

"There's something about going to the Gulf and serving in the Gulf that has caused something bad and persistent and real, but we have not found any evidence for a specific cause," said Dr. Harold C. Sox, chairman of a 2000 institute study and editor of the journal Annals of Internal Medicine.

Veterans blame the institute's reports for the difficulties they've faced in getting treatment for their problems.

"Everyone quotes the Institute of Medicine documents as meaning nothing's going on here," said Roberta F. White, associate dean of research at the Boston University School of Public Health and the congressional panel's scientific director. "Some people feel that the IOM reports have been permission to ignore these guys."

The new report cites dozens of research studies that have identified "objective biological measures" that distinguish veterans with the illness from healthy controls.

The major causes of the disorder appear to be self-inflicted. Pyridostigmine bromide was given to as many as half of the troops in the fear that the Iraqis would unleash chemical warfare against them.

According to the report, at least 64 pesticides containing 37 active ingredients were used during the war. They were sprayed not only around living and dining areas, but also on tents and uniforms, White said.

There was less evidence to support a link to the U.S. demolition of Iraqi munitions near Khamisiyah, which may have exposed about 100,000 troops to nerve gases stored at the facility, according to the panel.

The panel said it could not rule out a link between the illness and exposure to oil well fires and multiple vaccinations. But it could find no evidence linking it to depleted uranium shells, anthrax vaccine and infectious diseases.

In addition to increased rates of memory loss, fatigue and pain, Gulf War veterans have higher rates of brain cancer and amyotrophic lateral sclerosis, or Lou Gehrig's disease, the panel also noted.

The panel called on Congress to appropriate $60 million a year to conduct research into finding a cure for the disorder.

"The tragedy here is that there are currently no treatments," said the panel's chairman, James H. Binns, a former principal deputy assistant secretary of Defense and a Vietnam veteran.

Binns emphasized that the report was not written to yield recriminations about past actions.

"The importance . . . lies in what is done with it in the future," he said. "It's a blueprint for the new administration."

Engel and Maugh are Times staff writers.
© 2008 The Los Angeles Times


Subcommittee on National Security, Veterans’ Affairs and International Relations
January 24th 2002

Dr. Garth Nicolson is currently the President, Chief Scientific Officer and Research Professor at the Institute for Molecular Medicine in Huntington Beach, California. He was formally the David Bruton Jr. Chair in Cancer Research, Professor and Chairman 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. He was also Adjunct Professor of Comparative Medicine at Texas A & M University. Among the most cited scientists in the world, having published over 520 medical and scientific papers, edited 14 books, served on the Editorial Boards of 20 medical and scientific journals, including the Journal of Chronic Fatigue Syndrome, and currently serving as Editor of two (Clinical & Experimental Metastasis and the Journal of Cellular Biochemistry), Professor Nicolson has held numerous peer-reviewed research grants. He is a recipient of the Burroughs Wellcome Medal of the Royal Society of Medicine, Stephen Paget Award of the Metastasis Research Society and the U. S. National Cancer Institute Outstanding Investigator Award.

It is now over a decade since the Persian Gulf War, but over 100,000 U. S. veterans still suffer from various illnesses attributed to their service [1-4]. Although some Gulf War Illnesses (GWI) patients have unique signs and symptoms [5], most do not have some new syndrome (Gulf War Syndrome) [6]. These illnesses are more properly called GWI, and we believe that they are due to accumulated toxic insults that cause chronic illnesses with relatively nonspecific signs and symptoms [1-4,7].

Over the last few years researchers have published much higher prevalence rates of GWI in deployed than in non-deployed forces [8-10]. Case control studies of Gulf War veterans showed higher symptom prevalence in deployed than in non-deployed personnel from the same units [9,10]. For certain signs and symptoms, this difference was dramatic (for example, the rate of diarrhea in the deployed group was over 13-times greater than in the non-deployed group [9]). Steele [10] showed that in three studies, Gulf War-deployed forces had excess rates of GWI symptom patterns, indicating beyond a doubt that GWI is a major problem that needs to be adequately addressed.

Ten Years Later -- Obtaining an Adequate Diagnosis of GWI

For years the Departments of Defense (DoD) and Veterans’ affairs (DVA) promoted the notion that Post-Traumatic Stress Disorder (PTSD) was a major factor in GWI [11]. Most researchers doubt that stress is a major cause of GWI [1-5,7], and it certainly does not explain how some immediate family members presented after the war with the same signs and symptoms [2,3,12]. Even psychiatrists who have studied GWI do not believe that GWI is explainable as PTSD [13]. Researchers find that GWI cases differ from PTSD, depression, somatoform disorder and malingering [7,14]. Although most GWI patients do not appear to have PTSD, they are often paced in this diagnosis category by DoD and DVA physicians. GWI can be diagnosed within ICD-10-coded diagnosis categories, such as fatiguing illness (G93.3), but they often receive a diagnosis of ‘unknown illness.’ This, unfortunately, results in their receiving reduced disability assessments and benefits and essentially little or no effective treatments. It’s not that they are any less sick than their compatriots with ICD-10 diagnoses, they just don’t fit within the military’s or DVA’s diagnosis systems. In addition, many active-duty members of the Armed Forces are hesitant to admit that they have GWI, because they feel strongly that it will hurt their careers or result in their being medically discharged. They have good reason to fear this, because many officers that we have assisted eventually retired or resigned their commissions because of imposed limits to their careers [15].

Psychiatrists often decide in the absence of contrary laboratory findings that GWI is a somatoform disorder caused by stress, instead of organic or medical problems that can be treated with medicines or treatments not used for PTSD or other somatoform disorders. The evidence that psychiatrists have offered as proof that stress or PTSD is the source of most GWI is the assumption that most veterans must have suffered from stress by virtue of the stressful environment in which they found themselves during the Gulf War [15]. However, most veterans do not feel that stress-related diagnoses are an accurate portrayal of their illnesses. Testimony to the House Committee on Government Reform and Oversight questions the notion that stress is the major cause of GWI [16], and the General Accounting Office (GAO) has concluded that while stress can induce some physical illness, it is not established as the major cause of GWI [17]. Stress can exacerbate chronic illnesses and suppress immune systems, but most military personnel that we interviewed indicated that the Gulf War was not a particularly stressful war, and they strongly disagreed that stress was the origin of their illnesses [18]. However, in the absence of physical or laboratory tests that can identify possible origins of GWI, many DoD and VA physicians accept that stress is the cause. It has been argued that the arthralgias, fatigue, memory loss, rashes and diarrhea found in GWI patients are nonspecific and often lack a physical cause [19], but this conclusion may simply be the result of inadequate workup and lack of availability of routine tests that could define the underlying organic etiologies for these conditions [7].

It has also been claimed that there are no unique illnesses associated with deployment to the Gulf War--similar clusters of illness (albeit at lower rates) can be found in non-Gulf War veterans deployed to Bosnia [8]. Such epidemiological analyses have been criticized on the basis of self-reporting and self-selection [19], and the veterans under study may not be representative [8]. These criticisms notwithstanding, it remains important to characterize signs and symptoms and identify exposures, if possible, of Gulf War veterans in order to find effective treatments for specific subsets of GWI patients. We have been trying for years to get the DoD to acknowledge that different exposures can result in quite different illnesses, even though signs and symptoms profiles may overlap.

How Does GWI Differ from Other Chronic Fatiguing Illnesses?

GWI patients can have 20-40 or more chronic signs and symptoms, including chronic fatigue, headaches, memory loss, muscle pain, nausea, gastrointestinal problems, joint pain, lymph node pain, memory loss, increased chemical sensitivities, among others [1-5]. Often included in this complex clinical picture are increased sensitivities to various environmental agents and enhanced allergic responses. Civilian patients with similar signs and symptoms are usually diagnosed with Chronic Fatigue Syndrome (CFS), Fibromyalgia Syndrome (FMS) or Multiple Chemical Sensitivity Syndrome (MCS) [2,3,7]. Although clear-cut laboratory tests on GWI, CFS and FMS are not yet available, some tests that have been used in recent years for GWI are not consistent with a psychiatric origin for GWI [20-25].

Chronic Illnesses and Chemical Exposures

It has been documented that chemical and biological exposures occurred during the Gulf War, and many civilian patients may have been exposed to chemical and biological substances that could be the underlying causes of their illnesses [1-3,7]. The variable incubation times, ranging from months to years after presumed exposure, the cyclic nature of the relapsing fevers and other signs and symptoms, and the types of signs and symptoms of GWI are consistent with diseases caused by combinations of biological and/or chemical or radiological agents (Figure 1) [1,7].

Gulf War veterans were exposed to a variety of chemicals, including insecticides, such as the insect repellent N, N-dimethyl-m-toluamide, the insecticide permethrin and other organophosphates, fumes and smoke from burning oil wells, the anti-nerve agent pyridostigmine bromide, solvents used to clean equipment and a variety of other chemicals [1,2,7]. This also includes in some cases, possible exposures to low levels of Chemical Warfare (CW) agents. Some CW exposure may have occurred because of destruction of CW stores in factories and storage bunkers during and after the war as well as possible offensive use of CW agents [27]. Although some former DoD physicians feel that there was no credible evidence for CW exposure [19], many veterans have been notified by the DoD of possible CW exposures.

Figure 1. Hypothesis on how multiple toxic exposures, including multiple vaccines (2), chemical (3), radiological and biological (4) exposures, may have resulted in GWI in predisposed, susceptible individuals (1) [modified from Nicolson et al.(7)].

Exposures to mixtures of toxic chemicals can result in chronic illnesses, even if the exposures were at low-levels [20,21,28,29]. Such exposures can cause a wide variety of signs and symptoms, including chronic neurotoxicity and immune supression. Combinations of pyridostigmine bromide, N,N-dimethyl-m-toluamide and permethrin produce neurotoxicity, diarrhea, salivation, shortness of breath, locomotor dysfunctions, tremors, and other impairments in healthy adult hens [28]. Although low levels of individual organophosphate chemicals may not cause signs and symptoms in exposed, non-deployed civilian workers [30], this does not negate a causal role of multiple chemical exposures in causing chronic illnesses such as GWI. Organophosphate-Induced Delayed Neurotoxicity (OPIDN) [31] is an example of chronic illness that may be caused by multiple, low level chemical exposures (Figure 1). Multiple Chemical Sensitivity Syndrome (MCS) has also been proposed to result from multiple low level chemical exposures [32]. These syndromes can present with many of the signs and symptoms found in GWI patients, and many GWI cases may eventually be explained by complex chemical exposures.

In chemically exposed GWI patients, memory loss, headaches, cognitive problems, severe depression, loss of concentration, vision and balance problems and chemical sensitivities, among others, typify the types of signs and symptoms characteristic of organophosphate exposures. Arguments have been advanced by former military physicians that such exposures do not explain GWI, or that they may only be useful for a small subset of GWI patients [19]. These arguments for the most part are based on the effects of single agent exposures, not the multiple, complex exposures that were encountered by Gulf War veterans [33]. The onset of signs and symptoms of GWI for most patients was between six months and two years or more after the end of the war. Such slow onset of clinical signs and symptoms in chemically exposed individuals is not unusual for OPIDN [34]. Since low-level exposure to organophosphates was common in U.S. veterans, the appearance of delayed, chronic signs and symptoms similar to OPIDN could have been caused by multiple low-level exposures to pesticides, nerve agents, anti-nerve agents and/or other organophosphates, especially in certain subsets of GWI patients.

Radiological Exposures and GWI

Depleted uranium (DU) was used extensively in the Gulf War, and it remains an important battlefield contaminant. When a DU penetrator hits an armored target, it ignites, and between 10% and 70% of the shell aerosolizes, forming uranium oxide particles [35]. The particles that form are usually small (less than 5 µm in diameter) and due to their high density settle quickly onto vehicles, bunkers and the surrounding sand, where they can be easily inhaled, ingested or re-aerosolized. Following contamination, DU can be found in the lungs and regional lymph nodes, kidney and bone. Additionally, the Armed Forces Radiological Research Institute (AFRRI) found DU in blood, liver, spleen and brain of rats injected with DU pellets [36]. Studies on DU carriage should be initiated as soon as possible to determine the prevalence of contamination, and extent of body stores of uranium and other radioactive heavy metals. Procedures have been developed for analysis of DU metal fragments [37] and DU in urine [38]. However, urine testing does not detect uranium in all body sites [36]. So far, analysis of DU-contaminated Gulf War veterans has not shown them to have severe signs and symptoms of GWI [38], but few Gulf War veterans have been studied for DU contamination.

Other Environmental Exposures and GWI

In addition to chemical exposures, soldiers were exposed to burning oil well fires and ruptured petroleum pipelines as well as fine, blowing sand. The small size of sand particles (much less than 0.1 mm) and the relatively constant winds in the region probably resulted in some sand inhalation. The presence of small sand particles deep in the lungs can produce a pulmonary inflammatory disorder that can progress to pneumonitis or Al-Eskan Disease [39]. Al-Eskan disease, characterized by reactive airways, usually presents as a pneumonitis that can eventually progress to pulmonary fibrosis, and possibly immunosuppression followed by opportunistic infections. Although it is doubtful that many GWI patients have Al-Eskan Disease, the presence of silica-induced immune suppression in some soldiers could have contributed to persisting opportunistic infections in these patients.

Biological Exposures and GWI

System-wide or systemic chemical insults and/or chronic infections that can penetrate various tissues and organs, including the Central and Peripheral Nervous Systems, are important in GWI [1-5,7]. When such infections occur, they can cause the complex signs and symptoms seen in CFS, FMS and GWI, including immune dysfunction. Changes in environmental responses as well as increased titers to various endogenous viruses that are commonly expressed in these patients have been seen in CFS, FMS and GWI. Few infections can produce the complex chronic signs and symptoms found in these patients; however, the types of infection caused by Mycoplasma and Brucella species that have been found in GWI patients, can cause complex problems found in GWI [reviews: 23,40,41]. These microorganisms are now considered important emerging pathogens in causing chronic diseases as well as being important cofactors in some illnesses, including AIDS and other immune dysfunctional conditions [23,40,41].

Evidence for infectious agents has been found in GWI patients' urine [4] and blood [12,26,42-44]. We [12,26,42,43] and others [44] have found that most of the signs and symptoms in a large subset of GWI patients can be explained by chronic pathogenic bacterial infections, such as Mycoplasma and Brucella infections. In studies of over 1,500 U. S. and British veterans with GWI, approximately 40-50% of GWI patients have PCR evidence of such infections, compared to 6-9% in the non-deployed, healthy population [review: 23]. This has been confirmed in a large study of 1,600 veterans at over 30 DVA and DoD medical centers (VA Cooperative Clinical Study Program #475, S. Donta and C. Engel, statements at the NIH Chronic Fatigue Syndrome Coordinating Board, 2/00). Historically, mycoplasmal infections were thought to produce relatively mild diseases limited to particular tissues or organs, such as urinary tract or respiratory system [23,40,41]. However, the mycoplasmas detected in GWI patients with molecular techniques are highly virulent, colonize a wide variety of organs and tissues, and are difficult to treat [23,45,46]. The mycoplasma most commonly detected in GWI, Mycoplasma fermentans (found in >80% of those GWI patients positive for any mycoplasma), is found intracellularly. It is unlikely that this type of infection will result in a strong antibody response, which may explain the DoD’s lack of serologic evidence for these types of intracellular infections [47].

When civilian patients with CSF or FMS were similarly examined for systemic mycoplasmal infections 50-60% of these patients were positive, indicating another link between these disorders and GWI [23]. In contrast to GWI, however, several species of mycoplasmas other than M. fermentans were found in higher percentages of CSF/ME and FMS patients and most had multiple infections [48,49].
GWI can Spread to Immediate Family Members

During the last year we have documented the spread of GWI infections to immediate family members [12]. According to one U. S. Senate study [50], GWI has spread to family members, and it is likely that it has also spread in the workplace [18]. Although the official position of the DoD/DVA is that family members have not contracted GWI, these studies [12,50] indicate that at least a subset of GWI patients have a transmittable illness. Laboratory tests revealed that GWI family members have the same chronic infections [12] that have been found in ~40% of the ill veterans [42-44]. We examined military families (149 patients; 42 veterans, 40 spouses, 32 other relatives and 35 children) with at least one family complaint of illness) selected from a group of 110 veterans with GWI who tested positive (~41% overall) for mycoplasmal infections. Consistent with previous results, over 80% of GWI patients who were positive for blood mycoplasmal infections had only one Mycoplasma species, M. fermentans. In healthy control subjects the incidence of mycoplasmal infection was 7%, several mycoplasma species were found, and none were found to have multiple mycoplasmal species (P 0.001). In 107 family members of GWI patients with a positive test for mycoplasma, there were 57 patients (53%) that had essentially the same signs and symptoms as the veterans and were diagnosed with CFS or FMS. Most of these patients also had mycoplasmal infections compared to non-symptomatic family members (P 0.001). The most common species found in CFS patients in the same families as GWI patients was M. fermentans, the same infection found in the GWI patients. The most likely conclusion is that certain subsets of GWI can transmit their illness and airborne infections to immediate family members [12].

As chronic illnesses like GWI (and in some cases CFS and FMS) progress, there are a number of accompanying clinical problems, particularly autoimmune signs/symptoms, such as those seen in Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS or Lew Gehrig’s Disease, see below), Lupus, Graves’ Disease, Arthritis and other complex autoimmune diseases. Mycoplasmal infections can penetrate into nerve cells, synovial cells and other cell types [40,41]. The autoimmune signs and symptoms can be caused when intracellular pathogens, such as mycoplasmas, escape from cellular compartments and stimulate the host’s immune system. Microorganisms like mycoplasmas can incorporate into their own structures pieces of host cell membranes that contain important host membrane antigens that can trigger autoimmune responses or their surface antigens may be similar to normal cell surface antigens. Thus patients with such infections may have unusual autoimmune signs and symptoms

Involvement of Infections in Gulf War Veterans with ALS

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, idiopathic, progressive degenerative disease affecting both central and peripheral motor neurons. Patients with ALS show gradual progressive weakness and paralysis of muscles due to destruction of upper motor neurons in the motor cortex and lower motor neurons in the brain stem and spinal cord, ultimately resulting in death, usually by respiratory failure [51]. Gulf War veterans show at least twice the expected incidence of ALS.

We have recently investigated the presence of systemic mycoplasmal infections in the blood of Gulf War veterans and civilians with ALS [52]. Almost all ALS patients (~83%, including 100% of Gulf War veterans with ALS) showed evidence of Mycoplasma species in blood samples. All Gulf War veterans with ALS were positive for M. fermentans, except one that was positive for M. genitalium. In contrast, the 22/28 civilians with detectable mycoplasmal infections had M. fermentans (59%) as well as other Mycoplasama species in their blood, and two of the civilian ALS patients had multiple mycoplasma species. Of the few control patients that were positive, only two patients (2.8%) were positive for M. fermentans (P 0.001). The results support the suggestion that infectious agents may play a role in the pathogenesis and/or progression of ALS, or alternatively ALS patients are extremely susceptible to systemic mycoplasmal infections [52]. In the GWI patients mycoplasmal infections may have increased their susceptibility to ALS, which may explain the recent VA studies showing that there is an increased risk of ALS in Gulf War veterans.

Successful Treatment of GWI Mycoplasmal Infections

We have found that mycoplasmal infections in GWI, CFS, FMS and RA can be successfully treated with multiple courses of specific antibiotics, such as doxycycline, ciprofloxacin, azithromycin, clarithromycin or minocycline [45,46,53-55], along with other nutritional recommendations. Multiple treatment cycles are required, and patients relapse often after the first few cycles, but subsequent relapses are milder and most patients eventually recover [42,43]. GWI patients who recovered from their illness after several (3-7) 6-week cycles of antibiotic therapy were retested for mycoplasmal infection and were found to have reverted to a mycoplasma-negative phenotype [42,43]. The therapy takes a long time because of the microorganisms involved are slow-growing and are localized deep inside cells in tissues, where it is more difficult to achieve proper antibiotic therapeutic concentrations. Although anti-inflammatory drugs can alleviate some of the signs and symptoms of GWI, they quickly return after discontinuing drug 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 some of the signs and symptoms of GWI. In addition, not all antibiotics, even those that 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, and some antibiotics make the condition worse. Thus the antibiotic therapy does not appear to be a placebo effect, because only a few types of antibiotics are effective and some, like penicillin, 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 or increases in endogenous virus titers. We have also found Brucella infections in GWI patients but we have not examined enough patients to establish a prevalence rate among veterans with GWI.

The true percentage of mycoplasma-positive GWI patients overall is likely to be somewhat lower than found in our studies (41-45%) [12,42,43] and those published by others (~50%) [44]. This is reasonable, since GWI patients that have come to us for assistance are probably more advanced patients (with more progressed disease) than the average patient. Our diagnostic results have been confirmed in a large study DVA/DoD study (~40% positive for mycoplasmal infections, VA Cooperative Clinical Study Program #475). This DVA study is a controlled clinical trial that will test the usefulness of antibiotic treatment of mycoplasma-positive GWI patients. This clinical trial is based completely on our research and publications on the diagnosis and treatment of chronic infections in GWI patients [42,43,53-55]. This clinical trial is complete but the treatment results have not yet been analyzed. There is a major concern that the DoD/DVA will not be forthcoming about this trial.

Vaccines Given During Deployment and GWI

A possible source for immune disturbances and chronic infections found in GWI patients is the multiple vaccines that were administered close together around the time of deployment to the Gulf War. Unwin et al. [8] and Cherry et al. [56] found a strong association between GWI and the multiple vaccines that were administered to British Gulf War veterans. Unwin et al. [8] and Goss Gilroy [57] also noted an association specifically with anthrax vaccine and GWI symptoms in British and Canadian veterans. Steele [10] found a three-fold increased incidence of GWI in nondeployed veterans from Kansas who had been vaccinated in preparation for deployment, compared to non-deployed, non-vaccinated veterans. Finally, Mahan et al. [58] found a two-fold increased incidence of GWI symptoms in U.S. veterans who recalled they had received anthrax vaccinations at the time of the Gulf War, versus those who thought they had not. These studies associate GWI with the multiple vaccines given during deployment, and they may explain the high prevalence rates of chronic infections in GWI patients [59,60].

GWI signs and symptoms have developed in Armed Forces personnel who recently received the anthrax vaccine. On some military bases this has resulted in chronic illnesses in as many as 7-10% of personnel receiving the vaccine [60]. The chronic signs and symptoms associated with anthrax vaccination are similar, if not identical, to those found in GWI patients, suggesting that at least some of the chronic illnesses suffered by veterans of the Gulf War were caused by military vaccines [59,60]. Undetectable microorganism contaminants in vaccines could have resulted in illness, and may have been more likely to do so in those with compromised immune systems. This could include individuals with DU or chemical exposures, or personnel who received multiple vaccines in a short period of time. Since contamination with mycoplasmas has been found in commercial vaccines [61], the vaccines used in the Gulf War should be considered as a possible source of the chronic infections found in GWI. Some of these vaccines, such as the filtered, cold-stored anthrax vaccine are prime suspects in GWI, because they could be easily contaminated with mycoplasmal infections and other microorganisms [62].

Inadequate Responses of the DoD and DVA to GWI

In general, the response of the DoD and DVA to the GWI problem has been inadequate, and it continues to be inadequate. The response started with denial that there were illnesses associated with service in the Gulf War; it has continued with denial that what we (biological exposures) and others (chemical exposures) have found in GWI patients are important in the diagnosis and treatment of GWI, and it continues today with the denial that military vaccines could be a major source of GWI. For example, in response to our publications and formal lectures at the DoD (1994 and 1996) and DVA (1995), the DoD stated in letters to various members of Congress and to the press that M. fermentans infections are commonly found, not dangerous and not even a human pathogen, and our results have not been duplicated by other laboratories. These statements were completely false. The Uniformed Services University of the Health Sciences taught its medical students for years that this type of infection is very dangerous and can progress to system-wide organ failure and death [63]. In addition, the Armed Forces Institute of Pathology (AFIP) has been publishing for years that this type of infection can result in death in nonhuman primates [64] and in man [65]. The AFIP has also suggested treating patients with this type of infection with doxycycline [66], which is one of the antibiotics that we have recommended [53-55]. Interestingly, DoD pathologist Dr. Shih-Ching Lo holds the U. S. Patent on M. fermentans (“Pathogenic Mycoplasma”[67]), and this may be the real reason that in their original response to our work on M. fermentans infections in GWI, the DoD/DVA issued guidelines stating that GWI patients should not be treated with antibiotics like doxycycline, even though in a significant number of patients it had been shown to be beneficial. The DoD and DVA have also stated that we have not cooperated with them or the CDC in studying this problem. This is also not true. We have done everything possible to cooperate with the DoD, DVA and CDC on this problem, and we even published a letter in the Washington Post on 25 January 1997 indicating that we have done everything possible to cooperate with government agencies on GWI issues, including inviting DoD and DVA scientists and physicians to the Institute for Molecular Medicine to learn our diagnostic procedures on 23 December 1996 at a meeting convened at Walter Reed AMC. We have been and are fully prepared to share our data and procedures with government scientists and physicians. The DVA has responded with the establishment of VA Cooperative Clinical Study Program #475, but many Gulf War Referral Centers at VA Medical Centers continue to be hostile to non-psychiatric treatment of GWI. The DoD and DVA continue to deny that family members of Gulf War veterans could contract the illness or that there could be an infectious basis to GWI.

DoD/DVA Scorecard on GWI from Previous Testimony

In my previous testimony to the U. S. Congress in 1998 [15,18], some suggestions were made to correct for the apparent lack of appropriate response to GWI and the chronic infections found in GWI patients. It seems appropriate to go back and revisit these suggestions to see if any of these were taken seriously or corrected independently (Updates in italics).

1. We must stop the denial that immediate family members do not have GWI or illnesses from the Gulf War. Denial that this has occurred has only angered veterans and their families and created a serious public health problem, including spread of the illness to the civilian population and contamination of our blood supply. This item has still not been taken seriously by the DoD. The DVA has initiated a study to see if veterans’ family members have increased illnesses; however, they have decided to group GWI patients together independent of the possible origins of their illness. Since veterans who have their illness primarily due to chemical or environmental exposures that are not transmittable will be grouped with veterans who have transmittable chronic infections, it is unlikely that studying family members of both groups together will yield significant data. Whether intentional or not, this DVA study has apparently been designed to fail. Potential problems with the nation’s blood and organ tissue supply due to contamination by chronic infections in GWI and CFS patients are considered significant [68,69], but no U.S. government agency has apparently taken this seriously.

2. The ICD-9-coded diagnosis system used by the DoD and DVA to determine illness diagnosis must be overhauled. The categories in this system have not kept pace with new medical discoveries in the diagnosis and treatment of chronic illnesses. This has resulted in large numbers of patients from the Gulf War with ‘undiagnosed’ illnesses who cannot obtain treatment or benefits for their medical conditions. The DoD and DVA should be using the ICD-10 diagnosis system where a category exists for chronic fatiguing illnesses. Apparently little progress in this area has been made by the DoD or DVA.

3. Denying claims and benefits by assigning partial disabilities due to PTSD should not be continued in patients that have organic (medical) causes for their illnesses. For example, patients with chronic infections that can take up to or over a year to successfully treat should be allowed benefits. The DVA has recently shown some flexibility in this area. For example, Gulf War veterans with ALS will receive disability without having to prove that their disease was deployment-related. Similarly, GWI patients with M. fermentans infections (and also their symptomatic family members with the same infection) should receive disabilities. Thus far there has been no attempt to extend disability to GWI-associated infectious diseases. Instead of waiting for years or decades for the research to catch up to the problem, the DoD and DVA should simply accept that many of the chronic illnesses found in Gulf War veterans are deployment related and deserving of treatment and compensation.

4. Research efforts must be increased in the area of chronic illnesses. Unfortunately, federal funding for such illnesses is often re-budgeted or funds removed. For example, Dr. William Reeves of the CDC in Atlanta sought protection under the ‘Federal Whistle Blower’s Act’ after he exposed misappropriation of funds allocated for CFS at the CDC. It is estimated that over 3% of the adult U.S. population suffers from chronic fatiguing illnesses similar to GWI, yet there are few federal dollars available for research on the diagnosis and treatment of these chronic illnesses, even though each year Congress allocates such funds. There has been some progress at NIH on this issue, but in general little has changed. The DoD and DVA have spent most of the hundreds of millions of dollars allocated for GWI research on psychiatric research. Most of these funds have been spent on studies that have had negligible effect on veterans’ health.

5. Past and present senior DoD and DVA administrative personnel must be held accountable for the utter mismanagement of the entire GWI problem. This has been especially apparent in the continuing denial that chronic infections could play a role in GWI and the denial that immediate family members could have contracted their illnesses from veterans with GWI. This has resulted in sick spouses and children being turned away from DoD and DVA facilities without diagnoses or treatments. The responsibility for these civilians must ultimately be borne by the DoD and DVA. I believe that it is now accountability time. The files must be opened so the American public has a better idea as to how many veterans and civilians have died from illness associated with service in the Gulf War and how many have become sick because of an inadequate response to this health crisis. Unfortunately, little or no progress has been made on these items for the last decade or more, and the situation has not changed significantly since my last testimony in 1998.

References and Notes

1. Nicolson GL. Gulf War Illnesses—their causes and treatment. Armed Forces Med. Dev. 2001; 2:41-44.

2. Nicolson GL, Nasralla M, Haier J, Nicolson NL. Gulf War Illnesses: Role of chemical, radiological and biological exposures. In: War and Health, H. Tapanainen, ed., Zed Press, Helinsiki, 2001; 431-446.

3. Nicolson, G.L. and Nicolson, N.L. Chronic Fatigue Illness and Operation Desert Storm. J. Occup. Environ. Med. 1996; 38:14-16.

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

5. Murray-Leisure, K., Daniels, M.O., Sees, J., Suguitan, E., Zangwill, B., Bagheri, S., Brinser, E., Kimber, R., Kurban, R. Greene, W.H. Mucocutaneous-Intestinal-Rheumatic Desert Syndrome (MIRDS). Definition, histopathology, incubation period, clinical course and association with desert sand exposure. Intern. J. Med. 1998; 1:47-72.

6. Ismail K, Everitt B, Blatchley N, et al. Is there a Gulf War syndrome? Lancet 1999; 353:179-182.

7. Nicolson GL, Berns P, Nasralla M, Haier J, Nicolson NL, Nass M. Gulf War Illnesses: chemical, radiological and biological exposures resulting in chronic fatiguing illnesses can be identified and treated. J. Chronic Fatigue Syndr. 2002; 10:in press.

8. Unwin C, Blatchley N, Coker W, et al. Health of UK servicemen who served in the Persian Gulf War. Lancet 1999; 353:169-178.

9. Kizer KW, Joseph S, Rankin JT. 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. Morbid. Mortal. Week. Rep. 1995; 44:443-447.

10. Steele L. Prevalence and patterns of Gulf War Illness in Kansas veterans: association of symptoms with characteristics of person, place and time of military service. Am. J. Epidemiol. 2000; 152:992-1002.

11. Engel CC Jr, Ursano R, Magruder C, et al. Psychological conditions diagnosed among veterans seeking Department of Defense care for Gulf War-related health concerns. J. Occup. Environ. Med. 1999; 41:384-392.

12. Nicolson GL, Nasralla M, Nicolson NL, Haier J. High prevalence of mycoplasmal infections in symptomatic (Chronic Fatigue Syndrome) family members of mycoplasma-positive Gulf War Illness patients. J. Chronic Fatigue Syndr. 2002; 10:in press.

13. Lange G, Tiersky L, DeLuca J, et al. Psychiatric diagnoses in Gulf War veterans with fatiguing illnesses. Psychiat. Res. 1999; 89:39-48.

14. Haley RW, Kurt TL, Hom J. Is there a Gulf War Syndrome? Searching for syndromes by factor analysis of symptoms. JAMA 1997; 277:215-222.

15. Nicolson GL. Written testimony to the Subcommittee on Benefits, Committee on Veterans’ Affaris, U. S. House of Representatives, July 16, 1998.

16. U. S. Congress, House Committee on Government Reform and Oversight, Gulf War veterans’: DOD continue to resist strong evidence linking toxic causes to chronic health effects, 105th Congress, 1st Session, Report 105-388, 1997.

U. S. General Accounting Office, Gulf War Illnesses: improved monitoring of clinical progress and reexamination of research emphasis are needed. Report GAO/SNIAD-97-163, 1997.

18. Nicolson GL. Written testimony to the Special Oversight Board for Department of Defense Investigations on Gulf War Chemical and Biological Incidents, U. S. Senate, November 19, 1998.

19. Sartin JS. Gulf War Illnesses: causes and controversies. Mayo Clinic Proc. 2000; 75:811-819.

20. Baumzweiger WE, Grove R. Brainstem-Limbic immune dysregulation in 111 Gulf War veterans: a clinical evaluation of its etiology, diagnosis and response to headache treatment. Intern. J. Med. 1998; 1:129-143.

21. Haley RW, Fleckenstein JL, Marshall WW, et al. Effect of basal ganglia injury on central dopamine activity in Gulf War Syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels. Arch. Neurol. 2000; 280:981-988.

22. Magill AJ, Grogl M, Fasser RA, et al. Viscerotropic leishmaniasis caused by Leishmania tropica in soldiers returning from Operation Desert Storm. (1993) N. Engl. J. Med. 1993; 328:1383-1387.

23. Nicolson GL, Nasralla M, Franco AR, et al. . Mycoplasmal infections in fatigue illnesses: Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness and Rheumatoid Arthritis. J. Chronic Fatigue Syndr. 2000; 6(3/4):23-39.

24. Urnovitz HB, Tuite JJ, Higashida JM et al. RNAs in the sera of Persian Gulf War veterans have segments homologous to chromosome 22q11.2 Clin. Diagn. Lab. Immunol. 1999; 6:330-335.

25. Hannan KL, Berg DE, Baumzweiger W, et al. Activation of the coagulation system in Gulf War Illnesses: a potential pathophysiologic link with chronic fatigue syndrome, a laboratory approach to diagnosis. Blood Coag. Fibrinol. 2000; 7:673-678.

Nicolson, G.L., Nasralla, M, Hier, J. and Nicolson, N.L. Diagnosis and treatment of chronic mycoplasmal infections in Fibromyalgia Syndrome and Chronic Fatigue Syndrome: relationship to Gulf War Illness. Biomed. Therapy 1998; 16: 266-271.

27. Nicolson GL, Nicolson NL. Gulf War Illnesses: complex medical, scientific and political paradox. Med. Confl. Surviv. 1998; 14:74-83.

28. Abou-Donia MB, Wilmarth KR. Neurotoxicity resulting from coexposure to pyridostigmine bromide, DEET and permethrin: Implications of Gulf War exposures. J. Tox. Environ. Health 1996; 48:35-56.

29. Moss JL. Synergism of toxicity of N,N-dimethyl-m-toluamide to German cockroaches (Othopiera blattellidae) by hydrolytic enzyme inhibitors. J. Econ. Entomol. 1996; 89:1151-1155.

Baker DJ, Sedgwick EM. Single fibre electromyographic changes in man after organophosphate exposure. Hum. Expl. Toxicol. 1996; 15:369-375.

31. Jamal GA. Gulf War syndrome-a model for the complexity of biological and environmental interactions with human health. Adver. Drug React. Tox. Rev. 1997; 16:133-170.

32. Miller CS, Prihoda TJ. The Environmental and Exposure and Sensitivity Inventory (EESI): a standardized approacxh for quantifying symptoms and intolerances for research and clinical applications. Tox. Ind. Health 1999; 15:386-397.

Haley RW, Kurt TL. Self-reported exposure to neurotoxic chemical combinations in the Gulf War. A cross-sectional epidemiologic study. JAMA 1997; 277:231-237.

Gordon JJ, Inns RH, Johnson MK et al. The delayed neuropathic effects of nerve agents and some other organophosphorus compounds. Arch. Toxicol. 1983; 52:71-82.

Briefing Note 03/2001. Depleted Uranium Munitions. European Parliament Directorate General for Research-Directorate A. Scientific and Technological Options Assessment. January 2001.

36. U. S. Congress, House Subcommittee on Human Resources, Committee on Government Reform and Oversight. Status of efforts to identify Gulf War Syndrome: Multiple Toxic Exposures. June 26, 1997 hearing. Washington DC: U.S. Government Printing Office, 1998.

37. Kalinich JF, Ramakrishnan N, McClain DE. A procedure for the rapid detection of depleted uranium in metal shrapnel fragments. Mil. Med. 2000; 165:626-629.

38. Hooper FJ, Squibb KS, Siegel EL, et al. Elevated uranium excretion by soldiers with retained uranium shrapnel. Health Phys. 1999; 77:512-519.

39. Korényi-Both AL, Molnar AC, Korényi-Both AL, et al. Al Eskan disease: Desert Storm pneumonitis. Mil. Med. 1992; 157:452-462.

40. Baseman, J.B. and Tully, J.G. Mycoplasmas: Sophisticated, reemerging, and burdened by their notoriety. Emerg. Infect. Dis. 1997; 3:21-32.

41. Nicolson GL, Nasralla M, Haier J, et al. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Med. Sentinel 1999; 4:172-176.

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

. Nicolson, G.L., Nicolson, N.L. and Nasralla, M. Mycoplasmal infections and Chronic Fatigue Illness (Gulf War Illness) associated with deployment to Operation Desert Storm. Intern. J. Med. 1997; 1:80-92.

44. Vojdani A, Franco AR. Multiplex PCR for the detectimentanfghfghhhhhhhhhhggggggs, M. hominis and M. penetrans in patients with Chronic gggFatigue Syndrome, Fibromyalgia, Rheumatoid Arthritis and Gulf War Illness. J. Chronic Fatigue Syndr. 1999; 5:187-197.

Nicolson GL, Nasralla M, Nicolson NL. The pathogenesis and treatment of mycoplasmal infections. Antimicrob. Infect. Dis. Newsl. 1999; 17:81-88.

46. Nicolson GL, Nasralla M, Franco AR, et al. Diagnosis and integrative treatment of intracellular bacterial infections in Chronic Fatigue and Fibromyalgia Syndromes, Gulf War Illness, Rheumatoid Arthritis and other chronic illnesses. Clin. Pract. Alt. Med. 2000; 1:92-102.

47. Gray GC, Kaiser KS, Hawksworth AW, et al. No serologic evidence of an association found between Gulf War service and Mycoplasma fermentans infection. Am. J. Trop. Med. Hyg. 1999; 60:752-757.

48. Choppa, P.C., Vojdani, A., Tagle, C., Andrin, R. and Magtoto, L. Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M. penetrans in cell cultures and blood samples of patients with Chronic Fatigue Syndrome. Mol. Cell Probes 1998; 12:301-308.

Nasralla M, Haier J, Nicolson GL. Multiple mycoplasmal infections detected in blood of Chronic Fatigue and Fibromyalgia Syndrome patients. Eur. J. Clin. Microbiol. Infect. Dis. 1999; 18:859-865.

U. S. Congress, Senate Committee on Banking, Housing and Urban Affairs, U. S. chemical and biological warfare-related dual use exports to Iraq and their possible impact on the health consequences of the Persian Gulf War , 103rd Congress, 2nd Session, Report May 25, 1994.

51. Walling AD. Amyotrophic Lateral Sclerosis: Lou Gehrig’s Disease. Amer. Fam. Physician 1999; 59:1489-1496.

52. Nicolson GL, Nasralla M, Haier J, Pomfret J. High frequency of systemic mycoplasmal infections in Gulf War veterans and civilians with Amytrophic Lateral Sclerosis (ALS). J. Clin. Neurosci. 2002; in press.

53. Nicolson GL, Nicolson NL. Doxycycline treatment and Desert Storm. JAMA 1995; 273:618-619.

Nicolson GL. Mycoplasmal infections--Diagnosis and treatment of Gulf War Syndrome/CFIDS. CFIDS Chronicle 1996; 9(3): 66-69.

55. Nicolson GL. Considerations when undergoing treatment for chronic infections found in Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Gulf War Illnesses. (Part 1). Antibiotics Recommended when indicated for treatment of Gulf War Illness/CFIDS/FMS (Part 2). Intern. J. Med. 1998; 1:115-117, 123-128.

Cherry N, Creed F, Silman A, et al. Health and exposures of United Kingdom Gulf war veterans. Part II: The relation of health to exposure. J. Occup. Environ. Med. 2001; 58:299-306.

57. Goss Gilroy Inc. Health Study of Canadian Forces Personnel Involved in the 1991 Conflict in the Persian Gulf Volume I. Prepared for Gulf War Illness Advisory Committee. Ottawa: Department of National Defense. April 20, 1998.

58. Mahan CM, Kang HK, Ishii EK et al. Anthrax vaccination and self-reported symptoms, functional status and medical conditions in the national health survey of Gulf War era veterans and their families. Presented to the Conference on Illnesses among Gulf War Veterans: A Decade of Scientific Research. Military and Veterans Health Coordinating Board, Research Working Group. Alexandria, VA: January 24-26, 2001.

59. Nicolson GL, Nass M, Nicolson NL. Anthrax vaccine: controversy over safety and efficacy. Antimicrob. Infect. Dis. Newsl. 2000; 18(1):1-6.

60. Nicolson GL, Nass M, Nicolson NL. The anthrax vaccine controversy. Questions about its efficacy, safety and strategy. Med. Sentinel 2000; 5:97-101.

Thornton D. A survey of mycoplasma detection in vaccines. Vaccine 1986; 4:237-240.

Nass M. Anthrax vaccine linked to Gulf War Syndrome. Report to the Institute of Molecular Medicine, October 2, 2001.

63. Marty AM. Pathology Syllabus VI, Uniformed Services University of the Health Sciences, pp. 91-94, 1994.

64. Lo, S.-C., Wear, D.J., Shih, W.-K., Wang, R.Y.-H., Newton, P.B. and Rodriguez, J.F. Fatal systemic infections of nonhuman primates by Mycoplasma fermentans (incognitus strain). Clin. Infect. Dis. 1993; 17(Suppl 1):S283-S288.

65. Lo, S.-C., Dawson, M.S., Newton, P.B. et al. Association of the virus-like infectious agent originally reported in patients with AIDS with acute fatal disease in previously healthy non-AIDS patients. Amer. J. Trop. Med. Hyg. 1989; 41:364-376.

66. Lo, S.-C., Buchholz, C.L., Wear, D.J., Hohm, R.C. and Marty, A.M. Histopathology and doxycycline treatment in a previously healthy non-AIDS patient systemically infected by Mycoplasma fermentans (incognitus strain). Mod. Pathol. 1991; 6:750-754.

67. Lo S-C. Pathogenic mycoplasma. U.S. Patent 5,242,820. Issued September 7, 1993.

68. Hinshaw C. American Academy of Environmental Medicine, Personal Communication, 1997.

69. Gass, R., Fisher, J., Badesch, D., et al. Donor-to-host transmission of Mycoplasma hominis in lung allograft recipients. Clin. Infect. Dis. 1996; 22:567-568.

Under penalty of perjury, I swear that the statements above are true and correct to the best of my knowledge, information and belief.

Garth L. Nicolson, PhD
President, Chief Scientific Officer and Research Professor
The Institute for Molecular Medicine and Professor of Integrative Medicine

The Institute for Molecular Medicine (Website:
15162 Triton Lane
Huntington Beach, CA 92649
Tel (714) 903-2900
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Gulf War Syndrome

What is Gulf War Syndrome?

Gulf War syndrome is a widely used term to refer to the unexplained illnesses occurring in Gulf War veterans.

What are the symptoms of Gulf War syndrome?

The following are the most common symptoms of Gulf War syndrome. However, each person experiences symptoms differently. Symptoms may include:

  • fatigue
  • musculoskeletal pain
  • cognitive problems
  • skin rashes
  • diarrhea
Symptoms of Gulf War syndrome may resemble other medical conditions. Always consult your physician for a diagnosis. Symptoms continue to pose a frustrating problem for affected veterans and their physicians. Despite extensive research, the cause of the syndrome remains unexplained.

The impact of Gulf War syndrome:

According to the American College of Occupational and Environmental Medicine, at least 12 percent of Gulf War veterans are currently receiving some form of disability compensation because of Gulf War syndrome.

What are the possible causes of Gulf War syndrome?

Possible causes include:

  • chemical warfare agents, particularly nerve gas, or pyridostigmine bromide, which was given as a preventive measure to soldiers likely to be exposed to chemical warfare agents.
  • psychological factors, such as post-traumatic stress disorder. Veterans with Gulf War syndrome symptoms have high rates of accompanying psychiatric disorders.
  • other chemical agents, such as smoke from oil well fires, pesticides, depleted uranium or exposure to solvents and corrosive liquids used during repair and maintenance.

Treatment for Gulf War syndrome:

While there is no specific treatment for Gulf War syndrome, research suggests than an approach called cognitive-behavioral therapy may help patients with non-specific symptoms syndromes lead more productive lives by actively managing their symptoms.

The Department of Veterans Affairs is conducting a two-year, scientifically controlled study to determine the effectiveness of cognitive-behavioral therapy for veterans with these symptoms.

Other research involving Gulf War syndrome:

Research into Gulf War syndrome, which remains controversial, is taking place in research centers around the country.

The New Gulf War Syndrome

US soldiers in Iraq and Afghanistan are being exposed to toxic chemicals that pose serious health risks

What does a war injury look like? In the case of Iraq, we tend to picture veterans bravely getting on with their lives with the help of steel legs or computerized limbs. Trauma injuries are certainly the most visible of health problems – the ones that grab our attention. A campaign ad for congressman Tom Udall featured an Iraq war veteran who had survived a shot to his head. Speaking through the computer that now substitutes for his voice, Sergeant Erik Schei extols the top-notch care that saved his life.

As politicians argue about healthcare for veterans, it is generally people like Sgt Schei that they have in mind, men and women torn apart by a bullet or bomb. And of course, these Iraq war veterans must receive the best care available for such complex and catastrophic injuries.

Unfortunately, the dangers of modern war extend far beyond weapons. As Iraqis know only too well, areas of Iraq today are among the most polluted on the planet – so toxic that merely to live, eat and sleep (never mind to fight) in these zones is to risk death. Thousands of soldiers coming home from the war may have been exposed to chemicals that are known to cause cancers and neurological problems. What's most tragic is that the veterans themselves do not always realize that they are in danger from chemical poisoning. Right now, there is no clear way for Iraq war veterans to find out what they've been exposed to and where to get help.

In October, the Military Times reported on the open-air pits on US bases in Iraq, where troops incinerate tons of waste. Because of such pits, tens of thousands of soldiers may be breathing air contaminated with burning Freon, jet fuel and other carcinogens. According to reports, soldiers are coughing up blood or the black goop that has been nicknamed "plume crud".

In other cases, soldiers may have been exposed to poisons spread during efforts to restore Iraq's infrastructure. In 2003, for instance, members of the Indiana national guard were put in charge of protecting a water-treatment plant. They were told not to worry about the bright orange dust lying in piles around the plant, swirling in the air and gathering in the folds of their uniforms. In fact, Indiana soldiers spent weeks or months in a wasteland contaminated with sodium dichromate. The chemical, made famous after its role as the villain in the movie Erin Brockovich, is used to peel corrosion off of water pipes. It is a carcinogen that attacks the lungs and sinuses.

Today, a decade and a half after the first Gulf war, we know that such exposure may lead to widespread suffering. In 1991, veterans began to exhibit fatigue, fevers, rashes, joint pain, intestinal problems, memory loss, mood swings and even cancers, a cluster of symptoms and conditions referred to now as Gulf war syndrome (or illness). For years, the US department of defense maintained that stress caused the veterans' symptoms. Veterans groups blamed war-related toxins. This year, the National Academy of Sciences published an extensive review of years of scientific study of Gulf war illness that concluded a cause and effect relationship existed between the widespread illnesses among veterans and exposure to powerful neurotoxins. Complementing the US studies is an emerging body of epidemiological data linking increased incidence of Iraqi cancer, birth defects, infant mortality and multi-system diseases to toxic exposure.

Strangely enough, though, there has been almost no discussion of whether today's soldiers – those fighting in Iraq or Afghanistan – have also been injured by wartime poisons. We don't have a word yet for the constellation of cancers, psychological ills and systemic diseases that may be caused by toxins in today's wars.

In order to care for our veterans, we must do more than offer state-of-the-art hospitals and high-tech prosthetics. Veterans will need information about what poisons they have breathed or touched or drunk and when.

What would such an effort look like? First the military would need to disclose all known incidents of toxic exposure. Then it would have to reach out to veterans and give them information about how to receive care for conditions that arise from this exposure.

This summer, senator Evan Bayh made a first stab at such a system. Bayh pushed the national guard to track down hundreds of those Indiana soldiers who may have breathed orange dust back in 2003. Most of the soldiers are now civilians scattered across the US, unaware that they are at high risk for lung cancer and other respiratory diseases. Some of them may already be struggling with illness. The national guard is making an effort to search for these veterans and provide them with a phone number to call in order to seek medical help.

That's a good first step. But what about all the other veterans who believe that they have returned home from the war healthy? Without knowing it, they may be carrying a small bomb inside them. And they have a right to know. © Guardian News and Media Limited 2008

Gulf War Illness Confirmed

Tuesday 18 November 2008
Thomas D. Williams, truth out | Report
PDF for Gulf War Illness

A federal health panel released conclusions Monday that evidence strongly and consistently indicates hundreds of thousands of US troops in the first Gulf War contracted long-term illnesses from use of pills, given by their own military to protect them from effects of chemical weaponized nerve agents, and from their military's pesticide use during deployment.

Research Advisory Committee on Gulf War Veterans' Illnesses report covers a large range of scientific research and government investigations on Gulf War illness. Its authors claim their "comprehensive analysis" resolves many questions about what caused Gulf War illness and what types of health care can address these serious conditions, which affect at least one in four of the 697,000 Gulf War veterans.

A committee summary describes veterans' various, painfully nagging and long-term health obstacles. "Illness profiles typically include some combination of chronic headaches, cognitive difficulties, widespread pain, unexplained fatigue, chronic diarrhea, skin rashes, respiratory problems, and other abnormalities. This symptom complex, now commonly referred to as Gulf War illness, is not explained by routine medical evaluations or by psychiatric diagnoses and has persisted, for many veterans, for 17 years. While specific symptoms can vary between individuals, a remarkably consistent illness profile has emerged from hundreds of reports and studies of different Gulf War veteran populations from different regions of the US and from allied countries."

In addition to pills supposedly protecting soldiers from nerve agents, the deadly agents themselves ultimately became a crucial wartime exposure. During the January and February 1991 ground war and after, US and allied forces destroyed large stores of Iraqi chemical weapons. And, as the war itself progressed, thousands of military chemical alarms went off, causing soldiers to don chemical protective equipment. Since then, the US General Accountability Office (GAO) and veterans' advocates have repeatedly criticized the lack of quality of the chemical protective masks and protective suits worn by US troops.

Two of the most controversial after-war explosions of underground Iraqi chemical storage depots were set off by US forces themselves at Khamisiyah, Iraq, on March 4 and 10, 1991. Few of the troops were wearing protective gear at the time even though US forces had access to earlier intelligence reports detailing the chemicals inside the bombed bunkers. The Defense Department (DoD) first estimated that 5,000 troops were exposed, and then increased the estimates repeatedly until the number rose to 100,000. Another GAO report said the number is much higher than that but gave no specific figure. At the time and years afterward, the DoD claimed the troops' exposure to chemical warfare agents was too weak to have seriously harmed their health.

Still another of the Research Advisory Committee's conclusions says, "Studies indicate that Gulf War veterans have significantly higher rates of amyotrophic lateral sclerosis (ALS) than other veterans, and that Gulf War veterans potentially exposed to nerve agents have died from brain cancer at elevated rates. Although these conditions have affected relatively few veterans, they are cause for concern and require continued monitoring."

Pesticides, mentioned in Monday's committee report, were used routinely during the war to protect service members against harmful or molesting insects biting troops throughout the Iraq war zone. Common Gulf War insecticides included d-phenothrin, chlorpyrifos, resmethrin, malathion, methomyl and lindane, according to the US Department of Defense Deployment Health Clinical Center. Deet and permethrin (a pyrethroid), are technically repellents rather than insecticides, says the center, but they were also an ultimate health concern, the center opines.

The Research Advisory Committee's continued conclusions say that limited other evidence, not totally decisive, shows that the armed service members could have become sick from low-level exposure to chemical warfare nerve agents as well as their close proximity to oil well fires, their receipt of multiple so-called preventative vaccines, and the effects of combinations of their hazardous other Gulf War exposures.

The report was issued by the committee to US Secretary of Veterans Affairs James Peake. "The VA has accepted and implemented prior recommendations of the committee and values the work represented in the report presented today. Secretary Peake thanked the committee for its report and recommendations and directed VA to review and respond to the committee's recommendations in the near future," said Alison Aikele, a VA spokesperson. Despite receiving at least one adverse comment via email, the VA did not respond to that criticism. As well, Charlene Reynolds, a defense contract spokeswoman for the Pentagon, said the DoD is preparing a similar statement without yet being sure when it would be released.

The Committee report knocks down repeated theories of largely Pentagon-funded studies that one of the main causes of all these wartime illnesses was post-traumatic stress disorders or other mental ailments. "Gulf War illness fundamentally differs from trauma and stress-related syndromes described after other wars," concludes the report. "Studies consistently indicate that Gulf War illness is not the result of combat or other stressors and that Gulf War veterans have lower rates of post traumatic stress disorder than veterans of other wars." This discredits the Walter Reed Army Medical Center's extensive studies of Gulf War veterans, which concluded stress was a major cause of Gulf War illnesses.

The Research Advisory Committee's conclusions additionally minimize other allegedly sickening Gulf War exposures, including depleted uranium munitions blasts, anthrax vaccine use, fuels, solvents, sand and particulates, infectious diseases and chemical agent resistant coating (CARC). However, numerous other scientific reports have earlier concluded these exposures, too, sometimes proved extremely sickening for war veterans.

Highlighted by the committee's findings is what many veterans' advocates have called the gross negligence of responsible federal health and military agencies in repeatedly failing to get to the bottom of what the government labeled the "mysterious Gulf War syndrome" illnesses. What's more, during three presidential reigns and several sessions of US Congresses, the highest level officials continuously discussed these hazards and resulting troop illnesses and deaths, but never came to their own ultimate conclusions or scientific plans to deal with the health consequences.

Denise Nichols, a veteran nurse, retired Army major and vice chair of National Vietnam and Gulf War Veterans Coalition, has worked many years to assist sick Gulf War service members. "The veterans of the Gulf War 90-91 did not give up," wrote the nurse. "They knew that physically something in their bodies was damaged. They have been stating this since November 1993, when the first hearings [in Congress] occurred. Their family members have seen it and tried to hold their families together waiting for answers from the government. It has been an exceedingly difficult nightmare for these veterans and their families. Many were told that it was psychological or somatic and [so] families left their veteran loved ones behind. [And,] many of these veterans have died, [been] forgotten [or] misdiagnosed. It is time now that the government declassify all [wartime and post war] records that might provide more answers. After all, in 2003, we liberated Iraq, so many ask now, 'Why not let these records that may provide answers be fully declassified?'"

After the end of 43 days of dirty chemical and environmental Gulf War chaos when former President George H.W. Bush laid out conditions for a cease fire on Feb. 27, 1991, hundreds of thousands of US, allied, Iraqi troops and Iraqi civilians suffered resulting long-term illnesses and, ultimately, untold deaths. Very limited medical attention has ever been paid by US federal agencies to sick Iraqi civilians the US military and their private contractors were supposed to protect.

Today, close to 18 years later, US and foreign governments are still making promises, struggling and conversing over failed attempts to give the combatants and civilians proper health care. Meanwhile, as the US fights the second war in Iraq and continues along with the war in Afghanistan, the failed attempts to deal with US casualties and sicknesses continues at a similar dragged out pace. "When will they ever get it done?" war veterans have repeatedly asked themselves and others.

Monday, the 14-member Research Advisory Committee and a consultant, composed of doctors, scientists and veterans, confirmed these thousands of Gulf War One veterans' haunting and frustrating concerns. It concluded, "Federal Gulf War research programs have not been effective, historically, in addressing priority issues related to Gulf War illness and the health of Gulf War veterans. Substantial federal Gulf War research funding has been used for studies that have little or no relevance to the health of Gulf War veterans, and for research on stress and psychiatric illness ... A renewed federal research commitment is needed to identify effective treatments for Gulf War illness and address other priority Gulf War health issues."

"After 17 years of official government delays and denials, VA's Research Advisory Committee should be commended for their work providing facts about Gulf War illnesses," said Paul Sullivan, executive director of Veterans for Common Sense (VCS). "Veterans for Common Sense is concerned that there are up to 210,000 Gulf War veterans who remain ill after serving the 1991 Gulf War, and these veterans still need healthcare and disability benefits."

"VCS urges Congress to fund new research into why so many Gulf War veterans are ill as well as fund research into desperately needed medical treatments for veterans. VCS also urges top VA officials to review the conduct of the VA Central Office staff who blocked scientific research and treatments for veterans, especially VA's contracts with the Institute of Medicine that improperly excluded animal studies from scientific review. The VA Central Office staff who needlessly delayed research, treatment, and disability benefits for hundreds of thousands of Gulf War veterans should be held accountable for their actions," said Sullivan.

He continued, "The facts now show that top Pentagon officials failed to assist Gulf War veterans by clinging to the myth that Gulf War illnesses was related to stress." Sullivan went on to say that the US Army "neglected to consider the many toxic exposures as potential causes of Gulf War illnesses, even after Gulf War veterans raised these as serious possibilities."

The committee identified four areas of highest priority research to assist sick Gulf War veterans as follows:

1) Evaluate the effectiveness of currently available treatments used for Gulf War illness or conditions with similarities to Gulf War illness.

2) Pilot trials and/or observational studies capable of identifying promising treatments suitable for evaluation in larger clinical trials.

3) Identification of specific pathophysiological mechanisms underlying Gulf War illness that are potentially amenable to treatment interventions.

4) Assess novel therapies based on scientific findings as they emerge.


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