Testimony prepared For
The National Academy of Sciences
Institute of Medicine
meeting - August 14, 2000.
"Identifying Effective Treatments for Gulf War Veterans' Health Problems"

I am Lawrence A. Plumlee, a Johns Hopkins physisian formerly employed as medical science adviser by the Offices of Research and Development of agencies of the U.S. Public Health Service and the U.S. Environmental Protection Agency. I am currently copresident of the National Coalition for the Chemically Injured, which represents groups of chemically injured patients coast to coast.

Toxicology has traditionally focused on describing the acute effects ofchemicals, and the pathologically verifyable chronic effects of carcinogenicity, teratogenicity, and mutagenicity. But it is increasingly obvious that chronic fatigue, fibromyalgia, and multiple chemical sensitivity are much more common chronic toxic effects of chemical exposure which have been dismissed by toxicologists because they are less specific as to the causitive chemical, less easily measured quantitatively, less clear as to the mechanisms which produce them, and are seen in a variety of illnesses including toxic, infectious and psychiatric. Nevertheless, studies of Gulf War Illnesses, and other recent studies, have elucidated the role chemicals play in these chronic syndromes. Haley, Billecke, and LaDu, for example, found that ill Gulf War veterans with neurological symptoms were more likely to have low PON1 Type Q arylesterase activity than were controls, and the lower the enzyme activity, the sicker the veteran. Given that large numbers of military personnel were repetitively exposed to low levels of sarin and pesticides such as chlopyrifos and permethrin, while taking pyridostigmine during the Gulf War, such exposures would have covalently bound and inactivated much of the serum butyrylcholinesterase, which is the first line of toxicological defense against these chemicals. This left the paraoxonase/arylesterase Type Q allozyme as the primary remaining defense, and in personnel with genetically low levels, would have allowed these chemicals into the nervous tissue.

Whereas in the field of infectuous diseases, differences in susceptibility to a given pathogen are accepted, there has been an expectation in toxicology of greater consistency. But in the foregoing example, a seven-fold variation in detoxification enzyme levels was observed in human beings.

While some have argued that there is no mechanism to explain sensitivity to multiple chemicals, this and other examples make it clear that when a large number of chemicals are detoxified by a particular enzyme or enzyme system, increased sensitivity to all of those chemicals could occur when the enzyme is deficient.

In the study cited by Haley, Billeke, and LaDu, variations in arylesterase were explained by genetic differences among veterans, whether they carried Type Q or Type R alleles. But they also hypothesized that there were variations in butyrylcholinesterase occurring because chemicals had bound and inactivated this enzyme. Another instance where it is recognized that organophosphates may change an individual's susceptibility to future doses of the same or other chemicals is seen in the malathion material safety data sheet, which reads, "Repeated exposures to cholinesterase inhibitors such as Fyfanon ULV may, without warning, cause increased susceptibility to doses of any cholinesterase inhibitor." A large number of chemicals have been found to have some cholinesterase inhibiting properties, another possible explanation of susceptibility to multiple chemicals.

While we do not yet understand how to cure the syndromes of chronic fatigue, fibromyalgia, or multiple chemical sensitivity, clinicians have observed that symptoms can often be improved by reducing exposure to pesticides and other toxics which do not cause symptoms in most healthy persons. Nutrients to improve detoxification, such as glutathione and its precursor n-acetyl cysteine, are often helpful also. Antioxidants to reduce free-radical damage by chemicals bypassing detoxification systems help many. And correction of magnesium deficiency has been of great value empirically, as is the reduction in the percentage of yeasts among the normal intestinal flora. Antibiotic and antiparasitic treatment may eliminate chronic infections which evade the usual diagnostic techniques. Such infections often damage the intestinal mucosa, thus impairing intestinal absorption of nutrients and leading to nutritional deficiencies. Food sensitivities may have occurred because the infection-damaged mucosa allowed food proteins to enter the bloodstream. Treatment logically includes eliminating the infection, restoring normal flora, correcting nutritional deficiencies, and the recognition and avoidance of sensitive foods. Of course food sensitivities may also be due to impaired metabolism of certain biochemical constituents of food.

In summary, many Gulf War veterans have illnesses which appear similar to those seen in stateside individuals who have experienced pesticide poisoning, and others with increased susceptibility to pesticides and other common petrochemicals. Scientific explanations for such susceptibilities are being generated, and such explanations sometimes generate logical approaches to treatment. Other useful treatment approaches have been observed empirically, but have not yet been fitted into the enzyme deficiency model. The Departments of Defense and Veterans Affairs should have undertaken research of these treatments. Whatever nutritional cofactors support detoxification of chemicals encountered in the Gulf War should be determined, administered to poisoned veterans, and studied. For example, PON1 has a requirement for calcium.

Lawrence A. Plumlee, M.D.
CoPresident, National Coalition for the Chemically Injured
5717 Beech Avenue Bethesda, Maryland 20817-2563
Telephone and Fax: 301 897 9614