Response to Errors Prevalent in the Understanding of Environmental Illness, by Dr. G. Ross

Response to Errors Prevalent
in the
Understanding of Environmental Illness

        Dr. Gerald H. Ross, M.D., C.C.F.P., D.I.B.E.M., D.A.B.E.M.,
F.A.A.E.M., F.R.S.M.
                Past President, American Academy of Environmental Medicine
May 2000

     This article was generated in response to widely circulated assertions that there is no good data on the epidemiology of environmental illness and that the causal etiology of environmental illness is not known. That there is little objective evidence to support a causal link with environmental exposures and considerable evidence pointing to psychological factors as a cause.
Error #1 : "There is no good data on the epidemiology of environmental illness."
     There are a number of substantial studies on this topic. Some of the more recent studies are as follows:
A statewide telephone survey of 4000 randomly selected adults was conducted by the Health Department of California (1995 and 1996), by Kreutzer and colleagues. They found that 6% of those surveyed stated that they had been diagnosed with Multiple Chemical Sensitivity or
Environmental Illness, and about 16% stated that they were "unusually sensitive to everyday chemicals". (Agency for Toxic Substances and Disease Registry (ATSDR): Final Report: Evaluating Individuals Reporting Sensitivities to Multiple Chemicals. June 1996, ATSDR #PB96-187646)
To my understanding this foregoing study was also subsequently published in the American Journal of Epidemiology, where it was 'in press', as of June 1999.
A similar survey in New Mexico by Voorhees in 1997 found that 2% of those surveyed reported that they had been diagnosed with MCS or Environmental Illness, and once again, about 16% stated that they were "unusually sensitive to everyday chemicals". (Voorhees RE. Memorandum
rom New Mexico Deputy State Epidemiologist to Joe Thompson, Special Counsel, Office of the Governor, 13 March 1998)
On a much larger scale, a study by Meggs on 1027 people in North Carolina indicated that 33% of those surveyed were 'especially sensitive to chemicals'. (Meggs WJ, Dunn KA, Bloch RM, Goodman PE, Davidoff AL. Prevalence and Nature of Allergy and Chemical Sensitivity in a
General Population. Archives of Environmental Health (1996) 51(4): 275-82)
A study with 114 references, by the well-respected psychiatrist Iris Bell, (who was at Harvard and who is now in Phoenix), looked at 809 young adults, and found that 28% of that group were "especially sensitive" to chemicals. (Bell IR, Miller CS, Schwartz GE, et al. Neuropsychiatric
and somatic characteristics of young adults with and without self-reported chemical odor intolerance and chemical sensitivity. Archives of Environmental Health (1996) 51(1):9-21)
Another study by Bell and colleagues on 160 older veterans, found that 37% were reported to be "especially sensitivity to chemicals". (Bell IR, Walsh ME, Goss A et al. Cognitive dysfunction and disability in geriatric veterans with self reported intolerance to environmental chemicals. Journal of Chronic Fatigue Syndrome, (1997) 3(3):15-42)
In a study on 705 individuals in New Jersey, Kipen and colleagues found that 69% of patients diagnosed with MCS met the 'threshold score' for MCS on a 122-item exposure questionnaire, 54 % of asthmatics scored over the MCS threshold,20 % of general medicine clinic patients scored over the MCS threshold, and 15% of occupational medicine referrals scored over the threshold. Kipen is based at Johns Hopkins School of Medicine. (Kipen HM, Hallman W, Kelly-McNeil K, Fielder N. Measuring chemical sensitivity prevalence: a questionnaire for population studies. American Journal of Public Health (1995) 85:574-7)
Dr. Lance Wallace, of the U.S. Environmental Protection Agency, authored a publication in Indoor Air, on 3948 office workers in three buildings, which included the famous 'problem building' of the Waterside Mall EPA Headquarters. In that study, 32% of the employees in the Waterside Mall building reported that they were "especially sensitive" to common chemicals. In the two other buildings, the numbers were 32% and 29%. (Wallace LA, Nelson CJ, Highsmith R, Dunteeman G. Association of personal and workplace characteristics with health, comfort and odor: a survey of 3948 office workers in three buildings. Indoor Air(1993) 3:193-205)
These data on EPA employees were then compared with data from a control group of 3000 employees from the Library of Congress (Madison Building), 33 % of whom reported that they were "especially sensitive" to chemicals. (Wallace LA et al. Perception of indoor air quality among government employees in Washington, DC. Technology: Journal of the Franklin Institute (1995) 332A:183-198.)
It should be noted that these researchers were all connected with the EPA, and that the EPA approved of these findings for presentation and publication.
Among Gulf War veterans, the largest random survey conducted by the U.S. Department of Veterans' Affairs in 1998, was on 11,216 persons who had served in the Persian Gulf, compared to 9,761 who were not deployed to that area. Among those deployed to the Gulf, 15% reported chemical sensitivity, while the value was 5% among those not deployed. The chemical exposures associated with Gulf war service are notorious and very well known. (Kang HK, Mahan CM and Lee KY. Prevalence of chronic fatigue syndrome among U.S. Gulf War veterans. Boston, MA. Fourth Annual AACFS Conference on CFIDS, 10 October 1998 (abstract and presentation).
In a smaller study among Gulf War veterans who were hospital outpatients (i.e., they were sick enough to require health care), Bell and colleagues found that among those deployed to the Gulf, 86% complained of chemical sensitivity, compared to 30 % in a group of ill non-deployed veterans. (Bell IR et al. Self-reported chemical sensitivity and wartime chemical exposures in Gulf War veterans with and without decreased global health ratings. Military Medicine (1998) 163:725-32
In a study that specifically assessed MCS among veterans selected randomly from the VA registry, 36 % of 1004 veterans met common research criteria for MCS. (Fielder N, Kipen H, Natelson B. Civilian and veteran studies of multiple chemical sensitivity. Presented at: Multiple Chemical Sensitivity: Problems for Scientists and Society. 216th Annual Meeting of the American Chemical Society, Boston MA, 26 August 1998 (subsequently published in Toxicology and Industrial Health, (1999) Vol. 15
This is only a partial list of published scientific papers on the epidemiology of chemical sensitivity or 'environmental illness'. Some of these studies are from well respected bodies like the U.S. EPA, the California Department of Health, the U.S. Department of Veterans' Affairs, and presented at the American Chemical Society.

Error #2: "the causal etiology of environmental illness is not known. There is little objective evidence to support a causal link with environmental exposures and considerable evidence pointing to psychological factors as a cause."
Regarding the whole issue of causation (and many other factors connected with environmental illness), one of the best publications on this entire issue of chemical sensitivity is the scholarly book by Ashford and Miller. (Miller NA and Miller CS. Chemical Exposures: Low Levels and High Stakes. 2nd Edition, 1998, Van Nostrand Reinhold, New York.)
Ashford is the Professor of Technology and Policy at the Massachusetts Institute of Technology and Miller is an allergist/immunologist at the University of Texas at San Antonio. It is my understanding that their publication is the most widely cited reference in the published medical and scientific literature on chemical sensitivity. They clearly talk about the strong association between chemical exposure and the development of chemical sensitivity.
By way of example, Ashford and Miller were the first to identify the four main categories of the patients with chemical sensitivity.   They are:
1. Industrial workers exposed to chemicals,
2. Occupants of tight or problem buildings, (including schoolchildren), where the off-gassing of solvents and other indoor pollutants, and inadequate ventilation may play an important role,
3. Residents of contaminated communities, especially those near toxic waste sites, close to industrial facilities, or with groundwater contamination, and
4. Individuals with unique personal histories of chemical exposures to things like pesticides, domestic indoor contamination, consumer products, etc.

All of these groups are described as having some form of chemical exposure or contamination as an antecedent to the onset of the environmental illness or chemical sensitivity.
The published literature on chemical sensitivity, starting all the way back with the early papers by the pioneering allergist Dr. Theron Randolph in the 1940's and 1950's, related the association of chemical sensitivity to chemical exposures of various types. Randolph described its induction by petroleum products,especially natural gas exposures. (Randolph TG. Sensitivity to petroleum, including its derivatives and antecedents. Journal of Laboratory and Clinical Medicine (1952) 40:931-932)

One of the other early pioneers in the field, Dr. Clifton Brooks, also saw and reported on the induction of adverse reactions to low level chemical exposures. (Kailen E, and Brooks C. Systemic toxic reactions to soft plastic food containers. Medical Annals of Washington DC, (1963). 32:1-8.
Miller and Mitzel evaluated and reported on groups of chemically sensitive patients who cited home/office remodeling versus pesticide applications as initiating events. While the symptoms in these two groups were similar, the pesticide exposed group exhibited the more severe symptoms, as would be expected because of the greater neurotoxicity of that class of chemicals.
If the condition of MCS were truly psychological in nature, one would expect approximately an equal symptom response in each group, if psychological factors or 'chemophobia' were at work. (Chemophobia, or irrational fear of chemicals, has been suggested as one of the psychological causes for the condition.) This difference in the two groups, however, with more severe symptoms among the pesticide exposed group compared to the solvent exposed group, is highly consistent with a biological basis for the condition, with a common pathological induction pathway of MCS between the two exposed groups. (Miller CS and Mitzel HC. Chemical Sensitivity attributed to pesticide exposure versus remodeling. Archives of Environmental Health (1995) 50:119-129
Indeed, there has been a well-known animal model described for many years, which potentially explains the physiological induction of chemical sensitivity. Two of the many references on this matter are:

Bell IR Miller CS Schwartz GE. An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationships to limbic kindling and affective spectrum disorders. Biological Psychiatry. (1992) 32:218-242 and
Bell IR et al. Neural Sensitization and Physiological Markers in Multiple Chemical Sensitivity. Regulatory Toxicology and Pharmacology (1996) 24:S39-S47)
Dr. Theodore Simon, a Harvard-trained Nuclear Medicine specialist, is one of the most experienced physicians in the U.S. on the assessment of brain metabolism in patients reporting chemical sensitivity, by using brain metabolic SPECT scanning technology.

In one study by Simon, chemically sensitive patients who reported that their sensitivity problem started after the insertion of breast implants or solvent exposures were assessed with this scanning technology. These patients were found to have distinctive abnormalities on brain metabolism, that were described as neurotoxic in nature, and in patterns that are very different from the kinds of brain metabolic abnormalities often seen in psychiatric disease. (Simon TR, Hickey DC, Rea WJ, Johnson AR, Ross GH. Breast implants and organic solvent exposures can be associated with abnormal cerebral SPECT studies in clinically impaired patients. Radiology (1992) 185:234)
Even scientists who have nothing to do with the debate over the social issues of environmental illness, have reported that if animals are exposed to repeated low levels of chemicals over a period of time, the animals can become exquisitely reactive and sensitive to even the most minute traces of those chemicals. The process is called time-dependent sensitization, with limbic kindling, which is an electrical excitation in the primitive areas of the brain. (Rossi J. Sensitization induced by limbic kindling and kindling-related phenomena as a model formultiple chemical sensitivity. Toxicology (1996) 111:87-100)
In a paper that I presented at Princeton and which was subsequently published, I reported on the clinical characteristics of chemical sensitivity. Within that paper I cited a survey of the self-reported triggers of chemical sensitivity in a study of 200 patients who were evaluated at the Environmental Health Center-Dallas, a private clinic that treats a large number of chemically contaminated or sensitive patients. In that study, 30 % of the MCS patients cited those chemical exposures associated with a newly constructed home or work environment as the initiating event. Another 25 % cited other chemical exposures, such as pesticides, for a total of 55% of MCS patients directly attributing their sensitivity problems to chemical exposures. (Ross GH. Clinical Characteristics of Chemical Sensitivity: An Illustrative Case History of Asthma and MCS. Environmental Health Perspectives (1997) Vol. 105, Supplement 2:437-441)
Dr. William J Meggs, of the Department of Emergency Medicine, East Carolina University School of Medicine, Greenville, North Carolina, has reported on the unusual physical findings on nasal biopsies in MCS patients.
He found a very frequent defect in the "tight junctions" between cells, desquamation of the nasal epithelium, glandular hyperplasia, lymphocytic infiltrates, and peripheral nerve fiber proliferation. These findings are consistent with the chronic inflammation seen in these mucosal tissues with chemical exposures. Meggs describes the objective nature of these findings with biopsy results. The damaged and enflamed mucosa would permit the ready absorption of inhaled chemicals directly across the nasal mucosa, sometimes with rapid entry into the brain through the cribriform plate at the roof of the nose. (Meggs WJ. Hypothesis for Induction and Propagation of Chemical Sensitivity Based on Biopsy Studies. Environmental Health Perspectives (1997) Vol. 105 Supplement 2:473-478)
Meggs finding on nasal biopsies matches exactly what is seen in the metabolic SPECT brain scans of MCS patients. These patients very frequently have a greatly increased uptake of radioactive tracer into the nasal tissues, indicating a significant increase in metabolism there.
This significant uptake of tracer into the nasal area has been seen hundreds of times, on the SPECT scans on MCS patients, and is not seen in normal controls. This would be a physical finding that is very consistent with the physical basis of MCS, and points away from it being of psychological origin. I was invited to present a paper on these SPECT scan abnormalities in MCS patients at the very first meeting that the American Chemical Society (ACS) held regarding Chemical Sensitivity. It was in Boston in 1998, sponsored by the Agrochemicals Division (the manufacturers of pesticides). The papers presented there were subsequently peer reviewed and published in the journal Toxicology and Industrial Health.
Metabolic brain scans on patients with MCS, usually show distinct abnormalities of brain metabolism that are described by the nuclear medicine specialists as neurotoxic. These findings of abnormal brain metabolism in chemically-exposed and chemically sensitive patients have been seen by at least three independent groups of researchers (Simon in Dallas, Callender in Louisiana and Heuser in California). (Callender TJ, Morrow L and Submaranian K. Evaluation of chronic neurologic sequelae after acute pesticide exposure using brain SPECT scans. Journal of Toxicology and Industrial Health (1994) 41:275-284) (Heuser G, Mena I and Alamos F. Neurospect findings in patients exposed to neurotoxic chemcials. Toxicology and Industrial Health (1994) 10 (4/5):561-571)
What I demonstrated in my paper to the American Chemical Society, is that MCS patients have a neurotoxic pattern in brain metabolism that is very different from those abnormalities that are reported in psychiatric disease. These abnormalities correlate well with the common symptoms reported by MCS patients, of neurocognitive and intellectual impairment or emotional instability, upon certain chemical exposures.
Severe deterioration in the brain SPECT scans are seen in MCS patients who have baseline scans followed by low-dose ambient chemical challenges, under environmentally controlled conditions, and in concentrations that are found in everyday situations.
These challenge studies show a significant deterioration of the physical metabolic processes in the brain from low dose chemical challenges to substances to which the person is sensitized. These scientific, objective findings are totally consistent with a physiologic explanation, and highly inconsistent with a psychological origin. (Ross GH. Neurotoxicity in Single Photon Emission Computed Tomography brain scans of patients reporting chemical sensitivity. Toxicology and Industrial Health (1999) 15:415-420)
Fincher and colleagues have demonstrated that these neurotoxic findings are very frequently seen in chemically exposed and sensitive patients, and are not seen in healthy controls. (Fincher EF et al. Comparison of single photon emission computed tomography findings in cases of healthy adults and solvent exposed adults. American Journal of Industrial Medicine (1997) 31:4-14
Over 1500 SPECT brain scans have been performed by Simon and colleagues on MCS patients (including the use of controls and using ambient chemical challenges under environmentally controlled conditions). These nuclear medicine specialists report that over 90% of these MCS patients scanned in this manner exhibit a neurotoxic pattern of metabolic abnormalities in the brain, that is very different from the changes associated with psychiatric disease.
This is my personal knowledge from being intimately involved with these investigations, and from personal communications from the nuclear medicine specialists who perform these sophisticated scanning technologies, which techniques have been used and well accepted within the medical community for many years.

Now, regarding the statement made about considerable evidence pointing to psychological factors as a cause of environmental illness or chemical sensitivity, note the work of Davidoff and Fogarty.

In their scholarly paper in 1994, these authors carefully reviewed the ten most prominent published papers which had concluded that MCS likely had a psychological causation. They found that all of these studies had serious methodological flaws, and some had completely illogical conclusions. Six of the ten studies had no control group, and there were many problems related to sample selection, measurement and study design.
In one study, they found that the findings that were used by the author (Simon) to support a psychogenic basis, could have been used just as well, to support a physical causation.
Davidoff and Fogarty stated:
"This review suggests that existing research studies considered widely supportive of a psychogenic origin for MCS syndrome have serious methodological flaws... The nature, timing, and origin of these (psychiatric symptoms)...can be explained plausibly by at least six competing hypotheses... " (Davidoff A and Fogarty L. Psychogenic origins of Multiple Chemical Sensitivity syndrome: A critical review of the research literature. Archives of Environmental Health (1994) 49(5):316-325)

It is very important to note that this paper was reviewed and critiqued in the Journal of Occupational and Environmental Medicine, the official voice of the American College of Occupational and Environmental Medicine (ACOEM). This organization has been very sceptical and even critical of a physical causation for MCS.
The review by ACOEM stated the following about the Davidoff and Fogarty
publication:
"the authors... convey full awareness of widespread scepticism directed
towards patients exhibiting characteristics of multiple chemical sensitivity syndrome (MCS) and to supporters of MCS as a diagnostic entity. Their rigorous methodology, application of diagnostic criteria, and careful analysis may serve to convert some hardened nonbelievers at least into hardy agnostics." (Wittmer J. Selected reviews of the literature. Multiple Chemical Sensitivities. Journal of Occupational and Environmental Medicine. Nov (1996) 38(11):1085

     So the papers drawing the conclusion that MCS is of psychological origin have been called into very serious question, and indeed can not be relied upon to make the assertions that have been made. This stands in sharp contrast to the objective, verifiable abnormalities that are seen in other studies, especially the brain metabolism of MCS patients, through the use of a high tech methodology that leaves very little to subjective assessment.
     We all know that there are very vocal critics of the acceptance of MCS as a valid diagnosis. When it is grudgingly accepted, the patients are often dismissed as hysterical, or having psychiatric illness. Frequently, it has been shown that some of these most vocal critics of MCS are paid consultants or even apologists for the chemical industry. The chemical and related industries are scared to death at the idea of the acceptance of MCS as a valid condition that can be induced or worsened by common chemical exposures.
     The potential liabilities are enormous. Not surprisingly, spokespersons
for the perfume and chemical industries are doing all that they can to denigrate the afflicted patients and to obfuscate the issue. They seem uninterested in the true scientific facts, and in the weight of opinion in the medical research community about the reality and likely physical basis for environmental illness or chemical sensitivity. On this matter, I would refer you to the excellent review of this social/political aspect of MCS by Ashford and Miller, in their book, which I cited earlier.
     It is important to note that at the aforementioned meeting on MCS organized by the American Chemical Society, about 75% of the speakers presented data and conclusions that supported primarily a physical, organic causation for MCS, with the other 25% presenting mostly opinions about a psychological causation.
     There are now hundreds of articles that have been published in the medical and scientific literature related to the issue of environmental illness and chemical sensitivity. It amazes me that in spite of all these publications on MCS, that some people continue to loudly proclaim that is a non-existent illness. Why would this be? How can they possibly justify such a position, in the face of the weight of this evidence?
     MCS Referral and Resources is a clearinghouse and reference center on MCS that has done acareful assessment of the literature. Of the 425 articles on MCS published between 1952 and 1997 alone, 231 of the papers present findings of a physical or organic cause for MCS, while 104 present a psychological causation. Of these articles, 59 present both perspectives, and 25 present research protocols. Since then, many more articles have appeared, presenting scientific findings of physical abnormalities in MCS patients. More than 50% of these 425 articles were published since 1992, in contrast to the anti-MCS position papers of various medical groups, which almost all predate 1993.
     In summary, of these 425 articles, more than one half are suggesting a physical cause for MCS, with less than one quarter suggesting a psychogenic basis, and the gap is growing. Misinformed statements expressed by persons about a so-called "lack of evidence" on the prevalence and organic origins of chemical sensitivity are completely at odds with the weight of evidence and opinion in the published medical and scientific literature.