MULTIPLE CHEMICAL SENSITIVITY:
I'm sure most of the readers will be aware of the condition that has come to be called Multiple Chemical Sensitivity (MCS), a condition in which sufferers are several magnitudes more intolerant of various every day chemicals---such as those in perfumes/ colognes, hair sprays, paints and so forth---than the healthy population.
Much alleged controversy has surrounded the issue. Some critics say that MCS sufferers have no consistent biological abnormalities and that the condition is psychogenic (meaning it originates emotionally, rather than through organic processes).
In this literary critique I will discuss the flaws of some of the leading proponents of the psychogenic view.
Before moving on to my critique I'd like to discuss, briefly, some of what has been reported on MCS.
In 1999 a consensus definition for MCS was finally reached (Heuser et al., 1999). Prior to this Cullen's definition was the most widely used for studying MCS.
The animal literature is particularly fascinating: In a recent documentary on MCS ("Multiple Chemical Sensitivity How Chemical Exposures May Be Affecting Your Health" by Allison Johnson) Ashford and Bell discuss the animal research on MCS. It turns out, that if you expose animals to the very same chemicals reported to induce MCS in humans, then the animals often develop chemical sensitivity.
he Australian Chemical Trauma Alliance recently reported a case of a horse that was chemically sensitive.
Martin Pall (2002) discussed mouse models of MCS, in which mice developed chemical sensitivity after being exposed to certain chemicals. Pall wrote, "In a series of studies of a mouse model of MCS, involving partial kindling and kindling, both excessive NMDA activity and excessive nitric oxide synthesis were convincingly shown to be required to produce the characteristic biological response." In other words, excessive levels of nitric oxide (NO) and NMDA play a vital role in the development of MCS. Interestingly, chemicals reported to induce MCS in humans---such as certain pesticides, benzene, etc.---all increase levels of NO.
The fact that animals do develop chemical sensitivity is sufficient, in my mind anyway, to show that it is in fact a real, organic disease.
MCS has been observed in people of all races, various age groups, in various cultures, in very geographically diverse locations. In addition, different studies show that the number of people with signs of MCS is so high as to be called an epidemic (Donnay, 1999, 2002). In my judgement, it is unreasonable to say that these observations point to people who have health problems due solely to psychogenic mechanisms or are fakes.
In the human literature, consistent abnormalities have been found on challenge brain scans with and without control groups (Ross, 1999; Heuser, 1998, 2001, and others---some of the other studies include CFS and GWS patients, with control groups) and double blind 2,3-DPG blood tests (Panjwani, 1999). Inconsistent abnormalities include chronic T-cell activation and other immunologic disturbances (Ashford and Miller, 1998), suggesting that such are consequential and not associated with etiology.
Dudley's study (1998) of the P300 brain waves of 20 MCS patients is still one of the clearest studies available (contact me for details on the study). The profound implications of his research are undeniable for one simple reason: The P300 is not influenced by emotions/ belief systems. Thus any changes that take place upon challenge---whether double blinded or not---must be from organic, neurological processes.
Albert Donnay (1999, 2002) has suggested that carbon monoxide (CO) poisoning plays a role in MCS. Elevating CO in the body also elevates NO, so research should focus on the roles NO and CO play in the development of MCS. (In addition both gases bind to heme proteins, and can thus cause the 2,3-DPG excess mentioned above.)
In 1995, the CMA reclassified its anti-MCS position statement of 1985 as "a historical document only". Likewise, the American College of Physicians now has no position statement on MCS. In 1999 the British Health and Safety Executive commissioned a report on MCS that concluded MCS is an organic disease. The report was carried out by the Institute of Occupational Medicine and endorsed by the Department of Health (Independent, London, March 19, 1999). Excluding literature from the Journal of Clinical Ecology (which favor the organic view of MCS), over 1/2 of all the peer-reviewed literature on MCS favor the organic view rather than the psychogenic view, with less than 1/4 favoring the psychogenic view (Donnay, 1999, 2002). When reviewing the references of the ACOEM and AAAAI position statements on MCS it became apparent to me that both missed hundreds of peer-reviewed articles on MCS, which support its organic etiology. The position statements make no reference to Pall's latest works. Also strangely absent from these position statements is any reference to Heuser's and others' recent work in brain imaging. The list of omission goes on. So while I have tremendous respect for both organizations, it must be said that their MCS position statements should not be taken seriously due to the authors' lack of rigorous research. I strongly encourage the authors to review more literature.
Now I will move on to my criticisms of the skeptics. Most skeptics rely on the data from Herman Staudenmayer, who did a double blind chamber study of persons alleging to have MCS. His study has come under very unfavorable review by Ashford and Miller (1998) for alleged flaws in methodology, masking, waiting periods, and other problems. Even the Interagency Draft Report (1998) is somewhat skeptical of his data.
However, giving Staudenmayer the benefit of the doubt, most skeptics need to realize that Staudenmayer himself believes that there are persons who are genuinely and severely sensitive to various chemicals. His conclusion is that "at least half" of those claiming to have MCS most likely have psychogenic disorders, while most of the remainders have true sensitivities (Sorg's review, 1999).
Recently the AAAAI reported a high incidence of the cholecystokinin B receptor allele 7---CCK-B receptor---in MCS sufferers. This genetic linkage is alleged to be associated with a predisposition to "panic disorder." Thus, the researchers concluded MCS is most likely a panic disorder. However, CCK-B receptor modulates NMDA activity, which increases NO levels. Thus, the study ironically shows a genetic predisposition to NO poisoning among MCS sufferers, supporting Martin Pall's theory of MCS's etiology/ mechanisms (Pall, 2002). Perhaps this likelihood of panic attacks is why some MCS sufferers have reactions to [problem chemical-free] odors that smell similar to ones that caused them trouble.
There are seven major studies that are used to show MCS is a psychogenic condition. Dudley (1998) provided a devastating critique of these studies. In these seven studies, there were a total of 334 patients studied. However, no more than thirty-three of these patients actually had MCS. In five of the studies, none of the patients had MCS. Of the remaining two, in one study, eighteen out of forty-one had MCS, and in the other study no more than fifteen out of fifty-three had MCS. The studies have nothing to do with MCS, since it was not studied.
For more on this see "Psychogenic origins of multiple chemical sensitivities syndrome: A critical review of the research literature" by Davidoff et al., Arch of Environmental Health, Vol.49, 316-325, 1994.
A recent study in Japan by Ojima, et al., noted that some MCS sufferers felt "unpleasant" when exposed to harmless odors more often than controls (Tohoku J Exp Med 2002 Nov;198(3):163-73 ). There are several problems with this study: (1) Not all of the MCS sufferers demonstrated this phenomenon. (2) The researchers fail to realize that chemical-induced olfactory inflammation (which has been documented in MCS: See Meggs, 1993) or damage could cause a change in odor perception, and (3) that the high levels of biological, chemical, and mental stress in MCS sufferers elevates CO levels, which causes odor sensitivity (and thus symptoms in response to odors with harmless chemicals). The sufferers could also have been experiencing an anticipation or panic response (which would not necessarily mean they are not chemically sensitive). I also question how the diagnosis of MCS was made. What were the criteria? Who made the diagnosis? And why didn't the researchers do any relevant physiological testing?
Dr. Ronald E. Gots often "testifies" in court against MCS. Gots and other skeptics often claim MCS is contradictory to accepted principles of toxicology. That claim is based on the notion of "the dose makes the poison." Ashford and Miller severely criticized that notion and its frequent combination with pseudoscientific observations by skeptics. A notion more in line with scientific evidence is "the dose plus the host make the poison" (Ashford and Miller, 1998). For example---and I don't know why Ashford and Miller did not discuss this---, photosensitivity (frequent in porphyria) describes persons who are several magnitudes more sensitive to/ intolerant of sunlight than average persons are. That doesn't mean there is anything "toxic" about the sunlight, but rather the sufferers of such have biochemical/ metabolic abnormalities. The same is true of MCS (although many of the chemicals MCS sufferers react to are indeed poisonous. Disturbingly, some of such are even found in perfumes/ colognes: See Wallace, 1991).
Gots likes to focus on the fact that the exact cause and mechanisms of MCS have not yet been proven (though this may change due to Pall and Donnay's data). That is not a rational approach: MS (Multiple Sclerosis) has no known "uniform cause", nor even a diagnostic laboratory test---yet those would not be excuses to deny it's harsh biological reality.
In 1996 Gots wrote, "[e]verything that is known about MCS to date strongly suggests behavioral and psychogenic explanations for symptoms."
Based on the published literature now and even then, such a comment was/is unjustifiable, scientifically. Even if Gots were correct about the absence of biological abnormalities in sufferers (and he is not), the above statements are based on a presumption that psychological problems in sufferers = psychogenic origin, which is not a correct method of etiology research. (For example, we know that the organic brain abnormalities in MCS sufferers are largely in the limbic system, which influences emotions, thus creating psychological problems.) In addition, "The work of Fiedler et al. (1992), and that of Simon et al. (1990, 1993) amply demonstrate that there are MCS patients with no premorbid or subsequent psychological problems." (Ashford and Miller, 1998)
In his 1998 book, "Chemical Sensitivity: The Truth About Environmental Illness", co-authored with Stephen Barret, Gots wrote, "people do exist who are very sensitive to various micro-organisms, noxious chemicals, and common foods." He then goes on to say, "there is no scientific evidence that an immunologic basis exists for such a symptom pattern."
Gots and Barrett here take a narrow form of etiology research methodology by implicating that if a condition is not immunologic then by default it must be psychogenic (thereby ignoring recognized genetic, neurological, and blood diseases not related to the immune system). Since MCS does not meet the criteria of an immunologic disease they conclude that MCS is psychogenic. Dudley (1998) put it well when he wrote, "Multiple chemical sensitivity has none of the characteristics of an immunologic disease, and as long as immunologic criteria are required as proof of its existence, it will be seen as a non-disease."
Dr. Gots also lacks experience in this area, as he has never treated a patient with MCS. As far as I know he is trained in pharmacology, and neither he, nor Barrett have any training or certification in toxicology. I bring this up because Gots is often introduced as being "a Toxicologist."
In addition, Gots and Barrett have not actually done any peer-reviewed studies on MCS. They only offer their interpretations on anti-or-non-MCS studies. Of particular interest to me is the fact that at a MCS conference Barrett's adult daughter told people she had FM, which overlaps with MCS over 40% of the time (Donnay, 1999, 2002). This is interesting when one notes that Gots and Barrett never trash the literature on FM.
Gots founded the "Environmental Sensitivities Research Institute" (ESRI)---an Institute whose contributors and board members consist of pesticide manufacturers; representatives from The Cosmetic, Toiletry, and Fragrance Association; and other industry dominated representatives. Those representatives each pay up to 10,000 dollars per year for membership fees (See Ashford and Miller, 1998).
Gots' former ESRI associate, Frank Mitchell, had a very big role in the completion of the 1998 Interagency Draft Report on MCS. Interestingly, the report failed to mention the policies of at least 14 Federal Agencies, an EPA report that showed a very high incidence of MCS among persons poisoned by certain pesticides, the full extent of porphyrin metabolism's association with MCS, and much more.
Gots also likes to blame MCS on "risk perception." This, despite a recent study showing no abnormality in risk perception inventory among MCS sufferers (Scand J Psychol 2002 Apr;43:169-75).
In the late 1980s the National Academy of Sciences recommend to Congress that MCS be thoroughly investigated immediately, but no attempt was made on Congress' behalf to do so (and now, ironically, one study showed that 1/3 of the Library of Congress staff developed MCS [Donnay, 1999]). Over a decade ago Ashford and Miller recommended to the Government that research be undertaken, and they even demonstrated how such research should be carried out (Ashford and Miller, 1991). However, the Government still has not produced a significant and finite budget to go through with the recommendations, thus contributing to the vast misunderstanding (and lack thereof) of MCS.
The condition known as MCS---which has sadly reached epidemic proportions---has mounting support from both animal and human literature that it is an organic, not psychogenic, disease. The case for MCS's organic etiology is more overwhelmingly robust than the case for psychogenic etiology. This literature review article is just a small sample of data on the subject.
Much more research is needed, and such research should, in my opinion, focus on the roles NO and CO play in the condition's development.
Increased awareness is also greatly needed as schools, work offices, etc. should reasonably accommodate the sufferers so that they may actually be able to have a life.
"Multiple Chemical Sensitivity: A 1999 Consensus" by Gunnar Heuser, et al., Arch Env Health 1999;54:147-9
"On the Recognition of Multiple Chemical Sensitivity in Medical Literature and Government Policy" by Albert Donnay, International Journal of Toxicology, 18:383-392, 1999
"Multiple Chemical Sensitivity ... or MUSES Syndrome?" by Albert Donnay, MHS, presented to the Environmental Law Centre's International MCS Conference on April 8th, 2002, Conway Hall, London.
"NMDA sensitization and stimulation by peroxynitrite, nitric oxide and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity" by Martin Pall (Professor of Biochemistry and Basic Medical Sciences, Washington State University), FASEB J 16,1407-1417, 2002
"Multiple Chemical Sensitivity - The End of Controversy" by Martin Pall, at http://molecular.biosciences.wsu.edu/Faculty/pall/pall_mcs.htm [It should be noted at this time that Pall's research also strongly indicates that the etiologies of CFS, FM, GWS and PSTD are associated with excessive NO and NMDA levels. He can be contacted by phone at 509-335-1246.]
"Neurotoxicity in single photon emission computed tomography brain scans of patients reporting chemical sensitivities" by Gerald Ross, et al., Toxicol Ind Health 15:415-420, 1999
"Defining Multiple Chemical Sensitivity" by Bonnye Matthews (editor), pgs. 24 (summary of Dudley's chapter), 27-30 (part of Heuser's chapter), and 111-130 (Dudley's other chapter)
"Deep subcortical (incl. limbic) hypermetabolism in patients with chemical intolerance. Human PET studies" by Gunnar Heuser, et al., in the Annals of the NY Academy of Sciences
"MCS and SPECT Scans" by Jule Klotter in the Townsend letter for Doctors and Patients (in addition to the MCS patients, this study included CFS patients, with a control group)
"Teenager's discovery termed a medical breakthrough" by Latafat Ali Siddiqui at http://www.dawn.com/1999/19991223/int7.htm
"Neurogenic Inflammation and sensitivity to environmental chemicals" by William Meggs, Environ. Health Perspect.101:234-238
"Chemical Exposures Low Levels and High Stakes", 1998, by Nicholas Ashford and Claudia Miller
Barbara Sorg, Critical Reviews in Neurobiology, 13(3):283-316, 1999
"The Health Risks of Twenty Most Common Chemicals Found in Thirty-One
Fragrance Products" Compiled by the late Julia Kendall, referencing Lance
Wallace (Excerpts from "Health Hazard Information" in the Material Safety
Data Sheets [MSDS]), EPA
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