Dr. Ferran J. García

Deputy Chief of Staff - Medical
Policy
Canadian Forces Medical Group
1745 Alta Vista Drive
Ottawa ON KlA 0K6

Sous-chef d’état-major – Politique
médicale
Groupe médical des Forces canadiennes
1745, promenade Alta Vista
Ottawa (Ontario) KlA 0K6

1180-2 (MCS)

25 March 2002

All Guests and Participants:

RECORD OF PROCEEDINGS OF MULTIPLE CHEMICAL SENSITIVITY. SYMPOSIUM HELD 16-17 MAY 2001

The Minister of National Defence, the Honourable Arthur Eggleton, and the Department of National Defence, through the Director General Health Services, hosted a Multiple Chemical Sensitivity (MCS) Symposium on 16-17 May 2001 at the Château Cartier Hotel in Aylmer. The Multiple Chemical Sensitivity symposium was organized in consultation with members of the Environmental Illness Society of Canada.

The symposium’s goal was to provide a forum of international medical expertise on the subject of MCS.  The symposium’s learning objectives were to review the history of MCS, the various proposed definitions for MCS, the various theories around MCS, diagnostic methods, treatment modalities, and examine the controversies surrounding this diagnosis.  Presentations by representatives from both sides of this issue allowed CF health care workers and other attendees to develop a better appreciation of this important subject.

The Record of Proceedings from this symposium, in bilingual format, is enclosed

Sincerely,

original signed by

K.C. Scott Colonel Deputy Chief of Staff - Medical Policy

The Honourable Art Eggleton, Minister of National Defence

Mr. Eggleton thanked Dr. Scott and all those present, making special note of those who had come from far away—the U.S., England, and Australia—as well as from all parts of Canada.

This symposium is very important, said Mr. Eggleton. “That’s why I came this morning. It’s important to me both personally and professionally.” Mr. Eggleton related that he shares a close friendship with someone who has suffered from MCS, and although he was initially skeptical of the possibility, he is no longer.

Secondly, Mr. Eggleton said that, as the Minister of National Defence, he has heard from many who went into overseas service as robust individuals only to see their health deteriorate over subsequent years. Some have looked at depleted uranium as a possible cause, while others have looked at the red sand used in sandbags in Croatia. Their growing frustration is fuelling the search for a cause and an understanding of what has shattered their lives.

Mr. Eggleton acknowledged that traditional medicine debates the existence of MCS. While scientific evidence says that these illnesses are not caused by MCS, people continue to suffer. “We must look at what is needed to help try and solve the problem. That’s the bottom line,” he asserted. It is important to look to the beliefs of those who suffer—these individuals must be a key part of any solution.

“I hope there will be an open-mindedness today,” the Minister commented. That might involve a holistic approach to problem solving, and will almost certainly include a discussion of the associated psycho-social problems.

“I certainly hope you can look to the needs of those who suffer and focus on how you can come out of here looking to how to help,” said Mr. Eggleton, adding that this could include examining support systems and pensions. He urged participants to have an open mind, and implored them “to think outside the box.”

“I’d like to see this symposium be the start of finding solutions made in Canada. I’m prepared to provide that kind of leadership,” he concluded.

Basic Principles of Environmental Medicine and Multiple Chemical Sensitivity

Gerald Ross, M.D.

“Mister Minister, Surgeon General, and guests, it is indeed a pleasure to be here,” said Dr. Ross, adding that he was somewhat daunted by the task of presenting such large topics within a 30­minute time frame. He began with a slide of the lighthouse at Peggy’s Cove, saying that it not only reminds him of his roots, but of the need for all of us to be like that lighthouse, providing a sense of light, guidance, hope, and inspiration to our patients and others.

Dr. Ross said his views, like those of the Minister, had changed over the years. When he graduated as a medical doctor in 1974, he was very skeptical about MCS. Then in 1983 he became seriously ill and developed a neuropathic illness, which was confirmed on a nerve biopsy. He began to develop reproducible reactions to food and chemicals: certain triggers would produce certain symptoms.

It was then announced that there was dry cleaning fluid in the town’s drinking water, and blood tests confirmed that it was present in him as well. That class of chlorinated solvents is known to induce neuropathy.

He reported that he was disabled for a time, but was treated for environmental sensitivities, and with the financial support of the government of Nova Scotia, completed an International Fellowship in Environmental Medicine. He was able to go back to productive work. His opinions changed, based on having seen “both sides” of the issue of MCS and “low-level” environmental influences on health.

Dr. Ross urged attendees not to think that they have all the answers. He quoted former deputy editor of the New England Journal of Medicine Drummond Rennie, who in 1980 said of a 1959 issue of the journal, “This was the finest medical research of its time, and most of it has already been proved wrong. The best that can be said about today’s Journal is that we’re publishing today’s lies.”

Illustrating ubiquitous environmental exposures, Dr. Ross showed a slide of the plume of smoke from a tanker truck fire, taken from the balcony of his house in Utah. “We are all exposed to a variety of environmental toxins,” he said. The county to the west of his home is being reported as the most polluted county in the U.S., in terms of the release of neurotoxic and developmental toxins.

Showing an American Medical Association slide entitled “Triggers of Asthma,” Dr. Ross commented that 25 years ago this would never have been published, as it showed natural gas, propane, cigarette smoke, and smog as chemical triggers of asthma.

The next slide described the Canadian government’s plans to reduce the domestic use of pesticides and the refusal by Dow AgroSciences (Canada) to phase out production of the pesticide chloropyrifos, despite agreeing to do so in the U.S. Dr. Ross commented that either this chemical was dangerous in the U.S. but not in Canada, or that the manufacturer valued the health of Canadians significantly less than that of Americans.

Dr. Ross described the “total load” effect, that is, the cumulative and combined effect of all the patient’s stressors. A patient’s state of health depends on many factors: food, infections, stress, chemicals, inhalants, genetics, nutrition, and electromagnetic forces. Using a simple analogy, Dr. Ross explained that if a rain barrel can be used to represent a patient, the barrel’s capacity represents the patient’s capacity to tolerate a variety of stressors, which constitute the total load, or L. The patient can usually function reasonably well with almost a full load, but when an additional stressor, A, is added to the barrel, that patient’s capacity to cope becomes overloaded and the barrel overflows. This overflow represents the production of illness of symptoms.

Most people assume that the additional stress A caused the overflow, when in fact it is A + L (all the rest of the total load) that produces the symptoms. Dr. Ross stated that approaching his patients’ problems with the total load concept in mind had enabled him to do more for their treatment than any other information he had learned in medicine. The therapeutic message to lower the total load is a simple construct, but one that works.

As an example of the total load effect, Dr. Ross presented research done in 1970 by Taylor and Francis. Mice were exposed to a number of stressors, but cardiac arrhythmia only occurred with additive exposures, when a threshold or total load was exceeded.

The total load approach provides more options for therapy, as most of the factors are modifiable (food, water, air quality, emotional stress, infections, inhalants, etc.), with the possible exception of genetics. Air filters, detoxification, dietary modifications, and stress reduction are all ways to decrease the total load.

A second basic principle of environmental medicine is that of biochemical individuality. Because we are all different genetically, we are all different metabolically, Dr. Ross said, adding that the pharmaceutical industry has known this for years. Genetic polymorphism, for the purpose of discussing environmental effects, is defined as the genetic variation between individuals of a population, whereby specific genes may be present or absent, or expressed to different degrees, resulting in varied biologic, metabolic, and detoxification responses to the same medication or environmental pollutant. Research in this field goes back to 1994. We do not behave the same when confronted with either medications or environmental toxins, commented Dr. Ross.

The third principle is the non-linear response curve, whereby the old axiom, “the lower the dose, the less the effect” may not always apply. University of Texas research on exposure to various chemicals revealed that exposure to low doses of environmental toxins may be more hazardous than exposure to high doses. In military terms, Dr. Ross described this as “coming in under the radar.” There is more chromosomal damage with low and medium levels of exposure than with high levels. High exposure levels trigger enzyme induction that helps to clear the toxic material from the body, and therefore less genetic damage was seen at higher levels of exposure in this study.

“It’s almost as if there’s a threshold of recognition,” Dr. Ross remarked. With low doses, the body does not seem to recognize what is happening and does not induce the enzymes needed to detoxify the xenobiotics.

The next major concept, that of adaptation and withdrawal, is of fundamental importance to an understanding of MCS and environmental medicine. Adaptation is a physiological homeodynamic change that produces tolerance of a substance. Once adapted, the patient may associate few or no symptoms with exposure to the substance, even though the substance adds to the total load, and a “metabolic price is paid.” A classic example of this is cigarette smoking where, after the initial exposure, the smoker becomes acclimatised to the effects of the cigarettes, despite their known destructive effect. Withdrawal is the opposite: it is a de-adaptation that occurs with loss of exposure to a substance to which a person has adapted.

After a period of no exposure, the person will usually have symptoms on re-exposure (also known as re-challenge). Either adaptation or withdrawal can be uncomfortable and associated with physical or emotional signs and symptoms. Dr. Ross used the example of workers in a nitroglycerin factory. Initially they suffered from headaches until they became acclimatised to the environment. They then experienced headaches or withdrawal symptoms on weekends until they discovered that they could prevent this by putting nitroglycerin on their hatbands, which would be absorbed slowly over the weekend.

“Monday fever” in those working around grain dust or welding fumes is another example of what happens after a weekend of abstinence from the substances to which workers have become adapted during the week. Few physicians or patients understand that many foods, chemicals, and inhalants can produce adaptation and withdrawal effects, depending on the patient’s reactivity. Such withdrawal effects can be very much like narcotic withdrawal, with a lot of somatic pains.

In the last 50 to 60 years, Dr. Ross said, medicine has gone down a path that he believes is limiting and incomplete, toward an overdependence on pharmaceutical interventions. He showed a picture of a welder taken from an advertisement for an asthma inhaler. If the welding fumes trigger his asthma, the best treatment is to get him away from the stuff that’s causing it, not suppressing his symptoms with steroids and bronchodilators, Dr. Ross said. He quoted Dr. Doris Rapp, who asked, “Suppose you have a nail sticking through the bottom of your shoe and into your foot. What are you going to do? Keep putting a bandage over the wound in your foot? Or remove the nail?”

Dr. Ross said that much of modern medicine focuses on short-term symptom suppression with pharmaceuticals, but environmental medicine has a different philosophy—it tries to identify and remove the nail. The main message is to lower the total load, after seeking out individual initiating and exacerbating factors of illness.

Dr. Ross noted that MCS is variously thought of as a credible diagnosis, a pseudodisease, a belief system, a neural sensitization, or a toxic encephalopathy. The big question is whether it is psychological or physiological. Or could it be, as Dr. Claudia Miller suggests, that MCS is not an ordinary disease per se but a manifestation of an underlying and unrecognized mechanism of illness? Dr. Ross proposed that we may well be on the verge of such a recognition of a new mechanism of illness, of which MCS is only one manifestation.

Regarding MCS, Drs. Ashford and Miller were the first to identify four patient categories: industrial workers; occupants of “tight” buildings; residents of communities whose air or water is contaminated by chemicals; and individuals who have personal and unique exposures. Dr. Ross suggested that there is also a fifth category: those who have no identifiable prior chemical exposure, but who can nevertheless be diagnosed with MCS.

Many definitions have been proposed for MCS, but the one upon which most agree lists six key factors. These are that the condition is chronic, symptoms recur reproducibly, symptoms occur in response to exposure to low levels of chemicals, the chemicals are of multiple unrelated types, symptoms improve or resolve if exposure is removed, and symptoms occur in multiple organ systems. Women’s College Hospital in Toronto, which has a government-sponsored environmental medicine clinic, has chosen to operate using this consensus definition for MCS.

Dr. Ross showed two different pesticide labels. Both warned that repeated contact could, without the manifestation of symptoms, progressively increase susceptibility to poisoning. He related that the phenomenon of increasing susceptibility to lower and lower doses was a lot like MCS. Dr. Theron Randolph was the first to describe chemical sensitivity, and his name is linked to many publications going as far back as 1951. Dr. W. J. Rea’s four-volume Chemical Sensitivity provides thousands of literature references. Dr. Ross said that the best, and most cited, reference is Ashford and Miller’s Chemical Exposures: Low Levels and High Stakes Second Edition (1998). There are also a number of epidemiology studies, including one by Kreutzer (1996), who surveyed 4,000 Californians and discovered that 6% were diagnosed with MCS and 16% were unusually sensitive to everyday chemicals. Kipen (1995) found that 69% of those diagnosed with MCS met the threshold score, and Bell (1996) found that 28% of over 800 young adults said that they were especially sensitive to chemicals.

Drs. Davidoff and Fogarty (1994) undertook a review of papers reporting a psychiatric causation of chemical sensitivity. They concluded that studies considered widely supportive of a psychogenic origin for MCS had serious methodological flaws, a view upheld by a review of their paper in the Journal of Occupational Environmental Medicine (1996).

In a comprehensive review of more than 600 articles in the peer-reviewed MCS literature, MCS Referral and Resources (www.mcsrr.org) found—in addition to some papers with mixed conclusions—that 311 papers concluded that there was a physical or organic basis to MCS, as opposed to 137 papers that concluded there was a psychogenic basis. In other words, more than twice as many papers concluded that MCS has an organic basis, by a ratio of 2.26 to 1.

Drs. Brown-Gagne and McGlone (1998) showed that certain questionnaires used to help diagnose depression are not reliable in cases of MCS. They recommended that until the etiology of MCS is better understood, “caution should be used when estimating severity of depressive symptomology in individuals with MCS when measures include somatic items.” Davidoff and Fogarty (2000) reached similar conclusions, stating that “the use of psychometric tests in ill populations for the purpose of evaluating . . . psychogenic origins of illness was shown to be potentially misleading.”

The best way to diagnose MCS, Dr. Ross said, is to re-expose a patient to a suspected chemical, under environmentally controlled conditions, after appropriate withdrawal. Both inhaled and intradermal challenges can produce reliable, reproducible data. Binocular iriscorder printouts (precise measurement of autonomic neurological function) developed in Japan for ophthalmologists and SPECT (single photon emission computerized tomography) brain scans can also be used as objective, non-symptomatic measurements. Ross and Simon (1999) found that brain SPECT scans using the technique of Simon and Hickey indicate that over 90% of MCS patients have evidence of neurotoxicity. They also concluded that metabolic (SPECT) brain scans done before and after ambient or blinded challenges with very low concentrations of relevant chemicals show a high degree of neurotoxicity induced by the challenge in MCS patients. This pattern is not characteristic of psychiatric disease.

Dr. Ross showed a number of slides depicting SPECT brain scans, explaining that SPECT shows a profound deterioration of brain metabolism in the patient after exposure to low-dose concentrations of a chemical to which he or she had been sensitized. A subsequent slide showed SPECT scans before and after a chemically sensitive patient had undergone a sauna detoxification program, with dramatically improved results.

Dr. Ross described the sauna detoxification program and showed slides of the sauna interior and set-up. He said that chemicals can often be smelled coming out of patients (in breath or sweat) when they are in the sauna. He reported a court-mandated sauna detoxification program in Utah for repeat young offenders who are drug abusers. The results are being gathered, and the lower rates of recidivism have been very encouraging.

In summary, Dr. Ross asked participants to keep the total load theory in mind while remembering that medicine is a “work in progress.” It is important to remember the axiom, “lower the total load,” and to do as the Minister of National Defence has suggested, which is to think outside the box. Each person is biochemically unique and metabolizes differently. Low levels of chemicals may actually be more harmful than higher levels, as they do not induce detoxification enzymes. Adverse effects can occur with both adaptation and withdrawal to either food or chemicals. The long-term synergetic effects are unknown, but the data on MCS is growing, and epidemiology studies suggest a significant prevalence.

Questions and Comments

Saying that he was a nonbeliever, an internist asked how many of the studies cited were double­blind and placebo-controlled. Dr. Ross replied that the better ones were, but acknowledged that certain therapeutic interventions, such as a sauna program, do not lend themselves to being double-blinded.

Another doctor asked what controls there were for the asthma study. Dr. Ross replied that the asthma patients were placed in a hospital unit in England where the air was highly filtered, and they were first placed on a strict water diet for four days to allow them to become de-adapted. Afterward, only one food at a time was introduced, allowing the patients to act as their own controls. Some foods triggered asthma is certain patients, and these food reactions were unique to each patient.

Testing for sensitivity to extremely dilute chemicals was done sublingually in a double-blind manner, and some patients reacted with asthma to certain chemicals while others did not. Yet another doctor suggested that gelatine capsules containing a single food could be used to double­blind the food experiments.

When asked how he would design a study to prove the total load theory, Dr. Ross replied that such a study would likely require a think tank of research designers and clinicians. However, the total load principle is virtually self-evident in everyday situations, he said, noting that many people reach their threshold and become ill, once they go beyond a certain number of stressors. He gave the example of university students at exam time who are under emotional stress, are not eating or sleeping properly, and succumb to a serious infection. He acknowledged that demonstrating the total load concept scientifically would likely be difficult.

The Medical Work-up of the Environmentally Ill Patient

Gunnar Heuser, M.D., Ph.D.

“Good morning; guten Morgen; bonjour,” began Dr. Heuser, adding that it was “a pleasure to be here with such a distinguished audience.”

Saying that he was approaching MCS from the point of view of a clinical toxicologist, Dr. Heuser said that he sees patients from near and far who have been exposed to chemicals. Despite having already seen numerous doctors who could find nothing wrong, these patients still feel that they are sick. “We listen, and have a test for most symptoms. We take a protocol approach and do a thorough work-up. Almost every one of them has something wrong.”

The potential for chemical injury is acknowledged if the concentration of a given chemical is in excess of government-regulated limits for a specific time interval. However, Dr. Heuser said that although fewer people believe that one can get sick with lower levels of exposure, he does believe in chemical sensitivity and believes that MCS has a physical base. He said that he selected two concepts to cover in the 30 minutes allotted—mast cells and the limbic system. Both affect multiple organs and can manifest in multiple systems complaints.

Dr. Heuser recalled the history of one patient who came to him after repeated admissions to the emergency department at UCLA following exposure to very small amounts of chemicals. Despite testing and avoiding known triggers, she still suffered from very serious reactions. Upon questioning her, Dr. Heuser learned that she had a flushing sensation and a metallic taste in her mouth at the time of her reaction, both of which he knew may be symptoms of a mast cell disorder. Her history of exposure went back to an exposure to pesticides in the 1970s, and she was experiencing multisystem symptoms. A skin biopsy confirmed nests of mast cells in higher than normal concentrations. Suspecting that her son might also be affected, Dr. Heuser tested him as well. He too was positive, and proved to be “exquisitely sensitive to chemicals.”

Suspecting that there might be a connection between MCS and a mast cell disorder, Dr. Heuser contacted experts and support groups. The first issue he read of the Mastocytosis Chronicles described the triggers of a young boy with mastocytosis, triggers that sounded very similar to those for MCS. Communication by phone with many mastocytosis patients showed that more than half complained of sensitivity to small doses of chemicals (fumes, perfumes, others). Symptoms of mastocytosis include flushing and many dysfunctions of the central nervous system, and have a very similar symptom complex to that of MCS.

Dr. Heuser showed a slide entitled “Mast Cell Mediators and their Role in Interstitial Cystitis.” He said that elevated levels of one of the prestored mediators, tryptase, supports a diagnosis of mast cell disease. The diagnosis of both mast cell disorder and MCS has been confirmed by means of skin biopsies for close to 20 patients, a number that Dr. Heuser said was significant. When he attended a support group for those suffering from mastocytosis, Dr. Heuser said he noticed a button on display advocating a perfume-free environment, and was struck by how chemically sensitive mast cell patients are.

Dr. Heuser, who received his Ph.D. in Montreal under Dr. Hans Selye, author of a textbook on mast cells, said that he has now come full circle in his research. He urged others to allow for the possibility that those with MCS may in fact have mastocytosis, or at least a mast cell disorder.

The limbic system provides easy access to the brain when chemicals are inhaled. When one inhales through the nose, the little nerves in the roof of the nose—which Heuser described as “dangling in the wind”—pick up the chemical and, if the protective detoxification function of the mucosa fails, that chemical has easy access to the brain. The message will go through the olfactory bulb, which provides a pathway to the limbic system.

Dr. Heuser said the University of California at Irvine (UCI) has developed a baseline of over 60 normal PET (positron emission tomography) scans, answering the need for a control group. Twenty of Dr. Heuser’s patients have had PET scans at their own expense, and all were shown to be “exquisitely sensitive to chemicals.” The scans he showed depicted abnormalities in colour. Blue showed a decreased metabolism and uptake of glucose and was present in the cortical areas. Yellow and red indicated an increased uptake of glucose. The slides showed a decreased metabolism in the periphery and an increased metabolism (or “hot” area) in the limbic and brain stem areas. Tests on the most severe patients showed a “striking imbalance between hot and cold.”

All of this shows that the amygdala (part of the limbic system) is hot, and not normal, commented Dr. Heuser. Olfactory stimuli from the olfactory bulb travel to the extended amygdala complex (EAC), which functions as a way station to other structures, including the hypothalamus. Visual, auditory, somatosensory, and other sensory inputs acquire emotional significance by being interpreted in the EAC, which controls reactions of fear and other strong emotions. Dr. Heuser said that a number of his patients “fall apart,” and have a dramatic reaction when exposed to chemicals. He recounted that in an experiment, a patient with epilepsy had a seizure triggered by a discharge from the amygdala and displayed a panic reaction. He suggested that perhaps the reason that some patients with MCS are so emotional is that their emotional reactions are linked to a discharge deep down in the amygdala.

The EAC is one of the most easily kindled structures in the brain, and once kindled, the resultant changes in EAC function are long term. Experiments with animals showed that when given low­level electrical shocks there was no reaction at first. After close to 20 doses, some animals react with grand mal seizures after the same low-level electrical shock. That is kindling, a process that can take place with chemicals, as well. EAC function has been shown to play a significant role in kindling in animals exposed to pesticides, xylene, and other chemicals.

In summary, Dr. Heuser said that mast cells and/or the limbic system and its connections appear to play a significant role in patients with MCS. Although their potential interaction remains to be studied, he said he was confident that one day it will be.

Dr. Heuser said that as he is in private practice he receives no grants for his research and can only acknowledge his patients. He expressed a debt of gratitude to his wife, Sylvia, who helped to put this presentation together. “Merci beaucoup. C’était un grand plaisir d’être ici aujourd’hui,” he said in conclusion.

Questions and Comments

Saying that he wanted to turn his attention to neurodiagnostic imaging, a doctor asked if it had been validated. He also asked about the baseline, and suggested that findings were concurrent with that of an anxiety disorder. He asked if there was a control group.

Dr. Heuser replied that UCI is one of the few centres with a control population.

Dr. Ross noted that Dr. Simon will discuss control groups later on at this conference.

International Developments in the Recognition of the Effects of Low-Level Chemical Exposures

Nicholas A. Ashford, Ph.D., J.D.

Dr. Ashford began by congratulating the Canadian government for holding this symposium. In contrast, he said, the way the United States has treated its veterans is a “national disgrace.” After taking 20 years to recognise Agent Orange, the best the Gulf War Commission can do is to say they “can’t eliminate with certainty the possibility of a problem.”

Dr. Ashford noted that chemical sensitivity accounts for about 3% of his work. He’s often asked whether he believes in MCS. This is not about belief, he said, but about guessing and testing. His intention is not to persuade anyone that MCS exists, but to put it in context, discuss how it can be approached empirically, and outline where things stand in terms of international recognition.

Dr. Ashford first got involved in this area as a consultant to the New Jersey Department of Environmental Health and Protection. Dr. Ashford said that after initially assessing the area he’d been assigned to study, he’d submitted a two-week consulting estimate for anticipated work. He and his colleague Dr. Claudia Miller, an allergist-immunologist, spent the next two years researching the site without receiving additional financial support. “This area turned out to be a real eye-opener into emerging public health problems,” he said.

As a lawyer and a scientist, he believes in full disclosure, Dr. Ashford said. He and his colleague Dr. Claudia Miller neither accept money nor testify for a patient, which keeps them free “to change our minds and say as we please.”

There is mounting evidence that human exposure to chemicals at low levels once thought to be safe is now linked with adverse biological effects, including endocrine disruption, chemical sensitivity, and cancer. These health effects could be related. Endocrine disruption can make the fetus more generally susceptible to cancer. These effects quite possibly emerge from an underlying process of toxicant-induced loss of tolerance (TILT) that results in a number of different diseases, one of which is MCS. Furthermore, the better we understand cancer, the more we understand the effects of low-level exposures. Dr. Ashford remarked that a modern revision of Paracelsus’s statement, “The dose makes the poison” might be, “The host plus the dose makes the poison.” Humans in their developing state warrant special consideration, in their own right and as sentinel indicators.

While an emerging science associated with low-level exposure is changing how we think of chemicals and health, new theories emerge with difficulty. Not long ago, scientists were convinced that acid caused stomach ulcers. Then a bacterial cause was found, which responds to a two-week course of antibiotics. It took some 20 years from the time the cause was first suggested for this to emerge. “If we can’t deal with an ulcer problem straightforwardly, imagine how we’re trying to struggle with this,” Dr. Ashford said.

Increasingly, evidence links chemicals and autoimmune diseases (including lupus, scleroderma, and rheumatoid arthritis), attention deficit hyperactivity disorder (ADHD), autism (one out of six children in the U.S. has autism, aggression, or ADHD), depression, asthma (which has doubled in incidence in the last 10 years), and finally chemical sensitivity and its overlaps with sick building syndrome (SBS), chronic fatigue syndrome (CFS), fibromyalgia (FM), toxic encephalopathy, Gulf War syndrome (GWS), etc.

Six common threads provide a new perspective on disease. First, the nature of disease represents a departure from classical disease (e.g., tuberculosis, cardiac problems, etc.) in that communication systems or networks are the target, rather than specific organs (although they are ultimately affected). These networks include the endocrine, immune, and the neurological systems, all of which are mediated by the brain.

Second, no single cause has been identified, nor are there clear biomarkers for exposure or disease. Without these, classic epidemiology is unable to identify susceptible or sensitive subgroups.

Third, these emerging diseases are characterized by a multi-stage disease process, becoming manifest after two or more stages occur. Just as with cancer or infectious disease, there is “no evidence of a single disease entity” for MCS. We’re coming to believe, Dr. Ashford said, that MCS is a class of diseases. The distinction between a single disease entity and a class of diseases is crucially important. Imagine trying to distinguish between diphtheria and AIDS before infectious disease was understood. Physicians at the time could quite easily and correctly have said, “There is no evidence of a single disease entity.”

In many cancers, he continued, an initiation and alteration of the basic DNA/RNA structure is followed by a promotion to a recognized cancer. Similarly, TILT is postulated to have two stages: the original exposure to high levels (or repeated exposure to lower levels) of an initiating agent, followed by a triggering of symptoms by chemicals at everyday levels that don’t affect most people. Without knowing that the first step has taken place, one might think the cause is perfume, for example. “With MCS, we have unfortunately been concerned by the triggers,” said Dr. Ashford. “If we would focus on the initiating cause, we could eliminate many of the problems.”

The fourth common thread is time and timing. In cancer, the time from initiating cause to disease is measured in decades. Similarly with asbestos, only time ultimately revealed the relationship between cause and disease. That we can’t find an unequivocal causal relationship between chemical exposures and MCS doesn’t mean that one doesn’t exist. Part of the problem may be a focus on triggers rather than initiators. Also, the timing of initial doses is important. Smaller doses timed strategically can lead to a pathological loss of tolerance. There are animal models in which this is very clear, in work on time-dependent sensitization, Dr. Ashford said.

The apparent departure from classical explanations for disease is the fifth thread. Classically, a linear relationship would be expected between dose and response. Toxicological and epidemiological models are premised on single agents causing increasing levels of disease in a regular way. That does not explain these diseases. There is not a monotonic relationship between dose and response.

The final thread is that the underlying disease processes appear to differ from those underlying classical diseases. Endocrine disruption occurs at levels three to six orders of magnitude lower than what are traditionally associated with toxic effects. Furthermore, the disease processes underlying these emerging diseases may be interrelated. Endocrine disruption leads to immune system problems, which leads to cancer. It’s not that endocrine disrupters directly cause cancer, but if they allow more receptors to be set up in the breast or prostate, for example, individuals become more susceptible to cancer.

Dr. Ashford said he and Dr. Miller have reviewed the psychogenic, psychological, and physiological literature. The main difference between the second edition of their book (1998) and the first (1991) is that more than twice as much literature was published on the subject—and in peer-reviewed journals—in the intervening seven years than in the previous fifty. Mainstream science is now looking seriously at the pieces of the puzzle.

However, Dr. Ashford said, the three dimensions of disease—causes (physiological or psychogenic), symptoms, and the success or failure of interventions—are confused in the literature. He said that he hoped his voice would remain in attendees’ heads, whispering: “Is this author mixing up the success of psychological intervention with psychogenic cause?” Even though women with breast cancer live twice as long if they belong to a psychological support group, he said, that does not mean the disease is psychogenic. Likewise a psychological illness may respond to chemical treatment. “Advocates of the psychogenic origin of MCS sometimes deliberately obfuscate these three dimensions of disease,” Dr. Ashford said.

TILT suggests a step that causes the loss of tolerance, with manifestations labelled in different ways, including MCS, ADHD, depression, or mast cell problems, Dr. Ashford said. Dr. Mark Cullen, who first defined MCS, eliminated diagnoses like asthma and rhinitis from the MCS category. “If one eliminates these symptom-disease complexes because they can be described by a diagnostic label, all you have at the end is the garbage you can’t put a label on,” said Dr. Ashford. “Then you have the most complicated patients, those with both physiological and psychological problems.”

Dr. Ashford acknowledged that not only can chemicals change the brain—so does a traumatic event like an automobile accident. However, close scrutiny of the data from the last eight years reveals an overwhelming rejection of psychogenic initiators, and overwhelming support for chemical initiators. If there were a psychogenic origin, the amount of effort devoted to uncover it would have been successful. While Dr. Ashford noted that MCS can probably occur psychogenically, “those who see it may do so as a result of patient self-selection and physician bias, in the same way that allergists are self-selected as observers of certain patients.”

It would be relatively simple to answer the question, “Are people exquisitely sensitive in a reproducible way?” Double-blind studies could be constructed that would eliminate the possibility of nasal conditioningƒn and detect responses that might occur at levels far below classically recognized amounts, Dr. Ashford said, but it’s difficult to get funding for this work. Physician observations are useful if there’s a clue to the origin; if all in a group share an experience (e.g., the same neighbourhood or workplace); or in specialists’ patients with problems uncharacteristic of general illness.

As a chemist, Dr. Ashford said, he respects correlations. With disease outbreaks, or new building or consumer products, those with the same experience can be followed in a timely manner. There is statistically significant agreement in the rank ordering of symptoms by Gulf War veterans and by those claiming to have been made chemically sensitive from either pesticide exposure or from home remodelling activity. Characterizing MCS as psychosomatic does not explain this consistent ranking in three diverse groups. For discovery purposes, it’s better to follow people who have experienced the same event than to study patients with similar symptoms. “You can’t do it by looking at who’s sitting in your waiting room,” said Dr. Ashford. You have to follow previously exposed cohorts (i.e., do event-driven research) or work up selected persons in a common environment.

Dr. Ashford added that before and after challenges must also be done. “I accept that MCS patients have abnormal brains,” he said. “But what did their brain scans look like before?”

Finally, animal models may clarify the mechanisms for chemical sensitivity. “People don’t read the literature,” Dr. Ashford said. “‘The science isn’t there’ means ‘I haven’t read it.’”

Prevention cannot wait. The number of substances that cause the initial conditioning and sensitizing is much smaller than the number of substances that later act as triggers. “Go to the source of the problem,” he advised.

Dr. Ashford then mentioned the 1985 Thomson report (“still good reading”); his own New Jersey report, which was designed to be an objective evaluation of the then existing research; and a European study that found little MCS in southern Denmark, and a lot in neighbouring northern Germany, where pentachlorophenol wood preservative is used and a where disorder has been termed “wood preservative syndrome.”

A 1999 United Kingdom health executive report concluded that while there was no unequivocal epidemiological evidence, “the collated evidence suggests that MCS does exist.” It also states that “the available evidence seems most strongly to support a physical mechanism involving the sensitization of part of the midbrain known as the limbic system.” In striking contrast, the recently released US report does not review literature past 1995 and is generally uncritical of the literature it did select to review.

The Dutch have also issued a report on MCS, but their experience with neurotoxic problems resulting from a notorious plane crash in Holland was suppressed. The report concluded that no objective evidence connected exposure and disease—“Of course not,” Dr. Ashford said. “No one’s done the studies!” MCS can’t be looked at through the lens of traditional toxicology. Good peer-reviewed science must be done.

The evidence for a physiological basis has been strengthened over the last ten years, while the evidence for a psychogenic cause has not. The gestalt of the evidence confirms the obvious, as in global warming and mad cow disease (bovine spongiform encephalopathy, or BSE). A precautionary approach is needed. “You don’t need ironclad evidence when a variety of disparate compass needles are all pointing in the same direction. In my 30 years in the area of environmental health, I see that in no case have we been wrong about environmental problems. The problem either got worse, or the evidence became stronger. Only the most robust environmental and occupational problems ever get noticed: “That’s why we’ve never been wrong,” Dr. Ashford concluded.

Questions and comments

A participant from the Institute of Molecular Medicine spoke of the Bijl-mer crash in Holland. “We looked at three groups of patients,” he said—those living in the area, emergency personnel, and a group with no connection to the crash site who worked in the hangar where the remnants of the plane were reassembled. All came down with the same types of illnesses. Forty tons of cargo, which was never identified, was on its way to an Israeli government chemical warfare centre. Of the patients, 67% had chronic infections and fit the profile for CFS, as did a group located some kilometres distant. But while different types of infection were found in the control group, only one infection was found in all three Bijl-mer groups. Likewise, the percentage of Gulf War vets who test positive for infection is similar to civilians with CFS and MCS, where you find multiple species of infection. But 80% of Gulf War vets had the same infection. A lot of information is being withheld. This causes tremendous problems in identifying what’s causing the illness.

Neurotoxicity and Single Photon Emission Computed Tomography

Theodore R. Simon, M.D.

Dr. Theodore R. Simon began by taking Dr. Ashford’s “full disclosure” cue. He does testify for plaintiffs or defendants, though rarely, he said and, like Dr. Ashford, spends a “diminishingly small” portion of his time on MCS cases.

Dr. Simon said that he would explain how SPECT scans are used to confirm a diagnosis of MCS, CFS, or FM. SPECT is a huge umbrella, he said, adding that he would be talking about a particular test involving the localized distribution of radio tracers. A machine with three heads is used for its sensitivity, which is important when measuring counts. The machine’s moving parts (the size of a Volkswagen beetle) can be positioned to within a tenth of a centimetre in space.

A post-doctoral candidate used this particular protocol in her thesis for obtaining normal controls. These are hard to obtain, Dr. Simon said, and because they give him confidence in the data, he does not change the protocol. However, his images look similar to those obtained by a nuclear medicine physician who uses a different technique.

Before he knew anything about MCS, Dr. Simon said, there was interest in CFS. SPECT scans revealed a pattern a bit different from what is generally seen in neurotoxicity patients. SPECT stands for single photon emission computed tomography. It differs from PET scanning—another functional imaging technique—in which a positronium molecule or atom is created, which sends out gamma rays in almost opposite directions—thus, “dual photon.” A single photon travels in one direction.

Dr. Simon showed some slides of the machine. Electromagnetic fields, the amount of light, and the amount of sound inside the machine are all measured. “It’s over-controlled, if that’s

possible,” said Dr. Simon. So is the way the patient is prepared. The tracer is delivered with a Harvard pump, and precisely measured.
 

Dr. Simon explained that if a tracer is used to look at a large cardiac infarction, a donut shape will be seen, because the tissue at the centre is dead and does not see the tracer. This is why theseare called “donut lesions.” The extraction fraction times the amount of activity delivered is seen; thus one has to know how much material has been presented, and how it was delivered.

Although this patient told the psychologist on the case that he was normal, he had inhaled Scotchguard over the weekend, and seemed obviously different. The psychologist asked Dr. Simon to do a scan. “It was the most abnormal brain scan I’d seen to that point,” said Dr. Simon.
“But now I’ve got troubles: I can’t explain it.” His questions led him to patients with toxic exposures.

Dr. Simon described how the agent, [technetium-99m]exametazime, when injected into the blood, goes to the fat of the brain. There it encounters glutathione, which traps it by changing it from a fatty into a watery material. That is why it can be seen on the scans.

The pattern has four parts, he said:

Dr. Simon explained that the top two lines on the next slide were in the transaxial (canthomeatal) plane, with the small images showing flow and the large ones, function. Two rows of sagittal views (left to right) again show flow and function, as do two rows of coronal views (front to back). Dr. Simon pointed out the mismatch between the small and big images. “We’re most of the way to neurotoxicity,” he said. “We see some salt and pepper, some shunting.”

A sequence of different scans illustrated the pattern. A normal scan is symmetric and homogenous, with the same density of activity in both sides. A patient who is very sick clinically will have less activity than the controls because the tracer diffuses out of the brain again, leaving a lower count. “We’re seeing significant differences between sick and normal patients,” said Dr. Simon, showing a slide on which this difference was quantified: 8,154,147 versus 17,549,354 counts.

Dr. Simon then showed a sequence of slides from patients with different kinds of problems, ranging from solvents to unspecified materials to pesticides. He mentioned that subgroups have not yet been defined, “although we have thoughts about them.” He showed slides from a Gulf War patient and a breast-implant patient, noting that they didn’t differ much.

“What is the effect of using patients as their own controls?” Dr. Simon asked. Patients get significantly more abnormal when challenged, and significantly better with therapy. Showing slides taken before and after therapy, Dr. Simon noted that while “you can recognize neurotoxic patients, the scans look better with treatment.” This involves taking patients out of their environments and detoxifying them with saunas, etc.

Questions and comments

When asked how the controls were chosen, Dr. Simon answered that they were “fanatically assembled” by a Ph.D. candidate. After psychological, medical, and social histories were taken, patients were recruited according to age and gender requirements. While Dr. Simon read the scans and identified in which patients the pattern was present, he was not told their diagnoses or “who was being slipped through when.” Dr. Simon said, “I never did crack the code, because I don’t think its right.” Imaging with other agents follows the same pattern, whether glutathione, blood flow, or glucose metabolism is followed—all yield hot and cold spots, diffuse cortical involvement, etc. “We’re all looking at the same image, through different windows,” Dr. Simon said.

Asked how many MCS patients he’s scanned, Dr. Simon responded that he’d stopped counting at 3,000 or 4,000, 90% to 93% of which were evaluated as neurotoxic. “Dr. William Rea found a high correlation between a positive Romberg sign and a positive brain scan.” Dr. Simon repeated that this pattern is different from those seen in seizures and other psychological diseases.

Responding to a question about acute neurotoxic injury, Dr. Simon explained that the material used in this test works slowly and is very expensive. A scan might be done at the time of insult or presentation, then six months later, and only as a deliberate attempt to get at the bottom of what’s wrong. “ ‘When she’s wrecked I’ll do the SPECT,’” he quoted.”That’s a long way of saying we don’t do acute patients. This is not a first-line defence.” Long-term, he added, “I haven’t gotten anyone who’s gone back to normal, but I have seen significant improvement.”

Dr. Simon was asked how saunas work to detoxify patients, but answered that he doesn’t know what in the environmental doctor’s therapeutic arsenal might be responsible, only that the patient improved. A participant explained that chemically contaminated patients have often used up their glutathione in detoxification. The body makes it from three amino acids, glycine, phenylalanine, and cystine. Often cystine levels are found to be depleted, thus the body can’t make glutathione, and its detoxification ability is impaired. One treatment modality is intravenous glutathione, which the speaker said is marvellously effective.

MCS: The Rise of a Pseudodisease

Edward Shorter, PhD.

Dr. Shorter began his presentation with a slide showing a patient with pelvic tuberculosis. He used the disease as an example of physicians’ ease with diseases that have always existed and their tendency for suspicion of new diseases. The general presumption should be wariness.

He spoke of the recent explosion of disabilities such CFS, carpal tunnel syndrome (CTS), and SBS, adding that AIDS is obviously different. He illustrated his discussion of these disabilities with slides showing news reports of a worker bedridden by temporomandibular joint dysfunction and a lace maker disabled by CFS. He referred to an “illness attributions” epidemic over the last two decades.

Clemence von Pirquet, the Viennese doctor, coined the term “allergy,” beginning with food allergies. He explained connections between food and illness as immunological mechanisms and claimed to speak with the voice of science. From the early 1920s vague symptoms were explained as food allergies. They were “asthma equivalents” and therefore as dangerous. “There was a whiff of alternative science already in the air,” said Dr. Shorter.

Albert H. Rowe of the University of California argued in 1928 that food allergies were underdiagnosed. He said that skin tests were deemed unreliable, because patients failed the tests. He linked symptoms to diagnosis; for example, if patients throw up after eating pancakes, they must be allergic to them. Dr. Rinkle, another early specialist in food allergies, depended more on patient history for diagnosis of allergies.

The food allergy movement had one good scientist, Dr. Arthur F. Coca. He founded the Journal of Immunology, and was an illustrious scientific figure. In the late 1930s he fell into the “quicksand” of food allergies and in 1943 wrote a book on them. His views lent credence to the view that food allergies are responsible for much misery. Theron Randolph was his student in the 1940s. He launched the clinical ecology movement and his views became marginal to mainstream medicine. William Crook discovered the dangers of total body yeast infection, and the concept ballooned, with millions of people terrified that science stood behind such disabilities.

Returning to Randolph, Dr. Shorter gave a brief history of his career, noting that he became absorbed in his wife Tudie’s symptoms. She later developed a real organic disease and Randolph told Dr. Shorter that she had forgotten about her MCS. Although Randolph reported her case at a meeting in 1952, which became the launch of MCS, it was not immediately accepted. During his treatment of patients with MCS, he declared the gas kitchen range dangerous and was responsible for the removal of over 800 of them from patients’ kitchens. In 1958 Randolph used the word “ecology” publicly for the first time. At that time, when he wrote the founding document of the chemical sensitivity movement, he broke with the food allergies movement. From 1965 Randolph organized the clinical ecology movement and was not happy with the 1984 change of terminology to “environmental medicine.”

Dr. Shorter asked what permitted these ideas to radiate to other doctors and the general public. He said that there has always been chemical pollution. Inorganic chemicals have been around for about 100 years—formaldehyde since 1867, and coal tar and natural gas for longer. The skies of industrial England were black. Many workers could have been expected to have symptoms of MCS, yet they did not complain. The chronically miserable people were the fashionable middle­aged ladies—les dames �chaises longues—but they never blamed their symptoms on chemicals. It was only after the 1960s that concerns met epidemic proportions. The causes for this should be divided between manifest and latent ones. In the late 1960s a poll showed that 62% of Americans were concerned about the environment. Another poll showed that Canadians feared artificially manufactured chemicals more than natural ones. The massive social changes during the 1960s changed the nature of family life, which affected physical perceptions. In the past family discussions were more common. Tiredness and pain could be placed in the feedback loop of family experience. At present, half the households in Manhattan are one-person households. The television will assure these people of the existence of CFS or MCS and therefore people are somatically vigilant. At the same time, the doctor-patient relationship has changed. Doctors are perceived to have become more arrogant, more remote—“Why not drop in when you’re feeling better?” People flee to alternative medicine. Their anger at the arrogance makes them less receptive to reassurance. The media’s thirst for new diseases has staged a “psycho-circus” of suggestion. Without it, MCS would not have made its way into the world and taken over from CFS as it has.

There are similarities between GWS and MCS. There is the same media-inspired suggestion. Patients are convinced of the organicity of their complaints. They find the skepticism of the medical community offensive. They still have the right to be taken seriously; it is a question of spin control. But spin control in a medical context means the therapeutic use of the doctor-patient relationship. Another similarity is the political potency, which is probably the reason for this conference.

Speaking of the management of MCS, Dr. Shorter said that people do move on—that’s the good news—to discover other pseudodiseases. Even true believers in MCS are sensitive to the weight of evidence. All the great psychosomatic illnesses are abandoned once the weight of evidence makes then look bad. That is the march of science.

Questions and comments

Dr. Ashford commented that Dr. Shorter’s presentation was entertaining, if nothing else. He asked if Dr. Shorter believed that sick building syndrome, as defined by Scandinavian research, falls into the category of pseudodiseases. He also asked where the scientific basis was for Dr. Shorter’s opinion. Dr. Shorter responded that he is speaking as a historian and the historic perspective is an illuminating one. The agenda is driven by public fears and by physicians wanting to carve market niches. “If science were allowed to drive the agenda,” said Dr. Shorter, “we wouldn’t be here today.” In response to the first question, he said that SBS was propagated by the media.

A participant commented that, with regard to Randolph’s removal of gas ranges, they are now shown to be important triggers of asthma. He asked whether Dr. Shorter had ever met Tudie Randolph. Dr. Shorter responded that he had not. The participant said he wished to point out the “insulting phraseology” of his anecdote of Mrs. Randolph’s “forgetting” about having MCS. In fact, she suffered from Alzheimer’s disease in the years leading up to her death. Dr. Shorter replied that Theron Randolph had said in an interview that she also had a grave organic illness and intimated that it was cancer.

Exploring the Complex Relationship to the Immune System

Emil J. Bardana, Jr., M.D.

Dr. Bardana stated that although he is an academic, he sees patients and works mainly with people. He has seen hundreds of occupational illnesses, including problems related to indoor air quality. He said, in the spirit of disclosure, that he has to charge for everything he does for patients and to testify in court. The University of Oregon medical plan requires that every penny he earns goes to the Oregon Health Services, and Dr. Bardana earns a salary—“I am not a volunteer in life.” He deplores Dr. Ashford’s comment about how the American veterans were treated by the U.S. government. Dr. Bardana has respect for veterans; however Dr. Ashford’s comments were unpatriotic.

Dr. Bardana quoted Winston Churchill’s comment on Russia—“A riddle wrapped in a mystery inside an enigma.” It applies to MCS, he said.

He said he would focus on the issues of immunology. There would not be time to cover the science behind what he was about to say. He would provide a syllabus with key references that would be important to read. The references should not be measured by number or by weight, but by quality.

Theron Randolf, who founded the Society for Clinical Ecology in 1965, first discussed MCS in the 1950s. MCS is now covered by the American social security system, and with the emergence of the American legal system, is the focus of much litigation.

It is a matter of trigger versus cause. Triggers are often pointed to as the actual causes. Dr. Bardana said there has been a vast amount of literature on this. Idiopathic environmental intolerance (IEI) is a better descriptor. Dr. Bardana said he would not disagree that chemical sensitivity actually occurs. There are such diseases that occur, but none of them applys to MCS. The theory of the total toxic load on the body is a concept so simple that it almost demands acceptance. But it is an interesting theory with no back-up. All these things can happen, but it is like comparing apples and oranges. There is no scientific basis for MCS. He urged the audience to read the literature.

Dr. Bardana listed six parameters to study whether MCS is a true disease.

1.   Clinical features

∃   The symptom complex is usually presented as one with multiple symptoms, which are self­declared.

∃   There is no homogeneity of the symptom complex.

∃   Even some individuals without symptoms have been identified as having MCS.

∃   Complaints are extremely variable and include recognized diseases such as asthma, migraine, bronchitis, etc, into the symptom complex referred to as MCS.

∃   Hence, MCS cannot be defined as a disease using the usual clinical criteria.

∃   One is entirely dependent on a claim of “environmental exposure” rather than a defined clinical presentation.

∃   This self-declared approach results in any possible combination of air, food, or water in any amount and duration as a potential causative agent. The majority come in a litigation setting.

2. Pathology

∃   There is an absence of clinicopathologic correlates to MCS in the literature.

∃