Martin L. Pall, PhD, Professor Emeritus of biochemistry and basic medical sciences at Washington State University, is adding to the science of toxicology with a new research-based paper, “Multiple Chemical Sensitivity: Toxicological and Sensitivity Mechanisms.” Here he is kind enough to summarize and explain his findings for ProHealth.com readers.
Q: Dr. Pall, we were very encouraged to learn that you have a new evidence-based paper on multiple chemical sensitivity (MCS) that will be published in a prestigious toxicology book. How important is this for patients?
Martin L Pall: The article will be published in an important reference source for professional toxicologists – General and Applied Toxicology, 3rd Edition, part of a multivolume set.
This is a very important paper for several reasons.
• The toxicologists have largely ignored MCS, despite its high prevalence and major impact on human health. So this is an important recognition that MCS is a toxicological phenomenon, a response to chemicals acting as toxicants.
• Furthermore, the fact that I was asked to write it is important recognition for my own earlier work on MCS.
• It is also important to note that the three editors of this set – Drs. Bryan Ballantyne, Timothy C. Marrs, and Tore Syversen – each has distinguished publication records in toxicology. And each of the three has published on chemicals implicated in initiating cases of MCS.
Therefore, I think you can be assured that if there were major flaws in the case that I make that MCS is a toxicological phenomenon, they would certainly have detected them.
Q: What is the case that MCS is a toxicological phenomenon?
Dr. Pall: Cases of MCS are reported to be initiated by seven classes of chemicals.
• The organic solvents and related compounds;
• Three classes of pesticides (organophosphorus/carbamate pesticides, pyrethroid pesticides, and organochlorine pesticides);
• Hydrogen sulfide;
• And carbon monoxide.
(Some organic mercurials may act like mercury.)
Members of each of these seven classes of chemicals are known to be able to produce substantial increases in NMDA activity in the mammalian body. [NMDA is an "excitotoxin" – a substance that causes nerve cell damage.]
Furthermore, one can lower the toxic responses to members of each of these seven classes of chemicals by using an NMDA antagonist. This tells us that not only does the NMDA increase occur, but it is an important part – probably the dominant part – of the toxic response in the body to each of these seven classes of chemicals.
So we have a common response to all of these diverse chemicals that may explain how these chemicals may all initiate cases of MCS.
Furthermore, I had previously published six other types of evidence implicating excessive NMDA activity in MCS. It appears that increased MCS is produced by both:
• Chemicals in the initiating process,
• And also in chemicals triggering sensitivity responses in people who are already sensitive.
So chemicals in both situations may well involve the same pathways, leading to the same response – increased NMDA activity.
There is one other, very important, type of evidence showing that chemicals act as toxicants in MCS. There are now four different studies showing that people carrying certain forms of genes (that is, genetic polymorphisms) that have a role in the metabolism of these chemicals have increased susceptibility to MCS.
A total of six such genes are implicated in determining susceptibility.
When this paper was written, one of these studies was not published yet, so at that time only five such genes had been implicated. This genetic evidence provides compelling confirmation that chemicals acting as toxicants when they initiate cases of MCS, and people with changed metabolism of those chemicals, are therefore either more or less susceptible to getting MCS.
Since the Nobel prize-winning work of Beadle and Tatum in the 1940’s, it has been clear that genetics is THE MOST POWERFUL approach to understanding biological mechanisms. These genetic studies provide, therefore, compelling confirmation that chemicals are acting as toxicants in initiating cases of MCS. If one uses the nomenclature that Staudenmayer used earlier, this provides undeniable evidence that MCS is a toxicogenic disease and is not psychogenic.
[In 1999, Herman Strudenmayer, an insurance industry consultant, published Environmental Illness: Myth & Reality, a book attempting to debunk MCS by describing the illness as “psychogenic,” not “toxigenic” – “a myth encouraged by charlatans.”]
Q: We understand that people can access this information on MCS now, before the book you referred to above comes out?
Dr. Pall: Yes, there are a number of people who wanted to translate that MCS toxicology paper into other languages, but I was unable to get any clear guidance from the publisher on whether and under what conditions we could translate it. Therefore, I wrote what is a somewhat shorter version of that paper, one that I will control the copyright on, that is currently serving as the opening Multiple Chemical Sensitivities web page (at TheTenthParadigm.org) on my new web site.
This somewhat shorter paper is currently being translated into German, French, Spanish, and Italian, and I expect the translations to be available before the end of the year. These translations will provide substantial evidence of the international interest in my work on MCS.
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Q: Dr. Pall, do you believe, then, that the various psychogenic claims for MCS have clearly been shown to be false?
Dr. Pall: Yes, absolutely.
Those claims were severely criticized earlier, in Chapter 13 of my book, Explaining ‘Unexplained Illnesses for this group of multisystem illnesses – ME/CFS, FM, MCS, PTSD, Gulf War illness, etc. [In which Dr. Pall proposed that a dysregulated nitric oxide (NO/ONOO-) cycle explains the many symptoms of these illnesses, and that “a well-chosen regimen of antioxidants and other agents may help the body ‘downregulate’ this vicious cycle.”(1)]
The psychogenic claims were also severely criticized specifically for MCS, based on nine or ten reasons I address in the new MCS toxicology paper.
Furthermore, my web page paper provides the most comprehensive critique of “psychogenesis.” This new paper provides nine strong criticisms of that theory – five of which individually are, in my judgement, sufficient reason to reject psychogenesis (numbers 1, 2, 5, 8 & 9).
Advocates of a psychogenic theory of MCS and related illnesses have:
1. Ignored large amounts contrary evidence on the toxicological actions of chemicals otherwise implicated in MCS, on physiological changes occurring in patients suffering from MCS and related illnesses, on genetics of MCS susceptibility, on objectively measurable responses to low level chemical exposure in MCS patients, on animal models of MCS and on clinical trial studies of MCS-related illnesses.
2. Made sweeping inferences based on little or no data.
3. Based their hypothesis on the concepts of somatoform disorders and somatization [expression of psychological distress in the form of physical symptoms], concepts that have substantial flaws in both theory and practice and have been increasingly questioned in the scientific literature.
4. Based their view on an assumed dualism [an either-or distinction] between the psychological/psychiatric/mental disorders on the one hand and the physical/physiological/biological on the other. This dualism has been rejected by modern science.
5. Made repeated logically flawed arguments.
6. Ignored the long history of false psychogenic attribution in medicine, a history that raises the question of whether they are making the same errors that led to false psychogenic claims in the past.
7. Based many of their publications on substantial amounts of emotion-laden rhetoric, rather than following good scientific practice of letting sound theoretical structure, sound evidence and sound logic lead their arguments.
8. Dismissed large bodies of contrary literature based on little or no evidence.
9. Typically failed to make testable predictions – predictions that can be used to test and potentially falsify their hypothesis. Two rare exceptions to this pattern make predictions that have been falsified and lead, therefore, to rejection of their hypothesis.
Q: Did you describe any other new findings in this MCS toxicology paper, Dr. Pall?
Dr. Pall: There is a review of a whole series of studies of objectively measurable responses to low level chemical exposures among MCS patients.
These are very promising as potential specific biomarker tests for MCS. All of them are consistent with the NO/ONOO- cycle mechanism and three of them appear to be relatively easily applicable in clinical settings and thus may be things that physicians may be able to do in the future to confirm a possible diagnosis of MCS.
There is also the most comprehensive review of animal model studies of MCS. These collectively provide evidence for 13 different aspects of the NO/ONOO- cycle mechanism, as it is thought to play out in MCS. Consequently, the animal model data alone provide a strong case for our model of MCS.
There is one other thing, that is very important in terms of the whole field of toxicology, something that needs to be followed up with another paper. As you have seen from my second answer, we have seven classes of chemicals including three classes of pesticides and the huge class of organic solvents and related compounds that appear to produce their main toxic effects in the body by producing excessive NMDA activity.
This could well be a very important unifying concept in toxicology.
We have two previously documented “endpoints” of large numbers of toxicants: the action of many carcinogens as “genotoxins” producing changes in genetic structure and also the action of a substantial number of organic toxicants that act as endocrine disruptors. I think that chemicals acting via excessive NMDA activity is a third such class of toxicants, one that is more important than the chemicals acting as endocrine disruptors.
There is evidence that pesticides and organic solvents act as risk factors in Parkinson’s disease, ALS, multiple sclerosis, asthma and autism, but there has been no plausible mechanism for this. I think we now have such a plausible mechanism, namely that they act to produce a common endpoint, excessive NMDA activity. So, this concept may have broad applicability in toxicology and in environmental medicine.
Q: We know you have broad interests that go way beyond MCS and enviromental toxicants – the entire 10th Paradigm group of illnesses! Where are you going with those?
Dr. Pall: Unfortunately, I don’t have time to go into these other aspects at this time. Let me just respond by noting three different things:
• I have a paper in press on chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) which argues compellingly for a NO/ONOO- cycle mechanism. That paper will be published in a Nova Biomedical Publishers volume on chronic fatigue syndrome. I also have another requested paper on CFS/ME that will be submitted within a few days of this writing.
• I am very much interested in using therapy to treat and hopefully cure these illnesses. While we have been unable to get any reproducible cures to date, I am very optimistic that I know how to start getting some cures – I hope that this is not just my general optimism here, since it is based on a specific view of what may have been the defect in our approach.
• Thirdly, as you know, I have argued that there are many NO/ONOO- cycle diseases and that they differ from one another, mainly in what tissues must be impacted by the NO/ONOO- cycle in order to generate a specific disease. It is high time for me to start making a detailed case for specific diseases, one that will replace the much more superficial case that is presented in my book, Explaining ‘Unexplained Illnesses’.
To date, I have published only two detailed cases, on tinnitus and on post-radiation syndrome, but there are many others that need to be published. That will be a multiyear project, and an extraordinarily challenging one. Maybe we can catch up on some of this a year or two from now.
Q: We understand that you are retired from Washington State University – you’re a Professor Emeritus – but this sounds like an unusual retirement!
Dr. Pall: Yes, indeed it is. I look forward to updating you all on my latest ME/CFS research as the upcoming articles are published, and thank you.
1. See ProHealth’s earlier Q&A with Dr. Pall – “Nitric Oxide Cycle Theory: Will It Explain CFS, FM, and Other ‘Unexplained’ Illnesses?” It refers to Dr. Pall’s antioxidant suggestions for downregulation of the NO/ONOO- Cycle, which are available via ProHealth’s general store – search on "Dr. Pall."
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