Q&A with Martin Pall, PhD, on the Evidence that MCS is a Toxicological Illness

[Guest guest]

Q & A with Martin Pall, PhD, on the Evidence that MCS is a Toxicological

Illness

_http://www.prohealth.com/fibromyalgia/library/showArticle.cfm?libid=14758 & B

1=EM081209F_

(http://www.prohealth.com/fibromyalgia/library/showArticle.cfm?libid=14758 & B1=EM\

081209F)

August 4, 2009

 

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);

 

• Mercury;

 

• 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.â€]

 

* * * *

 

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 _http://thetenthparadigm.org/mcs09.htm_

(http://thetenthparadigm.org/mcs09.htm) ) 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.

 

* * * *

 

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?**

_http://www.prohealth.com//library/showArticle.cfm?libid=12896_

(http://www.prohealth.com//library/showArticle.cfm?libid=12896)

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.*

 

 

 

Note: This information has not been evaluated by the FDA. It is generic

and is not meant to prevent, diagnose, treat, or cure any illness, condition,

or disease. It is very important that you make no change in your

healthcare plan or health support regimen without researching and discussing it

in

collaboration with your professional healthcare team.