Article 01: Theory Attacks MS Diagnosis

This article appeared in The Scotsman newspaper recently. It is by Alistair Dalton, their science correspondent.

A CONTROVERSIAL new theory that doctors have failed to cure multiple sclerosis (MS) because they are treating the wrong disease has split medical opinion.

Neurologists at Glasgow University claim conventional wisdom about MS is based on a different condition altogether, which explains why no cure has been found for the disease.

MS affects 100,000 people in Britain and is the most common disabling nerve disorder among young adults.

Professor Peter Behan and Dr Abhijit Chaudhuri, who worked with Dr Bart Roep, from Leiden in the Netherlands, believe the prevailing century-old view that MS is caused by immune cells attacking a protein that insulates nerves is wrong.

They claim instead that MS is caused by support cells called astrocytes malfunctioning, possibly due to a combination of environmental and genetic factors.

The researchers said animal experiments in the late 19th century which underpin the accepted auto-immune theory were critically flawed.

They claim the scientists involved had wrongly believed they had induced an "animal model" of multiple sclerosis, when the two conditions were actually very different.

Prof Behan said: "There are huge differences and they've been skipped over."

He said the so-called animal version of MS either kills or permanently disables animals, while MS "comes and goes" and there are also big differences in the level of inflammation.

Despite this, almost all MS treatments have been based on the animal version.

Dr Behan said: "Not a single human has been cured using these approaches."

The research, which is reported in New Scientist magazine, will be published in the Journal of the Royal College of Physicians of Edinburgh next week.

Some doctors have backed the claims but others are vehemently opposed.

Dr Israel Steiner, a neurologist at the Hadassah University Hospital in Jerusalem, said the animal model had blocked effective progress for decades. He said: "I definitely believe it's high time to reconsider the entire field. It has not led us into understanding the disease or to a better therapy for patients."

However, other scientists dismissed the research.

Dr Stephen Reingold, the vice-president of research at the National Multiple Sclerosis Society, in New York, said: "It's presented as a comprehensive review but is highly selective."

He admitted that none of the available treatments for MS provided cures, but said some provided relative benefits.

Dr Charles Poser, of Harvard Medical School, in Boston, said the study failed to acknowledge the exact match between the damage in people with MS and that in marmoset monkeys with the animal version.

Comment by Ashton Embry

Andrew,

I saw this last week and was able to get a PDF of the article (This PDF can be downloaded by clicking on "Click here for more information" at the bottom of this article) .

I went through the paper in detail this weekend because I believe these types of papers have value. Although the authors quote Bertrand Russell (one of my heroes) to underscore their approach, I think it would have been more parsimonious to quote Mark Twain "When you find yourself on the side of the majority, it is time to stop and reflect". I would emphasize that parsimony is what science is all about, that is, what is the simplest hypothesis which explains all the current data on a given question. The reason for this is that it is impossible to prove anything correct. You can only prove something wrong and even this is debatable. Thus for any given phenomenon there will be many hypotheses to explain it and one has to base one's actions on the "best" (simplest) explanation until a better one comes along.

For MS there is reasonable consensus that it is an autoimmune disease driven by activated T cells which are sensitized to various myelin associated proteins. However I would point out that there are many hypotheses for the etiology of MS and these are mainly found in the journal "Medical Hypotheses" edited by the venerable David Horrobin. I have read everyone of these hypotheses and I have compared each hypothesis (eg HHV-6 infection, mercury poisoning) against the MS data base. In every case the hypothesis does not explain much of the MS data base and is no where as good as the autoimmune hypothesis for explaining the known facts.

So now we have another hypothesis for MS etiology. It is published in a rather obscure, seemingly brand new journal (Journal of the Royal College of Physicians of Edinburgh) but that is not surprising. The establishment hates having their "accepted" hypotheses challenged and that is the main reason Medical Hypotheses was established so as to allow an outlet for new ideas.

In their paper Behan et al take two separate approaches. Most of the article attempts to show that the autoimmune hypothesis does not explain the current data base very well. The authors use the classic strategy of very selective referencing (ie the omission of many critical references) in combination with circular reasoning, irrelevant data and unsupported statements. Such a strategy is standard in science when you are trying to attack the currently accepted hypothesis and promote your pet hypothesis. I have had personal experience in this from both perspectives - through my work on the origin of the Arctic Ocean which is the currently accepted hypothesis and my work on sequence stratigraphy which is challenging the currently accepted hypothesis.

The other part of Behan et al's paper is the argument for their hypothesis that MS is a neurogenerative disease unrelated to inflammation. This is not new but this is the most overt claim that such a hypothesis is the best one for MS. Their evidence for this is very weak and depends mainly on evidence which can be readily accommodated in the autoimmune hypothesis. For example they suggest that glioma (cancer of CNS glial cells) occurs with MS more often than random but do not cite any references which have established this. There is no doubt that the combined association of glioma and MS is rare and even if it was shown that such an association is greater than random this would not be a great surprise given that long term chronic inflammation could readily explain a slightly greater than random association of MS and glioma. Most importantly the neurogenerative hypothesis does not explain many facts about MS. For example, the great similarities (epidemiology, immunology) between MS and type 1 diabetes (IDDM), which Behan et al accept as an autoimmune disease, are completely ignored. I find when I read a paper on IDDM it is almost exactly the same as one on MS. How would a neurogenerative hypothesis explain the occurrence of myelin sensitive T cells in IDDM and beta cell sensitive T cells in MS?

Behan et al also ignore the common occurrence of activated myelin-sensitive T cells in PwMS and the almost complete absence of such in controls. Of course the fact that a drug like Copaxone has some positive effect on MS is really problematic for the authors. They try to wriggle out of this one by claiming the demonstrated positive effects (including MRI benefits) are due entirely to placebo effect which of course is nonsense. Blinded controls are used to eliminate placebo effect and the side effects of Copaxone are mild enough that most people did not know if they were on Copaxone or the placebo. Finally I would add that if MS was a neurogenerative disease rather than an autoimmune one, the BBD would help no one. And we know, even if the medical establishment doesn't, that this is not true.

If a person like me can readily see that their proposed hypothesis is severely wanting when it comes to explaining what we know about MS and that their attempt to discredit the autoimmune hypothesis is embarrassingly hollow, one wonders what a leading MS researcher would have to say about their paper. Hopefully one will take the time to write a discussion of this paper and point out its innumerable flaws and half truths. Just like the last "hypothesis of the month", that MS is a sexually transmitted disease, this one has little if anything to offer MS science (or persons with MS) and will be regarded in the MS scientific community as just one more addition to the huge pile unsupported and fanciful hypotheses for MS cause. This pile will undoubtedly continue to grow until it is realized that nutritional factors play a huge role in MS etiology and represent the key which would allow the autoimmune cause of MS to be understood and an effective therapy to be instituted.

Ashton