Dr Martin Pall on XMRV

[liverock]

Dr Pall is the founder of the NO/ONOO theory of the cause of CFS, as well as a number other disease states.

I've been incommunicado for quite a while, working on three things, two of which I will probably share with you a bit later. There were questions raised about the XMRV association with CFS/ME found by Judy Mikovits and her colleague in Nevada and elsewhere, so I wanted to summarize where we are on that, as best I can determine. You are welcome to share these comments elsewhere, if you wish.

Mikovits and her colleagues published a paper and accessory materials in the journal Science, a highly respected journal and have also provided additional and in some cases more recent information elsewhere.

In the Science publication they report that the XMRV retrovirus occurs in about 2/3rds of CFS/ME patients but only in 3.7% of normal controls. They also report that subsequently, using a more sensitive assay, XMRV occurs in over 90% of CFS/ME patients - we don't know what the percentage is for normal controls using that more sensitive assay.

The virus was originally isolated from some aggressive prostate cancer cells. In addition, in unpublished data, it is also apparently shows high prevalence in fibromyagia patients and in atypical multiple sclerosis (MS) patients.

Comment: These data apparently show that XMRV is not specific for CFS/ME but rather occurs in other disease states, as well as in some normals.

My own view is that this makes it much more likely to be an opportunistic disease, caused by the changes in immune function and other properties of these diseases, rather than a primary cause.

Specifically, the retrovirus, based on its DNA sequence, has its replication stimulated by NF-kappaB activity, an activity that is elevated as part of the NO/ONOO- cycle and has been reported to be elevated in CFS/ME.

Furthermore, the low NK cell activity and other types of immune dysfunction, that occurs in these various diseases, may also be expected to stimulate the ability of the virus to maintain itself in disease sufferers.

In order to show that it is the primary cause of CFS/ME, it is necessary to show that XMRV follows Koch's postulates, but so far it does not apparently follow Koch's first postulate, which requires that it always occurs in people with the disease but does not occur in normals. The other three Koch's postulates have not been tested.

In contrast to that, we have a good fit to the five principles underlying the NO/ONOO- cycle for both CFS/ME and fibromyalgia. Because one can argue that the fit to these five principles serve very much like Koch's postulates for NO/ONOO- cycle disease, I will argue that we have a substantially more compelling case for a NO/ONOO- cycle etiology than we do for an XMRV infectious etiology for either CFS/ME or fibromyalgia.

That does not mean that XMRV is unimportant, however. Even if it turns out to be an opportunistic infection, like mycoplasma and HHV-6 are, it still may contribute to the etiology of the disease.

And it still raises the question of whether we can cure cases of CFS/ME and fibromyalgia simply by normalizing the NO/ONOO- cycle as opposed to normalizing it and also using antivirals to depress XMRV and/or HHV-6. This is a question and I don't claim to have the answer to it, although my hope is that normalizing the cycle will also cure at least some of these infections, that may not be true.

There have been comments in the media to the effect that this finally shows that CFS/ME is physiological, not psychological. This is true, but this should have been obviously true anyway, at least six or seven years ago.

Nevertheless the media coverage of CFS/ME obtained by Mikovits and her colleagues must be viewed as a true gift to those interested in extending public knowledge of this disease.

Martin L. (Marty) Pall

[

 

[Summer]

I do not want to judge some of these folks, but I read on another board where a clinician/researcher was being quite negative on this work and had not even read the paper nor wanted to. Researchers can be influenced by their own bias and interests, which they are invested in, and sometimes for many years. Egos in this field are often inflated, and they are human, so I think we have to take that into consideration when we evaluate some of these evaluations.

This one comment, by Pall, is refuted by Dr. Judy, and she has put her entire reputation on the line, and I think they have much more research already than this current study which has only strengthened her assertion XMRV is absolutely causitive and not opportunistic:

"Comment: These data apparently show that XMRV is not specific for CFS/ME but rather occurs in other disease states, as well as in some normals.

My own view is that this makes it much more likely to be an opportunistic disease, caused by the changes in immune function and other properties of these diseases, rather than a primary cause."

 

[jenbooks]

I think he is misusing Koch's postulates, but in any case, the huge gap between infection in sick people and in healthy people demonstrates something different than opportunistic disease. That data is both alarming and impressive. Also, did he read the study or not? Over 90%? Why not cite the actual percentage?

In addition, because it's in prostate cancer and in "so far" normal controls (one would have to do a longitudinal sample over time, or look at the subsequent rate of cancer in the blood samples from the 80's--to know what else the "normal" controls suffered from), doesn't mean that it's opportunistic. It could be immunosuppressive like HIV, and lead to other infections and disease states.

Everybody who has worked for years to create a theory of illness and how to combat it that is NOT based on viral infection, is going to find this threatening and is going to find a way to try to minimize it so they can keep their theory front and center. You can expect it like clockwork.

 

[Summer]

Everybody who has worked for years to create a theory of illness and how to combat it that is NOT based on viral infection, is going to find this threatening and is going to find a way to try to minimize it so they can keep their theory front and center. You can expect it like clockwork.

Thank you for saying this so much better than me and so much more concise. I should delete my post.

 

[liverock]

I think he is misusing Koch's postulates, but in any case, the huge gap between infection in sick people and in healthy people demonstrates something different than opportunistic disease.

I agree there on the misuse of Koch's first postulate. Koch himself retracted it when cholera was first found and there were asymptomatic cases.

http://en.wikipedia.org/wiki/Koch's_postulates

However, Koch abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of cholera[1] and, later, of typhoid fever. Asymptomatic or subclinical infection carriers are now known to be a common feature of many infectious diseases, especially viruses such as polio, herpes simplex, HIV and hepatitis C. As a specific example, all doctors and virologists agree that poliovirus causes paralysis in just a few infected subjects, and the success of the polio vaccine in preventing disease supports the conviction that the poliovirus is the causative agent.

Everybody who has worked for years to create a theory of illness and how to combat it that is NOT based on viral infection, is going to find this threatening and is going to find a way to try to minimize it so they can keep their theory front and center. You can expect it like clockwork.

Good point, but all these detractors serve their purpose, although it may not be evident at first if we get too uptight about criticisms of XMRV as a causative agent. They serve as a spur to further define research and make those who are defending XMRV more definitive in there arguments and presentation. Judy Markovits has noticably had to do this in the space of 10 days since her first press conference.

 

[Summer]

Good point, but all these detractors serve their purpose, although it may not be evident at first if we get too uptight about criticisms of XMRV as a causative agent. They serve as a spur to further define research and make those who are defending XMRV more definitive in there arguments and presentation. Judy Markovits has noticably had to do this in the space of 10 days since her first press conference.

Very good point. My comments are directed to patients that want to be hopeful about this research who become easily discouraged when someone like this comes out and makes such definitive statements that this is not the cause. They feel that once again something hopeful is not going to work out. When a researcher will not even read the paper but trash it and admit they have their own theory, it's telling and patients somehow get caught in this crossfire.

 

[jenbooks]

I don't think Teitelbaum, Pall, Wessley or any other such "detractors" will in the slightest affect Mikovits' future research or its direction. She is working with peers in her field. She knows what questions she has to answer, and they won't be coming from alt health practitioners. And I'm all pro-alt-health, believe me. But you can expect *anybody* who has spent years developing a theory/practice and a line of SUPPLEMENTS to poo poo this research as they see it as directly threatening them.

 

[Summer]

I don't think Teitelbaum, Pall, Wessley or any other such "detractors" will in the slightest affect Mikovits' future research or its direction. She is working with peers in her field. She knows what questions she has to answer, and they won't be coming from alt health practitioners. And I'm all pro-alt-health, believe me. But you can expect *anybody* who has spent years developing a theory/practice and a line of SUPPLEMENTS to poo poo this research as they see it as directly threatening them.

Exactly. As I stated above, it's patients being discouraged that bothers me.

 

[MEKoan]

I find it fascinating that the bulk of the objections to the validity of this study is coming from those with a vested interest and the patient community online.

As Jen so eloquently states, "Everybody who has worked for years to create a theory of illness and how to combat it that is NOT based on viral infection, is going to find this threatening and is going to find a way to try to minimize it so they can keep their theory front and center. You can expect it like clockwork."

The language the detractors use betray the bias: 2/3rds instead of >67%, over 90% instead of >95%. And, of course, taking days to come up with pretty weak concerns - usually unfounded and often silly.

I am also a bit surprised at how many patients, with no medical or scientific training and armed with half baked scientific theories, are making passionate cases against XMRV having any relevance. Being sick for a long time and having access to Google does not a scientist make.

I don't know what XMRV will come to mean. I am quite comfortable waiting to find out its exact place in the condition. I welcome any and all reproducable findings which shed light and hope on this confounding illness. I also welcome the long sought after interest of mainstream scientists.

I take great comfort in knowing that Dr. Mikovits and her colleagues are not fools, were not born yesterday and were fully aware of the climate in which they worked before embarking on this often thankless business.

Thank you WPI!

Peace out,
Koan

 

[liverock]

I don't think Teitelbaum, Pall, Wessley or any other such "detractors" will in the slightest affect Mikovits' future research or its direction. She is working with peers in her field. She knows what questions she has to answer, and they won't be coming from alt health practitioners. And I'm all pro-alt-health, believe me. But you can expect *anybody* who has spent years developing a theory/practice and a line of SUPPLEMENTS to poo poo this research as they see it as directly threatening them.

I think Pall might be a little offended to be called an "alt health practitioner".

He is Professor of Biochemistry at Washington State University and is a member of the American Society for Biochemistry, on the Board of Ariston Pharmaceuticals
and advises the South Australian government on muliple chemical sensitivity.

I believe he has stated that he wished somebody would come up with a 'drug' that would down regulate the NO/NOO cycle instead of using supplements but he is stuck with them until somebody does.

BTW I am not a fan of his or the NO/NOO theory, as a matter of fact I am banned from his Yahoo site for criticising his theory too often.

 

[dannybex]

I think Pall might be a little offended to be called an "alt health practitioner".

He is Professor of Biochemistry at Washington State University and is a member of the American Society for Biochemistry, on the Board of Ariston Pharmaceuticals
and advises the South Australian government on muliple chemical sensitivity.

I believe he has stated that he wished somebody would come up with a 'drug' that would down regulate the NO/NOO cycle instead of using supplements but he is stuck with them until somebody does.

BTW I am not a fan of his or the NO/NOO theory, as a matter of fact I am banned from his Yahoo site for criticizing his theory too often.

While I agree that Pall is probably off the mark here -- I too am not in complete agreement with his NO-NO theory -- I don't think it's really fair to lump Teitelbaum and Pall in with Wessley. They may be defensive about their reputations and theories, but neither of them have ever claimed it's all in our heads.

Plus again, it's important to remember that neither of them make a dime off of the supplements they've created or put their name on. They donate their proceeds to research and charities.

 

[jenbooks]

I like Pall and think his approach has some merit but it's not the be all and end all.

 

[Aftermath]

The World is Flat

I don't think Teitelbaum, Pall, Wessley or any other such "detractors" will in the slightest affect Mikovits' future research or its direction. She is working with peers in her field. She knows what questions she has to answer, and they won't be coming from alt health practitioners. And I'm all pro-alt-health, believe me. But you can expect *anybody* who has spent years developing a theory/practice and a line of SUPPLEMENTS to poo poo this research as they see it as directly threatening them.

Time will tell as to whether or not XMRV is causative in this illness. From her statements after the science paper was released, we have a pretty good idea that Dr. Mikovits is optimistic that it is.

One way or the other, a lot of those who have staked their careers on other theories are acting in one of the two ways that logic would dictate they should behave:

1) Positing that the XRMV angle squares with the CFS mechanism that they have been advocating for years (e.g. "it is part of my theory"); or

2) Steadfastly denying that XMRV theory has relevance. This approach is more common with guys like Wessley, who are painted into a corner so hard that there is no way for them to use the first approach. These guys are on the same level as those who continue to maintain that the Earth is flat.

Hopefully within a couple of years, these researchers will be viewed in the same manner as the Flat Earth crew.

Still, we need to remember that in science, something is untrue until proven correct. While it certainly looks optimistic, at this point, XMRV is unproven as a cause of ME/CFS. Hopefully two years from now, there will be conclusive proof that this virus causes our illness.

 

[jenbooks]

I agree--flat earth society. I've seen the response you cite--either "My theory is valid and partakes of this finding or this finding is subsumed in my theory" or "My theory is valid and this finding is meaningless." Usually "My theory" has ego and money attached.

The evidence looks pretty compelling. This family of viruses is known to cause like disorders in animals--why not humans?

 

[Cort]

I don't think this little essay did Dr. Paul any good. He is amongst the most prickly of investigators that I've run across. With regards to research his opinion will have no effect at all because he's had very little effect in the research arena; he's been unable to raise much money to do his own research. While his theories have one some followers among physicians and patients - they have not extended into the research field.

He noted the 67% positive rate but I think aftermath is right; what we should be paying attention to is what's coming out of the Whittemore Peterson Institute now - and they're saying 100% of patients. (I'll bet CCD patients) They're obviously continuing to test as furiously as they can and we're continuing to hear nothing but positive statements from them - a very good sign.

That doesn't mean that there isn't some immune dysfunction that goes along with this pathogen. (By definition doesn't one have to be present?) Or that Dr. Pall's theory won't come to bear at some point. The WPI is reportedly looking very closely at cytokines with regards the virus. It maybe that cytokine problems help to open the door and it may be that Dr. Palls and Rich's others theories will come into play at some point. Dr. Mikovits did state that removing the hormonal and immune dysfunctions should help to silence the retrovirus.

Does anybody think, though, that either of those therapies 'cures' ME/CFS? My thought has always been that they will probably be helpful - but only in a few cases curative. There's nothing the matter with improvement that's for sure.

 

[lostinthedesert]

That doesn't mean that there isn't some immune dysfunction that goes along with this pathogen. (By definition doesn't one have to be present?) Or that Dr. Pall's theory won't come to bear at some point. The WPI is reportedly looking very closely at cytokines with regards the virus. It maybe that cytokine problems help to open the door and it may be that Dr. Palls and Rich's others theories will come into play at some point. Dr. Mikovits did state that removing the hormonal and immune dysfunctions should help to silence the retrovirus.

I worked in the lab of a medical researcher back in the 1970s. He was going head to head with another researcher who had a seemingly incompatible theory. They both had plenty of experimental evidence and had published papers in esteemed journals. There seemed to be no way to reconcile the two points of view but that was because everyone was taking the stance that one or the other had to be correct (yes, a sign of big egos is likely to be narrow mindedness). When I checked backed many years later, it turned out that both had been proven correct. When technology had developed sufficiently for the situation to be observed in detail, both mechanisms were taking place and a hybrid theory was developed that accounted for both researchers experimental results.

Dr Pall has been more of a research reviewer and theoretician than an experimenter. I do believe that some of the mechanisms he has proposed do occur and may contribute to the disease process. Still whenever someone makes the leap to causation without solid experimental evidence I tend to want to raise my hand (from the back of the class where all us troublemakers sit and call out BS.

Peace,
S

 

[shiso]

Keeping the common goal in sight

While I agree with much of what people have said, I like Pall (from reading his book; I didn't know he was prickly). He had the disease himself and if you read his book, you can clearly tell that he is a real scientist (unlike Teitelbaum) and how compassionate he is about the suffering of ME/CFS patients. The chapter in his book condemning proponents in the medical community of any psychogenic theory of the disease (i.e. the Wesselys of the world) is great.

I don't think he should be faulted for simply expressing his views about XMRV and how it compares with his theory, which could still turn out to have some relevance in the big picture of a disease as complex as ME/CFS, even if it may not be THE answer (which I too tend to think it's probably not). I imagine (as Cort notes) that he, like other scientists in the field, has had little access to funding required for large scale studies to test his theory.

I think WPI has shown us good reason to be hopeful for what their findings mean for us in the future. What they've accomplished, how they did it, it's all amazing. But as much as we may want to root for the theory that a virus like XMRV is THE cause and answer that will lead to effective treatment (I am as hopeful as anyone else), I think it's still important as patients to distinguish the Palls from the Teitelbaums (much less Wessely, who is simply an evil loser) and not automatically jump on every scientist who expresses any kind of skepticism about XMRV and its role in the disease especially when they are working towards the same goal as WPI - alleviating and ultimately eliminating our suffering.

I personally think it is a good thing that there are multiple players examining this disease from different angles and that they believe enough in their research that they are willing to stake their reputations on them. The fact that egos and money are involved is simply a fact that exists in any medical research and applies to everyone, Dr. Mikovits included. I don't think it lessens what they are each doing for all of us.

 

[hvs]

I don't think Teitelbaum, Pall, Wessley or any other such "detractors" will in the slightest affect Mikovits' future research or its direction.

Spot on, jenbooks. This is the amazing new reality that we have to get a grip on. As fun (and in many ways, important) as it is to see a Reeves humiliated and a fire lit under the CDC, the new reality is that Mikovits and the others who have (or will get) grants will just trudge on without them. They will continue to publish findings that rock the virology world. And scientists and ID docs will react--NOT because they give a $!&* about validating anyone, NOT because they're sorry for ignoring a class of patients, but because the new finding are simply right. Amazing things happen when you discover things that are correct.

 

[Eric Johnson from I&I]

Dr. Pall's statement about Koch's postulates and XMRV was simply incorrect. There is really no room for difference of opinion on this. I discussed it with him here. Note the two or three follow-up messages:
http://health.groups.yahoo.com/group/cfs_research/message/26707

 

[Holmsey]

Vested interests

I wasnt aware that those at the WPI were working on an altruistic basis, the impression I got was that they were taking research funding from anyone who would give it, and I presume salaries are paid, ambitions exercised etc?

As has been pointed out Pall (at least claims he) isnt some alternate practitioner, if the non Google using scientist earlier can rubbish his theory Id like to hear that, no really I would, may not specialise in this field but my IQ is more than high enough to follow up and further investigate and good science.

My impression so far is that Pall is actually trying hard to answer the basic questions, just like the WPI, so not immediately throwing his hands in the air and saying oh I must have got it wrong but rather asking more questions sounds like a solid approach to me. There are also allusions to Pall making personal gain from his work, such as selling supplements perhaps; can someone direct me to the evidence for this so that I can read up further?

Having spent the first two years of this illness letting so called experts tell me what was wrong and getting nowhere I now question everything and so to the point. From no position and with the aim of only improving my knowledge I welcome, with qualification if needs be, theories on the following.

If XMRV is prevalent in a minimum of 3.5% of the population does that not make it a virulent virus, should we not therefore have seen or expect to see an explosion of cases mirrored in those showing symptoms of CFS?

A German study found no XMRV in prostate cancer patients in their attempts to replicate the results which lead to the WPI study, what does this suggest about XMRV?

People do apparently, of their own volition, get well following CFS and go on to lead normal lives, what does this tell us about a virus based cause?

If the answer to the above is that the virus goes dormant, as happens with herpes simplex for instance, then what changes bring this about and what keeps it dormant?