The Fight is on...Imperial College XMRV Study

[Martlet]

I dont know anything about the moderators point being removed but I strongly suspect the possibity, of shall we say, outsiders getting on to this site trying to play divide and rule. I'm not saying its happened yet.

Hi Flex

I think that if anyone suspects that of a particular member, the best way to deal with it is to alert the moderators and then we can watch the person's posts for a while. That helps us immensely and if we think - after discussion - that we have trolls on board, we will take care of it.

 

[flex]

Thanks for posting, JayS! From the link above:



"Other venues" - is he talking about us??? Hi Dr Wessely, if you're reading! Thanks for the denial, but I think it's safe to say most of us are not convinced. Sorry!

"The patients in the Imperial study are typical of patients seen elsewhere". Is that elsewhere in the UK clinics that no real ME patient attends because they are bedridden or/and they can see straight through the pscho corruption so have nothing to do with it.
Or is it elsewhere like in other countries where "CFS" actually means real ME.
He resents the accusation that the patients in his study were, "more Psychiatric whatever that means". He should know, he is a psychiatrist!! Isnt that his job? Surely he gets that one. Is that why he gets sane people sectioned under the mental health act. Because he cant tell the difference. THAT ONE IS AN ABSOLUTE CLASSIC!!!

Wessely, why dont you just fly to Nevada and test the same group of patients as the WPI and see who can find XMRV or not in a real replication study.

Plus he talked about his patients being co morbid. What exactly are they co morbid with if there is no organic illness present.Are they co morbid with non existent XMRV, "not present" in the UK until yesterday as confirmed on this site. Or are they co morbid with ME the neurological disease coded by the WHO and "a bit sad and aggrieved about it" which qualifies them for the psychiatric label "depression".

Or were they just a bunch of specially selected cohorts who have been under his clinic for, in his own words "four years"
Why hasnt he cured them in four years, he can't be a very good psychiatrist!!

Maybe he hasn't cured them because they are "co morbid " with a chronic neuro immune disease, that can lead to people like Sophia Mirza dying whilst being abused by the NHS!!!!

So much for his CBT and GET!!!

 

[Sparklehorse]

Thanks for posting, JayS! From the link above:



"Other venues" - is he talking about us??? Hi Dr Wessely, if you're reading! Thanks for the denial, but I think it's safe to say most of us are not convinced. Sorry!

Interesting to note that the bit where they said "We draw attention to another study that compared two services run in the same London teaching hospital, one by an immunologist, the other a psychiatrist, but showed no fundamental differences between the two (White et al, 2004). " That would be the immunologist Prof. Anthony Pinching, long-time collaborator with the psyche school, no matter what he would claim, and long-time medical advisor to the psych-friendly AfME. So no potential bias there then or conflict of interests. Funny how the rats all like to stick together and work together.

Wessely and Cleare, read this. I despise you for all the hurt and trouble that you have caused ME patients in the UK. You WILL be brought to account for your actions. One day.

 

[thefreeprisoner]

To me the difference between the two studies seems obvious.
WPI study: from fresh samples.
Imperial study: samples frozen.

Isn't that the case, or has my brain fog become pea soup?
Maybe we should have a new classification: brain freezing fog. (Mmm, icecream.)

 

[Sparklehorse]

To me the difference between the two studies seems obvious.
WPI study: from fresh samples.
Imperial study: samples frozen.

Isn't that the case, or has my brain fog become pea soup?
Maybe we should have a new classification: brain freezing fog. (Mmm, icecream.)

Yes, I believe that you are correct. I also don't trust Wessely et al to have provided "untainted" blood. How do we know that the blood samples were kosher anyway?

 

[flex]

"Wessely strongly resents accusations that......... bla..... bla....bla..."

OH POOH....WE HAVE JUST HURT HIS FEELINGS!!!

 

[Esther12]

To me the difference between the two studies seems obvious.
WPI study: from fresh samples.
Imperial study: samples frozen.

Isn't that the case, or has my brain fog become pea soup?
Maybe we should have a new classification: brain freezing fog. (Mmm, icecream.)

Didn't the WPI originally find XMRV from frozen blood though?




As far as I can tell there are no clear problems with the Imperial study that explain the total absence of XMRV. It could well still be that they messed it up, and they certainly didn't use all the same techniques as the WPI, but if there was widespread XMRV in their patients, most scientists (to be clear, by 'most scientists' I mean 'most scientists who've written about this on the internet' - this is as close an indication as I have to what the scientific communitie's thinking, and it''s not much to go on) seem to think that they should have been able to find it. I expect the study did use a looser definition of CFS, and the patients were all ones able to attend a day clinic, but even so, if 96% of Canadian definition CFS patients had XMRV in Britain you'd expect a fair few of this sample should too (unless you think Wessely totally stacked the deck, which would be a totally stupid thing for him to do, and would surely be revealed by the other replication attempts going on).

I understand people focusing on the cohort because of Wessely's involvement, but to me it seems likely the problem is more likely to have come from the testing. Either Imperial's or the WPI's. Further replication studies should let us know. Someone mentioned that the CDC's was expected today (only a rumour)? Anyone know anything more? Imperial seem confident that further studies will back them up. The WPI must be in contact with those doing replication studies, and their press release gave the impression that they were still sure they were right about this.

 

[Martlet]

Someone here (I am too tired to research this) said that SW recently coyly stated that he was not working on ME matters any longer. Even as he was working to publish the PLoSONE article. I need a source for this, because it is an apparent untruth that the PLoSONE editors might take note of. Can anyone help out?

Hi Levi

Were you perhaps thinking of his email to me? When I emailed him, I asked for permission to publish, so here it is again:

Your story is a familiar one, and I am of course very pleased that you have done well. Many people do, but sadly not everyone.

Certainly I would like to feel that you would have been treated with equal respect within our medical system - although one cannot be sure of that. However, I am certain you would have been treated with courtesy and respect at our service, which exists solely to look after CFS patients here on our national health service. We have seen now over 3000 sufferers, and I really don't think that would have been the case if we did not show kindness, courtesy and patience to our patients.

However, I would like to point out that it is not "my" definition of CFS that we all use around the world - I happen to think it is a reasonably good one for the moment, but I am afraid I cannot take the credit for it.

Like you, our patients also say in half the cases - I definitely got sick after a virus - and in another good proportion "I probably got sick after a virus" - if you do read our papers, all of which are on our website, free access, you would see that we regularly draw attention to that finding, which remains consistent. Hence one term in frequent use in this country is post viral fatigue syndrome as a synoymn for ME. We have over the years published several papers looking at viral and other infective risk factors for CFS, and for example showed that viral menignitis for example is a proven risk factor, and we have contributed to the literature showing that EBV is likewise.

I have to say that is one reason why I am not convinced that XMRV is the explanation for three quarters of cases of CFS - it would imply that all the other studies, that use longitudinal and hence powerful designs were wrong, and I don't think that they are, because they are robustly designed and also replicated.

But as I seem to have said on several occasions in the last few weeks, science is a great thing. One thing that I am sure about is that in the coming months we will know if this really is a great break thorough - and make no mistake - if the finding is replicated at the same level of signficance that is being reported (and I read that the authors are now saying that they are finding evidence of XMRV in 95% of cases) then it is a great break thorough indeed and will change our views of the illness, and will of course lead to improved management and treatment, which is what everyone wants, including yours truly. I genuinely believe that the treatmetns that we offer, some of which we helped pioneer (and by the way, they don't involve psychotropic medication!) , have been shown to improve outcome in CFS, and I am proud of the way in which myself and many colleagues have contributed to this. But I also see a large group of patients who have not been helped, and whom I see for basic support, and help with the myriad twists and turns of our welfare state. So if something new comes along that improves outcome even further, no one will be more pleased than myself and my colleagues. Why on earth would we not be?

So we shall see. Science is a self regulating system, and the truth does come out, albeit sometimes slower than we might wish. In my opinion, for what it is worth, I would be surprised if in a few months time we still find that XMRV is associated with two thirds of cases of CFS. I have been around a long time now, and have seen other spectacular claims fail to pass the utterly essential test of replication by other groups, in other places. If I was a betting man, which I am not, this is not something I would bet my house on. But as I say, we shall see, that is for sure.

My advice is to be patient - if this is indeed a genuine advance, it is worth waiting a little longer for.

One last thing, no, I won't be making any statements. I am not a politician. I also do very little these days around CFS - I still see patients every week, and I keep reasonably abreast of the literature, but it hasn't been my main interest now for many years. But can I say how refreshing it is to have someone ask if they can publish my reply to them - it is nice to meet someone who also believes like I do in old fashioned courtesies like that. Sadly as I know from bitter experience, many do not. . Thanks for asking, yes you can, but with one proviso - it must be in full or not at all.

With kind regards


Simon Wessely

 

[Martlet]

I expect the study did use a looser definition of CFS, and the patients were all ones able to attend a day clinic

Even if they only used completely healthy people, they surely should be finding close to 4% positive? - if it is indeed in close to 4% of the healthy population. The fact that they found none makes me think their methods were wrong. And now that we have seen at least one positive from UK testing, it makes me more convinced that that IP did not use the right methods.

 

[gracenote]

Were you perhaps thinking of his email to me? When I emailed him, I asked for permission to publish, so here it is again:

Martlet,

Thanks for reposting this. Do you have a date for this email? Obviously the communication is from after the Science article was published, but I'm curious as to exactly when.

Thanks.

 

[flex]

To all our American and non British cousins please let me clarify this.

The estimated amount of ME sufferers in the UK is 250,000
Wesselys says in the UK there are 1 million "CFS" sufferers.

He also says that three quarters of them do not have neurlogical ME!!

He has directly confirmed in an email to Holmsey above that he does not expect three quarters of the UK "CFS" sufferers to have XMRV. (before Imperial study)

Now go figure!!

Who is looking after the ME patients under governmental obligation?

No one because doctors have been lead to believe that ME and "CFS" (Oxford Criteria) is the same thing!!

Surely that is the case closed!!

 

[kwietsol]

.... Professor Wessely's credibility is about to become an issue with the PLoSONE editorial board. They are taking the possibility of undeclared competing interests for this report quite seriously. Someone here (I am too tired to research this) said that SW recently coyly stated that he was not working on ME matters any longer. Even as he was working to publish the PLoSONE article. I need a source for this, because it is an apparent untruth that the PLoSONE editors might take note of. Can anyone help out?

Levi,

Thanks for your part in making sure PLoSONE's ascertains that SW did not violate its competing interest policy.

For those interested, that policy is here: http://www.plosone.org/static/competing.action.

An excerpt of PLoSONE's policy:

Financial

Financial competing interests include but are not limited to:

Ownership of stocks or shares
Paid employment or consultancy
Board membership
Patent applications (pending or actual), including individual applications or those belonging to the institution to which authors are affiliated and which the authors may benefit from
Research grants (from any source, restricted or unrestricted)
Travel grants and honoraria for speaking or participation at meetings
Gifts
Authors must declare all potential financial competing interests involving people or organizations that might reasonably be perceived as relevant....

As a guide, any competing interest that arose within the five years either before or after the commencement of the research described, or within five years of the article being written, or within five years of events described in the article, should be declared. However, interests outside this time frame may also be relevant; if so, they should also be declared so that their relevance can be judged by the editorial team.

Non-financial

Non-financial competing interests include but are not limited to:

Professional
Acting as an expert witness
Membership in a government or other advisory board
Relationship (paid or unpaid) with organisations and funding bodies including nongovernmental organisations, research institutions, or charities
Membership in lobbying or advocacy organisations
Writing or consulting for an educational company
Personal
Personal relationships (i.e., friend, spouse, family member, current or previous mentor, adversary) with individuals involved in the submission or evaluation of a paper, such as authors, reviewers, editors, or members of the editorial board of a PLoS journal
Personal convictions (political, religious, ideological, or other) related to a paper's topic that may interfere with an unbiased publication process (at the stage of authorship, peer review, editorial decision making, or publication)
Authors, reviewers, editors, and anyone wishing to comment on a published paper must consider and then disclose whether they have any non-financial interests that might influence their reporting, handling, or review of the paper, or that might be negatively or positively affected by publication of the paper.​

 

[Martlet]

Martlet that will do. Would you be willing to forward this email to them if requested to do do by PLoSONE editors? When was it dated? I may need it.

It was dated 11/16/09 and I would be more than willing to forward it. I asked for permission to publish. I did not say where and he did not make any stipulations. Just PM me if you need it.

 

[kwietsol]

Or any others with university research capability. This is a shot in the dark, but would bring matters to a quick close. Can you find any publication in which SW and PLoSONE editor Dr Dixon were collaborators or co-authors? Not just cited in the same work. I would find it amazing to believe they could be that arrogant, but stranger things have happened.

Typo, I think, Levi. It is Dr. Nixon, not Dixon.

Editor: Douglas F. Nixon, University of California San Francisco, United States of America
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008519

An excellent question.

 

[gracenote]

From Wessely's email: One last thing, no, I won't be making any statements. I am not a politician. I also do very little these days around CFS - I still see patients every week, and I keep reasonably abreast of the literature, but it hasn't been my main interest now for many years. But can I say how refreshing it is to have someone ask if they can publish my reply to them - it is nice to meet someone who also believes like I do in old fashioned courtesies like that. Sadly as I know from bitter experience, many do not. . Thanks for asking, yes you can, but with one proviso - it must be in full or not at all.

Maybe chronic fatigue syndrome hasn't been his MAIN interest for many years, but he sure has published A LOT on CFS and related topics. And one would hope for someone publishing so extensively on a topic that he be more than "reasonably" abreast of the literature.

Here are some of his papers going back just until 2007.

Roberts A, Papadopoulos A, Wessely S, Chalder T, Cleare A.
Salivary cortisol output before and after cognitive behavioural therapy for chronic fatigue syndrome.
Journal of Affective Disorders May 2009;115(1-2):280-286.

Harvey S, Wessely S, Kuh D, Hotopf M.
The relationship between fatigue and psychiatric disorders: Evidence for the concept of neurasthenia.
Journal of Psychosomatic Research. May 2009;66(5):445-454.

Cho H, Menezes P, Hotopf M, Wessely S, Bhugra D.
Comparative epidemiology of chronic fatigue syndrome in Brazilian and British primary care: Prevalence and recognition.
British Journal of Psychiatry. February 2009;194(2):117-122.

Cho H, Menezes P, Bhugra D, Wessely S.
The awareness of chronic fatigue syndrome: A comparative study in Brazil and the United Kingdom.
Journal of Psychosomatic Research. April 2008;64(4):351-355.

Cho H, Wessely S.
The prevalence and associations of unexplained chronic fatigue in Brazilian primary care.
Primary Care & Community Psychiatry. 2008;12(2):81-87.

Quarmby L, Rimes K, Deale A, Wessely S, Chalder T.
Cognitive-behaviour therapy for chronic fatigue syndrome: Comparison of outcomes within and outside the confines of a randomised controlled trial.
Behaviour Research and Therapy. June 2007;45(6):1085-1094.

 

[Martlet]

The relationship between fatigue and psychiatric disorders: Evidence for the concept of neurasthenia.

Just from the above, it would seem that Florence Nightingale was mentally ill, thought herself into sickness and then, from her bed, organised the entire nursing-care system in the UK. Damn! Just imagine what she might have achieved if she had not had this sickness thinking!!! (sorry, had to get it off my chest)

 

[kurt]

Someone had asked, what did the "Spiking experiment" mean? From what I understand, they added a known quantity of XMRV into the test tubes of patient samples - to see if they COULD indeed find XMRV if it was there.

Many questions were raised about the Imperial College's ability to detect XMRV. For example, the Polymerase Chain Reaction (PCR) bands illustrated in the figures accompanying the IC were very weak - even for the XMRV control. Some readers said things like, "if your control bands are that weak - when you know XMRV IS present, how dim (or nonexistent) might they be when there is a very low concentration of XMRV present? In other words, might a test that is already perceptibly weak, yield false negatives?

On the results of the spiking experiment:

@Kurt, can you help interpret the spiking results further?

1) From McClure's PLoS January 11th response @ http://www.plosone.org/annotation/l...notation/6bfbac4a-5ace-4a2d-a9bb-60f017ae24d8 , she said,

" We randomly chose 22 of the CFS patient samples and spiked the DNA with 10 copies of XMRV plasmid DNA. The XMRV /MLVsequences were amplified in every case.
Positive and negative controls worked beautifully"
​

Wouldn't that just prove that their test was sensitive enough to pick up THAT particular viral threshold? What if patient samples had say, 1 copy of XMRV plasmid DNA? Or 3? For example, I know from the persistent PVB19 viral research that persistent infections DO often have very low findings on serology. Tests need to be exceptionally sensitive to pick up low viral levels, and even then sometimes they are only found in tissue, not in bloodwork.

2) There still remain, as you rightly say, "other confounding issues in their study", not the least of which is their cohort selection. Do you have any other thoughts on that?

Thanks Kurt!:Retro smile:

Hello parvofighter,
1) Yes, as I understand PCR testing you are correct. Their spiking may have been too strong to show the threshold necessary in a clinical test. But I believe earlier IC reported that they could detect a single copy of XMRV plasmid DNA. So this small post-study experiment is a bit curious. If they had spiked water or a plasma media with single copies before, why did they use ten copies for the in vivo sample in blood? You would probably have to know all their calculations to know their reasoning, I doubt we can figure that out with the information given. For example, what was their test volume? If they were testing a larger quantity of blood than water in the new testing, they might have needed to use more copies to keep the same detection threshold. You just have to assume that these are competent technicians and they are using valid calculations, most of these lab people are detail oriented, I am not too worried about errors. At this point what is curious is that WPI has not worked with a third party lab and showed them how to run the test, then presented evidence that their test works.

All of these issues apply to the WPI study just as well. There are fine details that they could also have gotten wrong, not errors but just some false findings that nobody could have predicted. And until they are challenged that is not revealed. This type of science does not have an opinion, either side in this could be wrong and it might not show for some time, maybe we will know more when other replications have been completed. What we do know is that other labs are not finding XMRV and I am sure they are trying very, very hard to find it, because whoever finds XMRV, and can produce a reliable test, will have significant reward, in many ways. If IC had found XMRV you can be sure they would be shifting their focus and taking advantage of their position as first to replicate. No 'conspiracy' mindset would persuade them to run a sloppy study just to oppress ME patients with so much at stake in this race, that is just a bad idea (ME patients no doubt have every right to be a little paranoid, but still, look at the reality here, this study was real, and says something).

2) As I have said elsewhere, cohort selection is a dead issue. Anyone raising that issue, including WPI, needs to take a moment and think about the claims WPI is making. If XMRV is found in 98% of PWC, it would be found in almost any study with sufficient detection tolerances and even a few 'real' ME/CFS patients.

The controversy about GWS is the virus connection. Soldiers were given 10 vaccinations in a period of a few days before they were rushed of to the first Gulf War. The normal period for such an attack on the nervous system is 6 months. Vaccinations contain a small dose of a harmful agent that your body is supposed to fight and you are then protected against that virus.

Why did they need 10 vaccinations. What were they being protected from. What effect did this bombardment have on their health.

Were they being vaccinated to protect them from chemical warfare.

Why were scientists bragging in eighties that they had cultured and developed in labs the same harmful agent found present in lyme disease from tick bites.

US supported Afganistan in the war against the Soviets. What did they supply them with. Did they supply Iran and Iraq with chemical warfare. Is that what ME is. Is this what the soldiers were vaccinated with in fear that they would encounter such attacks. Were the soldiers over vaccinated.

Why is a SW at the forefront of denying GWS.

Why dont scientists take care when developing things in labs and controlling substances that cause hazard to public health. Why do governments dump toxic products in poor countries and pay them.

Why did West Nile River Virus happen. Why was it denied as all being down to"hysteria" by YOU KNOW WHO.

Why is XMRV being described as a retro virus but its very existence being denied in the UK by YOU KNOW WHO

Why did the UK government place issues relating to ME under the official secrets act until 2030

Why has the above period been extended to 2071.

Why is the blood study so slow.

Why are the government in denial.

Why is you KNOW WHO in denial.

Why do they seem to be on the same side.

Who is working for who.

Why is the truth in the denial.

YOU KNOW WHO? So is SW now 'He who shall not be named?' LOL

Seriously, I know people in the UK have been abused in some novel ways by their medical system. SW probably deserves this dislike and should find a new line of work. But as an outsider, what I see in his comments is not much different from the attitudes of most physicians in the US and pretty much everywhere. He is just following his old paradigm, refusing to adapt to a changing reality. The US CDC is only a few steps behind him, the difference is that they have learned to talk the talk and now say 'CFS is serious' but they still do nothing, they do not 'walk the walk' of helping us and just throw us some bread crumbs.

At least Wessely is honest about his disbelief in ME/CFS. In the US we have a deeper type of dishonesty. Doctors nod and tell you it is real and they wish they could help, then they secretly go off and write 'somatoform' on their charts. And we have dozens of studies, many by the CDC, that prove the point of physiological cause and the CDC still refuses to give us any real funding. We will have a cure when enough money is spent, hundreds of millions, maybe a billion US dollars are required just to open up serious disease research areas like this. We get next to nothing.

 

[Hysterical Woman]

Kurt/YOU KNOW WHO?

Kurt said:

"YOU KNOW WHO? So is SW now 'He who shall not be named?' LOL"

Oh my, so does that make an unnamed employee of the CDC Nagini? Or Wormtail?

Where is J.K. Rowling when you need her??

Maxine

 

[_Kim_]

Or any others with university research capability. This is a shot in the dark, but would bring matters to a quick close. Can you find any publication in which SW and PLoSONE editor Dr Nixon were collaborators or co-authors? Not just cited in the same work. I would find it amazing to believe they could be that arrogant, but stranger things have happened.

I made that my mission on the first day of the publication. I found loose associations, but no collaborations or co-authorship. Same with McClure and Nixon - only loose associations. I searched pretty deep into the pile, but nothing turned up...

Except the uncanny likeness...

..............Nixon...................................................... SW

 

[parvofighter]

Spiking experiment: meaningless @ 10 of XMRV plasmid?

Further to the spiking experiment performed by McClure (from my post #902 on this thread):

1) From McClure's PLoS January 11th response @ http://www.plosone.org/annotation/l...notation/6bfbac4a-5ace-4a2d-a9bb-60f017ae24d8 , she said,

" We randomly chose 22 of the CFS patient samples and spiked the DNA with 10 copies of XMRV plasmid DNA. The XMRV /MLVsequences were amplified in every case.
Positive and negative controls worked beautifully"
​

Wouldn't that just prove that their test was sensitive enough to pick up THAT particular viral threshold? What if patient samples had say, 1 copy of XMRV plasmid DNA? Or 3?

I think this remains a germane question. Then consider this quote from VPI Dx on how challenging it can be to find XMRV:

Have just been reading about XMRV testing on the VIP Dx site ...:
Q: Does a negative result definitively mean that I am not infected?
A: Although we strive to offer the most sensitive test available, XMRV is typically present at a very low-copy number and may be below the limit of detection at the time your sample was tested...

Q: Is it possible to have a positive result at one point in and a negative result at a later time?

A: Although retroviruses are integrated into the cellular DNA of white blood cells and are considered life-long infections it is possible that your immune system may hold the virus to a level below the limit of detection from time to time. http://www.vipdx.com/

I had tremendous concerns about the science used in the Imperial College study - and still do. It helps to put McClure's assertion (that the spiking test proves their original lab methodology was sufficiently sensitive) in the context of how low that PCR limbo pole has to be in order to detect XMRV. And it underscores why WPI is working on version 2.0 of the XMRV tests. In other words, McClure's gotta limbo a little lower, according to my understanding, before they can even begin to claim their lab science is as sensitive as that of the Science researchers. Now where's a limboing smiley?

Other thoughts?