The Fight is on...Imperial College XMRV Study

[Holmsey]

I kind of knew I'd get asked this and can only answer it honestly, I was sent the original paper by Simon Wessley because I asked him to keep me informed ofany articles of interest which came his way, he obliged. Since receiving that I've discussed and questioned him on many of the questions raised here. I haven't posted any of them because I'm aware how my even speaking to the man will be received.

 

[Navid]

Irresponsible quote by Lombardi?!?!

"Chronic Fatigue Syndrome Attacked Again

By Sam Kean
ScienceNOW Daily News
6 January 2010

But some scientists, including Coffin and McClure, fear that Lombardi's clinic took advantage of that hunger by offering the $650 diagnostic test, 300 of which have been administered so far. Lombardi's group never claimed XMRV caused CFS, so it's not clear what a patient could do with a positive result. Lombardi argues that patients can avoid infecting other people with XMRV and have their diagnoses validated, if nothing else. "


wow...this is a major statement...it hasn't ever been said definitively how/if xmrv is passed from one person to another....i am alarmed how this stmt was just thrown out there in such a nonchalant way by lombardi. we'll soon have a panic from people about passing or receiving this yet to be fully validated retrovirus...i think this stmt was irresponsible.


tx, lisa

 

[spit]

On another forum, someone with a science background has expressed their opinion that the EDTA used in the blood collecting tubes they use at Imperial is a fairly violent detergent and chelating agent. if this is so, would it have affected the results?


I'm also wondering if this study result was deliberately rushed out ahead of the publicity that's bound to result from Kay Gilderdale's trial for assisted suicide of her severely affected daughter on Jan 12th

If I'm remembering right, EDTA is a pretty common thing to use in DNA extraction to stop the action of enzymes in the mixture that would otherwise degrade the DNA -- I've used it in this before, though I don't know if there are specific cases where it might be a bad idea for some reason. Extraction always uses detergents, to my knowledge, to get rid of lipid membranes in the mix. EDTA specifically isn't particularly nasty in small doses, it's also often used as a food preservative and most of us probably eat it in tiny amounts all the time.

Still, extraction procedures can certainly have effects on the quality of the sample, especially if you're dealing with a tiny amount of viral genome, so they're important questions to ask. I don't know how the extraction for the WPI study was conducted.

And I'd personally guess that the rush to get these results out was more about publicity and a sort of "getting into the game", more than anything. It's a lot better for one's reputation to get into the mix of studies as quickly as possible, become a big player early in the research. Beyond that, I'm not going to even try to guess about motivations or whatnot -- I assume that this team wanted to run a good study and find solid evidence either way, honestly, I just also think they went about it hastily and with poor cross-checking of their procedures.

My complaint is honestly mostly that I see many questions they should have asked themselves when they got no positives, and also when their amplification of their one known positive doesn't seem to have been very good. They don't seem to have asked those questions or tried to show more clearly that there wasn't a problem with their experimental design, which makes the study look shaky to me -- in my mind, if you get results like this -- I mean, zero positives, really? -- you fiddle around with your procedures to try to cross-check the results through other means, just to make sure you've covered the potential problems in your experiment. It's not that your data is necessarily wrong, it's that you should consider and try to correct for things that increase confidence that it's right. They don't honestly seem to have done that at all, and their discussion section in the publication brings up no potential experimental issues for further thought, even.

They then took that and made very, very bold statements both in the study itself and to the media. Even if the study were really strong, I'd have phrased the interpretation of results more carefully, if I were them. And the study just doesn't look very strong, so it's a little bit jaw-dropping to me that they'd make such strongly worded arguments from it without any other discussion on why they may have found different results from WPI.

To be fair, some of it is also a media problem. There aren't many good science editors out there in the popular media, and they tend to jump on a flashy study without questioning it much. And if they interview a scientist, they're going to use the clearest sounding quotes even if there are others that are more thoughtful and nuanced. Add to that that the popular press loves itself a good fight, and you've got a situation where I'm unsurprised that the articles we've found are pretty bad.

 

[fresh_eyes]

Following the WPI's publication Imperial contacted the clinic still run by Simon Wessely enquiring if they had samples. As the leading UK authority on retroviruses they were apparently already well informed regarding XMRV and were genuinely excited at the prospect of doing research.
The clinic had frozen samples and simply forwarded these as per the request. Following the study, neither Simon Wessely or anyone else involved in providing the samples had any power or censorship, and with respect to results these would have been published independently regardless of the prevelance found. Apparenlty it was said at the press conference that this is just another paper and that there will be many more.

I was sent the original paper by Simon Wessley because I asked him to keep me informed of any articles of interest which came his way, he obliged. Since receiving that I've discussed and questioned him on many of the questions raised here. I haven't posted any of them because I'm aware how my even speaking to the man will be received.

Thanks for the full disclosure, Holmsey. I'm sure, regardless of how we feel about Wessely, we'd all be very interested to hear as much as you'd be willing to share of what he's said to you.

 

[Dx Revision Watch]

UK: The Economist print edition 07 Jan 10

http://www.economist.com/sciencetechnology/displaystory.cfm?story_id=15211401

Chronic fatigue syndrome

Seconds out
Jan 7th 2010
From The Economist print edition

A fight over the cause of a mysterious disease

LAST October a discovery was made that brought hope to millions of sufferers from chronic fatigue syndrome (CFS). A group of researchers found a bug with the long-winded name of xenotropic murine leukaemia virus-related virus (XMRV) in 67% of American patients with CFS (as opposed to 4% of healthy controls). This figure increased dramatically when the patients were retested.

The news was exciting for patients because CFS is a debilitating disorder of long-term tiredness for which there is no simple explanation, and certainly no sniff of a cure. It has even attracted a certain degree of media scepticismbeing dubbed, at one time, yuppie flu.

XMRV is certainly a reasonable candidate to cause CFS. It has also been implicated in prostate cancer, breast cancer and lymphoma. Last years study, published in Science by Judy Mikovits of the Whittemore Peterson Institute in Reno, Nevada, and her colleagues, caused such excitement that it quickly led to commercial testing for XMRV infection. Furthermore, because XMRV is a retrovirus, like HIV, several preclinical studies have been looking at whether antiretroviral drugs might have an effect on it. One of these studies has found that of the ten licensed compounds tested, only AZT inhibited replication of XMRV.

The new year, though, has brought new complications, in the form of a study that has been unable to replicate Dr Mikovitss work. Writing in the Public Library of Science, Otto Erlwein of Imperial College, London, and his colleagues report that they are unable to find XMRV in any of almost 200 CFS patients in Britain.

One possible explanation is that one of the two groups of scientists made a mistake in their testing, something that both are adamant is not the case. As scientific punch-ups go, this is shaping up to be a good one, with blows (albeit polite ones) being thrown across the Atlantic.

The Americans say that the British were not looking for DNA directly in white blood cells, and by using whole blood they diluted their samples too much. Kerpow! They add that the design of the British experiment did not prove that it could actually pick up XMRV in patients. Zapp! Finally, they say the British must prove they can actually detect XMRV in one of the American samples, something that they would have been delighted to provide had they been asked. Biff!

For their part, the British insist their controls are just fine and hint that the American laboratory may have had contamination problems. Blam! They also add that a number of other labs are about to publish results of similar studies looking for XMRV and say they are very confident about their findings. Splat!

Frustrating though this may be for sufferers from CFS, it is discussions like these, as one group of researchers tries to replicate the results of another, that lead to scientific progress. In the meantime, one of the companies licensed to do the American XMRV test claims that of the 300 patients, including some from Britain, who have sent samples in for testing, 36% have tested positive for XMRV. It seems likely that the causes of CFS will continue to be a subject of controversy for a while yet.

 

[starryeyes]

Holmsley and all,

There is something very suspicious and unprofessional about this.

Imperial College is very close to me. They didn't need to approach Simon Wessely for blood samples. They should have done their own patients. I am seen under the umbrella of "Imperial College".

Simon Wessely is from a different hospital and not connected to Imperial College at all. So they went "out of area" and deliberately chose to do this.

Imperial College had their own patients to use for a research project. There are seen at a clinic and we have been used for another research project (Dr Kerr's gene expression).

They could have had taken fresh blood samples from a group already studied, defined etc.

Imperial College chose not to do this. My own personal opinion is that they made a mistake.

When sending blood samples to VIP dx in Reno they insist on fresh blood samples. Imperial College chose to use frozen ones from a doctor who has a known psychiatric bias instead of fresh samples from their own CFS clinic.

It may not have been a deliberrate error (psychiatric patients instead) but it does sound like a poor decision and an indication of their poor judgement and haste.

This sounds deliberate to me especially given the history and politics of ME/CFS. Thank you for letting us know about this Alice Band.

 

[Navid]

I kind of knew I'd get asked this and can only answer it honestly, I was sent the original paper by Simon Wessley because I asked him to keep me informed ofany articles of interest which came his way, he obliged. Since receiving that I've discussed and questioned him on many of the questions raised here. I haven't posted any of them because I'm aware how my even speaking to the man will be received.

you are brave to have admitted that here. kudos to you.

regards, lisa : )

 

[Katie]

I kind of knew I'd get asked this and can only answer it honestly, I was sent the original paper by Simon Wessley because I asked him to keep me informed ofany articles of interest which came his way, he obliged. Since receiving that I've discussed and questioned him on many of the questions raised here. I haven't posted any of them because I'm aware how my even speaking to the man will be received.

It might be prudent to ask people's permission to pass questions on. Although this is a public forum and anyone can read this discussion, if you have the opportunity to say "can I run this by Simon Wessely?" it would be a good idea to do that. I can't imagine anyone saying no, if fact they might think a little harder about the question and phrase it in a clearer and more concise way, but I would feel that some might be nervy about our discussions being fed to a person not highly regarded by themselves. It would also be nice to hear his answers if he is willing.

Personally, you can talk to him all you want but I really would advise you communicate how you're using the board in light of the hectic times we are currently experiencing.

On a slightly related note, have you checked out Orla's thread about the psychiatric paradigm in the UK? It's jam packed with papers, references and quotes from the Wessely school. It's in her sig, if you haven't read through it let me know and I'll dig up the link if you can't find it. As I read it I thought it would be right up your alley.

Here's the link, minimal effort, click and read away.
The Psychiatric view of ME/CFS - What is it?

 

[garcia]

I kind of knew I'd get asked this and can only answer it honestly, I was sent the original paper by Simon Wessley because I asked him to keep me informed ofany articles of interest which came his way, he obliged. Since receiving that I've discussed and questioned him on many of the questions raised here. I haven't posted any of them because I'm aware how my even speaking to the man will be received.

Perhaps you should make it more widely known that you are acting as the unofficial spokesman for Simon Wessely so that people don't feel misled? If I'm going to read Wessely's words/opinions on here, I think a minimal courtesy is that they are attributed to him, rather than it being done surreptitiously through the mouth of some third party.

 

[Esther12]

Esther,

Please end the snarky comments.

I was torn between deleting that part of your post and allowing it to stand. I chose the latter, since others have responded but any more such comments and I will have to start editing your posts.

The comment I was replying to was more snarky than my own, yet you did not comment on this. I do not think that you are being fair.

 

[Dx Revision Watch]

@ME Agenda aka Suzy... Great work, Suzy...

You are a very kind Gibbon. Your clear and thoughtful posts are much appreciated.

Answering my own question, here:

From the Imperial College London Press Release:

http://www3.imperial.ac.uk/newsande...wssummary/news_6-1-2010-15-34-39?newsid=80061

"After reading the US study, clinical researchers from King's College London sent
blood samples from 186 CFS patients to the Imperial Retrovirology Laboratory
team. King's has been running an NHS service for CFS patients for nearly twenty
years, and the previously stored samples came from patients had been fully
investigated and examined, meaning that CFS was the correct diagnosis...

 

[starryeyes]

Dr. Yes wrote: By the end of the paper it is unclear whether they used Fukuda only for its psychiatric exclusionary criteria or for all physical selection criteria as well. Was an extra "layer" of physical exclusion placed on the selection process, as the passage you quoted seems to suggest? Were EBV positive (or anything-else-positive) patients removed from the study? And, as ME Agenda asked, were samples taken exclusively from patients who were examined recently or were they stored samples from patients who had been examined by Wessely in the past (perhaps many years ago)?

I wrote to Jennie Spotila regarding these and related concerns and asked if they could be conveyed to Dr. Vernon and the board as questions to publically pose to the IC team (and Wessely in particular), and to voice in a second press release. Jennie said she will pass them on appropriately (thanks, Jennie!). I'm not sure what the best strategy is for getting to the bottom of this issue, but somehow forcing a comprehensive clarification on the public record from Wessely et al is the best I can think of.

Does anyone think we should ask them separately, as well? Especially given that any CAA response will take some time, if they address this vital issue at all?

If so, should we (at this forum) do it jointly?

Yes, we should! Great suggestion Dr. Yes.

 

[fresh_eyes]

Yes, we should! Great suggestion Dr. Yes.

Holmsey says he has been in touch with Wessely. Holmsey, would you be willing to pass a question from us along to Dr. Wessely? *But please don't do so until we have finalized our wording!* :Retro smile:

 

[kwietsol]

Questions for Cort

Cort,

If there is a better place to post this query, let me know.

On your BUZZ page and re-posted by you on (way) earlier on this thread, you quote Suzanne Vernon:

"The U.S. Department of Health and Human Services Blood XMRV Scientific Research Working Group is conducting a rigorous study to detect XMRV. Multiple laboratories will standardize methods to optimize sensitive detection of XMRV proviral DNA and viral RNA and then, once methods are standardized, these same laboratories will test coded panels of blood samples obtained from healthy blood donors and CFS patients. We look forward to the results of this study and urge that it be completed expeditiously, especially in light of this report from the U.K. In the meantime, be prepared to read about more studies with conflicting findings. Rather than simply accept or dismiss new information, we will help make sense of why discrepant results occur."

And then you state:

It sounds like this study will most likely be the gold standard for XMRV study. It may, is more than any other study, be the one that validates does not validate the Whittemore Peterson Institute's findings.


My understanding of the HHS study is that it incorporates the CDC study which is testing samples from the Witchita and Georgia cohorts (as well as samples provided by the WPI).

Three questions:

• Is that your understanding also?
  
  
• And if I'm right there, isn't it true that that portion of the HHS study cannot be regarded as a replication of the WPI study (since the members of the Wichita and Georgia cohorts are not required to meet either the Fuduka or the Canadian Consensus definitions)?
  
  
• And if that is true, even if the WPI samples end up testing 67% positive for XMRV, won't that whole HHS study be vulnerable to political and media spin claiming that XMRV is not a major factor in many/most CFS patients?

If all that is true, I'm uncomfortable with setting up the HHS's forthcoming study as the "gold standard."

 

[Martlet]

The comment I was replying to was more snarky than my own, yet you did not comment on this. I do not think that you are being fair.

I could see nothing objectionable in the original post to which you were replying, especially in light of your earlier comments, whereas your response was way out of line.

 

[usedtobeperkytina]

ok, after a couple of hours catching up, here's my two cents.

I actually liked the Science Now article. I can see some of the criticism, and on a second look, I might agree. But my first read left me the impression that both sides were fairly quoted. I also appreciate that they got comments from Coffin, and included the part about both of them willing to swap samples. Glad to hear that. I mean, why don't they even spend a day in one lab doing it together. Within a week, all of it could be solved. I am glad to see an article that addresses not just a new discovery related to CFS, but one that looks at the controversy itself. Most articles just mention, "mysterious controversial illness that used to be called Yuppie Flu" This article, and the one with the zingers as commentary, posted later, are stories of the controversy and the conflict as an angle.

That is a story by itself. Especially since the controversy and conflict is what impacts the patients the most, leaving them with confusion, and as the article said, anger, in addition to lack of adequate care. I can think of no other illness with as much conflict and controversy right now except Morgellon's. Gulf Ware Syndrome used to be like that. HIV used to be like that. But right now, on the conflict scale, CFS and Morgellon's is top of the list.

Hillary's book took that angle, from a biased point of view. (Please don't get upset. I am not criticizing her work, by no means. It's ok if it is biased, it wasn't a news article, it was a book meant to expose and tell the story of the conflict.) I think both these articles or commentary posted in this thread are fair. And glad to see the conflict / controversy part be the main part of the story. Remember, conflict is one of the things that attracts more news coverage.

Oh and for "the sickest of the sick," I think that just meant they were people who met Canadian and Fukuda criteria, as opposed to the CDD and UK defined CFS patients.

In the public arena, in a matter of public concern, the comments questioning the motive is not a legal problem. Just as a politician's motives are up for debate, so are the motives for a business or non-profit that is selling a product or service. I don't agree and don't see any evidence that bad results are being held back for the purpose of getting more money from the tests. But, I don't see a legal problem with making the accusation, questioning the motives, just as many have questioned the motives of McClure and Wesseley. When someone is in place of public trust, claiming to represent the interests of patients, then whether they are or not is a matter for debate. This would be true of the other non-profit organizations, as well. As long as you are factually correct, in that you give the right price and you accurately say what the money is used for, then the rest is just opinions. Now if any of that information is put out inaccurately, which isn't about motives but proposed facts, then that could be a legal problem.

Maybe we need to do what this man suggested: http://www.youtube.com/watch?v=dib2-HBsF08

Tina

 

[Esther12]

I could see nothing objectionable in the original post to which you were replying, especially in light of your earlier comments, whereas your response was way out of line.

Lets look at this.

I'd be worried if people started seeing this as the big psychiatric vs medical showdown.

I don't have such faith in the WPI (or anyone else), and it seems that the psychiatric model wins by default when there's no compelling evidence of a physical cause, rather than needing to provide their own evidence.

We'll have to wait and see...

I find your comments disingenuous, unsolicited and an insult to the memory of those that have died because of ME, in particular Sophia Mirza.
Not only is there 'compelling' evidence of a physical cause, but there is proof. I am not able to comment further, I am simply too unwell. Reply if you wish, remain silent if you must, but I hope others will condemn your comments, whatever their 'context'.
You have also stated that all this is rather 'exciting'. Please be mindful of the fact that for some this is a life or death struggle.

Kind regards, Mark

Drat - you realised I was cunningly try to slip in an unsolicited insult to Sophia Mirza. Anyway, you're not allowed to condemn my comments now - Bwah-ha-ha!

I said that I would be worried if this started to be seen as the big showdown between those who think CFS is psychological vs physical, as I'm not sure the WPI results will hold up, and that could be interpreted as a win by default for the psychologists.

I was then accused of being dishonest. I was told that my comments were an insult to those who have died of ME, especially Sophia Mira.

I then made fun of these absurd accusations.


You think that my reply was out of line? I'd be interested to hear your reasoning.

 

[fresh_eyes]

I understand that people may want to dispute the modding, but would you consider taking it to pm, or perhaps its own thread? There's enough actual info to wade through here without adding multiple posts objecting to a single instance of moderation.

 

[Esther12]

I understand that people may want to dispute the modding, but would you consider taking it to pm, or perhaps its own thread? There's enough actual info to wade through here without adding multiple posts objecting to a single instance of moderation.

Sorry. I'll move it to the discussion of forum rules, as it seems relevent to that.

 

[fresh_eyes]

Thanks, Esther12 - appreciate it.