Proposition to put the XMRV discussion here on a more profound and scientific basis

[Sam Carter]

I was replying to a specific point raised in a previous post, and it looks like I over-simplified my discussion.

To answer your point, I'll refer to you Annette Whittemore's list of differences in the methodologies:
http://treatingxmrv.blogspot.com/2011/06/comparison-of-methods-for-detection-and.html

Thanks for the link Bob.

I'm not comfortable with the inconsistent arguments presented against researchers whose findings are not in accordance with Lombardi and colleagues. It is often said that PCR-only studies are inadequate, yet the Lo/Alter paper was welcomed as a positive confirmation, as is the unpublished work of Maureen Hanson.

If Lombardi / Lo claim that XMRV/MLVs can be be detected in the blood of people with ME and healthy controls using PCR then other groups should be able to reproduce their results.

 

[Bob]

Thanks for the link Bob.

I'm not comfortable with the inconsistent arguments presented against researchers whose findings are not in accordance with Lombardi and colleagues. It is often said that PCR-only studies are inadequate, yet the Lo/Alter paper was welcomed as a positive confirmation, as is the unpublished work of Maureen Hanson.

If Lombardi / Lo claim that XMRV/MLVs can be be detected in the blood of people with ME and healthy controls using PCR then other groups should be able to reproduce their results.

Well, I find that there are very inconsistent, and uninformed, arguements are coming from people who have decided that XMRV is a contaminant.

Lo has very specifically said that other researchers have not replicated the WPI's methodology in the careful way that he has. So there's your answer to that. I can give you a link to his quote if you want it. It ties in neatly with the link I gave you for the list of methodology comparisons.

I'm not comfortable when the researchers who can't find XMRV declare that because they can't find it, it doesn't exist, even though there is plenty of research that says it does exist. It just seems like stupidity to me. I can give you a long list of published positive XMRV research papers if you would like one.

Some of us wish to see XMRV research continue so that we can get a full picture of the facts. I don't understand why people want to shut down XMRV research. There is absolutely no reason to stop XMRV research, just because the evidence is inconclusive at this stage.

 

[Sam Carter]

...

Lo has very carefully said that other researchers have not replicated the WPI's methodology in the careful way that he has. So there's your answer to that. I can give you a link to his quote if you want it. It ties in neatly with the link I gave you for the list of methodology comparisons.

...

Which parts of Lombardi did Lo replicate?

 

[Bob]

Which parts of Lombardi did Lo replicate?

Lo specifically mentioned that he was careful to accurately replicate specific details like the annealing temperature and magnesium concentration, whereas other researchers hadn't done so. I can find a link to his presentation if you want it.

 

[Sam Carter]

Lo specifically mentioned that he was careful to accurately replicate specific details like the annealing temperature and magnesium concentration, whereas other researchers hadn't done so. ...

Any culturing? Serology?

And what about the internal primers? Same / different? Always the same / sometimes different?

Lo was fishing, Bob, and that's no bad thing.

 

[Bob]

Any culturing? Serology?

And what about the internal primers? Same / different? Always the same / sometimes different?

I can give you links to the all details if you are interested Sam.

Lo was fishing, Bob, and that's no bad thing.

I don't understand what you mean Sam?

 

[Sam Carter]

I can give you links to the all details if you are interested Sam.



I don't understand what you mean Sam?

No probs, Bob, I don't think we're heading towards a consensus here!

Can we call a truce? (I need my bed and although I'm sure between us we could resolve the role of XMRV in human disease I'm minded to suggest we leave it, for now at least, to Ian Lipkin and the BWG )

 

[WillowJ]

This is widely accepted amongst M.E/CFS affected people as being an unchallengeable given, IMO however it is a fundamentally flawed proposition. For criteria sets to act as confounding aspects in research designed to identify potential causative agencies, competing sets would have to be so divergent as to produce patient cohorts that were 100% mutually exclusive of one another. None of the proposed sets of diagnostic criteria come anywhere near to doing that; even Reeves, which must be the least satisfactory of all, would allow inclusion of individuals who would meet the Canadian criteria at rates which would be meaningful in anything other than unreasonably small study numbers.

This is not necessarily the case, because Reeves and Oxford do not merely include anyone who who is persistently fatigued, but they may also exclude persons who do not fit their idea of who is CFS-ish, in their idea of what CFS is (i.e. they believe it to be stress-related fatigue, burnout, depression, but not related to ongoing infection or neurological disease). So if you look at, for instance, the Switzer paper where they did not find XMRV in persons with Reeves disease, you will see the authors specifically criticise the Canadian criteria thus:

The Lombardi et al. study specifies that samples were selected from patients fulfilling the 1994 international CFS case definition [23] and the 2003 Canadian Consensus Criteria for CFS/ME [sic] [25]... The 1994 International CFS case definition and the Canadian Consensus Criteria are different and do not necessarily identify similar groups of ill persons.

Most notably, the Canadian Criteria include multiple abnormal physical findings such as spatial instability, ataxia, muscle weakness and fasciculation, restless leg syndrome, and tender lymphadenopathy. The physical findings in persons meeting the Canadian definition may signal the presence of a neurologic condition considered exclusionary for CFS and thus the XMRV positive persons in the Lombardi et al. study may represent a clinical subset of patients [11].

Reeves is suspicious of such findings as tender lymphs (!), balance problems, muscle weakness, muscle twitches, gait changes, and restless legs. This is an extraordinary complaint because one of these is Fukuda-diagnostic, and others of these appear on the 2003 CDC update containing a list of noted signs and symptoms.

Be that as it may, persons meeting Canadian criteria are not necessarily eligible to be included under the broader Reeves and Oxford rubrics, at least not when used for research purposes.

 

[Bob]

Can we call a truce? (I need my bed and although I'm sure between us we could resolve the role of XMRV in human disease I'm minded to suggest we leave it, for now at least, to Ian Lipkin and the BWG )

Yes, I'm happy to do that Sam.
But I can't understand why you feel so strongly about the subject.
There is obviously a reason why I have strong feelings about the subject - because I would like to see the research be allowed to run its course.
But I don't understand why someone who believes that XMRV is contamination, just doesn't watch the research unfold, content that science is taking its course.

 

[joshualevy]

I would like someone to please provide me with one single piece of conclusive evidence that XMRV is contamination.

One piece?

Sigh. The DNA sequences checked into genbank by Dr. Mikovitz (et al) show the very minor differences of a contaminate, and not the much bigger differences that would be seen if there were an infection.

Every Virologist, who is not on the WPI payroll, who has looked at these sequences (the first three, or the larger group added in May) has said the same thing: those sequences are direct evidence of contamination, and evidence that there is no actual infection with XMRV. This includes the crew at TWIV, as examples of several different Virologists, none of whom "have skin in the game" and all of whom make it clear that those sequences show contamination. (Listen to TWIV #136.)

If you think otherwise, find a quote from a Virologist (not paid by WPI) who has looked at those genbank sequences and says they are not contamination.

Joshua (not Jay!) Levy

 

[Bob]

Sigh. The DNA sequences checked into genbank by Dr. Mikovitz (et al) show the very minor differences of a contaminate, and not the much bigger differences that would be seen if there were an infection.

Every Virologist, who is not on the WPI payroll, who has looked at these sequences (the first three, or the larger group added in May) has said the same thing: those sequences are direct evidence of contamination, and evidence that there is no actual infection with XMRV. This includes the crew at TWIV, as examples of several different Virologists, none of whom "have skin in the game" and all of whom make it clear that those sequences show contamination. (Listen to TWIV #136.)

If you think otherwise, find a quote from a Virologist (not paid by WPI) who has looked at those genbank sequences and says they are not contamination.

Joshua (not Jay!) Levy

Why are you 'sighing' at my question josh? That's not a very friendly or supportive way to start a response.

Josh, you keep on repeating the same argument, but you haven't been receptive to the counter-arguements, and haven't considered all of the evidence.

As people have already explained, similar virus sequences do not confirm contamination, for two reasons: 1) Infection could be caused through another route such as vaccines. 2) XMRV could behave like HTLV, which has a very low mutation rate.
There are possibly also other reasons that we haven't even considered, as we know so little about this novel virus.

"The crew at TWIV" have not written a conclusive peer reviewed paper on the nature and implications of the variation of the new sequences, so I suggest we hold off before announcing conclusive evidence based on an episode of TWIV, or an amateur discussion on TWIV's discussion page. The analysis that I've seen suggests that there is a higher degree of variability in the new sequences.

When you say "every virologist", I would like to see evidence of this.

But whatever the status of the new sequences, they do not provide conclusive evidence of contamination, as I have explained.

It's interesting that you are not open to the possibility that XMRV is not a contaminant when there is no conclusive evidence that it is a contaminant.

 

[markmc20001]

Sigh. The DNA sequences checked into genbank by Dr. Mikovitz (et al) show the very minor differences of a contaminate, and not the much bigger differences that would be seen if there were an infection.

Every Virologist, who is not on the WPI payroll, who has looked at these sequences (the first three, or the larger group added in May) has said the same thing: those sequences are direct evidence of contamination, and evidence that there is no actual infection with XMRV. This includes the crew at TWIV, as examples of several different Virologists, none of whom "have skin in the game" and all of whom make it clear that those sequences show contamination. (Listen to TWIV #136.)

If you think otherwise, find a quote from a Virologist (not paid by WPI) who has looked at those genbank sequences and says they are not contamination.

Joshua (not Jay!) Levy

Just a quick point here folks. My two cents. You can all carry on.

Regarding this statement:

"Every Virologist, who is not on the WPI payroll, who has looked at these sequences (the first three, or the larger group added in May) has said the same thing: those sequences are direct evidence of contamination, and evidence that there is no actual infection with XMRV"

During the recent BP oil spill disaster in the Gulf of Mexico. BP hired, or tried to hire, about every available Gulf area scientist available to work for BP. It seems like a effective tactic if one has enough money.

http://uwire.com/2010/08/05/bp-buying-time-buying-truth-and-buying-people/

The company has approached numerous gulf area scientists, offering $250/hour and a healthy bonus to join BP as consultants. And now, as National Public Radio reports, some are worried that the brightest minds are being paid to keep quiet about the true nature of the spill.

Bob Shipp, a marine biologist at U. Southern Alabama, says that BP tried to hire his entire department to do research on the spill. But the contract prohibited them from publishing their findings without BPs consent, or until after three years pass.

They wanted the oversight authority to keep us from publishing things if, for whatever reason, they didnt want them to be published, Shipp said when interviewed for the NPR story. People were muzzled as part of the contract. They were muzzled, and certainly its not something we could live with.

 

[WillowJ]

Just a quick point here folks. My two cents. You can all carry on.

Regarding this statement:

"Every Virologist, who is not on the WPI payroll, who has looked at these sequences (the first three, or the larger group added in May) has said the same thing: those sequences are direct evidence of contamination, and evidence that there is no actual infection with XMRV"

During the recent BP oil spill disaster in the Gulf of Mexico. BP hired, or tried to hire, about every available Gulf area scientist available to work for BP. It seems like a effective tactic if one has enough money.

are you saying the virologists not working for WPI are working for the government? or the best virologist are working for WPI? or what?

 

[jace]

Jemal, at 7.16pm, quotes from a paper in PlosONE http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019953

Here is another quote from that paper,

We do not believe that our observations serve to indicate that XMRV/pMLV sequences detected ex vivo in human materials inevitably will have come from the amplification reagents. Nor for that matter can we explain how in some studies there have been very significant differences between the detection rates in cases and comparator groups.

The authors? Philip W. Tuke, Kate I. Tettmar, Asif Tamuri, Jonathan P. Stoye, Richard S. Tedder

 

[In Vitro Infidelium]

Hmm, that's a very negative view of the ME community. And it's a sweeping generalisation. It seems that you've completely missed the point in relation to some of our attitudes towards some researchers. Many of us in the ME community want to see XMRV research continue until enough research has been carried out so that we know the facts. I think this is a very reasonable, scientific and logical position to take.

What is the "M.E community" ? What is the qualification to 'belong, and Who is entitled to speak for 'it' ? The notion of a single monolithic entity "The M.E Community" seems to me to be wholly fanciful and to function only as a defencible 'us v them' construction in which even 'non believing' M.E/CFS affected people are consigned to the 'them' as heretical.

I don't consider M.E/CFS affected people when acting as groups, to be above criticism. The group behaviour of M.E/CFS affected people in relation to XMRV has been in large measure both anti science (partialism) and deeply flawed from a public relations perspective. Waverunner's contention is that the involvement of expert opinion, which by its very nature has to be accepted with a degree of deference - otherwise there's no acknowledgement of the 'expertness' - would assist forum discussion. However as is acknowledge there are 'experts' who are considered unacceptable, merely on the basis that their expressed expert opinion does not accord with the views of some M.E/CFS affected people. On that basis why would any 'expert' accept an invitation to participate, knowing that they would likely face an endless round of inexpert circular argument ? Waverunner's contention seems wholly reasonable, therefore the fact that it is not achieveable stands as a potential criticism of how M.E/CFS affected people (us !) are conducting themselves. Of course one can defend the staus quo, and those who express disatisfaction can be characterised as 'offenders of the community' but some 'community members' may feel constrained to ask whether that really is the most effective way to make progress.

IVI

 

[ukxmrv]

It's in the eye of the beholder though IVI

Where is the "inexpert circular argument" here that this hypothetical expert would run up against?

Patients on this forum regardless of their views seem to be able to put forward good arguments for both sides.

There are areas of dispute even amoung Virologists and there are areas we simply do not have the answers for as yet. My guess would be that is where the disputes would come from. When we start trying to fill in those areas with theories.

It would be up to the moderator to ensure that any poor behaviour on behalf of the patients or on behalf of the expert is kept under control.

I think Waverunner should be left to talk for him / herself as that appears to be a not very subtle criticism of both the patients here and the moderators.

 

[In Vitro Infidelium]

This is not necessarily the case, because Reeves and Oxford do not merely include anyone who who is persistently fatigued, but they may also exclude persons who do not fit their idea of who is CFS-ish, in their idea of what CFS is (i.e. they believe it to be stress-related fatigue, burnout, depression, but not related to ongoing infection or neurological disease). So if you look at, for instance, the Switzer paper where they did not find XMRV in persons with Reeves disease, you will see the authors specifically criticise the Canadian criteria thus:

..........................The physical findings in persons meeting the Canadian definition may signal the presence of a neurologic condition considered exclusionary for CFS ..............................

.....................persons meeting Canadian criteria are not necessarily eligible to be included under the broader Reeves and Oxford rubrics, at least not when used for research purposes.

Reeves is undoubtedly of questionable value - the point is that even Reeves doesn't serve to exclude all those who would likley meet the CCC - Reeves and the CCC laying at the two extremes of inclusiveness and exclusiveness of criteria sets. I'm not clear whether Switzer et al are actually saying that 'any evidence of 'neurological' symptoms is a basis for exclusion from a CFS diagnosis - if they are that is an a extreme conclusion. My assumption is that what that part of the text implies is that the CCC may prduce evidence of identifiable neurological conditions (i.e something that could be named other than CFS)), which would indeed exclude M.E/CFS, which would accord with Fukada, NICE and Oxford. Oxford is often misrepresented as excluding all possible neurological evidence - that isn't the case, it excludes 'known neurological conditions'.

IVI

 

[Bob]

What is the "M.E community" ? What is the qualification to 'belong, and Who is entitled to speak for 'it' ? The notion of a single monolithic entity "The M.E Community" seems to me to be wholly fanciful and to function only as a defencible 'us v them' construction in which even 'non believing' M.E/CFS affected people are consigned to the 'them' as heretical.

Then why do you keep making such sweeping generalisations then, where you insult the entire patient population in your posts?

 

[Bob]

I don't consider M.E/CFS affected people when acting as groups, to be above criticism. The group behaviour of M.E/CFS affected people in relation to XMRV has been in large measure both anti science (partialism) and deeply flawed from a public relations perspective.

You are making sweeping generalisations again... So we aren't a community, but we do act in groups? And we act irrationally and unreasonably in groups, because we are anti-science? Like 'pack' behavior? And we are deeply flawed. You have interesting views on the ME patient community.

I'd like you to demonstrate this 'anti-science' to me please because, in my opinion, this is a very scientific forum where we rigorously discuss, assess, scrutinise, criticise, employ and utilise the science all the time.

As for public-relations, we aren't a public relations company. We are patients with a disease. So it is up to us, as individuals, how we wish to represent ourselves in public. And your opinion about how our behaviour would be assessed, by a public relations manager, is a subjective view for starters, but it is also an inappropriate way to assess what patients are trying to achieve, and is irrelevant to me.

When people are trying to achieve fundamental change in society, they don't always worry about how they superficially present themselves.
Are we trying to achieve fundamental change? I think we are, specifically in relation to how our disease is treated by the establishment.

We are a minority group that is treated abysmally by the medical establishment and the government.
When other groups in history have achieved change, they have often done so by making a nuisance of themselves, and not with a glossy public relations exercise.

For example, when the suffragettes were campaigning to get the vote, they weren't thinking about if they looked presentable enough to get on the front cover of Vogue everyday, or whether their actions might upset some establishment figures. They were purposefully making a nuisance of themselves. I expect that a lot of people, especially men, thought that they were going about things in the wrong way, and making too many enemies, and doing themselves a disservice by ruffling so many establishment feathers. But in the end, it was by loud and disruptive action that they achieved results. This has been repeated throughout history time and time and time again.

Waverunner's contention is that the involvement of expert opinion, which by its very nature has to be accepted with a degree of deference - otherwise there's no acknowledgement of the 'expertness' - would assist forum discussion.

Well, you can go through your life differing to authority if you want to. That is up to you. Others choose to scrutinise authority and to challenge it when appropriate.

 

[In Vitro Infidelium]

Select your patients carefully. Take the time. Subject them to gene arrays on liver, muscle and PBMCs. Do this again after moderate exercise - "CFS" is an illness revealed by challenge - and crunch the numbers. Then we can get started.....

That's a very workable research description - but what percentage of those who currently have a CFS diagnosis, have a condition that isn't evidenced substantially as "an illness revealed by challenge" ? If we are happy to use high illness population numbers for PR purposes, doesn't it bespeak a certain hypocrisy to actually envisage a much lower number as actually being worthy of illness research ? There is anyway a practical problem - how to get multiple research teams, Health Services and medical disciplines to agree a new criteria set/disease description ? Neither Fukada or NICE would exclude people from a "CFS" is an illness revealed by challenge" research approach, prevalence figures may be skewed but that's not relevant if causation or disease processes are the focus of research. New criteria set and or disease description is not a campaign that could be won any time soon, meanwhile research could be pursued, accepting Fukada/NICE as good enough, while disputing Reeves and other ad hoc rewrites (PACE), and encouraging subtyping where appropriate is a way forward.

IVI