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Science asks authors to retract XMRV/CFS paper

Jemal

Senior Member
Messages
1,031
And also, from Mindy's CFS Central blog: "the Mikovits study found antibody reactions to XMRV in patients. You don't get an antibody reaction to a contaminant.

The contaminists are saying that the human body could produce non-specific antibodies to a contaminant. That sounds plausible as well, so I am not sure what to believe regarding this particular issue? Has it been proven the antibodies are specific to XMRV?
 

Angela Kennedy

Senior Member
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1,026
Location
Essex, UK
The contaminists are saying that the human body could produce non-specific antibodies to a contaminant. That sounds plausible as well

Um- the human body produces non-specific antibodies to an XMRV contaminant, AWAY from the body, IN THE LAB FRIDGE, i.e. the BLOOD produces antibodies in the fridge?

Edit- I'm questioning the above scenario by the way- thought I'd better make that clear... :rolleyes:
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
For whatever reason WPI is continuing to promote XMRV after there is strong evidence it is a lab creation, non viable in humans, and common contaminant. They are using old technologies, probably because the newer technologies prove XMRV is a contaminant.

1. XMRV maybe a lab creation, but that doesn't mean it isn't a wild human virus. Even Switzer of the CDC now says it is a human virus.
2. There is plenty of evidence to say XMRV is viable in humans. How do you come to the conclusion that it isn't?
3. No one has yet found XMRV contaminating any equipment, or reagents, anywhere, as far as I am aware. Where is the evidence that it is a contaminant?
4. Mikovits and Lo have used many different means to search for contamination. There is a scientific dispute about which is the best and most effective technology to use to search for contamination.
 

Bob

Senior Member
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16,455
Location
England (south coast)
The contaminists are saying that the human body could produce non-specific antibodies to a contaminant. That sounds plausible as well, so I am not sure what to believe regarding this particular issue? Has it been proven the antibodies are specific to XMRV?

Yes, I'm not sure about that either Jemal. I thought that the WPI's antibody test isn't 100% specific, but I don't fully understand this area of their research.

Um- the human body produces non-specific antibodies to an XMRV contaminant...

So is it not possible to have a virus-specific anti-body then?
 

kurt

Senior Member
Messages
1,186
Location
USA
So what are your thoughts on Lo/Alter's findings? As far I can tell, the contamination theories do not apply to them. Also how exactly does XMRV not fit in the epidemiology of CFS? It's really annoying to read about people saying how unscientific the WPI is and in the same breath make absolute statements with no supporting evidence.

There is no evidence I am aware of that CFS is a blood-borne infection. Outbreaks suggest a different epidemiology.
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Yes, exactly, if those antibodies were non-specific antibodies to some contaminant, then what contaminant is statistically significantly found more often in the bodies of people with ME/CFS compared to healthy people?
I don't believe this anyway, but even if it was true it would mean we have a problem, wouldn't it? How did that "contaminant" get into our bodies?
This "excuse" doesn't make sense at all to me...
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
2. There is plenty of evidence to say XMRV is viable in humans. How do you come to the conclusion that it isn't?
I think the latest Coffin study concluded this (or it might have been the other one). This does of course not necessarily mean it's true...
3. No one has yet found XMRV contaminating any equipment, or reagents, anywhere, as far as I am aware. Where is the evidence that it is a contaminant?
What was it that Ila Singh found on her equipment? Was it mouse material containing mouse endogenous retroviruses (and not XMRV)? And what was it in Brigitte Huber's case?
 

eric_s

Senior Member
Messages
1,925
Location
Switzerland/Spain (Valencia)
Everyone is entitled to their own view here without being put-down, my view is that until we get validating evidence of XMRV in CFS from a majority of labs running modern tests, the consensus that has emerged that there is some type of problem with XMRV testing is probably correct.
Ok, fair enough, but i think in a case where there is something that for whatever reason is very difficult to find (which might be the case here) your way of reaching a conclusion might lead you to believe it's not there when it actually is. And this might be dangerous, because it could mean research is being stopped before the truth is found.

I think if there is even one serious lab (and now it's more than one and some of the people involved are of the highest caliber) reporting a finding in a sufficently convincing study (mutliple types of assays, multiple labs involved etc.) and they stick to it and there is no evidence something in their lab went wrong, i want to know what happened.
 

Bob

Senior Member
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16,455
Location
England (south coast)
There are various levels of proof in science. What Stoye probably means by 'no definitive proof' is that a verifiable source of contamination in the original WPI study has not been found. Other study authors have suggested contamination studies that apparently WPI has not run, and unless WPI runs them and finds contamination there can be no definitive proof (I refer to tests such as IAP and using dUTP-UNG for nested PCR).

The type of proof that Stoye is inferring by saying that XMRV in CFS is a myth is the proof of a scientific consensus process, which might be considered a preponderance of evidence that a hypothesis is true (or false in this case).

But you don't have to prove exactly how a study is wrong to prove it is wrong. If multiple follow-on studies calibrated to similar or superior standards of accuracy to the original, fail to find the target organism, the preponderence of evidence proves that the original study was flawed. This is the development of a scientific consensus, which Stoye believes has proven XMRV in CFS to be a myth.

WPI does not have to agree, and this is a free country, they can continue studying XMRV as long as they like. But they may not make scientific claims about XMRV or their testing without violating accepted scientific ethics when a consensus view is accepted by the retroviral community. All researchers must accept the process of science, to have any credibility. You can't just accept scientific processes when they decide in your favor.

The WPI have given a reason for why they do not wish to use the IAP test, and that is that there are concerns that it can show false positives for contamination. I can't remember all the details, but they seemed legitimate to me when I read about them.
There seem to be scientific disagreements about which are the best tests to use to search for contamination.
Alter says that he has run better tests than anything Coffin has used.

XMRV is a novel virus which, if a human virus, is likely to exist in extremely low copy numbers in the blood.
Maybe established methodologies just can't detect it easily in the blood, whereas it is easier to detect it in tissues such as prostate cancer.
Switzer of the CDC has confirmed that this is the case, and has admitted that he is unable to detect the virus in the blood using existing technologies in XMRV+ prostate cancer patients.

To me, it seems like arrogance for some researchers to say that they have used superior technologies, and so because they can't find XMRV, then this is proof that it doesn't exist.

Consensus is not proof, it is just consensus. So, in which case, why are Stoye and others trying to close down XMRV research? It is one thing to declare your beliefs, but quite another to aggressively try to close down a legitimate area of research.

What is their agenda? It certainly isn't the welfare of CFS patients.
I would have thought that a better scientific approach to the situation would be to say that there are a number of very interesting studies that suggest that XMRV is a human retrovirus that some other researchers have not been able to replicate, so we will continue researching to see if we can get to the bottom of the differences.

Where is the scientific curiosity to get to the bottom of the subject?

Stoye has used some very strong and personal language against both the WPI and XMRV, and it doesn't seem to be a dispassionate, disinterested, objective scientific position that he is taking, or language that he is using.

Why are we reading all of these aggressive statements against XMRV researchers and the entire ME community by a whole range of scientists and researchers?
Why the need to accuse the ME community all the time?

This isn't science that we are seeing at play. It's politics.


We will find out all of the answers about XMRV.
All I ask for is for people to keep an open mind, and to remember who our friends are.
If XMRV does come to nothing, then we will need to stick together as a community, and stick up for those researchers who support us.

We will never hear from Coffin and Stoye again if XMRV disappears, but we will be hearing a heck of a lot from the likes of Wessely, White, Sharpe and Chalder.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
What was it that Ila Singh found on her equipment? Was it mouse material containing mouse endogenous retroviruses (and not XMRV)? And what was it in Brigitte Huber's case?

As far as I'm aware, no one has specifically found XMRV as a contaminant. Only MLV's or MLV-like sequences, as far as I'm aware.
 

kurt

Senior Member
Messages
1,186
Location
USA
1. XMRV maybe a lab creation, but that doesn't mean it isn't a wild human virus. Even Switzer of the CDC now says it is a human virus.
2. There is plenty of evidence to say XMRV is viable in humans. How do you come to the conclusion that it isn't?
3. No one has yet found XMRV contaminating any equipment, or reagents, anywhere, as far as I am aware. Where is the evidence that it is a contaminant?
4. Mikovits and Lo have used many different means to search for contamination. There is a scientific dispute about which is the best and most effective technology to use to search for contamination.

Good questions. The evidence XMRV is viable in humans is based on WPI's/VIP's assay, which can not currently be validated by RT-PCR techniques, or even by other labs running the older nested PCR assays using accepted chemical decontamination processes (Singh tried). If WPI wants to prove their point they need to provide a step-by-step process that any lab can run and find XMRV. The argument that more advanced PCR is somehow unable to detect a the XMRV gene sequence just does not work with people who know PCR testing.

The evidence of contamination is indirect. However, WPI might not be running the tests required to detect their issues, as you point out, there are differences of opinion on how to find contamination.

WPI may end up standing alone in this and I think reasonable people have to ask if this is really because everyone else in the retrovirology community is incompetent or morally bankrupt.
 

Jemal

Senior Member
Messages
1,031
Yes, exactly, if those antibodies were non-specific antibodies to some contaminant, then what contaminant is statistically significantly found more often in the bodies of people with ME/CFS compared to healthy people?
I don't believe this anyway, but even if it was true it would mean we have a problem, wouldn't it? How did that "contaminant" get into our bodies?
This "excuse" doesn't make sense at all to me...

Well, what if the contaminant was added in the lab somehow, because of a reagant for example. The sample is then contaminated.
My question still stands I think: is it possible the WPI are detecting non-XMRV-specific antibodies?

I am playing devil's advocate here by the way! If the WPI is detecting XMRV specific antibodies, great.
 

kurt

Senior Member
Messages
1,186
Location
USA
The contaminists are saying that the human body could produce non-specific antibodies to a contaminant. That sounds plausible as well, so I am not sure what to believe regarding this particular issue? Has it been proven the antibodies are specific to XMRV?

Last I heard nobody has found XMRV-specific antibodies that have been verified. Antibodies can be cross-reactive, and antibody studies are only suggestive of a class of infection and not as specific as PCR testing. For all we know the MLV and other antibodies that are reacting in CFS samples could be cross-reactive to other viruses or even HERVs. We do know that CFS patients carry more viral activations and co-infections than controls, so logically we are more likely to have antibody reactions and cross-reactions.
 

Angela Kennedy

Senior Member
Messages
1,026
Location
Essex, UK
Just to be clear, what is being said here is that the actual blood, of ME/CFS sufferers, produces antibodies to contaminants, outside the body, in the fridge (after the little mice have run amok and dipped their XMRV infected toes in that blood)?
 

kurt

Senior Member
Messages
1,186
Location
USA
The WPI have given a reason for why they do not wish to use the IAP test, and that is that there are concerns that it can show false positives for contamination. I can't remember all the details, but they seemed legitimate to me when I read about them.
There seem to be scientific disagreements about which are the best tests to use to search for contamination.
Alter says that he has run better tests than anything Coffin has used.

The labs that found contamination with IAP were able to narrow down the source and eliminate the contamination source (a reagent), then when they dealt with the problem the IAP came up negative. So the IAP worked for them.

XMRV is a novel virus which, if a human virus, is likely to exist in extremely low copy numbers in the blood.
Maybe established methodologies just can't detect it easily in the blood, whereas it is easier to detect it in tissues such as prostate cancer.

That is a possibility, but then we have to ask how WPI detected XMRV in the first place with a basic PCR test?

Switzer of the CDC has confirmed that this is the case, and has admitted that he is unable to detect the virus in the blood using existing technologies in XMRV+ prostate cancer patients.
To me, it seems like arrogance for some researchers to say that they have used superior technologies, and so because they can't find XMRV, then this is proof that it doesn't exist.

Perhaps that is arrogance, but I think we are seeing plenty of arrogance on both sides of this debate.

Consensus is not proof, it is just consensus. So, in which case, why are Stoye and others trying to close down XMRV research? It is one thing to declare your beliefs, but quite another to aggressively try to close down a legitimate area of research.

Stoye and others don't have the ability to close down XMRV research, labs can continue studying XMRV. The scientific situation here in the US is not authoritarian, not a socialistic system. They just feel strongly about their views and promote them, everyone is doing that. But Stoye and others are stating the obvious, and the emerging consensus may make it difficult for labs to get public funding for XMRV studies that just attempt to repeat what we already know. However, if someone came up with a new angle and a new hypothesis that had not been disproven yet, they should still qualify for funding.

What is their agenda? It certainly isn't the welfare of CFS patients.
I would have thought that a better scientific approach to the situation would be to say that there are a number of very interesting studies that suggest that XMRV is a human retrovirus that some other researchers have not been able to replicate, so we will continue researching to see if we can get to the bottom of the differences.

I think their agenda is to promote empiricism in CFS research, they are persuaded by the data. There is no indication they don't care about the welfare of CFS patients, I suspect they believe they are protecting CFS patients. But I agree with your suggestion, more even-handed position statements would be nice from all parties.

We will find out all of the answers about XMRV.

Indeed we will eventually. I would not be surprised if there will have to be adjustments in many of the views on both sides of this debate.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Hi, the problem with human antibodies to pathogens is they are based on targeting relatively short amino acid sequences. Many proteins in the body, either endogenous or introduced (such as from gut bacteria) might be targets of the same antibodies. So the presence of an antibody to XMRV might not be because of XMRV at all - this kind of evidence is secondary, used to support other lines of evidence. I think there was a paper some time ago (last year?) that discussed anti-XMRV antibody targets, and listed a few possibilities that were native proteins. I do not recall the details, does anyone remember it? Bye, Alex
 

Bob

Senior Member
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16,455
Location
England (south coast)
Good questions. The evidence XMRV is viable in humans is based on WPI's/VIP's assay, which can not currently be validated by RT-PCR techniques, or even by other labs running the older nested PCR assays using accepted chemical decontamination processes (Singh tried). If WPI wants to prove their point they need to provide a step-by-step process that any lab can run and find XMRV. The argument that more advanced PCR is somehow unable to detect a the XMRV gene sequence just does not work with people who know PCR testing.

I just ask that the WPI be given the space to do the research that they want to do, without people with their own agendas trying to close down the research. If established methodologies don't work, then maybe the researchers should try to be innovative, like Judy Mikovits has been. I agree that the WPI need to provide a step-by-step process, but many other researchers are only interested in doing things in their own established ways anyway. But this will all be resolved in the end. There are other researchers finding XMRV now, so it's not just the WPI.

WPI may end up standing alone in this and I think reasonable people have to ask if this is really because everyone else in the retrovirology community is incompetent or morally bankrupt.

I think the words that I would use are 'arrogant' or 'over-confident' or 'lacking in curiosity'.
When scientists say "I didn't find XMRV so it doesn't exist", then all I see is bias and arrogance.
But if a scientist says "I didn't find XMRV, and I would like to find out why my results are different to the positive XMRV studies", then I would feel some respect.

I would not be surprised if there will have to be adjustments in many of the views on both sides of this debate.

I will be happy to adjust my views when presented with evidence.

I will be content if XMRV is proved to be a contaminant, whereas you seem to have already made up your mind that it is a contaminant without solid evidence, but with only theories and negative studies to go by.

That's what I don't understand, however much you talk about consensus.

If we take your consensual approach to science, in its purest form, and commit ourselves to only take a consensus view, then the world would still be flat, and the Sun would still revolve around the Earth.

Anyway, I can't see us agreeing about the subject. Whereas you see Stoye, Coffin et al. as being on the scientific and moral high ground, and I see the complete opposite.

I see their behaviour as being rather bullying because I can't see how they could be so passionate about a negative... About something that they believe isn't there.

If they believe that XMRV isn't there, then that's fine... Forget about it, and let others get on with the research.

I understand the WPI being passionate about the subject, because they believe in their science, and they believe that they have discovered an active virus.

Kurt, maybe you haven't read all of the comments from Stoye, but I don't really see how they can be defended, when other scientists are just trying to get on with their work, researching something that they believe passionately about.
 

Jemal

Senior Member
Messages
1,031
Hi, the problem with human antibodies to pathogens is they are based on targeting relatively short amino acid sequences. Many proteins in the body, either endogenous or introduced (such as from gut bacteria) might be targets of the same antibodies. So the presence of an antibody to XMRV might not be because of XMRV at all - this kind of evidence is secondary, used to support other lines of evidence. I think there was a paper some time ago (last year?) that discussed anti-XMRV antibody targets, and listed a few possibilities that were native proteins. I do not recall the details, does anyone remember it? Bye, Alex

Thanks for the explanation Alex!

I think the words that I would use are 'arrogant' or 'over-confident' or 'lacking in curiosity'.
When scientists say "I didn't find XMRV so it doesn't exist", then all I see is bias and arrogance.
But if a scientist says "I didn't find XMRV, and I would like to find out why my results are different to the positive XMRV studies", then I would feel some respect.

I think we have seen a lot of arrogance, from both sides really. It seems to be a side effect of certain titles...
If it was all so easy, we would have cured both ME/CFS and HIV by now. But it is not so easy and there's still a lot these scientists don't know.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
The evidence XMRV is viable in humans is based on WPI's/VIP's assay, which can not currently be validated by RT-PCR techniques, or even by other labs running the older nested PCR assays using accepted chemical decontamination processes (Singh tried).

You are only taking into account the research relating to CFS. There is other evidence that suggests that XMRV is a human virus. Singh, for example, believes that it is a human virus, so does Switzer. They just don't buy into the association with CFS.
 

kurt

Senior Member
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1,186
Location
USA
I just ask that the WPI be given the space to do the research that they want to do, without people with their own agendas trying to close down the research. If established methodologies don't work, then maybe the researchers should try to be innovative, like Judy Mikovits has been. I agree that the WPI need to provide a step-by-step process, but many other researchers are only interested in doing things in their own established ways anyway. But this will all be resolved in the end. There are other researchers finding XMRV now, so it's not just the WPI.

I think the words that I would use are 'arrogant' or 'over-confident' or 'lacking in curiosity'.
When scientists say "I didn't find XMRV so it doesn't exist", then all I see is bias and arrogance.
But if a scientist says "I didn't find XMRV, and I would like to find out why my results are different to the positive XMRV studies", then I would feel some respect.

I will be happy to adjust my views when presented with evidence.

I will be content if XMRV is proved to be a contaminant, whereas you seem to have already made up your mind that it is a contaminant without solid evidence, but with only theories and negative studies to go by.

That's what I don't understand, however much you talk about consensus.

If we take your consensual approach to science, in its purest form, and commit ourselves to only take a consensus view, then the world would still be flat, and the Sun would still revolve around the Earth.

Anyway, I can't see us agreeing about the subject. Whereas you see Stoye, Coffin et al. as being on the scientific and moral high ground, and I see the complete opposite.

I see their behaviour as being rather bullying because I can't see how they could be so passionate about a negative... About something that they believe isn't there.

If they believe that XMRV isn't there, then that's fine... Forget about it, and let others get on with the research.

I understand the WPI being passionate about the subject, because they believe in their science, and they believe that they have discovered an active virus.

Kurt, maybe you haven't read all of the comments from Stoye, but I don't really see how they can be defended, when other scientists are just trying to get on with their work, researching something that they believe passionately about.

No I have not read all of Stoye's comments, only some that were quoted here. I'm not defending everything he said, just trying to put in context the emerging consensus view. As I explained above, consensus in this type of measurement disagreement is important, and is not analogous with politically-incorrect break-through findings such as Gallileo's claims. This is a situation where measurement is difficult and multiple efforts must be made to validate a novel finding. That validation has so far failed to the extent that most virologists are 'calling the game'. I agree with you this has not played out all the way, the game is not over, but when your team is behind by 22 points with a few minutes left to play, things do start to look grim.

And you are right, we are not likely to agree on this. I trust PCR science and when large numbers of researchers say a sequence is not there, believe them. They can find a 'needle in a haystack' by RT-PCR, and their tests of conserved ares of the XMRV/MLV genome that MUST be present if people have XMRV infection fail. WPI did not even report any testing of the conserved region (the Poll gene). WPI also has not run all the contamination studies other researchers say are important. WPI is relying on secondary assays and ignoring the failure of the primary method of validation of a new viral claim today (RT-PCR). I take all those factors into consideration, as well as the fact that every single 0/0 study included a calibration process that proves they can find the target sequence, the same type of calibration used by WPI. The emerging belief of the research community that XMRV is a false finding (I agree 'myth' is a stretch) has a basis in the data, when you consider all the factors. Anyway, I am not a conspiracy theorist, I just don't buy into the 'persecution of CFS patients' mindset, at least not in the case of these researchers. I believe they are making rational comments based on the way they evaluate this type of information. However, when it comes to ordinary MDs and govt administrators persecuting CFS, I do think we would agree. I just don't see how people can conflate the two issues, researchers saying a virus is not there based on evidence are not the same as political administrators denying general acceptance and funding for CFS.

Everyone is behaving rationally in this situation, WPI is doing what we might expect for a lab believing they have found something important. And the labs not finding XMRV with what they believe are superior measures are behaving exactly as we might expect as well. There really is nothing unusual going on here, we just have to wait for more information to accumulate, enough to convinced everyone that XMRV is or is not involved in CFS. Some researchers say we are already at that point. Maybe in a year or two we will say they were right, or maybe not. I think we are at that point because there are so many problem in the XMRV hypothesis, and because I think emerging alternative explanations for CFS are a better match-up with CFS (proteomic study, Lights studies, enteroviruses, NO/methylation, the new Bateman/Light genetic study, etc.). I could be wrong, so could you, time will tell.