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At this point, how likely do you think it is that HMRVs are the cause of CFS/ME?

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by Esther12, Sep 28, 2011.

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At this point, how likely do you think it is that HMRVs are the cause of CFS/ME?

  1. 70-100%

    29 vote(s)
    42.0%
  2. 40-69%

    6 vote(s)
    8.7%
  3. 10-39%

    12 vote(s)
    17.4%
  4. 2-9%

    8 vote(s)
    11.6%
  5. 0-1%

    14 vote(s)
    20.3%
  1. ukxmrv

    ukxmrv Senior Member

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    Esther,

    Have you read the full paper published in Science in it's entirety of the methods and results of Phase iii of the BWG?
  2. Firestormm

    Firestormm Guest

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    At this point - damned unlikely.

    I am no scientist. Nothing has been published that I am aware of that says anything other than 'XMRV' was 'found' to be prevalent in patients with 'CFS' or 'ME' in either their BLOOD or some sneaky part of their body (thought that is now questionable if not defunct).

    If you want to speculate about retroviruses and possibilities that they are the cause of human disease - well we might as well be asking it of ALL humans at this juncture I guess.

    I mean retroviruses exist in humans - that's a given and for some humans we (as in science) don't even know what they are or what they might do. And this is the whole point I guess - even with the BWG results and with whatever Lipkin 'finds' or doesn't 'find' - there will always be that 'out'.

    People will always be able to say 'Well we are looking for retroviruses and we know they are there somewhere...' And so long as this continues the whole 'XMRV/Whatever' will continue.

    Anyway, I voted 0-1% obviously :)
  3. Esther12

    Esther12 Senior Member

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    No. I have looked at it, but only to check some results and details. I don't understand a lot of the specifics, so reading the all of the methods would not be helpful for me. I'm not trying to claim any sort of expertise in virology, and am quite happy to listen to and learn from others if they were to present an explanation of the BWG results (eg: I did look in to the claim that the WPI were not allowed to use their more accurate testing techniques - and it seems it was just an internet rumour, contradicted by Science).

    If there are any specific aspects of it that others think are important, or would explain the results from the WPI and Ruscetti, I'd be happy to go back and have another look. I don't have any expertise here, but I am happy work to understand the arguments of others.

    It seems that most independent virologists and experts writing about this now think XMRV is not related to CFS, and I'm pretty sceptical of the professed expertise of some patients on the other forum who seem so sure this is not the case - but I always try to look carefully at any new arguments being presented, and not just follow what the experts say.
  4. Bob

    Bob

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    I haven't read up on the details yet either.
    But my comments were based on what I understood about the BWG before the results came out.
    I thought that the methodology was a compromise, and that Judy could not do all aspects of it exactly the way she wanted.
    Maybe the Science article meant that they could use 'any testing' within certain parameters...
    You know how badly these types of things get reported.

    But nevertheless, the BWG was a complete failure, and I had expected at least some mixed results.


    I agree, but I still find it an interesting subject, so I enjoy discussing it.


    I don't think it's the BWG results that people are saying strengthens the WPI's position... It's the partial retraction of the Science paper...
    The authors now say that VP62 was an artificial construct... It was not cloned from a full isolate... It was cloned from partial sequences that were stiched together in the lab (don't ask me how they do that!)... (apparently this was common knowledge, but I don't think that I knew this before.)
    And they now say that VP62 was not present in the samples in the Science paper after all... The samples were contaminated by Silverman's positive control VP62 plasmids, and that's what he detected and sequenced in his lab...

    So it seems that it was other MLV-related viruses (not VP62) that were present in the WPI's research...

    The reason why this might strengthen the WPI's work is because it could explain why no one can find XMRV when looking for VP62. It just doesn't exist in nature, as far as we now know.
    Using very low specificity in her tests, Mikovits has always found a diverse range of sequences, and not just VP62-like sequences.
    This could also explain the discrepancy between Alter's work and Mikovits' work (i.e. possibly, there is no difference.)

    But this does all seem like speculation at the moment... I feel that we are all out of the loop about it all, and don't really know what's going on.

    If Mikovits and Alter and the prostate cancer scientists are only finding contamination, then there's a heck of a lot of contamination going around in the labs of the top scientists that they need to get to grips with.
    It also seems that a new man-made retrovirus, with an affinity for human tissue, is on the loose, and could potentially contaminate medicine products and vaccines.

    And it also seems that Mikovits may, at the very least, have found a biomarker. She says that it is very hard to contaminate your samples with anti-bodies.
    So her antibody results in themselves seem like a very worthwhile research avenue to pursue even if the rest of it comes to nothing.

    Just my thoughts.
  5. Esther12

    Esther12 Senior Member

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    I see. I misunderstood, and that makes more sense than the BWG, but I still don't see how this error could strengthen the WPI's hands, especially as researchers have been aware of the possibility of wider sequence diversity since Lo/Alter.

    It's possible, but it did say "All labs could use whatever assays they chose" - which is pretty forthright. I've not seen any reason to think this is wrong yet, and that many on the other forum seemed so sure it was, in the absence of any evidence, is a bad thing. It does seem like there's something of a bubble over there, and it's resulting in some misleading claims.


    I know what you mean, but discussions like this can easily go wrong when we're all so personally involved. When some people are really hoping/expecting XMRV to lead to successful treatment, and I'm telling them that I think they're wrong, it's easy to feel like a bully crushing hope, instead of just someone laying out their own beliefs. Pleased to hear you're enjoying it (I find it knackering!).

    It seems that there is a really widespread problem with contamination and these MRVs. A few different researchers have reported problems with this affecting their results, and the extreme measures they've needed to take to avoid problems with contamination.

    I'm not at all confident that the realisation that VP62 was contamination means that the WPI were therefore detecting other MLV-related viruses - they've not yet shown that they were detecting anything at a greater rate in CFS patients than healthy controls, at least, not when under independently blinded conditions.

    At the moment, I'm going to be sceptical of any testing results that haven't held up under independent blinding - and that includes the antibody results. Maybe they will lead on to something, at some point, but maybe not. If anti-body testing is particularly reliable, then it would have been nice if that had been used under the independently blinded conditions of the BWG.

    The results from the BWG undermine the claim that the WPI are detecting positives for 'something' at a greater rate in CFS patients than healthy controls. Maybe they've still identified some bug which will allow the development of a test at some later date, but it seems like the 2009 Science paper is pretty fundamentally flawed, and it would be a strange coincidence if this did lead on to a really significant discovery for CFS.

    edit: We've still got the Lipkin study coming. The greater numbers there meaning that there can be no concern about crazy twists of fate or bizarre coincidences, but it would be pretty amazing if the results claimed in the Science paper were replicable given the results we now have from the independently blinded BWG.
  6. Bob

    Bob

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    Ah, well that's not the same as 'any methodology'.
    So even if they could use their assay of choice, there is still the issue of the difficulty of detecting these viruses in the blood. Was Judy able to cultivate the cells for a month, for example? Was she allowed to follow her usual blood collecting, preparation and testing regime?
    But I don't know the details, so i can't really discuss the BWG results...
    I'll get round to have a look at it soon.

    Yes, i knew what you meant... These discussions can go round in circles, and can be totally unproductive.
    Sorry you not enjoying it...
    I find the science really interesting anyway...
    And I'm usually (but not always) able to separate my emotional expectations from my academic interest. So I'm lucky there. Although I have been frustrated at times, because i want to see the research completed, and I don't understand why some people seem to think it's finished. That seems like a premature conclusion to me.
    I always knew that XMRV research would take at least 5 years to come up with any definitive answers, but it is far more of a mess than I expected it to be.

    It's always healthy to be a sceptic.
    I suppose I take a slightly different approach to it... I follow the research with enthusiastic curiosity, because I enjoy the subject...
    And I want the research to continue until we have definite answers... I don't believe that we know the answers yet...
    Like i said earlier... My expectations could be 10% or 90%... I just don't know.

    I've always been interested in science... So I'm lucky that I enjoy following the subject.
    But I understand that other people get very frustrated by it, and many are desperate for early answers for our illness.
    I get extremelly frustrated and angered by other aspects of the world of ME, such as the PACE Trial, and CBT/GET etc etc.


    Once the Lipkin study comes out, and if it's negative, then I think that I will have to accept that we aren't going to get any answers from this line of research.
    I really hope that Lipkin sets it up such that people cannot find holes in it.
    Mikovits has said that she is 100% happy with the way it is being run.
  7. Esther12

    Esther12 Senior Member

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    The conversation is appealing - but the fatigue makes these things more of a strain. I had a wander in the sun today, which was very nice, but has left me feeling wiped. Always a pleasure to read your thoughts though Bob!

    I expect that there will always be something that some people will point to as a potential flaw.

    It's almost impossible to prove that HGRVs are not associated with CFS (I'm not sure if there's been anything yet published that even uses the term HGRV). But it does look like the WPI's Science paper was the result of error, with Lipkin giving them one last chance to try to distinguish between CFS and control samples using their techniques under blinded conditions.
  8. ukxmrv

    ukxmrv Senior Member

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    Esther, what struck me about the procedure used by the BWG was how little control that the individual labs had on the collection, storage and preservation/processing of the blood samples. It's not enough to say that a lab can chose their assay when all the other conditions are taken out of their control.

    I would encourage you to go back and read the paper fully and then compare it to the original Science paper and what we know about how the WPI would carry out a study that they can control.

    Also have a read about HIV/AIDS and how that test developed. The contaminations, fights, false starts etc. XMRV/HGRV's deserve a level playing field and they haven't got it yet.

    If you only read the editorials and the media reports they don't give you the full picture.

    At the IiME conference Dr Mikovits said that the BWG was only to find a method for the mass testing of bloods and that she would not chose the methods they were using as any definitive test of XMRV or HGRV's. They were asked to perform their part in conditions that they did not consider they had done before and would not choose to do, it didn't work and that's no reflection on the WPI or on the original Science paper.

    The WPI should be congratulated for being willing to take part in the very important job of keeping the blood supply safe from XMRV/HGRV's. All the labs involved failed to find a method using the constraints on them. It should be back to the drawing board and the idea that this is the end of XMRV/HGRV's is absurd.
  9. Esther12

    Esther12 Senior Member

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    ukxmrv - but remember the experiments being done in the earlier phase of the BWG to try to find the best way of collecting blood to allow for the detection of XMRV? They thought that might be important, and tried to find the best way of doing it, without much luck. IF there is a special way of doing it, then the WPI don't seem to know what it is. There will always be variables which could have been tinkered with, or could be used to try to explain why a test failed, but the WPI had an opportunity to explain to the BWG how to get those conditions right prior to the samples being blinded. The danger of a retroviral infection being passed on by blood transfusions was being treated seriously, and the BWG rightly wanted to know if the blood supply was at risk. I've not seen any reason to think that they were placing restrictions upon the labs involved, or doing anything other than trying to ascertain the risk to the blood supply.
  10. ukxmrv

    ukxmrv Senior Member

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    I do remember that Esther, but the WPI weren't given any executive veto or any control over which exact methods were used in Phase iii from collection to end. Being given an opportunity to tell the BWG how to get the conditions right is not the same as determining the decisions made by the BWG.

    They were still restricted like all the other labs to many variables out of their control. Have a complete read of the BWG paper.

    It's wrong to say that the WPI doesn't know the right way to find a HGRV. The BWG only proves that the WPI (and all the other labs) could not find the version of XMRV that the BWG wanted them to try reliably and find and more importantly, under conditions that did not replicate the Science paper or conditions they would choose to use if given the right to make that decision.
  11. Esther12

    Esther12 Senior Member

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    All of the samples needed to be collected in the same way, as part of the blinding, but I've not seen anything which indicates that anyone knows that particular collection/storage is required, and that this was not done by the BWG. The BWG would have been trying to get this right.

    Do we have any reason to believe that the WPI do know the 'right' conditions, informed the BWG of them, and then had the BWG insist on other conditions instead? That would be a really strange way for the BWG to behave, and so far, I see no reason to believe it happened.

    Equally, I've seen no reason to believe that the WPI were able to distinguish between patients previously positive for HGRV and healthy controls, but that the BWG were only interested in a virus called 'XMRV'. That sounds crazy!:

    "Well, they can consistently detect this other retrovirus in the blood supply under blinded conditions, and distinguish between controls and patients, but we're not going to worry about that because we're only interested in XMRV."

    Why would the BWG be interested in semantics, if a retrovirus was being spread through blood transfusions? I don't think that makes sense.

    If the WPI had a test for 'whatever-retro-virus' that was able to distinguish between those patients who previously tested positive for 'whatever-retro-virus' and healthy controls, then that alone would have been massively significant. But that wasn't the case.
    wdb likes this.
  12. Bob

    Bob

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    Do any of us actually know any facts about the BWG methodology?

    There doesn't seem much point in debating it until we understand exactly how it was carried out.

    I still don't know what assay the WPI used.

    I can see some bed-time reading looming. At least it will sort out my insomnia!
  13. ukxmrv

    ukxmrv Senior Member

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    Bob, I've read the full BWG paper plus the supplementary papers. Maybe catch up with this when others have read the full papers.

    Would ask people not to make assumptions without reading the papers.

    Esther, I have no idea of what the WPI told the BWG and I'm hoping at some point a statement will be released. What I do remember is what Dr Mikovits said at the IiME conference about the conditions being imposed on them. The BWG was designed as a way of mass testing blood and theyr failed to find a method.

    I can't understand why people would equate phase III results of the BWG as having any bearing on the original Science paper. These are quite different things.
  14. Esther12

    Esther12 Senior Member

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    Currently, I'm only working on these general points:

    - The BWG wanted to find out if there was a risk of a retrovirus circulating in the blood supply, as the WPI's Science paper indicated that there was.

    - 'Positive' samples were taken from those who had previously tested positive by either the WPI or Lo/Alter, control samples were taken from healthy individuals, and had been tested by all labs who agreed that they were 'negative'.

    - All samples were taken in the same way, and independently blinded, prior to being sent to the labs involved.

    - We've been told that the labs were free to use whatever assay they thought would be best, and have no reason to think that is not true.

    - Only the WPI and Ruscetti reported any positives. They reported different samples were positive to one another, and previously 'positive' patients were not more likely to be 'positive' under blinded conditions than healthy controls. I also read that re-testing of these new 'positives' did not lead to consistent results, but I don't remember having checked that out myself.

    If the above is accurate, then I'm not sure if it's worth looking in to the specifics of which labs used which assays (certainly not for me, as this is not an area I know much about).

    Perhaps because I don't have much knowledge of virology, I've been waiting for the WPI to be put under blinded conditions like this since the initial paper - testing their test like this and the Lipkin study are doing should lead to results which don't need much interpreting.

    edit: ukxmrv - I was typing as you replied, but I think some of the above exaplains why I think the BWG results have a bearing on the Science paper. Maybe the WPI will release a statement explaining that they had told the BWG that different collection/storage methods were needed in order for their tests to be accurate, and were rebuffed. It would be very strange if something like that did happen, and in the absence of any statement claiming that it did, I think it's fair for us to assume that it did not.
  15. barbc56

    barbc56 Senior Member

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    Bob, haven't had a chance to answer your question until now. This thread is about how likely we think HGRV's are the cause of ME/CFS. I gave my opinion, voted 0-1% and won't be sidetracked nor drawn in by your post and go round and round with these stale arguments.

    I don't know what Singh is saying now, I was specifically talking about her not finding XMRV in CFS patients. The NCI is saying it's contamination but I won't assume what she thinks. I could email her and get her take, but we can't assume one way or another, can we? I haven't found any statements from her since the results of the BWG.

    The point I want to make is that there's not necessarily a nefarious reason for Singh to change her mind. This is how science works. It's a process where knowledge can change depending on the data. So Singh does not have to retract earlier studies. The next study would include the previous study and why they are changing their methods.

    The latest retraction, by Silverman was the right thing to do. It's the other authors who are stubbornly holding back or simply ignoring the fact they were asked to retract the paper. Articles aren't often asked to be retracted unless something serious is going on.

    I know what I think. I am not someone who sits back and blindingly follows anyone. I have a good working knowledge about Science and how to read a science paper. I don't think we all need a virology degree to discern what is going on and people can make a judgement on which scientiest to follow based on other things. I am not talking about appealing to authority, here.

    Science is showing it's contamination and IMHO, we need to look into other things that might be a factor in ME/CFS. However, if you want to debate other issues, put them up on another thread if they are not already there and not sidetrack this one. I am tired of this type of debating but am keeping a close eye on what is happening.

    Have a good day.
  16. Jemal

    Jemal Senior Member

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    Eh? This thread is about the probability of XMRV/HGRV's association with ME/CFS. Of course there's going to be discussion and debating in here.

    Anyway, I picked 40-69%. I was high in the 70-100% category, but dropped down a bit after the recent papers. For me, the 40-69% translates into: HGRV causing ME/CFS still likely, but need more research. In a way the recent papers reset the science. As a patient, that hurt. When the original Science paper appeared I believed help would be coming in a few years and it looks like we will have to wait a bit longer.

    In a way the recent papers also strengthened the case for HGRV association (possibly explaining many of the negative papers), so that's why I didn't pick a lower category. The ball is definitely in the WPI's court, but it always was I guess. I am hoping for some brilliant stuff from them.
  17. mellster

    mellster Marco

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    I wonder what happened to Tate's announcement..
  18. Jemal

    Jemal Senior Member

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    Tate's announcement? I have no idea what you are talking about here. Could you explain?
  19. mellster

    mellster Marco

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    This doc in New Zealand I think who has a daughter with ME/CFS and was about to publish some breakthrough retroviral related stuff I think - this was gathered from a radio interview posted on this forum some time ago.
  20. Jemal

    Jemal Senior Member

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    Ah ok, thanks for explaining. I haven't read any news about it.

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