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A Little Poisoning Along the Road to ME/CFS
Looking at my symptoms, many of which are far less these days and some are gone, it would be easy to figure that I'd just been dealing with some heavy-duty menopausal issues.
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Comparing PreXMRV-2 gag sequence diversity in laboratory and wild mice

Discussion in 'XMRV Research and Replication Studies' started by Jemal, Jul 10, 2012.

  1. Mula

    Mula Senior Member

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    Is there a reason why different tests would be thought to find the same retroviral sequences? Lombardi had but one set of primers, Lo used a separate test with several primers and Lee had a range of primers with variations in temperature. PCR is not considered to be reliable for HIV diagnosis and if it is used it would be with a range of primers.
    http://nar.oxfordjournals.org/content/25/3/654.short
     
  2. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Yes, proprietary. This is the reason no real effort was made to replicate. There are lab connections and patents associated with many of the negative papers.
     
  3. Firestormm

    Firestormm Guest

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    I can of course see how you might think that. I simply wish that Mikovits had published a paper that attempted to support all the speculation she has prompted. Only published papers can really attempt to substantiate things. And only if those papers include blinded samples from patients with our condition can the 'link' be maintained/re-established to 'MRVs' rather than 'XMRV'. [edit: Though of course it would be essential really to establish a link to an identifiable MRV and to publish a sequence.]

    You know I was reading yesterday of that post from ME Advocacy and a subsequent thread on PeoplewithME.com and it concerns me that people appear to think that the 'XMRV tests' not only worked but in actual fact did not really reveal XMRV as was repeatedly claimed, but something else and that something being assumed to equate with what Mikovits herself speculated upon. I mean what is all that based upon? It certainly isn't science.

    There have been other studies. Work is continuing on mouse-viruses. Work will continue. But someone has to re-establish a link with our condition. And that paper must be far, far, better and substantiated than Lombardi et al and Lo et al. and anything else produced since then.

    There has to also be a link established not only to human disease and the ability of any virus to overcome our defence mechanism, but to our particular condition (and assuming our condition is specific is another massive hurdle to overcome as is establishing that the current criteria reveal a definitive group).

    There's nothing 'wrong' with pursuing an interest in this area but I really think it's going too far to base associations on little more than speculation and to say so in such authoritative ways - examples of which we have seen. The statements that get issued, the science promoted as being supportive of them, are speculative and hopeful at best. Again, nothing wrong with that if you say so but some individuals and 'advocacy' groups don't.

    I am sure that when the XMRV/MRV study from Lipkin and all the others so engaged is published we will all be able to take another look at this and perhaps it will reveal something thus far unsubstantiated.

    Edit:
    You know this thread:
    http://forums.phoenixrising.me/inde...2-cfs-patients-positive-for-mulv.18706/page-5 in which we talked about the following study:


    well ProHealth have just published it too. But with the same title as that thread, i.e.



    Why? The answer is pretty obvious but without really considering the paper they have latched on to the 'fact' that it is in some way supportive of the speculation being promoted and it's not even correct is it - the title I mean?

    But to what purpose was this done? Who does it serve? I don't know who advised them to do this (I can guess) but why haven't they properly read the paper and reached the conclusions/discovered that/what we did? It's just another example really of what I was trying to explain I think.

    Why am I so bothered? Well without wanting you to think I am again being insincere, it is because I care. I care that some people will be unduly influenced by these sort of things. That it might even influence their decisions when it comes to 'treatment' of what remains a speculation i.e. that some retrovirus of even murine origin is causing their suffering.

    I am also concerned about what impression all of these things afford others who don't have ME. These authoritative statements, these claims made by 'advocacy' groups or individuals claiming some authoritative scientific knowledge that no-one else possibly does - they risk giving the impression that everyone with ME believes as they do.

    I don't like it. I don't like anyone claiming to represent me or claiming to have an 'answer' when there is no answer.

    Hypothesise by all means - but don't claim to know what 'must' be correct about what is or what isn't causing people to suffer not unless you can substantiate your reasoning and are willing to admit you are wrong, and amend your thinking accordingly, even disregard what you have proposed.

    And I don't like what came out of the WPI or from Mikovits either if I'm honest. I don't like where it took us and I don't like how it was done and the hope it offered 'many' people. Hope based on speculation and incitement.

    Sorry. Banged on a bit.
     
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  4. asleep

    asleep Senior Member

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    She did publish papers, one of which was retracted for what really appear to be political reasons. The idea that she has had ample funding and time to conduct follow-up research and the idea that the peer review process is not deeply influenced by political and other ignoble motivations (which have essentially precluded and/or slowed publication of positive papers) are nothing but fantastical illusions, necessary to distract interested observers from the wholesale corruption of honest scientific inquiry we have witnessed.

    You are essentially claiming that no new evidence of RV involvement (or even simply disease correlation) can be considered unless an entire disease mechanism is simultaneously proven. This is placing an "all or nothing" burden of proof on future research, which runs completely counter to the spirit of science where evidence comes in all shapes and sizes and strengths and must all be carefully considered on its own relative merits in reaching tentative conclusions. This method of placing unreasonable demands on future evidence was/is a favorite tool of politicized attacks on scientific research (by tobacco companies, chemical companies, pharma companies, etc), as it conveniently allows for irrational rejection of all new pieces of evidence as they come in (since no piece by itself can prove the whole picture).

    You are right. Which is why I and many others have been tirelessly explaining how it is completely unscientific for thoroughly speculative claims such as those made by Paprotka/Coffin to be trumpeted about as "proven" with such authoritative air. Same with the many negative studies that illogically and authoritatively speculated that the inability of their (novel) methods to find anything meant that they had proven nothing was there. The unscientific extrapolation of these speculations and logical failures is quite wrong.

    The title ("2 of 12 CFS patients positive for XMRV/MLV sequences: Italian study") is closer to being correct than the contorted title of the published paper. They did find MLV sequences in blood from those patients while controlling for contamination.

    And here you are again trying to manufacture some sort of negative consensus by implying that "we" have reached a conclusion about the importance of this study.

    Claims and arguments are being made on all sides. The vast majority of claims from the retroviral proponents have been carefully measured and been made in response to perpetual, over-reaching, and illogical assertions from the "anti-RV" camp. Claiming something akin to "because Z studies couldn't find the virus it doesn't exist in humans" is far more definitive and authoritative than claiming "that conclusion is unsupported and over-reaching for the following reasons..." The preponderance of claims about what "must" be correct are coming from those vehemently discouraging additional MRV research. Trying to frame the situation to obscure this is another form of misrepresentation.

    We have no control over how we are misrepresented and how these misrepresentations are blasted across the media. Just witness last year's claims of "death threats" that were never actually substantiated yet spread like wildfire. Being powerless against misrepresentation is no reason, in and of itself, to acquiesce to corruption and abuse of scientific "authority."
     
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  5. Bob

    Bob

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    Hi asleep and Firestormm,

    I think you both make valid points.

    The Science paper was retracted partly because of (small-p) political pressure, but if you publish a paper in which you claim to have found a new virus in ME patients, and then the XMRV sequences turn out to be contamination from a clone, and you then admit (allegedly) that the samples were contaminated with XMRV in a freezer, then it's a bit difficult to say: "Oh sorry, our study was contaminated, could you please just cross out the bits that apply to the contamination."
    The whole thing has been a very messy affair.
    Mikovits seems to have admitted that there was contamination, so I don't see how the original paper can be defended now.

    With regards to Mikovits not being able to publish her subsequent work, I don't know the reasons, but unless we see any good quality studies published, then whatever she has said about her sequences in the past is meaningless.
    I say this partly out of frustration. We don't know what's going on behind the scenes, but there does seem to be a lot going on, between Mikovits and the WPI, that we aren't/weren't aware of. And also the reality has never lived up to the promised expectations.
    As an example, we were promised NGS of some of the WPI sequences, months ago, and it didn't come to fruition, and neither have we been told why not. It's just all gone quiet.

    I agree with asleep that science should be allowed to progress in a messy fashion, but I think Firestormm is correct to say that there is currently no proper solid evidence for MLVs in ME patients, and that patients have been promised too much.

    There is some still-valid evidence that points towards MLVs being associated with ME, such as the Hanson paper, but that's about all at the moment.

    ME patients are very vulnerable, and to be told that a cause and a cure is in sight, only to have our hopes dashed because the unfolding science doesn't live up to expectations can be very difficult for people. So I think that Firestormm, is correct to raise these points. However, we all live in the real world, and this is just real world science, and politics-of-science, at play. And everyone makes mistakes in terms of presentation, so I don't think it's helpful to vilify anyone for doing their work, unless they've gone out of their way to purposely cause difficulty for others.


    With regards to the behaviour of various scientists, unfortunately, I think the behaviour of scientists has been disappointing on all sides. The WPI over-reached with their claims, and the XMRV tests, possibly to raise their profile. And the anti-XMRV brigade were also far too arrogant and also over-reached with their claims, and also have created some disappointingly unsubstantial research papers (e.g. Paprotka et al.) I think there's been imperfect behaviour on all sides, and it's shown science for what it is... A bunch of humans doing their stuff.


    I think it's probably wise for us to save our arguments until Lipkin has published, because then I'm certain that a lot of proverbial stuff is going to hit a lot of proverbial fans within our community, when it's published. I think that a lot of frustration might be vented. But, you never know, Lipkin might surprise us, or convince us with a very well executed study, with unexpectedly inspired and helpful insights. I reckon that Mikovits has a very good relationship with Lipkin, so there might be a good deal of trust there. Let's wait and see.
     
  6. Firestormm

    Firestormm Guest

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    You are right. I should perhaps have used the word 'observations'. My use of 'we' was meant a la Phoenix Rising and those who contributed to the thread under discussion. I don't even think I contributed anything of substance but there were some very good points raised.

    There is no 'manufactured negative consensus' (what a silly phrase). There are alternate explanations, alternate considerations, ways of looking at these things differently, discussion, understanding, hopefully some education, etc. etc.

    And that is no different than what you do or those on peoplewithme.com either or elsewhere or here. We kick around opinions and have a say. We agree and disagree and probably don't say all we want or are able to anyway.

    It was obvious to see that there were 2 out of 12 'positives' in that study - what wasn't as obvious was why this might have happened. Again, one of the explanations could be that yes this was a genuine infection, but come on - do you honestly believe that all the other possible explanations should not be considered as well? And that past papers shouldn't have an impact?

    If Lipkin and company publish a paper that contains a similar report in respect of some aspect of the blinded results - the report of that will be obvious, yes? What won't be immediately obvious perhaps is how they might have arrived at that result. Remember the Blood Working Group study? Same thing. Just because I personally don't state what seems an obvious at face value explanation but posit alternates doesn't mean I haven't considered them.

    If I am being seen as 'negative' without perhaps giving due consideration to all the research, well I don't have a problem with that Asleep. But given that I am not a scientist and haven't read all the published papers inside out and upside down let alone understood the minutiae; I tend to consider the arguments as a balance. A set of scales if you like.

    And I do not consider there to be anything weighing the scales in favour of a murine connection to ME. Not now and not really at any time previously. It didn't add up and the arguments posted in favour of a mouse virus jumping into humans and causing disease let alone surviving, didn't either.

    Still, as a non-scientist and patient - what the hell do I know? ;)
     
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  7. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    I don't think the phrase is silly. The term 'consensus' has been used by negative researchers, and their supporters, to describe the current situation with regard to XMRV and other MRVs. And it is a 'manufactured' assessment of the state of the science if there is not conclusive evidence that MRVs don't exist in humans.

    After all, 20 negative studies do not overturn a single positive study, unless it can be proven that that study was completely flawed. Only part of the Mikovitz study has been shown to be flawed. Lo has not been shown to be flawed. Nor has the Italian study been shown to be flawed.

    There is only one inescapable conclusion that can be made: you shouldn't be looking for this bug with current PCR techniques. Given this fact, then no one can say there are no MRVs.

    The word 'consensus' is being used by the negative researchers because the science is not conclusive. Therefore it is apt and important to point out that it is only a consensus.

    Furthermore, irrespective of the outcome of Lipkin's studies, evidently he doesn't think the science is conclusive as yet or he would not have gone ahead (although I concede there are other reasons to proceed, but not science-related).

    And it is okay to consider unpublished work. Of course you can't cite it or use it as evidence in a paper, but there are plenty of reasons why work is not published, and we know one of them is fear of sanctions. On a personal level, I would not ignore unpublished work, particularly when I see some of the poor quality published work.
     
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  8. Bob

    Bob

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    Well, the mouse virus did 'jump' into human tissue in at least one cell line. It doesn't seem like such an impossible 'jump' from the cell line to humans.
     
  9. Firestormm

    Firestormm Guest

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    Impossible? In theory, no perhaps not, but it still has to be proved that any individual strain is capable of surviving in a human host and overcoming or adapting to our defence mechanisms whilst maintaining the ability (assuming their is one) to cause disease. That's not necessarily meaning ME of course.
     
  10. Bob

    Bob

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    Yes, I agree that it has to be proved, but it hasn't been proved that XMRV cannot survive our defence mechanism. As for disease, MLVs are well known to cause disease in mice.
     
  11. Firestormm

    Firestormm Guest

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    There is always I think a need for more evidence Bob. More conclusive evidence. Chasing down the angles. Conclusive studies. And I'm not trying to dilute or discredit your point. MLVs are indeed known for this I believe - in mice. Again, scientists I do not believe have stopped looking. They haven't decried that further study of these viruses are not worthy, should not be funded, or that the results should be discarded. I'm sure they will continue. I hope they do. It's interesting stuff.
     
  12. Bob

    Bob

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    Well, that's exactly what did happen with regards to XMRV and ME. All three of those points were asserted by various scientists, at various times, which contributed towards so many patients' frustration about it all.

    But I agree that research into MRVs will continue.
     
  13. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Actually, it has been shown that XMRV can replicate despite Apobec3. As for other mechanisms, no one else has looked.

    I think one Mikovits study did establish MRV pathology in me/cfs patients - remember the immunological study. The point is no one else has bothered to look. And of course, if the consensus is MRVs don't exist, then there is no need.to look.
     
  14. Bob

    Bob

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    Yes, there has been research to show possibly infection mechanisms, but I was referring to actual infection of a human.
    The actual mechanism of infection of humans isn't really understood, if it has happened at all.

    Firestormm was asking for proof, and I agree with him that there is very limited evidence. Very limited. But unlike Firestormm, I don't think that XMRV research has been a waste of time, and I don't think it has wasted resources, and I don't think it has been bad for our community, although the whole situation could have been handled better by all sides. I think it's been a win, win, win situation for our illness, and I also want to see the research into MLVs continue.

    Yes, the immunological study was helpful, but Lombardi has said that the study would stand up with or without XMRV infection. So it's a very helpful study in itself, in terms of ME patients, but it doesn't confirm XMRV infection. That's my understanding of it anyway, going from memory.
     
  15. currer

    currer Senior Member

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    Bob, you are being very reasonable, and I dont disagree. However IF we were infected with MRVs I cannot see that the medical establishment would be able to admit it. Paprotka being an excellent example of this desperation to grasp at any theory, however weak, to dismiss "XMRV"
    So the whole situation is a stalemate.
    I am inclined to put more emphasis on political motives than you are.
     
  16. Bob

    Bob

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    I think that whatever politics is at play, the science will win in the end. If there is a novel virus to find, I believe that it will inevitably be found, and in the near future. I think that for all the noise coming from all directions, there must be a lot of retrovirologists who would be ecstatic to be the first ones to confirm a novel human virus. It would be a career highlight for many. So I can't believe that this field is being neglected. I also can't buy into any conspiracies re Lipkin. I can't see why he'd so completely surrender his integrity because of any misplaced political pressure. And I wouldn't be surprised if he and Mikovits have a very good working relationship. He seems to like her.

    Anyway, just my opinions. I'm mentally preparing myself for the results!
     
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  17. Firestormm

    Firestormm Guest

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    I happened to be re-reading this article from March 12 2011: Amid War on a Mystery Disease, Patients Clash With Scientists: http://online.wsj.com/article/SB100...468402.html?KEYWORDS=XMRV#articleTabs=article

    I actually don't remember reading it at the time but am pretty sure I did. Was rather an interesting piece from Dockser-Marcus I thought (ignoring now perhaps the title) and in some ways I think it says much of what we've been talking about.

    Science remains fluid. At this point in time it might feel like Poprotka drew a line under XMRV and ME as an infectious agent and concluded it was a contaminant/whatever, but it doesn't mean - as I said above - that we have seen the end of XMRV or indeed MRV's or any other potential human virus.

    I forget now how long Mikovits and Lombardi and Ruscetti and Silverman were working on their CFS paper - but it literally came out of the blue. It wasn't expected. Science hadn't been moving in that direction - although the Prostate Cancer work might be seen as such.

    My personal feeling - and it does mean absolutely buggar all in the grand scheme of things - is that it would take (as I said again above somewhere) a huge and very solid piece of research to re-establish any link of XMRV with ME - and I can't see that happening and neither would I want any ME/CFS state funding diverted in that direction. Neither would I want to see any (further) state funding given to work on ME/CFS and MRVs post-Lipkin. Unless of course... but I can't see that happing. Be damn interesting if it does - for a while - but no. I don't think so.
     
  18. currer

    currer Senior Member

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    "At this point in time it might feel like Poprotka drew a line under XMRV and ME as an infectious agent and concluded it was a contaminant/whatever,"

    Firestormm - please please please - stop being impressed by Paprotka!!!!!!!
     
  19. Firestormm

    Firestormm Guest

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    I wasn't. You mentioned Paprotka. I was interpreting that feeling i.e. for some it feel's that Paprotka is being 'used' as an unfair paper with which to close the case on XMRV and ME. I wasn't in this instance passing my own judgement on the paper. However, until something better comes along...
     
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  20. Mula

    Mula Senior Member

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    Having run gag assays in the original Lombardi paper the designation of the isolates may not be XMRV.

    http://www.ncf-net.org/forum/2012winter3.htm
     

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