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Negative study: XMRV in prostate cancer cells likely represents a laboratory artifac

Discussion in 'XMRV Research and Replication Studies' started by Jemal, Jun 7, 2011.

  1. Jemal

    Jemal Senior Member

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    I don't think this study brings anything new to the table, but I am posting it here for the record.

    http://www.impactjournals.com/oncot...et&page=article&op=view&path[]=287&path[]=438

    The fight is definitely on though, XMRV prostate cancer research is a target for the contaminists. This could be a good thing, as one can hope it forces researchers like Silverman, Klein, Singh, etc to take a stand. Silverman is out there defending his work, let's see Singh do the same.
  2. Bob

    Bob

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    Thanks Jemal.
  3. alex3619

    alex3619 Senior Member

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    Hi Jemal I tried to post this in another thread but the link was broken by PR, I had to manually format it. While this paper clearly says 22Rv1 XMRV is probably an artifact, it leaves the door open as to what it means in my opinion. This is a lot more balanced than Coffin's statements, although the science is similar. It also leaves open the possibility that the cell line was contaminated by XMRV, just as I have been wondering. In other words, yes, it appeared suddenly in the developing cell line, but that does not nail down why.

    I still think XMRV is way too adapted to these cells. I think it is pre-adapted - it has a long history of infecting this type of cell. If so, this might be an old virus, just unusually capable of contaminating everything. Which raises the question: how many in the public are at risk of infection just from random virus particles? I hope Levy is right that we can stomp it before it takes hold, but I doubt it - mucous membranes, particularly the lungs, are viable targets. This could be an airborne retrovirus, but I do think that there is evidence that the transimission rate is very low, regardless of the mode of transmission.

    So even in the prostate cancer and ME/CFS links are a bust, which I dont think will be the case, this virus is still a threat.

    It is fine to argue that XMRV is problematic because we can't be sure we are finding it and not contamination. That is a two way argument though - it could imply we are not capable of effectively detecting a new retroviral epidemic that has been left unchecked for an unknown number of years. If the WPI cannot reliably find it, if nobody else can reliably find it, and it is really out there, then there are major problems on the horizon if this virus is pathogenic. Thats a lot of ifs, but the downside is very worrying.

    Bye, Alex
  4. Bob

    Bob

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    I totally agree with you Alex.

    The paper is far more balanced that Coffin's paper, and the authors raise some issues relating to why Coffin's study might have come to the wrong conclusions.


    There's a number of reasons why Coffin's conclusions are premature:

    1. A wider variety of XMRV sequences have now been detected and published in genbank.

    2. The original prostate cancer sample, which initiated the cell line, may have harboured undetectable minuscule quantities of XMRV, which then flourished as the cell line was propagated, making it detectable in later samples of the cell line.

    3. Switzer's recent abstract challenges Coffin's conclusions, because Switzer has worked out many other possible recombinations.

    4. Apparently, not all mice have yet been tested for XMRV, so it is possible that some mice, somewhere, harbour XMRV.

    5. Coffin might have only detected contamination in his own study, in which case all of his results and conclusions are invalid.


    That's all I can think of right now... There may be other reasons.
  5. Jemal

    Jemal Senior Member

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    Can they even find XMRV in mice? I mean, they are detecting 0/0 in patients, could they be detecting 0/0 in mice too? They all say they can find XMRV, yet I remain suspicious of their assays and tests.

    Also, maybe they should not be looking in mice only?
  6. Bob

    Bob

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    Good point!

    If it's an endogenous mouse virus, then it would be more straightforwards to detect than an exogenous mouse virus.

    Do you know if it could it theoretically be an exogenous mouse virus, based on current knowledge?

    Another good point!
  7. Jemal

    Jemal Senior Member

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    I have no idea, though I do think some mouse viruses can be both exogenous and endogenous. Mouse mammary tumor virus (MMTV) is such an example. It's not a gammaretrovirus.
  8. Cort

    Cort Phoenix Rising Founder

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    I think you have some good reason but I think they're more based on hope :)

    yes new sequences were posted to GenBank but the CAA reported that they are much the same as the other sequences.....and nobody other the WPI seems to feel otherwise - not a good sign.

    Yes, there could have been miniscule amounts of XMRV present but they looked very hard for it with very sensitive tests....so while that could be true - my guess is that it probably isn't.....

    It is true that not all mice have been tested but a heck of alot of mice have..probably most that are available - so again - you're kind of hoping for something unusual to happen...that one strain of mice that has XMRV has been missed.

    Switzer - the Paprotka paper suggested that there was a 1 in a trillion chance that some other recombination event could have caused this strain of XMRV to show up.

    These are all longshots, in my opinion.....unfortunately.
  9. Bob

    Bob

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    Cort, I was just pointing out why the Coffin paper is not conclusive. And there are a number of reasons.
    Some of my points were 'longshots' (but not invalid), but some were strong points.

    Switzer's new study challenges the Paprotka study, and basically says that the info re recombinations is nonsense.
    Have you read it? It's a brand new publication.

    There's been no professional or peer reviewed analysis of the new sequences in genbank, as far as I'm aware, so it is premature to make any firm conclusions about them either way. The analysis that I've seen does suggest increased variation. And the WPI say that they have a whole load of viruses that they can't afford to sequence.

    But even if there is no significant variation, this does not confirm that it is contamination, for a couple of reasons:
    1. A possible different route of infection, such as via vaccines.
    2. A possible virus mutation pattern similar to HTLV.
  10. jace

    jace Off the fence

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    They will never find xenotropic murine leukaemia-related viruses in mice. Polytropic, yes, xeno, no, by definition a xeno cannot infect the originating species. However, the polytropic HGRV's such as those being found now in various labs are near enough to XMRV to be called the same species, just as there is only 85% homology in the various strains of HIV and HTLV varies too.

    Beware of the nomenclature trap. When something new is named for the first time, it is named with the best of knowledge and belief at that time by the discoverer. It does not mean that the name is real. The thing is real, but imperfectly understood. The name may well prove later to be inaccurate, with greater knowledge. We would do better to talk about HGRVs, which fits the understanding of the retrovirus we are discussing better now that the name that was given it in 2006.

    Does anyone here have knowledge of the sequences recently published in Genbank by the WPI? Can someone provide a link, so I can see for myself? I'm not interested in hearsay or the CAA's assessment, I want to compare for myself.
  11. Bob

    Bob

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    http://phoenixrising.me/forums/showthread.php?11714-New-WPI-and-CDC-XMRV-sequences-in-genbank

    Keep in mind that it has been said that there is usually more variability in the unpublished sections of the genome, so that the amount of variability in the published section might not indicate the total variability.

    So it seems to be more complex than it first appears, and I think that we need a proper scientific, peer reviewed analysis before we make any conclusions.
  12. Jemal

    Jemal Senior Member

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    Yes, the name... it might not have been the best.

    http://www.ncbi.nlm.nih.gov/pubmed/2991590

    This is a really old publication from 1985, but I think I remember seeing a more recent paper that said the same.

    edit: ah yes, from the same author in 2010: http://jvi.asm.org/cgi/reprint/JVI.01863-10v1
  13. Bob

    Bob

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    Well it seems that you may have fallen into your own trap, jace! :D :

    The 'xenotropic' label is a 'nomenclature trap' because it does not apply to all mouse species. I can't remember the exact details now, but some mice have now been discovered that can be infected by X-MLV's. So X-MLV's do behave like P-MLV's in some strains of mice.

    ETA: Ah, I see that Jemal has given you more info.
  14. Bob

    Bob

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    I had forgotten about this, but in one of his recent studies, Switzer specifically says that the XMRV sequence variation that he has detected is "consistent with virus evolution during spread and persistence." Switzers's evidence and conclusions directly contradicts the conclusions that Coffin and his co-authors have come to in relation to there being no variety in any XMRV sequences. Switzer indicates there is evidence of virus evolution expected during normal human infection in the wild.

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