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Science Mag: Fresh Doubts About Connection Between Mouse Virus and Human Disease

Discussion in 'Media, Interviews, Blogs, Talks, Events about XMRV' started by dmholmes, Mar 9, 2011.

  1. dmholmes

    dmholmes Senior Member

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  2. Jemal

    Jemal Senior Member

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    Article about XMRV in Science

    I noticed a new article about XMRV popped up on the Science website:

    http://www.sciencemag.org/content/331/6022/1253.citation

    Don't have access to the entire article...
  3. Cort

    Cort Phoenix Rising Founder

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    Well, we definitely know where Coffin stands now.

  4. SOC

    SOC Moderator and Senior Member

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    Isn't this journalist at all concerned that these labs inadvertently created an infectious human retrovirus? And didn't figure it out for 15 years? Seems to me there ought to be major journalist fodder there.
  5. illsince1977

    illsince1977 A shadow of my former self

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  6. jace

    jace Off the fence

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    Here's Gerwyn's analysis:



    Reply to Cohen et al - http://www.sciencemag.org/content/331/6022/1253.short

    The research in CROI established that at least some strains of XMRV could have hypothetically originated by recombination of two endogenous retroviruses found in one particular strain of nude mouse. However, it has not been established that this strain of mouse was actually used in creating the cell line in question. The results published by Garson et al (published in Retrovirology) (1) also need to be considered.

    They demonstrated that a strain of XMRV could have entered the human population during the creation of the DU145 cell line in 1978. This research did not involve mice, and does not make any comment about the pathogenicity of the gamma retroviruses which are now replicating in the human population, it merely comment about their origin. The*act of two erv sequences recombining to form a replicative entity has thus far never been demonstrated (2).
    *
    Scientists use their own terminology which is often misunderstood by the lay public. Lawyers and doctors do likewise. Words used by such people do not have the same meaning as the words would have in an everyday normal context. It would be a tragedy if the hard won reputation of someone like John Coffin was tarnished by the quite accidental misunderstanding of the meaning of his words.

    The word "contamination" in the context used by Dr Coffin means "recombination", and he is referring to the process of how the recombination of two harmless "fossilised" viral segments in mouse DNA can spontaneously recombine to form virulent pathogenic viruses. Sadly this recombination often leads to a situation where the virus can infect new hosts.

    Dr Coffin is in no way saying that human gamma retroviruses are not now endemic in the human population, nor is he saying that these viruses are not the cause of ME/CFS or prostate cancer. I am sure that Dr Coffin will clarify his position once he realises the manner in which his comments (again quite innocently) have been misinterpreted. I did feel however that it was appropriate to write in his defence at this early stage.

    *Detecting XMRV in prostate tissue* by PCR is difficult (3). Dr Pathak had not used a tried and tested PCR assay and thus had no way of knowing whether XMRV actually existed in prostate tissue before xenograft formation. The fact that is assay could not find it is not the same thing as proving that it was not present. This has to be proven or the study falls

    It falls because testosterone pellets are used in the formation of xenografts (4). Testosterone both activates and increases the replication rate of XMRV via its effects on the CRE region within the long terminal repeat sequences (5). Thus the results can be readily explained by the fact that the use of testosterone rapidly raised the titre of XMRV to a level comparable to the concentration that most PCR assays can detect.

    It is a shame that Dr Pathak did not see the flaw in his research. He has not established that the mouse*strain in question had been used in the creation of this cell line.

    it should also be stated that the partial xenotropic sequence reported by Dr Coffin was in a different strain of mouse (129X1/SvJ), known not to play any part in the creation of the 22rv1 cell line (Robinson et al). Whatever the origin of XMRV one thing is very clear, it was first isolated from the RNA of prostate cancer sufferers (5). The only way that genomic viral RNA can be formed from the proviral DNA suggested by Coffin and Pathak is by replication.

    Thus we now know that there is at least one species of replicating oncovirus in the human population. This class of virus causes severe pathology and death in other species and there is no reason that they will not do so in humans. Thus when Dr Coffin quite innocently uses the word contamination it must be clarified that he means recombination and that recombination can increase a MLV virus's host range and increase its pathogenicity.

    Given the potential gravity of the situation researchers such as Dr Pathak should discuss alternative explanations of their findings with as much vigour as those that support their preconceived beliefs.

    1) http://onlinelibrary.wiley.com/doi/10.1002/ijc.2910210305/abstract

    2) http://www.ncbi.nlm.nih.gov/pubmed/10542419

    3) http://www.ncbi.nlm.nih.gov/pubmed/20936978

    4) http://www.ncbi.nlm.nih.gov/pubmed/8433392

    5) http://www.ncbi.nlm.nih.gov/pubmed/16609730

    6) http://www.retrovirology.com/content/7/1/108
  7. Cort

    Cort Phoenix Rising Founder

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    http://www.ncbi.nlm.nih.gov/pubmed/18684813

    The DU145 cell line may have been created in 1978 but I don't think they're saying XMRV was present in it. My reading of the paper infected the cell line first and then looked to see where XMRV integrated itself.

    Is that Gerwyn or Jane Clout or are they the same or did Jane take Gerwyn's stuff?
  8. Cort

    Cort Phoenix Rising Founder

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    I think this is an interesting point.

    Pathak should have used a PCR technique that was as effective as other techniques as finding XMRV. Was it? I have no idea. Clearly researchers should start ploughing through their stocks of that cell line.

    The problem is that if they conclude that XMRV is a contaminant they will assume that's how it got in there. On the other hand they can compare the genetic sequences; if XMRV is not a contaminant it should show distinct variability over time. If it is a contaminant it will probably look much the same.

    Then again it is a real virus! So if they find it it should change over time.....that is, if it is growing ini the D cells....its tricky stuff. Still I think they should be able to do a 'parental analysis' aka Hue and determine the logical parent....If its 22RV1 - then it probably came from there and got into other cultures. If its not then it has a different origin.
  9. kurt

    kurt Senior Member

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    If anyone here is concerned that Coffin's words are somehow being misconstrued, please observe that John Coffin was the CHAIR of the Scientific Program Committee at the 2011 CROI conference. This entire conference program was reviewed, managed and no doubt approved by Dr Coffin. He has reportedly stated directly that he believes XMRV findings are all contamination. That is not something subject to interpretation.

    Here is a direct quote from that new Cohen article in Science.

    The source of that Coffin quote was not mentioned in the article. But this does not sound like someone who is expecting XMRV to work out for CFS.
  10. ukxmrv

    ukxmrv Senior Member

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    Can it not be both though?

    A recombinant virus from a cancer cell line that is both a "contamination" there but has moved onto the human population and is now in people with CFS, prostate cancer etc. Being a "contaminate" in a call line doesn't preclude it from being anything else as well, does it?

    I have not seen anything presented that negates the findings originally published in Science.
  11. Ernie

    Ernie Senior Member

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    Well Coffin is not the only scientist involved and obviously others were shut out of the conference from presenting their findings. Just because John Coffin says doesn't make it so. It only makes you wonder what Coffin is trying to hide.
  12. Sean

    Sean Senior Member

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    It only makes me wonder about how genuinely interested some patients are in the truth about XMRV.

    Ill considered, knee jerk, gutter level, conspiracy theory smears do not help us IN ANY WAY. Coffin may genuinely believe it is contamination. Honourable and competent people can disagree.

    You want to scare off legit researchers, who might be able to help us? If so, then you are going about it the right way.

    Some in the patient community have invested waaaaaaaaay too much emotional commitment to XMRV, independent of the facts. Which is exactly what we patients accuse the CBT/GET fans of doing (and rightly so).

    As best I can tell, the facts about XMRV are that it has not yet been clearly demonstrated (in independent multiple studies) to consistently turn up in ME/CFS patients, and it certainly has not yet been demonstrated to be THE primary cause of our health problems. Neither has contamination been firmly ruled out. We simply don't know at this point.

    XMRV may not be the answer for us, and we better be ready for that possibility.
  13. Ernie

    Ernie Senior Member

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    I've tested positive for XMRV and have been ill for 16 years. It has nothing to do with conspiracy but might have everything to do with carelessness in the laboratory (possibly years ago). mouse retroviruses caused neuroimmune disease and cancers originally in mice, and it's highly possible that once crossed into humans they could do the same. I have 3 people in my immediate family with neuroimmune diseases and 2 with cancer. No other history of these illnesses in grandparents or distant relatives. Just read the data that being presented on previous science papers on how mouse viruses have been used and you will be surpised. And there are plenty of legit researchers continuing to work on XMRV. What we say has no impact. The facts will present the truth. And the truth will be published.

    If Coffin believed the contamination theory then why did he say it came from a cell line that was not even used in Silverman/Klein or The Science paper? Having a mouse retrovirus end up in people has no more conspiracy to it just as having the other 500 chemicals showing up in our breast milk and Cord blood. Many of which have been FDA approved for uses in all kinds of products we use.

    Oh and by the way I haven't invested waaaaaaaaay too much emotional commitment to XMRV. I have the paper that says I carry the retrovirus. That's all I need to know. I also know that baby forumla cans are lined with a hormone disrupter that is in most plastics we use. Wonder what the consequenses of that will be in say 20 years. Oh but that was just recently found out. Do you know what you've been drinking in your favorite plastic container? Just look it up.
  14. Cort

    Cort Phoenix Rising Founder

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    More Fun from Science. Here is the complete article in Science it is a doozy. The recent events have changed Coffin's view completely.

    Here's how these researchers believed XMRV was created. It's an amazing theory. This scenario will undoubtedly be assessed and examined and pondered in retrovirology community for a long time.

    Busch still awaits the results of the BWG tests and others.....but given the evidence presented here he believes if they don't work out - its over.

  15. Sean

    Sean Senior Member

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    Ernie, if you have any genuine technical issues with researchers/clinicians, fine, go for it. If you have any solid evidence that any of them is behaving unethically, then put your evidence in the public domain. I strongly support your right to do so in both cases.

    But don't just smear Coffin because he has a different take on it to you. I have no idea if he is correct. But he is no fool or novice, and he has earned the right to have his opinion on this issue taken seriously and respectfully, even if you do not agree with it.

    I don't recall if Coffin said it wasn't pathogenic. It could be that XMRV is both contamination (in that it was unknowingly created in a laboratory and distributed via a number of vectors, including cell lines), and is also significantly pathogenic.

    It also remains a serious possibility that XMRV is a dead end for us, and if that turns out to be so then I certainly do not want any more of the very precious and limited ME/CFS research resources spent on it, when they could be better spent on (for example) objective lab based studies on post-exertional malaise or spinal fluid, both very promising lines of research.
  16. kurt

    kurt Senior Member

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    Coffin and other retrovirus researchers also know the track record of previous retroviral hunts. I think they see a familiar pattern emerging in their XMRV findings. There is a good pub that can give some perspective. Read the 'Rumor Viruses' article for some details of the history.

    This has always been a possibility, I was worried about XMRV as soon as I learned it was a blood-borne retrovirus, which seems inconsistent with CFS epidemiology. In particular, CFS is not an STD, and not a drug user disease, not a hemopheliac disease. And CFS is not ubiquitous so it is not a 'vaccination disease.' Also CFS outbreaks are inconsistent with a bood-borne pathogen. This creates some doubt in my mind. Of course there are many other issues, pro and con, this is just an example. I think we should try to take a balanced view of the science, not presuming prejudice on the part of researchers. If bias is an issue, we should consider that prejudice can exist on either side of this debate.

    Definitely CSF/proteonomic and PEM/Fatigue Receptors are promising lines of research, and don't forget the Hydrogen Sulfide findings of deMeirlier.
  17. CBS

    CBS Senior Member

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    Just wanted to say, love the self confidence in the face of so many unknowns.

    The statement of fact that you made about CFS not being an STD will do nicely to illustrate my point.

    Sexual transmission may not be the only way to get CFS but to rule it out so confidently, I'm impressed. What do you know that we don't?

    There are a lot of subsets of CFS, many of which we may have not yet have even considered and yet your statement does not leave that open as a possibility.

    Twenty five years ago , would most people have described cervical cancer as being derived from an STD? Now the prevailing wisdom is this:

    "Persistent HPV infections are now recognized as the cause of essentially all cervical cancers."

    http://www.cancer.gov/cancertopics/factsheet/Risk/HPV

    As Laurie Anderson might say, "I could go on and on but not tonight dear, I have a headache."

    [video=youtube;DZkjoXyexKk]http://www.youtube.com/watch?v=DZkjoXyexKk[/video]
  18. kurt

    kurt Senior Member

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    AIDS is an STD, that became apparent early in the epidemic. Yes, there are other ways to contract AIDS, but those ways are all consistent with a blood-borne retrovirus (HIV).

    There may be a few cases where some of the infections in a specific CFS case are transmitted sexually. I was not trying to make an exclusive comment and did not say CFS could not be transmitted sexually, but was merely pointing out the obvious. If CFS was primarily caused by a blood-borne retrovirus it would be an STD, we would know that by now. A high percent of spouses and partners would be contracting CFS, and children, teens and adults with no sexual experiences, or who have always been monogamous along with their partners, would not be. And there could not be outbreaks the way we have seen them in CFS.

    CFS patient's partners generally do not contract CFS and sexually inexperienced or exclusive people do get CFS just the same as more sexually active people. This is not something I know that others do not, this is just a basic observation.

    I do know people who think they acquired CFS from their lifestyles, maybe a few did 'catch' some part of CFS from a sick partner, so they feel CFS could be an STD, but the evidence contradicts that fear, people with CFS come from all walks of life, from all lifestyles.
  19. Snow Leopard

    Snow Leopard Senior Member

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    The above is making assumptions about the infectivity of the virus. Virology studies (both in vivo and in vitro) so far show that XMRV/MLVs are not terribly infectious and likely to be as a result of laboratory mistakes. This may make it hard for it to spread as an STD. It is quite possible that the only way to be infected is through contaminated biological products as hypothesised here: http://www.frontiersin.org/virology/10.3389/fmicb.2010.00147/abstract

    But for the current prostate cancer/CFS/ME studies to make any sense, there needs to be multiple cases of contamination of products given to the general public.

    Actually, for that matter, there must have been multiple laboritory contamination events, to explain the difference between the Lo et al results and the other XMRV/disease studies, as well as the Retrovirology studies which failed to pinpoint the sources of contamination. Gvien that these labs didn't use 22rV1, nor mice cells, there are potentially multiple reagents that may be contaminated. It makes you wonder how easily other viruses could be common contaminants of such products.

    Given that evidence of chromosomal integration of XMRV in patients is still unproven, it's role in disease will remain questionable. But even if XMRV has not infected any humans, it is still both worrying and scientifically curious to see how pervasive it is in the laboratory.
  20. Sean

    Sean Senior Member

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    Whatever XMRV's causal role in disease turns out to be (or not to be), it will have taught scientists and health authorities some important lessons.

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