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Hunting down the cause of ME/CFS & other challenging disorders - Lipkin in London
In a talk to patients in London on 3rd September, Dr. W. Ian Lipkin described the extraordinary lengths he and his team are prepared to go to in order to track down the source of an illness, with examples ranging from autism to the strange case of Kawasaki disease.
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CROI (Retrovirology and Opportunistic Infections, Boston) on XMRV and CFS

Discussion in 'XMRV Research and Replication Studies' started by Ecoclimber, Feb 28, 2011.

  1. free at last

    free at last Senior Member

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    Its interesting seeing whats going on here, one big question that keeps being asked is why would anyone not want to find xmrv.
    The battle of words that is increasingly hotting up here elsewhere is proof that indeed, egos ( on both sides ) need defending at all cost.

    No one wants to be the loser in this battle of words, battle of science, battle of validation or not, and to try to find xmrv at all costs, or try to prove its a contaminate AT ALL COSTS.

    This really isnt how this science should be addressed. why ?

    Because when ego takes over, and losing face becomes more important than actual good solid correct science, then thats science with a agenda, its science of trying to prove something even if the evidence is misleading, or possibly contradictory.

    Its not science of the truth, but science of the, we must find a way to win the argument at all costs. this IS BIASED SCIENCE, science with a ego agenda. and its a very dangerouse way to look for the truth.

    In a hurry to be so vindicated means they make mistakes, it means they do certain things to get the answer there egos are ultimately craving.

    If something could be done differently, to get a different result. one which the ego does not want, then that test will not be performed in preferance for the other one.

    That is heading for the goal of there EGO VALIDATION, this is the worst science that could ever be happing on a important issue such as this, and one i think that everybody on both sides should be ashamed of, because its clouding the truth, its manipulating the truth, its leading to decisions being made that will likely back up the egos thirst for being correct, thirst for not losing face, thirst for looking so blatently wrong to our peers.

    And the discussions here tonight once and for all proves to me that actually could be happening in labs around the world as we speak. if things can get this bad, on a forum, god knows the power of the ego, with scientists having to answer to there peers, the media the world stage.

    Its just starting to get frightening now, seeing all this pan out on a ME forum.

    No wonder everything is so confused. when the science of the caring, has now been replaced by the science of the ego.

    We are all in trouble if this doesnt stop. but its all gone too far hasnt it. To many statements have been made. Your either on that side of the fence with us, or your with the enemy.

    Only problem is depending on which side of the fence your sitting on. BOTH SIDES IS NOW THE ENEMY.

    Maybe we need a boxing match, and then can actually get on with finding the truth for sick people. one that will likely find the truth. Not a ego driven truth, that could be falsehoods in the making, ( Again from both sides ) in so many different ways.

    Its just frightening, really it is. Unity from patients, unity from scientists, what a joke. theres one thing thats become painfully obviouse, one thats uniting everyone here, and likely in labs around the world if this is anything to go by. yeah that word again EGO. God help us all. I suspect eco climber is telling the truth, as the ego will be badly bruised when it becomes obviouse he is not. But personally we will have to have the information verified, as often people can misinterpret what they think was said to them. lets hear it from the horses mouth first before we panic.
     
  2. Sean

    Sean Senior Member

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    Can we all stop with the legal threats bullshit, and accusations of fraud or whatever.

    This benefits nobody. Except lawyers and CBT/GET lovers.

    KEEP YOUR EYES ON THE MAIN GAME
     
  3. free at last

    free at last Senior Member

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    Silverblade i think we was thinking the same thing at the same time, after i posted, i read what you said two souls sharing the same thought in time. different ways of explaing it. but the same nonethe less, good post
     
  4. biophile

    biophile Places I'd rather be.

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    The dark side clouds everything

    Researching the literature on ME/CFS has made me weary of rubbish research and spin doctoring, so please excuse me for being a little suspicious about how this XMRV/MLV debate is unfolding.

    I am very uncertain whether gamma-retroviruses are relevant to ME/CFS or not, the stakes are high and one side is in for a smackdown, but I believe the research deserves a fair chance and it does not appear it is receiving one. I don't have the capacity or skills to fully analyze all the details in order to arrive at a firm conclusion for myself right now, and I will be occupied with exploring the PACE trial results and other issues for a long time. However after reading some of the posts from [kurt and Ecoclimber and Cort] vs [Gerwyn and asleep and omerbasket] on both forums regarding this issue, the latter groups' arguments seem more convincing to me, I am glad these people are raising the important points they have, these issues of contamination and lack of positive results are far from settled.

    One possibly naive criticism I would have for the pro-XMRV/MLV researchers is what I suspect is a reluctance to publish in a low impact factor journal like PLoS ONE. The first study which failed to find XMRV in CFS patients was criticized for being rapidly published there (among methodological flaws of course) and it still had a major impact on how scientists and the public perceived XMRV. Getting published in PLoS ONE is better than not getting published at all while naysayers are being published frequently elsewhere without trouble. The recent study finding a protein signature in the CSF of CFS patients was also published in PLoS ONE.

    I agree with Sean, talk of legal action is out of place. I laughed when someone commented "ah, the American way"! Ecoclimber is issuing legal threats for "defamation of character or libel" but has no problem calling Gerwyn a "troll from the dark side of the internet" (I doubt the Forum Rules would allow for that if interpreted strictly). And as Esther12 implied, good luck getting anyone to care.

    [​IMG]

    I don't really understand how the moderators on this forum can be offended at or censor the suggestion that people are spreading "lies", but then tolerate personal attacks and very serious legal threats. The Forum Rules does not say anything about threats of legal action AFAIK, but threats of violence is definitely listed as unacceptable, so ask this to yourself, would you rather be dragged through the courts and face financial ruin for the rest of your natural life, or would you rather receive a one off physical beatdown in the street? If you answered "beatdown", then you have a good idea how serious the threat from Ecoclimber is. He is openly threatening to ruin the lives of a bunch of people on a public forum and apparently the moderators of this forum have no problem with this.

    I think Ecoclimber made a bad move, because empty legal threats are common on the internet, so Ecoclimber's credibility will be questioned if these threats aren't carried out, but his character will be questioned if he does carry it out. Perhaps there are aspects of this situation that I am unaware of, but the more I think about it the more I am disgusted by it.

    Anyway, back to the science, I would like an explanation for this:

    Edit: How can this be reconciled with claims of contamination?
     
  5. Cort

    Cort Phoenix Rising Founder

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    If its true that Lo/Alter did both tests I would think (laymen speaking) that would rule out contamination. The way the mtDNA test was explained to me is that it is actually more sensitive than the IAP test but during the mtDNA test some elements are 'filtered' out (I know I'm slaughtering this :)). Those elements are not filtered out during the IAP test - that brings up the question if those elements could harbor contamination...

    That's my take and it may be wrong; mtDNA more sensitive but could miss something; IAP less sensitive but more complete in a way.
     
  6. Cort

    Cort Phoenix Rising Founder

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    CROI: XMRV Possibly a Lab Product Produced by Nude Mice

    My take - as best as I can...

    Xenograft - What is a xenograft? It is a piece of tissue from one species grafted onto another species. The xenograft here is the original prostate tumor tissue that was passaged in nude mice. (I believe this mean the tumor tissue was grafted onto nude mice and grown?).

    The researchers went back to early samples of the xenograft and found that it contained both tumor and mouse DNA (it was ‘contaminated' with mouse DNA). They found two endogenous proviruses which when put together essentially produced XMRV. Because we know the 22Rv1 cell line produces XMRV they then looked for XMRV to see when it appeared.

    The Key Point - They found that XMRV was not present in the prostrate tumor tissue (or the mouse cells) early in the process. It only showed up after they started passaging the prostate tissue through the nude mice cells. This suggests that during the grafting process the proviruses from the nude mice combined in the prostate cell line to produce XMRV. The gist is XMRV was never present in the human the 22RV1 cells came from - it was a virus that was probably created in the lab.

    XMRV can infect prostate cells but there’s a huge difference between a virus that can infect cells in the lab and a virus that can pass into the human body through the mouth or semen, get by all the body’s defenses and then infect cells. Remember that the entire XMRV situation with CFS was generated by Dr. Silverman's discovery that it was present in prostate cancer tissues. This study suggests it was never present in those tissues. Dr. Silverman, of course, is now checking those prostate samples out to see if there is human DNA flanking XMRV. If there is then it actually did infect them; if there isn't then it didn't.

    I think this reports also kind of highlights how dangerous these labs can be. It suggests that lab created a mouse virus that can infect human cells! That’s a potentially very dangerous situation.

    One problem, though, with the idea of XMRV being created in the lab and then spreading throughout the human population and causing CFS is that even in human samples, at least so far as we know, XMRV still looks very much like the 22RV1 strain; ie it looks like it just came out of the lab - it doesn’t look like a virus that has been battered about by the immune system. Dr. Rein on Dr. Raccaniello’s blog, however, suggested that they didn’t know enough about XMRV to say that it should look really different. It seems like it should but they don’t know that for sure. So the jury is still open on that question.

    The macaque studies showed XMRV can infect primates but that study has been criticized for the enormous number of viruses they infected the monkeys with because it’s inconceivable that the monkeys could have been exposed to that much virus naturally. One report said that amount of HIV would have quickly killed the monkeys. Even with all that virus the monkey’s immune system appears to have handled it pretty well - knocking it down so completely it was quickly hard to find. For XMRV to be a viable virus it has to go from person to person (show up in the saliva or semen or breast milk, etc). So the jury is still out here - it can infect primate cells - but would it do so in real life circumstances?

    In order to find that it has infected humans researchers have to show that it's integrated into human DNA; that is when they grow out its sequences they find they are flanked by human DNA - not mouse DNA. That is what Dr. Silverman has purportedly been doing recently and what Alter and Lo are believed to have been doing.
     
  7. SOC

    SOC Senior Member

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    Can we please leave the nasty, ugly arguments on ME/CFS forums over there?

    I, and others, don't go there because we don't want to deal with that garbage. We don't need their incivility creeping over here.

    Finally, I don't like be yelled at in proxy for others someone can't yell at directly.
     
  8. George

    George waitin' fer rabbits

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    Here is the link to the actual talk given at the CROI for anyone who missed it.

    http://www.retroconference.org/2011/data/files/webcast_2011.htm

    I was surprise to see them state that the virus could not have been created prior to this 92-96 lab event. In November, we went over the Christine Kozack paper here on the forum which states that most likely the virus arose via an Asian and European mouse event most likely in the California area. Yet here Dr. Coffin denies the possibility?????

    (note: so are like John and Johnathan (Stoye that is) attached at the hip or what???)
     
  9. Cort

    Cort Phoenix Rising Founder

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    Here's from Dr. Racaniello's blog; it seems like it was present in 1978?

     
  10. Cort

    Cort Phoenix Rising Founder

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    They have been publishing together for over 25 years!

    Virology. A new virus for old diseases?
    Coffin JM, Stoye JP.
    Science. 2009 Oct 23;326(5952):530-1. Epub 2009 Oct 8. No abstract available.
    PMID: 19815721 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    2.
    Role of APOBEC3 in genetic diversity among endogenous murine leukemia viruses.
    Jern P, Stoye JP, Coffin JM.
    PLoS Genet. 2007 Oct;3(10):2014-22. Epub 2007 Sep 10.
    PMID: 17967065 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    3.
    A provirus put to work.
    Stoye JP, Coffin JM.
    Nature. 2000 Feb 17;403(6771):715, 717. No abstract available.
    PMID: 10693785 [PubMed - indexed for MEDLINE]
    Related citations

    4.
    Endogenous retroviruses: a potential problem for xenotransplantation?
    Stoye JP, Le Tissier P, Takeuchi Y, Patience C, Weiss RA.
    Ann N Y Acad Sci. 1998 Dec 30;862:67-74. Review.
    PMID: 9928207 [PubMed - indexed for MEDLINE]
    Related citations

    5.
    The dangers of xenotransplantation.
    Stoye JP, Coffin JM.
    Nat Med. 1995 Nov;1(11):1100. No abstract available.
    PMID: 7584963 [PubMed - indexed for MEDLINE]
    Related citations

    6.
    Structure and expression of the hairless gene of mice.
    Cachon-Gonzalez MB, Fenner S, Coffin JM, Moran C, Best S, Stoye JP.
    Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7717-21.
    PMID: 8052649 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    7.
    Molecular analysis of viable spontaneous and radiation-induced albino (c)-locus mutations in the mouse.
    Rinchik EM, Stoye JP, Frankel WN, Coffin J, Kwon BS, Russell LB.
    Mutat Res. 1993 Apr;286(2):199-207.
    PMID: 7681531 [PubMed - indexed for MEDLINE]
    Related citations

    8.
    Characterization of the endogenous nonecotropic murine leukemia viruses of NZB/B1NJ and SM/J inbred strains.
    Frankel WN, Lee BK, Stoye JP, Coffin JM, Eicher EM.
    Mamm Genome. 1992;2(2):110-22.
    PMID: 1311971 [PubMed - indexed for MEDLINE]
    Related citations

    9.
    Virological events leading to spontaneous AKR thymomas.
    Stoye JP, Moroni C, Coffin JM.
    J Virol. 1991 Mar;65(3):1273-85.
    PMID: 1847454 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    10.
    A linkage map of endogenous murine leukemia proviruses.
    Frankel WN, Stoye JP, Taylor BA, Coffin JM.
    Genetics. 1990 Feb;124(2):221-36. Erratum in: Genetics 1990 Jun;125(2):455.
    PMID: 2155154 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    11.
    Genetic identification of endogenous polytropic proviruses by using recombinant inbred mice.
    Frankel WN, Stoye JP, Taylor BA, Coffin JM.
    J Virol. 1989 Sep;63(9):3810-21.
    PMID: 2547997 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    12.
    Genetic analysis of endogenous xenotropic murine leukemia viruses: association with two common mouse mutations and the viral restriction locus Fv-1.
    Frankel WN, Stoye JP, Taylor BA, Coffin JM.
    J Virol. 1989 Apr;63(4):1763-74.
    PMID: 2564439 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    13.
    Genetics of endogenous murine leukemia viruses.
    Coffin JM, Stoye JP, Frankel WN.
    Ann N Y Acad Sci. 1989;567:39-49. Review.
    PMID: 2552892 [PubMed - indexed for MEDLINE]
    Related citations

    14.
    Fv-1 N- and B-tropism-specific sequences in murine leukemia virus and related endogenous proviral genomes.
    Boone LR, Glover PL, Innes CL, Niver LA, Bondurant MC, Yang WK.
    J Virol. 1988 Aug;62(8):2644-50.
    PMID: 2839691 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    15.
    Role of endogenous retroviruses as mutagens: the hairless mutation of mice.
    Stoye JP, Fenner S, Greenoak GE, Moran C, Coffin JM.
    Cell. 1988 Jul 29;54(3):383-91.
    PMID: 2840205 [PubMed - indexed for MEDLINE]
    Related citations

    16.
    Highly preferred targets for retrovirus integration.
    Shih CC, Stoye JP, Coffin JM.
    Cell. 1988 May 20;53(4):531-7.
    PMID: 2836061 [PubMed - indexed for MEDLINE]
    Related citations

    17.
    Polymorphism of murine endogenous proviruses revealed by using virus class-specific oligonucleotide probes.
    Stoye JP, Coffin JM.
    J Virol. 1988 Jan;62(1):168-75. Erratum in: J Virol 1988 Jul;62(7):2530.
    PMID: 2824845 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    18.
    The four classes of endogenous murine leukemia virus: structural relationships and potential for recombination.
    Stoye JP, Coffin JM.
    J Virol. 1987 Sep;61(9):2659-69.
    PMID: 3039159 [PubMed - indexed for MEDLINE] Free PMC Article
    Free full text Related citations

    19.
    Molecular basis of host range variation in avian retroviruses.
    Dorner AJ, Stoye JP, Coffin JM.
     
  11. August59

    August59 Daughters High School Graduation

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    They are butt buddies and let there be confusion about this statement!!
     
  12. free at last

    free at last Senior Member

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    Think i read somewhere that judy didnt trust the IAP test, regardless if the OAKS paper dected contamination in 90 to 100% depending on what test was used, suggests it had no trouble finding most of the contamination in that lab, with only a 10% difference in both contamination tests. It surely indicates if Judys samples are as contaminated as what the oaks papers would like us to belive. then she should have picked up something, and the oaks paper kind of shoots itself in the foot on that i think ? I think it should be made aware to Silverman what is being said on open access forums, so he knows what is being discussed, maybe he would like to comment ?
     
  13. eric_s

    eric_s Senior Member

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    I'm no scientist, but if we assumed the hypothesis that XMRV originated from 2 mouse endogenous retroviruses was correct, would then a test for mouse mtDNA or IAP pick up the contamination?
    I'm not sure, because the contamination would then be with a new virus, that originates from the human cell line xyz (don't remember the exact name) and not with mouse material.
     
  14. eric_s

    eric_s Senior Member

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    Ecoclimer, you have stated things like "fellow researchers and institutions in good standing within the community" and "This is a warning shot across the bow of members of the ME/CFS Forum who wish to engage in such jocular comments against myself, the researchers and institutions I represent."

    Given the circumstances, i would like to ask you to provide more information about yourself. You have made yourself something different than an "average forum member" through your actions, which were very positive in their general nature (the chance for more research, providing inside information), so i think it is more or less logical that forum members ask themselves questions about where you're coming from.

    Talking about "fellow researchers" and "researchers and institutions you represent", to me, implies that you are a researcher and are in one way or another affiliated with researchers and institutions. This is news to me and i think it is important. I think people should play openly and not hide who they are, unless necessary, because disclosing it might have negative consequences for them, which is a possibility i can't see here. I remember when i first came here, i got into an argument and people accused me of having an agenda as well. I posted my passport and ID card, with the critical information blacked out. I would not necessarily recommend this to anyone else, but i think you should provide more clarity as well. So, i'd like to ask you to step forward and shed light on things.

    We will know in a couple of days the latest anyway wheter what was reported here was objective or not, i guess. And i think it will have some consequences anyway, not matter in what direction things turn.

    As far as the other argument is concerned, i think Ecoclimer is totally right to consider legal action, this is a possibility anyone has, he, just as well as the other side of the argument. I'm thinking about the Drs. Silverman, Mikovits etc., for example.
    This is serious business, we are talking about the health and lives of millions, careers, reputations, a lot of money etc. The internet is in no way a vacuum, the law applies here just as anywhere else. There is no problem in "threatening" others with legal action, this is generally not a threat that is illegal in any way. This is the way conflicts are solved in a civilized society, it's better than picking up arms. And everybody is free to feel about this statement as he wishes, if someone thinks there is no danger, fine, you can go on and don't have to worry, if you think legal action might be succesful, then this is somewhat of a proof that you have stepped over the line.
    We, as a community, should probably make better use of those possibilities as well.
     
  15. alex3619

    alex3619 Senior Member

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    the nature of science

    Hi, I wanted to quote some things from one of my favorite philosophers of science. Untested scientific claims are not to be trusted. Here are three quotes from Karl Popper, a logician who wrote about falsifiability in science:

    http://www.brainyquote.com/quotes/authors/k/karl_popper.html

    Good tests kill flawed theories; we remain alive to guess again.

    In so far as a scientific statement speaks about reality, it must be falsifiable; and in so far as it is not falsifiable, it does not speak about reality.

    Whenever a theory appears to you as the only possible one, take this as a sign that you have neither understood the theory nor the problem which it was intended to solve.


    There are multiple hypotheses in these debates. The final verdict is not in. This debate will continue until there is sufficient evidence to declare a winner (on the then current evidence). That is what should happen, not that new evidence cannot upset any conclusion.

    Sorry to wax philosophical, but science is about uncovering the nature of reality. I welcome debate, but the debate should be about quality of the science, the evidence, and the interpretations. It is not so much about the people.

    Here is something I like to say, paraphrased from very old opinions on truth:

    "Truth from a peasant is better than lies from a King."

    It is the "truth" (actually, evidence and argument) that matters, not who said it. Personal attacks help nobody.

    Bye
    Alex (unashamedly a Popperian)
     
  16. SilverbladeTE

    SilverbladeTE Senior Member

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    Somewhere near Glasgow, Scotland
    *bows* :)
    The history, morality/ethics of sceince over the years are very interesting. Also a lot of tragedy, too, people bakc "then" are no different from "now", just maybe bit more informed and hus maybe, hopefully, bit more enlightened.
    Ego, research grants, patent rights ($$$) etc all cause serious problems. If it wasn't for the fact most researchers are honest, they do it for the sheer LOVE of it, we'd be in a hell of state.
     
  17. Mya Symons

    Mya Symons Mya Symons

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    This is what I don't understand. How can they say every positve study is the result of contamination when they found XMRV in the organs of monkeys after they were infected (lymph) and in human tonsils? Are all research and medical supplies contaminated with MuLv's? Because that is the only way I can see this happening.

    You would think the studies done later would be careful not to use anything that others have claimed to be contaminated, like certain kinds of PCR. Or did they not think of that?

    Regarding the cell line that was contaminated--Did they use this contaminated line in all of their experiments?

    Any scientists or smarties here who can explain? Please.
     
  18. currer

    currer Senior Member

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    Hi,
    Nobody has responded to my post - it got forgotten in the upset over ecoclimber. Perhaps it wasn't very relevant but - if this conference is set to bury XMRV how does this affect Alter and Lo's findings of other PMLVs in CFS?
    The conference is focusing on XMRV. When Alter and Lo published they were dismissed because they did not find XMRV. Perhaps that is a strength? I thought further MLV's were being found in CFS - a wide range. Unless they all turn out to be contamination. But Alter defended his MLV findings strongly. Remember the retesting they did where they thought the virus had mutated over time?
    As long as this research is purely on XMRV and its origins it cannot relate to the other findings of PMLVs. I thought even Mink focus forming virus had been found. Suppose there is a broad cocktail of MLV's in CFS all adding to disease - not just one?
    Also remember that PCR has never validated a connection between a suspected viral cause and a disease. It may just be the wrong technology and lead to too many conflicting findings that are too sensitive to tiny perturbations for anyone to know with certainty what is going on at a cellular level.

    Please ecoclimber do not take legal action - that really is upsetting. We are all ill here, and if you have been attacked dont retaliate in this way. I think we should all be more alert to unfair things that are posted on the forums and be more ready to post in defence of other people when they are attacked, not leave them to defend themselves. Then perhaps things would not get so out of proportion. Why cant we police ourselves and not waste money going to lawyers. I was shocked by what they were posting on the other forum but I felt it should be ignored because they were all clearly ill. Please just let it go ecoclimber.
    The CFS/ME world is full of argument and hurt feelings because we are ill and under strain. It causes a lot of problems but then what other group of sickies have to advocate for themselves as well as deal with illness and financial problems etc etc. It is not surprising that some are a bit unbalanced.
     
  19. Mya Symons

    Mya Symons Mya Symons

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    " Integrated virus was found in Klein's flash frozen prostate tissue by the same lab studying XMRV integration sites in a human cell line directly infected with XMRV. The cell line would contain thousands to millions of integration sites at high concentration, so contamination of the patient samples with this material is not unlikely."

    Hi Ecoclimber. I don't know how they use cells lines in experiments. Do you know the answer to these questions? Do they always use a cell line in every experiment and was the same cell line used for all of the XMRV experiments?

    PS I am very sorry you are pulling out of CFS research. My son would have very much liked to meet you (He was diagnosed with CFS and FMS a few years ago. He wants to help other people also. He has had the video of Nada and the Message from Libya on his Facebook status for about a week now. He wants people here to know what is going on. His message was this--anarmed civilian protestors are being killed, please call your politicians and ask them to put pressure on the protestors governments. They want to be free.

    Oh, one more thing: He wants to be a lawyer when he grows up!
     
  20. Cort

    Cort Phoenix Rising Founder

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    Good question Eric...I don't think it would...They know XMRV's sequence so they should know if mtDNA and IAP would falsely suggest it was mouse.....I would guess.
     

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