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link that shows XMRV is basically identical to man-made virus from the 80's?

Discussion in 'XMRV Testing, Treatment and Transmission' started by markmc20001, May 31, 2011.

  1. markmc20001

    markmc20001 Guest

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    This is a question folks. But has been on my mind for awhile now. Kind of grinding away in back of my mind.

    I believe is was moderator Mark that posted a paper that showed XMRV was basically identical to a man-made virus from the 80's.

    Anybody have that link by any chance? Can anybody clarify that? Interested in knowing if it is the exactly the same virus.
  2. Mark

    Mark Acting CEO

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    Sorry mark, I'm not sure what you're referring to here. Coffin et al have claimed that XMRV has high sequence identity with two sequences present in a species of mice through which the prostate cancer cell line VP62 may have been passed - and based on this data they conclude that XMRV was created in the lab in about 1992 (I think).

    I don't think it was me that posted that link, though, and I'm not sure whether this is what you're referring to anyway.
  3. Bob

    Bob

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    I'm pretty sure that there's an old paper about a man-made virus but it wasn't identical to XMRV.
    I can't remember the details though.
    Mark (moderator Mark), I think you've posted details about a man made virus before?
    markmc, if I come across the research, I'll post it here for you.
  4. currer

    currer Senior Member

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    I remember this.
    It was a genetically modified MLV for gene insertion which had not been authorised for use and it escaped and ended up contaminating a tissue culturethat was tested together with squirrel monkey virus.
    I'll look for it.
  5. Sam Carter

    Sam Carter Guest

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    Retrovirology. 2009 Sep 22;6:86.

    Unintended spread of a biosafety level 2 recombinant retrovirus.

    Stang A, Petrasch-Parwez E, Brandt S, Dermietzel R, Meyer HE, Sthler K, Liffers ST, Uberla K, Grunwald T.

    http://www.retrovirology.com/content/6/1/86
  6. currer

    currer Senior Member

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  7. Bob

    Bob

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    A great bit of team work!!! :D
  8. markmc20001

    markmc20001 Guest

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    thanks folks.

    Mark. I remember somebody (Coffin?) claimed it was similar to the one from the 1990's. But weren't the blood samples from patients taken from Dr Peterson back into the 1980's from the incline village folks? There was some confusing stuff going on around that 1990 claim from my re-collection?

    That's kind of what I was trying to figure out Bob. Just trying to find out if it was determined that XMRV was man-made in the 1980's. Didn't articulate it well.
  9. markmc20001

    markmc20001 Guest

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    thank you.
  10. Bob

    Bob

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    Oh OK, I think I know what you mean mark.
    There is a study which suggests which year XMRV was formed. Is that the recombination study? I can't remember the year that they came up with, but i'll look it up.
    Did Mikovits test some of Peterson's deep frozen samples? If so, I don't know which year they were drawn.
    Alter and Lo tested some deep frozen patient samples, from a number of years ago (1980's?), but I can't remember exactly from which year. I'll look that up as well.
  11. markmc20001

    markmc20001 Guest

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    Hey Bob, Apppreciate that. Please don't knock yourself out. I can see I'm not able to think well enough to put together a meaningful question at the point, or read any of the stuff you give me.

    I know where I got that idea though. "contamination"=man made virus? is that true? (The "contamination" is only an allegation at this point, but contamination is a man facilitated event that might happen intentionally or unintentionally during lab handling?
  12. Bob

    Bob

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    Mi mark,

    Yes, one of the theories is that XMRV was originally created in a lab, in a prostate cancer cell line. The study says that when the cell line was passaged through mice, the MLV recombination event took place which created XMRV. This is the study you were refering to, and like you say, they have worked out a year for when they think XMRV was created.

    This study is a theory about how and when XMRV was created, and it doesn't prove that there is any contamination anywhere. The authors suggested that their investigation shows that XMRV is not a wild human virus and that the WPI research was due to contamination, based on their findings, but they don't have proof for that.

    The authors of that study are saying that all the XMRV that has been found to date is due to contamination from cell lines.

    They say this for two reasons:
    1. That there isn't enough variety in the XMRV gene sequences found so far for it to be a wild human virus. (They say we would expect more mutations in a wild human virus.)
    2. That the recombination event is such a rare occurrence that it is highly unlikely to have happened at any other time, and so XMRV can only be a lab virus, and not a human virus.

    There's a couple of weaknesses with this argument:
    1. There have now been further genetic variety of XMRV discovered by various researchers including the WPI, who have now published the gene sequences.
    2. Even if there wasn't much variety, there may be other reasons that this is the case, such as: the virus could be spread by another method other than person to person infection (e.g. vaccines); or the virus might just have very different behaviour to other known human retroviruses.

    Like you said, the date issue is also very important, but I can't remember any of the details...
    I'll post them here when i come across them.
  13. Jemal

    Jemal Senior Member

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    Would it be possible for a recombination event to happen in nature as well? Because I just read that the mice who carry pre-XMRV were used in the US as early as 1930. If I understand correctly you have mice that carry pre-XMRV1 and mice that carry pre-XMRV2. If they breed, couldn't a recombination happen as well? I have no clue (obviously).
  14. Bob

    Bob

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    Here's the info from the study, mark:

  15. Bob

    Bob

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    I thought it was possible Jemal, but I don't know for sure.

    The authors thought that this specific event was unlikely to have occurred on another occasion, purely (I think) based on the probability of it happening (see my quote, in previous post.)
  16. Jemal

    Jemal Senior Member

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    Thanks!
    "Essentially negligible"... how would they know that. Hmmm.

    These mice have also been used in laboratories since 1930 by the way, so who knows what happened earlier!?
  17. Bob

    Bob

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    Yes... I've heard their theory, about the recombination being unlikely to happen anywhere else, being questioned, but I can't remember where I was reading about that. If I come across it again, I'll post it here.
  18. alex3619

    alex3619 Senior Member

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    Hi Jemal, the short answer to your question is Yes. The long answer is complicated.

    My understanding of this was based on a thread on PR mid-late last year. George has studied the history of this. In the early 1930s, at the site of the earliest strongly suspected outbreak of ME in California in 1934, they were investigating a problem called mouse encephalitis. They showed it was transmissible. I ran a search and found a scanned newspaper clipping from the time. It think I might be able to dredge it up, but I would have to rerun a search to find the link.

    They also vaccinated some people, I think, but I do not recall well enough to be sure. These people became sick and sued, received a million each in compensation. Could that be how XMRV got into the population?

    Pre-XMRV genes seem to be scattered over different mouse species and populations. It could have arisen many times.

    However, Coffin et. al. assert that the exact recombination events that gave rise to XMRV are so unlikely that they could not have occurred twice. In addition, the virus appeared in the process of developing a cell line - so it they claim it must have arisen in that cell line. They could be be right about that point.

    On the other hand, if contamination is so easy from this virus, and it was pre-existing, it might be that this cell line, which is unusually susceptible to XMRV, might have itself been contaminated.

    In addition, the argument that the crossover event could not have happened twice (or three, or a hundred) times is not a strong one in my view. Based purely on math, it does look strong from one perspective - one chance in a very big number that it could happen (I would have to go back to CROI to find that number). However, this calculation presumes a random chance of recombination, which is misleading. It is probably far less than random. This means the probability calculation is flawed, as probability requires equal weight to all possibilities for this kind of calculation.

    In my view, recombination events are more likely to occur at specific points in a viral strain genetic sequence. In addition, most recombinations will be flawed and non viable. However, what if there were a dozen recombination events, and those virus recombined several times? What happens to the odds then? Mix and match and genetic drift, together with high viral replication rates and convergent evolution, could have led to XMRV being formed several times in history. There are a lot of mice, and a lot of mammals, in the world. I am not saying this is the case, only that there is room for doubt.

    The strongest argument against the lab recombination theory during cell line manufacture causing experiment contamination comes from the data of WPI and other researchers. It should be in all the controls at the same rate. It should be detectable in reagents etc. It has not been found in the reagents, nor in most of the controls.

    Bye
    Alex
  19. insearchof

    insearchof Senior Member

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    Hi Alex

    Were the compensation details in this article Alex? I would really like to read it. If you find the link to the article could you please post it?

    In the 1930s, they were using mice that were capable of creating XMRV as I understood it.

    The mice were supplied to the hospital lab associated with the first identifiable outbreak of ME at the County Genreal Hospital in LA 1934.

    From 1932/33 there were outbreaks of encephalitis. In 1933 the outbreak was St Louis Encephalitis and these outbreaks were killing people. So they started to research in or around July of 1933 if my memory serves me. However the report on the research suggests it could have been earlier than this.

    Also, of note poliomyelitis outbreaks were also occuring at the same time

    In 1934 there was an outbreak at the County General Hospital , but it was not poliomyelitis. It was regarded as a very unusual case of atypical poliomyelitis. It was the first noted case of ME.

    With regard to the 1933 experiments on encephalitis, the outcome of that experiment was, that they found a prophylactic human serum protected against St Louis encephalitis for a period of 2.5 years.

    The experient itself used the ground up human brain tissue of those who had died from encephalitis and injected into mice, monkeys and other animals. Then they took the sera from humans who had been exposed to not only encephalitis but also to poliomyelitis and tested this on animals exposed to St Louis Encephalitis. It was effective in about 82% of cases.

    Encephalitis + poliomyelitis = encephalomyelitis, myalic anyone?

    In 1934, polio cases were admitted to the infectious diseases wards of the County Gen Hospital LA. 198 medical personel fell ill with what looked like polio but was not. Gilliam who investigated the outbreak reported that it was a atypical poliomyelitis and a very unsual case of it. This outbreak was later called ME and is referred to as the first known case of such.

    With the fear of polio - the medical staff at this hospital received a mysterious prophylatic made from human sera. They subsequently all fell ill with what we now all ME and sued both the hospital and the government I believe. It was settled for a substantial sum, reportedly enough for each member to buy 3 pieces of prime LA real estate. From my reading, I understood the exact details were not known, because of a non disclosure clause as a condition of the settlement.

    Is it possible that the human prophylactic serum given to the medical staff, was the sera the subject of the experiments? Remeber the sera given to the mice and other animals in those experiments was sera of humans who had been exposed to encephalitis and poliomyelitis.

    It was noted to have subsequently spread in the US and then a couple of years later was being detected in Europe.

    Was ME a lab creation of 1934?

    What happened to the XMRV capable producing mice that were also injected with the prophylactic encephalitis/poliomyelitis mix?
  20. Jemal

    Jemal Senior Member

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    Thanks for the reply, Alex! Also like the additional information, insearchof.

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