Trust science, not scientists

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XMRVWhether or not the retrovirus XMRV is a human pathogen has been debated since the virus was first described in 2006. The answer is now clear: the results of Blood XMRV Scientific Research Group, along with a partial retraction of the 2009 Science paper describing identification of the retrovirus in patients with chronic fatigue syndrome (CFS) show that detection of XMRV in patient samples is a result of contamination.

The Blood XMRV group obtained new blood samples from 15 individuals previously shown to be positive for XMRV (Lombardi et al., 2009) or MLV (Lo et al., 2010) ; 14 of these were from CFS patients. Fifteen blood samples were also obtained from healthy donors. The samples were coded and sent to 9 laboratories for analysis. These laboratories (Abbott Molecular, Abbott Diagnostics, CDC, FDA/Lo, FDA/Hewlett, Gen-Probe, NCI/DRP, and WPI) conducted validated assays for viral nucleic acid, viral replication, or viral antibodies. Positive control samples were also included that were ‘spiked’ with XMRV, in the form of cell culture fluids from the cell line 22Rv1. Each laboratory was at liberty to choose which assays to carry out.

Two laboratories reported evidence of XMRV in the coded samples.  Only WPI identified positive specimens by PCR: two from negative controls, and one from a CFS patient. The FDA/Lo laboratory did not detect any positives by PCR, using the same nested assay that they had previously reported in their published study. The samples tested included 5 specimens that were positive in the Lo et al. study.

Lombardi and colleagues have previously concluded that viral culture is the most sensitive method for detecting XMRV; however the FDA/Hewlett laboratory failed to culture virus from CFS samples. This laboratory did culture virus from positive control specimens, demonstrating the sensitivity of their methods. The FDA/Ruscetti laboratory recovered virus from 3/15 CFS samples but also from 6/15 negative control specimens. WPI did not carry out viral culture assays due to contamination of their cell lines with mycoplasma.

Four laboratories tested the samples for the presence of antibodies that react with XMRV proteins. Only WPI and NCI/Ruscetti detected reactive antibodies, both in CFS specimens and negative controls. There was no statistically significant difference in the rates of positivity between the positive and negative controls, nor in the identity of the positive samples between the two laboratories.

These results demonstrate that XMRV or antibodies to the virus are not present in clinical specimens. Detection of XMRV nucleic acid by WPI is likely a consequence of contamination. The positive serology reported by WPI and NCI/Ruscetti laboratories remained unexplained, but are most likely the result of the presence of cross-reactive epitopes. The authors of the study conclude that ‘routine blood screening for XMRV/P-MLV is not warranted at this time’.

One of the authors on Lombardi et al., Robert Silverman, decided to reexamine some of the DNA preparations from CFS patients that were originally used to detect XMRV DNA by PCR. He found that all the positive specimens from CFS patients were contaminated with XMRV plasmid DNA. Therefore the authors of the original study have retracted Figure 1 (single-round PCR detection of XMRV in CFS PBMC DNA); table S1, XMRV sequences, and figure S2, phylogenetic analysis of XMRV sequences.

A puzzling aspect of Silverman’s results is that XMRV plasmid DNA was detected only in samples from CFS patients, not healthy controls. This pattern would not be expected if the specimens were properly blinded, that is, coded so that the investigators did not know which were controls and which were from CFS patients. The authors offer no explanation of these findings.

The paper reporting contamination of samples with XMRV is entitled ‘Partial Retraction‘. It’s not clear to me why the entire paper has not been retracted. After removing the PCR and nucleic acid sequencing results, there is no evidence indicating the presence of XMRV in the patient samples. The remaining experiments show detection of a retrovirus by cell culture experiments, and the presence of viral proteins or antibodies to the virus in clinical specimens. None of these findings prove that what is being studied is XMRV. The title of the original paper ‘Detection of an infectious retrovirus’, XMRV, in blood cells of patients with chronic fatigue syndrome‘, is unsupported.

In an accompanying article on the XMRV story entitled ‘False Positive‘, Judy Mikovits of WPI notes that “Anyone who says this is a lab contaminant has drawn the wrong conclusion and has done a disservice to the public”. She goes on to imply that a gammaretrovirus is likely involved in CFS. On the contrary, pursuing the CFS-gammaretrovirus hypothesis is a disservice to those with CFS, and detracts from efforts to solve the disease. There are no data to support such an association, and to suggest that a lab contaminant, XMRV, has pointed the way to a bona fide etiologic agent seems implausible.

XMRV does not cause CFS. The virus arose in mice between 1993-96, and its detection in patient samples is clearly a result of contamination. Reaching these conclusions has required a long and often contentious journey that has highlighted the best and worst aspects of scientific research. There are many lessons to be learned from XMRV, but an important one is that science progresses not from the work of a single investigator, but from the collective efforts of many laboratories. XMRV reminds us to trust science, not scientists.

344 thoughts on “Trust science, not scientists”

  1. Anonymous

    Mikovits and Ruscetti have said this at several conferences and the Lombardi et al. proves they didn’t use VP62.  You have never read the paper RRM.  All you will do is avoid ever accusing them to their faces.  You have shown yourself to be below contempt.  You would never dare make such comments to Robert Siverman, Frank Ruscetti or Judy Mikovits.  This is why you won’t contact them. 

    The quote is for you before you state making up any more lies.  Here it is again.”Neither 22Rv1 nor any of the cell lines reported to be contaminated with XMRV or cell lines growing the VP62 infectious molecularly cloned virus was in the laboratories where the patient cells were isolated.”  

  2. RRM

    Was my explanation really that bad? I hope Drosha has some experience in explaining this to five year olds, and then he or she might help you understand. I really can’t make it any simpler. Sorry.

  6. RRM

    – Lo stated that either primer set could detect a “high frequency” of positives in PATIENTS as well as in controls.

    – Do you happen to have a ‘Hanson talk’ source that is more reliable than mine, and are you willing to share said source? I take it the answer is “no”.
    – Science Editor in Chief: ‘they were unwilling to share their data’

    – Science reporter, hot from the press: “WPI did use VP62, in contrast to claims posted here.”
    http://news.sciencemag.org/scienceinsider/2011/09/insider-looking-out-how-people.html

  7. RRM

    If it is a fact, would you happen to have a source? 

    You do know that is the way to convince other people. Screaming you are right does not make it so.

  8. Anonymous

    Silverman has set it straight.  Email him.  You are avoiding the truth.  Wouldn’t matter what I post.  You won’t believe it and will make up more lies.  You have to contact them.

    Cohen has had a dirty trick played on him.  The paper shows they did not use VP62. Cohen should name who told him this so that person can be shown to be a liar.  

  9. RRM

    No, that is not the reason at all. 

    In fact, if you would make Judy Mikovits or Frank Ruscetti contact me, I would gladly repeat what I have stated here.
    Again, Science reporter Jon Cohen, who interviewed all scientists involved, just stated the folowing:”WPI did use VP62, in contrast to claims posted here.”http://news.sciencemag.org/scienceinsider/2011/09/insider-looking-out-how-people.html?ref=hpYou see, I am not lying.

  10. Anonymous

    The WPI and NCI samples have been proven to not contain VP62/22Rv1.    Again, what is your scientific reason for saying that the findings are not related?  They are the same viruses.  Lo opened up his primers, that will pick up more diversity.  But what is the scientific reason you refuse to name that would make them not the same viruses?  Lo and Alter still agree they are the same findings.

    http://3.bp.blogspot.com/-LE3KbJjEN2g/TnzsXvAzL0I/AAAAAAAAAEE/Otc07jeQbFs/s1600/Slide07.jpghttp://1.bp.blogspot.com/-pCSELs4zkeM/TnzsYR_SI9I/AAAAAAAAAEI/JpeGZc6kkyQ/s1600/Slide08.jpg

  11. Anonymous

    I will say this again.

    There is no sign of the VP-62 plamid or any other nucleic acid sequence in Lombardi et al.  

    You are a liar RRM.  

  12. Dorian McILROY

    Thanks for a very clear and well-worded summary of the story. There is really nothing else to say on the subject.

  13. RRM

    Nope, this does apply to the partial sequences from WPI as well. The sequence alignment I posted earlier, was derrived from the WPI sequences.

    In scientific terms: there is no “gold standard” method of showing viruses are “different” (not really a scientific term you used there, I think you should have used the word “distinct”, but whatever) or not. Generally, phylogenetic analysis is considered to be the most robust method of detemining if viruses are “different” or not.

    When a ball is round and the earth is round, this does not show that this ball is a planet. Likewise, the fact that two distinct viruses share some properties, this is not prrof that they are “the same”.

    And Alter (from the False Positive Science article):

    “Alter now says he regrets asserting that the paper confirmed the XMRV results. [..]”“That is something I shouldn’t have said because we really hadn’t found it,” he says”

    Cohen says this about Lo in the same article:
    “Lo agrees that the team didn’t find the virus that Mikovits and Lombardi had reported.”

     

  15. RRM

    Why don’t you email him and post his response? I am not avoiding anything – I have posted evidence of my assertion. Just saying that I should check with other sources in not a very intelligent way to rebut the argument.

  17. RRM

    The fact that they didn’t use it for their study DOES NOT MEAN IT WAS NOT IN THEIR LAB.

    There are probably a lot of other things in their lab that weren’t mentioned in their study. Didn’t they have chairs in their study for instance? There weren’t any chairs named in the paper, after all. If you think this logic is stupid, you might be right…

    WPI had VP62 in their lab but didn’t use it for their study. This doesn’t mean that the VP62 that was in the lab but not in their study could still have contaminated the samples that were in their lab and in the study.

  18. Anonymous

    Cohen needs to state categorically that he has statements from mikovits and ruscetti that they had VP-62 in either the WPI or NCI labs.  

    Your new quote is not a quote from Alter or Lo.  Again, whoever has posted that needs to state categorically  that they have statements from them that show exactly that, and they should quote the words.  

    Again, you are proving no scientific reason why the viruses are not the same.  Both Lo and Lombardi found HGRVs.  You may wish that were not true and cry about it, but you will have to get used to it.

  19. Anonymous

    Cohen is not a scientist RRM.   

    There is no sign of the VP-62 plamid or any other nucleic acid sequence in Lombardi et al.  Read it, the papers proves you and Cohen to be wrong.

    VP62 has also never been in the WPI or NCI labs.  Mikovits an Ruscetti have been very clear about this.  

    Cohen needs to state categorically that he has statements is from Mikovits and Ruscetti that they had VP62 in either the WPI or NCI labs. 

  20. Anonymous

    Cohen is not a scientist.  His incorrect statement was only made a few hours ago.

    The WPI and NCI/Ruscetti have never had VP62 in their labs.  Stop lying.

    Cohen needs to state categorically that he has statements from Mikovits and Ruscetti that they had VP62 in either the WPI or NCI labs.  He wont.

  21. Anonymous

    The sources are Lo and Blood working group papers.  

    You are not scientists and are proving you are unable to understand the text.

    Throwing tantrums as you are won’t change these facts.  

  23. Pet101

    You are still not reading my comment. The Lo samples were not checked with clinically validated assays and they use the wrong test in the blood study. Its all there in print.

  24. Anonymous

    You are avoiding

    You will not accept facts and all you are doing is making out that Frank Ruscetti, Robert Silverman and Judy Mikovits are not honest.  Who are you to call into question those scientists?

  25. Anonymous

    The viruses were given the wrong name by Silverman, as was the issue when HIV was wrongly called HTLV-III.  The data now proves that Lo found the same viruses.  

  26. RRM

    “That is something I shouldn’t have said because we really hadn’t found it,” Harvey Alter

  28. RRM

    Yes, it is. 

    The controls show that the PBMC’s/RNA were not degraded. That is why intergated copies of the retrovirus should still have been amplified. 

    You do know that retroviruses integrate into the host’s genome and you do know that controls are (i.a.) in place to check the integrity of the sample? If you do, you should understand Drosha’s argument.

  29. RRM

    “The papers” in not a good argument. I could say “the papers” prove that evolution is incorrect or “the papers” prove that the earth is flat, but that doesn’t make it so. I would have to say things like “this and that section of this and that paper have reported this”  and then I would have to draw some meaningful coinclusion from all that evidence I have gathered. Until then, nobody will believe an anonymous loser like me when I say evolution is wrong, ‘because, it’s in the papers, stupid’. 

    Now, I have presented a quote from the Lo paper that stated Lo et al. used the very same assay as the one used for the BWG. Perhaps I am even less intelligent than I fear I am and I am wrong, but you have to substantiate your claims with evidence. “The papers” is not proper evidence. 

  30. RRM

    Like I explained to your fellow “debunker, “the papers” is not a good argument.I have presented a quote from the Lo paper that stated Lo et al. used the very same assay as the one used for the BWG and it magically worked the first time around.

    Like I have done, you’s have to substantiate your claims with proper references too.

  31. RRM

    Then please quote me the text from the papers that show this. 

    Ruscetti’s test is not clinically validated? Nice to see we agree for once.

  33. RRM

    There are no chairs in the paper. Does this prove that there were no chairs in the lab?

    Cohen has just disclosed his sources:

    “My sources are both Judy Mikovits and Robert Silverman. Silverman sent it to WPI in March 2008.”

    Now surely Mikovits will come out and correct him? 

  35. RRM

    Cohen now has:

    “My sources are both Judy Mikovits and Robert Silverman. Silverman sent it to WPI in March 2008..”Someone can contact me through Phoenix Rising (I cab recieve direct messages). If not, somone can send me a private message through my twitter account (Regumm). If someone prefers to email me, then I will first have to setup an email sccount as I don’t want to get spammed.

  36. RRM

    Cohen has now stated on Twitter that he has it confirmed through both Judy Mikovist and Robert Silverman.

  37. Anonymous

    Controls are artificially spiked with a clone not found in nature.  You are no where near understanding this science.  

    Mikovits’s tests are based on activating a culturing PBMCs and detecting RNA.  Therefore damaged degraded PMBCs and RNA, which will occur in the abscence of trizol, will  mean that the tests wont function.  Understanding Drosha’s argument is one thing realising that it lacks any scientific validity is quite another.

  38. Anonymous

    Cohen is categorically wrong.  The VP62 plasmid was never in the WPI or NCI labs.  He has gone too far.

  39. Anonymous

    Cohen is a member of an CFS forum and not a scientist.  The VP62 plasmid was never in the WPI or NCI labs.  THis is a fact.

    That is your name RRM? Are you saying you are Cohen?

  42. Anonymous

    Cohen who is not a scientist is wrong.  The VP62 plasmid was not in the  WPI or NCI labs.  Stop spreading this lie.

  44. Anonymous

    They have not confirmed that, because it is not true.  The VP62 plasmid has never been in the WPI or NCI labs.  It was Sivlerman who had the contamination and gave the wrong name to the viruses, which are HGRV.  The same that Lo found.

    Stop questioning their integrity.

  47. Anonymous

    Doesn’t change the fact that the VP62 plasmid was not in the WPI or NCI labs.  He should get his facts straight.  This is the trouble when you go to journalists for you data.

  48. Laurie B.

    Wow, that’s very mature.  I bet RRM  is really upset by your comment.  What do you think this says about you? Will it make your arguments credible? I think not.

    What you and others in your camp are doing is fitting the science around your preconceived theory that xmrv/mlvs have to be the cause of ME/CFS. This is not how science works. It’s a process driven from the data, questioning that data, as well as peer review . It’s a collaborative effort.

    Conclusions come from the data and not the other way around.

    I like the title of this blog,  Go by the science not the scientist. If nothing else,  the last two years have shown that this principle is important in  Science.

    Laurie B.
     
     
     

  49. kipper7

    Wrong again, Gob.

    From Lombardi et al 2009, supporting online materials p8:

    ”
    Lysates were prepared from XMRV-VP62-infected Raji (lane 1), LNCaP (lane 2) or Sup-T1 (lane 3).
    “

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