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A request regarding the 33 XMRV negative patient samples in Lombardi et al. 2009

Discussion in 'XMRV Research and Replication Studies' started by Tony Mach, Feb 3, 2012.

  1. Tony Mach

    Tony Mach Show me the evidence.

    Upper Palatinate, Bavaria
    I need to write something about myself first apologizes for that. If you want to skip that, jump right down to the first headline (Lombardi et al. 2009) below.

    It was sometime around February 2011 that I learned of CFS and subsequently of XMRV.

    My symptoms were getting worse since 2010. Since the end of 2010 I have been going through the medical information I found on the internet. I was getting desperate. I found all kind of things like "Adrenal Fatigue" and "Chlamydia Pneumoniae". My (new) doctor wanted to shoehorn me into a "Burnout Syndrome" diagnosis. When I found CFS on the internet, I initially rejected Chronic Fatigue Syndrome because it is easy to mistranslate Fatigue into Tiredness in German and I thought to myself: I am not tired!

    So in early 2011, after looking more carefully into CFS, after seeing that some of my symptoms might be CFS symptoms and realizing even though my illness was clearly gradual onset (and how some things that I though were "normal" for me, were actually anything but normal), I realized I might actually have CFS.

    That was the time I first saw online video of a lecture by Dr. Mikovits. And her talk persuaded me. Especially one part: After the initial CFS/XMRV study (Lombardi et al. 2009) they went back and took the all the 34 patient samples that were negative for XMRVby PCR, and retested these samles with the other methods they had. And Dr. Mikovits reported that they found evidence for XMRV in 31 of the 33 PCR negative patient samples. So this raised the evidence to 99 out of 101 patient samples.

    And I thought: "This must be it. If Dr. Mikovits can find evidence for XMRV so easily in practically all patients, then it must be XMRV!" I thought this was a slam dunk.

    As probably most of you know, there were some researchers who disagreed with these findings. Well, I read Osler's Web at that time, so dissenting researcher did not bother me too much let them criticize. After all, Dr. Mikovits found XMRV in 99 out of 101 patients!

    I was contemplating getting an XMRV test. The cost of a XMRV test would have blow my budget for medical issues, so I choose to wait. Instead I did other blood tests, as I had a long list of things I wanted tested

    Over the last months I started to look more carefully into the XMRV research and the one point I will focus in this post is the 34 PCR negative patients as this was the evidence that convinced me XMRV is clearly associated with CFS.

    If you find something that I have written here below that is not supported by the facts as reported by Dr. Lombardi or Dr. Mikovits: Please point me to the correct information!

    (all highlights are mine)

    Lombardi et al. 2009:
    33 PCR negative patient samples
    68 of 101 with XMRV gag sequence

    This study was submitted May 7th 2009, accepted August 31st 2009 and published online October 8th 2009.

    It found:
    (The PDF is available e.g. here)

    So with 68 out of 101 reported positive, this makes 33 CFS samples negative in May 2009.

    October 2009:
    33 PCR negative patient samples retested
    99 of 101 with evidence of XMRV infection

    In the CFSAC October 2009 meeting Dr. Peterson of the WPI reported that the 33 PCR negative samples were retested with all methods and 31 were found with evidence of XMRV infection:
    This slide of was used by Dr. Mikovits in her talks and is present for the talk on January 22nd 2010.

    (Slides available e.g. here and here)

    So in October 2009 we have the report of "evidence of XMRV infection in 99 of 101 US patients".

    Mikovits et al. 2010:
    34 PCR negative patient samples
    XMRV detected in more than 75%

    In the study Mikovits et al. 2010 (Called "Addendum to Lombardi et al. 2009" by some), which was submitted Feburary 26th 2010, revised May 20th 2010 and accepted May 24th 2010, the following was reported:
    (PDF available here)

    Why has the detection gone down from 99 of 101 in October 2009 down to 75% of 101 in May 2010? Is there an explanation somewhere?

    Furthermore this addendum states:
    The discrepancy between 33 and 34 is fretful, but probably only a typo that wasn't catched.

    Mikovits et al. 2010, Table 4:
    Only 93 patient samples reported
    20 to 28 PCR negative patient samples
    73 of 93 patient samples are positive
    Seemingly several inconsistencies

    Now in table 4 of the "Addendum" it gets really weird.

    (You can find the table in the PDF, a copy of the table is available here).

    First of all only 93 samples are reported, 8 are missing. Ok, this might be some benign mistake of accidental omission but is annoying as heck if we should take this as evidence that a retrovirus is circulating in the population.

    None of the controls are reported. Not even the positive controls. Why? What about the 8 out of 218 (3.7%) of healthy controls infected with XMRV? Why aren't they reported? Were more controls tested by other methods? There are several questions that arise from the controls, that would probably bust the scale of this topic.

    73 of the 93 are positive by PCR. Lombardi 2009 reported 68 PCR positive. How did 5 samples turn positive?

    20 of the 93 are negative by PCR. If we assume all 8 missing patient samples are negative we now have 28 PCR negative samples at max. This is clearly at odds with the quote above ("34 patients whose PBMCs were negative for XMRV by DNA or cDNA PCR"). What is going on here?

    But wait, it gets better!

    The following patients were negative by PCR, but not tested (nt) by other methods.
    Now what the heck is going on here?

    But wait, it gets better!

    Table 2 (that is mentioned above to show the 34 PCR negative patient samples) show first of all the results only for 11 patient samples:
    But wait, it gets better!

    If we take the patient number from table 2 and look them up in table 4, this is what we find:
    All samples reported in table 2 (some of the "34 PCR negative samples") are PCR positive in table 4 (with the patient sample 1199 missing).

    This simply does not add up.

    Is there some benign explanation I am missing for this all?

    I would dearly like to have an explanation for this.
  2. ukxmrv

    ukxmrv Senior Member

    I remember that at the time there was a great deal of discussion about the numbers of the patients samples and the descrpencies. Some patients even asked Dr's Peterson and Mikovits at the time and answers were given to lots of questions like this. I personally sent q's to them at the time and also when they were at the IiMe conferences in London. They were kind enough to go through lots of things with me.

    The problem is that you were not around in late 2009 when we were all asking these questions and missed the long threads as we worked through all these issues. I don't know if the patients who asked all the similar questions to yourself are still on this board or if they departed to other pastures.

    It's rather like stepping into a party after a long conversation has taken place and then hoping someone will do a recap of what was said earlier on.

    Sorry, I am not trying to fob you off and not trying to pretend that all questions were answered to our satisfaction. You are posing things that were asked at the time and I hope that someone will go back through those threads and find the answers for you and let you know. Lots of discussion on patient numbers and why they were different / didn't add up.

    I just hope that someone has the physical / mental strength to do this or you find the relevant bits as I am really struggling right now.
  3. currer

    currer Senior Member

    Hi Tony,

    As it is quiet on the forum at the moment, why not take the opportunity to go through the older threads fron 2009/10 on XMRV and follow the discussions there? I agree with ukxmrv that it is important to know some of the history of the debate.

    I remember the early discussions as being very interesting and informative.
  4. barbc56

    barbc56 Senior Member


    @ Tony. Bingo!!! It doesn't add up and this is why the original paper was retracted. :D

    It's important to go back and see why the original study was not what many thought. It's important to keep asking these questions, to understand how the science evolved or we lose sight of what science is about.

    These critical thinking skills, whether someone was a patient from the beginning of that time or just learning about it today, are imparative.

    Don't know if it is necessary to go back and read every single post/thread from that time but then it would be somewhat arrogant of me to assume that you haven't.

    Thanks for sharing your experience.

    Barb C. :>)

    ETA Tony, with just a bit of expansion, your OP would make a great blog post on PR. Have you thought about that?
  5. barbc56

    barbc56 Senior Member


    With all due respect, I am having difficulty understanding why your reaction to Tony's post is negative.

    I'm not sure he was actually asking for information. but was being a bit more subtle than that by using a rhetorical question at the end of his post. He was relating his journey as a patient, what he was thinking when the science paper first came out, and how his opinions evolved as the evidence started changing, eventually asking himself why the data didn't "add up".

    This is obviously my interpretation and only Tony, if he so chooses, can answer this.

    Sorry you are unwell right now. I know how it feels to be about struggling. Hopefully some relatively better days are ahead for you as sometimes that is all we can hope for. Take care.

    Barb C. :>)

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