I just want to pick up on a specific point about patient selection and blood processing. My understanding was that Judy decided the patient selection criteria. That's definitely why specific criteria for viral-like onset was required, and it maybe why well known ME clinicians were used. The recruitment criteria was specifically tailored to copy Judy's criteria in her own studies. I don't see how it could have been done differently, except to use exactly the same patients. But considering the unpublished UK results, that wasn't necessary. I'm not sure about the processing of the blood, but I would imagine that Judy was quite specific in her requirements for that as well. I can't see that collection or processing were a problem, if Judy gave it the go-ahead, esp because absolutely no XMRV was found. If it was a case of some XMRV being found, in small quantities, then I might have some questions. With no XMRV being found, either it wasn't there, or it was purposely tampered with to destroy it.
One might take note of the speculative language required to make this case. (I’ve emphasized some of it.) Such language is necessary to support the conclusions of the study because, unfortunately, numerous questions remain unanswered and many details remain undisclosed. For example, regarding just the particulars of the collection and processing:
Did Judy have complete control over collection and processing protocols? This study used EDTA tubes, despite the fact that
she had previously reported great difficulty with them during the BWG. Even if Judy did have complete control, were there perhaps differences in protocol that affected the results in a manner that was unforeseen by Judy (i.e. unknown unknowns)? Clearly, the use of EDTA does establish the existence of differences in protocol. We are left to speculate about the full spectrum of differences and their possible effects since these differences were subjected only to “prior agreement” instead of actual empirical testing. Even if Judy did have complete control and somehow knew that all the changes in protocol would have no unforeseen effects, how do we know that collection and processing were conducted precisely as “agreed upon”? Beyond the possibility of intentional or unintentional mistakes undermining the process, there could have been issues as innocuous as subtle, unaddressed discrepancies in convention during otherwise routine portions of the protocol.
No one can answer these questions because they were either not disclosed by, not answerable by, or not controlled for by this study. Hence the need for presumptive language in order to gloss over them. Such an exercise in guesswork could be considered acceptable as a provisional step in guiding further research. But in this case we are being told to accept such speculation
in place of further inquiry due to the unscientific characterization of this study as “definitive.” At the risk of sounding normatively imposing, I suggest that this state of affairs should be deeply unnerving to anyone who cherishes scientific inquiry, more so if their future is also on the line.
Furthermore, the appeal to “agreement” by certain “individuals” to justify brushing aside or ignoring unanswered questions and uncontrolled variables is inherently unscientific. Empirical reality has an annoying habit of defying the concords of humanity’s most credentialed investigators. The use of “agreement” in defining truth exists exclusively under the purview of politics and religion. To use a well-worn but germane example, Galileo (ostensibly) “agreed” with the Catholic Church that heliocentrism was unfounded. The Catholic Church made the mistake of not declaring this agreement “definitive” and indefinitely discouraging further exploration.
Lastly, it is somewhat beside the point that Judy has publicly endorsed the study’s conclusions. It’s almost as though no one in the history of the world—especially someone under the trying circumstances that Judy has endured—has said something publicly that they disagree with privately. Or as though no one has ever been falsely convinced that they were previously wrong about something when in fact they were actually correct. There are many open, empirically-supported questions and issues that this study has not addressed, which
have been anticipated for quite some time. What I find most peculiar is how people who recognized the importance of these questions up until the release of this study--in defiance of constant accusations of “following scientists instead of science” no less--are suddenly so willing to discount the continued pertinence of these questions simply because Judy publicly agreed with the results. This constitutes the essence of “following scientists instead of science.” Quite strikingly, the same chorus that so fervently voiced this refrain about “following scientists instead of science” in order to discourage interest in RVs prior to the Lipkin study has gone eerily quiet afterwards despite the fact that such admonitions are actually more appropriate now than ever before. I suppose consistency no longer matters once the “correct” outcome is reached.
I can't see that collection or processing were a problem, if Judy gave it the go-ahead, esp because absolutely no XMRV was found. If it was a case of some XMRV being found, in small quantities, then I might have some questions. With no XMRV being found, either it wasn't there, or it was purposely tampered with to destroy it.
It’s strange that you say there was no XMRV found because—in addition to the casually discarded serology positives—PCR positives
were found and mentioned in the study (discussed below). However, they were reported as "all negative" due to arbitrary, interpretive requirements imposed by this study that effectively hid this data. Each lab had to report both aliquots from a given subject as positive for the subject to be reported as positive by that lab.
Each lab had additional lab-specific requirements for reporting individual aliquots as positive. E.g. the CDC ran three PCR assays on each aliquot (gag, pro, pol) and had to find 2 of the 3 positive in order to report the aliquot as positive.
Taken together, these requirements did result in non-reporting of positives which could very well have obscured important correlations and associations: Were there more unreported PCR positives in patients than controls? Was there a subject-level correlation between unreported PCR positives and reported serology positives (thereby making casual assumptions that serology positives were irrelevant cross-reactions rather cavalier)? Were there any assay-specific associations that were obscured by the data-aggregation rules (e.g. the CDC could theoretically have found strong evidence of gag presence but been forced to report all of it as negative due to difficulty in finding pro and pol sequences)? None of these questions can be answered because the raw data was not reported. Only the high-level,
implicitly interpreted results were supplied.
As noted above, the presence of unreported PCR positives is not speculation, as they are mentioned in the paper itself. Consider the following quotes:
Regarding the Mikovits/Ruscetti/Hanson PCR results:
DNA was not available for IAP PCR for six gag-positive cultures.
This clearly establishes that there were PCR positive cultures. The paper does not state why these were ultimately reported as negative, but presumably it is either because they were discarded due to inability to run IAP or because their corresponding aliquots were negative. In either case, information was lost.
There are additional, indirect indications that unreported PCR positives were found in all three labs.
CDC:
To test for mouse DNA contamination, a quantitative real-time PCR assay for mouse intracisternal A particle (IAP) sequences was performed on samples that were PCR positive for XMRV/pMLV sequences.
Alter/Lo:
PCR for detection of mouse mitochondrial DNA (mtDNA) was performed on all positive samples using a seminested PCR targeting the mouse-specific D-loop sequence as described previously.
Mikovits/Ruscetti/Hanson:
All gag-positive cDNA samples were negative for mouse IAP sequences.
Given that the first quote above explicitly establishes the presence of unreported PCR positives and given that these generic references to PCR positive samples do not make explicit reference to them being exclusively positive control samples, it is quite reasonable to interpret these statements as referring to positives found in actual subject samples. Additionally, there is no mention of contamination being found in the labs, thereby making it unlikely that all of these unreported positives were discarded due to indications of contamination.
It is therefore warranted to conclude that PCR positives were found in study subjects in each participating lab. The fact that only the post-aggregation data (which implicitly imposes an interpretation on the raw data), should be seen as suspicious given that it clearly resulted in the hiding of potentially relevant correlations.