Some observations on why it is sensible to wait for more complete contextual information and not get carried away with all the wild and aggressive speculation out there about what these discrepancies mean for the validity of HGRV research and the integrity of Mikovits, Ruscetti and others...
- It is perhaps highly relevant to remember some of the history of how Lombardi et al was reviewed by Science. The paper went through a very extensive review process over (as I recall) nearly a year from the time when it was first presented for publication. According to what I read, it was cut down to about 1/3 of its original length, and many details which the researchers wanted to include were omitted at the request of Science. In that context, omission of what now seems to be key information may be more understandable and excusable.
- The slides in figure 2c of Lombardi et al only refer to a very small subset of the samples tested. Many tests were run by Mikovits et al over the course of several years. There's no reason at this stage to assume that the selective application of 5AZA to patient samples featured in any of the other tests - in fact it would be so ridiculous if it did that this seems quite implausible.
- Mikovits et al have previously stated that the core of the experiments they conducted were blinded and coded, and that the tests on controls and patient samples were treated in exactly the same way. Although it now appears this didn't apply to the specific slide referred to in figure 2c, there's no reason (that I'm aware of) to assume that the 5AZA treatment was applied selectively to the rest of their tests. It is an extrapolation to suggest that it did, based on insufficient evidence.
- Indeed, since Ruscetti says that the failure to mention the 5AZA treatment of patient samples in Figure 2c was a trivial omission not necessary
to the paper, and since Mikovits has asserted that the bulk of samples were treated exactly the same for patients and for controls, the most reasonable way to reconcile all these statements is that Figure 2c was included in the paper as the most clearly-defined image from their various experiments, because it best illustrated the contrast. That may seem a little misleading, but in the wider context of all the materials the researchers had at their disposal, and in the context of the review process re-editing the original paper down to a fraction of its original length, it seems to me most likely that they just presented the case in the strongest possible way by selecting the strongest image. If other slides which did not depend on the use of 5AZA, or where 5AZA was applied to both patient and control samples, showed similar contrasts, then this choice may not have been particularly misleading.
- At this point, trust in the researchers and references to their professional reputations and their career history
are relevant because the attempt is now being made to destroy the reputations and careers of these scientists based on little more than this single omission in the labelling of one figure in the Science paper. As Lee has noted, the publication process does always critically depend on trust in researchers; like any other researchers it would have been possible for them to just make the whole thing up, and when one reads a paper, one really has no way to prove that the scientists involved really did what they say they did. This applies to pretty much any paper. Insinuating misconduct and claiming a wholesale loss of trust in such experienced and high-profile researchers, based on a single discrepancy, before the researchers have had adequate opportunity to fully explain their side of the story...this is harsh and premature, to say the least.
- A tangential point: failures in the methylation process which Lee mentioned have for many years been posited as central to ME/CFS, and treatments exist specifically aimed at unblocking the methylation cycle. Those treatments are not yet widely accepted scientifically, but they worked out just fine for me and a friend of mine, both of us experiencing much improved health after decades of illness and ineffective treatments. The wider context of ME/CFS science, which fits so well with many aspects of the XMRV/HGRV hypothesis, is relevant background knowledge which many scientists from outside the ME community are unaware of.
- Finally: IMO the biggest issue that has caused so much consternation on this forum in recent days is the readiness of sceptics to selectively attack specific types of researchers, but not others, at the slightest pretext. This is a phenomenon we have all observed throughout the XMRV saga, and beyond it. If only it were true that the following principle were even-handedly applied:
Once a scientist has shown that they are willing to intentionally say something not true about their methods or their data, they cease to be scientists. They will no longer be trusted in science. It's a career-ender, and it makes all their work suspect, and it means that everyone who was relying on their work for their own research and research decisions cant trust the things they were relying on.
If only it were true that such behaviour is universally a 'career-ender', then why have Wessely and Chalder not been consigned to the wastebasket because of misrepresentations like this one?
http://www.bmj.com/content/320/7233/515.2.full
"Somewhere between the analysis and the printed copy we have been attacked by gremlins." - and that was all they needed to say. Where was the outrage and criticism from sceptics about this? What happened to the peer review process on this paper, allowing obviously false and statistically impossible results to pass through unchallenged?
Where was the censure from the sceptic community when Myra McClure claimed "1000% certainty" or when Reeves and Wessely spoke of their "expectation" that the Lombardi results would (should?) not be replicated, before a single attempt had been made to investigate the findings?
And where was the intense scrutiny and criticism of the PACE trial from the scientific community? No, it is
not irrelevant to the issues at hand to highlight the double-standards applied here, certainly not, when some people's reputations are being impugned and some researchers are once again being scared away from researching ME/CFS while others continue to get away unchallenged. It is fundamentally important to notice that some science is waved through, while other science - highly inconvenient and controversial science - is bombarded with vicious attacks until the researchers crack. That kind of distortion of the process is not scientific at all.
The PACE trial started out by promising to use pedometers to objectively measure the actual changes in participants' activity levels. Measurements of activity levels at baseline were taken, but part-way through the trial, research was published by psychologists elsewhere in which the pedometer evidence clearly showed that, although patients
self-reported increased activity levels after CBT and GET, in actual fact their activity levels had slightly
decreased. The PACE trial promptly ditched the use of pedometers part way through - changing their experimental methods halfway, and at a time when they almost certainly had data indicating whether this, the only objective measure in their experimental design, would show what they wanted the trial to show. The reason they gave for this? It wasn't fair to ask the participants to wear these wrist-watch-sized devices after everything they had been through in the trial.
Was this a credible explanation? Was this good practice, changing the agreed experimental design partway through? Does this behaviour qualify as deception, even as fraud? None of these questions, of course, were asked by the peer reviewers or sceptics about this particular research. Nor were the many other serious flaws in the paper addressed by these people.
Wessely, Chalder, and the PACE trial authors have been cut the most enormous amount of slack by the scientific world, so it would only be fair to apply similar caution before calling for the heads of researchers with decades of experience based on a single mislabeled slide. As Lee put it:
This is really basic virology. I know it as an out-of-date evolutionary geneticist, because the endogenous retrovirus story has been a fundamental story in evolution. Its been a fundamental story in virology,in cell biology, in genetics. Ruscetti and Mikowits had to of known this.
That should read "Had to
have known this". Or, rather, "must have known this". But it isn't fair or reasonable to call somebody out or undermine their entire reputation based on simple mistakes...
What Lee set out above
is really basic virology, and it was a well set out and useful summary of the technical issues involved here. But as others here have noted, most of those of us here who have been following the XMRV saga are well aware of all this background information by now, and as Lee notes, Ruscetti and Mikovits are surely well aware of
all these issues too, and much more besides. Nobody expects their science to be accepted based purely on an appeal to their authority. But their credentials, and the fact that they continue to stake their reputations and stand by their research - based on greater knowledge of the science than any of us here, and based on their unpublished as well as published data - do strongly suggest that there is
something in this science that is still worthy of further investigation.
Whether that something eventually turns out to be XMRV, HGRVs, or ERV activation, few ME/CFS patients would really care either way. What should concern us all, though, is that this promising line of research should be allowed to run its course, and the different results found by Lombardi et al in ME/CFS patients vs controls should be fully and completely explained. A premature end to the research, and the destruction of the career of yet more researchers who showed an interest in ME patients, would do nothing to diminish the anger, distrust and sense of alienation felt by large sections of the ME patient community - and such an outcome would be in nobody's best interests in the long run.
) - please don't be sidetracked by the technical jargon that's being used. Look for the value judgements and the good faith or bad faith indications nestling in the technical comments. You might not know how to change a tyre or do plumbing - but it doesn't mean you would accept without demur any old flannel from these 'experts' either. 
