New Paper - Gammaretroviruses - Maureen Hanson, David Bell

Just read through this. It highlights what a complex and cutting-edge question this is; they used lots of different assays and did a whole lot of work, and they did initially find suggestive results with more positives in patients than controls, but then weren't able to reproduce those results using other assays, and in the end they weren't able to conclude they weren't contamination but also weren't able to identify the contamination, although they did find some evidence of some contamination.

A couple of quotes...

So they too found higher levels in patients than in controls. It looks like 50% of the 10 severely affected, 30% of 10 'recovered', and 15% of the 20 controls, with 1 severe and one recovered testing 'double positive'.

But subsequent analysis generally failed to detect anything using many different methods, and they couldn't maintain this association they found initially.

This is highly relevant to recent discussions:

So they have a specific hypothesis here for systematic higher levels in patients vs controls, both in their own study and in Lombardi et al and Lo et al. But they weren't able to confirm their analysis in their own case.

Interestingly, they propose a highly plausible theory for the different levels of detection in both Lombardi et al and Lo et al: in both, large batches of patient and control samples were assayed at different times. So different levels of reagent or environmental contamination at the time of the assays are a possible explanation.

I think this is interesting because it is a different hypothesis to "patient samples were handled more frequently", which I never bought. This hypothesis is more subtle than that: it is the potential for different levels of environmental contamination at a stage in the process that nobody previously suspected might be subject to contamination. This is significant because it emphasises that whatever 'mistakes' may have been made, there were not obvious risks to anybody before these experiments - that removes the burden of blame placed on Dr Mikovits by some.

This is important because it is only fair to emphasise again that nobody knew about these risks before Lombardi et al, in that the levels of contamination of lab products with XMRV and related MLVs are now extremely widespread. That's significant because again it shows that Dr Mikovits could not have been expected to expect this to be the case - it is a shock to everyone. It's an even more significant point, IMO, because the completely unexpected and unknown spread, which has been going on for 15 years or more, ofthis particular lab-created retrovirus that infects human cells, is a big surprise finding, and it is surely an important one - and should be bigger news. How much more of this has been going on? And has any such agent, ever in history, infected anything which has been distributed for human use (such as specific cell lines used to grow vaccines)? The scale of this problem and the length of time it has been occurring, by the law of averages suggests: Almost certainly, yes. No pathogenic example has yet been identified, but that is not to say that one does not exist. Sporadic cases of H1N1-induced novel forms of narcolepsy, anyone?

Two points I've recently highlighted elsewhere on these forums are re-iterated again here.

It is still unknown whether unkown retroviruses are inciting factors in ME/CFS. Obviously, but seems to need stating.

Most of the studies of ME/CFS samples have not used primers that would detect all groups of MLVs. So MLVs, other than XMRV specifically, have not been much searched for.

And as a final comment: after all this time, after all the analysis in this study, all the experiments performed, it still was not possible to nail the question of whether the sequences they sporadically detected really did come from the patients' blood, or not. That just illustrates how cutting-edge and difficult the science of this is, and shows that there is still a great deal of work to be done before all the mysteries around these viruses will be fully explained.

Absolutely - I couldn't agree more: it is just so refreshing to see clear, accurate, scientific statements that don't overreach.

When that is not the case, it is clearly visible to even non-experts such as ourselves, and this engendered an enormous amount of quite legitimate distrust of many researchers in the early days. When you can clearly see a scientist's bias on display, from the illogicality of their conclusions which are not just not remotely justified by their own findings, on points of simple logic alone, that is a very frightening thing to see.

Reading a paper like this one, where the language is sober, logical, reasonable, and fair, and the conclusions are justified, is such a massive breath of fresh air that it really takes my breath away. I do hope that this sort of thing is the norm in science, and that what we see regularly from the likes of White and Wessely et al, and what we saw from McClure and many other early researchers and commentators on XMRV, is very much the exception.

One other point I meant to add, which seems to me quite crucial.

Although there have now been many published studies (I can count at least 7, I think there are more), in both ME/CFS and prostate cancer, which have reported statistically significant higher levels of XMRV/MLV detection in patients vs controls, I have yet to hear of a single example of a study or even part of a study which found more XMRV/MLVs in controls rather than patients.

Now: while the explanations of differential handling of samples do make sense, there are now quite enough results to make it seem most peculiar that this is a one-way street.

This could potentially be explained by many studies having been done which did find much more XMRV or MLVs in controls than in patients, but which were not published due to embarrassment. But it seems most odd that anyone should not publish in this circumstance, because such a study would massively affect the debate and would be very significant. I doubt this is the case, but if anyone has evidence of a counter-example, let them come forward...

If we approach this question on the balance of probabilities: The odds of flipping a coin and getting heads 8 times in a row are one in 128.

So we might reasonably conclude that it is more than 99% probable that the unexplained discrepancies are something specifically to do with the patient samples themselves, and not due to random contamination of batches at the time when the assay was performed.

Wow, I like that currer, I missed that one. It also seemed odd to me that out of all the different tests they ran, the only one that found results was the very first one. Bit of an odd coincidence.

Now wouldn't that be a thing: if reagents you were using progressively suppressed replication, the more pre-test calibration you did before running the tests proper, the less chance you would find anything - a potential explanation for negative results, and it'd almost be like the more carefully and rigorously you prepare and the harder you try, the less likely you are to find anything at all. That appeals to my sense of irony...