A Guide To XMRV Research: the WPI Answers Back

View attachment 434 The inability of the second UK XMRV study this time from a friendly research group headed by Dr. Groom to find any XMRV in a very large sample of patients was rough news for sure. The ME Action Group in the UK took a rather resigned tone in their response while Dr. Vernon highlighted a few methodological issues but mainly concentrated on questions about that original cohort. Neither presented much good news for CFS patients as a cohort answer to the current problems would mean the virus is only present in a very select subset of patients.

In their response to the latest paper the WPI defined the pitfalls they believe researchers face in validating their work thus basically giving them a guide on how to find XMRV and doing everybody a big favor.

No Replications Studies Yet Done: They noted that no one has yet attempted to replicate, i.e. exactly duplicate, their original study. In the best of worlds, of course, a true replication study isnt necessary and is, in fact, irrelevant. How one found the virus, after all, is not particularly important; pathogens can be uncovered by several techniques and researchers typically use different techniques to validate the presence of a pathogen. In fact, a positive validation study using a different technique is considerably more valuable than a replication study because it definitively demonstrates the pathogen is there. Its only when the validation studies are unable to validate a finding that the issue of a true replication study becomes important as it now has.

Looking Back This replication/validation issue was prominent in Dr. DeFreitas retrovirus of almost 20 years ago. The CDC and Gow teams were well versed in retrovirology and had used standard procedures again and again to find viruses. Given their track record they felt little need to change their procedures. (Ultimately the CDC did at least to some degree). But Dr. DeFreitas felt her bug was different. Given her inability to replicate her results she may have been wrong; the question now is whether XMRV is different as well.

Both UK studies used standard XMRV samples to ensure they could find the virus and their results indicated that they could but they couldnt find it in the CFS patients. It may be important, though, that outside of one Japanese study these are the first attempts to find XMRV in the blood and researchers are treading new ground here.

We know that two US prostate cancer studies found XMRV but two German ones did not. We know the German prostate cancer researcher is redoing his study using a different technique. Its clear that, irrespective of CFS, the field of XMRV research (as small as it is), is quite muddled at this point perhaps we shouldnt be so surprised about the bumps in the road encountered thus far.

View attachment 433 The WPI took the UK study to task somewhat for not using their reagents, blood, etc. stating that there is only one way to look for XMRV in the blood thats been validated and thats their approach and they have a point. The WPI was the first group to ever look for XMRV in the blood and they validated their results as best they could using the Cleveland Clinic and NCI labs. To be fair the Groom study researchers, some of whom have long track records in CFS research, didnt have any reason to think their procedures wouldnt work since apparently they do work for most viruses. Its possible that both they and the Imperial College researchers underestimated the difficulty of finding this virus in the blood.

To their credit they were careful not to overstate their case simply stating in the paper they were unable to find XMRV DNA in their samples and not making broad conclusions about XMRV and CFS. Once the paper came out theyve stayed out of the spotlight - they appear to be waiting to see what other studies turn up.

The WPIs Issues

Most of the issues pointed out by the WPI dont appear by themselves to be able to account for the differing results in the UK. String them together, though, and you get an interesting scenario.


  • Blood Harvesting and Storage The idea that different blood storage and harvesting procedures couldve altered the results seems possible but seems unlikely (to this laymen) given that the Groom study used three cohorts from three locations -each of which could have used different storage techniques. We know that XMRV is robust enough for Dr. Peterson to be able to pull XMRV out of a 20 year frozen sample but the possibility does remain that the Groom study inadvertently used blood storage techniques suitable for other viruses but not for XMRV. Laymens Conclusion possibly a significant factor but not likely.
  • Different Patients - The idea that the WPI had one set of patients and everyone else had a very different group has come up again and again. The very large size of the British study with patients from several different groups appears to make this scenario an unlikely one (and a decidedly unattractive one since then XMRV would apply only to very special patient groups.) On the other hand some differences in patient selection could start to lower the prevalence rate. Laymens conclusion not It- but a possibly a contributing factor.
  • Different Geographical Prevalence - that XMRV is simply not found in the UK (but is found in the US and Japan) seems have little plausibility given the fact both Dr. Mikovits and VIP Dx labs have stated theyve found XMRV in samples from UK patients but its certainly possible that XMRV could be less prevalent there thus driving down the prevalence a bit (more?). Laymens conclusion not It either but prevalence rates could be lower we just dont know.
  • Very , Very Low Levels of a Very Difficult to Detect Virus While the other issues could reduce an investigators ability to find the virus with the exception of the blood storage issue its hard to believe they could result in being unable to find any XMRV in a large group of patients. This low viral level issue seems to be more significant, however.


The WPI did two things the other groups didnt do to find the virus.

  • They Usually Grew the Virus in White Blood Cells First in Order to Increase its Numbers. (This presumably involves hitting the white blood cells with a substance designed to enhance viral replication). Dr. Mikovits reported earlier that while XMRV appears to be able to readily infect immune cells it simply doesnt have the tools to replicate readily in them hence its viral loads are expected to be low. Not culturing white blood cells first could, then, reduce prevalence rates markedly but note not completely as the WPI said they usually, but not always, had to use this technique.
  • WPI researchers Had to Search Multiple Times Both in Time and Space to Find the Virus - Not only did they look at a sample multiple times sometimes they had to look at samples taken at different times from the same patient in order to find the virus. The UK studies, on the other hand, presumably looked at the same samples once or twice. (The Retrovirology study looked at their samples twice, once using a more sensitive technique).
  • Does perhaps a bit different cohort, perhaps reduced rates of XMRV infection in the UK, maybe some blood storage issues and a much more difficult to find than expected virus equal zero findings in two UK studies? With true replication studies purportedly on the horizon well know in the not too distant future.

A Confident Group The WPI asserted, as well, that the best test of XMRV infection, given the difficulty finding it using PCR, is an antibodies test. The Retrovirology group did use an antibodies test but the WPI asserted that it was flawed and theirs is superior.

At the end they stated the only reliable to find XMRV in CFS is to use their approach and basically that no-ones going to find it until they start using their techniques.

Comments

A logical thought from a laymen:

SOMETHING has to cause CFS. What ever SOMETHING is, it has to be hard to find
since some devoted doctors and scientists couldn't find the cause in so many years.
That makes XMRV a good possibility right there.

There is a chance that not everyone with CFS has it due to the same cause though.
So XMRV might be the cause for some but not all. While we would all like to know
what causes us to be sick, it would already be of value to know what the cause is for
a subgroup.

It would be wonderful if we found one cause for all (and could treat it), I but think we need to step back from the idea that there HAS to be one cause for all as this might be stopping us from finding answers.

Research should also be focusing on other causes and in my humble opinion, genes
would be a good place to look too.
 

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