Why did Alter not detect xmrv

[Riley]

That was a nice explanation Otis! - thanks

After talking to retrovirologist I think this is where the problem lies

Alter/Lo think they are closely enough related to XMRV for them to be put in the same category...Stoye and Coffin do not; we have the lumpers and the splitters. As Otis said, we'll only know when Lo/Alter more fully sequence what they found - which will, I assume, happen at some point in the not too distant future - and we'll know.

A journal is going to devote an entire issue to XMRV next year; hopefully Alter/Lo will have a paper in there describing exactly what they found.

Is sequencing what they found something that they can definitely do, and it's only a matter of time until it is done, or are there reasons that they may not be able to sequence it out?

 

[illsince1977]

The only specific item I've seen regrading the additional testing requested came from a peer reviewer on the PNAS paper asking for proof the virus had integrated into human DNA. Alter was able to fight that off being too high of a standard, albeit a desirable goal.

How do they prove the virus has integrated into human DNA? I apologize if this has been covered exhaustively elsewhere on the forum, but I am really ignorant about all this and struggling to understand even basic questions like what makes a retrovirus so insidious? I used to feel a whole lot smarter, but I just don't get it! Would someone please indulge me with "A Dummy's Guide to Retroviruses?" and its sequelae of how we can all be sick for so long and not able to defeat this thing?

 

[bullybeef]

I don’t mean to state the obvious, but didn’t Alter announce hid DID find XMRV at the Zagreb conference, and then he seemed to have be forced to change his findings in light of the CDC Switzer paper??

BB

 

[biophile]

I dont mean to state the obvious, but didnt Alter announce hid DID find XMRV at the Zagreb conference, and then he seemed to have be forced to change his findings in light of the CDC Switzer paper??

Looking again at the leaked slides from the Zagreb Blood Conference, Alter didn't explicitly claim to have found XMRV, only to have "confirmed" the findings of Lombardi et al. Here is a modified excerpt from an earlier post about what I think happened:

Lo/Alter's methods detected MLV's rather than XMRV, which they thought were closely related enough to XMRV to conclude the results "clearly support the central argument by Lombardi et al that MLV-related viruses are associated with CFS and are present in some blood donors" (XMRV being a MLV-related virus). Regarding the sentence in the slide, the "XMRV" + "3%" are from Lombardi et al and the "related MLV's" + "7%" were lated revealed to be from Lo/Alter et al. These were combined because Alter believed they are the same issue. Mention of "related MLV's" didn't suddenly appear after the intervention, they were right there in the leaked slide.

And in hindsight, I remember seeing the leaked slide for the first time and wondering WTF they meant by "related MLV's", because up until that point in June 2010 all the buzz was about XMRV. Both the general confusion and the DHHS intervention were probably prompted by Lo/Alter's claim that they had "confirmed" the findings of Lombardi et al, which apparently contradicted the CDC, even if it was revealed they didn't find XMRV as such. As far as I know, the additional review of the PNAS paper was all about testing those frozen samples, which actually resulted in a stronger paper (edit: according to a CFS Central post the extra testing was about further ruling out contamination). We have good reason to be suspicious by default, and the intervention did seem dodgy, but I doubt that Lo/Alter were forced to lie about or omit crucial findings. Also, I don't know for certain if the CDC's XMRV study would have been able to detect other MLV's as well, but if so, that would have been an even more obvious contradiction.

From the CDC's Q&A on XMRV:

Are the different findings due to differences in the research tests to detect XMRV and MLVs?

No. An independent assessment of the laboratory methods used by CDC and FDA showed that both laboratories were able to detect XMRV at low levels in blinded samples. In addition, CDC's laboratory provided samples from its study to FDA for testing, and initial analysis shows the FDA results were generally consistent with those of CDC.

What other reasons might explain the differences in results?

It is not clear why the findings of the reports differ. Possible explanations include selection criteria for inclusion of CFS patients, differing clinical subsets of CFS, and possible variations in XMRV and MLV infection rates among populations in different geographic regions. There also may be other, as-yet-unknown factors that could help explain the different results of the studies. Scientists involved in these studies are working collaboratively to design experiments to answer these scientifically puzzling questions.

One important consideration is that XMRV is a newly identified virus, first reported in 2006, and much remains to be learned about this and related viruses, such as MLVs. As additional research is done on XMRV and similar viruses, it is possible that new findings might emerge that differ from those reported to date.

 

[Sean]

It turns out there are a ton of "pieces and parts" to a retrovirus. It appears that what you find depends on which pieces/parts you're looking at.

I think we currently have a classic case of the three blind men each holding a different part of an elephant. This is pretty standard confusion in the early days of figuring something out.

 

[Snow Leopard]

I don’t mean to state the obvious, but didn’t Alter announce hid DID find XMRV at the Zagreb conference, and then he seemed to have be forced to change his findings in light of the CDC Switzer paper??

BB

No, he simply stated that his group has 'independently confirmed' the Lombardi findings. But I do think the whole MLV vs XMRV thing is due to hairsplitting by the paper authors or referees.