Science and the Hold on XMRV Studies
A positive XMRV study in CFS conducted by a NIH/FDA research team was accepted for publication in the Proceedings of the National Academy of Sciences (PNAS) but was then put on hold apparently in June, 2010. As reported in an online editorial in Nature (July 2; http://www.nature.com/news/2010/100702/full/news.2010.332.html), one scientist familiar with the issue said that the journal's editor-in-chief sent the paper out for further review after government agencies requested the publication delay. That review came back with requests for additional studies.
Stephen Monroe, director of the CDC's Division of High-Consequence Pathogens and Pathology, called the delay a "strategic pause" given the conflicting findings between the CDC’s own XMRV negative study in CFS -- also put on hold but recently published in Retrovirology --and the positive XMRV findings of the NIH/FDA group (still unpublished). Of course, we’re concerned about a full airing of the scientific data on XMRV. But it appears that the transparency and timely reporting that is so essential to science was not in evidence in this unusual government action.
Examining the Rationale of the Hold
Although the specific purpose of the hold was the subject of speculation among scientists and others, it was not clearly explained by any government official or journal editor. If the purpose of the hold was to re-examine conflicting data with an effort toward reconciling disparate findings, the approach taken here did not achieve this goal (as of this writing). In my view, if the extraordinary step is taken to delay conflicting peer-reviewed studies accepted for publication, then both studies should be held until all further analyses are done.
Once all additional work is completed, the research groups should review each other’s manuscripts. This should be followed, in one of the journals, with a thoughtful discussion among the investigators that examines the discrepancies between the studies with the goal of providing informed recommendations for subsequent research. Finally, both articles should be published simultaneously or as close to it as possible. This process has the potential to advance the science.
By contrast, the CDC article alone was published weeks ago without considering or even citing the findings of the PNAS paper. I argue that the CDC paper should have been held until its authors could respond to the NIH/FDA study when its additional work is completed. If there’s still time, I would like to see the CDC and NIH/FDA research groups have a discussion of their conflicting findings with the aim of publishing their talks in the issue of PNAS that contains the NIH/FDA study.
Implications of a Second Positive XMRV Study
Once we get past the hold period, the publishing of the second XMRV positive paper is likely to change the nature of the debate. Prior to this second positive report, the original Science paper was becoming an outlier study that could be dismissed in light of several published failures to replicate. With the new replication, the XMRV link to CFS, whatever it may be, will become an ongoing controversy that demands resolution of key issues such as the differences in testing protocols for XMRV as well as the characteristics of patient groups that are tested.
XMRV and the Ottawa 2011 Conference
Our Sept. 2011 biennial conference in Ottawa will devote a full session to XMRV. And we will put together an expert discussion panel representing different points of view about XMRV. This is the kind of scientific forum that we need to constructively address this ongoing research issue.
Fred Friedberg, PhD