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Cleveland Clinic's Klein:
Possible XMRV Link To Human Disease
 Not Disproven by Retrovirology Papers


(Craig Maupin on January 7, 2011 for

In an interview with the CFS Report this morning, Dr. Eric Klein of the Cleveland Clinic responded to recent media reports stemming from four studies published in the Journal of Retrovirology (December 21, 2010).   Several researchers involved in the four studies were publically critical of a possible link between XMRV and human disease.  Klein stated that, while the papers highlighted various pitfalls of research on XMRV and viruses, particularly the risk of contamination, the papers did not pass the threshold of evidence required to disprove a possible role for XMRV in human diseases. 

Klein emphasized that recent research findings merit the continued investigation of a possible link between XMRV, prostate cancer, and other diseases.   In particular, recent findings have shown XMRV grows in prostate cells.  XMRV's growth is fueled by testosterone, giving XMRV a "predilection for the prostate".   These preliminary findings deserve further study. 

 According to Klein, those working on XMRV are well-aware that proof of causation requires more published evidence:   "No one who knows about the field has suggested that we know XMRV causes any known human disease, whether it is prostate cancer or chronic fatigue syndrome.  That has not been proven, in any way, shape or form."   

 Klein stated that his team was aware of the risk of contamination:   "You have to be careful when testing for XMRV using PCR that you don't have any mouse DNA contaminating things,...or you can come to the wrong conclusion".  In fact, Klein added that a test kit labeled in the Retrovirology papers as contaminated was already considered suspect by researchers in his clinic: "We did some experiments with that reagent a few years ago, so we knew that was a problem and we stopped using it because of [what we learned]".

Klein said much of the publicity of the four studies did not address differences in testing methods between various studies:

"I would like to point out that there are a lot of other studies, many of which are published, some of which aren't. These studies used other standard virological methods which are not PCR-based.... So, if you go back to the original Science paper that showed the presence of XMRV in patients with chronic fatigue syndrome, you'll find there were five different methods used, four of which are not PCR-based. So, that was what was lost in the publicity surrounding these papers in Retrovirology"


Klein also raised concerns about the conclusions drawn from a study where human cell line 22rv1 contained XMRV sequences:

 "The authors of that paper concluded, inappropriately, that the virus came from the mouse and infected the cell line... That is a possibility.  But, there is also a possibility -- of equal chance -- that the patient had the XMRV and it was propagated in the nude mouse, and then it became established in the cell line."

Shortly after publication of the Retrovirology studies, a press release was circulated wherein a few researchers involved essentially declared their work the beginning of the end of the association between XMRV and human disease.   Klein said that whether or not recent media coverage of those statements has an effect on the pace, progress, or funding of XMRV research "remains to be seen".  The effect of such media releases, he says, "depends on the influence that coverage has on the individuals who make those decisions".   While Klein believes the studies provide fair warning about the risks of laboratory contamination, he suggested some of the conclusions drawn from the studies were an "overreach".

Klein emphasized that his clinic is "excited by our work and the whole field" of XMRV research. When asked about whether the Cleveland Clinic planned to continue collaborations with CFS researchers on XMRV, he said:

"Absolutely. Not everything that we have collaborated on is ready for prime time or to be shared with the public. But, I assure you, there is a lot of work still going on. We are excited by the idea that XMRV may infect the human population and it may be something important. We haven't proven that, but we still believe that is a serious possibility and we continue to work on it."


The full interview with Dr. Klein can be read here