Just fours days after the editors of Science took it upon themselves to retract the 2008 Science paper, Lo/Alter, the authors of the FDA study at one time championed as proof that a family of XMRV-like viruses was present in ME/CFS, have retracted their PNAS findings as well.
In their conclusion to be published next week they stated
Although a more definitive, National Institute of Allergy and Infectious Diseases (NIAID)–sponsored, coded panel of samples from 150 well-characterized and geographically diverse CFS patients and controls is being assembled for further study, in consideration of the aggregate data from our own laboratory and that of others, it is our current view that the association of murine gamma retroviruses with CFS has not withstood the test of time or of independent verification and that this association is now tenuous. Therefore, we retract the conclusions in our article.”
The Alter/Lo retraction deepens one conundrum as they reported that extensive tests for contamination tests still failed to find any. Their retraction rested on
- Their inability to find the MLV’s in the same patients they found them in before (as well as other CFS patients) in the Blood Working Group study
- The inability of numerous other laboratories to find evidence of MLV’s (6 labs in the BWG study and others in published studies)
- Their and other labs inability to find anti-XMRV antibodies, XMRV virions, or viral integration sites in patient samples that would confirm their original findings.
- The lack of a match between the MLV’s they found in stored samples and in the same patients over a decade later. (This was known at the time of publication but for some reason was not released. Reports at the time suggested that the present day MLV’s sequences were descendants of the earlier MLV’s found but this was not true.)
- Their inability to give any more of the original samples to other labs.
Earlier this week Lipkin gave his vote of no-confidence in the original XMRV finding stating that he felt the only reason left for the 2.3 million NAIAD study to go forward was the possibility that Dr. Mikovit had found other closely related viruses. The Lo/Alter retraction may increase calls for the Lipkin study to be pared back. Raccaniello simply stated that the Lipkin study seemed ‘less compelling’ in light of the recent findings and questioned whether in light of the ‘many negative’ studies one more study will make any difference.
(Lipkin’s scenario seems a bit tenuous. The idea that the WPI researchers had found a contaminant (XMRV) that just happened to look like another retrovirus (MLV’s) that was present seems highly improbable; the equivalent of a researcher throwing a dart into a milky way of genetic sequences and just happening to land on the right one. If XMRV was present in CFS patients then the idea of similar ‘HGRV’s’ made sense; if it wasn’t; ie if it was just a contaminant, then it beggared the mind to think the WPI would, by happenstance, happen to find another retrovirus that looked similar to it.)
Agonizingly Powerful Technology – If anything the XMRV/pMLV saga underscores a technology (PCR) whose sensitivity has, to some extent, outrun researchers ability to easily interpret it. Hanson’s report that she could find the virus in one PCR machine but not the other and Singh’s conclusion that a supposedly clean machine harbored XMRV-like sequences underscored how difficult it is to interpret positive results in this field. Both researchers undertook painstaking and time-consuming re-examinations of their work before they were able to conclude their results were due to contamination.
Despite calls from colleagues to do the same the WPI does not appear to have investigated the issue rigorously until Silverman found evidence of contamination in his samples. At that point the WPI used an independent lab to determine whether contamination was present in their samples; that lab found contamination in at least some of the WPI’s samples.
Last Chance for XMRV – Dr. Mikovits and Dr. Ruscetti are in the odd situation of agreeing with all the findings; they accept that contamination was present in the original study and also believe that XMRV as well as XMRV-like sequences are present as well. Dr. Mikovits will, with Dr. Ruscetti, be looking for ‘XMRV’ in the Lipkin NAIAD study due to wrap up, David Tuller of the New York Times reported, in March of next year.
- Dig Deeper – The Racaniello Article