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Study linking chronic fatigue syndrome with retrovirus is partially retracted

BMJ 2011; 343 doi: http://dx.doi.org/10.1136/bmj.d6097 (Published 26 September 2011) Cite this as: BMJ 2011;343:d6097
  1. Anna Sayburn
  1. 1London

The authors of a controversial paper published in Science that linked chronic fatigue syndrome to a mouse retrovirus have partially retracted their findings, admitting that some of their samples were contaminated. At the same time new research casts further doubt on the original findings.

However, the study’s authors, led by Vincent Lombardi at the Whittemore Peterson Institute in Reno, Nevada, say that their research (Science 2009;326:585, doi:10.1126/science.1179052) didn’t rely solely on the data they are retracting.

The paper created much interest when it was published in 2009. It seemed to show that 67% of a group of patients with chronic fatigue syndrome but only 3.7% of healthy controls showed signs of infection with xenotropic murine leukaemia virus related virus (XMRV).

The study was welcomed by patients’ groups, who saw it as a validation of the clinical basis for the syndrome and as an area for researching a cure. Antiretroviral drugs were proposed as a potential treatment for the syndrome.

But before long, researchers were questioning the study’s validity. Attempts to find XMRV in other groups of patients with chronic fatigue syndrome, including one paper in the BMJ (2010;341:c1018, doi:10.1136/bmj.c1018), failed. Other studies pointed to the possibility that the strain of XMRV picked up by Lombardi and colleagues’ study was created inadvertently during work on a mouse cell line to investigate prostate cancer and had subsequently contaminated laboratories and reagents (BMJ 2010;341:c7358, doi:10.1136/bmj.c7358).

In June this year the editors of Science published an “editorial expression of concern” after asking the authors to retract their paper, which they declined to do (BMJ 2011;342:d3505, doi:10.1136/bmj.d3505). Science’s editor in chief, Bruce Alberts, said that “the validity of the study by Lombardi et al is now seriously in question.”

In their partial retraction, published as an online letter this week (doi:10.1126/science.1212182), the authors say: “In our 23 October 2009 report, ‘Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome,’ two of the coauthors, Silverman and Das Gupta, analyzed DNA samples from chronic fatigue syndrome (CFS) patients and healthy controls. A re-examination by Silverman and Das Gupta of the samples they used shows that some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA.”

The letter goes on to say that two figures and one table in the report were based on this contaminated DNA and are being retracted. A press release from Science says, “The authors feel the Lombardi et al paper’s conclusions do not stand on these figures and table alone and can be supported by the remaining evidence reported in the study.”

However, Dr Silverman, who is named by Science as the media contact for the partial retraction, would only say in a statement, “Dr Silverman requested that Cleveland Clinic data and his name be removed from the paper. The journal holds the authority to make the decision about retracting the whole paper (or partial), not us.”

The editors of Science say they stand by their earlier expression of concern and are “discussing next steps” with the authors.

At the same time a study casting further doubts on the validity of the research has been published, also in Science (doi:10.1126/science.1213841). The study was conducted by the Blood XMRV Scientific Research Working Group, sponsored by the US National Heart, Lung and Blood Institute. The original researchers took part in this study.

It is a multi-laboratory analysis of blood samples taken from 15 patients with chronic fatigue syndrome who had previously been identified as testing positive for XMRV and 15 control subjects previously identified as XMRV negative. The study participants had previously been included in the 2009 report.

Seven of the nine laboratories found no traces of XMRV in the blood samples either of patients with the syndrome or of healthy controls. Only the two laboratories involved in the 2009 research found XMRV—and their findings were not consistent, with the virus being found in controls as often as patients with the syndrome. When the positive samples were divided and retested, some tested positive and others did not. The two laboratories did not agree on which samples were contaminated.

The authors of the new study say that this shows that the laboratory tests for XMRV are unreliable, because results were inconsistent and could not be reproduced, even when testing the same sample.

They conclude: “The inconsistent reactive results from the two laboratories that previously reported detection of XMRV . . . and the negative results from all other laboratories . . . strongly suggest that the positive reactivity in this study represents false positive results due to assay nonspecificity or cross-reactivity.”

Notes

Cite this as: BMJ 2011;343:d6097