Nature Medicine | Spoonful of Medicine

There’s no tiring of controversy in the XMRV–chronic fatigue syndrome link


It’s been a hectic couple of weeks for Judy Mikovits. First, her controversial research on the viral cause of chronic fatigue syndrome was condemned by the journal that published it. Then, her alternative hypothesis — that a new gammaretrovirus closely related to the originally proposed culprit, xenotropic murine leukemia virus-related virus (XMRV), is responsible for chronic fatigue — was received with misgivings by the scientific community at a major international conference. Add to the mix allegations of fabricated results and a blow-out with her boss, and Mikovits ended up being fired from her job at the Whittemore Peterson Institute (WPI) for Neuro-Immune Disease in Reno, Nevada.

The research that spawned the drama was originally published in Science in October 2009, and purported to show a link between the infectious retrovirus XMRV and chronic fatigue syndrome in two-thirds of CFS patients examined. The study, conducted by Mikovits and her collaborators, was the first sign of an infectious cause for the disease. However, follow-up studies since 2009 showed that other labs could not reproduce these results and scientists began to suspect that Mikovits’ original patient samples had been contaminated.

On 22 September, a large study published by Science showed that, of nine national laboratories, none could find XMRV in their patients’ blood — including Mikovits’ own lab. Notably, Science issued a partial retraction of the original 2009 paper on the same day, stating that one of Mikovits’ collaborators had found XMRV contamination in the patient blood samples. The saga was documented in a long feature by Science, ending with Mikovits pledging to continue studying the CFS and its viral links.

The next day, Mikovits presented the results of the latest study negating her research at a CFS conference in Ottawa, Canada, where she shared the podium with retrovirologist John Coffin of Tufts University in Boston, an opponent of her hypotheses. As a Science news article reported, Mikovits did not make a case for XMRV, admitting she may have been wrong about it. Instead, she proposed that CFS patients were infected with an XMRV-like virus from the gammaretrovirus family. Few at the meeting swallowed this alternative theory. As Swedish retrovirologist Jonas Blomberg told Science: “It’s like the argument follows the availability of the data.”

Another controversy that came out of the Ottawa meeting was more serious: the Chicago Tribune reported that Mikovits used a figure from her original paper in her Powerpoint presentation — except it carried different labels and established proof of a different concept. The discrepancy was spotted by a graduate student from Oklahoma, who blogged about it on Friday. To assess if there had been figure manipulation, Science’s editors told the Tribune that they were investigating the allegations.

The biggest consequence of this particular controversy, according to the Tribune, seems to have been Mikovits’ termination from her position as Director of Research at WPI. However, the Wall Street Journal’s Health Blog throws in another confounding factor into the events of last week — a falling out between Mikovits and WPI President Annette Whittemore. The WSJ reported that Mikovits refused a direct request from Whittemore to turn over her patient samples to another scientist, leading to her termination from employment.

The situation is currently at a stalemate, with the grant funding, provided by the US National Institutes of Health (NIH) hanging in the balance. The NIH has yet to decide whether Mikovits can take the money with her, or whether the WPI will continue to participate in the study, cutting Mikovits out of the story for good.

Something tells me we haven’t reached the end of this chronic saga.

Image: David Calvert/AP/Nature


  1. Report this comment

    Shane said:

    It has already been proven that the viruses Lombardi et al. discovered are human gamma retroviruses (HGRVs), not VP62/XMRV. This is Indisputable.

    Silverman HAD VP62 plasmid contamination in his samples in his lab. So he incorrectly sequenced the Contaminant and note the viral late to heaven. The WPI and NCI Already Have Their test samples before They left are not contaminated with VP62 plasmid. In fact the VP62 plasmid hock Never Been In The WPI or NCI labs. Ask Frank Ruscetti and Judy Mikovits.

    So the WPI and NCI Discovered polytropic sequences. What the Rest of Those viruses Will Be When Fully sequenced is not yet known. Some Could Still Have A xenotropic host range, some polytropic, some a mix. Some May Be Just Like VP62/XMRV, but Will not ask VP62/XMRV. However, They Are the Same viruses That Lo et al. Confirmed finding in people with ME / CFS.

    She was very well received by all the scientists in Ottawa, except John Coffin who has his own agenda to push. Is he really trying to get Science to retract Lombardi et al. because Frank Ruscetti, who performed all the western blots, put the wrong slide, with the real patient codes, into the presentation for Ottawa?

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    Justin Reilly said:

    Science issued a ‘statement of concern’ about the paper. You characterize this as ‘condemned’ but that’s a bit harsh! Also it’s ME (“CFS”) not ‘chronic fatigue.’

    I hadn’t heard anywhere that ‘most’ people at the conference disagreed with her. Where did you get this from?

    I don’t understand Blomberg’s disapproving comment here: “It’s like the theory follows the availability of the data.” Isn’t that the definition of science??

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    Andrew said:

    Scientists make mistakes all the time because they are only human. The difference in this case is the scale of the controversy.

    Meanwhile Chronic Fatigue Syndrome receives an order of magnitude less research funding than any other category on the NIH website:

    Economic costs study:

    If there was more actual science into the biology of the disease, then perhaps the scale of this controversy wouldn’t have been of the same magnitude. Instead all patients get are lame puns from journalists, such as the above mention of “chronic saga”.