Science 7 January 2011: News of the Week

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http://www.sciencemag.org/content/331/6013/17.short

Science 7 January 2011:
Vol. 331 no. 6013 p. 17

DOI: 10.1126/science.331.6013.17

News of the Week

Chronic Fatigue Syndrome


Martin Enserink
Jocelyn Kaiser*

Summary

The stormy debate over a potential cause of chronic fatigue syndrome (CFS) is nearing hurricane force. Last month, it prompted headlines suggesting that researchers have reached a dead end, scores of blog posts from disappointed patients, and accusations that scientists had gone beyond their data. The 14-month-old row intensified when four papers appeared in Retrovirology suggesting that reports linking the virus XMRV to CFS were based on false positives.

* With reporting by Martin Enserink.

Read full text: http://www.sciencemag.org/content/331/6013/17.full
PDF: http://www.sciencemag.org/content/331/6013/17.full.pdf
 

CBS

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Good to see this:

“The data shown … do not justify some of the sweeping statements made,” says Ila Singh of the University of Utah, Salt Lake City, who has reported XMRV in prostate cancer samples."
And this is interesting:

One outspoken scientist wavered on the significance of the Retrovirology papers. Columbia University virologist Vincent Racaniello, who runs a popular virology blog and podcast, initially e-mailed a Chicago Tribune reporter to say that they were “probably the beginning of the end of XMRV and CFS.” But he retracted that statement (and a similar comment to Science) after reviewing the studies more closely. “It’s pretty complicated,” Racaniello concludes.
 

urbantravels

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I wished they'd given more of that quote from Dr. Singh (I'm dying to know what's behind that ellipsis!) and that they hadn't given the last word to our buddy Stoye. If this "we're wasting all this money on studies just to satisfy patients" meme gets much traction, it'll be a black day for all of us. But overall a fairly reasonable article.
 

CBS

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I wished they'd given more of that quote from Dr. Singh (I'm dying to know what's behind that ellipsis!) and that they hadn't given the last word to our buddy Stoye. If this "we're wasting all this money on studies just to satisfy patients" meme gets much traction, it'll be a black day for all of us. But overall a fairly reasonable article.
Overall a good article with a terrible title. Interesting to see that the number of patients in the Lipkin study is up to 150. Not sure I agree with his comment about his study being definitive but there's always the chance that he knows something we don't.;)
 

Sean

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"we're wasting all this money on studies just to satisfy patients"
Yeah, those pesky damn patients. Ingrates, the lot of 'em.

Practising medicine would be so much easier if doctors didn't have to deal with patients at all.
 

Esther12

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Full paper thanks to the ME association (and presumably Science): http://www.meassociation.org.uk/?p=3737

Studies Point to Possible Contamination in XMRV Findings

The stormy debate over a potential cause of chronic fatigue syndrome (CFS) is nearing hurricane force. Last month, it prompted headlines suggesting that researchers have reached a dead end, scores of blog posts from disappointed patients, and accusations that scientists had gone beyond their data. The 14-month-old row intensified when four papers appeared in Retrovirology suggesting that reports linking the virus XMRV to CFS were based on false positives.

The debate began in 2009 with a report in Science that XMRV, a retrovirus recently reported to have been found in prostate tumors, had been detected in 67% of a set of CFS patients but in only 4% of controls (Science, 9 October 2009, p. 215). Since then, one other group has found XMRV- like viruses in CFS patients’ blood. But sev- eral teams have failed to detect the virus in CFS or cancer patients or in healthy peo- ple. Researchers have struggled to explain the discrepancies (Science, 17 September 2010, p. 1454).

The potential link to CFS has had important consequences: Some CFS patients have begun taking antiviral drugs, which can have side effects. Last month, after being briefed on the original XMRV studies, advisers to the U.S. Food and Drug Administration recommended that CFS patients be barred from donating blood.

The Retrovirology papers point to contamination as a possible source of positive results in previous studies. The polymerase chain reaction (PCR) test used to detect XMRV (a mouse retrovirus adapted to infect humans) could actually be picking up minute amounts of mouse DNA or similar mouse viruses.

Two of the four studies in Retrovirology used highly sensitive assays for mouse DNA and found that samples positive for XMRV-like viruses also tested positive for mouse DNA. Another study found mouse viral RNA in a commercial PCR kit. And the fourth study argues that XMRV sequences previously reported in patient samples don’t show the diversity expected if the virus were spreading through the human population. Instead, these authors report, the sequences are similar to those found in a popular pros- tate cancer cell line, 22Rv1. This cell line, used in lab experiments, was already known to contain an XMRV-like sequence.

Greg Towers of University College London (UCL), who led the study of XMRV diversity, says the evidence linking this virus and human disease “is really looking pretty shaky now.” The Wellcome Trust, which cosponsored the research, and UCL issued a press release last week declaring flatly that the Towers study showed that “chronic fatigue syndrome is not caused by XMRV,” a message some newspapers repeated. Towers says he was “comfortable” with the release. But John Coffin of the U.S. National Cancer Institute (NCI) and Tufts University Sackler School of Graduate Biomedical Sciences in Boston, who co-authored two of the contamination papers, is wary.

He says these studies “just point out how careful one must be.”

Virologists who have found a virus-disease link disagree with coverage of the Towers paper. “The data shown … do not justify some of the sweeping statements made,” says Ila Singh of the University of Utah, Salt Lake City, who has reported XMRV in prostate cancer samples. Moreover, the lead author of the Science paper on CFS and XMRV, Judy Mikovits of the Whittemore Peterson Institute (WPI) in Reno, Nevada, points out that PCR wasn’t the only test her studies used: For example, Mikovits’s team also showed that XMRV-positive patients make antibodies to the virus and that XMRV isolated from their blood can infect cultured human cells. Mikovits said in a statement, “Nothing that has been published to date refutes our data.”

One outspoken scientist wavered on the significance of the Retrovirology papers. Columbia University virologist Vincent Racaniello, who runs a popular virology blog and podcast, initially e-mailed a Chicago Tribune reporter to say that they were “prob- ably the beginning of the end of XMRV and CFS.” But he retracted that statement (and a similar comment to Science) after reviewing the studies more closely. “It’s pretty complicated,” Racaniello concludes.

Some had hoped that a project in which several U.S. labs are testing for XMRV in the same samples would clear up the picture. But so far this effort has been incon clusive. Four CFS patients’ blood initially tested positive for XMRV at WPI and the U.S. Centers for Disease Control and Pre- vention but not at an NCI lab. When all three labs tested new samples from the same patients, none found XMRV—for reasons that aren’t yet clear, says Coffin. The group now plans to test blood from several dozen CFS patients and controls.

A bigger study is now under way. Funded by the U.S. National Institute of Allergy and Infectious Diseases, virologist W. Ian Lipkin of Columbia University is lead- ing a project that will collect blood from 150 CFS patients and 150 controls from six U.S. clinical sites. The samples will be tested blindly by several labs. Because all the clinicians have agreed on standard methods, the study should help resolve concerns that differences in how CFS patients are selected or how samples are handled could explain clashing conclusions, Lipkin says: “Results will be definitive.”

As the new study gets started, some wonder whether it’s worth the $1.3 million it will cost. Jonathan Stoye of the MRC National Institute for Medical Research in London concedes that the Towers study was “over- hyped.” But he says “it’s pointing people in a certain direction,” away from chasing an elusive link to XMRV. Still, he says, a larger study may be the only way to satisfy patients.
 

SOC

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As the new study gets started, some wonder whether its worth the $1.3 million it will cost. Jonathan Stoye of the MRC National Institute for Medical Research in London concedes that the Towers study was over- hyped. But he says its pointing people in a certain direction, away from chasing an elusive link to XMRV. Still, he says, a larger study may be the only way to satisfy patients.
Has Stoye actually met any real PWCs (as opposed to Reeves-type)? Has he never seen a seriously ill clearly viral patient?

The scorn of patients with which he speaks is shocking from any medical professional.
 

redo

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A bigger study is now under way. Funded by the U.S. National Institute of Allergy and Infectious Diseases, virologist W. Ian Lipkin of Columbia University is lead- ing a project that will collect blood from 150 CFS patients and 150 controls from six U.S. clinical sites. The samples will be tested blindly by several labs. Because all the clinicians have agreed on standard methods, the study should help resolve concerns that differences in how CFS patients are selected or how samples are handled could explain clashing conclusions, Lipkin says: “Results will be definitive.”
Anyone who knows how the progress is going on this one?
 

redo

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What makes you say that (that we're not going to hear for a while)? I guess there are other threads on this topic, but I am too foggy to look now.
 

Jemal

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What makes you say that (that we're not going to hear for a while)? I guess there are other threads on this topic, but I am too foggy to look now.
The Lipkin study was supposed to be complete by the end of this year. It started late however and it's more likely we will see results early 2012. It's a timeconsuming study, Mikovits has commented that it will take them a long time to test all the samples.

We should see results from the Blood Working Group in the summer (phase 2), or as least that was their schedule...
 
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Minor correction: phase II of the BWG has been completed (and results have been reported), it's phase III results that are due this summer.
 

Jemal

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Minor correction: phase II of the BWG has been completed (and results have been reported), it's phase III results that are due this summer.
Thanks for the correction RRM. Phase 3 it is then!

In other news, I should just look these things up to be sure and not rely on my memory... it's not what it used to be.
 

redo

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Thanks. Can you sum up what this blood working group is in a sentance or two? I am too foggy to browse through the threads.
 

Jemal

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Thanks. Can you sum up what this blood working group is in a sentance or two? I am too foggy to browse through the threads.
The Blood Working Group was formed by the National Institutes of Health (NIH). The group includes people from several organisations, like the FDA, CDC, but also blood banks and others. There's six labs involved, including the WPI. Their mission is to evaluate whether XMRV poses a threat to blood safety.