PNAS lifts embargo on virus-chronic fatigue syndrome study after break, but the real story is the study’s delayed publication
At 2:55 p.m. Eastern today, just five minutes before the embargo on this week’s Proceedings of the National Academy of Sciences (PNAS) issue was set to lift, PNAS sent out a note to its press list saying that the embargo on one paper was being lifted early because of an embargo break.
I’m fuzzy on who broke the embargo — the only thing I can find is a PRNewswire release that went out about 2:30 — and why PNAS would bother lifting it five minutes early. I’ve emailed the journal’s press office for details and will update with anything I find out. [Update, 4:45 p.m. Eastern, 8/23/10: PNAS emailed back and confirmed that it was the PRNewswire release that prompted the early lift.]
In the study, researchers found bits of DNA related to murine leukemia viruses (MLV), which cause leukemia in mice, in the blood of a large percentage of people with chronic fatigue syndrome. When they looked at the blood of healthy blood donors, relatively few had that DNA on board.
The findings — which follow on others — are likely to bolster claims of a virus-fatigue syndrome link. MLV is a variant of xenotropic murine leukemia virus-related virus (XMRV), which has been in the news lately as a potential link to prostate cancer as well as chronic fatigue syndrome. But those studies have been contradictory, so the new study could shed some light on an ongoing scientific investigation that some hope could lead to new targets for chronic fatigue syndrome targets.
That recent buzz brings me to what’s far more interesting, from an Embargo Watch perspective: An editorial accompanying the study by PNAS editor in chief Randy Schekman. Excerpt (I’ve added links to a relevant paper):
Although the paper had undergone peer review and was accepted for publication in PNAS on May 27, on June 4, the authors contacted PNAS and requested a delay of publication while conflicting results from another government-funded study by Switzer et al. (2) that was submitted to Retrovirology were considered. Switzer et al. (2) did not find XMRV or other MLV-related virus sequences or associated antibodies in their chronic fatigue syndrome patient population or in healthy controls. The Retrovirology paper published online July 1.
In light of the conflicting findings, on June 18, PNAS provided Lo et al. with additional comments including a recommendation that direct evidence of viral gene integration into the host genome be provided. The authors submitted a revision on July 22 that was evaluated by the PNAS editors. The final version of the article, which is published in this issue of PNAS, was received on July 30. The following comment was added to the paper, “The ultimate proof of low-grade infection by MLV-related viruses in humans may rely on demonstrating the integration of the viral genes into the human genome (3). The identification of provirus integration sites will take more time and effort to investigate, given that we estimate only one virus gene copy in every 400–4,000 nucleated peripheral blood mononuclear cells. Previous work with XMRV indicates that integration sites are quite variable (4) and that the same may be true for the polytropic mouse endogenous retroviruses, which are predominant in this study.”
As a publisher, when authors or their funding agencies request additional time to ensure that work is ready for public release, particularly when there are public health implications, we strive to work closely with them to promptly address their concerns. Although PNAS was urged not to delay the paper by Lo et al., our greatest concern has been the documentation and validity of the evidence in light of the possible public health implications of this work. We trust that the revisions to the paper have resulted in a stronger article.
My former colleagues at The Scientist evidently thought that was where the real money was too. They’ve got an illuminating Q&A with Schekman that I’d urge you to read. Excerpt from the piece, in which Schekman calls the situation “nothing routine”:
…as I became aware of [the Retrovirology] paper, I decided on my own authority to solicit an independent review of the work from an established person in the field — someone who has very high standards and who has not been involved in this controversy. He wrote a critique, which I then conveyed to Alter, which called for the paper not to be published until they could demonstrate that the virus’ genes were integrated into the human genome. Alter then responded several weeks later saying he of course understood this. This was indeed the highest standard that would prove the case, but he felt that his data and the care that he had used in the selection and maintenance of the samples made his data very strong. He felt that by delaying this further, that would be a disservice to the community to hold the data that much longer. So then he sent us a revised version of the paper and I sent it to an independent member of my editorial board, another retrovirus expert. He said on balance he felt the paper should be published now. He agreed that this additional work was crucial but that the data were strong enough to be published now. And so we accepted it.
Here at Embargo Watch, we often wonder why a particular paper wasn’t published sooner, and when we don’t hear a good answer — particularly when something could change clinical practice, or is government-funded — we are left wondering whether it was just because a journal wanted to maximize its time in the limelight of the news cycle.
But here’s a case in which the editor of a prominent journal is providing the kind of transparency we hope for from all journals. Kudos to Schekman and the journal. Whether this decision was the right or wrong one — and based on what Schekman writes and says it’s the right one — being forthright is most certainly the right thing here.
Now while we have you, PNAS, can you do anything about making sure all papers are available online when their embargo lifts?
Related on Embargo Watch: What happened when a PNAS study broke a data embargo
Related on Retraction Watch: 2005 PNAS Arabidopsis cold sensitivity gene paper retracted