By K. Kimberly McCleary, President & CEO
Nature is the world’s leading weekly scientific journal. It was founded in 1869 to “place before the general public the grand results of scientific work and scientific discovery; and to urge the claims of science to a more general recognition in education and in daily life, and, Secondly, to aid scientific men themselves, by giving early information of all advances made in any branch of natural knowledge throughout the world and by affording them an opportunity of discussing the various scientific questions which arise from time to time.” Today, the Nature Publishing Group (NPG) serves these diverse needs and the journal Nature is supplemented by a group of journals in the Nature Reviews series as well as other specialty journals for the scientific audience. Scientific American is NPG’s public consumer magazine.
There has not yet been a report of original research specific to CFS in Nature. But last month I noticed an interesting trend when on July 27 Nature Reviews Neuroscience published a six-page Q&A about CFS. It was the sixth article that month about CFS in an NPG publication. So, I did a little more research. (Note: At our request, Nature Reviews Neuroscience has made a full-text copy of the article available through Sept. 8, 2011 at http://www.nature.com/nrn/journal/v12/n9/full/nrn3087.html.)
A search of NPG’s publications for “chronic fatigue syndrome” yields 1,734 resulting references. I looked closely at the first 1,000 that date back to July 2005. The large majority of the articles returned in the search are about a grab-bag of other conditions, from fibromyalgia and irritable bowel syndrome (not unexpected, given the frequent overlap) to obesity, leukemia, Parkinson’s disease, spinal cord injury and a variety of infectious and autoimmune diseases. Most of the articles can only be accessed by subscribers or for a fee, so it’s hard to tell why they might be indexed to CFS.
Between 2005 and October 2009, there were three articles with CFS in the title published in NPG journals:
- Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome (research paper)
Lucile Capuron, Leonie Welberg, Christine Heim, Dieter Wagner, Laura Solomon, Dimitris A Papanicolaou, R Cameron Craddock, Andrew H Miller & William C Reeves
Neuropsychopharmacology (open access), Jan. 4, 2006
- Chronic fatigue has genetic roots (news story about the CDC’s CFS Computation Challenge)
Nature News, Apr. 21, 2006
- Chronic enterovirus infection might contribute to chronic fatigue syndrome development (news story about John Chia’s research)
Nature Clinical Practice Gastroenterology & Hepatology, Dec. 2007
On Oct. 8, 2009, when closest-rival journal Science published a research report linking CFS to XMRV (Lombardi et al.), Lizzie Buchen covered the news in Nature News: Virus linked to chronic fatigue syndrome. Nature ran a brief news article in its Oct. 14, 2009, issue, Virology: Infectious fatigue. Two other NPG publications did likewise and one included the XMRV link in its 2009 year-end news round-up. The first three studies that failed to confirm the link prompted a short update in the April 2010 issue of Nature Reviews Microbiology.
Katherine Harmon reported on the PLoS One paper from Dr. Ila Singh’s group at University of Utah about antiretroviral drugs’ action against XMRV in laboratory (not clinical) tests. “HIV drugs could have second life as treatment for retrovirus correlated with prostate cancer,” was posted to Scientific American’s website on Apr. 1, 2010.
Led by Dr. Robert Silverman, a Cleveland Clinic team reviewed the literature on XMRV, prostate cancer and CFS in this June 1, 2010, article: The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome in Nature Reviews Urology (open access).
One month later, after the CDC’s negative study of XMRV was published and a positive FDA-NIH study was held until additional experiments could be run, Heidi Ledford covered the controversy with Chronic fatigue findings were held back in Nature News on July 2, 2010.
Nature Precedings, a publication for pre-publication research and preliminary findings, published an early report from Christopher Carter, Proteins of the XMRV retrovirus implicated in chronic fatigue syndrome and prostate cancer are homologous to human proteins relevant to both diseases (open access, July 2010). (This appears to be the only XMRV-related publication by this author.)
The Aug. 23, 2010, publication of the long-awaited report from Lo et al., in Proceedings of the National Academy of Sciences (considered the third leading science journal) led to brief news coverage in two NPG publications:
Chronic controversy continues over mysterious XMRV virus
Nature Medicine, August 2010
In the news
Nature Reviews Microbiology, August 2010
Science-Business eXchange published the first of two articles about XMRV testing on Sept. 2, 2010: Diagnostic markers for a virus associated with CFS. A follow-up report, Diagnostic markers for a virus associated with chronic fatigue syndrome (CFS) or prostate cancer, was published on Jan. 27, 2011. In between these reports, Nature Reviews Microbiology included a news item in its Feb. 2011 issue about four studies published on Dec. 20, 2010, in Retrovirology that pointed to contamination as the source of positive results.
Then, on Mar. 14, 2011, came Ewen Callaway’s four-page profile of Dr. Judy Mikovits, the senior author of the original report linking CFS and XMRV, in Nature: Fighting for a cause. It was accompanied by an editorial, Cause for concern. The two articles attracted hundreds of comments and spurred speculation about what results might be forthcoming from a collaboration between Drs. Dan Peterson and Jay Levy reported by Callaway. Dr. Peterson was the inspiration for the Whittemore Peterson Institute (WPI) where Dr. Mikovits made the initial discovery, but he left quietly in 2010. Dr. Levy was among the first to isolate HIV; he is a renowned retrovirologist who studied CFS in the early 1990s.
The Levy study results were published on May 31, 2011, in Science. They were negative, even for 14 CFS patients who had tested positive at WPI, and some assay results identified sources of contamination that could lead to falsely positive results. Callaway made a follow-up report in Nature News on June 3, 2011, Chronic fatigue syndrome: life after XMRV. Erica Westly covered the developments for Scientific American, Retrovirus no longer thought to be cause of CFS. A second report in Scientific American by Nina Bai addressed the issue of deferring blood donors who had CFS, Donor fatigue, published June 14, 2011.
The steady coverage by NPG publications expanded in July with six articles, all but the last of which was about the Levy study and a companion report in Science by Paprotka et al. that tracked the origins of XMRV to a lab recombination in the early 1990s:
- News in brief
Nature Medicine, July 7, 2011
- Too soon to translate? (Editorial)
Nature Medicine, July 7, 2011
- Prostate cancer: XMRV—contaminant, not cause? (Research Highlights)
Suzanne J. Farley
Nature Reviews Urology, July 12, 2011
- Righting scientific wrongs (Editorial)
Nature Reviews Microbiology, July 17, 2011
- Is XMRV a causal virus for prostate cancer? (Review article)
Zhen-Zhen Zhang, Bao-Feng Guo, Zhuang Feng, Ling Zhang & Xue-Jian Zhao
Asian Journal of Andrology, July 18, 2011
- Chronic fatigue syndrome: understanding a complex illness (Perspectives)
Stephen T. Holgate, Anthony L. Komaroff, Dennis Mangan & Simon Wessely
Nature Reviews Neuroscience, July 27, 2011
The “Righting scientific wrongs” editorial examined the scientific community’s response to two recent controversies that had sprung from original research published in Science – arsenic-fueled bacteria and XMRV. Discussing XMRV, the editors write, “In this case, the experimentation-publication-retesting process has clearly worked; the response from the scientific community has all but discredited the initial erroneous link between XMRV and CFS.” They go on to caution that, “…scientists and the media have a duty to be aware of the potential outcomes of their work and should not be tempted to make sweeping claims. The possibility always remains that the result was incorrect owing to circumstances outside the researchers’ control. So, it is alright to be wrong — but we should always be very cautious when reporting controversial findings.”
The six-page feature story published on July 27 followed a question-and-answer format about each of the four scientists’ “views on CFS, its causes and the future of research aimed at improving understanding of this chronic illness.” Dr. Holtgate is U.K. Medical Research Council clinical professor of immunopharmacology at the School of Medicine, University of Southampton. Dr. Komaroff, professor of medicine at Harvard Medical School, has studied CFS for 25 years. Dr. Mangan is the chair of the Trans-NIH ME/CFS Research Working Group at the National Institutes of Health. Dr. Wessely, the most controversial contributor to the article, is the chair of psychological medicine and vice dean for academic psychiatry at King’s College in London. All four researchers responded to the following questions:
- Why do we not know what causes CFS and why is the field so polarized?
- Why do studies use different classifications of CFS and how crucial are these differences for research into CFS?
- How strong is the evidence that viral infections and/or immune dysregulation play a part in the aetiology of CFS?
- Does CFS have a psychiatric and/or psychological component? Why is there such resistance from patient groups against this idea?
- Is CFS ultimately a disease of the CNS (neurological and/or psychiatric)?
- What is the best way for the field to make progress? How will the recent negative XMRV findings affect research directions in this field? What could be the role of neuroscience in advancing the field?
Their answers point to the need for standardized case definitions and deeper exploration of many “leads” that already exist in the literature, applying new technologies across a range of scientific disciplines. (Note: At our request, the journal has made available a link to the full text until Sept. 8 at http://www.nature.com/nrn/journal/v12/n9/full/nrn3087.html; see comment below.) Simon Wessely’s participation in the Q&A got extra attention two days later when he was interviewed by BBC radio and television programs about harassment by some CFS patients. Overall, it’s a detailed and well-balanced article providing extensive coverage about a range of important research issues in a journal with a very high impact factor (29.51).
We will continue tracking the Nature Publishing Group’s attention to CFS, hoping the heightened editorial interest demonstrated over recent weeks and months will soon translate to publications of original research. Coverage of CFS by top journals like these will help accomplish an essential task that Dr. Komaroff highlights in the Nature Reviews Neuroscience article: “In my experience, most sceptics are unaware of the extensive literature citing [documented] abnormalities [of the central and autonomic nervous systems] and become less sceptical upon reading it.”
K. Kimberly McCleary has served as the Association’s chief staff executive since 1991August 3, 2011