Should scientific journals publish gain-of-function (GOF) studies, especially those involving pathogens with pandemic potential? While journal editors at the American Society for Microbiology have done so after careful consideration, some scientists expressed concern over that decision. A series of letters to and responses from the editors, and a new editorial on the situation, appear in this week's mBio.
At issue is an April report in the ASM's Journal of Virology of sequence changes in highly pathogenic avian influenza virus A H7N1 associated with airborne transmission in mammals. Authors found that serial inoculation of A/H7N1 into ferrets led to mutations allowing airborne transmission of the virus to other ferrets housed in the same area.
The JV study was accompanied by two editorials from ASM, one detailing a rigorous, multistep evaluation of the paper for the possibility of dual use research of concern (DURC) --- research that could be misapplied to pose a significant threat to public health and safety --- before editors decided it made important contributions toward understanding of influenza virus transmission. A second editorial called for a federal board to assess DURC. DURC evaluations are now conducted by journal editors with occasional consultation from individuals serving on a national science advisory board for biosecurity.
Even so, Simon Wain-Hobson of the Institut Pasteur in Paris wrote that he disagreed with both the decision to publish the paper and the editorial explaining its publication, "for the underlying science is not as strong as it appears." H7N1 is not a threat to humans, his letter said, and because flu lineages come and go, the scientists should have used a currently circulating H7 virus. The number of ferrets used also was "too small to yield statistically robust results," he said.
"We are left with a highly pathogenic H7N1 virus that is transmissible via the airborne route," he said. "This lab-engineered H7N1 strain would constitute a novel danger for humans if it ever escaped."
Editors defended their position in a reply, noting that reviewers "concurred that the results were novel, significant and scientifically sound," that they carefully debated whether the study represents DURC, and that although they could not spell out a concrete risk-benefit analysis they felt the potential risks of the study were low. "The risk of some type of laboratory accident is not zero, but we think that appropriate steps were taken to diminish risk to a minimum degree."
Others responded to a September editorial from mBio editors discussing the epistemological perspective on the value of GOF studies. There, Editor-in-chief Arturo Casadevall and colleagues wrote that GOF experiments, in generating microbes with new functions and new phenotypes, inform experimenters on the possibility of additional outcomes and provide insight into how microbes acquire new functions. With no alternatives to GOF experiments for seeking answers to certain biological questions, "we all think that some risks are reasonable for the gain that comes from scientific progress."
Nicholas Evans of the University of Pennsylvania, and Marc Lipsitch of the Harvard School of Public Health, took issue with the original report and the September editorial. "Arguing that bodies of knowledge are valuable for their own sake says nothing about how we ought to weigh this value against other considerations," Evans wrote. "Even less clear is how we account for the marginal increases in value—of knowledge for its own sake—that we receive from GOF/PPP experiments." Lipsitch argued that in a world of scarce scientific resources, it's essential to judge the epistemic value of GOF/PPP experiments versus other approaches with safer viral genetic backgrounds: "Can a risk to the life and health of large numbers of people ever be balanced by the benefit of pure scientific knowledge?"
In an editorial, mBio editors note that debating the risks and benefits of such experiments will continue. Proponents of GOF emphasize the potential benefits of research and link the work to benefits like the development of better vaccines, improved public health surveillance tools and new basic science knowledge, they said, while opponents cite the risk of these experiments, including nefarious use of the information to lab accidents unleashing new pandemics. Only time will reveal the answer, they said, but meanwhile individuals should not over-rely on apocalyptic scenarios when arguing their position. History has shown that humans are "notoriously bad" at assessing risks and benefits, they noted, and "rhetoric never gave us a single medical advance."
Recognizing the importance of the public health emergency of the ebola outbreak in western Africa, the ASM has compiled a list of informational resources available from the Society and other sources on the disease. This list will be updated as new material becomes available.
ASM Journal Articles on Ebola
A compendium of every journal article published by the ASM on Ebola. No subscription required.
October 2, 2014 - ASM Provides Ebola Resources for Clinical Laboratory Scientists
The ASM sent out a notice to clinical members about Ebola Virus resources.
September 23, 2014 - ASM Letter to the US HHS Concerning Scientific Resources in Response to the Ebola Virus Outbreak
The ASM sent a letter to Sylvia M. Burwell, Secretary US Department of Health & Human Services with recommendations concerning scientific resources that are needed in response to the Ebola virus outbreak.
September 23, 2014 - ASM Letter to the UN Concerning Scientific Resources in Response to the Ebola Virus Outbreak
The ASM sent a letter to David Nabarro, M.D., Senior United Nations System Coordinator for Ebola Virus Disease with recommendations concerning scientific resources that are needed in response to the Ebola virus outbreak.
September 17, 2014 - ASM Statement on Ebola Response
The ASM sent a statement about the Ebola response on September 17, 2014 to ASM members and members of Congress.
Interim Laboratory Guidelines for Handling/Testing Specimens from Cases or Suspected Cases of Hemorrhagic Fever Virus
The Committee on Laboratory Practices of ASM's Public and Scientific Affairs Board (PSAB) has prepared a document to assist laboratory personnel with testing in accordance with the current CDC Ebola Interim Guidance.
On September 8, 2014, 3 speakers presented information about the current Ebola outbreak in West Africa at the ASM’s annual infectious disease meeting, the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
- Ebola Outbreak Response in West Africa: A Diagnostic, Scientific, and More Importantly, Humanitarian Perspective
Gary Kobinger; Natl. Microbiol. Lab., Winnipeg, Canada
- Responding to the Ebola Outbreak in West Africa: Current Status and Lessons Learned
Barbara Knust, Centers for Disease Control and Prevention, Atlanta, GA
- Managing Patients Infected with Ebola Virus in Developed Countries: Lessons Learned
Aneesh Mehta, Emory University School of Medicine
Watch the video of their press conference.
View their full scientific presentations:
Other Ebola Resources
General Outbreak Information:
- What's New from the U.S. Centers for Disease Control and Prevention (CDC)
- CDC's Ebola Hemorrhagic Fever Resources Page
- World Health Organization Disease Outbreak News
- National Library of Medicine Emergency Access Initiative - Freely Available Biomedical Literature on Ebola
New Or Updated Guidance Documents:(Full range of guidance documents can be found on the CDC Ebola Web site http://www.cdc.gov/ebola
- Guidance on Personal Protective Equipment To Be Used by Healthcare Workers During Management of Patients with Ebola Virus Disease in U.S. Hospitals, Including Procedures for Putting On (Donning) and Removing (Doffing) – posted 10/20/2014
- Interim Guidance Regarding Compliance with Select Agent Regulations for Laboratories Handling Patient Specimens (NEW)
- U.S. National Science Foundation RAPID Funding for Ebola Research – posted 10/19/2014
- To Fight Ebola, Create a Health Workforce Reserve Force (Op-Ed, Los Angeles Times)
- A United Nations Security Council Resolution is Essential to Preventing the Threat to International Peace and Security Posed by Ebola (The O’Neill Institute for National and Global Health Law)
- Ebola: Towards an International Health Systems Fund (The Lancet -- Subscription Required)
Garth Hogan, ASM Office of Communications