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."