Gain-of-Function Research: Unknown Risks

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Science  18 Oct 2013:
Vol. 342, Issue 6156, pp. 311
DOI: 10.1126/science.342.6156.311-a

We were astonished by the recent letter by R. A. M. Fouchier et al. (“Gain-offunction experiments on H7N9,” 9 August, p. 612; published online 7 August) and the simultaneous publication in Nature (1). We find it odd that an H7N9 influenza A research manifesto signed by a number of flu virologists should be aired so prominently, coming as it does from a distinguished but unrepresentative group. The Letters were disavowed within 24 hours by opinions from two influential Chinese influenza scientists (2, 3). Publishing research manifestos is de rigueur for projects that require setting up colossal infrastructure, such as the hunt for the Higgs boson. However, the proposed agenda for H7N9 research is obvious to any experienced infectious disease researcher. Indeed, H7N9 in the Fouchier et al. Letter could be replaced by MERS-coronavirus or any newly discovered virus that poses a perceived threat.

More egregiously, Fouchier et al. try to make the point that gain-of-function (GOF) experiments are now a standard part of a virology research agenda. This astonishing assertion is simply not true. There are some very strong arguments to the contrary; for example, avian influenza GOF experiments cannot prove their point because the deliberate infection of humans is impossible. They can infer and suggest, but no more. Apart from the implausibility of predicting what nature might turn up (4, 5), inferences are of limited value to a health minister. Solid data are what counts. Questions have been raised about the statistical robustness of the findings from the key H5N1 GOF studies given the small numbers of animals used (6).


Even though there are substantial risks involved in GOF research, surprisingly, no independent risk-benefit assessment has been undertaken, which is deeply troubling given the magnitude of the risk—a man-made flu pandemic. Given that scientists still have not reached a consensus regarding GOF research, the benefits cannot be currently quantified. By contrast, the risks are real and can and should be quantified. A compelling argument can be made that GOF work should be frozen until we have a comprehensive risk assessment.


  1. “Engineered viruses are hazardous to humans,” Handelsblatt (8 August 2013); www.handelsblatt.com/technologie/das-technologie-update/healthcare/vogelgrippemanipulierte-viren-sind-gefahr-fuer-menschheit/8611922.html [in German].

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