Pandemic influenza viruses: time to recognize our inability to predict the unpredictable and stop dangerous gain‐of‐function experiments

> There are known knowns. There are things we know we know. We also know there are known unknowns. That is to say we know there are some things we do not know. But there are also unknown unknowns, the ones we don't know we don't know. D.H. Rumsfeld, U.S. Secretary for Defense, February 12, 2002 For almost as long as the civil war in Syria, the scientific community has been locked in a controversy about the utility of gain‐of‐function (GOF) research to increase the transmissibility of highly pathogenic avian influenza H5N1 viruses that resulted in a year‐long moratorium (Nature, 2012a, 2012b, 2013a, 2013b). Now, for the first time since the controversy erupted in November 2011, there is a growing recognition among scientists that GOF virology – experiments with H5N1 and now H7N9 and H7N7 viruses – will not help us predict a pandemic (Morse et al, 2012; Merson et al, 2013), nor will it help us develop more effective vaccines (Butler, 2012; Malakoff, 2013), the two principal arguments for doing the research. Chinese officials have gone one step further by signalling their view that GOF research has no benefit for humanity (Malakoff, 2013; http://www.handelsblatt.com/technologie/das‐technologie‐update/healthcare/vogelgrippe‐manipulierte‐viren‐sind‐gefahr‐fuer‐menschheit/8611922.html). There will be no end to the GOF saga until virologists, epidemiologists and public health officials acknowledge our fundamental inability for the moment to predict the unpredictable and until policy makers and funders move to rein in their support for GOF research. To start its business, a virus generally has to replicate well. This process isn't invariably accompanied by pathology, but it often is. For a virus the key factor is transmission because without it the virus goes to extinction very quickly. Transmission studies, which have been the poor cousin in virology, incorporate features such as droplet size, coughing, …