This chapter makes the case against performing exceptionally dangerous gain-of-function experiments that are designed to create potentially pandemic and novel strains of influenza, for example, by enhancing the airborne transmissibility in mammals of highly virulent avian influenza strains. This is a question of intense debate over the last 5 years, though the history of such experiments goes back at least to the synthesis of viable influenza A H1N1 (1918) based on material preserved from the 1918 pandemic. This chapter makes the case that experiments to create potential pandemic pathogens (PPPs) are nearly unique in that they present biosafety risks that extend well beyond the experimenter or laboratory performing them; an accidental release could, as the name suggests, lead to global spread of a virulent virus, a biosafety incident on a scale never before seen. In such cases, biosafety considerations should be uppermost in the consideration of alternative approaches to experimental objectives and design, rather than being settled after the fact, as is appropriately done for most research involving pathogens. The extensive recent discussion of the magnitude of risks from such experiments is briefly reviewed. The chapter argues that, while there are indisputably certain questions that can be answered only by gain-of-function experiments in highly pathogenic strains, these questions are narrow and unlikely to meaningfully advance public health goals such as vaccine production and pandemic prediction. Alternative approaches to experimental influenza virology and characterization of existing strains are in general completely safe, higher throughput, more generalizable, and less costly than creation of PPP in the laboratory and can thereby better inform public health. Indeed, virtually every finding of recent PPP experiments that has been cited for its public health value was predated by similar findings using safe methodologies. The chapter concludes that the unique scientific and public health value of PPP experiments is inadequate to justify the unique risks they entail and that researchers would be well-advised to turn their talents to other methodologies that will be safe and more rewarding scientifically.
Keywords: Evolution; Ferret; Gain-of-function; Influenza; Passage; Potential pandemic pathogen; Selection; Transmissibility; Virulence.