Risks and Benefits of Gain-of-Function Experiments with Pathogens of Pandemic Potential, Such as Influenza Virus: a Call for a Science-Based Discussion

Casadevall, Arturo; Imperiale, Michael J.

As a result of these experiments humanity has much more knowledge and stands warned of the potential perils these viruses pose. This information emerged from GOF experiments. In fact, it is difficult to imagine another mechanism for obtaining the information that has been gained from GOF-type experiments, particularly because it is only through experiments that can control the expression of given determinants that proof can be obtained. Since proof of the germ theory, modern scientific proof generally requires the use of approaches that attribute a given property to a given determinant. Hence, GOF-type experiments are of particular epistemological value because they directly imply causality. Apart from informing on the potential for virulence and transmissibility, GOF experiments are powerful tools for dissecting questions concerning viral pathogenesis. For example, H5N1 mutational analysis showed that the efficiency of viral replication in avian and mammalian cells is dependent on hemagglutinin polymorphisms that facilitate activation at lower pH (7, 8) . This finding could be exploited to increase the yield of virus during preparation of vaccine stocks. Furthermore, the identification of sequence changes associated with GOF could in theory lead to the identification of new antiviral targets, thus providing a potential societal benefit. The power of GOF experiments is that they are a highly efficient, reliable, and effective tool that can identify certain phenotypes that often cannot be identified by using other scientific approaches. Hence, we feel that there is ample evidence that GOF experiments can provide important information and are useful tools for investigation of influenza virus-related questions. In fact, we believe that the crux of the debate surrounding GOF experiments is not their value but their potential risk.