An Epistemological Perspective on the Value of Gain-of-Function Experiments Involving Pathogens with Pandemic Potential

In recent years, scientists have engaged in a vigorous debate re-garding the value of so-called gain-of-function (GOF) experi-ments involving highly pathogenic avian influenza virus (HPAIV) and other pathogens with pandemic potential (PPP). Of particu-lar concern have been experiments whereby something is done to PPP, such as HPAIV, and the pathogen acquires a new property, or GOF, that makes the microbe more dangerous, such as mam-malian transmissibility, increased virulence, and/or the ability to defeat immunity and antimicrobial drugs. The debate has in-cluded arguments focused on biosecurity, biosafety, and ethics (1–5). Proponents ofGOF experiments emphasized the utilitarian aspects of the work such as potential uses in vaccine development and strain surveillance, while opponents focused on risk (1). However, the debate has largely ignored the question of the epis-temological value of such experiments, which is central to any scientific discussion of the merits of such work. Here we conside