Reply to "Can limited scientific value of potential pandemic pathogen experiments justify the risks?".

Abstract

We thank Dr. Lipsitch for his comments (1). Dr. Lipsitch does not argue with the notion that gain-of-function experiments are epistemologically valuable, but he does feel that their practical value is limited. Likewise, we would not argue that reasonable people cannot come to different conclusions about the relative epistemic value of any given experiment. He makes several points to which we will respond. The first point is that the epistemic yield of influenza virus GOF experiments in ferrets is limited. Dr. Lipsitch questions the value of the experiments establishing H5N1 transmissibility in ferrets (2, 3) on the basis of underpowered experiments and the possibility that the information is limited to ferrets. That may be true for quantitative data, although arguments have been made to the contrary (4), but the experiments on H5N1 transmissibility unequivocally established that H5N1 had the biological potential to become mammalian transmissible, and that observation was a qualitative, all-or-nothing, result for which there is no need for statistical analysis: it happened. The fact that it happened is the epistemic gain, and the definitive nature of the result makes it of high epistemic value. Prior to these experiments, the question of whether highly pathogenic avian influenza viruses (HPAIV) had the biological potential for mammalian transmissibility was in doubt. Since the completion of these experiments, we know with great confidence that H5N1 can …