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.

Given the problems in calculating the numerator and denominator of a risk-benefit assessment, we urge both sides to approach this complex problem with consideration of the opposite view and with humility. To argue that the risk is overwhelming relative to the perceived benefit is not a tenable position, given the precedent that GOF experiments have arguably already provided useful information and the fact that the actual benefit may not be appreciated at present. Similarly, to argue that the risk is minimal relative to the benefit defies hard evidence of human fallibility and a history of serious laboratory accidents. Perhaps an initial meeting point for GOF proponents and opponents would be to agree that risk-benefit calculations are difficult to perform with the data at hand. That said, we note that in other contexts, risk-benefit calculations are routinely done in everyday science and medicine, even with incomplete data. For example, institutional biosafety and human subjects review committees debate risk routinely and do make decisions despite having to make judgment calls. We assert that actually doing a risk-benefit analysis with available data can lead to discussions and experimental modifications that could minimize risk and enhance benefit. Even though proponents and opponents of influenza virus GOF research place very different values on the parameters of the calculations, both sides are actually already doing risk-benefit analyses and using them to support their respective positions. Despite the disagreements on the value of the numerator and the denominator, risk-benefit analyses are always a good idea. They stimulate discussion, and such discussion can lead to improved experimental design and safety, and generate and prioritize the acquisition of additional knowledge. Therefore, we argue that risk-benefit discussions should not be avoided because the parameters are difficult to quantify.