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.

What is the case-fatality ratio of HPAIV in humans? The mortality associated with H5N1 virus is a key driver of the GOF risk-benefit debate. Although there seems to be no debate that the case-fatality ratio of individuals who come to medical attention with H5N1 is high, the ratio of asymptomatic to symptomatic infections has been the subject of debate in the literature (17, 18) . This is a key parameter for which additional information could become available with additional studies. If the case-mortality ratio is indeed as high as 50%, then the risk is greater, while a much lower ratio would portend a significantly reduced risk. It is worthwhile for experts on serological studies and influenza epidemiology to come to agreement on the type of information needed and then carry out the studies to address this important issue. Such studies should be prioritized. Irrespective of where one stands in the case-fatality debate, it is worthwhile to note that even a casefatality ratio as low as Ͻ0.1%, such as that associated with the 2009 pandemic, would cause immeasurable suffering to affected individuals and could create significant societal havoc.