Michael J. Imperiale, Arturo Casadevall

In the twenty-first century, biology faces a problem that has previously vexed other disciplines such as physics, namely the prospect that its knowledge domain could be used to generate biological agents with altered properties that enhanced their weapon potential. Biological weapons bring the additional dimension that these could be self-replicating, easy to manufacture and synthesized with commonly available expertise. This resulted in increasing concern about the type of research done and communicated, despite the fact that such research often has direct societal benefits, bringing the dual-use dilemma to biology. The conundrum of dual use research of concern was crystallized by the so-called "gain-of-function" type of experiments in which avian influenza viruses were endowed with new properties in the laboratory such as increased virulence and the capacity for mammalian transmission. After more than a decade of intensive discussion and controversy involving biological experiments with dual-use potential, there is no consensus on the issue except for the need to carry out such experiments in the safest conditions possible. In this essay, we review the topic with the hindsight of several years and suggest that instead of prescribing prohibitions and experimental limitations the focus should be on the importance of scientific questions at hand. We posit that the importance of a scientific question for medical and scientific progress provides a benchmark to determine the acceptable level of risk in biological experimentation.