Ethical Criteria for Self-Identifying Societal Risk Associated with Dangerous Gain-of-Function Research

The 5 May 2025 executive order (EO) "Improving the safety and security of biological research" established a federal funding pause for dangerous gain-of-function (DGoF) research, defined as seeking certain experimental outcomes and deemed capable of resulting in significant societal consequences. These moves place institutional biosafety committees central in the identification and self-reporting of DGoF. The previous federal review for research anticipated to result in enhanced potential pandemic pathogens involved a multidisciplinary board, including a bioethicist. From our experience on those boards and based on the EO’s mandate to assess the significance of the societal consequences that might result from proposed DGoF research, we suggest a layered review process for the assessment of societal consequences to inform implementation of the EO. In the layered review, proposed research, initially identified based on anticipated experimental outcomes, is confirmed as DGoF through an assessment that is informed by ethical frameworks.