The Evolution of United States Governance Policies for Research Using Pathogens with Enhanced Pandemic Potential.

Background: Prompted by publications in 2012 involving the enhancement of a highly virulent but poorly transmissible human pathogen to make it more transmissible, the research community and the U.S. government have implemented policies to oversee research involving enhanced pathogens that pose the risk of causing a pandemic. Method: This article reviews the evolution of policies governing high consequence, government-funded research that has been called "gain-of-function-research-of-concern," research with "enhanced potential pandemic pathogens" (ePPPs), and research with "pathogens with enhanced pandemic potential" (PEPPs). It analyzes features that these policies share and points out some of their shortcomings, challenges, and ambiguities. Results: These policies, culminating in the 2024 United States Government Policy for Oversight of Dual-Use Research of Concern and Pathogens with Enhanced Pandemic Potential, all define a set of consequential research activities that trigger the need for additional high-level review, and they all set out principles that must be satisfied before the research can be funded. Conclusion: The 2024 policy, like its predecessors, only applies to government-funded research. Extending it to cover privately funded research would require either new regulations under existing statutory authority or new legislation. Like its predecessors, the 2024 policy requires that the benefits of PEPP research justify its potential pandemic risk. Unlike its predecessors, however, the 2024 policy is missing an important principle that prevents construction of a pandemic pathogen that-were it not for its creation in the proposed research-would have little likelihood of ever causing an actual pandemic.