Abstract
BACKGROUND: Governance of high-risk biological research, specifically dual-use research of concern (DURC) and pathogens with enhanced pandemic potential (PEPP), is a topic of renewed interest. This study considers the historical evolution of biosecurity policies, highlighting current challenges in balancing scientific progress with national security and public safety. METHODS: A historical analysis and a literature review were conducted, examining significant events and policy developments shaping biosafety and biosecurity in the United States. The study also reviews possible frameworks for governing DURC and PEPP, assessing ethical, political, and regulatory perspectives from relevant literature. RESULTS: Findings indicate that biosafety and biosecurity policies have historically been reactionary, responding to specific incidents rather than proactively managing risks. Despite significant policy efforts, gaps in transparency, oversight, and international collaboration persist, raising concerns about the effectiveness of governance structures. However, looking at past frameworks for managing high-risk biotechnological risks may be beneficial in establishing future governance strategies. DISCUSSION: The study suggests the need for a balanced approach that integrates ethical, social, legal, and other considerations to ensure robust oversight of DURC and PEPP. Continuous policy evolution, informed by empirical evidence and interdisciplinary collaboration, is needed for mitigating risks associated with high-stakes biological research. CONCLUSION: Effective governance of DURC and PEPP requires comprehensive, interdisciplinary approaches that incorporate historical lessons, ethical considerations, and adaptive policymaking. Collaboration between policymakers, scientists, biosafety and biosecurity professionals, as well as members of the public, is required to ensure scientific innovation benefits national security and public health while minimizing risks.