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Introduction: Affordable and accurate nucleic acid synthesis is foundational to modern biotechnology, but raises security concerns because it facilitates the construction of pathogens and other potentially dangerous biological agents. Nucleic acid synthesis screening can reduce the risk of providing potentially harmful nucleic acids to those without a legitimate use for them. Governments, industry associations, and biosecurity organizations have offered guidance on synthesis screening for a decade, and are now considering how to translate industry best practices into regulatory frameworks., Methods: A review of existing guidance documents, policy proposals, and other published literature was performed., Results: We distinguish five categories of practical questions for policymakers: challenges associated with customer screening, sequence screening, the interaction between domestic and global regulations, commercial implications of screening, and finally, challenges associated with benchtop nucleic acid synthesis devices. There are a number of recommendations in public literature that target the implementation of robust customer and sequence screening, several of which have been incorporated into the recent United States White House Executive Order on artificial intelligence. There appears to be fewer solutions proposed to address challenges associated with the global screening landscape, or the commercial implications of screening requirements, and limited discussion on securing the benchtop synthesis landscape., Discussion and Conclusion: This paper aims at providing a comprehensive resource for policymakers, outlining a set of questions governments, and other stakeholders, must answer when implementing screening requirements to secure nucleic acid synthesis., (© Sophie Rose et al., 2024; Published by Mary Ann Liebert, Inc.)

Introduction: Nucleic acid synthesis is a powerful tool that has revolutionized the life sciences. However, the misuse of synthetic nucleic acids could pose a serious threat to public health and safety. There is a need for international standards for nucleic acid synthesis screening to help prevent the misuse of this technology., Methods: We outline current barriers to the adoption of screening, which include the cost of developing screening tools and resources, adapting to existing commercial practices, internationalizing screening, and adapting screening to benchtop nucleic acid synthesis devices. To address these challenges, we then introduce the Common Mechanism for DNA Synthesis Screening, which was developed in consultation with a technical consortium of experts in DNA synthesis, synthetic biology, biosecurity, and policy, with the aim of addressing current barriers. The Common Mechanism software uses a variety of methods to identify sequences of concern, identify taxonomic best matches to regulated pathogens, and identify benign genes that can be cleared for synthesis. Finally, we describe outstanding challenges in the development of screening practices., Results: The Common Mechanism is a step toward ensuring the safe and responsible use of synthetic nucleic acids. It provides a baseline capability that overcomes challenges to nucleic acid synthesis screening and provides a solution for broader international adoption of screening practices., Conclusion: The Common Mechanism is a valuable tool for preventing the misuse of synthetic nucleic acids. It is a critical step toward ensuring the safe and responsible use of this powerful technology., (© Nicole E. Wheeler et al., 2024; Published by Mary Ann Liebert, Inc.)

Gene drives have already challenged governance systems. In this case study, we explore the International Genetically Engineered Machine (iGEM) competition's experiences in gene drive-related research and lessons in developing, revising, and implementing a governance system. iGEM's experiences and lessons are distilled into 6 key insights for future gene drive policy development in the United States: (1) gene drives deserve special attention because of their potential for widescale impact and remaining uncertainty about how to evaluate intergenerational and transboundary risks; (2) an adaptive risk management approach is logical for gene drives because of the rapidly changing technical environment; (3) review by individual technical experts is limited and may fail to incorporate other forms of expertise and, therefore, must be complemented with a range of alternative governance methods; (4) current laboratory biosafety and biosecurity review processes may not capture gene drive research or its components in practice even if they are covered theoretically; (5) risk management for research and development must incorporate discussions of values and broader implications of the work; and (6) a regular technology horizon scanning capacity is needed for the early identification of advances that could pose governance system challenges.

Synthetic biology offers exciting possibilities to deal with local and global challenges over the coming decades. As we make greater use of biological engineering, it will be increasingly important to balance potential risks and benefits. The rate, scale, and diffusion of relevant capabilities will make this challenging. There will be a growing need for flexible risk management approaches, which can be rapidly adapted as technology and societal needs change. This study details efforts by the International Genetically Engineered Machine (iGEM) competition in creating and implementing an adaptive risk management approach. It concludes with key lessons and challenges: working with hazardous materials, such as dangerous pathogens, toxins and chemicals; managing risks to plants, animals and the environment; use of samples from people, animals, and the environment; improving the hazards identified; variations in risk perception and tolerance; variation in terminology that complicates interpretation of risk management plans; and connections with broader societal or ethical questions, such as animal use, gender and sexuality, or benefit sharing., Competing Interests: Both authors work for the International Genetically Engineered Machine (iGEM) Foundation., (© 2021 The Authors. Engineering Biology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)