Biodefense in the Age of Synthetic Biology (2018) / Chapter Skim
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Department of Defense, working with other agencies involved in biodefense, asked the National Academies of Sciences, Engineering, and Medicine to develop a framework to guide an assessment of the security concerns related to advances in synthetic biology, to assess the levels of concern warranted for such advances, and to identify options that could help mitigate those concerns. An excerpted version of the study charge highlights the key tasks undertaken (see Chapter 1, Box 1-2 for the more detailed statement of task)
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The nation's experience preparing for naturally occurring diseases provides a strong foundation for developing strategies to prevent and respond to emerging biologically enabled threats, particularly those based on naturally occurring pathogens. But synthetic biology approaches also have the potential to be used in ways that could change the presentation of an attack, for example, by modifying the properties of existing microorganisms, using microorganisms to produce chemicals, or employing novel or unexpected strategies to cause harm.
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synthetic biology capabilities thus contributes to biodefense planning and facilitates consideration of expert opinions about specific synthetic biology–enabled capabilities or combinations of capabilities. SYNTHETIC BIOLOGY EXPANDS WHAT IS POSSIBLE Synthetic biology expands what is possible in creating new weapons.
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Capabilities warranting a lower relative level of concern include re-creating known pathogenic bacteria and creating new pathogens; these capabilities involve major design and implementation challenges. The use of human gene drives warrants a minimal level of concern because it would be impractical to rely on generations of sexual reproduction to spread a harmful trait through a human population.
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some barriers will be overcome. Table S-1 identifies a number of technical developments that may contribute to overcoming such bottlenecks and barriers to increase the feasibility or impact of a potential attack and the level of biodefense concern warranted for a capability.
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engineering to make toxins natural metabolic pathways toxin tolerable to the host organism synthesizing the toxin Pathway not known Pathway elucidation and/or demonstrations of combinatorial approaches Challenges to large-scale Improvements in intracellular and industrial productivity production Manufacturing chemicals or Tolerability of toxins to the Pathway elucidation and/or improvements in circuit design biochemicals by creating novel host organism synthesizing the and/or improvements in host ("chassis") engineering to make metabolic pathways toxin toxins tolerable to the host organism synthesizing the toxin Engineering enzyme activity Increased knowledge of how to modify enzymatic functions to make specific products Limited knowledge of Improvements in directed evolution and/or increased requirements for designing knowledge of how to build pathways from disparate organisms novel pathways Challenges to large-scale Improvements in intracellular and industrial productivity production Making biochemicals via in Limited understanding of Improvements in knowledge related to microbiome situ synthesis microbiome colonization of host, in situ horizontal transfer of genetic elements, and other relationships between microbiome organisms and host processes Modifying the human Limited understanding of Improvements in knowledge related to microbiome microbiome microbiome colonization of host, in situ horizontal transfer of genetic elements, and other relationships between microbiome organisms and host processes
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manage emerging risk better than current agent-based lists and access control approaches. Strategies based on lists, such as the Federal Select Agent Program Select Agents and Toxins list, will be insufficient for managing risks arising from the application of synthetic biology.
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Although current approaches to defense and public health preparedness remain valuable, there are also clear limitations to current approaches such as pathogen list–based screening tools. To comprehensively assess the preparedness and response capabilities of existing military and civilian defense and public health enterprises or to determine how to address gaps lies outside the scope of this study; however, exploration of the following areas is suggested to address some of the challenges posed by synthetic biology: Developing capabilities to detect unusual ways in which a synthetic biology–enabled weapon may (a)
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