Biodefense in the Age of Synthetic Biology.

Description

Biotechnology in the age of synthetic biology expands the landscape of potential defense concerns. The U.S. Department of Defense (DoD) and its partnering agencies should continue to pursue ongoing strategies for chemical and biological defense; these strategies remain relevant in the age of synthetic biology. DoD and its partners also need to have approaches to account for the broader capabilities enabled by synthetic biology, now and into the future. A FRAMEWORK FOR ASSESSING CONCERN CONTRIBUTES TO PLANNING Recommendation The Department of Defense and its interagency partners should use a framework in assessing synthetic biology capabilities and their implications. (a) A framework is a valuable tool for parsing the changing biotechnology landscape. (b) Using a framework facilitates the identification of bottlenecks and barriers, as well as efforts to monitor advances in technology and knowledge that change what is possible. (c) A framework provides a mechanism for incorporating the necessary technical expertise into the assessment. A framework enables the participation of technical experts in synthetic biology and biotechnology along with experts in complementary areas (e.g., intelligence and public health). SYNTHETIC BIOLOGY EXPANDS WHAT IS POSSIBLE Synthetic biology expands what is possible in creating new weapons. It also expands the range of actors who could undertake such efforts and decreases the time required. Based on this study’s analysis of the potential ways in which synthetic biology approaches and tools may be misused to cause harm, the following specific observations were made: (a) Of the potential capabilities assessed, three currently warrant the most concern: (1) re-creating known pathogenic viruses, (2) making existing bacteria more dangerous, and (3) making harmful biochemicals via in situ synthesis. The first two capabilities are of high concern due to usability of the FIGURE S-1 Framework for assessing concern. The framework consists of four factors, along with descriptive elements within each factor. The factors are Usability of the Technology, Usability as a Weapon, Requirements of Actors, and Potential for Mitigation. These factors delineate the information used to assess the level of concern for particular synthetic biology– enabled capabilities. Biodefense in the Age of Synthetic Biology Copyright National Academy of Sciences. All rights reserved. 4 BIODEFENSE IN THE AGE OF SYNTHETIC BIOLOGY technology. The third capability, which involves using microbes to produce harmful biochemicals in humans, is of high concern because its novelty challenges potential mitigation options. (b) With regard to pathogens, synthetic biology is expected to (1) expand the range of what could be produced, including making bacteria and viruses more harmful; (2) decrease the amount of time required to engineer such organisms; and (3) expand the range of actors who could undertake such efforts. The creation and manipulation of pathogens is facilitated by increasingly accessible technologies and starting materials, including DNA sequences in public databases. A wide range of pathogen characteristics could be explored as part of such efforts. (c) With regard to chemicals, biochemicals, and toxins, synthetic biology blurs the line between chemical and biological weapons. High-potency molecules that can be produced through simple genetic pathways are of greatest concern, because they could conceivably be developed with modest resources and organizational footprint. (d) It may be possible to use synthetic biology to modulate human physiology in novel ways. These ways include physiological changes that differ from the typical effects of known pathogens and chemical agents. Synthetic biology expands the landscape by potentially allowing the delivery of biochemicals by a biological agent and by potentially allowing the engineering of the microbiome or immune system. Although unlikely today, these types of manipulations may become more feasible as knowledge of complex systems, such as the immune system and microbiome, grows. (e) Some malicious applications of synthetic biology may not seem plausible now but could become achievable if certain barriers are overcome. These barriers include knowledge barriers, as is the case for building a novel pathogen, or technological barriers, as in engineering complex biosynthetic pathways into bacteria or re-creating known bacterial pathogens. It is important to continue to monitor advances in biotechnology that may lower these barriers. SUMMARY 1 1 INTRODUCTION 9 Understanding Synthetic Biology, 11 Assessing Potential Biodefense Concerns, 12 Mitigating Potential Biodefense Concerns, 12 Study Approach, 13 2 BIOTECHNOLOGY IN THE AGE OF SYNTHETIC BIOLOGY 15 What Is Synthetic Biology, 15 Implications of the Age of Synthetic Biology, 18 Specific Synthetic Biology Technologies and Applications, 21 3 FRAMEWORK FOR ASSESSING CONCERN ABOUT SYNTHETIC BIOLOGY CAPABILITIES 23 Approach to Developing the Framework, 23 Factors for Assessing Concern, 25 Applying the Framework in the Assessment of Concern, 31 4 ASSESSMENT OF CONCERNS RELATED TO PATHOGENS 37 Re-Creating Known Pathogens, 38 Making Existing Pathogens More Dangerous, 44 Creating New Pathogens, 54 Summary, 57 5 ASSESSMENT OF CONCERNS RELATED TO PRODUCTION OF CHEMICALS OR BIOCHEMICALS 59 Manufacturing Chemicals or Biochemicals by Exploiting Natural Metabolic Pathways, 61 Manufacturing Chemicals or Biochemicals by Creating Novel Metabolic Pathways, 64 Biodefense in the Age of Synthetic Biology Copyright National Academy of Sciences. All rights reserved. xii CONTENTS Making Biochemicals via In Situ Synthesis, 65 Summary, 69 6 ASSESSMENT OF CONCERNS RELATED TO BIOWEAPONS THAT ALTER THE HUMAN HOST 71 Modifying the Human Microbiome, 71 Modifying the Human Immune System, 74 Modifying the Human Genome, 77 Summary, 81 7 RELATED DEVELOPMENTS THAT MAY IMPACT THE ABILITY TO EFFECT AN ATTACK USING A SYNTHETIC BIOLOGY–ENABLED WEAPON 85 Barriers to the Use of Bioweapons, 85 Relevant Convergent Technologies, 87 Summary, 92 8 OPTIONS FOR MITIGATING CONCERNS 95 Current Mitigation Approaches and Infrastructure, 95 Mitigation Challenges Posed by Synthetic Biology, 100 Potential Opportunities to Advance Mitigation Capabilities, 104 Summary, 112 9 MOVING FORWARD: CONCLUSIONS AND RECOMMENDATIONS 115 Overarching Recommendation, 116 Concerns Posed by Synthetic Biology–Enabled Capabilities, 116 Future Use of the Framework, 125 Biodefense Implications of the Age of Synthetic Biology, 126 REFERENCES 129 APPENDIXES A Specific Synthetic Biology Concepts, Approaches, and Tools 147 B Selected Prior Analyses Used to Inform the Framework 157 C Questions to Stimulate Consideration of Framework Factors 163 D Committee Biographies 167 E Disclosure of Conflict of Interest 171 F Study Methods 173