Genome Editing and Biological Weapons: Assessing the Risk of Misuse

Description

This monograph introduces current genome editing technologies―clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) systems, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs)―and provides an assessment of the risk of misuse of these technologies based on the following parameters: accessibility, ease of misuse, magnitude of potential harm, and imminence of potential misuse. The findings from this assessment are applied to analyze and evaluate the threat posed by the intentional misuse of genome editing technologies to develop biological weapons.  Furthermore, the book discusses the implications of misuse for different applications of genome editing, such as making existing pathogens more dangerous, modifying the human microbiome, weaponizing gene drives, engineering super soldiers, and augmenting the general population to confer economic advantages.    Technologies that enable genome editing with programmable nucleases―including CRISPR, TALEN, and ZFN―allow for the precise genetic modification of organisms and cultured cells. While these technologies are used for a variety of beneficial applications, intelligence and defense experts have raised concerns that genome editing technologies, especially CRISPR, could be misused to develop new and improved biological weapons. Furthermore, experts worry that the number and type of actors who could potentially misuse genome editing is dramatically increasing given the democratization of biology, which is allowing biology to become more accessible to everyone including nonexperts.   The book provides a comprehensive assessment of how feasible it is for users with different levels of knowledge and skill to acquire and then to apply the technologies to develop a biological weapon. It also provides an assessment of governability and a tailored set of recommendations that address security concerns. These recommendations are sensitive to the cost-benefit trade-off of regulating genome editing technologies. The book targets researchers as well as intelligence analysts, defense and security personnel, and policymakers.   Foreword Acknowledgements About the Book Contents List of Abbreviations and Symbols List of Figures List of Tables Chapter 1: Introduction: Rapid Technological Advancements Amid Rising Concerns of Misuse 1.1 Calibrating the Threat 1.2 Warnings of Misuse 1.3 Approach 1.4 Key Issues 1.5 Organization References Chapter 2: Background: Genome Editing with Programmable Nucleases 2.1 Genes, Genetic Engineering, and Genome Editing 2.2 ZFN 2.2.1 Zinc-Finger 2.2.2 Structure and Mechanism 2.3 TALEN 2.3.1 TALE 2.3.2 Structure and Mechanism 2.4 CRISPR 2.4.1 CRISPR-Cas System 2.4.2 Structure and Mechanism 2.4.3 CRISPR Workflow 2.5 Comparison of Technologies 2.5.1 ZFN, TALEN, and CRISPR 2.5.2 Other Technologies 2.6 Conclusion References Chapter 3: Applying Genetic Engineering to Biological Weapons 3.1 Threat of Genetic Engineering 3.1.1 Framing Assessments 3.1.2 Types of Agents 3.1.2.1 Non-genetically Engineered 3.1.2.2 Genetically Engineered 3.1.3 Attributes Targeted for Modification 3.1.3.1 Increased Virulence 3.1.3.2 Resistance to Drugs and Preventatives 3.1.3.3 Protection of Own Forces 3.1.3.4 Ability to Evade Host Immunological Response 3.1.3.5 Ability to Avoid Detection and Diagnostics 3.1.3.6 Enhanced Environmental Resistance 3.1.3.7 Enhanced Production, Storage, and Dissemination 3.1.3.8 Increased Vector Efficiency 3.1.3.9 Ability to Control Agents 3.1.3.10 Ability to Alter Host Tropism 3.1.4 Obstacles to Modification 3.1.4.1 Technical 3.1.4.2 Social Knowledge and Skill Foreign Technical Assistance 3.1.4.3 Organization and Management 3.2 Misuse of Genome Editing Technologies 3.2.1 Monitoring for Dual-Use Technologies 3.2.2 Applications of Misuse 3.3 Conclusion References Chapter 4: Risk of Misuse Assessment: Part I 4.1 Parameter 1: Accessibility 4.1.1 Methodology 4.1.2 Ease of Acquiring Hardware and Software 4.1.2.1 Hardware Addgene 4.1.2.2 Software 4.1.3 Cost 4.1.4 Dependence on Other Technologies 4.1.4.1 Delivery Technologies 4.1.4.2 Validation Technologies 4.2 Parameter 2: Ease of Misuse 4.2.1 Methodology 4.2.2 Skill and Tacit Knowledge Needed to Use Technology 4.2.2.1 Step 1: Choose Target 4.2.2.2 Step 2: Design Components 4.2.2.3 Step 3: Build Components 4.2.2.4 Extra Step: Build Repair Template 4.2.2.5 Step 4: Deliver 4.2.2.6 Step 5: Validate 4.2.3 Ways to Acquire Skill and Knowledge 4.2.3.1 Services Offered by Providers 4.2.3.2 Forums Online JoVE Video Article Protocols In-Person 4.2.4 Transferability of Skill and Knowledge 4.2.4.1 Videos 4.2.4.2 Classes 4.3 Conclusion References Chapter 5: Risk of Misuse Assessment: Part II 5.1 Parameter 3: Magnitude of Potential Harm 5.1.1 Methodology 5.1.2 Making Pathogens More Dangerous 5.1.3 Weaponizing the Human Microbiome 5.1.4 Weaponizing Gene Drives 5.1.5 Augmenting Humans: Super Soldiers and the General Population 5.1.5.1 Super Soldiers 5.1.5.2 General Population 5.2 Parameter 4: Imminence of Potential Misuse 5.2.1 Methodology 5.2.2 Ability to Be Exploited Based on Maturity 5.2.2.1 Scientific Publications 5.2.2.2 Clinical Studies 5.2.2.3 Patents 5.2.2.4 Companies 5.2.2.5 Global Market Size Projections 5.3 Conclusion References Chapter 6: Raising the Alarm on CRISPR 6.1 Overview of the Risk of Misuse Assessment 6.1.1 Relative Risk of Misuse 6.1.2 Expanding the Pool of Potential Misusers 6.1.3 Overcoming Tacit Knowledge and Skill Barriers 6.1.4 Benefits and Drawbacks of Kits 6.1.5 Constraints on Applying Learning Tools and Experimental Aids 6.1.6 Persistence of Technical Barriers to Biological Weapons 6.1.7 Technology Maturation and Risk of Misuse 6.2 Implications of Misuse for Specific Applications of Genome Editing 6.2.1 Making Pathogens More Dangerous 6.2.2 Weaponizing the Human Microbiome 6.2.3 Weaponizing Gene Drives 6.2.4 Augmenting Humans 6.3 Conclusion References Chapter 7: Conclusion: Reducing the Perils from the Misuse of Genome Editing 7.1 Assessment of Governability 7.2 Strategies to Address Security Concerns 7.2.1 Norms Against Misuse 7.2.2 Responsible Research Culture 7.2.3 Product Screening and Sales Training 7.2.4 Financial Loophole Closure 7.2.5 Bioengineered Attack Indicators 7.2.6 Diagnostics, Vaccines, and Other Medical Countermeasures 7.3 The Future of Biodefense and Biosecurity References Appendix A: Providers of Genome Editing Technologies Appendix B: Computational Design Tools Appendix C: JoVE Video Articles Appendix D: Forums to Acquire Skill and Knowledge Appendix E: Company Startups