Excerpt

In 2006, the National Science Advisory Board for Biodefense (NSABB) issued Addressing Biosecurity Concerns Related to the Synthesis of Select Agents, which called for expert evaluation to determine whether an alternative framework based on predicted features and properties encoded by nucleic acids, such as virulence or pathogenicity, can be developed and used in lieu of the current finite list of specific agents and taxonomic definitions. Our committee was tasked with identifying “the scientific advances that would be necessary to permit serious consideration of developing and implementing an oversight system for Select Agents that is based on predicted features and properties encoded by nucleic acids rather than a relatively static list of specific agents and taxonomic definitions.”

Contents

• The National Academies
• Committee on Scientific Milestones for the Development of a Gene Sequence-Based Classification System for the Oversight of Select Agents
• Board on Life Sciences
• Preface
• Acknowledgments
• Summary
• 1. The Select Agent Regulations
  • CHARGE TO THE COMMITTEE
  • ORGANIZATION OF THE REPORT
  • CONTEXT OF THE SELECT AGENT REGULATIONS
  • CURRENT STATUS OF THE SELECT AGENT PROGRAM
  • CRITERIA FOR SELECT AGENT DESIGNATION
• 2. Challenges of Predicting Pathogenicity from Sequence
  • INTRODUCTION
  • THE ART OF SEQUENCE-BASED PREDICTION
  • THE NATURE OF INFECTIOUS DISEASE AND THE ART OF PREDICTING PATHOGENICITY
  • THE SPECIAL CASE OF SYNTHETIC BIOLOGY
  • WHAT CAN CURRENTLY BE PREDICTED FROM SEQUENCE ABOUT THE IDENTIFICATION OF PATHOGENIC MICROORGANISMS, INCLUDING SELECT AGENTS?
• 3. A Proposal for Consideration: Sequence-Based Classification of Select Agents
  • NOVEL AGENTS: SYNTHETIC GENOMICS AND THE SELECT AGENT REGULATIONS
  • CLASSIFICATION IS DISTINCT FROM PREDICTION
  • SYNTHETIC GENOME CLASSIFICATION UNDER THE CURRENT SELECT AGENT REGULATIONS
  • CLASSIFICATION DEPENDS ON BOTH GENE CONTENT AND GENETIC DISTANCE
  • USING “PARTS LISTS” TO DEFINE GENE CONTENT
  • SEQUENCE ANALYSIS OF INDIVIDUAL “PARTS”
  • METHODS FOR SEQUENCE SUBFAMILY CLASSIFICATION
  • OUTLINE OF A POSSIBLE SYSTEM FOR PROFILE-BASED CLASSIFICATION OF SELECT AGENTS
  • CONSIDERATIONS FOR IMPLEMENTATION OF A PROFILE-BASED CLASSIFICATION SYSTEM
  • ROLE OF PREDICTION AND CLASSIFICATION IN BIOSAFETY
  • RAISING A YELLOW FLAG FOR “SEQUENCES OF CONCERN”
  • SHOULD SUCH A SYSTEM BE BUILT?
• 4. Committee Findings and Conclusions
  • FINDINGS AND CONCLUSIONS
  • The Yellow Flag System
  • NEAR-TERM MILESTONES FOR SEQUENCE-BASED CLASSIFICATION
  • LONG-TERM MILESTONES FOR GENOME SEQUENCE-BASED SELECT AGENT REGULATIONS
  • CONCLUSION
• References
• Appendixes
  • Appendix A Statement of Task
  • Appendix B Committee Member and Staff Biographies
  • Appendix C HHS and USDA Select Agents and Toxins
  • Appendix D 2009 Workshop Agenda
  • Appendix E Applicability of the Select Agent Regulations to Issues of Synthetic Genomics
  • Appendix F Summary of Relevant Legislation, Regulation, and Guidance
  • Appendix G Influenza A and SARS-CoV
  • Appendix H Virus-Host Interactions
  • Appendix I Botulinum Neurotoxin, B. Anthracis and Variola Virus
  • Appendix J Pathogenicity Acquisition
  • Appendix K Interactions of Infectious Agents with the Host
  • Appendix L Near-Term Milestones for Consideration
  • Appendix M Executive Order: Optimizing the Security of Biological Select Agents and Toxins in the United States

This study was supported by Contract No. NO1-OD-4-2139 (Task Order #216) between the National Academy of Sciences and the National Institutes of Health.

The content of this publication does not necessarily reflect the views or policies of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.