Heritable human genome editing — making changes to the genetic material of eggs, sperm, or any cells that lead to their development, including the cells of early embryos, and establishing a pregnancy — raises not only scientific and medical considerations but also a host of ethical, moral, and societal issues. Human embryos whose genomes have been edited should not be used to create a pregnancy until it is established that precise genomic changes can be made reliably and without introducing undesired changes — criteria that have not yet been met, says Heritable Human Genome Editing. From an international commission of the U.S. National Academy of Medicine, U.S. National Academy of Sciences, and the U.K.'s Royal Society, the report considers potential benefits, harms, and uncertainties associated with genome editing technologies and defines a translational pathway from rigorous preclinical research to initial clinical uses, should a country decide to permit such uses. The report specifies stringent preclinical and clinical requirements for establishing safety and efficacy, and for undertaking long-term monitoring of outcomes. Extensive national and international dialogue is needed before any country decides whether to permit clinical use of this technology, according to the report, which identifies essential elements of national and international scientific governance and oversight.

Contents

• INTERNATIONAL COMMISSION ON THE CLINICAL USE OF HUMAN GERMLINE GENOME EDITING
• INTERNATIONAL OVERSIGHT BOARD
• Special Acknowledgments
• Foreword
• Summary
  • CURRENT STATE OF SCIENTIFIC UNDERSTANDING
  • IMPORTANCE OF SOCIETAL DECISION MAKING ABOUT HERITABLE HUMAN GENOME EDITING
  • CATEGORIZING POTENTIAL USES OF HERITABLE HUMAN GENOME EDITING
  • A TRANSLATIONAL PATHWAY FOR HERITABLE HUMAN GENOME EDITING
  • SCIENTIFIC VALIDATION AND STANDARDS FOR ANY PROPOSED USE OF HERITABLE HUMAN GENOME EDITING
  • FUTURE DEVELOPMENTS AFFECTING REPRODUCTIVE OPTIONS
  • ESSENTIAL ELEMENTS OF OVERSIGHT SYSTEMS FOR HERITABLE HUMAN GENOME EDITING
• 1. Introduction
  • INTERNATIONAL DISCUSSIONS OF HERITABLE HUMAN GENOME EDITING
  • CLINICAL USE OF HERITABLE HUMAN GENOME EDITING REPORTED
  • FORMATION OF THE INTERNATIONAL COMMISSION AND WORLD HEALTH ORGANIZATION EXPERT COMMITTEE
  • MITOCHONDRIAL REPLACEMENT TECHNIQUES: MODIFYING THE EMBRYO
  • A TRANSLATIONAL PATHWAY FOR HERITABLE HUMAN GENOME EDITING
  • STUDY FOCUS AND APPROACH
  • ORGANIZATION OF THE REPORT
• 2. The State of the Science
  • MONOGENIC DISEASES: GENETICS AND REPRODUCTIVE OPTIONS
  • GENOME EDITING: SCIENTIFIC BACKGROUND FOR A TRANSLATIONAL PATHWAY
  • FUTURE ISSUES IN ASSISTED REPRODUCTION: IMPLICATIONS OF IN VITRO STEM CELL–MEDIATED GAMETOGENESIS
  • ADDITIONAL COMPONENTS OF ANY CLINICAL TRANSLATIONAL PATHWAY FOR HERITABLE HUMAN GENOME EDITING
  • OTHER POSSIBLE USES OF HERITABLE HUMAN GENOME EDITING
  • CONCLUSIONS AND RECOMMENDATIONS
• 3. Potential Applications of Heritable Human Genome Editing
  • DEFINING APPROPRIATE USES OF HERITABLE HUMAN GENOME EDITING
  • CRITERIA FOR DEFINING RESPONSIBLE TRANSLATIONAL PATHWAYS FOR INITIAL USES OF HERITABLE HUMAN GENOME EDITING
  • CRITERIA FOR POSSIBLE INITIAL USES OF HERITABLE HUMAN GENOME EDITING
  • CATEGORIES OF USES OF HERITABLE HUMAN GENOME EDITING
  • CIRCUMSTANCES FOR WHICH A RESPONSIBLE TRANSLATIONAL PATHWAY COULD BE DEFINED
  • HOW COMMON ARE THE CIRCUMSTANCES FOR THE INITIAL CLINICAL USES OF HERITABLE HUMAN GENOME EDITING?
  • THE NEED FOR CONTINUED RESEARCH
  • CONCLUSIONS AND RECOMMENDATIONS
• 4. A Translational Pathway to Limited and Controlled Clinical Applications of Heritable Human Genome Editing
  • CONTEXT FOR ANY HERITABLE HUMAN GENOME EDITING TRANSLATIONAL PATHWAY
  • BASIC RESEARCH FOUNDATION TO ESTABLISH SAFE AND EFFECTIVE GENOME EDITING METHODOLOGIES
  • PRECLINICAL EVIDENCE TO SUPPORT A PROPOSED USE
  • DECISION POINTS AND REQUIRED APPROVALS
  • CLINICAL EVALUATION OF THE PROPOSED USE
  • HERITABLE HUMAN GENOME EDITING USING IN VITRO STEM CELL–DERIVED GAMETES: WHAT A POTENTIAL TRANSLATIONAL PATHWAY WOULD ENTAIL
  • CONCLUSION AND RECOMMENDATIONS
• 5. National and International Governance of Heritable Human Genome Editing
  • A RESPONSIBLE GOVERNANCE SYSTEM FOR HERITABLE HUMAN GENOME EDITING
  • HERITABLE EDITING IN THE CONTEXT OF CURRENT REGULATORY SYSTEMS
  • REQUIREMENTS FOR NATIONAL OVERSIGHT SYSTEMS FOR HERITABLE HUMAN GENOME EDITING
  • THE NEED FOR A SYSTEM OF GLOBAL COORDINATION AND COLLABORATION
  • CONCLUSION AND RECOMMENDATIONS
• References
• A. Information Sources and Methods
• B. Commissioner Biographies
• C. Glossary
• D. Acronyms and Abbreviations
• Acknowledgment of Reviewers
• NATIONAL ACADEMY OF MEDICINE

Suggested citation:

National Academy of Medicine, National Academy of Sciences, and the Royal Society. 2020. Heritable Human Genome Editing. Washington, DC: The National Academies Press. https://doi.org/10.17226/25665.

Digital Object Identifier: https://doi.org/10.17226/25665

Library of Congress Control Number: 2020949045

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