Gene Drives on the Horizon

Advancing Science, Navigating Uncertainty,
and Aligning Research with Public Values

Committee on Gene Drive Research in Non-Human Organisms:
Recommendations for Responsible Conduct

Board on Life Sciences

Division on Earth and Life Studies

THE NATIONAL ACADEMIES PRESS

Washington, DC

www.nap.edu

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by Contract No. 040815 with the Foundation for the National Institutes of Health, Contract No. 10002551/10002584 with the US Department of Health and Human Services/National Institutes of Health. The activities received additional support from the National Academy of Sciences Biology and Biotechnology Fund. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.

International Standard Book Number-13: 978-0-309-43787-5
International Standard Book Number-10: 0-309-43787-3
Library of Congress Control Number: 2016946673
Digital Object Identifier: 10.17226/23405

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values. Washington, DC: The National Academies Press. doi: 10.17226/23405.

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COMMITTEE ON GENE DRIVE RESEARCH IN NON-HUMAN ORGANISMS: RECOMMENDATIONS FOR RESPONSIBLE CONDUCT

Co-Chairs

JAMES P. COLLINS, Arizona State University

ELIZABETH HEITMAN, Vanderbilt University Medical Center

Members

NICOLE L. ACHEE, University of Notre Dame

VICKI CHANDLER, NAS,¹ Minerva Schools at Keck Graduate Institute

JASON A. DELBORNE, North Carolina State University

BRANDON S. GAUT, University of California, Irvine

STEPHEN HIGGS, Kansas State University

GREGORY E. KAEBNICK, The Hastings Center

ANN KINGIRI, African Centre for Technology Studies

WAYNE LANDIS, Western Washington University

LYNN RIDDIFORD, NAS,¹ Howard Hughes Medical Institute

JOYCE TAIT, University of Edinburgh

LISA A. TANEYHILL, University of Maryland

JOSEPH TRAVIS, Florida State University

PAUL E. TURNER, Yale University

DAVID E. WINICKOFF, University of California, Berkeley; Organisation for Economic Co-operation and Development, Paris

Project Staff

KEEGAN SAWYER, Project Director

AUDREY THÉVENON, Associate Program Officer

ROBIN MILLER, Christine Mirzayan Science and Technology Policy Graduate Fellow

FRANCES SHARPLES, Director, Board on Life Sciences

ANGELA KOLESNIKOVA, Administrative Assistant

ANNE FRANCES JOHNSON, Editor

___________________

¹National Academy of Sciences.

BOARD ON LIFE SCIENCES

Chair

JAMES P. COLLINS, Arizona State University

Members

ENRIQUETA C. BOND, Burroughs Wellcome Fund

ROGER D. CONE, Vanderbilt University

NANCY D. CONNELL, Rutgers, New Jersey Medical School

JOSEPH R. ECKER, Salk Institute for Biological Studies

SARAH C.R. ELGIN, Washington University, St. Louis

LINDA G. GRIFFITH, Massachusetts Institute of Technology

ELIZABETH HEITMAN, Vanderbilt University Medical Center

RICHARD A. JOHNSON, Global Helix LLC

JUDITH KIMBLE, University of Wisconsin, Madison

MARY E. MAXON, Lawrence Berkeley National Laboratory

JILL P. MESIROV, University of California, San Diego

KAREN E. NELSON, J. Craig Venter Institute

CLAIRE POMEROY, Albert and Mary Lasker Foundation

MARY E. POWER, University of California, Berkeley

MARGARET RILEY, University of Massachusetts, Amherst

LANA SKIRBOLL, Sanofi

JANIS WEEKS, University of Oregon

Staff

FRANCES SHARPLES, Director

KATIE BOWMAN, Senior Program Officer

JO HUSBANDS, Senior Scholar

JAY LABOV, Senior Scholar

KEEGAN SAWYER, Program Officer

MARILEE SHELTON-DAVENPORT, Senior Program Officer

AUDREY THÉVENON, Associate Program Officer

BETHELHEM MEKASHA, Financial Associate

JENNA OGILVIE, Research Associate

ANGELA KOLESNIKOVA, Administrative Assistant

AANIKA SENN, Senior Program Assistant

Preface

Historians of science and engineering illuminate how discoveries related to theory, observation, and technology change our understanding of the natural world and the ways in which we interact with the organisms around us. Occasionally, the pace of discovery in a particular research area is so rapid it is impossible to miss. If the current pace of change in general genetics is thrilling, the pace of change in gene drive research is breathtaking. Not surprisingly, the depth, breadth, and practical implications of scientific advances in gene drive research are simultaneously raising many challenges at the interface of science and society.

The National Institutes of Health and the Foundation for the National Institutes of Health asked the Board on Life Sciences of the National Academies of Sciences, Engineering, and Medicine to convene a consensus committee to summarize current understanding of the scientific discoveries related to gene drives and their accompanying ethical, legal, and social implications.

This report reflects the committee’s consensus conclusions regarding the state of the science and expectations for responsible research. The committee’s analyses are based on reviews of the multidisciplinary literature, interviews of experts, and presentations from natural and social scientists working at the leading edges of research on gene drives and related technologies. Appropriate for such a task, the committee’s 16 members have diverse interdisciplinary expertise and a range of backgrounds across the natural and social sciences, ethics, and the law. The committee often had to re-examine fundamental aspects of genetics, population biology, probability, public policy, and the law in order to understand the full scope of gene drive research and its effects. To ensure that the audience has a common understanding of the scientific, social, and regulatory knowledge essential to responsible research with gene drives, the report also outlines some of these fundamentals before moving to the complex picture we ultimately describe.

This report would not have been possible without the exceptional contributions of the Academies staff members: Keegan Sawyer, Audrey Thévenon, Robin Miller, Nancy Huddleston, and Frances Sharples. Angela Kolesnikova provided the committee with outstanding logistical support. We acknowledge gratefully all of their efforts.

A special thanks goes out to our colleagues on the committee for their thoughtful review and analysis of an enormous amount of information some of which changed on a daily or weekly basis as new discoveries were made. It was an honor to work with all of them.

James P. Collins, Co-Chair

Elizabeth Heitman, Co-Chair

Committee on Gene Drive Research in Non-Human Organisms: Recommendations for Responsible Conduct

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Acknowledgment of Reviewers

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this report:

Austin Burt, Imperial College

R. Alta Charo, University of Wisconsin-Madison

Roger D. Cone, Vanderbilt University

Rebecca A. Efroymson, Oak Ridge National Laboratory

Fred Gould, North Carolina State University

Anthony A. James, University of California, Irvine

Calestous Juma, Harvard University

James Lavery, St. Michael’s Hospital and University of Toronto

Morven A. McLean, International Life Sciences Institute Research Foundation

Stephen S. Morse, Columbia University

Robert D. Newman, US Centers for Disease Control and Prevention

Sarah P. Otto, University of British Columbia

Kenneth Oye, Massachusetts Institute of Technology

Ronald Sandler, Northeastern University

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the report’s conclusions or recommendations, nor did they see the final draft of the report before the release. The review of this report was overseen by Stephen Barthold, University of California, Davis, and Barbara Hansen, University of South Florida. They were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

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Contents

SUMMARY

1 INTRODUCTION

Purpose of the Study

What Are Gene Drives? And, How Could They Be Used?

Case Studies

Key Definitions and Concepts

Conclusions

References

2 THE STATE OF KNOWLEDGE OF THE MOLECULAR BIOLOGY, POPULATION GENETICS, AND ECOLOGY OF GENE-DRIVE MODIFIED ORGANISMS

Selfish Genetic Elements and Their Drive Mechanisms

CRISPR/Cas9-Based Gene Drives

Population Ecology and Ecosystem Considerations

Conclusions

References

3 CASE STUDIES TO EXAMINE QUESTIONS ABOUT GENE-DRIVE MODIFIED ORGANISMS

Basic Criteria for the Development of Gene-Drive Modified Organisms

Case Study 1: Using Aedes Aegypti and Aedes Albopictus Mosquitoes to Manage Dengue

Case Study 2: Using Anopheles Gambiae Mosquitoes to Combat Human Malaria

Case Study 3: Using Culex Quinquefasciatus Mosquitoes to Combat Avian Malaria in Hawaii

Case Study 4: Controlling Populations of Non-Indigenous Mus Musculus Mice to Protect Biodiversity on Islands

Case Study 5: Controlling Non-Indigenous Centaurea Maculosa Knapweeds to Protect Biodiversity in Rangelands and Forests

Case Study 6: Controlling Palmer Amaranth to Increase Agriculture Productivity

Case Study 7: Developing a Vertebrate Model for Gene Drive Research Using Zebrafish

References

4 CHARTING HUMAN VALUES

Central Value Considerations in Debates About Genetic Engineering

Potential Human Benefits of Gene Drives

Potential Human Harms of Gene Drives

Values Relevant to Potential Environmental Effects

Concerns About Justice

Conclusions

References

5 PHASED TESTING AND SCIENTIFIC APPROACHES TO REDUCING POTENTIAL HARMS OF GENE DRIVES

The Phased Testing Pathway

Containment, Confinement, and Mitigation Strategies

Learning from Field Research and Biocontrol Efforts with Other Types of Modified Organisms

Conclusions and Recommendations

References

6 ASSESSING RISKS OF GENE-DRIVE MODIFIED ORGANISMS

What Is Risk?

Assessing Environmental Impacts Versus Assessing Risks

Key Considerations for Ecological Risk Assessments of Gene-Drive Modified Organisms

A Conceptual Cause-Effect Model

Illustrating a Conceptual Cause-Effect Model Using Two Case Studies

Conclusions and Recommendations

References

7 ENGAGING COMMUNITIES, STAKEHOLDERS, AND PUBLICS

Communities, Stakeholders, and Publics

Motivations for Engagement

Challenges of Engagement

Frameworks to Guide Engagement

Conclusions and Recommendations

References

8 GOVERNING GENE DRIVE RESEARCH AND APPLICATIONS

What Is Governance?

Key Considerations for Governing Gene Drives

Relevant Governance Frameworks for Gene Drive Research and Applications in the United States

Biosecurity Considerations

Governance of Gene Drives in Global Contexts

Conclusions and Recommendations

References

9 GENE DRIVES ON THE HORIZON: OVERARCHING CONSIDERATIONS

GLOSSARY

ACRONYMS

APPENDIXES

A AGENDA FOR THE WORKSHOP ON THE SCIENCE, ETHICS, AND GOVERNANCE CONSIDERATIONS FOR GENE DRIVE RESEARCH

B LIST OF GENE DRIVE WEBINARS

C MOSQUITO CONTROL STRATEGIES

D RODENT CONTROL STRATEGIES

E A BRIEF HISTORY OF ECOLOGICAL RISK ASSESSMENT

F BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS