Supporting Responsible
Innovation of Synthetic Cells

Biosafety, Biosecurity, and Environmental
Considerations

_______

Committee on the External Review of Environmental, Biosafety, and Biosecurity Considerations for Synthetic Cell Research and Development

Life Sciences and Biotechnology Program Area

Social and Economic Systems Program Area

Center for Health, People, and Places

Consensus Study Report

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This study was supported by a contract between the National Academy of Sciences and National Science Foundation (49100424C0045). 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: 978-0-309-60204-4
Digital Object Identifier: https://doi.org/10.17226/29325
Library of Congress Control Number: 2026941965

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A colored scanning electron micrograph (SEM) of Mycoplasma mycoides JCVI-syn1.0 cells, developed by scientists at the J. Craig Venter Institute. These were the first bacterial cells controlled by a chemically synthesized genome and capable of self-replication. See: Gibson et al. (2010), https://doi.org/10.1126/science.1190719. Image credit: https://www.sciencephoto.com/contributor/tde THOMAS DEERINCK, NCMIR / SCIENCE PHOTO LIBRARY.

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2026. Supporting Responsible Innovation of Synthetic Cells: Biosafety, Biosecurity, and Environmental Considerations. Washington, DC: National Academies Press. https://doi.org/10.17226/29325.

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COMMITTEE ON THE EXTERNAL REVIEW OF ENVIRONMENTAL, BIOSAFETY, AND BIOSECURITY CONSIDERATIONS FOR SYNTHETIC CELL RESEARCH AND DEVELOPMENT

PETER A. CARR (Co-Chair), RTX BBN Technologies (Co-Chair from May 2025)

FELICIA WU (Co-Chair), Michigan State University

KATE ADAMALA, University of Minnesota (joined committee May 2025)

MARIA CHAVEZ, BioCurious

CHRISTOPHER L. CUMMINGS, U.S. Army Engineer Research and Development Center

JASON DELBORNE, University of Wisconsin-Madison

DAVID A. DUNNING, University of Michigan

EMMA FROW, Arizona State University

DAVID GILLUM, University of Nevado, Reno (joined committee May 2025)

INDIA HOOK-BARNARD, Engineering Biology Research Consortium

CAMERON KIM, Duke University

RICHARD M. MURRAY, California Institute of Technology (Co-Chair until May 2025)

RONI REITER-PALMON, University of Nebraska at Omaha

ROBIN SCHEFFLER, Massachusetts Institute of Technology

ZARA SUMMERS, LanzaTech

R. ALTA CHARO, University of Wisconsin (resigned from committee April 2025)

RAYVON FOUCHÉ, Northwestern University (resigned from committee April 2025)

MELINDA KLIEGMAN, Independent Consultant (resigned from committee April 2025)

Study Staff

TRISHA TUCHOLSKI, Co-Study Director, Program Officer (from March 2025)

EMILY VARGAS, Co-Study Director, Program Officer (until October 2025)

ANDREW BREMER, Co-Study Director, Program Officer (until March 2025)

KATHRYN ASALONE, Associate Program Officer (until May 2025)

JESSICA DE MOUY, Research Associate

LAYLA GARYK, Senior Program Assistant (until October 2025)

GARIS GRANT, Mirzayan Fellow (until May 2025)

THOMASINA LYLES, Senior Program Assistant (from November 2025)

CHRISTL SAUNDERS, Program Coordinator (until October 2025)

SABINA VADNAIS, Associate Program Officer

KAVITA BERGER, Senior Program Director, Life Sciences and Biotechnology Program Area

DANIEL J. WEISS, Director, Board on Behavioral, Cognitive, and Sensory Sciences

Reviewers

This Consensus Study Report was 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 National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We thank the following individuals for their review of this report:

SHERRY BOHN, ABSA International

DIANE DIEULIIS, Independent Consultant

SAM WEISS EVANS, Federation of American Scientists

KHARA GRIEGER, North Carolina State University

KEITH MATTHEWS, Matthews Law LLC

KATHERINE MCCOMAS, Cornell University

ELIZABETH STRYCHALSKI, National Institute of Standards and Technology

CHRIS WOZNIAK, Wozniak Biopesticides Consulting LLC

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by WYLIE BURKE, University of Washington, and DAVID WALT, Harvard Medical School. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Acknowledgments

The Committee on the External Review of Environmental, Biosafety, and Biosecurity Considerations for Synthetic Cell Research and Development and the staff of the National Academies of Sciences, Engineering, and Medicine gratefully acknowledge the National Science Foundation (NSF) for its support and guidance in shaping the scope of this study. The committee particularly thanks Theresa Good, Anthony Garza, Charles Cunningham, Steve Perretti, Wenda Bauchspies, and Montona Futrell-Griggs of NSF for their sustained engagement and guidance throughout the study.

The committee also thanks the speakers who participated in the open sessions of the public information gathering meetings and provided essential expertise in support of the committee’s work (see Appendix C). Specifically, the committee thanks Steve Evans, Chris Wozniak, Leyma P. De Haro, Vaughn Cooper, the National Security Commission on Emerging Biotechnology team (Caitlin Frazer, Sam Weiss Evans, Steven Moss), Mike Imperiale, Gigi Gronvall, Lauren Junker, James Diggans, Megan Palmer, Ernie Glover, Valerie Martindale, Andrea Hodgson, Michael Zaroukian, Dietram Scheufele, and Christina Agapakis for their contributions to discussions on environmental, safety, and security considerations in engineering biology; the convergence of artificial intelligence (AI) and automation with engineering biology; and perspectives from government, industry, and funders on fostering responsible research and public trust. The committee thanks Lynn Rothschild, John Glass, George Church, Elizabeth Strychalski, Cheemeng Tan, Michael Booth, Neha Kamat, Juan Perez-Mercader, Rebecca Moritz, Ben Trump, Richard Lenski, and Greg Jaffe for their insights into the frontiers of synthetic cell research, including emerging applications, scientific advances, broader implications, and approaches to biotechnology risk assessment and mitigation. The committee thanks Patrick Boyle, Rebecca Caruso, Yonatan Chemla, Liyam Chitayat, Igor Linkov, Juan Perez-Mercader, Granger Morgan, Felix Moser, Josef Oehmen, Pam Silver, Abhi Singharoy, and Jeff Zaleski for their perspectives on potential benefits and

risks of synthetic cell applications, including in agriculture, as well as decision making and risk management frameworks relevant to this emerging field.

The National Academies staff thanks the committee members for their participation in this study and their collaboration in the development of this report. The committee, in turn, thanks the study staff and additional National Academies staff for their support, particularly Tucker Nelson, Julie Eubank, and Christopher Lao-Scott, as well as the staff of the Center for Health, People, and Places, for their feedback and contributions to the successful completion and publication of this report.

Generative AI tools were used at various stages of report preparation to assist with outlining and drafting. All content produced with the assistance of these tools was reviewed, verified, and edited by the authors to ensure accuracy, completeness, and consistency with National Academies standards.

Contents

EXECUTIVE SUMMARY

Defining Synthetic Cells: A Continuum-Based Conceptual Foundation

Assessing Risks, Benefits, and Uncertainties

Oversight and Governance: Fragmentation, Gaps, and the Need for Adaptation

Cases Across the Continuum: How Design and Context Shape Risk and Governance

A National Biotechnology Governance Strategy Supporting Responsible Synthetic Cell Innovation

1 INTRODUCTION

The Potential Promise of Synthetic Cells

The Potential Risks of Synthetic Cells

Historical and Policy Context for Synthetic Cell Governance

Study Charge, Scope, and Approach

References

2 DEFINING SYNTHETIC CELLS: SCIENTIFIC, TECHNICAL, AND CONCEPTUAL FOUNDATIONS

Definitional Dilemmas and Governance

The Synthetic Cell Continuum

Building a Synthetic Cell

History and Motivations of Synthetic Cell R&D

Emerging Opportunities and Technical Challenges

Summary and Conclusions

References

3 ANALYTICAL APPROACHES FOR ASSESSING RISKS, BENEFITS, AND UNCERTAINTIES IN SYNTHETIC CELL RESEARCH

Analytical Foundations for Assessing Risks and Benefits

Managing Unknowns in Evolving Fields

Summary and Conclusions

References

4 GOVERNANCE FRAMEWORKS, GAPS, AND FUTURE OVERSIGHT FOR SYNTHETIC CELLS

Existing Governance Frameworks and Policy Landscape

The Synthetic Cell Innovation Ecosystem

Oversight Across Technology Readiness Levels

Gaps, Uncertainties, and Emerging Challenges

Adaptive Governance: Principles for Evolving Oversight

Options for Addressing Gaps and Managing Risks

Summary and Conclusions

References

5 CASES ACROSS THE CONTINUUM: BIOSAFETY, BIOSECURITY, AND ENVIRONMENTAL CONSIDERATIONS

Case 1 – Basic Research: Chemotaxis

Case 2 – Consumer Product: Household Hazard Detection

Case 3 – Bioremediation: Environmental Contaminants Removal

Case 4 – Medicine: Targeted Gastrointestinal Therapy

Case 5 – Agriculture: Crop Nutrient Delivery

Case 6 – Biomanufacturing: Robust Protein Manufacturing

Case 7 – Basic Research: Origins-of-Life Synthetic Cell

Case 8 – Basic Research: Mirror Microorganism for Carbon Sequestration

Summary and Conclusions

References

6 A NATIONAL STRATEGY FOR RESPONSIBLE INNOVATION FOR SYNTHETIC CELLS

Overarching Objectives for a National Governance Strategy

A Unifying Federal Vision

Coordination Needs Across the Federal Government

Social Foundations for Responsible Synthetic Cell Governance

Operationalizing Responsible Synthetic Cell Governance

Summary and Conclusions

References

7 OVERARCHING SUMMARY, CONCLUSIONS, AND RECOMMENDATIONS

Establish a Unified National Biotechnology Governance Strategy to Support Synthetic Cell Governance

Strengthen the Evidence and Data Infrastructure for Risk-Benefit Assessment

Implement an Adaptive Framework for Oversight and Risk-Benefit Evaluation

Update and Modernize Biosafety and Biosecurity Oversight

Advance Responsible Innovation and Public Engagement

Build Institutional and Human Capacity for Oversight and Standards

Promote International Coordination and Harmonization

References

Appendix A Biotechnology Governance: Historical Foundations and Emerging Relevance for Synthetic Cells

References

Appendix B Biographical Sketches

Appendix C Public Meeting Agendas

Appendix D Biosecurity, Dual Use, and Cross-Domain Oversight Questions for Synthetic Cell Research

Boxes, Figures, and Tables

BOXES

S-1 Core Questions Guiding Classification and Risk-Benefit Evaluation

1-1 Statement of Task

2-1 Core Questions Guiding Classification and Risk-Benefit Evaluation

4-1 Risk Categories and Containment Systems

4-2 Illustrative Decision-Support Framework for Identifying When Enhanced Biosecurity Consideration May Be Warranted

FIGURES

S-1 The synthetic cell continuum

S-2 Translating national biotechnology leadership into coordinated governance for synthetic cells

1-1 Societal benefits of synthetic cells across scientific, engineering, and applied domains

2-1 The synthetic cell continuum

3-1 Illustrative decision tree for evaluating the application of synthetic cells to environmental remediation

4-1 Examples of synthetic cell research and development activities across the technology readiness level spectrum

6-1 Translating national biotechnology leadership into coordinated governance for synthetic cells

A-1 Evolution of scientific advances and policy and governance milestone

TABLES

S-1 Synthetic Cell Cases Across the Continuum

S-2 Crosswalk of Themes Underlying Conclusions and Recommendations for Supporting Responsible Synthetic Cell Innovation

1-1 Crosswalk of Statement of Task Elements, Key Questions Addressed, and Report Components

2-1 Definitional Boundaries for Synthetic Cells

2-2 Synthetic Cell Cases Across the Continuum

3-1 Five-Step Risk Assessment Framework and Illustrative Applications to Synthetic Cell Research and Development

4-1 Governance Domains and Major Policies and Frameworks Relevant to Synthetic Cell Research and Applications

4-2 Risk Group Classification of Biohazardous Agents

4-3 Overview of Biosafety Level Containment Practices

4-4 Governance Responsibilities and Risk-Management Focus Across TRLs for Synthetic Cell Research and Applications

5-1 Synthetic Cell Cases Across the Continuum

7-1 Crosswalk of Themes Underlying Conclusions and Recommendations for Supporting Responsible Synthetic Cell Innovation

D-1 Supplemental Biosecurity, Dual Use, Chemical Safety, and Environmental Oversight Questions for Synthetic Cell Research

Acronyms and Abbreviations

Preface

Synthetic cells represent a new horizon in biological sciences and engineering. If humans become capable of synthesizing cells, then they could be said to have gained understanding of how to create the building blocks of life. Upon this foundational and applied knowledge, we may be able to synthesize fundamental life forms in the not-too-distant future. The question is: What risks and benefits might occur as a result of these explorations?

In late 2024, the National Academies, at the request of the National Science Foundation, assembled our committee to evaluate a range of issues surrounding the engineering of biological systems. In early 2025, our committee focus was honed to specifically consider the biosafety, biosecurity, and environmental considerations of synthetic cell research and applications. In navigating this transition, committee composition and roles evolved to adapt, while maintaining the broad expertise and set of perspectives required to fulfill our purpose.

We found that the focus of our study and of this report—synthetic cells—serves as a testbed for the challenges of evaluating and regulating rapidly advancing technologies. Synthetic cells face uncertainties in their very definition, bridge nonliving and living systems, involve multiple disciplines, and show potential for a wide range of application areas. While synthetic cells represent only a fraction of current biotechnology research, they help illustrate needs for filling gaps across the larger biotechnology policy and regulatory landscape.

We wish to express our deep appreciation for the talents, character, and efforts of this committee and the National Academies staff who have worked so closely with us. We especially wish to recognize our Co-Study Directors Trisha Tucholski and Emily Vargas, and Associate Program Officer Sabina Vadnais, who have been a tremendous pleasure to work alongside. Their tireless labors, patience, positive attitudes, and expert

skills have served this study and this committee exceptionally well. And we are profoundly grateful for the keen insights and direction of Kavita Berger and Daniel Weiss. Our thanks also go out to the many speakers who gave their valuable perspectives and greatly informed us in carrying out our task. Excelsior!

Peter A. Carr, Co-Chair

Felicia Wu, Co-Chair

Committee on the External Review of Environmental, Biosafety, and Biosecurity Considerations for Synthetic Cell Research and Development

April 2026