Proceedings of a Workshop

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This activity was supported by contracts between the National Academy of Sciences and Mirror Biology Dialogues 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.

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2026. Mirror Image Biology: Pushing the Envelope in Designing Biological Systems: Proceedings of a Workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/29091.

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MIRROR IMAGE BIOLOGY: PUSHING THE ENVELOPE IN DESIGNING BIOLOGICAL SYSTEMS

NICHOLAS MORGAN ADAMS (Co-Chair), Thermo Fisher Scientific

HARSHINI MUKUNDAN (Co-Chair), Lawrence Berkeley National Laboratory

DOUGLAS C. CAMERON, NAE, Alberti Advisors, LLC

PHILIP E. DAWSON, Scripps Research

MARKITA DEL CARPIO LANDRY, University of California, Berkeley

DIANE DiEULIIS, National Defense University

MICHAEL C. JEWETT, Stanford University

KARL M. THOMPSON, Howard University

Staff

SARAH JUCKETT, Senior Program Officer

NIA JOHNSON, Senior Program Officer

JESSICA DE MOUY, Research Associate

KAVITA BERGER, Senior Program Director, Life Sciences & Biotechnology Program

MARIAH WAUL, Senior Program Assistant (as of October 2025)

LAYLA GARYK, Senior Program Assistant (until October 2025)

DASIA MCKOY, Senior Program Assistant (until July 2025)

CHRISTL SAUNDERS Program Coordinator (until August 2025)

Consultants

JANET IWASA, University of Utah

RACHEL TORREZ, University of Utah

REBECCA MORGAN, Senior Research Librarian, National Academies of Sciences, Engineering and Medicine

Reviewers

This Proceedings of a Workshop 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 proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.

We thank the following individuals for their review of this proceedings:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen PAUL AHLQUIST, NAS, from the University of Wisconsin-Madison. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the National Academies.

Acknowledgments

The Mirror Image Biology: Pushing the Envelope in Designing Biological Systems planning committee and National Academies staff would like to thank the workshop sponsor, the Mirror Biology Dialogues Fund, for their support in forming the scope for our project. Additionally, we thank all speakers who participated in the workshop panels and provided indispensable expertise and background on the current state of the science tying into our charge (see Box 1-3); we also thank the speakers, committee, and participants for the challenging questions and lively discussion related to mirror biology and mirror life (see Box 2-1 and Table 2-1 for terminology).

The National Academies staff thanks the committee (see Appendix C) for their participation in this workshop. The committee thanks the National Academies staff for their support in ensuring the successful completion and publication of these proceedings summarizing the discussions from September 2025.

Contents

1. INTRODUCTION

Overview

Introduction

Project Origination

Biotechnology Regulatory Perspectives

Mirror Biology Dialogues Fund Concerns

Planning Committee Technical Framing

2. CHIRALITY AND ITS POSSIBLE ORIGINS

Chirality

Studies on Emergence Of Chirality

3. ROAD TO MIRROR CELLS

Mirror Molecules

Mirror Molecules - Discussion

Cell-Free Systems for Creating Minimal Cells

Impact of Chirality on BioMaterials

4. OPPORTUNITIES AND RISKS

Commercial Development of Mirror Molecules

Immunological Considerations

Environmental and Ecological Impacts

5. CONSIDERATION OF RISK OF MIRROR LIFE

Building Decision Points into Research’s Slipperiest Slopes

Mirror Life Considerations and Potential Experiments

REFERENCES

Appendix A Statement of Task

Appendix B Public Meeting Agendas

Appendix C Biographical Sketches of Workshop Planning Committee and Speakers

Boxes, Figures, and Table

BOXES

1-1 Attendee-Highlighted Take-Aways

1-2 Technical Questions Highlighted by Attendees

1-3 Statement of Task

2-1 Participant Terminology

FIGURES

1-1 2D Illustration of a Natural Endonuclease binding to D-DNA but not L-DNA

1-2 2D Cell Surface Proteins

1-3 3D Illustration Natural and Mirror Bacteria interacting (or not) with a natural form macrophage, a component of the innate immune system

2-1 Making Mirror Component versus Making Mirror Cells

2-2 Progression of Chirality from Prebiotic World to DNA Coup

2-3 Origins of Biological Homochirality

3-1 L-Oligonucleotides

3-2 L –Oligonucleotides – Applications

3-3 Z-DNA and Z-RNA

3-4 Two Different Mirrors – Z-RNA and L-RNA

3-5 Zα Domains Bridge the Two Worlds

3-6 Bottom Up CFE Synthetic Cells Determinants of health and their contributions to premature death

3-7 Rippled Sheets Facilitate the Formation of Nested Hydrophobic Interactions

4-1 Diagrammatic view of the Landscape with Our Terminology

4-2 Driving Demand for Efficient Production of Larger D-proteins

4-3 Potential Pathways Towards Developing a Mirror Cell

4-4 Host Immune responses to pathogens can diagnose presence, type and severity of infection

4-5 What Can We Learn from Synthetic Polymers

4-6 Fate of mirror cells in the environment

4-7 Potential Sources and Sinks of Engineered Mirror Organism in the Environment

5-1 Will Mirror Organisms have a growth advantage in the wild?

TABLE

2-1 Discussions on Defining Mirror Components

Acronyms and Abbreviations