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SYNTHETIC BIOLOGY BUILDING ON NATURE'S INSPIRATION

INTERDISCIPLINARY RESEARCH TEAM SUMMARIES

Conference

Arnold and Mabel Beckman Center

Irvine, California

November 20–22, 2009

THE NATIONAL ACADEMIES PRESS

Washington, D.C.
www.nap.edu



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Synthetic OF THE FUTURE Biology HUMAN HEALTHSPAN building on nature's inspiration InterdIscIplInary research team summarIes Demography, E volution, M edicine, a nd B ioengineering TA S K G R O U P S U M M A R I E S Conference Arnold and Mabel Beckman Center Irvine, California November 20–22, 2009

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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The Interdisciplinary Research (IDR) team summaries in this publication are based on IDR team discussions during the National Academies Keck Futures Initiative Conference on Synthetic Biology held at the Arnold and Mabel Beckman Center in Irvine, California, November 20-22, 2009. The discussions in these groups were sum- marized by the authors and reviewed by the members of each IDR team. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the IDR teams and do not necessarily reflect the view of the organizations or agencies that provided support for this project. For more information on the National Academies Keck Futures Initiative visit www.keckfutures.org. Funding for the activity that led to this publication was provided by the W.M. Keck Foundation. Based in Los Angeles, the W. M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. In recent years, the Foun - dation has focused on five broad areas: Science and Engineering research; Undergraduate Education; Medical Research; and Southern California. Each grant program invests in people and programs that are making a difference in the quality of life, now and for the future. For more information visit www.wmkeck.org. International Standard Book Number-13: 978-0-309-14942-6 International Standard Book Number-10: 0-309-14942-8 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. Copyright 2010 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a man- date that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine. The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the Na- tional Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE SYNTHETIC BIOLOGY STEERING COMMITTEE BONNIE L. BASSLER (Chair) (NAS), Investigator, Howard Hughes Medical Institute; Professor of Molecular Biology, Department of Molecular Biology, Princeton University FRANCES H. ARNOLD (NAS/NAE/IOM), Dick and Barbara Dickinson Professor of Chemical Engineering and Biochemistry, California Institute of Technology R. ALTA CHARO (IOM), Senior Advisor, Office of the Commissionor; Food & Drug Administration MICHAEL ELOWITZ, Associate Professor of Biology and Applied Physics; California Institute of Technology; Investigator, Howard Hughes Medical Institute CHAITAN KHOSLA (NAE), Chair, Chemical Engineering, Wells H. Rauser and Harold M. Petiprin Professor in the School of Engineering, Professor of Chemical Engineering, Chemistry, and Biochemistry, Stanford University ERIN K. O’SHEA (NAS), Investigator, Howard Hughes Medical Institute; Professor, Department of Chemistry and Chemical Biology, Harvard University CHRISTINA D. SMOLKE, Assistant Professor of Bioengineering, Stanford University DAVID A. TIRELL (NAS/NAE), Ross McCollum-William H. Corcoran Professor and former Chairman, Division of Chemistry and Chemical Engineering, California Institute of Technology JONATHAN S. WEISSMAN (NAS), Investigator, Howard Hughes Medical Institute; Professor of Cellular and Molecular Pharmacology, Professor of Biochemistry and Biophysics, University of California, San Francisco Staff KENNETH R. FULTON, Executive Director KIMBERLY A. SUDA-BLAKE, Program Director ANNE HEBERGER, Senior Evaluation Associate CRISTEN KELLY, Program Associate RACHEL LESINSKI, Program Associate v

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The National Academies Keck Futures Initiative The National Academies Keck Futures Initiative was launched in 2003 to stimulate new modes of scientific inquiry and break down the conceptual and institutional barriers to interdisciplinary research. The National Acad- emies and the W. M. Keck Foundation believe that considerable scientific progress will be achieved by providing a counterbalance to the tendency to isolate research within academic fields. The Futures Initiative is designed to enable scientists from different disciplines to focus on new questions, upon which they can base entirely new research, and to encourage and reward outstanding communication between scientists as well as between the sci- entific enterprise and the public. The Futures Initiative includes three main components: Futures Conferences The Futures Conferences bring together some of the nation’s best and brightest researchers from academic, industrial, and government labora- tories to explore and discover interdisciplinary connections in important areas of cutting-edge research. Each year, some 150 outstanding research- ers are invited to discuss ideas related to a single cross-disciplinary theme. Participants gain not only a wider perspective but also, in many instances, new insights and techniques that might be applied in their own work. Ad- ditional pre- or post-conference meetings build on each theme to foster further communication of ideas. Selection of each year’s theme is based on assessments of where the vii

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viii THE naTIonal acadEmIES kEck FUTURES INITIATIVE intersection of science, engineering, and medical research has the greatest potential to spark discovery. The first conference explored Signals, deci- sions, and meaning in Biology, chemistry, Physics, and Engineering. The 2004 conference focused on designing nanostructures at the Interface between Biomedical and Physical Systems. The theme of the 2005 conference was The Genomic Revolution: Implications for Treatment and control of Infectious dis- ease. In 2006 the conference focused on Smart Prosthetics: Exploring assistive devices for the Body and mind. In 2007 the conference explored The Future of Human Healthspan: demography, Evolution, medicine and Bioengineering. In 2008 the conference focused on complex Systems. The 2009 conference explored Synthetic Biology: Building on nature’s Inspiration and the 2010 conference will focus on Imaging Science. Futures Grants The Futures Grants provide seed funding to Futures Conference partici- pants, on a competitive basis, to enable them to pursue important new ideas and connections stimulated by the conferences. These grants fill a critical missing link between bold new ideas and major federal funding programs, which do not currently offer seed grants in new areas that are considered risky or exotic. These grants enable researchers to start developing a line of inquiry by supporting the recruitment of students and postdoctoral fellows, the purchase of equipment, and the acquisition of preliminary data—which in turn can position the researchers to compete for larger awards from other public and private sources. NAKFI Communications The Communication Awards are designed to recognize, promote, and encourage effective communication of science, engineering, medicine, and/or interdisciplinary work within and beyond the scientific community. Each year the Futures Initiative awards $20,000 prizes to those who have advanced the public’s understanding and appreciation of science, engi- neering, and/or medicine. The awards are given in four categories: books, magazine/newspaper, online, and film/radio/TV. The winners are honored during Futures Conferences. NAKFI cultivates science writers of the future by inviting graduate students from six science writing programs across the country to attend the

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ix THE naTIonal acadEmIES kEck FUTURES INITIATIVE conference and develop IDR team discussion summaries and a conference overview for publication in this book. Students are selected by the depart- ment director or designee, and prepare for the conference by reviewing the Podcast tutorials and suggested reading, and selecting an IDR team in which they would like to participate. Students then work with NAKFI’s science writing student mentor to finalize their reports following the conferences. Facilitating Interdisciplinary Research Study During the first 18 months of the Keck Futures Initiative, the Acad- emies undertook a study on facilitating interdisciplinary research. The study examined the current scope of interdisciplinary efforts and provided recommendations as to how such research can be facilitated by funding or- ganizations and academic institutions. Facilitating Interdisciplinary Research (2005) is available from the National Academies Press (www.nap.edu) in print and free PDF versions. About the National Academies The National Academies comprise the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council, which perform an unparalleled public service by bringing together experts in all areas of science and technology, who serve as volunteers to address critical national issues and offer unbiased advice to the federal government and the public. For more information, visit www. nationalacademies.org. About the W.M. Keck Foundation Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of Science and Engineering; Undergraduate Education; Medical Research; and Southern California. Each grant program invests in people and programs that are making a difference in the quality of life, now and in the future. For more information visit www.wmkeck.org.

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x THE naTIonal acadEmIES kEck FUTURES INITIATIVE National Academies Keck Futures Initiative 100 Academy, 2nd Floor Irvine, CA 92617 949-721-2270 (Phone) 949-721-2216 (Fax) www.keckfutures.org

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Preface At the National Academies Keck Futures Initiative Conference on Synthetic Biology, participants were divided into twelve Interdisciplinary Research (IDR) teams. The teams spent nine hours over two days exploring diverse challenges at the interface of science, engineering, and medicine. The composition of the teams was intentionally diverse, to encourage the generation of new approaches by combining a range of different types of contributions. The teams included researchers from science, engineering, and medicine, as well as representatives from private and public funding agencies, universities, businesses, journals, and the science media. Research - ers represented a wide range of experience—from postdoc to those well established in their careers—from a variety of disciplines that included sci- ence and engineering, medicine, physics, biology, math/computer science and behavioral science. The teams needed to address the challenge of communicating and working together from a diversity of expertise and perspectives as they at- tempted to solve a complicated, interdisciplinary problem in a relatively short time. Each team decided on its own structure and approach to tackle the problem. Some teams decided to refine or redefine their problems based on their experience. Each team presented two brief reports to all participants: (1) an interim report on Saturday to debrief on how things were going, along with any special requests; and (2) a final briefing on Sunday, when each team: xi

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xii PREFacE • Provided a concise statement of the problem; • Outlined a structure for its solution; • Identified the most important gaps in science and technology and recommended research areas needed to attack the problem; and • Indicated the benefits to society if the problem could be solved. Each IDR team included a graduate student in a university science writing program. Based on the team interaction and the final briefings, the students wrote the following summaries, which were reviewed by the team members. These summaries describe the problem and outline the approach taken, including what research needs to be done to understand the funda- mental science behind the challenge, the proposed plan for engineering the application, the reasoning that went into it and the benefits to society of the problem solution. Due to the popularity of some topics, two teams were assigned to explore the subjects. Eleven Podcasts were launched throughout the summer to help bridge the gaps in terminology used by the various disciplines. Participants had the opportunity to ask questions of the Podcast speakers during the panel dis- cussion, which took place immediately prior to the IDR team discussions.

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Contents Conference Summary 1 IDR TEAM SUMMARIES 1 What new foundational technologies and tools are required to make biology easier to engineer? 7 IDR Team Summary, Group A, 9 IDR Team Summary, Group B, 13 2 What are the significant differences, if any, between risk assessment capacity and religious analyses of the moral for synthetic permissibility biology applications and other biotechnology applications? 19 3 Reconstructing gene circuitry: How can synthetic biology lead us to an understanding of the principles underlying natural genetic circuits and to the discovery of new biology? 25 IDR Team Summary, Group A, 28 IDR Team Summary, Group B, 31 4 Designing communities of cells: how do we create communication and collaboration between cells to allow for specialization and division of labor? 37 xiii

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xiv conTEnTS 5 Why are human-designed biological circuits and devices fragile and inaccurate relative to their natural counterparts? 45 6 How can genomics be leveraged to develop coherent approaches for rapidly exploring the biochemical diversity in and engineering of non-model organisms? 53 7 How do we move beyond genetics to engage chemical and physical approaches to synthetic biology? 61 IDR Team Summary, Group A, 63 IDR Team Summary, Group B, 67 8 What is the role of evolution and evolvability in synthetic biology? 71 9 How do we maximally capitalize on the promise of synthetic biology? 77 APPENDIXES List of Podcast Tutorials 85 Agenda 89 Participants 95 To view the podcast tutorials or conference presentations, please visit our website at www.keckfutures.org.