Industrialization
of Biology
A Roadmap to Accelerate the Advanced
Manufacturing of Chemicals
Committee on Industrialization of Biology:
A Roadmap to Accelerate the Advanced Manufacturing of Chemicals
Board on Chemical Sciences and Technology
Board on Life Sciences
Division on Earth and Life Studies
NATIONAL RESEARCH COUNCIL
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by the U.S. Department of Energy under Grant DE-SC0010761 and the National Science Foundation under Grant CBET-1344363.
This report was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to a specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or agency thereof.
International Standard Book Number-13: 978-0-309-31652-1
International Standard Book Number-10: 0-309-31652-9
Library of Congress Control Number: 2015937241
Additional copies of the report are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2015 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
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 mandate 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. C. D. Mote, Jr., 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. Victor J. Dzau 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 National 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. C. D. Mote, Jr., are chair and vice chair, respectively, of the National Research Council.
COMMITTEE ON INDUSTRIALIZATION OF BIOLOGY:
A ROADMAP TO ACCELERATE THE
ADVANCED MANUFACTURING OF CHEMICALS
Members
THOMAS M. CONNELLY, JR. (Chair), E. I. du Pont de Nemours & Company (ret.)
MICHELLE C. CHANG, University of California, Berkeley
LIONEL CLARKE, UK Synthetic Biology Leadership Council
ANDREW D. ELLINGTON, University of Texas at Austin
NATHAN J. HILLSON, Lawrence Berkeley National Laboratory
RICHARD A. JOHNSON, Global Helix LLC
JAY D. KEASLING, University of California, Berkeley
STEPHEN S. LADERMAN, Agilent Technologies, Inc.
PILAR OSSORIO, University of Wisconsin Law School
KRISTALA L. J. PRATHER, Massachusetts Institute of Technology
RESHMA P. SHETTY, Ginkgo Bioworks, Inc.
CHRISTOPHER A. VOIGT, Massachusetts Institute of Technology
HUIMIN ZHAO, University of Illinois, Urbana-Champaign
National Research Council Staff
DOUGLAS FRIEDMAN, Study Director, Board on Chemical Sciences and Technology
INDIA HOOK-BARNARD, Senior Program Officer, Board on Life Sciences
CARL-GUSTAV ANDERSON, Research Associate
ELIZABETH FINKELMAN, Program Coordinator
NAWINA MATSHONA, Senior Program Assistant
JOHN SADOWSKI, Christine Mirzayan Science & Technology Policy Fellow (Winter 2014)
BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY
Members
TIMOTHY SWAGER, (Co-Chair), Massachusetts Institute of Technology
DAVID WALT, (Co-Chair), Tufts University
HÉCTOR D. ABRUÑA, Cornell University
JOEL C. BARRISH, Bristol-Myers Squibb
MARK A. BARTEAU, University of Michigan
DAVID BEM, The Dow Chemical Company
ROBERT G. BERGMAN, University of California, Berkeley
JOAN BRENNECKE, University of Notre Dame
HENRY E. BRYNDZA, E. I. du Pont de Nemours & Company
MICHELLE V. BUCHANAN, Oak Ridge National Laboratory
DAVID W. CHRISTIANSON, University of Pennsylvania
RICHARD EISENBERG, University of Rochester
JILL HRUBY, Sandia National Laboratories
FRANCES S. LIGLER, University of North Carolina, Chapel Hill, and North Carolina State University
SANDER G. MILLS, Merck Research Laboratories (ret.)
JOSEPH B. POWELL, Shell
ROBERT E. ROBERTS, Institute for Defense Analyses
PETER J. ROSSKY, Rice University
National Research Council Staff
TERESA FRYBERGER, Director
DOUGLAS FRIEDMAN, Senior Program Officer
KATHRYN HUGHES, Senior Program Officer
CAMLY TRAN, Postdoctoral Fellow
CARL-GUSTAV ANDERSON, Research Associate
ELIZABETH FINKELMAN, Program Coordinator
NAWINA MATSHONA, Senior Program Assistant
COTILYA BROWN, Senior Program Assistant
BOARD ON LIFE SCIENCES
Members
JAMES P. COLLINS (Chair), Arizona State University
ENRIQUETA C. BOND, Burroughs Wellcome Fund (ret.)
ROGER D. CONE, Vanderbilt University Medical Center
JOSEPH R. ECKER, Salk Institute for Biological Studies
SEAN EDDY, HHMI Janelia Farm Research Campus
SARAH C. R. ELGIN, Washington University in St. Louis
DAVID R. FRANZ, Former Commander USAMRIID; Consultant
STEPHEN FRIEND, Sage Bionetworks
ELIZABETH HEITMAN, Vanderbilt University Medical Center
JOHN G. HILDEBRAND, University of Arizona
RICHARD A. JOHNSON, Global Helix LLC
JUDITH KIMBLE, University of Wisconsin, Madison
MARY E. MAXON, Science Philanthropy Alliance
KAREN E. NELSON, J. Craig Venter Institute
ROBERT M. NEREM, Georgia Institute of Technology
MARY E. POWER, University of California, Berkeley
MARGARET RILEY, University of Massachusetts, Amherst
LANA SKIRBOLL, Sanofi
JANIS C. WEEKS, University of Oregon
MARY WOOLLEY, Research!America
Staff
FRANCES E. SHARPLES, Director
JO L. HUSBANDS, Scholar/Senior Project Director
JAY B. LABOV, Senior Scientist/Program Director for Biology Education
KATHERINE W. BOWMAN, Senior Program Officer
MARILEE K. SHELTON-DAVENPORT, Senior Program Officer
KEEGAN SAWYER, Program Officer
AUDREY THEVENON, Associate Program Officer
BETHELHEM MEKASHA, Financial Associate
ANGELA KOLESNIKOVA, Administrative Assistant
P. KANOKO MAEDA, Senior Project Assistant
JENNA OGILVIE, Senior Project Assistant
Preface
The efficient production of useful and beneficial goods and services has been the cornerstone of industrial development, driving economic growth for more than two centuries. Throughout this period, the underpinning technologies driving industrialization have evolved in response to new scientific understanding, new technological capabilities, and new market demands. Insights into the chemical nature of matter, reaction mechanisms, and the role of physical and catalytic processes transformed the industrial landscape during the 19th century. By the early 20th century, a new understanding of chemistry transformed crude oil into a feedstock for a vast array of chemical products ranging from plastics and paints to detergents and textiles—transforming nearly every aspect of our lives.
Today, we are at a new inflection point. The tremendous progress in biology over the past half century—from Watson and Crick’s elucidation of the structure of DNA to today’s astonishing, rapid progress in the field of synthetic biology—has positioned us for the new round of innovation in chemical production. This observation provided the impetus for this study, commissioned by the U.S. Department of Energy and the National Science Foundation. Our committee was charged with understanding how to accelerate biological production of chemicals and also to create a roadmap to that future.
The committee of 13 members (Appendix C) convened from approximately February 2014 through December 2014 and met in person four times. Expertise included synthetic biology, metabolic engineering, molecular biology, microbiology, systems biology, synthetic chemistry, chemical
engineering, bioinformatics, systems integration, metrology, chemical manufacturing, and law and bioethics. The committee heard from researchers at the leading edge of microbial biotechnology and from industry leaders, including large, established chemical companies and technology-rich startups. We had dialogue with representatives of U.S. government agencies and with nongovernment organizations. In May 2014 the committee held a 2-day workshop (Appendix D), which laid the foundation for the conclusions, recommendations, and roadmap found in this report.
Any roadmap is an ephemeral guide—a snapshot in time. The committee took care to set ambitious goals that emphasize outcomes over individual technologies. As science and technology advance and economic circumstances change, it is often the road-mapping process that can provide lasting value. This observation, coupled with the broad, outcome-oriented goals herein, led the committee to discuss the road-mapping process as a continuing activity that the sponsoring agencies may wish to consider on a regular basis in order to ensure acceleration of this field and maintenance of the roadmap in a living, evergreen process.
As stated in the National Bioeconomy Blueprint released in 2012, “[e]conomic activity that is fueled by research and innovation in the biological science, the ‘bioeconomy,’ is a large and rapidly growing segment of the world economy that provides substantial public benefit.” The picture that emerged through the course of the study was that of a field with tremendous potential for innovation, economic impact, and great discovery—if only we can accelerate its maturity.
Thomas M. Connelly, Jr., Chair
Acknowledgment of Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. 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 deliberative process.
We wish to thank the following individuals for their review of this report:
Scott Baker, Pacific Northwest National Laboratory
Sean Eddy, HHMI Janelia Farm Research Campus
Jennifer Holmgren, LanzaTech
Sang Yup Lee, KAIST
James Liao, University of California, Los Angeles
Richard Murray, California Institute of Technology
Kathie Olsen, ScienceWorks, LLC
Markus Pompejus, BASF Corporation
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report
before its release. The review of this report was overseen by Klavs Jensen of the Massachusetts Institute of Technology and Michael Ladisch of Purdue University. Appointed by the National Research Council, 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.
Contents
The Potential of Industrial Biotechnology
The Gaps Have Been Characterized
Technical Conclusions, Recommendations, and Roadmap Goals
Nontechnical Insights and Societal Concerns
Charge to the Committee and Interpretation of Scope
2 INDUSTRIAL BIOTECHNOLOGY: PAST AND PRESENT
The Bioeconomy and Global Challenges
Societal Benefits in Addressing Global Grand Challenges
Climate Change and Environmental Sustainability
Competitiveness and Innovation
The Time Is Right: Current State and Advances in Science and Industry
Opportunities Arising from DNA Technologies, Systems Biology, Metagenomics, and Synthetic Biology
New High-Value Chemical Products Unobtainable by Traditional Chemical Synthesis
Implementing Computation in Cells
Biofuels: Moving to Commercial
3 VISION OF THE FUTURE: WHAT NEW CHEMICALS COULD BE MADE?
Tapping New Structural Diversity
Engineering the Production of Complex Building Blocks
Engineering the Stereo- and Regioselective Transformation of Synthetic Building Blocks
Catalysis with Key Functional Groups and for New C-C Bond-Making Chemistry
Polymers for Templating the Formation of Inorganic Materials
Business Models for Future Industrial Biotechnology
Multiple Generations of Feedstocks
Additional Bioprocessing Operations
Introduction: The Design-Build-Test-Learn Loop
Fully Integrated Design Toolchain
5 WHAT IS SUCCESS AND HOW TO GET THERE: RECOMMENDATIONS