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 report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.
This Board on Biology study was supported by the National Science Foundation, the Department of Energy, the U. S. Department of Agriculture, the National Aeronautics and Space Administration, the National Institute of Standards and Technology, and the National Academy of Engineering.
Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the sponsors of this report.
Library of Congress Catalog Card Number 92-61717
International Standard Book Number 0-309-04785-4
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Copyright 1992 by the National Academy of Sciences. All rights reserved.
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COMMITTEE ON BIOPROCESS ENGINEERING
Michael R. Ladisch (Chairman),
Purdue University, West Lafayette, Indiana
Charles L. Cooney,
Massachusetts Institute of Technology, Cambridge, Massachusetts
Robert C. Dean, Jr.,
Dean Technology, Inc., Lebanon, New Hampshire
Arthur E. Humphrey,
Pennsylvania State University, State College, Pennsylvania
T. Kent Kirk,
U.S. Department of Agriculture, Madison, Wisconsin
Larry V. McIntire,
Rice University, Houston, Texas
Alan S. Michaels,
Alan Sherman Michaels, Sc.D., Inc., Chestnut Hill, Massachusetts
Paula Myers-Keith,
Pitman-Moore, Inc., Terre Haute, Indiana
Dewey D.Y. Ryu,
University of California, Davis, California
James R. Swartz,
Genentech, Inc., San Francisco, California
Daniel I.C. Wang,
Massachusetts Institute of Technology, Cambridge, Massachusetts
Janet Westpheling,
University of Georgia, Athens, Georgia
George M. Whitesides,
Harvard University, Cambridge, Massachusetts
National Research Council Staff:
John E. Burris, Study Director
Oskar Zaborsky, Study Director (until April 1992)
Marietta Toal, Administrative Secretary
Norman Grossblatt, Editor
BOARD ON BIOLOGY
Harold E. Varmus (Chairman),
University of California, San Francisco, California
Ananda M. Chakrabarty,
University of Illinois Medical Center, Chicago, Illinois
Michael T. Clegg,
University of California, Riverside, California
Richard E. Dickerson,
University of California, Los Angeles, California
Gerald D. Fischbach,
Harvard Medical School, Boston, Massachusetts
Richard E. Lenski,
Michigan State University, East Lansing, Michigan
Barbara J. Mazur,
E. I. du Pont de Nemours & Company, Wilmington, Delaware
Daniel E. Morse,
University of California, Santa Barbara, California
Philip Needleman,
Monsanto Company, St. Louis, Missouri
Mary Lou Pardue,
Massachusetts Institute of Technology, Cambridge, Massachusetts
Michael E. Soulé,
University of California, Santa Cruz, California
Geerat J. Vermeij,
University of California, Davis, California
National Research Council Staff:
John E. Burris, Study Director
Oskar Zaborsky, Study Director (until April 1992)
Marietta Toal, Administrative Secretary
COMMISSION ON LIFE SCIENCES
Bruce M. Alberts (Chairman),
University of California, San Francisco, California
Bruce N. Ames,
University of California, Berkeley, California
J. Michael Bishop,
University of California Medical Center, San Francisco, California
David Botstein,
Stanford University School of Medicine, Stanford, California
Michael T. Clegg,
University of California, Riverside, California
Glenn A. Crosby,
Washington State University, Pullman, Washington
Leroy E. Hood,
California Institute of Technology, Pasadena, California
Marian E. Koshland,
University of California, Berkeley, California
Richard E. Lenski,
Michigan State University, East Lansing, Michigan
Steven P. Pakes,
University of Texas Southwestern Medical Center, Dallas, Texas
Emil A. Pfitzer,
Hoffmann-La Roche Inc., Nutley, New Jersey
Malcolm C. Pike,
University of Southern California School of Medicine, Los Angeles, California
Thomas D. Pollard,
Johns Hopkins University Medical School, Baltimore, Maryland
Paul G. Risser,
University of New Mexico, Albuquerque, New Mexico
Jonathan M. Samet,
University of New Mexico School of Medicine, Albuquerque, New Mexico
Harold M. Schmeck, Jr.,
Armonk, New York
Carla J. Schatz,
University of California, Berkeley, California
Susan S. Taylor,
University of California, San Diego, La Jolla, California
Roy P. Vagelos,
Merck & Company, Inc., Rahway, New Jersey
Torsten N. Wiesel,
Rockefeller University, New York, New York
National Research Council Staff:
John E. Burris, Executive Director
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Preface
Biotechnology is broadly defined in a 1991 Office of Technology Assessment report as "any technique that uses living organisms (or parts of organisms) to make or modify products, to improve plants or animals, or to develop microorganisms for specific uses." This technology has been instrumental in the development and implementation of processes for the manufacture of antibiotics and other pharmaceuticals, industrial sugars, alcohols, amino acids and other organic acids, foods, and specialty products through the application of microbiology, fermentation, enzymes, and separation technology. Engineers, working with life scientists, often achieved scale-up to industrial production in remarkably short periods. A relatively small number helped to catalyze, over a period of 50 years, the growth of the pharmaceutical, food, agricultural-processing, and specialty-product sectors of the U.S. economy to the point where sales now exceed $100 billion/year.
The introduction of the new biotechnology since 1970 enabled directed manipulation of the cell's genetic machinery through recombinant-DNA techniques and cell fusion. Its application on an industrial scale since 1979 has fundamentally expanded the utility of biological systems and positioned a number of industries for explosive global growth. Scientists and engineers can now change the genetic makeup of microbial, plant, and animal cells to confer new characteristics. Biological molecules, for which there is no other means of industrial production, can now be generated. Existing industrial organisms can be systematically altered (i.e., engineered) to enhance their function and to produce useful products in new ways. The new biotechnology, combined with the existing industrial, government, and university infrastructure in biotechnology and the pervasive influence of biological substances in everyday life, has set the stage for unprecedented growth in products, markets, and expectations.
Substantial manufacturing capability will be needed to bring about the full application of biotechnology for the benefit of society. A wide array of engineering fundamentals applied to biological systems will be required to produce and purify biological products on a commercial scale. Bioprocess engineers will be essential for translating the discoveries of biotechnology into tangible commercial products, thereby putting biotechnology to work. The Committee on Bioprocess Engineering was convened in the National Research Council's Board on Biology to address issues that are of critical importance if the nation is to reap the full benefits of its success in fundamental biotechnology research: What discoveries and concepts in biology and chemistry are important to bioprocess engineering? What barriers to their exploitation exist? What is the position of the United States in relation to other countries' efforts in bioprocess engineering, especially those of Japan and Germany? What actions are required to ensure that research and training are adequately organized and supported so that the United States can maintain and improve its position? The committee met five times from May 1991 to May 1992 and found that much needs to be done, and done quickly. This report represents a consensus of the committee, which hopes to impart a sense of urgency to the planning for bioprocess-engineering needs in biotechnology manufacturing in the United States.
The committee carefully considered the best way to present its findings and to organize the report, given the wide range of products, services, and needs that will be affected by bioprocess engineering and the diverse backgrounds of those who will read this report. The committee decided that the reader should first be provided a definition of bioprocess engineering, a discussion of its economic impact on biotechnology, and a summary of major barriers to the exploitation of biotechnology. Further definitions and a historical perspective were to be addressed in Chapter 2, to illustrate the role of bioprocess engineering in a substantial portion of the economic sectors of the United States. We decided to present the current status of U.S. capabilities, and those of Japan and Europe next, because of the importance of international competitiveness for U.S. economic activities, particularly those affected by bioprocessing. The many areas already affected by bioprocess engineering are presented in Chapter 4, to help the reader become more aware of the language and technologies encompassed by biotechnology. Having "set the stage," the committee chose to present, in Chapter 5, what needs to be done now to address needs that will not be fully understood for some years to come. Chapter 6 addresses future scenarios of biotechnology development and how the education, training, research, and technology-transfer issues related to current opportunities (described in Chapter 5) will prepare bioprocessing to address future needs.
The committee thanks those who contributed to its work and shared their expertise at our meetings. In particular, we would like to thank the Nation-
al Science Foundation (NSF) Directorate for Engineering (Biotechnology Program and Divisions of Biological and Critical Systems, Engineering Education Centers, and Chemical and Thermal Systems), the NSF Directorate for Biological Sciences (Divisions of Behavioral and Cognitive Sciences, Biological Instrumentation and Resources, Social and Economic Science, and Molecular Biosciences), the Department of Energy (offices of Industrial Technologies, Fossil Energy, and Alcohol Fuels), the Department of Agriculture (Office of the Assistant Secretary for Science and Education and Agricultural Research Service), the National Aeronautics and Space Administration (Life Sciences Division, Microgravity Science Division, and Office of Commercial Programs), the Department of Commerce (National Institute of Standards and Technology, Chemical Science and Technology Laboratory), and the National Academy of Engineering for funding this study. Duane Bruley, Luther Williams, and Carl Hall of NSF deserve special mention for their support of this study in its early stages and Fred Heineken of NSF for serving as the contact person of the lead agency on logistic matters.
The chairman thanks Purdue University for making time available to carry out the tasks associated with the committee's work, Carolyn Wasson for excellent assistance in preparing the various drafts of this report, and Norma Leuck for coordinating the numerous communications with committee members. The chairman also thanks Michael Shuler of Cornell University for making his expertise available and contributing to the technical completeness of the report; Charles Scott of Oak Ridge National Laboratories for comments on bioprocess-engineering needs; Edith Munroe of the Corn Refiners Association, Inc., and Matthew Rendlemen and Betsy Kuhn of the Department of Agriculture Economic Research Service for helpful information on value-added products from corn; and Karl H. Kroner of the German National Research Center for Biotechnology (GBF) for providing information on German bioprocess engineering. The committee thanks Donald Henninger, Doug Ming, and Glenn Spaulding of the National Aeronautics and Space Administration Johnson Space Center for arranging a subcommittee visit to the center and is indebted to Marietta Toal of the Board on Biology for her excellent assistance with committee meetings. The committee also thanks numerous individuals and organizations that rapidly responded to inquiries from the committee. Norman Grossblatt, of the National Research Council's Commission on Life Sciences, edited the report. Special thanks are due to Oskar Zaborsky, director of the Board on Biology, whose vision, hard work, and many capabilities enabled this study to be initiated and carried out in a timely manner, and to him and John Burris, executive director of the Commission on Life Sciences, for the long hours they spent in guiding this report through many drafts to its successful conclusion.
Michael R. Ladisch, Chairman,
Committee on Bioprocess Engineering