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Page i Opportunities in Biotechnology for Future Army Applications Committee on Opportunities in Biotechnology for Future Army Applications Board on Army Science and Technology Division on Engineering and Physical Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C.
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Page ii NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, DC 20418 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 Contract No. DAAD 19-99-L-0052 between the National Academy of Sciences and the Department of Defense. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the organizations or agencies that provided support for the project. International Standard Book Number 0-309-07555-6 Library of Congress Catalog Card Number: 2001090219 Additional copies of this report are available from National Academy Press , 2101 Constitution Avenue, 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 2001 by the National Academy of Sciences . All rights reserved. Printed in the United States of America
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Page iii THE NATIONAL ACADEMIES National Academy of Sciences National Academy of Engineering Institute of Medicine National Research Council 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. Bruce M. Alberts 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. William A. Wulf 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. Kenneth I. Shine 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. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.
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Page iv COMMITTEE ON OPPORTUNITIES IN BIOTECHNOLOGY FOR FUTURE ARMY APPLICATIONS MICHAEL R. LADISCH, NAE, chair, Purdue University, West Lafayette, Indiana ILHAN AKSAY, Princeton University, Princeton, New Jersey ERIC BAER, Case Western Reserve University, Cleveland, Ohio ROBERT R. BIRGE, University of Connecticut, Storrs ROGER BRENT, Molecular Sciences Institute, Berkeley, California SHEILA H. DEWITT, ArQule, Inc., Woburn, Massachusetts MAURO FERRARI, Ohio State University, Columbus CHRISTOPHER C. GREEN, General Motors, New Baltimore, Michigan NILE F. HARTMAN, Photonic Sensor Systems, Inc., Atlanta, Georgia PAUL E. LAIBINIS, Massachusetts Institute of Technology, Cambridge VERNE L. (LARRY) LYNN, Defense Advanced Research Projects Agency (retired), Williamsburg, Virginia M. ALLEN NORTHRUP, Cepheid, Inc., Sunnyvale, California THOMAS C. RANSOHOFF, TranXenoGen, Inc., Shrewsbury, Massachusetts DANIEL I.C. WANG, NAE, Massachusetts Institute of Technology, Cambridge JANET WESTPHELING, University of Georgia, Athens KENSALL D. WISE, NAE, University of Michigan, Ann Arbor Board on Army Science and Technology Liaison KATHRYN V. LOGAN, Georgia Institute of Technology (retired), Roswell, Georgia JOHN H. MOXLEY III, IOM, Korn/Ferry International, Los Angeles, California MILLARD F. ROSE, National Aeronautics and Space Administration, Huntsville, Alabama CLARENCE G. THORNTON, Army Research Laboratory (retired), Colts Neck, New Jersey National Materials Advisory Board Liaison MIKE JAFFE, Rutgers, The State University of New Jersey, Piscataway National Research Council Staff ROBERT J. LOVE, Study Director JIM MYSKA, Research Associate GWEN ROBY, Senior Project Assistant LINDA VOSS, Technical Consultant
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Page v BOARD ON ARMY SCIENCE AND TECHNOLOGY WILLIAM H. FORSTER, chair, Northrop Grumman Corporation, Baltimore, Maryland RICHARD A. CONWAY, Union Carbide Corporation (retired), Charleston, West Virginia GILBERT F. DECKER, Walt Disney Imagineering, Glendale, California PATRICK F. FLYNN, NAE, Cummins Engine Company, Columbus, Indiana HENRY J. HATCH, NAE, U.S. Army (retired), Oakton, Virginia EDWARD J. HAUG, University of Iowa, Iowa City ROBERT J. HEASTON, Guidance and Control Information Analysis Center (retired), Chicago, Illinois GERALD R. IAFRATE, University of Notre Dame, Notre Dame, Indiana MIRIAM E. JOHN, Sandia National Laboratories, Livermore, California DONALD R. KEITH, Cypress International, Alexandria, Virginia KATHRYN V. LOGAN, Georgia Institute of Technology (retired), Roswell, Georgia JOHN E. MILLER, Oracle Corporation, Reston, Virginia JOHN H. MOXLEY III, IOM, Korn/Ferry International, Los Angeles, California STEWART D. PERSONICK, Drexel University, Philadelphia, Pennsylvania MILLARD F. ROSE, National Aeronautics and Space Administration, Huntsville, Alabama GEORGE T. SINGLEY, Hicks & Associates, McLean, Virginia CLARENCE G. THORNTON, Army Research Laboratory (retired), Colts Neck, New Jersey JOHN D. VENABLES, Martin Marietta Laboratory (retired), Towson, Maryland ALLEN C. WARD, Ward Synthesis, Inc., Ypsilanti, Michigan Staff BRUCE A. BRAUN, Director MICHAEL A. CLARKE, Associate Director BILL CAMPBELL, Administrative Coordinator CHRIS JONES, Financial Associate REBECCA LUCCHESE, Senior Project Assistant DEANNA SPARGER, Senior Project Assistant
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Page vii Preface This report has been an extremely challenging endeavor. First, the topic of biotechnology is so dynamic that new developments are being announced almost daily. Consider that the impact of sequencing the human genome in 2000 has already translated into accelerated programs for development of new medicines and of other useful molecules. I believe, as many others do, that biotechnology will continue to develop at a rate that has not been seen since the birth of microprocessor-based personal computers. It was against this backdrop of a rapidly changing science, and an even more rapidly changing translation of science into technology, that the committee addressed the issues in this report. Second, the scope of biotechnology is expanding so fast that scientists and engineers have difficulty reconciling their perceptions of what is and isn’t included; in fact, new and important subdisciplines with linkages to future technologies, such as proteomics, have just emerged in the last few years. A third challenge has been to prepare a report that could satisfy and be understood by an audience composed of both generalists and specialists, as well as by those in the Army who must make the hard decisions on S&T priorities among all technology areas. The committee examined the basis of new technologies and the probabilities that they could have a future impact on Army capabilities. I believe the report also provides a valuable snapshot of the nature of biotechnology and how its many facets can affect the Army. Although biotechnology is a “moving target,” actions can be taken to help track the progression of new biological concepts that will lead to products with the highest potential for Army use. I wish to thank the committee members for their excellent efforts and the many hours they spent gathering, analyzing, summarizing, and interpreting information, debating the messages that this information contained, and assembling an excellent product. I would also like to thank Mr. Robert Love, study director, for assembling the committee’s findings into this report. His ability to coordinate the genesis and writing of this multidisciplinary report was essential to the success of this project. His patience, dedicated effort, insights, and disciplined approach are much appreciated. Michael R. Ladisch, chair Committee on Opportunities in Biotechnology for Future Army Applications
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Page ix Acknowledgments 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 NRC’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: Claudia Benack, ENSCO, Inc. Corale L. Brierley, NAE, Brierley Consultancy LLC R. John Collier, Harvard Medical School Joseph M. Davie, IOM, Biogen, Inc. (retired) Gary S. Fischman, University of Illinois at Chicago David K. Gifford, Massachusetts Institute of Technology John Halver, NAS, U.S. Army (retired) Larry Lehowicz, U.S. Army (retired), Quantum Research International Matthew S. Meselson, NAS, IOM, Harvard University Mehmet Sarikaya, University of Washington Phillip A. Sharp, NAS, IOM, Massachusetts Institute of Technology Joseph F. Soukup, Science Applications International 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 John C. Bailar, IOM, University of Chicago. Appointed by the National Research Council, he was 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.
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Page xi Contents EXECUTIVE SUMMARY 1 1 INTRODUCTION 7 Statement of Task, 8 Finding the Way, 9 Definition of Biotechnology, 9 Report Organization, 10 2 BIOTECHNOLOGY AND THE ARMY 11 History of Biotechnology, 11 Scope of Biotechnology, 14 Central Role of Biology, 14 Biomimetics, 14 Genomics and Proteomics, 15 3 SENSING THE BATTLEFIELD ENVIRONMENT 16 Biological Sensors, 16 Biochips, 17 Biosensor Network, 17 Assay Formats, 17 Immunossays, 17 Nucleic-Acid Assays, 18 Detection Methods, 19 Optical Sensors, 20 DNA Chips, 21 Protein Chips, 21 Sensors That Detect Proteins in Biological Samples, 22 Cells on a Chip, 23 Barriers to the Development of Portable Sensors, 23 Key Recommendations, 24 4 ELECTRONICS AND COMPUTING 25 Protein-Based Electronic Devices, 25 Bacteriorhodopsin, 25 Optical-Holographic and Three-Dimensional Memories, 27 Associative Memories and Processors, 28 Artificial Retinas, 28 Pattern-Recognition Systems, 29
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Page xii Contents Spatial Light Modulators, 30 Biomolecular Hybrids, 30 Technical Enablers and Barriers, 30 Biocomputing, 31 Biological Models, 31 DNA Computing, 32 Key Recommendations, 33 5 IN SEARCH OF NEW MATERIALS 34 Biomaterials for In Vivo Use, 34 Wound Healing, 34 Tissue Engineering, 36 Bioinspired and Hybrid Materials, 40 Biocomposites, 40 Biomineralization: Organic/Inorganic Nanocomposites, 43 Biomaterials for Clothing and Concealment, 44 Production of Biomaterials, 44 Manufacturing Trends and Barriers, 44 Key Recommendations, 45 6 REDUCING LOGISTICS REQUIREMENTS 46 Miniaturization of Biological Devices, 46 Microtechnology, 47 Microfluidic Pumping Methods and Actuators, 47 Microreaction Technologies, 48 MEMS-Based Microfluidic Systems, 48 Chip Architectures, 50 Nanotechnology, 51 Direct Readout of DNA at the Atomic Level, 51 Key Recommendation, 53 Functional Foods, 53 Genetically Engineered Foods, 54 Edible Vaccines, 54 Key Recommendations, 55 Biological Photovoltaics, 55 Photosynthesis, 55 Biomolecular Diodes, 55 Key Recommendation, 57 Renewable Resources, 57 Renewable Fuels, 57 Specialty Products, 57 Life-Support Applications, 58 Key Recommendations, 58 7 SOLDIER HEALTH AND PERFORMANCE 59 Genomics, 59 Genomics Information-Gathering Techniques, 59 Impact of Genomics on the Prevention and Treatment of Disease, 62 Prediction and Enhancement of Soldier Performance, 63 Key Recommendations, 64 Trends in Drug Development, 64 Protein Therapeutic Compounds, 65 Small-Molecule Therapeutic Compounds, 65 Countering Chemical and Biological Threats, 65
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Page xiii Contents Examples of Army-Industry Cooperation, 67 Improved Technologies for Drug Delivery, 67 Barriers to Development of Therapeutics and Vaccines, 71 Key Recommendations, 72 8 CONCLUSIONS AND RECOMMENDATIONS 73 Biotechnology Development Areas, 73 Overarching Conclusions, 73 Priorities for Research, 75 Barriers Not Amenable to Research, 77 REFERENCES 79 APPENDIXES A BIOGRAPHICAL SKETCHES OF COMMITTEE MEMBERS 87 B MEETINGS AND ACTIVITIES 90 C CHEMICAL SENSING USING MEMS DEVICES 92 D VACCINATION 96
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Page xv Figures, Tables, and Boxes FIGURES 2-1 Timeline of significant events in biotechnology, 13 4-1 Simplified protein structures, 26 4-2 Protein-based, 3-D memory, 27 4-3 Fourier transform holographic (FTH) associative memory, 29 5-1 Dolly the sheep, 37 5-2 Generation of chimeric mouse embryos, 38 5-3 Scanning electron micrograph of a multisite, micromachined, neural-recording probe, 39 5-4 Structure of an abalone shell, 42 6-1 MEMS device for integrated DNA analysis, 49 6-2 A micromachined cantilever and tip-mounted stylus, 52 6-3 An Interdigitated cantilever and fixed reference plate, 52 6-4 Schematic and structure of a single-electron transistor for measuring electronic charge, 53 6-5 The photosynthetic apparatus of plants, 56 7-1 Drug-delivery chip, 68 7-2 Cell-transplant biocapsule, 69 C-1 Vibrating-beam vapor sensor based on surface micromachining, 92 C-2 “Micro-hot-plate” gas sensor, 93 C-3 Monolithic gas chromatography system, 94 TABLES ES-1 Prospective Army Applications, 2 ES-2 Biotechnology Development Areas, 5 1-1 Future Army Applications for Biotechnology, 9 2-1 Biotechnology Industry Statistics, 1993–1999, 14 8-1 Prospective Army Applications, 74 8-2 Biotechnology Development Areas, 76
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Page xvi BOXES 1-1 Scenario of Possible Army Applications, 8 2-1 The Polymerase Chain Reaction, 12 2-2 The Hantavirus: A Detective Story, 12 3-1 Roles of DNA, mRNA, and Proteins, 19 3-2 Micro Total Analysis Systems (MicroTAS), 20 4-1 Technical Enablers and Barriers to the Development of Biomolecular Hybrid Devices, 31 5-1 Overview of Wound Healing, 35 5-2 Determining the Structure and Function of Proteins, 41 7-1 Determining Function Through Protein Structure, 60 7-2 Single Nucleotide Polymorphisms, 61 7-3 Monoclonal Antibodies, 66 D-1 Malaria, 100