Future Biotechnology Research on the International Space Station

Task Group for the Evaluation of NASA's Biotechnology Facility for the International Space Station

Space Studies Board

Commission on Physical Sciences, Mathematics, and Applications

National Research Council

NATIONAL ACADEMY PRESS
Washington, D.C.



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Future Biotechnology Research on the International Space Station Future Biotechnology Research on the International Space Station Task Group for the Evaluation of NASA's Biotechnology Facility for the International Space Station Space Studies Board Commission on Physical Sciences, Mathematics, and Applications National Research Council NATIONAL ACADEMY PRESS Washington, D.C.

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Future Biotechnology Research on the International Space Station 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 task group responsible for the report were chosen for their special competences and with regard for appropriate balance. Support for this project was provided by Contract NASW 96013 between the National Academy of Sciences and the National Aeronautics and Space Administration. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsor. Images on the front cover: Top left: Red blood cells in a cross section of a small blood vessel in the mouse lung. Scanning electron micrograph courtesy of Jacob Bastacky, Lawrence Berkeley National Laboratory. Top right: A ligand complex, a designed, sequence-specific minor groove binding compound (Geierstanger et al., 1996). Image courtesy of David Wemmer, University of California at Berkeley. Bottom left: Nitrogen Regulatory Protein C (NtrC), a bacterial transcription factor regulated by phosphorylation (Volkman et al., 1995). Image courtesy of David Wemmer, University of California at Berkeley. Bottom right: The apicoplast is a nonphotosynthetic plastid, acquired by endosymbiosis of a eukaryotic alga and retention of the algal chloroplast. This essential organelle is found in all members of the phylum Apicomplexa, including malaria parasites and the AIDS pathogen Toxoplasma gondii (shown), providing a promising target for therapeutic drug design (Köhler et al., 1997). Electron micrograph courtesy of David Roos and Lewis Tilney, University of Pennsylvania. International Standard Book Number 0-309-06975-0 Copies of this report are available free of charge from: Space Studies Board National Research Council 2101 Constitution Avenue, NW Washington, DC 20418 Copyright 2000 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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Future Biotechnology Research on the International Space Station 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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Future Biotechnology Research on the International Space Station TASK GROUP FOR THE EVALUATION OF NASA'S BIOTECHNOLOGY FACILITY FOR THE INTERNATIONAL SPACE STATION PAUL B. SIGLER, Yale University, Chair* ADELE L. BOSKEY, Hospital for Special Surgery, New York NOEL D. JONES, Molecular Structure Corporation and Eli Lilly (retired) JOHN KURIYAN, Rockefeller University WILLIAM M. MILLER, Northwestern University MICHAEL L. SHULER, Cornell University GARY S. STEIN, University of Massachusetts Medical School ** BI-CHENG WANG, University of Georgia ELIZABETH L. GROSSMAN, Program Officer CARMELA J. CHAMBERLAIN, Senior Project Assistant * Deceased, January 11, 2000. ** Acting chair as of January 12, 2000.

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Future Biotechnology Research on the International Space Station SPACE STUDIES BOARD CLAUDE R. CANIZARES, Massachusetts Institute of Technology, Chair MARK R. ABBOTT, Oregon State University FRAN BAGENAL, University of Colorado DANIEL N. BAKER, University of Colorado ROBERT E. CLELAND, University of Washington MARILYN L. FOGEL, Carnegie Institution of Washington BILL GREEN, former member, U.S. House of Representatives JOHN H. HOPPS, JR., Morehouse College CHRISTIAN J. JOHANNSEN, Purdue University RICHARD G. KRON, University of Chicago JONATHAN I. LUNINE, University of Arizona ROBERTA BALSTAD MILLER, Columbia University GARY J. OLSEN, University of Illinois, Urbana-Champaign MARY JANE OSBORN, University of Connecticut Health Center GEORGE A. PAULIKAS, The Aerospace Corporation JOYCE E. PENNER, University of Michigan THOMAS A. PRINCE, California Institute of Technology PEDRO L. RUSTAN, JR., U.S. Air Force (retired) GEORGE L. SISCOE, Boston University EUGENE B. SKOLNIKOFF, Massachusetts Institute of Technology MITCHELL SOGIN, Marine Biological Laboratory NORMAN E. THAGARD, Florida State University ALAN M. TITLE, Lockheed Martin Advanced Technology Center RAYMOND VISKANTA, Purdue University PETER W. VOORHEES, Northwestern University JOHN A. WOOD, Harvard-Smithsonian Center for Astrophysics JOSEPH K. ALEXANDER, Director

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Future Biotechnology Research on the International Space Station COMMISSION ON PHYSICAL SCIENCES, MATHEMATICS, AND APPLICATIONS PETER M. BANKS, Veridian ERIM International, Inc., Co-chair W. CARL LINEBERGER, University of Colorado, Co-chair WILLIAM F. BALLHAUS, JR., Lockheed Martin Corp. SHIRLEY CHIANG, University of California MARSHALL H. COHEN, California Institute of Technology RONALD G. DOUGLAS, Texas A&M University SAMUEL H. FULLER, Analog Devices, Inc. JERRY P. GOLLUB, Haverford College MICHAEL F. GOODCHILD, University of California at Santa Barbara MARTHA P. HAYNES, Cornell University WESLEY T. HUNTRESS, JR., Carnegie Institution CAROL M. JANTZEN, Westinghouse Savannah River Company PAUL G. KAMINSKI, Technovation, Inc. KENNETH H. KELLER, University of Minnesota JOHN R. KREICK, Sanders, a Lockheed Martin Company (retired) MARSHA I. LESTER, University of Pennsylvania DUSA M. McDUFF, State University of New York at Stony Brook JANET L. NORWOOD, Former Commissioner, U.S. Bureau of Labor Statistics M. ELISABETH PATÉ-CORNELL, Stanford University NICHOLAS P. SAMIOS, Brookhaven National Laboratory ROBERT J. SPINRAD, Xerox PARC (retired) MYRON F. UMAN, Acting Executive Director

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Future Biotechnology Research on the International Space Station Foreword Under current NASA plans, investigations in the area of biotechnology will be a significant component of the life sciences research to be conducted on the International Space Station (ISS). They encompass work on cell science and studies of the use of microgravity to grow high-quality protein crystals. Both these subdisciplines are advancing rapidly in terrestrial laboratories, fueled by federal and industrial research budgets that dwarf those of NASA's life science program. Forging strong and fruitful connections between the space investigations and laboratory-bench biologists, a continual challenge for NASA' s life sciences program, is thus of great importance to ensuring the excellence of ISS research. This report evaluates the plan for NASA's biotechnology facility on the ISS and the scientific context that surrounds it, and makes recommendations on how the facility can be made more effective. In addition to questions about optimizing the instrumentation, the report addresses strategies for enhancing the scientific impact and improving the outreach to mainstream terrestrial biology. No major redirection of effort is called for, but collectively the specific, targeted changes recommended by the task group would have a major effect on the conduct of biotechnology research in space. The sudden death of the task group's chair, Dr. Paul Sigler of Yale University, came when this document was nearly completed. Dr. Sigler was a world-renowned scientist; indeed he was a superb example of the terrestrial biologists who need to be drawn toward NASA's research program in larger numbers. His wisdom and insight are evident throughout the report. Claude R. Canizares, Chair Space Studies Board

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Future Biotechnology Research on the International Space Station Preface This report was prepared by the Task Group for the Evaluation of NASA's Biotechnology Facility for the International Space Station (ISS) in response to a request from the National Aeronautics and Space Administration (NASA). The task group was formed to examine NASA's ongoing program on biotechnology in the microgravity environment, including the plans for relevant instrumentation to be installed on the ISS (a complete statement of task is provided in Appendix C). Previous National Research Council (NRC) reports have touched on issues related to NASA's biotechnology program and on equipment for the ISS. Microgravity Research Opportunitiesfor the 1990s (NRC, 1995) offered recommendations about promising areas of potential research for NASA's microgravity sciences program; suggestions specifically for biotechnology work were included. Future Materials Science Research on the International Space Station (NRC, 1997) looked in detail at the Space Station Furnace Facility, which was designed to support and enable materials science research on the ISS, and at NASA's priorities and project selection process for materials science research. A Strategy for Research in Space Biology and Medicine in the New Century (NRC, 1998) provides a broad survey of opportunities and priorities for NASA research in a variety of areas, including cell biology. Institutional Arrangements for Space Station Research (NRC, 1999) discusses the formation of a nongovernmental organization designed to facilitate research on the ISS. This report, Future Biotechnology Research on the International Space Station, covers both scientific and technical questions related to NASA's future plans for biotechnology research on the ISS and has a scope similar to that of the materials science report. NASA's biotechnology program consists of two distinct research areas: protein crystal growth and cell science. In the first area, NASA scientists and NASA-sponsored researchers study macromolecular crystallization processes and production of high-quality crystals in the microgravity environment. In the second area, research focuses on the study of cell and tissue culture, growth, and differentiation. The composition of the task group, which included researchers with expertise in macromolecular crystallography for structure determination, instrumentation for crystallization and X-ray diffraction, tissue engineering, and in vitro studies of cell differentiation and proliferation, reflected the dual nature of the NASA program. The task group also included a mix of scientists familiar with the constraints imposed by research in a microgravity environment and those with no previous experience in space-based experiments but with a broad-based understanding of the research communities' current issues and potential future needs. Brief biographical information about the task group members is available in Appendix B. The task group held two meetings and two site visits over the course of the study to gather information on past results of NASA's program and on future plans for utilization of the ISS for biotechnology research. The task group has provided background on the NASA biotechnology program and a discussion of the scientific goals in each field in Chapter 1. In Chapter 2, the instrumentation planned for the ISS is described, and the task group

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Future Biotechnology Research on the International Space Station comments on the equipment, on the hardware development process, and on effective use of the ISS. Finally, in Chapter 3, the task group examines NASA's approach to project selection and community outreach and offers suggestions for strengthening these processes. This study was conducted under the auspices of the NRC's Space Studies Board and its staff, and the task group acknowledges this support. The task group also would like to thank the many people from NASA and other institutions who supplied extensive background materials, hosted site visits, and provided thorough presentations. Particular recognition is due to Steve Davison at NASA headquarters, Neal Pellis at the Johnson Space Center, and Craig Kundrot and Ron Porter at the Marshall Space Flight Center.

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Future Biotechnology Research on the International Space Station Acknowledgment of Reviewers This report has been reviewed by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council's (NRC's) Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the authors and the NRC in making the 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 contents of 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 participation in the review of this report: Michael J. Bentenbaugh, Johns Hopkins University, Kenneth I. Berns, University of Florida, Shu Chien, University of California, San Diego, Howard M. Einspahr, Bristol-Myers Squibb Pharmaceutical Research Institute, Donald E. Ingber, Children's Hospital and Harvard Medical School, Kenneth H. Keller, University of Minnesota, and J. Keith Moffat, University of Chicago. Although the individuals listed above have provided many constructive comments and suggestions, responsibility for the final content of this report rests solely with the authoring task group and the NRC.

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Future Biotechnology Research on the International Space Station Contents     EXECUTIVE SUMMARY   1  1   BACKGROUND AND SCIENTIFIC SCOPE OF NASA PROGRAMS   10      Introduction,   10      Protein Crystal Growth,   11      The Significance of Crystallographic Resolution Limits,   11      Goals and History of the NASA Protein Crystal Growth Effort,   12      Results to Date: Examples of Successful Experiments and the Importance of Defining Controls,   13      Potential Areas of Future Impact,   15      Potential Benefits of the Space Station Platform,   17      Potential for Interest from Commercial Entities,   18      Cell Science,   18      Goals and Potential Impacts of the NASA Cell Science Effort,   18      Experimental Design and Instrumentation,   21      Requirements for Interprogrammatic Coordination Within NASA,   22  2   INSTRUMENTATION   23      Logistics for Using the International Space Station as a Biotechnology Research Platform,   23      Protein Crystal Growth,   24      The Hardware Development Process,   24      Key Characteristics of Protein Crystal Growth Hardware on the ISS,   25      The X-ray Crystallography Facility,   26      Cell Science,   27      Cell and Tissue Culture Hardware,   28      Experiment Management,   32      Storage, Transport, and Throughput of Samples,   35      Overall Volume Allotment for Biotechnology Research on the ISS,   36

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Future Biotechnology Research on the International Space Station  3   SELECTION AND OUTREACH   38      Selection Process, Outreach Efforts, and Communication Among Program Participants,   38      Improving the Dissemination of NRAs and NASA Program Results,   38      Improving the Selection Process,   40      Improving Connections to Relevant Communities and Attracting the Best Science,   41      Coordination: Investigators and Operations Personnel,   42      Protein Crystal Growth,   43      The Guest Investigator Program,   43      Funding Research on Biologically Challenging Problems,   44      Cell Science,   46      Cooperation with NASA's Life Sciences Division and with Other Federal Agencies,   46      Resource Management and Communication in Times of Crisis,   46     BIBLIOGRAPHY   48     APPENDIXES       A  Hardware Available or in Development and Schedule for Biotechnology Research on the International Space Station   53      Hardware for Protein Crystal Growth in Space,   53      Hardware for Cell Science in Space,   58      Schedule,   61     B  Biographical Sketches of Task Group Members   62     C  Statement of Task   64     D  Glossary   65     E  Acronyms and Abbreviations   68

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Future Biotechnology Research on the International Space Station This report is dedicated to the memory of Professor Paul B. Sigler (1934 – 2000) a distinguished scholar and researcher whose leadership and insight made him a vital contributor to this report.

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