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Review of NASA’s Biomedical Research Program Review of NASA’s Biomedical Research Program Committee on Space Biology and Medicine Space Studies Board Commission on Physical Sciences, Mathematics, and Applications National Research Council NATIONAL ACADEMY PRESS Washington, D.C.
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Review of NASA’s Biomedical Research Program 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. 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 report are those of the authors and do not necessarily reflect the views of the sponsor. Copyright 2000 by the National Academy of Sciences. All rights reserved. Copies of this report are available from: Space Studies Board National Research Council 2101 Constitution Avenue, N.W. Washington, D.C. 20418 Printed in the United States of America
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Review of NASA’s Biomedical Research Program 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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Review of NASA’s Biomedical Research Program COMMITTEE ON SPACE BIOLOGY AND MEDICINE MARY JANE OSBORN, University of Connecticut Health Center, Chair NORMA M. ALLEWELL, Harvard University JAY C. BUCKEY, JR., Dartmouth-Hitchcock Medical Center LYNETTE JONES, Massachusetts Institute of Technology ROBERT A. MARCUS, VA Palo Alto Health Care System LAWRENCE A. PALINKAS, University of California at San Diego KENNA D. PEUSNER, George Washington University Medical Center STEVEN E. PFEIFFER, University of Connecticut Medical School DANNY A. RILEY, Medical College of Wisconsin RICHARD SETLOW, Brookhaven National Laboratory GERALD SONNENFELD, Morehouse School of Medicine T. PETER STEIN, University of Medicine and Dentistry of New Jersey JUDITH L. SWAIN, Stanford University School of Medicine Staff SANDRA J. GRAHAM, Study Director ANNE K. SIMMONS, Senior Program Assistant
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Review of NASA’s Biomedical Research Program 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 CHRIS J. JOHANNSEN, Purdue University ANDREW H. KNOLL,* Harvard University RICHARD G. KRON, University of Chicago JONATHAN I. LUNINE, University of Arizona ROBERTA BALSTAD MILLER, Columbia University GARY J. OLSEN, University of Illinois at Urbana-Champaign MARY JANE OSBORN, University of Connecticut Health Center GEORGE A. PAULIKAS, The Aerospace Corporation (retired) 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 * Former member.
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Review of NASA’s Biomedical Research Program 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 Corporation SHIRLEY CHIANG, University of California at Davis 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 of Washington 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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Review of NASA’s Biomedical Research Program Preface In 1998, the Committee on Space Biology and Medicine (CSBM) completed a comprehensive report, A Strategy for Research in Space Biology and Medicine in the New Century (National Academy Press, Washington, D.C., 1998), that reviewed the status of space life sciences research in all of the disciplines funded by the National Aeronautics and Space Administration’s (NASA’s) life sciences program and laid out a detailed strategy for research during the International Space Station era. In that report, numerous biomedical research questions related to astronaut health and safety were identified as critical to NASA’s long-duration flight program. Shortly after the report’s publication, NASA requested that CSBM assess the agency’s entire current program in biomedical research, both intramural and extramural, in light of the recommendations of the Strategy report. After a series of discussions with NASA’s Life Sciences Division, the committee began reviewing NASA’s entire biomedical research program in December 1998 in order to assess the degree to which the program seemed likely to meet research needs over the next 10 years. The research priorities given in the 1998 Strategy report were to be used as a point of departure when considering future needs and priorities. Specifically, the committee agreed to examine the relationship between intramural and extramural biomedical research activities sponsored by the agency and to review the content and program organization of both. The roles of the NASA Specialized Centers of Research and Training and the National Space Biomedical Research Institute, in the biomedical program, were also to be examined. The review was to cover all NASA biomedical research activities, including those currently conducted in conjunction with operational medical and aerospace medicine programs. Some of the specific points the committee considered in developing its recommendations were the following: The balance of discipline areas emphasized in the current program; The degree to which studies of fundamental cellular and physiological mechanisms are addressed in each discipline program; The balance between ground and flight investigations;
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Review of NASA’s Biomedical Research Program NASA plans for the development and validation of physiological and psychological countermeasures; Plans for epidemiology and monitoring; Plans for validation of animal models; and The extent to which programs are supporting new, advanced technologies and methodologies. The committee made use of a variety of sources in gathering information for this study. Documents available to the committee included FY 1998 and FY 1999 life sciences budget information, the 1998 and 1999 Life Sciences Task Book, the first annual report of the National Space Biomedical Research Institute (NSBRI) and 1998 and 1999 program budget information, the Countermeasure Evaluation and Validation Project Plan, the International Space Station Medical Operations Requirements Document and relevant sections of the Astronaut Medical Evaluation Requirements Document, and NASA Research Announcements for 1998 and 1999. In addition, the Proceedings of the First Biennial Biomedical Investigators’ Workshop, held in January 1999, provided valuable current information. In addition to receiving briefings from NASA and NSBRI spokespersons, the committee as a whole held one meeting at Johnson Space Center, and a subgroup visited Ames Research Center to learn about the activities at that site relevant to biomedical research. These visits provided a vast amount of useful information, and the committee wishes to express its considerable appreciation of the hard work that went into the centers’ preparation for the visits and the thoroughness and candor of the briefings and discussions.
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Review of NASA’s Biomedical Research Program 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. The committee wishes to thank the following individuals for their participation in the review of this report: James Bagian, Environmental Protection Agency, Norman Bell, Medical University of South Carolina, Robert A. Greenes, Harvard Medical School, Robert Langer, Massachusetts Institute of Technology, Robert Nerem, Georgia Institute of Technology, Gary Paige, University of Rochester, and Edward Schultz, University of Wisconsin Medical School. 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 committee and the NRC.
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Review of NASA’s Biomedical Research Program Contents EXECUTIVE SUMMARY 1 1 INTRODUCTION 7 Reference, 10 2 SENSORIMOTOR INTEGRATION 11 Introduction, 11 NASA’s Current Research Program in Sensorimotor Integration, 12 Programmatic Balance, 15 Balance of Subdiscipline Areas, 15 Balance of Ground and Flight Investigations, 15 Emphasis Given to Fundamental Mechanisms, 15 Utilization and Validation of Animal Models, 15 Development and Validation of Countermeasures, 16 Epidemiology and Monitoring, 17 Support of Advanced Technologies, 17 Summary, 18 Bibliography, 18 3 BONE PHYSIOLOGY 19 Introduction, 19 NASA’s Current Research Program in Bone Physiology, 20 Basic Research, 20 Animal Studies, 21 Human Studies, 21
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Review of NASA’s Biomedical Research Program Programmatic Balance, 22 Balance of Subdiscipline Areas, 22 Balance of Ground and Flight Investigations, 22 Emphasis Given to Fundamental Mechanisms, 22 Utilization and Validation of Animal Models, 22 Development and Validation of Countermeasures, 23 Epidemiology and Monitoring, 23 Support of Advanced Technologies, 24 Summary, 25 Bibliography, 25 4 MUSCLE PHYSIOLOGY 26 Introduction, 26 NASA’s Current Research Program in Muscle Physiology, 27 Programmatic Balance, 28 Balance of Subdiscipline Areas, 28 Balance of Ground and Flight Investigations, 28 Emphasis Given to Fundamental Mechanisms, 28 Utilization and Validation of Ground and Animal Models, 29 Development and Validation of Countermeasures, 29 Epidemiology and Monitoring, 30 Plans for Monitoring Crew Health and Fitness on the International Space Station, 30 Support of Advanced Technologies, 31 Summary, 31 References, 32 5 CARDIOVASCULAR AND PULMONARY SYSTEMS 33 Introduction, 33 NASA’s Current Research Program in Cardiovascular and Pulmonary Systems, 34 Programmatic Balance, 35 Balance of Subdiscipline Areas, 35 Balance of Ground and Flight Investigations, 35 Emphasis Given to Fundamental Mechanisms, 36 Utilization and Validation of Animal Models, 36 Development and Validation of Countermeasures, 36 Epidemiology and Monitoring, 37 Orthostatic Intolerance, 38 Cardiac Atrophy, 38 Arrhythmias, 38 Pulmonary, 38 Support of Advanced Technologies, 39 Summary, 39 Bibliography, 39
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Review of NASA’s Biomedical Research Program 6 ENDOCRINOLOGY AND NUTRITION 40 Introduction, 40 NASA’s Current Research Program in Endocrinology and Nutrition, 40 Programmatic Balance, 42 Balance of Subdiscipline Areas, 42 Balance of Ground and Flight Investigations, 43 Emphasis Given to Fundamental Mechanisms, 43 Utilization and Validation of Ground and Animal Models, 43 Development and Validation of Countermeasures, 44 Epidemiology and Monitoring, 45 Support of Advanced Technologies, 45 Summary, 45 References, 45 7 IMMUNOLOGY AND MICROBIOLOGY 46 Introduction, 46 NASA’s Current Research Program in Immunology and Microbiology, 47 Programmatic Balance, 48 Balance of Subdiscipline Areas, 48 Balance of Ground and Flight Studies, 48 Emphasis Given to Fundamental Mechanisms, 48 Utilization and Validation of Animal Models, 49 Development and Validation of Countermeasures, 49 Epidemiology and Monitoring, 49 Support of Advanced Technologies, 50 Summary, 50 References, 50 8 RADIATION BIOLOGY 51 Introduction, 51 NASA’s Current Research Program in Radiation Biology, 52 Programmatic Balance, 54 Balance of Subdiscipline Areas, 54 Balance of Ground and Flight Investigations, 55 Emphasis Given to Fundamental Mechanisms, 55 Utilization and Validation of Animal Models, 55 Development and Validation of Countermeasures, 56 Epidemiology and Monitoring, 56 Support of Advanced Technologies, 56 Summary, 57 References, 57 9 BEHAVIOR AND PERFORMANCE 58 Introduction, 58 NASA’s Current Research Program in Behavior and Performance, 59
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Review of NASA’s Biomedical Research Program Programmatic Balance, 62 Balance of Subdiscipline Areas, 62 Balance of Ground and Flight Investigations, 62 Emphasis Given to Fundamental Mechanisms, 63 Utilization and Validation of Animal Models, 63 Development and Validation of Countermeasures, 64 Epidemiology and Monitoring, 66 Support of Advanced Technologies, 66 Summary, 67 References, 67 10 SETTING PRIORITIES IN RESEARCH 68 Loss of Weight-bearing Bone and Muscle, 68 Vestibular Function, the Vestibulo-ocular Reflex, and Sensorimotor Integration, 69 Orthostatic Intolerance Upon Return to Earth Gravity, 69 Radiation Hazards, 70 Physiological Effects of Stress, 70 Psychological and Social Issues, 70 References, 71 11 PROGRAMMATIC AND POLICY ISSUES 72 International Space Station: Utilization and Facilities, 72 Countermeasure Testing and Validation, 73 Controlled Trials in Space, 74 Use of Historical Data, 75 Empirical Observation, 75 Operational and Research Use of Biomedical Data, 76 The Role of Medical Operations in Human Research and Countermeasure Validation, 76 Effects of Spaceflight on Drug Efficacy and Pharmacokinetics, 77 Availability of Stored Clinical Samples, 77 Data Archive, 77 Science Policy Issues, 78 Support of Operational Research, 78 International Cooperation, 78 Integration of Research Activities, 79 References, 80 APPENDIXES A A Strategy for Research in Space Biology and Medicine in the New Century, Executive Summary 83 B Letter of Request from NASA 100 C Glossary 103 D Acronyms 107 E Biographies of Committee Members 110