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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/Grant No. 1 R13 RR11835 between the National Academy of Sciences and the National Center for Research Resources, National Institutes of Health, Department of Health and Human Services. 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.
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Library of Congress Cataloging-in-Publication Data
Biomedical Models and Resources: Current Needs and Future Opportunities
International Standard Book Number 0-309-06035-4
Library of Congress Catalog Card Number 97-81454
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COMMITTEE ON NEW AND EMERGING MODELS IN BIOMEDICAL AND BEHAVIORAL RESEARCH
Muriel T. Davisson (Chair),
The Jackson Laboratory, Bar Harbor, Maine
Stephen W. Barthold,
University of California, Davis, California
Bennett Dyke,
Southwest Foundation for Biomedical Research, San Antonio, Texas
Roger T. Hanlon,
Marine Biological Laboratory, Woods Hole, Massachusetts
Robert Russell,
Harlan Sprague Dawley, Inc., Indianapolis, Indiana
Philip A. Wood,
University of Alabama, Birmingham, Alabama
Staff
Ralph Dell, Director
Thomas Wolfle, Study Director
Kathleen Beil, Project Assistant
The Institute for Laboratory Animal Research (ILAR), formerly known as the Institute of Laboratory Animal Resources, was founded in 1952 under the auspices of the National Research Council. A component of the Commission on Life Sciences, ILAR develops guidelines and disseminates information on the scientific, technological, and ethical use of animals and related biological resources in research, testing, and education. ILAR promotes high-quality, humane care of animals and the appropriate use of animals and alternatives. ILAR functions within the mission of the National Academy of Sciences as an adviser to the federal government, the biomedical research community, and the public.
INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL
John VandeBerg (Chair),
Southwest Foundation for Biomedical Research, San Antonio, Texas
Christian R. Abee,
Department of Comparative Medicine, University of South Alabama, Mobile, Alabama
Muriel T. Davisson,
The Jackson Laboratory, Bar Harbor, Maine
Bennett Dyke,
Southwest Foundation for Biomedical Research, San Antonio, Texas
Gerald F. Gebhart,
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa
James W. Glosser,
Massillon, Ohio
Margaret Landi,
Department of Laboratory Animal Science, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania
Charles R. McCarthy,
Kennedy Institute of Ethics, Georgetown University, Washington, DC
Robert J. Russell,
Harlan Sprague Dawley, Inc., Indianapolis, Indiana
Richard C. Van Sluyters,
School of Optometry, University of California, Berkeley, California
John G. Vandenbergh, Professor,
Department of Zoology, North Carolina State University, Raleigh, North Carolina
Peter A. Ward,
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan
Tom Pollard, Ex Officio, Chairman,
Commission on Life Sciences, President, Salk Research Institute, La Jolla, California
ILAR Staff:
Ralph Dell, Director
Thomas Wolfle, Study Director
Kathleen Beil, Project Assistant
Carol Rozmiarek, Research Assistant
Susan Vaupel, Managing Editor, ILAR Journal
COMMISSION ON LIFE SCIENCES
Thomas D. Pollard (Chair),
The Salk Institute for Biological Studies, La Jolla, California
Frederick R. Anderson,
Cadwalader, Wickersham & Taft, Washington, DC
John C. Bailar, III,
University of Chicago, Illinois
Paul Berg,
Stanford University, Stanford, California
Joanna Burger,
Rutgers University, Piscataway, New Jersey
Sharon L. Dunwoody,
University of Wisconsin, Madison
John L. Emmerson,
Eli Lilly and Co. (Ret.), Indianapolis, Indiana
Neal L. First,
University of Wisconsin, Madison, Wisconsin
Ursula W. Goodenough,
Washington University, St. Louis, Missouri
Henry W. Heikkinen,
University of Northern Colorado, Greeley, Colorado
Hans J. Kende,
Michigan State University, East Lansing, Michigan
Cynthia J. Kenyon,
University of California, San Francisco, California
David M. Livingston,
Dana-Farber Cancer Institute, Boston, Massachusetts
Thomas E. Lovejoy,
Smithsonian Institution, Washington, DC
Donald R. Mattison,
University of Pittsburgh, Pennsylvania
Joseph E. Murray,
Harvard University, Wellesley Hills, Massachusetts
Edward E. Penhoet,
Chiron Corporation, Emeryville, California
Malcolm C. Pike,
Norris/USC Comprehensive Cancer Center, Los Angeles, California
Jonathan M. Samet,
The Johns Hopkins University, Baltimore, Maryland
Charles F. Stevens,
The Salk Institute for Biological Studies, La Jolla, California
John L. VandeBerg,
Southwest Foundation for Biomedical Research, San Antonio, Texas
Staff
Paul Gilman, Executive Director
Preface
Models and model systems are a critical component of biomedical research aimed at improving human health. They include living animals of many taxa, cells and cultures, and computer and mathematical simulations, and they provide valuable surrogates for experimental research that cannot be carried out on human beings. The detailed understanding of the human genome and some model organisms' genomes achieved with advances in genome technology have opened wide the door for research to understand the function of genes and to use that understanding for disease prevention and therapy. Models will be more important than ever for functional genomics (the study of the behavior and physiology of genes) for research on the complex disease systems that remain to be conquered, and for preclinical testing of preventive or therapeutic approaches. The plethora of possibilities for developing model systems and doing research with them will always exceed the projected levels of funding available from the National Institutes of Health (NIH); that fact led the NIH National Center for Research Resources (NCRR) to ask the National Research Council for this report.
The Comparative Medicine Program of NCRR has played a strong role in the development and support of biologic models. To help assist in continuing this role, NCRR sought guidance for setting funding priorities. Specifically, NCRR asked that the NRC identify the models and technologies necessary to support biomedical research in the most rapidly advancing fields over the next 5–10 years, NCRR's role in facilitating model and technology development, and strategies that NCRR might use in allocating scarce resources to competing needs in model and technology development and maintenance. This report attempts to provide that guidance through an assessment of the opportunities and needs for model development and use.
Although the committee bears full responsibility for the content of the report, we would be remiss if we did not acknowledge the assistance of the many others who contributed their time, expertise, and advice. A workshop on biological models, held in Washington, DC, on 11–12 December 1997, was organized to address the subject through three approaches—scientific disciplines, overriding issues that affect many scientific disciplines, and types of biologic models (the agenda and list of participants are provided in Appendix B). The workshop was attended by 20 participants and an equal number of discussants, including representatives of NCRR, speakers who summarized critical components of the report and led discussions, breakout group leaders, and participants who developed, for the committee, their recommendations. The committee found the process extremely informative and hopes that all those people will find this report a suitable expression of its appreciation.
A survey was developed and distributed through the directors of the categorical NIH institutes to intramural and extramural scientists who receive NIH funding and who use biologic models. The survey was also sent to the directors of major academic biomedical research institutions for dissemination to key investigators in their institutions and disseminated electronically through the Mouse Genome Informatics and
Comparative Medicine bulletin boards. The survey (attached as Appendix A) sought to characterize important research fields of the future, models and technologies that would be needed to support that research, and the proper role of NCRR. We are indebted to those who took time to complete the survey and provide us with their thoughtful comments.
The report also drew information of the scientific literature, related NRC reports on biologic models and the sharing them among scientists, NCRR's Scientific Forum (September 1997), and NCRR's own survey conducted through the Federal Register (62:4781-2).
This report has been reviewed 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 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 content 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:
Franklin D. Costantini, Columbia University, New York, NY
John C. Donovan, Rhone-Poulenc Rorer, Collegeville, PA
James Fox, Massachusetts Institute of Technology, Cambridge, MA
Alan M. Goldberg, Johns Hopkins University, Baltimore, MD
John E. Halver, University of Washington, Seattle
Leland H. Hartwell, Fred Hutchinson Cancer Research Center, Seattle, WA
Alan Hillyard, Base4 Bioinformatics, Mississauga, Ontario
Cynthia Kenyon, University of California, San Francisco
Theodore W. Kurtz, University of California, San Francisco
John J. McGlone, Texas Tech University, Lubbock
Daniel Pomp, University of Nebraska, Lincoln
Joseph E. Wagner, University of Missouri, Columbia
Peter A. Ward, University of Michigan Medical School, Ann Arbor
John L. VandeBerg, Southwest Foundation for Biomedical Research, San Antonio, TX
While 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.
To the committee, reviewers, and staff, I extend my deepest appreciation. Members of the committee devoted weekends and tireless energy to meet short deadlines. To the reviewers, who also worked under short deadline and whose efforts greatly improved the science and comprehension of our report, I am most appreciative. The value of this report to NIH and biomedical science in general is a measure of their effort.
I appreciate the guidance and support provided by the Institute for Laboratory Animal Research (ILAR) staff throughout. Kathleen Beil provided timely and important communications to the committee and workshop participants in arranging travel and
lodging and in disseminating and receiving the survey. Regis Krah developed the survey instrument and assisted in the analysis. Ralph Dell's persistent nudging to meet deadlines and to stay focused when the topic seemed to lack focus and his management of the review and publication were of inestimable value. Norman Grossblatt's editing made the report eminently more readable, for which all readers will be appreciative. And, finally, I appreciate working with Tom Wolfle, who assisted in numerous ways throughout the study, as well as in the development of the report.
Errors of omission or commission should be communicated to ILAR, NAS 347, National Research Council, 2101 Constitution Avenue, Washington, DC 20418.
Muriel Davisson, Chair
Committee on New and Emerging Models in Biomedical and Behavioral Research