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.

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