International Perspectives

THE FUTURE OF NONHUMAN PRIMATE RESOURCES

PROCEEDINGS OF THE WORKSHOP HELD APRIL 17–19, 2002

Institute for Laboratory Animal Research

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
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International Perspectives: The Future of Nonhuman Primate Resources International Perspectives THE FUTURE OF NONHUMAN PRIMATE RESOURCES PROCEEDINGS OF THE WORKSHOP HELD APRIL 17–19, 2002 Institute for Laboratory Animal Research NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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International Perspectives: The Future of Nonhuman Primate Resources THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 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 Grant No. RR11611 between the National Academy of Sciences and the National Institutes of Health. Other contributions were from GlaxoSmithKline, Association of Primate Veterinarians, and Pfizer. 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 0-309-08945-X (Book) International Standard Book Number 0-309-51723-0 (PDF) Additional copies of this report are available from the National Academies Press, 500 Fifth Street, 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 2003 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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International Perspectives: The Future of Nonhuman Primate Resources THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine 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. Wm. 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. Harvey V. Fineberg 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. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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International Perspectives: The Future of Nonhuman Primate Resources INTERNATIONAL PERSPECTIVES: THE FUTURE OF NONHUMAN PRIMATE RESOURCES PROGRAM COMMITTEE John L VandeBerg, PhD (Chair), Southwest Foundation for Biomedical Research, San Antonio, Texas Christian R. Abee, DVM, University of South Alabama, Mobile, Alabama Janet C. Gonder, DVM, PhD, Consultant, Pinehurst, North Carolina Hilton J. Klein, VMD, Merck Research Laboratories, West Point, Pennsylvania William R. Morton, VMD, Washington National Primate Research Center, University of Washington, Seattle, Washington Emilie F. Rissman, PhD, University of Virginia, Charlottesville, Virginia William S. Stokes, DVM, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina John G. Vandenbergh, PhD, North Carolina State University, Raleigh, North Carolina Staff Joanne Zurlo, PhD, Director, Institute for Laboratory Animal Research Charlotte Kirk Baer, MS, Director, Board on Agriculture and Natural Resources Marsha Barrett, Project Assistant Kathleen Beil, Administrative Assistant Jennifer Obernier, Program Officer Susan Vaupel, Editor

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International Perspectives: The Future of Nonhuman Primate Resources INSTITUTE FOR LABORATORY ANIMAL RESEARCH COUNCIL Peter A. Ward (Chair), Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan Stephen W. Barthold, Center for Comparative Medicine, University of California, Davis, California Rosemary W. Elliott, Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York Michael F. Festing, MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom Janet C. Gonder, Pinehurst, North Carolina Coenraad F.M. Hendriksen, Central Animal Laboratories, National Institute of Public Health and the Environment, Bilthoven, Netherlands Jay R. Kaplan, Department of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina Hilton J. Klein, Department of Laboratory Animal Resources, Merck Research Laboratories, West Point, Pennsylvania William Morton, Washington National Primate Research Center, University of Washington, Seattle, Washington Randall J. Nelson, Department of Anatomy and Neurobiology, University of Tennessee, Memphis, Tennessee Emilie F. Rissman, Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia Lilly-Marlene Russow, Department of Philosophy, Purdue University, West Lafayette, Indiana William S. Stokes, Animal and Alternative Resources, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina Michael K. Stoskopf, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina Thomas Wolfle, Cambridge, Maryland Staff Joanne Zurlo, Director Marsha Barrett, Senior Project Assistant Kathleen Beil, Administrative Assistant Ralph Dell, Associate Director Jennifer Obernier, Study Director Susan Vaupel, Managing Editor, ILAR Journal

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International Perspectives: The Future of Nonhuman Primate Resources Preface Nonhuman primates (NHP) continue to play an important role in the research of many human diseases such as malaria and AIDS. As long as NHP are needed for biomedical research, it is essential that suppliers, users and transporters of these animals work together to establish the best standards of characterization and maintenance to ensure that they are treated humanely, used efficiently and that data obtained from experiments on NHP are scientifically useful. Indeed, the harmonization of standards for NHP should allow for effective reproducibility among laboratories throughout the world. In addition, since NHP resources are limited, it is necessary to ensure that adequate conservation practices are considered, and that the quality of the animals used for research is high. Characterization of the genetics of NHP promises to provide valuable information that may impact the potential use of some species for certain types of studies. For example, with the escalating use of rhesus macaques for AIDS research, it has become important to further characterize the genetic basis of lentiviral infections. In addition, since NHP are used as models for human diseases, knowledge of the genetics will assist researchers in recognizing homology between NHP and human genes as well as give insights into how interindividual variability can contribute to prediction of risk for certain diseases. The microbiological status of NHP is also critical to research outcomes in these animals as well as to the occupational health and safety of those who work with them. Increased efforts have been initiated to create

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International Perspectives: The Future of Nonhuman Primate Resources specific pathogen-free (SPF) macaque research colonies that have been selectively screened for important simian viruses. In addition to SPF colonies, international standardization of assays utilized for virological assessment of NHP must be addressed. Finally, there is a crisis with regard to transportation of NHP. Most national and international airline carriers now refuse to transport NHP and, consequently, research and breeding institutions in the United States have had to rely on one of the Chinese carriers for this purpose. In addition to the dearth of transportation sources, there are duplications of national and international regulations for international transport of research animals that must be addressed with the expectations that recommendations for consolidation will be sought. All of these issues concern scientists, veterinarians and funding authorities from countries that are major users of nonhuman primates for research as well as those from countries that produce and supply these animals. Many of those in the scientific community who direct or support NHP resources or who use these animals for research had expressed a need for addressing these issues on an international level. The Institute for Laboratory Animal Research, within the National Academies, took advantage of its unique position as a focal point for laboratory animal research issues both in the United States and internationally to organize and host a much needed and important workshop. Participants from all over the world gathered in Washington, DC, to discuss critical issues concerning NHP resources. The proceedings from this workshop are reported in the pages of this publication.

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International Perspectives: The Future of Nonhuman Primate Resources Contents KEYNOTE SPEAKER   1     Primate Priorities—An International Perspective John P. Hearn   3 SESSION 1: CONSERVATION AND SUPPLY, PART 1   11     Sustainable Utilization of Kenyan Nonhuman Primates for Biomedical and Conservation Research Jason M. Mwenda   13     Supply and Use of Nonhuman Primates in Biomedical Research: A South African Perspective Jürgen Seier   16     Sustainable Primate Resources Through SPF Breeding Programs in Indonesia Joko Pamungkas and Dondin Sajuthi   20     Use of Nonhuman Primates in Biomedical Research in India: Current Status and Future Prospects A. J. Rao   21     Initiative for Primate Resources, Biomedical Research, and Conservation in Nepal Mukesh K. Chalise   29     Chinese Primate Status and Primate Captive Breeding for Biomedical Research in China Zhiyong Fan and Yanling Song   36

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International Perspectives: The Future of Nonhuman Primate Resources     The Breeding of Naturally Occurring B Virus-free Cynomolgus Monkeys (Macaca fascicularis) on the Island of Mauritius Mary Ann Stanley   46     Primates for 21st Century Biomedicine: The St. Kitts Vervet (Chlorocebus aethiops, SK) Frank Ervin and Roberta Palmour   49 SESSION 1:   PANEL DISCUSSION   54 SESSION 2: CONSERVATION AND SUPPLY, PART 2   61     Nonhuman Primates in Preclinical Research: The EU Situation Gerhard Hunsmann   63     Providing Investigators and Vaccine Producers with Laboratory Primates in the Russian Federation Boris A. Lapin   69     Nonhuman Primate Resource Needs: A Moving Target Jerry Robinson and Greg Beattie   72     Center for the Breeding and Conservation of Primates of the Peruvian Primatology Project Enrique Montoya   81 SESSION 2:   PANEL DISCUSSION   91 SESSION 3: NUTRIENT REQUIREMENTS OF NONHUMAN PRIMATES   97     Nutrient Requirements of Nonhuman Primates Committee on Animal Nutrition, Board on Agriculture and Natural Resources, NRC   99 SESSION 4: GENETICS   105     Nonhuman Primates in Genetic Research on Common Diseases John L. VandeBerg and Sarah Williams-Blangero   107     Genetic Considerations in the Management of Captive Nonhuman Primates Sarah Williams-Blangero and John L. VandeBerg   114     Influence of MHC Gene Products on Immune Control of AIDS Virus Infection: Consideration for Use in Nonhuman-Primate Resources Thomas C. Friedrich and David I. Watkins   122

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International Perspectives: The Future of Nonhuman Primate Resources     Indian- and Chinese-origin Rhesus Macaques for AIDS-related Research: Comparison of Vaginal Transmission Efficiency of Simian Immunodeficiency Virus (SIV), Viral Loads, and Virus-specific Antibody Responses Marta L. Marthas, Ding Lu, M. C. T. Penedo, Andrew G. Hendrickx, and Christopher J. Miller   128 SESSION 4:   PANEL DISCUSSION   131 SESSION 5: MICROBIOLOGY   141     Microbiological Problems in Nonhuman Primates Used in Research Gary Baskin   143     Nonhuman Primate Importation and Quarantine: United States, 1981-2001 Tom DeMarcus   149     Diagnosis of Tuberculosis in Nonhuman Primates S.L. Motzel, R.D. Schachner, R.W. Kornegay, M.A. Fletcher, B. Kanaya, J.A. Gomez, D.T-W Ngai, W.J. Pouch, M.V. Washington, L.A. Handt, J.L. Wagner, and H.J. Klein   156     Specific Pathogen-free Rhesus Macaques Keith Mansfield   160 SESSION 5:   PANEL DISCUSSION   174 SESSION 6: TRANSPORTATION   179     OLAW Perspective on Transportation of Nonhuman Primates Nelson Garnett   181     Transportation of Primates and the Animal Welfare Act Jerry DePoyster   183     International Transportation of Nonhuman Primates: US Fish and Wildlife Service Perspective Michael Kreger and Monica Farris   187     The Toronto Zoo William A. Rapley   193     Chinese Macaques—East Meets West C. K. Hsu and Ruishen Jia   197 SESSION 6:   PANEL DISCUSSION   200 SESSION 7: UNRESOLVED ISSUES   207 SESSION 7:   PANEL DISCUSSION   209

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International Perspectives: The Future of Nonhuman Primate Resources CONFERENCE SUMMARY William R. Morton   229 APPENDIX A: INTERNATIONAL PERSPECTIVES: THE FUTURE OF NONHUMAN PRIMATE RESOURCES PROGRAM   237 APPENDIX B: GLOSSARY OF ABBREVIATIONS   243 APPENDIX C: COMMITTEE BIOS   247