Nonhuman Primate Models in Biomedical Research: State of the Science and Future Needs (2023)
Chapter: Front Matter
Consensus Study Report
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by a contract between the National Academy of Sciences and the National Institutes of Health (Contract No. HHSN263201800029I/75N98021F00018). Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-69936-5
International Standard Book Number-10: 0-309-69936-3
Digital Object Identifier: https://doi.org/10.17226/26857
This publication is available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2023 by the National Academy of Sciences. National Academies of Sciences, Engineering, and Medicine and National Academies Press and the graphical logos for each are all trademarks of the National Academy of Sciences. All rights reserved.
Printed in the United States of America.
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2023. Nonhuman primate models in biomedical research: State of the science and future needs. Washington, DC: The National Academies Press. https://doi.org/10.17226/26857.
The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.
The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president.
The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.
The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.
Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.
Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.
Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.
Rapid Expert Consultations published by the National Academies of Sciences, Engineering, and Medicine are authored by subject-matter experts on narrowly focused topics that can be supported by a body of evidence. The discussions contained in rapid expert consultations are considered those of the authors and do not contain policy recommendations. Rapid expert consultations are reviewed by the institution before release.
For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.
COMMITTEE ON THE STATE OF THE SCIENCE AND FUTURE NEEDS FOR NONHUMAN PRIMATE MODEL SYSTEMS1
KENNETH S. RAMOS (Chair), Alkek Chair of Medical Genetics, The Texas A&M University System, Executive Director, Texas A&M Institute of Biosciences and Technology, Associate Vice President for Research, Texas A&M University Health Science Center, Assistant Vice Chancellor for Health Services
CHRISTIAN ABEE, Professor Emeritus, Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center
ASHUTOSH AGARWAL, Associate Professor of Biomedical Engineering, Director of Engineering and Applied Physics, Desai Sethi Urology Institute, University of Miami, Florida
SZCZEPAN BARAN, Chief Scientific Officer, VeriSIM Life
ELIZA BLISS-MOREAU, Professor, Department of Psychology, Core Scientist, California National Primate Research Center, University of California, Davis
RICARDO CARRION JR., Professor and Program Co-Lead, Disease Intervention & Prevention, Texas Biomedical Research Institute
J. MARK CLINE, Professor of Pathology/Comparative Medicine and Radiation Oncology, Wake Forest University School of Medicine
MYRTLE DAVIS, Scientific Vice President, Discovery Toxicology, Bristol Meyers Squibb
ASGERALLY FAZLEABAS, University Distinguished Professor and Associate Chair of Research, Department of Obstetrics, Gynecology and Reproductive Biology, Director of the Center for Women’s Health Research, Michigan State University
MELANIE GRAHAM, Robert and Katherine Goodale Chair in Minimally Invasive Surgery, Professor of Surgery, Department of Surgery, Medical School and Professor of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota
KELLY A. METCALF PATE, Dorothy W. Poitras Associate Professor of Biological Engineering, Director, Division of Comparative Medicine, Massachusetts Institute of Technology
GUO-LI MING, Perelman Professor of Neuroscience, Department of Neuroscience, University of Pennsylvania Perelman School of Medicine
STEVEN PIANTADOSI, Professor in Residence, Harvard Medical School
JOHN QUACKENBUSH, Professor of Computational Biology and Bioinformatics and Chair, Department of Biostatistics, Harvard T.H. Chan School of Public Health, and Professor, Dana-Farber Cancer Institute
PETER L. STRICK, Thomas Detre Professor & Chair of Neurobiology, and Scientific Director, Brain Institute, University of Pittsburgh
JERROLD TANNENBAUM, Professor Emeritus, Veterinary and Animal Ethics and Law, School of Veterinary Medicine, University of California, Davis
Study Staff
AUTUMN DOWNEY, Study Director, Board on Health Sciences Policy
OLIVIA C. YOST, Program Officer, Board on Health Sciences Policy
CORRINE LUTZ, Senior Program Officer, Institute for Laboratory Animal Research (until July 2022)
___________________
1 NOTE: See Appendix D, Disclosure of Unavoidable Conflicts of Interest.
SUSANA RODRIGUEZ, Program Officer, Institute for Laboratory Animal Research (from January 2023)
KYLE CAVAGNINI, Associate Program Officer, Institute for Laboratory Animal Research (from July 2022)
KELSEY BABIK, Associate Program Officer, Board on Health Sciences Policy
LYDIA TEFERRA, Research Associate, Board on Health Sciences Policy
APARNA CHERAN, Senior Program Assistant, Board on Health Sciences Policy (from June 2022)
BRADFORD CHANEY, Senior Program Officer, Committee on National Statistics
TERESA SYLVINA, Director, Institute for Laboratory Animal Research (until March 2023)
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy (until July 2022)
CLARE STROUD, Senior Director, Board on Health Sciences Policy (from July 2022)
Consultants
RONA BRIERE, Briere Associates, Inc.
LAUREN TOBIAS, Maven Messaging
EMILY YAHN, Tangible Designs
Reviewers
This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individuals for their review of this report:
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions of this report nor did they see
the final draft before its release. The review of this report was overseen by ELI Y. ADASHI, Brown University and BARBARA A. SCHAAL, Washington University in St. Louis. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
Preface
Biomedical research provides insights into the underlying biologic processes that define health and disease. The information generated by these scientific investigations is in turn used to develop interventions designed to prevent, diagnose, and treat human disease and to promote the well-being of humans and other living creatures. Undeniably, the advances made possible by biomedical research have saved countless human lives.
In a perfect world, biomedical research questions across varied research domains would be tested in humans; however, a number of ethical, logistical, and ancillary challenges often call for the use of alternative model systems that can best reproduce the human condition. A primary challenge, then, is to identify the model(s) or model system(s) best suited to answering the scientific question(s) at hand. In several areas of biomedical research, nonhuman primates (NHPs) are regarded as the best available model to reproduce the human condition.
For the past year, at the request of the National Institutes of Health (NIH) and in response to a congressional mandate, our committee explored the current landscape of biomedical research using NHP models and their future roles in NIH-supported research, while also considering the research and development status of new approach methodologies, such as in vitro and in silico models, that may complement and/or reduce reliance on NHP models. Although at the outset the task appeared straightforward, the committee quickly learned that the landscape of NHP research is exceedingly complex, and that evaluation of the current and future status of this research can be challenging given the current limitations of the available data on NHP use in NIH-funded research. While the committee was not asked to make recommendations or to prioritize research domains that currently benefit from the use of NHP models and are likely to do so in the future, our hope is that the landscape analysis and conclusions presented in this report will inform decision makers as they consider strategies for supporting the mission of NIH going forward. To this end, the committee emphasizes the critical importance of investments in domestic NHP resources and tools and strategies that can enhance research using NHP models, as well as qualification and/or validation efforts needed to realize the future potential of new approach methodologies. Finally, we hope that this report will stimulate efforts to create more opportunities for researchers working with
NHPs and those developing and using non-NHP models to collaborate around the common goals of advancing human health and reducing human suffering. The national dialogue on NHPs and alternative methodologies is far too often framed using an opportunity cost model that advances a false dichotomy and that may lose sight of the critical scientific and societal issues that drive decision making. In reality, future advances in human health will require approaches that leverage the complementarity of in vitro and in silico methodologies and NHPs and other animal models for the foreseeable future. Overcoming the silos created and reinforced by current funding mechanisms will be vital to advancing the nation’s biomedical research agenda.
The committee would like to thank NIH for sponsoring and supporting this important study, particularly Lyric Jorgenson and Jessica Creery, who served as our points of contact. We are deeply appreciative of their efforts to coordinate and gather responses to the committee’s requests for information on NIH programs and priorities. We are also grateful to the many experts who gave presentations and participated in discussions with the committee during its public meetings. The information they shared was invaluable as we undertook our landscape analysis. We also wish to acknowledge the thousands of members of the public who informed our efforts by taking the time to share their perspectives on NHP research with us. Those too informed the committee’s efforts and provided essential perspectives to the committee.
The committee’s work over the last year was supported by the dedicated project staff at the National Academies of Sciences, Engineering, and Medicine—Autumn Downey, Olivia Yost, Kyle Cavagnini, Kelsey Babik, Lydia Teferra, Aparna Cheran, Bradford Chaney, Susana Rodriguez, and Corrine Lutz. We are deeply appreciative of their tireless and outstanding efforts to keep us on track and facilitate the study’s completion. The committee is also grateful for the science writing contributions of Lauren Tobias and for the editing of this report performed by Rona Briere and her talented team, particularly Allie Boman.
Finally, as committee chair, I would like to thank and acknowledge my fellow committee members who generously gave their time and shared their expertise and perspectives, all of which were essential to addressing our task. I have appreciated your passion and engagement and the opportunity to learn from you as we navigated the process of deliberating on the challenging issues inherent in this topic. I am confident that this report and its conclusions will guide strategic decision making for years to come, and I thank you for your outstanding contributions.
It is now time for the nation’s leaders to take the action necessary to ensure that the United States maintains its scientific leadership and that biomedical investigators nationwide have the tools necessary to advance vital NIH-supported biomedical research. Indeed, patients are waiting.
Kenneth S. Ramos, Chair
Committee on the State of the Science and Future
Needs for Nonhuman Primate Model Systems
4 THE LANDSCAPE OF NEW APPROACH METHODOLOGIES
A Pathway for Adoption of New Approach Methodologies
Regulatory Guidance on Technologies and Approaches to Complement or Reduce Reliance on NHP Models
5 FUTURE NEEDS AND OPPORTUNITIES FOR NONHUMAN PRIMATE MODELS IN BIOMEDICAL RESEARCH
Factors Influencing the Future Need for NHPs in Biomedical Research
Research Domains in Which the Need for NHPs is Likely to Grow
Future Needs for Specific NHP Species
Opportunities for Enhancing NIH-Supported Research with NHPs
B Data on Nonhuman Primate Use in NIH-Supported Biomedical Research
C Biographical Sketches of Committee Members and Staff
D Disclosure of Unavoidable Conflicts of Interest
Supplemental Appendix1
E Nonhuman Primate Investigator Survey and Responses
___________________
1 Supplemental materials are available at https://nap.nationalacademies.org/26857.
Boxes, Figures, and Tables
BOXES
1-2 Key Terminology Used in This Report
1-4 Prior Assessments of NHP Use in NIH-Supported Research
2-4 Case Study: The Critical Role of NHPs in the War Against Polio
2-5 Case Study: Accelerating Vaccine Development During the Global COVID-19 Pandemic
2-6 Case Study: The Development of Breakthrough Biologics for Organ Transplantation
2-7 Case Study: Use of NHP Models to Guide a Gene Therapy Approach to Sickle Cell Disease
3-3 Potential impact of Changes in Wild Macaque Populations on Biomedical Research
4-1 Biomedical Applications of Tissue-Specific Organoids and MPS
5-1 Examples of NIH Support for Collaborative NHP Research
B-1 Tissue Archiving and Sharing Practice at NPRCs
B-2 Tissue Archiving and Sharing Practice at National Resources
FIGURES
1-1 Leading causes of death in the United States, 2017–2021
1-2 Elements of oversight of animal research in the United States
3-3 Performance of leading science nations on the nature index
3-4 P51 National Primate Research Center awards, fiscal years 2012–2022, adjusted for inflation
4-2 Generation and differentiation of induced pluripotent stem cells
TABLES
1-1 Nonhuman Primate Species Used in Biomedical Studies
3-1 Overview of Common National Institutes of Health (NIH) Funding Mechanisms
3-2 Number of Nonhuman Primates Imported to the United States, by Species and Fiscal Year (FY)
3-5 Nonhuman Primates (NHPs) Planned versus Used, by Source
3-6 Factors Contributing to Decreased Enrollment of Nonhuman Primates (NHPs), by Source
3-8 Average Wait Times for Nonhuman Primates (NHPs), Fiscal Years 2018–2021
5-1 Research Domains in Which the Need for Nonhuman Primates (NHPs) Is Likely to Grow
B-4 Total Nonhuman Primates Imported into the United States, by Fiscal Year (FY)
B-5 Number of Nonhuman Primates Imported, by Species and Fiscal Year (FY)
B-6 Number of Nonhuman Primates Imported, by Country and Fiscal Year (FY)
B-7 Number of Nonhuman Primates Imported by Species, Country, and Fiscal Year (FY)
B-14 Total Number of Nonhuman Primates Produced Annually at National Resources, Fiscal Year 2021
Acronyms and Abbreviations
| 2D | two dimensional |
| 3D | three dimensional |
| AAV | adeno-associated virus |
| ACP | Animal Care Policy |
| ACD | Advisory Committee to the Director |
| AD | Alzheimer’s disease |
| AI | artificial intelligence |
| AIDS | acquired immunodeficiency syndrome |
| ALS | amyotrophic lateral sclerosis |
| APHIS | Animal and Plant Health Inspection Service |
| ARRIVE | Animal Research: Reporting of In Vivo Experiments |
| ART | antiretroviral therapy |
| ATSC | adult human tissue stem cell |
| AWA | Animal Welfare Act |
| AWAR | Animal Welfare Act and Animal Welfare Regulations |
| BRAIN | Brain Research Through Advancing Innovative Neurotechnologies |
| CARES | Coronavirus Aid, Relief, and Economic Security (Act) |
| CAR-T | chimeric antigen receptor T cell |
| CDC | Centers for Disease Control and Prevention |
| CFTR | cystic fibrosis transmembrane conductance regulator |
| CiPA | Comprehensive in vitro Proarrhythmia Assay |
| CITES | Convention on International Trade in Endangered Species of Wild Fauna and Flora |
| COU | context of use |
| CoVTEN | Coronavirus Vaccine and Therapeutic Evaluation Network |
| CRISPR | Clustered Regularly Interspaced Short Palindromic Repeats |
| CRO | contract research organization |
| CT | computed tomography |
| DART | developmental and reproductive toxicity |
| DBS | deep brain stimulation |
| EU | European Union |
| FDA | U.S. Food and Drug Administration |
| FY | fiscal year |
| HDN | hemolytic disease of the newborn |
| hiPSC-CM | human iPSC–derived cardiomyocytes |
| HIV | human immunodeficiency virus |
| HREA | Health Research Extension Act |
| HSC | hematopoietic stem cell |
| IACUC | institutional animal care and use committee |
| ICOs | institutes, centers, and offices |
| ILAR | Institute for Laboratory Animal Research |
| IMPC | International Mouse Phenotyping Consortium |
| iPSC | human induced pluripotent stem cell |
| ISTAND | Innovative Science and Technology Approaches for New Drugs |
| IUCN | International Union for Conservation of Nature |
| mAbs | monoclonal antibodies |
| MERS | Middle East respiratory syndrome |
| mCODE | minimal common oncology data elements |
| mGAP | macaque Genotype and Phenotype |
| MHC | major histocompatibility complex |
| ML | machine learning |
| MPS | microphysiological systems |
| MPTP | 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine |
| MRI | magnetic resonance imaging |
| NCATS | National Center for Advancing Translational Sciences |
| NCCIH | National Center for Complementary and Integrative Health |
| NCI | National Cancer Institute |
| NEI | National Eye Institute |
| NHGRI | National Human Genome Research Institute |
| NHLBI | National Heart, Lung, and Blood Institute |
| NHP | nonhuman primate |
| NIA | National Institute on Aging |
| NIAAA | National Institute on Alcohol Abuse and Alcoholism |
| NIAID | National Institute of Allergy and Infectious Diseases |
| NIAMS | National Institute of Arthritis and Musculoskeletal and Skin Diseases |
| NIBIB | National Institute of Biomedical Imaging and Bioengineering |
| NICHD | National Institute of Child Health and Human Development |
| NIDA | National Institute on Drug Abuse |
| NIDCD | National Institute on Deafness and Other Communication Disorders |
| NIDCR | National Institute of Dental and Craniofacial Research |
| NIDDK | National Institute of Diabetes and Digestive and Kidney Diseases |
| NIH | National Institutes of Health |
| NINDS | National Institute of Neurological Disorders and Stroke |
| NIMH | National Institute of Mental Health |
| NPRC | National Primate Research Center |
| OAR | Office of AIDS Research |
| OLAW | Office of Laboratory Animal Welfare |
| ORIP | Office of Research Infrastructure Programs |
| PAR | protease-activated receptor |
| PCTS | precision-cut tissue slices |
| PD | pharmacodynamic |
| PERV | porcine endogenous retrovirus |
| PET | positron emission tomography |
| PHS | Public Health Service |
| PI | principal investigator |
| PK | pharmacokinetic |
| RFA | request for applications |
| RhoGAM | anti-Rh immunoglobulin |
| SCD | sickle cell disease |
| SIV | simian immunodeficiency virus |
| SPECT | single photon emission computed tomography |
| SPF | specific pathogen free |
| USDA | U.S. Department of Agriculture |
| VA | U.S. Department of Veterans Affairs |
| XR | extended reality |
This page intentionally left blank.
