Advancing Disease Modeling
in Animal-Based Research in
Support of Precision Medicine
PROCEEDINGS OF A WORKSHOP
Erin Hammers Forstag and Lida Anestidou, Rapporteurs
Roundtable on Science and Welfare in Laboratory Animal Use
Institute for Laboratory Animal Research
Division on Earth and Life Studies
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
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This project was supported by the American Veterinary Medical Association; Baylor College of Medicine; Emory University; Genentech; GlaxoSmithKline; Indiana University; Johns Hopkins University; Johnson & Johnson; Massachusetts General Hospital; Massachusetts Institute of Technology; Medical College of Wisconsin; Merck and Co., Inc.; National Institutes of Health (Contract No. HHSN263201200074I; Task Order HHSN26300122); National Primate Research Centers; Novartis; University of California, Davis; University of Miami; University of Michigan; University of Pittsburgh; and Yale University. Funding for this conference was made possible, in part, by the U.S. Food and Drug Administration through grant 5 R13 FD 005298-02. Views expressed in written conference materials or publications and by speakers or moderators do not necessarily reflect the official policies of the U.S. Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organizations imply endorsement by the U.S. government. This material is based on work supported by the National Science Foundation under Grant No. IOS-1639899. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. 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: 978-0-309-47116-9
International Standard Book Number-10: 0-309-47116-8
Digital Object Identifier: https://doi.org/10.17226/25002
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Printed in the United States of America
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Advancing Disease Modeling in Animal-Based Research in Support of Precision Medicine: Proceedings of a Workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25002.
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PLANNING COMMITTEE ON ADVANCING DISEASE MODELING IN ANIMAL-BASED RESEARCH IN SUPPORT OF PRECISION MEDICINE: A WORKSHOP
Members
Brian R. Berridge, GlaxoSmithKline (Co-Chair)
K.C. Kent Lloyd, University of California, Davis (Co-Chair)
Cory Brayton, Johns Hopkins University
Robert M. Califf, Duke University School of Medicine
Melissa Haendel, Oregon Health & Science University
John P.A. Ioannidis, Stanford University
ROUNDTABLE ON SCIENCE AND WELFARE IN LABORATORY ANIMAL USE
Co-Chairs
Robert C. Dysko, University of Michigan Medical School
K.C. Kent Lloyd, University of California, Davis
Liaison to ILAR Council
Paul A. Locke, Johns Hopkins Bloomberg School of Public Health
Members
Jill Ascher, U.S. Food and Drug Administration
Szczepan Baran, Novartis Institutes for Biomedical Research, Inc.
Bonnie V. Beaver, Texas A&M University
Cindy Buckmaster, Baylor College of Medicine
Saverio (Buddy) Capuano III, University of Wisconsin–Madison
Carol Clarke, U.S. Department of Agriculture
Michael DuVall, Janssen Pharmaceuticals
James G. Fox, Massachusetts Institute of Technology
Alema Galijatovic-Idrizbegovic, Merck & Co., Inc.
Gail C. Golab, American Veterinary Medical Association
Debra L. Hickman, Indiana University School of Medicine
Michael Huerkamp, Emory University
Donna Matthews Jarrell, Massachusetts General Hospital
Bruce W. Kennedy, Chapman University
David M. Kurtz, National Institute of Environmental Health Sciences
Margaret S. Landi, GlaxoSmithKline
Joseph T. Newsome, University of Pittsburgh
Patricia Preisig, Yale University
Edda (Floh) Thiels, National Science Foundation
Joseph Thulin, Medical College of Wisconsin
Rhonda J. Wiler, Genentech
Axel Wolff, National Institutes of Health
Robert H. Wurtz, National Institutes of Health
Julia Zaias, University of Miami
Staff
Lida Anestidou, Director, Roundtable on Science and Welfare in Laboratory Animal Use
Angela Kolesnikova, Senior Program Assistant, Board on Life Sciences
Jenna Ogilvie, Research Associate, Board on Life Sciences (until November 27, 2017)
Consultant
Erin Hammers Forstag, Writer
INSTITUTE FOR LABORATORY ANIMAL RESEARCH
Members
Margaret S. Landi, Chief of Animal Welfare, Ethics and Strategy, GlaxoSmithKline (Chair)
Karin Blumer, Scientific Affairs, Novartis International AG
Cory Brayton, Associate Professor of Molecular and Comparative Pathobiology, Johns Hopkins University
Joseph J. DeGeorge, Global Head of Safety Assessment and Laboratory Animal Resources, Merck Research Laboratories
Michael DuVall, Scientific Director, Head of Toxicology and Laboratory Animal Medicine, Johnson and Johnson, Janssen Pharmaceuticals
Lewis B. Kinter, Independent Consultant
Paul A. Locke, Associate Professor, Department of Environmental Health and Engineering Director, DrPH Program in Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health
Daniel S. Marsman, Head, Safety and Regulatory Affairs, Procter & Gamble Health Care
Melinda A. Novak, Professor of Psychology, University of Massachusetts
James A. Roth, Clarence Hartley Covault Distinguished Professor, Director, Center for Food Security and Public Health, College of Veterinary Medicine, Iowa State University
Lawrence B. Schook, Edward William and Jane Marr Gutsgell Professor of Animal Sciences and Radiology, University of Illinois at Urbana-Champaign
Robert S. Sikes, Professor of Biology, University of Arkansas at Little Rock
Staff
Gregory Symmes, Interim Director (from November 1, 2017)
Dorothy Zolandz, Interim Director (until October 31, 2017)
Lida Anestidou, Senior Program Officer
Acknowledgments
This Proceedings of a Workshop 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 proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
Mary E. Dickinson, Baylor College of Medicine
Alema Galijatovic-Idrizbegovic, Merck & Co., Inc.
Charles L. Sawyers, Memorial Sloan Kettering Cancer Center
Joe V. Selby, Patient-Centered Outcomes Research Institute
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by Huda Akil, University of Michigan Medical School. She was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
The support of the Roundtable on Science and Welfare in Laboratory Animal Use was vital to the planning and conduct of the workshop on Advancing Disease Modeling in Animal-Based Research in Support of Precision Medicine. Federal sponsors are the National Institutes of Health, the National Science Foundation, and the U.S. Food and Drug Administration. Nonfederal sponsorship was provided by the American Veterinary Medical Association; Baylor College of Medicine; Emory University; Genentech; GlaxoSmithKline; Indiana University; Johns Hopkins University; Johnson & Johnson; Massachusetts General Hospital; Massachusetts Institute of Technology; Medical College of Wisconsin; Merck and Co., Inc.; National Primate Research Centers; Novartis; University of California, Davis; University of Miami; University of Michigan; University of Pittsburgh; and Yale University.
The Roundtable on Science and Welfare in Laboratory Animal Use expresses deep gratitude to the members of the planning committee for developing an expansive and multifaceted workshop agenda and to the expert speakers who took part in the workshop’s discussions.
Contents
1 INTRODUCTION TO PRECISION MEDICINE AND ANIMAL MODELS
Organization of This Proceedings of a Workshop
What Is Precision Medicine and How Did We Get Here?
Regulation of Precision Medicine
Ethical Considerations of Animal-Based Research
Bioethics, Public Opinion, and Community Advisory Boards
2 EXISTING PRECISION MEDICINE INITIATIVES
United Kingdom: 100,000 Genomes
France: The French Plan for Genomic Medicine
Japan: Initiative on Rare and Undiagnosed Diseases
World Economic Forum: Center for the Fourth Industrial Revolution
3 THE PROMISE AND PERILS OF ANIMAL MODELS
Unique Animal-Based Approaches
Mouse Hospital Co-Clinical Trials
Pets with Naturally Occurring Tumors
Challenges of Using Animal Models for Precision Medicine
The Animal Rule and Appropriate Modeling
4 REPRODUCIBILITY AND PREDICTIVITY
Translational Stroke Research: The “Worst Practices” of Animal Research
Reproducibility in Large Shared Datasets
The Paradoxes of Precision Medicine
5 IN VITRO ALTERNATIVES TO ANIMAL MODELS
iPSCs to Model Chemotherapy-Induced Cardiotoxicity
In Vitro Cardiac Disease Models
Human Microphysiological Systems
Quantitative Systems Pharmacology and Microphysiological Systems
Human Microphysiological Systems
6 ASSESSING SAFETY AND TOXICOLOGY
Patient Susceptibilities in Preclinical Drug Safety Assessment
Co-expressed Gene Network Analysis as a Bridge for Extrapolation Between Species
Using Genetically Diverse Mice to Test Susceptibility to Toxins
To Identify Specific Polymorphisms Associated with Xenobiotic Toxicity
To Evaluate Biomarker Performance Toward Assessing Human Clinical Adverse Outcomes
As a Tool for Population-Based Estimates of Chemical Potency for Risk Assessment
Personalized Medicine Coalition
B PLANNING COMMITTEE BIOGRAPHIES
BOX
FIGURES
1-1 Building a knowledge network
3-1 Genetic background of mouse models
3-3 Co-clinical mouse trials for cancer
3-4 Comparative oncology with dogs
6-1 Founder strains of Diversity Outbred mice
6-2 Individual epidemiological study ratings
6-4 Table to summarize evidence synthesis and integration judgments
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