Transgenic Neuroscience
Research
Exploring the Scientific
Opportunities Afforded by
New Nonhuman Primate Models
PROCEEDINGS OF A WORKSHOP
Lisa Bain, Sheena M. Posey Norris, and Clare Stroud,
Rapporteurs
Forum on Neuroscience and Nervous System Disorders
Board on Health Sciences Policy
Health and Medicine Division
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; Cohen Veterans Bioscience; Department of Health and Human Services’ Food and Drug Administration (5R13FD005362-02) and National Institutes of Health (NIH) (HHSN26300089 [Under Master Base #DHHS-10002880]) through the National Center for Complementary and Integrative Health, National Eye Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, and NIH Blueprint for Neuroscience Research; Department of Veterans Affairs (VA240-14-C-0057); Eli Lilly and Company; Foundation for the National Institutes of Health; Gatsby Charitable Foundation; George and Anne Ryan Institute for Neuroscience at The University of Rhode Island; Janssen Research & Development, LLC; The Kavli Foundation; Lundbeck Research USA; Merck Research Laboratories; The Michael J. Fox Foundation for Parkinson’s Research; National Multiple Sclerosis Society; National Science Foundation (BCS-1064270); One Mind; Sanofi; Society for Neuroscience; Takeda Pharmaceuticals International, Inc.; and Wellcome Trust. 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: 978-0-309-48873-0
International Standard Book Number-10: 0-309-48873-7
Digital Object Identifier: https://doi.org/10.17226/25362
Additional copies of this publication are 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 2019 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2019. Transgenic neuroscience research: Exploring the scientific opportunities afforded by new nonhuman primate models: Proceedings of a workshop. Washington, DC: The National Academies Press. doi:https://doi.org/10.17226/25362.
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PLANNING COMMITTEE ON TRANSGENIC AND CHIMERIC NEUROSCIENCE RESEARCH: EXPLORING THE SCIENTIFIC OPPORTUNITIES AFFORDED BY NEW NONHUMAN PRIMATE MODELS1
FRANCES JENSEN (Chair), University of Pennsylvania
SUSAN AMARA, National Institute of Mental Health
SARAH CADDICK, Gatsby Charitable Foundation
MARINA EMBORG, University of Wisconsin–Madison
GUOPING FENG, Massachusetts Institute of Technology
JOSHUA GORDON, National Institute of Mental Health
HENRY T. GREELY, Stanford University
JEFFREY KAHN, Johns Hopkins University
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
JOHN MORRISON, University of California, Davis
WILLIAM NEWSOME, Stanford University
KAREN PARKER, Stanford University
MICHAEL STEINMETZ, National Eye Institute
ANDREW WELCHMAN, Wellcome Trust
STEVIN ZORN, MindImmune Therapeutics, Inc.
Health and Medicine Division Staff
CLARE STROUD, Director, Forum on Neuroscience and Nervous System Disorders
SHEENA M. POSEY NORRIS, Program Officer
DANIEL FLYNN, Research Associate (until November 2018)
PHOENIX WILSON, Senior Program Assistant
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
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FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS1
STORY LANDIS (Co-Chair), Director Emeritus, National Institute of Neurological Disorders and Stroke
JOHN KRYSTAL (Co-Chair), Yale University
SUSAN AMARA, Society for Neuroscience
RITA BALICE-GORDON, Sanofi
KATJA BROSE, Chan Zuckerberg Initiative
EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology
DANIEL BURCH, Pharmaceutical Product Development, LLC
JOSEPH BUXBAUM, Icahn School of Medicine at Mount Sinai
SARAH CADDICK, Gatsby Charitable Foundation
ROSA CANET-AVILES, Foundation for the National Institutes of Health
MARIA CARRILLO, Alzheimer’s Association
E. ANTONIO CHIOCCA, Harvard Medical School
TIMOTHY COETZEE, National Multiple Sclerosis Society
JONATHAN COHEN, Princeton University
ROBERT CONLEY, Eli Lilly and Company (from October 2018)
JAMES DESHLER, National Science Foundation
BILLY DUNN, Food and Drug Administration
MICHAEL EGAN, Merck Research Laboratories
JOSHUA GORDON, National Institute of Mental Health
HENRY T. GREELY, Stanford University
RAQUEL GUR, University of Pennsylvania
MAGALI HAAS, Cohen Veterans Bioscience
RAMONA HICKS, One Mind
RICHARD HODES, National Institute on Aging
STUART HOFFMAN, Department of Veterans Affairs
STEVEN HYMAN, Broad Institute of Massachusetts Institute of Technology and Harvard University
MICHAEL IRIZARRY, Eli Lilly and Company (until October 2018)
FRANCES JENSEN, University of Pennsylvania
GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
ALAN LESHNER, American Association for the Advancement of Science (Emeritus)
HUSSEINI MANJI, Janssen Research & Development, LLC
CAROLINE MONTOJO, The Kavli Foundation
ATUL PANDE, Tal Medical
STEVEN PAUL, Voyager Therapeutics, Inc.
EMILIANGELO RATTI, Takeda Pharmaceuticals International, Inc.
DOUGLAS SHEELEY, National Institute of Dental and Craniofacial Research
TODD SHERER, The Michael J. Fox Foundation for Parkinson’s Research
DAVID SHURTLEFF, National Center for Complementary and Integrative Health
PAUL SIEVING, National Eye Institute
NORA VOLKOW, National Institute on Drug Abuse
ANDREW WELCHMAN, Wellcome Trust
DOUG WILLIAMSON, Lundbeck
STEVIN ZORN, MindImmune Therapeutics, Inc.
Health and Medicine Division Staff
CLARE STROUD, Forum Director
SHEENA M. POSEY NORRIS, Program Officer
DANIEL FLYNN, Research Associate (until November 2018)
PHOENIX WILSON, Senior Program Assistant
BARDIA MASSOUDKHAN, Financial Associate
ANDREW M. POPE, Senior Director, Board on Health Sciences Policy
Reviewers
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:
ROBERT DESIMONE, Massachusetts Institute of Technology
HENRY T. GREELY, Stanford University
JON HENNEBOLD, Oregon National Primate Research Center
KAREN PARKER, Stanford University
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 ELI ADASHI, Brown University. He 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.
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Contents
Organization of the Proceedings
Overcoming the Limitations of Mouse Models with Nonhuman Primate Models
Opportunities Provided by Nonhuman Primate Models to Foster Neuroscience Research
Challenges of Genetically Modified Nonhuman Primate Models
3 STATE OF THE SCIENCE OF TRANSGENIC NONHUMAN PRIMATE MODELS FOR NERVOUS SYSTEM DISORDERS
Genetically Modified Nonhuman Primate Models of Disease
4 TRANSLATING RESEARCH FROM NONHUMAN PRIMATES TO HUMANS
A Translational Research Roadmap in Autism
Assessment Tools for Nonhuman Primates
Brain Mapping and Imaging in Genetically Modified Nonhuman Primates
5 BIOETHICAL CONSIDERATIONS FOR TRANSGENIC NONHUMAN PRIMATE MODELS IN NEUROSCIENCE RESEARCH
3R Principles and Harm–Benefit
Importance of Proactive Communication with the Public
6 UNDERSTANDING THE POLICY, INFRASTRUCTURE, AND FUNDING NEEDED TO ADVANCE NEUROSCIENCE RESEARCH
Training and Educating the Next Generation of Researchers
Organizing Efforts to Meet Infrastructure and Scientific Needs