FROM MOLECULES TO MINDS

Challenges for the 21st Century

WORKSHOP SUMMARY

Matthew Hougan and Bruce Altevogt, Rapporteurs

Forum on Neuroscience and Nervous System Disorders

Board on Health Sciences Policy

INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.
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Matthew Hougan and Bruce Altevogt, Rapporteurs Forum on Neuroscience and Nervous System Disorders Board on Health Sciences Policy

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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 project was supported by contracts between the National Academy of Sci- ences and the Alzheimer’s Association; AstraZeneca Pharmaceuticals, Inc.; CeNeRx Biopharma; the Department of Health and Human Services’ National Institutes of Health (NIH, Contract No. N01-OD-4-213) through the National Eye Institute, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH Blueprint for Neuroscience Research; Eli Lilly and Com- pany; GE Healthcare, Inc.; GlaxoSmithKline, Inc.; Johnson & Johnson Pharma- ceutical Research and Development, Inc.; Merck Research Laboratories, Inc.; the National Multiple Sclerosis Society; the National Science Foundation (Con- tract No. OIA-0753701); the Society for Neuroscience; and Wyeth Research, Inc. The views presented in this publication are those of the editors and attribut- ing authors and do not necessarily reflect the view of the organizations or agen- cies that provided support for this project. International Standard Book Number-13: 978-0-309-12092-0 International Standard Book Number-10: 0-309-12092-6 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. For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu. Copyright 2008 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: IOM (Institute of Medicine). 2008. From molecules to minds: Challenges for the 21st century: Workshop summary. Washington, DC: The National Academies Press.

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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 gov- ernment on scientific and technical matters. Dr. Ralph J. Cicerone 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 out- standing 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. Charles M. Vest 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 sci- entific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Re- search Council. www.national-academies.org

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WORKSHOP ON GRAND CHALLENGES IN NEUROSCIENCE PLANNING COMMITTEE* ALAN LESHNER (Chair), American Association for the Advancement of Science, Washington, DC ALAN BREIER, University of Indiana, Indianapolis DAVID COHEN, Columbia University, Society for Neuroscience representative, New York RICHARD HODES, National Institute on Aging, Bethesda, MD STEVEN HYMAN, Harvard University, Cambridge, MA JUDY ILLES, University of British Columbia, Vancouver, Canada THOMAS INSEL, National Institute of Mental Health, Bethesda, MD STORY LANDIS, National Institute of Neurological Disorders and Stroke, Bethesda, MD TING-KAI LI, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD MICHAEL OBERDORFER, National Institutes on Health Neuroscience Blueprint, Bethesda, MD KATHIE OLSEN, National Science Foundation, Arlington, VA WILLIAM POTTER, Merck Research Laboratories, Inc., North Wales, PA ROBERT RICHARDSON, Cornell University, Ithaca, NY PAUL SIEVING, National Eye Institute, Bethesda, MD RAE SILVER, Columbia University, New York ROY TWYMAN, Johnson & Johnson Pharmaceutical Research and Development, Inc., Titusville, NJ NORA VOLKOW, National Institute on Drug Abuse, Bethesda, MD IOM Staff BRUCE ALTEVOGT, Forum Director SARAH HANSON, Senior Program Associate LORA TAYLOR, Senior Project Assistant DIONNA ALI, Anderson Intern ________________________________ ∗ IOM planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution. v

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FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS* ALAN LESHNER (Chair), American Association for the Advancement of Science, Washington, DC HUDA AKIL, University of Michigan–Ann Arbor MARC BARLOW, GE Healthcare, Inc., Buck, United Kingdom DANIEL BURCH, CeNeRx Biopharma, Research Triangle Park, NC DENNIS CHOI, Emory University, Atlanta, GA TIMOTHY COETZEE, National Multiple Sclerosis Society, New York DAVID COHEN, Columbia University, Society for Neuroscience representative, New York RICHARD FRANK, GE Healthcare, Inc., Princeton, NJ RICHARD HODES, National Institute on Aging, Bethesda, MD STEVEN HYMAN, Harvard University, Cambridge, MA JUDY ILLES, University of British Columbia, Vancouver, Canada THOMAS INSEL, National Institute of Mental Health, Bethesda, MD STORY LANDIS, National Institute of Neurological Disorders and Stroke, Bethesda, MD TING-KAI LI, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD HUSSEINI MANJI, Johnson & Johnson Pharmaceutical Research and Development, Inc., Titusville, NJ (since September 2008) MICHAEL OBERDORFER, National Institutes on Health Neuroscience Blueprint, Bethesda, MD KATHIE OLSEN, National Science Foundation, Arlington, VA ATUL PANDE, GlaxoSmithKline, Inc., Research Triangle Park, NC MENELAS PANGALOS, Wyeth Research, Inc., Princeton, NJ STEVEN PAUL, Eli Lilly and Company, Indianapolis, IN WILLIAM POTTER, Merck Research Laboratories, Inc., North Wales, PA SCOTT REINES, Foundation for the NIH, Bethesda, MD PAUL SIEVING, National Eye Institute, Bethesda, MD RAE SILVER, Columbia University, New York WILLIAM THIES, Alzheimer’s Association, Chicago, IL _______________________ * IOM forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution. vi

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ROY TWYMAN, Johnson & Johnson Pharmaceutical Research and Development, Inc., Titusville, NJ (until September 2008) NORA VOLKOW, National Institute on Drug Abuse, Bethesda, MD FRANK YOCCA, AstraZeneca Pharmaceuticals, Wilmington, DE CHRISTIAN ZIMMERMAN, Neuroscience Associates, Boise, ID IOM Staff BRUCE ALTEVOGT, Forum Director SARAH HANSON, Senior Program Associate LORA TAYLOR, Senior Project Assistant DIONNA ALI, Anderson Intern vii

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BOARD ON HEALTH SCIENCES POLICY* FRED H. GAGE (Chair), The Salk Institute for Biological Studies, La Jolla, CA DONALD S. BURKE, University of Pittsburgh, Pittsburgh, PA C. THOMAS CASKEY, University of Texas, Houston Health Science Center GAIL H. CASSELL, Eli Lilly and Company, Indianapolis, IN JAMES F. CHILDRESS, University of Virginia, Charlottesville, VA DENNIS CHOI, Emory University, Atlanta, GA LINDA C. GIUDICE, University of California, San Francisco LYNN R. GOLDMAN, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD LAWRENCE O. GOSTIN, Georgetown University Law Center, Washington, DC MARTHA N. HILL, Johns Hopkins University School of Nursing, Baltimore, MD PAUL E. JARRIS, Association of State and Territorial Health Officials, Arlington, VA DAVID KORN, Association of American Medical Colleges, Washington, DC RICHARD C. LARSON, Massachusetts Institute of Technology, Cambridge, MA ALAN LESHNER, American Association for the Advancement of Science, Washington, DC LINDA B. MILLER, Volunteer Trustees Foundation, Washington, DC E. ALBERT REECE, University of Maryland School of Medicine, Baltimore, MD LINDA ROSENSTOCK, University of California, Los Angeles KEITH A. WAILOO, Rutgers, The State University of New Jersey, New Brunswick, NJ MICHAEL J. WELCH, Washington University School of Medicine, St. Louis, MO OWEN N. WITTE, University of California, Los Angeles _________________________________ * IOM boards do not review or approve individual products. The responsibility for the content of the workshop summary rests with the rapporteurs and the institution. viii

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IOM Staff ANDREW M. POPE, Director AMY HAAS, Board Assistant DONNA RANDALL, Financial Associate ix

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Independent Report Reviewers This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its pub- lished report as sound as possible and to ensure that the report meets in- stitutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confi- dential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: William Bialek, Department of Physics, Princeton University Fred H. Gage, The Salk Institute for Biological Studies David J. Kupfer, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine Tom M. Mitchell, Machine Learning Department, Carnegie Mellon University Robert C. Richardson, Cornell University Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the report before its release. The review of this report was overseen by Dr. Sid Gilman, Michigan Alzheimer’s Disease Research Center, Department of Neurology, University of Michigan. Appointed by the Institute of Medicine, he was responsible for making certain that an in- dependent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully xi

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considered. Responsibility for the final content of this report rests en- tirely with the authoring committee and the institution. xii

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Contents INTRODUCTION 1 What Can We Achieve, 2 About This Workshop, 3 GRAND CHALLENGE: HOW DOES THE HUMAN BRAIN WORK AND PRODUCE MENTAL ACTIVITY? 4 Mapping the Human Brain, 5 Technological Advance: The Brainbow, 6 Technological Advance: Neuronal “Light Switch,” 7 Technological Challenge: Spatial and Temporal Resolution, 8 The Importance of Neural Networks, 11 The Way Forward, 13 GRAND CHALLENGE: NATURE VERSUS NURTURE: HOW DOES THE INTERPLAY OF BIOLOGY AND EXPERIENCE SHAPE OUR BRAINS AND MAKE US WHO WE ARE? 14 Brain Plasticity, 14 Gene-Environment Interactions, 17 Huge Clinical Importance, 17 The Way Forward, 18 xiii

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GRAND CHALLENGE: HOW DO WE KEEP OUR BRAINS HEALTHY? HOW DO WE PROTECT, RESTORE, OR ENHANCE THE FUNCTIONING OF OUR BRAINS AS WE AGE? 19 The Question of Aging, 19 Starting at Square One, 20 The Complicated Role of Genetics, 21 The Trouble with Current Treatments, 21 INSPIRING THE NEXT GENERATION OF SCIENTISTS 22 CHALLENGES AND TECHNICAL LIMITATIONS 23 Integrating Neuroscience and Working Toward a Common Goal, 24 Working with Psychological Concepts and Defining Behavior, 24 New Technological Requirements, 25 ETHICAL CONSIDERATIONS 26 Clinical Concerns, 26 Fostering a Dialog, 27 CONCLUSION 27 On the Cusp, 28 APPENDIXES A References 31 B Workshop Agenda 33 C Registered Workshop Attendees 41 D Biographical Sketches of Invited Speakers, Planning Committee Members, Forum Members, and Staff 45 xiv