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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; Amgen Inc.; AstraZeneca Pharmaceuti- cals, Inc.; the Centers for Disease Control and Prevention; the Department of Health and Human Services’ National Institutes of Health (NIH, Contract No. N01-OD-4-213) through the National Institute on Alcohol Abuse and Alcohol- ism, the National Institute on Aging, the National Institute on Drug Abuse, the National Eye Institute, the NIH Blueprint for Neuroscience Research, the Na- tional Institute of Mental Health, and the National Institute of Neurological Dis- orders and Stroke; Eli Lily and Company; GE Healthcare, Inc.; GlaxoSmith- Kline, Inc.; Johnson & Johnson Pharmaceutical Research and Development, Inc.; Merck Research Laboratories, Inc.; the National Multiple Sclerosis Soci- ety; the National Science Foundation (Contract No. OIA-0647541); Pfizer Global Research and Development, Inc.; and the Society for Neuroscience. The views presented in this publication are those of the editors and attributing au- thors and do not necessarily reflect the view of the organizations or agencies that provided support for this project. International Standard Book Number-13: 978-0-309-10881-2 International Standard Book Number-10: 0-309-10881-0 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: Institute of Medicine (IOM). 2008. Autism and the environ- ment: Challenges and opportunities for research. Workshop proceedings. Wash- ington, DC: 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 AUTISM AND THE ENVIRONMENT CHALLENGES AND OPPORTUNITIES FOR RESEARCH PLANNING COMMITTEE* ALAN LESHNER (Chair), American Association for the Advancement of Science, Washington, D.C. DUANE ALEXANDER, National Institute of Child Health and Human Development, Bethesda, Maryland MARK BLAXILL, SafeMinds, Tyrone, Georgia LAURA BONO, National Autism Association, Nixa, Missouri SOPHIA COLAMARINO, Autism Speaks, New York ERIC FOMBONNE, McGill University, Montreal, Canada STEVEN HYMAN, Harvard University, Cambridge, Massachusetts JUDY ILLES, University of British Columbia, Vancouver, Canada THOMAS INSEL, National Institute of Mental Health, Bethesda, Maryland DAVID SCHWARTZ, National Institute of Environmental Health Sciences, Triangle Park, North Carolina ALISON TEPPER SINGER, Autism Speaks, New York SUSAN SWEDO, National Institute of Mental Health, Bethesda, Maryland CHRISTIAN ZIMMERMAN, Neuroscience Associates, Boise, Idaho IOM Staff BRUCE ALTEVOGT, Project Director SARAH HANSON, Senior Program Associate AFRAH ALI, Senior Project Assistant LORA TAYLOR, Senior Project Assistant ∗ The planning committee was solely responsible for organizing the workshop, identifying topics, and choosing speakers. They were not responsible for the publication of the workshop proceedings. v

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FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS ALAN LESHNER (Chair), American Association for the Advancement of Science, Washington, D.C. HUDA AKIL, University of Michigan, Ann Arbor MARC BARLOW, GE Healthcare, Inc., Buck, United Kingdom DANIEL BURCH, CeNeRx Biopharma, Research Triangle Park, North Carolina DENNIS CHOI, Emory University, Atlanta, Georgia TIMOTHY COETZEE, National Multiple Sclerosis Society, New York DAVID COHEN, Columbia University, Society for Neuroscience representative, New York RICHARD FRANK, GE Healthcare, Inc., Princeton, New Jersey RICHARD HODES, National Institute on Aging, Bethesda, Maryland STEVEN HYMAN, Harvard University, Cambridge, Massachusetts JUDY ILLES, University of British Columbia, Vancouver, Canada THOMAS INSEL, National Institute of Mental Health, Bethesda, Maryland STORY LANDIS, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland TING-KAI LI, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland MICHAL OBERDORFER, NIH Neuroscience Blueprint, Bethesda, Maryland KATHIE OLSEN, National Science Foundation, Arlington, Virginia ATUL PANDE, GlaxoSmithKline, Inc., Research Triangle Park, North Carolina STEVEN PAUL, Eli Lilly and Company, Indianapolis, Indiana WILLIAM POTTER, Merck Research Laboratories, Inc., North Wales, Pennsylvania PAUL SIEVING, National Eye Institute, Bethesda, Maryland RAE SILVER, Columbia University, New York, New York WILLIAM THIES, Alzheimer’s Association, Chicago, Illinois ROY TWYMAN, Johnson and Johnson Pharmaceutical Research and Development, Inc., Titusville, New Jersey NORA VOLKOW, National Institute on Drug Abuse, Bethesda, Maryland vi

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FRANK YOCCA, AstraZeneca Pharmaceuticals, Wilmington, Delaware CHRISTIAN ZIMMERMAN, Neuroscience Associates, Boise, Idaho STEVIN ZORN, Pfizer Global Research and Development, Ann Arbor, Michigan IOM Staff BRUCE ALTEVOGT, Project Director SARAH HANSON, Senior Program Associate LORA TAYLOR, Senior Project Assistant IOM Anniversary Fellow LISA BARCELLOS, University of California, Berkeley vii

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BOARD ON HEALTH SCIENCES POLICY* FRED H. GAGE (Chair), The Salk Institute for Biological Studies, La Jolla, California C. THOMAS CASKEY, University of Texas–Houston Health Science Center GAIL H. CASSELL, Eli Lilly and Company, Indianapolis, Indiana JAMES F. CHILDRESS, University of Virginia, Charlottesville ELLEN WRIGHT CLAYTON, Vanderbilt University Law School, Nashville, Tennessee LINDA C. GIUDICE, University of California, San Francisco LYNN R. GOLDMAN, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland LAWRENCE O. GOSTIN, Georgetown University Law Center, Washington, D.C. MARTHA N. HILL, Johns Hopkins University School of Nursing, Baltimore, Maryland DAVID KORN, Association of American Medical Colleges, Washington, D.C. ALAN LESHNER, American Association for the Advancement of Science, Washington, D.C. JONATHAN D. MORENO, University of Pennsylvania, Philadelphia E. ALBERT REECE, University of Maryland School of Medicine, Baltimore LINDA ROSENSTOCK, University of California, Los Angeles MICHAEL J. WELCH, Washington University School of Medicine, St. Louis, Missouri OWEN N. WITTE, University of California, Los Angeles IOM Staff ANDREW M. POPE, Director AMY HAAS, Board Assistant DONNA RANDALL, Financial Associate * IOM Boards do not review or approve workshop proceedings. The responsibility for the content of the proceedings rests with the institution. viii

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Independent Report Reviewers These workshop proceedings have been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Coun- cil’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 published workshop proceedings as sound as possible and to ensure that the proceedings meet institutional standards for 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 wish to thank the following individuals for their review of these proceedings: Lisa Croen, Kaiser Permanente Northern California, Oakland, CA Gary W. Goldstein, Kennedy Krieger Institute and Johns Hopkins University School of Medicine and School of Hygiene and Public Health, Baltimore, MD Carlos A. Pardo-Villamizar, Johns Hopkins University School of Medicine, Baltimore, MD Lyn Redwood, National Autism Association, Nixa, MO Although the reviewers listed above have provided many construc- tive comments and suggestions, they were not asked to endorse the final draft of the workshop proceedings before their release. The review of these proceedings was overseen by Dr. Floyd E. Bloom, The Scripps Research Institute, Professor Emeritus. Appointed by the National Re- search Council, he was responsible for making certain that an independ- ent examination of these proceedings was carried out in accordance with ix

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x INDEPENDENT REPORT REVIEWERS institutional procedures and that all review comments were carefully considered. Responsibility for the final content of these workshop pro- ceedings rests entirely with the institution.

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Preface Autism spectrum disorders (ASD) constitute a major public health problem, affecting one in every 150 children and their families. Unfortunately, there is little understanding of the causes of ASD, and, despite their broad societal impact, many people believe that the overall research program for autism is incomplete, particularly as it relates to the role of environmental factors. One reason for that may well be that there have been relatively few occasions that have brought together all the key stakeholders⎯scientists, clinicians, parents of autistic children, patient advocates, and major sponsors of autism-related research⎯to engage in a full discussion of autism causality and scientific research priorities. In response to these challenges, the U.S. Secretary of Health and Human Services (HHS) asked that the Institute of Medicine’s (IOM) Forum on Neuroscience and Nervous System Disorders (the Forum) host a workshop that would bring together the key public and private stakeholders to discuss potential ways to improve the understanding of the ways that environmental factors may affect ASD. The Forum provided an ideal setting to facilitate this request, since it is designed to provide its members⎯representatives from government, industry, academia, and patient advocacy organizations⎯with a venue for openly exchanging information and discussing critical scientific and policy issues related to nervous system functioning. Thus, on April 18 and 19, 2007, the Forum hosted a workshop, “Autism and the Environment: Challenges and Opportunities for Research” organized by an ad hoc planning committee. This workshop and its development epitomized what is called by many people “public engagement” by and with the scientific community. Members of the broader public were involved in every aspect of the workshop. The xi

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xii PREFACE planning committee included not only academic leaders and top government scientists, including three institute directors from the National Institutes of Health, but also four members of the autism advocacy community, three of whom are parents of autistic children. Many of the workshop participants and invited speakers were members of the advocacy community. The result was an activity that fully explored from all angles the range of issues surrounding environmental factors and ASD, and resulted in an array of new ideas for research projects and programs. There is no question that this workshop and its product, this volume, were greatly enriched by this broad participation. As chair of the Forum and the workshop planning committee, I want to acknowledge the hard work and dedication displayed by every member of the planning committee, Forum, and workshop participants. I would also like to thank the leadership of the IOM and HHS for providing the Forum with the opportunity to host this very important event. This workshop was a huge success, both in helping to identify potential scientific opportunities and in demonstrating the utility of moving from a strategy of public education about science toward fuller public engagement, with science where both sides—scientists and members of the public—listened and learned from each other. Alan Leshner, Chair Workshop Planning Committee Forum on Neuroscience and Nervous System Disorders

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Foreword This workshop originated at the suggestion of advocates for patients with autism. In a meeting with the two of us, they broached the idea of engaging with the scientific community to help shape a new research agenda. The Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders provided a neutral venue to bring together key stakeholders—scientists, parents of autistic children, other patient advocates, and major sponsors of autism-related research—specifically to identify scientific opportunities to further the understanding of environmental factors that may contribute to autism. The presentations and discussions at the workshop identified a number of promising directions for research on the possible role of different environmental agents in the etiology of autism. Equally important was the opportunity for dialogue and the exchange of ideas that took place in an atmosphere of mutual respect and learning. The payoff will be new directions for scientific research that are more fully informed by different perspectives on the reality of autism. From that, everyone stands to gain. William F. Raub, Ph.D. Harvey V. Fineberg Science Advisor to the Secretary President Department of Health and Human Institute of Medicine Services xiii

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Contents INTRODUCTION 1 PROCEEDINGS* 5 Day 1, 5 Day 2, 165 APPENDIXES A Index of Scientific Opportunities 283 B Workshop Agenda 293 C Registered Workshop Participants 305 D Biographic Sketches of Workshop Planning Committee, Forum Members, Invited Speakers, and Staff 311 * Throughout various speaker presentations, speakers may refer to slides that can be found online at http://www.iom.edu/?id=42481. xv

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