THE GENOMIC REVOLUTION

IMPLICATIONS FOR TREATMENT AND CONTROL OF INFECTIOUS DISEASE

WORKING GROUP SUMMARIES

Conference

Arnold and Mabel Beckman Center of the National Academies

Irvine, California

November 10-13, 2005

THE NATIONAL ACADEMIES PRESS
Washington, D. C.
www.nap.edu



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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries THE GENOMIC REVOLUTION IMPLICATIONS FOR TREATMENT AND CONTROL OF INFECTIOUS DISEASE WORKING GROUP SUMMARIES Conference Arnold and Mabel Beckman Center of the National Academies Irvine, California November 10-13, 2005 THE NATIONAL ACADEMIES PRESS Washington, D. C. www.nap.edu

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001 NOTICE: The working group summaries in this publication are based on working group discussions during the National Academies Keck Futures Initiative The Genomic Revolution: Implications for Treatment and Control of Infectious Disease Conference held at the Arnold and Mabel Beckman Center of the National Academies in Irvine, CA, November 10-13, 2005. The discussions in these groups were summarized by the authors and reviewed by the members of each working group. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the working groups and do not necessarily reflect the view of the organizations or agencies that provided support for this project. Funding for the activity that led to this publication was provided by the W.M. Keck Foundation. Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research, science, and engineering. The Foundation also maintains a Southern California Grant Program that provides support in the areas of civic and community services with a special emphasis on children. For more information, visit www.wmkeck.org. International Standard Book Number 0-309-10109-3 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, www.nap.edu. Copyright 2006 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries THE NATIONAL ACADEMIES Advisers to the Nation on Science, Engineering, and Medicine 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 government 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 outstanding 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. Wm. A. Wulf 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 scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE GENOMICS STEERING COMMITTEE ROBERT H. WATERSTON (Chair) (NAS/IOM),* William H. Gates III Endowed Chair in Biomedical Sciences, Chair and Professor, Department of Genome Sciences, University of Washington ARUP K. CHAKRABORTY (NAE), Warren and Katherine Schlinger Distinguished Professor and Chairman, Department of Chemical Engineering, University of California, Berkeley RONALD W. DAVIS (NAS), Professor of Biochemistry and Genetics, Director, Stanford Genome Technology Center, Stanford University School of Medicine HELENE D. GAYLE, M.D. (IOM), Director of HIV, TB and Reproductive Health, Bill & Melinda Gates Foundation DAVID GINSBURG, M.D. (IOM),** Investigator, Howard Hughes Medical Institute, James V. Neel Distinguished University Professor, Departments of Internal Medicine and Human Genetics, University of Michigan Medical School RICHARD M. KARP (NAS/NAE), University Professor, University of California, Berkeley, Senior Research Scientist, International Computer Science Institute DIANE MATHIS (NAS), William T. Young Chair in Diabetes Research, Professor of Medicine and Co-Head, Section on Immunology and Immunogenetics, Joslin Diabetes Center, Harvard Medical School *   Also Chair, Planning Committee. **   Also Member, Planning Committee.

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries THE NATIONAL ACADEMIES KECK FUTURES INITIATIVE GENOMICS PLANNING COMMITTEE BRUCE BEUTLER, M.D., Professor, Department of Immunology, The Scripps Research Institute SHU CHIEN (NAS/NAE/IOM), University Professor of Bioengineering and Medicine, Chair, Department of Bioengineering, University of California, San Diego VANESSA NORTHINGTON GAMBLE, M.D. (IOM), Director of the National Center for Bioethics in Research and Health Care, Tuskegee University ALAN E. GUTTMACHER, M.D., Deputy Director of the National Human Genome Research Institute, National Institutes of Health DAVID HAUSSLER, Director of the Center for Biomolecular Science & Engineering, Professor of Computer Science, Howard Hughes Medical Institute, University of California MUIN J. KHOURY, M.D., Director of the Office of Genomics and Disease Prevention, Centers for Disease Control and Prevention LEONID KRUGLYAK, Professor of Ecology and Evolutionary Biology and the Lewis-Sigler Institute for Integrative Genomics, Princeton University RICK LIFTON, M.D. (NAS/IOM), Chairman of the Department of Genetics, Professor of Medicine, Genetics, Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine DAVID LOCKHART, President and CSO (Co-founder and Director), Ambit Biosciences DEIRDRE MELDRUM, Director of the NIH Center for Excellence in Genomic Sciences (CEGS) Microscale Life Sciences Center, Professor of Electrical Engineering, University of Washington PAUL SCHAUDIES, Assistant Vice President and Division Manager, Biological and Chemical Defense Division, Science Applications International Corporation Staff KENNETH R. FULTON, Executive Director MARTY PERREAULT, Program Director MEGAN ATKINSON, Senior Program Specialist RACHEL LESINSKI, Senior Program Specialist ALEX COHEN, Research Associate / Programmer

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries The National Academies Keck Futures Initiative The National Academies Keck Futures Initiative was launched in 2003 to stimulate new modes of scientific inquiry and break down the conceptual and institutional barriers to interdisciplinary research. The National Academies and the W.M. Keck Foundation believe that considerable scientific progress will be achieved by providing a counterbalance to the tendency to isolate research within academic fields. The Futures Initiative is designed to enable scientists from different disciplines to focus on new questions, upon which they can base entirely new research, and to encourage and reward outstanding communication between scientists as well as between the scientific enterprise and the public. The Futures Initiative includes three main components: Futures Conferences The Futures Conferences bring together some of the nation’s best and brightest researchers from academic, industrial, and government laboratories to explore and discover interdisciplinary connections in important areas of cutting-edge research. Each year, some 100 outstanding researchers are invited to discuss ideas related to a single cross-disciplinary theme. Participants gain not only a wider perspective but also, in many instances, new insights and techniques that might be applied in their own work. Additional pre- or postconference meetings build on each theme to foster further communication of ideas.

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries Selection of each year’s theme is based on assessments of where the intersection of science, engineering, and medical research has the greatest potential to spark discovery. The first conference explored Signals, Decisions, and Meaning in Biology, Chemistry, Physics, and Engineering. The 2004 conference focused on Designing Nanostructures at the Interface between Biomedical and Physical Systems. The theme of the 2005 conference was The Genomic Revolution: Implications for Treatment and Control of Infectious Disease. In 2006, the conference will focus on Smart Prosthetics: Exploring Assistive Devices for the Body and Mind. Futures Grants The Futures Grants provide seed funding to Futures Conference participants, on a competitive basis, to enable them to pursue important new ideas and connections stimulated by the conferences. These grants fill a critical missing link between bold new ideas and major federal funding programs, which do not currently offer seed grants in new areas that are considered risky or exotic. These grants enable researchers to start developing a line of inquiry by supporting the recruitment of students and postdoctoral fellows, the purchase of equipment, and the acquisition of preliminary data—which in turn can position the researchers to compete for larger awards from other public and private sources. National Academies Communication Awards The Communication Awards are designed to recognize, promote, and encourage effective communication of science, engineering, medicine, and interdisciplinary work within and beyond the scientific community. Each year the Futures Initiative honors and rewards individuals with three $20,000 prizes, presented to individuals who have advanced the public’s understanding and appreciation of science, engineering, and/or medicine. Awards are given in three categories: book author; newspaper, magazine, or online journalist; and TV/radio correspondent or producer. The winners are honored during the Futures Conference. Facilitating Interdisciplinary Research Study During the first 18 months of the Keck Futures Initiative, the Academies undertook a study on facilitating interdisciplinary research. The study

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries examined the current scope of interdisciplinary efforts and provided recommendations as to how such research can be facilitated by funding organizations and academic institutions. Facilitating Interdisciplinary Research (2005) is available from the National Academies Press (www.nap.edu). About the National Academies The National Academies comprise the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council, which perform an unparalleled public service by bringing together experts in all areas of science and technology, who serve as volunteers to address critical national issues and offer unbiased advice to the federal government and the public. For more information, visit www.national-academies.org. About the W.M. Keck Foundation Based in Los Angeles, the W.M. Keck Foundation was established in 1954 by the late W.M. Keck, founder of the Superior Oil Company. The Foundation’s grant making is focused primarily on pioneering efforts in the areas of medical research, science, and engineering. The Foundation also maintains a Southern California Grant Program that provides support in the areas of civic and community services with a special emphasis on children. For more information, visit www.wmkeck.org. The National Academies Keck Futures Initiative 5251 California Avenue – Suite 230 Irvine, CA 92617 949-387-2464 (Phone) 949-387-0500 (Fax) www.keckfutures.org

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries Preface At the National Academies Keck Futures Initiative The Genomic Revolution: Implications for Treatment and Control of Infectious Disease conference, participants were divided into interdisciplinary working groups. The groups spent eight hours over four days exploring diverse challenges at the interface between science, engineering, and medicine. The goals of the working groups were to spur new thinking, to have people from different disciplines interact, and to forge new scientific contacts across disciplines. The working groups were not expected to solve the particular problems posed to the group, but rather to come up with a consensus method of attack and a thoughtful list of what we know and don’t know how to do, and what’s needed to get there. The composition of the groups were intentionally diverse, to encourage the generation of new approaches by combining a range of different types of contributions. The groups included researchers from science, engineering, and medicine, as well as representatives from private and public funding agencies, universities, businesses, journals, and the science media. Researchers represented a wide range of experience—from postdoc to those well-established in their careers—from a variety of disciplines that included genetics, microbiology, immunology, bioengineering, electrical engineering, chemistry, ecology, mechanical engineering, philosophy/ethics, law, medicine, epidemiology, and public health. The conference committee had five objectives for the working groups: To approach the application of genomics to infectious disease from the perspective of problems having potentially revolutionary impact, rather than from the perspective of extensions of existing technology;

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries To allow a group of people with a broad range of backgrounds to pool their insights and creativity to work on a shared interesting problem; To identify ideas and insights common to a number of working groups, and to identify how advances in genomics and their application might have a very large impact on the treatment and control of infectious disease; To identify the best (by whatever metrics seem to fit) big problems in the treatment and control of infectious disease to which genomics might be applied, and to identify gaps in knowledge that limit progress in the solution of these problems; and To allow individuals to make connections with one another in small working groups. The groups needed to address the challenge of communicating and working together from a diversity of expertise and perspectives, as they attempted to solve a complicated, interdisciplinary problem in a relatively short time. Each group decided on its own structure and approach to tackle the problem. Some groups decided to refine or redefine their problems, based on their experience. Each group presented two brief reports to the whole conference: (1) an interim report on Friday to debrief on how things were going, along with any special requests (such as an expert in DNA sequencing to talk with the group); and (2) a final briefing on Sunday where each group: Provided a concise statement of the problem Outlined a structure for its solution Identified the most important gaps in science and technology and recommended research areas needed to attack the problem Indicated the benefits to society if the problem could be solved Each working group included a graduate student in a university science writing program. Based on the group interaction and the final briefings, the students wrote the following summaries, which were reviewed by the group members. These summaries describe the problem and outline the approach taken, including what research needs to be done to understand the fundamental science behind the challenge, the proposed plan for engineering the application, the reasoning that went into it, and the benefits to society of the problem solution.

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries Contents     Conference Summary   1     WORKING GROUP SUMMARIES         Technology         Identify What Technological Advances in the Fields of Science and Engineering Need to Be Developed (Either New Technology or Novel Integration of Existing Technologies) to Improve Rapid Response to New or Emerging Diseases   9     Develop an Inexpensive (and Cost-Effective) Diagnostic Test That Could Be Deployed in Countries with Little Scientific Research Infrastructure   17     Vaccines / Genomic Analysis and Synthesis         How Would You Spend $100 Million Over the Next Five Years to Prevent the Next Pandemic Flu?   25     How Can Genomics Facilitate Vaccine Development?   33

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The Genomic Revolution: Implications for Treatment and Control of Infectious Disease - Working Group Summaries     Diagnosis         Develop a Device to Rapidly and Sensitively Detect and Identify Pathogens in an Environment or Population, Spread Either Naturally or Through Deliberate Acts   41     Are There Shared Pathways of Attack That Might Provide New Avenues of Prevention?   49     Explore the Emerging Role of Public Health in Integrating Genomics in Surveillance, Outbreak Investigations, and Control and Prevention of Infectious Diseases   57      Working Group 1 Summary,   60      Working Group 2 Summary,   66     Natural Variation         What Will It Take to Sequence an Individual’s Genome for Under $1,000 in Less Than 10 Years?   73     How Can We Use Natural Variation in Disease Resistance to Understand Host Pathogen Interactions and Devise New Therapies?   83      Working Group 1 Summary,   84      Working Group 2 Summary,   90     APPENDIXES          Conference Program   97      Participants   107