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Health and Medicine: Challenges for the Chemical Sciences in the 21st Century (2004)
Board on Chemical Sciences and Technology (BCST)

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CHALLENGES FOR THE CHEMICAL SCIENCES IN THE 21ST CENTURY HEALTH AND MEDICINE ORGANIZING COMMITTEE FOR THE WORKSHOP ON HEALTH AND MEDICINE COMMITTEE ON CHALLENGES FOR THE CHEMICAL SCIENCES IN THE 21 ST CENTURY BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY DIVISION ON EARTH AND LIFE STUDIES NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMY PRESS Washington, D.C. www.nap.edu

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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 Insti- tute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. Support for this study was provided by the National Research Council, the American Chemical Society, the American Institute of Chemical Engineers, E.I. Dupont de Nemours and Company, Merck and Company, Inc., Novartis Institutes for Biomedical Research, the Camille and Henry Dreyfus Foundation, Inc. under contract No. SG00-093, the Defense Advanced Research Projects Agency under contract No. MDA972-01-M-0001, the Na- tional Institute of Standards and Technology under contract No. NA1341-01-W-1070, the National Institutes of Health/National Cancer Institute under contract No. N0-OD-4-2139, the National Science Foundation under contract No. CTS-9908440, the U.S. Department of Energy/Basic Energy Science under contract No. DE-FG02-OOER15040, the U.S. De- partment of Energy/Office of Industrial Technologies under contract No. DE-AT01- 01EE41424, and the U.S. Environmental Protection Agency under contract No. CR828233- 01-0. All opinions, findings, conclusions, or recommendations expressed herein are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for this project. International Standard Book Number 0-309-08720-1 (Book) International Standard Book Number 0-309-52956-5 (PDF) Additional copies of this report are available from: The National Academies Press SOO 5th Skeet, N.W. Lockbox 285 Washington, DC 20055 800-624-6242 202-334-3313 (in the Washington Metropolitan Area) http://www.nap.edu Copyright 2004 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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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. Bruce M. Alberts 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 Sci- ences to secure the services of eminent members of appropriate professions in the exami- nation 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 Insti- tute 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. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-c~ccedemies.org

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ORGANIZING COMMITTEE FOR THE WORKSHOP ON HEALTH AND MEDICINE DOUGLAS A. LAUFFENBURGER, Massachusetts Institute of Technology, Co-chair CHRISTOPHER T. WALSH, Harvard Medical School, Co-chair PAUL S. ANDERSON, Bristol-Meyers Squibb Company (retired) MICHAEL A. MARIETTA, University of California, Berkeley C. DALE POULTER, University of Utah ELLEN LEAHY, Celera DAGMAR RINGE, Brandeis University L· ~ lalsons MICHAEL L. SHUEER, Cornell University PAUL J. REIDER, Amgen, Inc. SANGTAE KIM, Eli Lilly and Company CHI_HUEY WONG, SCriPPS Research Institute Staff ANDRIA L. HOBBS, Christine Mirzayan Intern CHRISTOPHER K. MORPH{, Program Officer DOUGLAS J. RABER, Senior Scholar DAVID C. RASMUSSEN, Program Assistant ERIC L. SHIPP, Postdoctoral Associate DOROTHY ZOEANDZ, Director v

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COMMITTEE ON CHALLENGES FOR THE CHEMICAL SCIENCES IN THE 21ST CENTURY RONALD Brow, Columbia University, Co-Chair MATTHEW V. TIRRELL, University of California, Santa Barbara, Co-Chair MARK A. BARTEAU, University of Delaware JAcQuEE~NE K. BARTON, California Institute of Technology CAROLYN R. BERTOZZI, University of California, Berkeley ROBERT A. BROWN, Massachusetts Institute of Technology ALICE P. GAST,! Stanford University IGNACIO E. GROSSMANN, Carnegie Mellon University JAMES M. MEYER,2 E. I. du Pont de Nemours & Co. ROYCE W. MURRAY, University of North Carolina, Chapel Hill PAUL J. REIDER, Amgen, Inc. WIGWAM R. ROUSH, University of Michigan MICHAEL L. SHULER, Cornell University JEFFREY J. SITROLA, Eastman Chemical Company GEORGE M. WHITESIDES, Harvard University PETER G. WOLYNES, University of California, San Diego RICHARD N. ZARE, Stanford University Staff JENNIFER J. JACK1W, Program Officer CHRISTOPHER K. MURPHY, Program Officer SYBIE A. PAIGE, Administrative Associate DOUGLAS J. RABER, Senior Scholar DAVID C. RASMUSSEN, Program Assistant ERIC L. SHIPS, Postdoctoral Associate DOROTHY ZOEANDZ, Director Committee member until July 2001. 2Committee member until March 2002. Vl

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BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY WILLIAM KEEMPERER, Harvard University, Co-Chair AR~o~D F. STANcE~, Georgia Institute of Technology, Co-Chair DENISE M. BARNES, Amalan Networks A. WELFORD CASTLEMAN, JR., The Pennsylvania State University ANDREA W. CHOW, Caliper Technologies Corp. THOMAS M. CoNNE~Y, JR., E. I. du Pont de Nemours and Company MARK E. DAVIS, California Institute of Technology JEAN DE GRAEVE, Institut de Pathologic, Liege, Belgium JOSEPH M. DESIMONE, University of North Carolina, Chapel Hill, and North Carolina State University CATHERINE FENSELAU, University of Maryland MAURICTO FurRAN, Bristol-Myers Squibb Company MARY L. GOOD, University of Arkansas, Little Rock Lou ANN HEIMBROOK, Merck & Co. NANCY B. JACKSON, Sandia National Laboratories MARTHA A. KREBS, Science Strategies WIGWAM A. LESTER, JR., University of California, Berkeley GREGORY O. NE~soN, Eastman Chemical Company ROBERT M. SUSSMAN, Latham & Watkins Staff TINA MASCIANGIOEI, Program Officer CHRISTOPHER K. MURPHY, Program Officer SYBIE A. PAIGE, Administrative Associate DAVID C. RASMUSSEN, Program Assistant DOROTHY ZOLANDZ, Director . . V11

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Preface The Workshop on Health and Medicine, held in Irvine, California, on De- cember 2-4, 2002, was the last of six workshops that will make up the study Challenges for the Chemical Sciences in the 21st Century. The task for each workshop was defined as follows: Each workshop and its subsequent report will address a series of com- mon themes: · Discovery: Identify major discoveries or advances in the chemical sci- ences during the last several decades. · Interfaces: Identify the major discoveries and challenges at the interfaces between chemistry/chemical engineering and such areas as biology, environmen- tal science, materials science, medicine, and physics. · Challenges: Identify the grand challenges that exist in the chemical sci- ences. · Infrastructure: Identify the issues and opportunities that exist in the chemi- cal sciences to improve the infrastructure for research and education, and demon- strate the value of these activities to society. The Workshop on Health and Medicine brought together a diverse group of participants (see Appendix D) including speakers on a variety of issues and chal- lenges for the chemical sciences as they relate to health and medicine. The pre- sentations served as a starting point for discussions and comments by the partici- pants. The workshop participants were then divided into small groups that met ix

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x PREFACE periodically during the workshop to further discuss and analyze the issues. Each group provided its discussions to the workshop as a whole. This report is intended to reflect the concepts and opinions discussed at the Workshop on Health and Medicine; it is not intended to be a comprehensive overview of all the potential challenges for the chemical sciences in health and medical technology. Additionally, the report is a meeting summary and not a consensus report. This study was conducted under the auspices of the National Research Council's Board on Chemical Sciences and Technology, with assistance provided by its staff. The committee acknowledges this support. Douglas A. Lauffenburger Christopher T. Walsh Co-chairs, Organizing Committee for the Workshop on Health and Medicine

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Acknowledgment of Reviewers This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures ap- proved by the National Research Council's Report Review Committee. The pur- pose of this independent review is to provide candid and critical comments that will assist the institution in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manu- script remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their participation in the review of this report: Paul Bartlett, University of California, Berkeley Cynthia Burrows, University of Utah Joel Huff, Merck & Co., Inc. Laura Kiessling, University of Wisconsin Dorothy Margolskee, Prospect Ventures Anna Maria Pyle, Yale University Ian Tomlinson, Dow Chemical Company Although the reviewers listed above have provided many constructive com- ments and suggestions, they were not asked to endorse the conclusions or recom- mendations nor did they see the final draft of the report before its release. The review of this report was overseen by Gregory Petsko, Brandeis University. Ap- pointed by the National Research Council, he was responsible for making certain Xl

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. . X11 ACKNOWLEDGMENT OF REVIEWERS that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

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Contents EXECUTIVE SUMMARY 1 NEW TOOLS AND APPROACHES FOR DISCOVERY, DIAGNOSTICS, AND PREVENTION 2 NEW METHODS IN SYNTHESIS AND DEVELOPMENT FOR PHARMACEUTICALS 1 7 13 3 NEW DIRECTIONS IN MANUFACTURING AND DELIVERY 21 4 ACCOMPLISHMENTS AND CHALLENGES IN HEALTH AND MEDICINE FOR CHEMISTRY AND CHEMICAL ENGINEERING APPENDIXES A STATEMENT OF TASK B BIOGRAPHIES OF THE ORGANIZING COMMITTEE MEMBERS C WORKSHOP AGENDA D PARTICIPANTS E REPORTS FROM THE BREAKOUT SESSION GROUPS . . . X111 27 37 38 41 44 46

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