Research at the Intersection of the Physical and Life Sciences

Committee on Research at the Intersection of the Physical and Life Sciences

Board on Physics and Astronomy

Board on Life Sciences

Board on Chemical Sciences and Technology

Division on Engineering and Physical Sciences

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

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Research at the Intersection of the Physical and Life Sciences Committee on Research at the Intersection of the Physical and Life Sciences Board on Physics and Astronomy Board on Life Sciences Board on Chemical Sciences and Technology Division on Engineering and Physical Sciences Division on Earth and Life Studies

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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 the Department of Energy under Award No. DE-FG02-07ER46378, the National Science Foundation under Award No. CHE-0554275, the Department of Health and Human Services under Award No. N01-OD-4-2139, the Burroughs Wellcome Fund under Award No. 1007560, and the Research Corporation for Science Advancement under Award No. 7827. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the views of the sponsors. International Standard Book Number-13: 978-0-309-14751-4 International Standard Book Number-10: 0-309-14751-4 Library of Congress Control Number: 2010921434 Cover: Work at the intersection of the life sciences and the physical sciences has often been depicted in new ways of imaging or modeling biological specimens, some of which are illustrated on the cover: (1) three-dimensional distribution of membrane proteins within a cell revealed through iPALM imaging (courtesy of Harald F. Hess, Howard Hughes Medical Institute); (2) xylose isomerase crystal (courtesy of Department of Energy Office of Basic Energy Research (BER)-funded neutron Protein Crystal- lography Station at Los Alamos National Laboratory (LANL)); (3) simulation of confinement of DNA in viral capsid (courtesy of Molecular Dynamics and Statistical Mechanics Research Group, University of Wisconsin at Madison); (4) diffusion tension imaging of the human brain (courtesy of Thomas Schultz, University of Chicago); (5) chromosome pairs; (6) modeled structure for the enzyme D-xylose isomerase (courtesy of Department of Energy BER- funded neutron Protein Crystallography Station at LANL; (7) anglerfish ovary obtained using autofluorescence (courtesy of James E. Hayden, Wistar Institute, Philadelphia); and (8) rat cerebellum obtained using two-photon excitation fluorescence microscopy (courtesy of the National Center for Microscopy and Imaging Research at the University of California at San Diego and the National Institutes of Health. IMAGE SOURCES: (1) Harald F. Hess, Howard Hughes Medical Institute; (2) Department of Energy Office of Basic Energy Research (BER)-funded neutron Protein Crystallography Station at Los Alamos National Laboratory (LANL); (3) Molecular Dynamics and Statistical Mechanics Research Group, University of Wisconsin at Madison; (4) Thomas Schultz, University of Chicago; (6) Department of Energy BER-funded neutron Protein Crystallography Station at LANL; (7) James E. Hayden, Wistar Institute, Philadelphia; and (8) National Center for Microscopy and Imaging Research at the Univer- sity of California at San Diego and the National Institutes of Health. Copies of this report are available from: National Academies Press, 500 Fifth Street, N.W., Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet ; and the Board on Physics and Astronomy, National Research Council, 500 Fifth Street, N.W., Washington, DC 20001; Internet . Copyright 2010 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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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 govern - ment 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. 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 scientific 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 Research Council. www.national-academies.org

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COMMITTEE ON RESEARCH AT THE INTERSECTION OF THE PHYSICAL AND LIFE SCIENCES ERIN K. O’SHEA, Co-Chair, Harvard University PETER G. WOLYNES, Co-Chair, University of California at San Diego ROBERT H. AUSTIN, Princeton University BONNIE L. BASSLER, Princeton University CHARLES R. CANTOR, Sequenom, Inc. WILLIAM F. CARROLL, Occidental Chemical Corporation THOMAS R. CECH, Howard Hughes Medical Institute CHRISTOPHER B. FIELD, Carnegie Institution Department of Global Ecology GRAHAM R. FLEMING, University of California at Berkeley ROBERT J. FULL, University of California at Berkeley SHIRLEY ANN JACKSON, Rensselaer Polytechnic Institute LAURA L. KIESSLING, University of Wisconsin at Madison CHARLES M. LOVETT, JR., Williams College DIANNE NEWMAN, Massachusetts Institute of Technology MONICA OLVERA de la CRUZ, Northwestern University JOSÉ N. ONUCHIC, University of California at San Diego GREGORY A. PETSKO, Brandeis University ASTRID PRINZ, Emory University CHARLES V. SHANK, Lawrence Berkeley National Laboratory (retired) BORIS I. SHRAIMAN, University of California at Santa Barbara H. EUGENE STANLEY, Boston University GEORGE M. WHITESIDES, Harvard University Staff DONALD C. SHAPERO, Director, Board on Physics and Astronomy FRANCES E. SHARPLES, Director, Board on Life Sciences DOROTHY ZOLANDZ, Director, Board on Chemical Sciences and Technology ADAM P. FAGEN, Senior Program Officer, Board on Life Sciences JAMES C. LANCASTER, Program Officer, Board on Physics and Astronomy KATHRYN J. HUGHES, Program Officer, Board on Chemical Sciences and Technology NATALIA MELCER, Program Officer, Board on Physics and Astronomy LAVITA COATES-FOGLE, Senior Program Assistant v

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SOLID STATE SCIENCES COMMITTEE BARBARA JONES, Chair, IBM Almaden Research Center MONICA OLVERA de la CRUZ, Vice-Chair, Northwestern University DANIEL AROVAS, University of California at San Diego COLLIN L. BROHOLM, The Johns Hopkins University PAUL CHAIKIN, New York University GEORGE CRABTREE, Argonne National Laboratory ANDREA J. LIU, University of Pennsylvania JOSEPH ORENSTEIN, University of California at Berkeley ARTHUR P. RAMIREZ, LGS, a subsidiary of Alcatel-Lucent, and Columbia University RICHARD A. REGISTER, Princeton University MARK STILES, National Institute of Standards and Technology DALE J. VAN HARLINGEN, University of Illinois at Urbana-Champaign FRED WUDL, University of California at Santa Barbara Staff DONALD C. SHAPERO, Director, Board on Physics and Astronomy MICHAEL H. MOLONEY, Associate Director JAMES C. LANCASTER, Program Officer LAVITA COATES-FOGLE, Senior Program Assistant BETH DOLAN, Financial Associate vi

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BOARD ON PHYSICS AND ASTRONOMY MARC A. KASTNER, Chair, Massachusetts Institute of Technology ADAM S. BURROWS, Vice-Chair, University of Arizona JOANNA AIZENBERG, Harvard University JAMES E. BRAU, University of Oregon PHILIP H. BUCKSBAUM, Stanford University PATRICK L. COLESTOCK, Los Alamos National Laboratory RONALD C. DAVIDSON, Princeton University ANDREA M. GHEZ, University of California at Los Angeles PETER F. GREEN, University of Michigan LAURA H. GREENE, University of Illinois at Urbana-Champaign MARTHA P. HAYNES, Cornell University JOSEPH HEZIR, EOP Group, Inc. MARK KETCHEN, IBM Thomas J. Watson Research Center ALLAN H. MacDONALD, University of Texas at Austin PIERRE MEYSTRE, University of Arizona HOMER A. NEAL, University of Michigan JOSE N. ONUCHIC, University of California at San Diego LISA J. RANDALL, Harvard University CHARLES V. SHANK, Lawrence Berkeley National Laboratory (retired) MICHAEL S. TURNER, University of Chicago MICHAEL C.F. WIESCHER, University of Notre Dame Staff DONALD C. SHAPERO, Director MICHAEL H. MOLONEY, Associate Director ROBERT L. RIEMER, Senior Program Officer JAMES C. LANCASTER, Program Officer DAVID B. LANG, Program Officer CARYN J. KNUTSEN, Research Associate BETH DOLAN, Financial Associate vii

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BOARD ON LIFE SCIENCES KEITH YAMAMOTO, Chair, University of California at San Francisco ANN M. ARVIN, Stanford University BONNIE L. BASSLER, Princeton University VICKI L. CHANDLER, Gordon and Betty Moore Foundation SEAN EDDY, HHMI Janelia Farm Research Campus MARK D. FITZSIMMONS, John D. and Catherine T. MacArthur Foundation DAVID R. FRANZ, Midwest Research Institute LOUIS J. GROSS, University of Tennessee at Knoxville JO HANDELSMAN, University of Wisconsin at Madison CATO T. LAURENCIN, University of Connecticut JONATHAN D. MORENO, University of Pennsylvania ROBERT M. NEREM, Georgia Institute of Technology CAMILLE PARMESAN, University of Texas at Austin MURIEL E. POSTON, Skidmore College ALISON G. POWER, Cornell University BRUCE W. STILLMAN, Cold Spring Harbor Laboratory CYNTHIA WOLBERGER, Johns Hopkins University School of Medicine MARY WOOLLEY, Research! America Staff FRANCES E. SHARPLES, Director JO L. HUSBANDS, Scholar/Senior Project Director ADAM P. FAGEN, Senior Program Officer ANN H. REID, Senior Program Officer MARILEE K. SHELTON-DAVENPORT, Senior Program Officer INDIA HOOK-BARNARD, Program Officer ANNA FARRAR, Financial Associate CARL-GUSTAV ANDERSON, Senior Program Assistant AMANDA P. CLINE, Senior Program Assistant AMANDA MAZZAWI, Program Assistant viii

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BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY F. FLEMING CRIM, Co-Chair, University of Wisconsin at Madison GARY S. CALABRESE, Co-Chair, Corning, Inc. BENJAMIN ANDERSON, Lilly Research Laboratories PABLO G. DEBENEDETTI, Princeton University RYAN R. DIRKX, Arkema, Inc. MARY GALVIN-DONOGHUE, Air Products and Chemicals Materials PAULA T. HAMMOND, Massachusetts Institute of Technology CAROL J. HENRY, Advisor and Consultant RIGOBERTO HERNANDEZ, Georgia Institute of Technology CHARLES E. KOLB, Aerodyne Research, Inc. MARTHA A. KREBS, California Energy Commission CHARLES T. KRESGE, Dow Chemical Company SCOTT J. MILLER, Yale University DONALD PROSNITZ, RAND Corporation MARK A. RATNER, Northwestern University ERIK J. SORENSEN, Princeton University WILLIAM C. TROGLER, University of California at San Diego THOMAS H. UPTON, ExxonMobil Staff DOROTHY ZOLANDZ, Director ANDREW CROWTHER, Postdoctoral Research Associate KATHRYN J. HUGHES, Program Officer TINA MASCIANGIOLI, Senior Program Officer ERICKA McGOWAN, Associate Program Officer JESSICA L. PULLEN, Administrative Assistant SHEENA SIDDIQUI, Research Assistant LYNELLE VIDALE, Project Assistant ix

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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 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 published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsive- ness 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 this report: Marlene Belfort, New York State Department of Health Robert Dimeo, National Institute of Standards and Technology James Heath, California Institute of Technology Jennifer Lippincott-Schwartz, National Institutes of Health Andrea Liu, University of Pennsylvania Peter Moore, Yale University Aravi Samuel, Harvard University Philip Sharp, Massachusetts Institute of Technology Erik Sorensen, Princeton University 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 xi

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Acknowledgment RevieweRs xii of review of this report was overseen by W. Carl Lineberger, University of Colorado at Boulder. Appointed by the National Research Council, he was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were care- fully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

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Contents SUMMARY 1 1 INTRODUCTION 9 2 GRAND CHALLENGES 12 Grand Challenge 1. Synthesizing Lifelike Systems, 12 Grand Challenge 2. Understanding the Brain, 14 Grand Challenge 3. Predicting Individual Organisms’ Characteristics from Their DNA Sequence, 15 Grand Challenge 4. Interactions of the Earth, Its Climate, and the Biosphere, 16 Grand Challenge 5. Understanding Biological Diversity, 18 3 SOCIETAL CHALLENGES 20 Identifying and Combating Biological Threats, 21 Early Detection and Intervention, 21 Prediction of Susceptibility to Disease and Its Prevention, 22 Climate and Its Interface with Biology, 23 Complex Feedback Loops in Climate Science, 23 Implications of Renewable Energy, 23 Medicine, 24 Imaging, 24 Treatment and Devices, 25 xiii

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contents xiv Agriculture as a Resource for Food and Energy, 25 Building Better Plants and Getting More Out of Them, 26 Hydrogenases and Synthetic Photosynthesis, 27 Beyond Combustion, 27 Materials Science, 28 Opportunities, 28 References, 29 4 COMMON THEMES AT THE INTERSECTION OF BIOLOGICAL 30 AND PHYSICAL SCIENCES Interaction and Information: From Molecules to Organisms and Beyond, 30 Dynamics, Multistability, and Stochasticity, 36 Self-organization and Self-assembly, 42 Conclusion, 48 References, 49 5 ENABLING TECHNOLOGIES AND TOOLS FOR RESEARCH 51 Introduction, 51 Physical Basis of Molecular Recognition, 52 Structures and Dynamics Within Cells, 53 Cellular Environment, 53 Interactions Within Cells, 55 Examining Structures Within Cells, 56 Theory and Simulations, 60 Collective Dynamics, 64 Complex Community Signals and Shared Resources at Large Length Scales, 65 References, 68 6 ENABLING RESEARCH AT THE INTERSECTION: PROMOTING 69 TRAINING, SUPPORT, AND COMMUNICATION ACROSS DISCIPLINES Connections Between Disciplines, 70 Culture of Separation Between the Life and Physical Sciences, 70 Culture and Organization of Academia, 72 Organization of Support for Research, 73 Supporting Transformative Research, 78 Educating Scientists at the Intersection of the Physical and Life Sciences, 82

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contents xv Enabling Interdisciplinary Research Starting at the Undergraduate Level, 82 Integrating Life and Physical Sciences for Graduate Students and Postdoctoral Researchers, 85 References, 89 APPENDIXES A Statement of Task 93 B Meeting Agendas 94 C Biographies of Committee Members 99

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