BRIDGES TO INDEPENDENCE

FOSTERING THE INDEPENDENCE OF NEW INVESTIGATORS IN BIOMEDICAL RESEARCH

Committee on Bridges to Independence: Identifying Opportunities for and Challenges to Fostering the Independence of Young Investigators in the Life Sciences

Board on Life Sciences

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS
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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research BRIDGES TO INDEPENDENCE FOSTERING THE INDEPENDENCE OF NEW INVESTIGATORS IN BIOMEDICAL RESEARCH Committee on Bridges to Independence: Identifying Opportunities for and Challenges to Fostering the Independence of Young Investigators in the Life Sciences Board on Life Sciences NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW 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 study was supported by Contract No. N01-OD-4-2139 (Task Order #89) between the National Academy of Sciences and the National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. International Standard Book Number 0-309-09626-X (Book) International Standard Book Number 0-309-54965-5 (PDF) Library of Congress Control Number 2005927466 Additional copies of this report are available from the National Academies Press, 500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu. Cover image: Golden Gate Bridge looking north from the south tower, Golden Gate National Recreation Area, National Park Service. Photo by Jeff Weisenburger, WideVisionPans.com. Copyright 2005 by the National Academy of Sciences. All rights reserved. Printed in the United States of America.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research 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 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. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council. www.national-academies.org

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research COMMITTEE ON BRIDGES TO INDEPENDENCE: IDENTIFYING OPPORTUNITIES FOR AND CHALLENGES TO FOSTERING THE INDEPENDENCE OF YOUNG INVESTIGATORS IN THE LIFE SCIENCES THOMAS R. CECH (Chair), Howard Hughes Medical Institute, Chevy Chase, Maryland AARON DIANTONIO, Washington University, St. Louis, Missouri JANICE G. DOUGLAS, Case Western Reserve University, Cleveland, Ohio SUSAN A. GERBI, Brown University, Providence, Rhode Island BRUCE R. LEVIN, Emory University, Atlanta, Georgia CAROL L. MANAHAN, AAAS Science and Technology Policy Fellow,1 Arlington, Virginia GEORGINE M. PION, Vanderbilt University, Nashville, Tennessee DAGMAR RINGE, Brandeis University, Waltham, Massachusetts JULIE A. THERIOT, Stanford University, Stanford, California KEITH R. YAMAMOTO, University of California, San Francisco, California Staff ADAM P. FAGEN, Study Director KERRY A. BRENNER, Senior Program Officer CARA B. ALLEN, Christine Mirzayan Science and Technology Policy Graduate Fellow SETH H. STRONGIN, Senior Program Assistant BRENDAN BRADLEY, Program Assistant/Research Intern KATHI E. HANNA, Writer PAULA T. WHITACRE, Editor 1   Placed at the National Science Foundation through the AAAS/NSF Science and Engineering Fellowship Program.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research BOARD ON LIFE SCIENCES COREY S. GOODMAN (Chair), Renovis, Inc., South San Francisco, California ANN M. ARVIN, Stanford University School of Medicine, Stanford, California JEFFREY L. BENNETZEN, University of Georgia, Athens, Georgia RUTH BERKELMAN, Emory University, Atlanta, Georgia R. ALTA CHARO, University of Wisconsin, Madison, Wisconsin DENNIS CHOI, Merck Research Laboratories, West Point, Pennsylvania JEFFREY L. DANGL, University of North Carolina, Chapel Hill, North Carolina PAUL R. EHRLICH, Stanford University, Stanford, California JAMES M. GENTILE, Research Corporation, Tucson, Arizona ED HARLOW, Harvard Medical School, Boston, Massachusetts DAVID HILLIS, University of Texas, Austin, Texas KENNETH H. KELLER, University of Minnesota, Minneapolis, Minnesota RANDALL MURCH, Virginia Polytechnic Institute and State University, Alexandria, Virginia GREGORY A. PETSKO, Brandeis University, Waltham, Massachusetts STUART L. PIMM, Duke University, Durham, North Carolina BARBARA A. SCHAAL, Washington University, St. Louis, Missouri JAMES TIEDJE, Michigan State University, East Lansing, Michigan KEITH R. YAMAMOTO, University of California, San Francisco, California Staff FRANCES E. SHARPLES, Director KERRY A. BRENNER, Senior Program Officer MARILEE K. SHELTON-DAVENPORT, Senior Program Officer ROBERT T. YUAN, Senior Program Officer ADAM P. FAGEN, Program Officer ANN H. REID, Program Officer EVONNE P. Y. TANG, Program Officer JOSEPH C. LARSEN, Postdoctoral Research Associate DENISE GROSSHANS, Financial Associate SETH H. STRONGIN, Senior Program Assistant MATTHEW MCDONOUGH, Program Assistant

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research Foreword The year is 2029. Alarmed by the evidence that most of the break-throughs in biomedical science are coming from Asia and Europe, the newly inaugurated President of the United States asks the National Academy of Sciences (NAS) to help the nation understand how we lost our preeminent leadership position. The concern was not merely academic, not just the fact that Americans were now only occasionally seen in the ranks of awardees of Nobel Prizes and constituted fewer and fewer of the authors of articles in the very top scientific journals. Instead, the public’s concern was mostly economic: several new blockbuster pharmaceuticals were coming onto the market each year, highly successful treatments for several kinds of cancer, diabetes, Parkinson’s disease, and schizophrenia. Most were invented, patented, tested, and manufactured in Asia and Europe; none in the United States. Essentially all of the economic stimuli created by these drugs—including all of the jobs—had been unintentionally “outsourced.” Worse yet, a country that had developed powerful antiviral compounds to treat the last two pandemic bird flu viruses was on rocky political terms with the United States and had refused shipments of the drugs; a vigorous black market had developed, but there was no legal supply. It was not difficult for the NAS Committee in 2029 to trace the root causes of the U.S. fall from preeminence in biomedical science. American college students had always paid close attention to what their peers had to say: The stories of a decade-long post-baccalaureate training period characterized by long hours and low pay were discouraging enough, but when coupled with the slim chance of advancing to an independent re-

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research search position before the age of 40, few of the most talented American students were enticed. Further, the supply of foreign scholars who wished to study or obtain jobs in the United States had dwindled. The intellectually hungry from abroad, who had increasingly filled in the workforce gap in U.S. biomedical sciences during the 1990s and 2000s, now found vibrant opportunities in their home countries and were no longer clamoring to immigrate, or even to visit. At U.S. universities and medical schools, the decades of training required before appointments to faculty positions had combined with tenure without a mandatory retirement age to increase the median faculty member’s age at research institutions to nearly 60 years old. Ironically, the problems had their root in the very success of the National Institutes of Health (NIH) system, which continued to fund most academic biomedical research. The NIH system had been the envy of the world in the 1990s: Research grant funds were distributed through a merit-based, peer-reviewed, non-political process. The system was steeped in integrity. But the very success of the system led to a complacency that became its downfall. Competency and productivity were honored to the point that they became the enemies of greatness. The system placed too much emphasis on the number of papers published, too little on whether really important problems were even being tackled. Because requests for grant funds from new investigators were evaluated on the basis of “preliminary results,” most funded research became constrained to well-worn research paths—those previously pursued by the new investigators when they were postdoctoral fellows in established laboratories. In short, innovation was the victim of a system that had become much too risk adverse. Well, it is 2005, not 2029. Although we fear that our nation may be traveling the path described above, there is still time to redirect our steps. This National Research Council (NRC) report on Bridges to Independence is but the most recent of an ongoing series of recommendations for reform of the NIH grant system and of the treatment of postdoctoral researchers. The Committee notes that many of the ideas in this report have been recommended in earlier reports—but not implemented. After examining some of the reasons why previous recommendations have not been implemented, the Committee urges that the NIH treat the suggested innovations as a collection of bold ideas to be tried at least on an experimental basis, if not implemented full scale, to improve support for researchers making the transition to independence. The goal is a transformation of NIH support for biomedical research that strongly promotes the new ideas of our best early career stage scientists, while preserving the peer review and integrity of current NIH processes. The status quo will certainly not do: it is well past time for our

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research scientific leadership to be bold in ensuring the future of our nation’s remarkably successful biomedical research system. Thomas R. Cech, PhD President, Howard Hughes Medical Institute; Chair, Authoring Committee Bruce Alberts, PhD President, National Academy of Sciences; Chair, National Research Council

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research Acknowledgments The report benefited from the contribution of many individuals who provided their expertise, insight, and research. The committee would like to especially thank the speakers and participants in the June 16, 2004, public workshop, for providing data on the issues confronting new investigators in the life sciences; the workshop agenda and participant list are included in Appendix B. Data on issues related to career progression was provided by James Voytuk of the Board on Higher Education and Workforce at the National Research Council. Data on NIH grant applications and success rates was provided by the Office of Extramural Research at the National Institutes of Health (NIH); the committee would like to especially acknowledge the assistance of Norka Ruiz Bravo, Walter Schaffer, Bill McGarvey, Bob Moore, James Onken, and Karl Malik. Additional information and insight from NIH was provided by Ruth Kirschstein, Jeremy Berg, Ellie Ehrenfeld, Brent Stanfield, Belinda Seto, Walter Schaffer, and Deborah Swope. Information about postdoctoral policies was provided by Keith Micoli and Alyson Reed of the National Postdoctoral Association. Data on postdocs was also provided by Maxine Singer and Laurel Haak. Information about model programs was taken from program websites as well as from program officials and recipients including Douglas Hanahan, Martin Ionescu-Pioggia, George Reinhart, Allan Spradling, Kevin Eggan, Alan Jasanoff, Saurabh Jha, Dmitri Petrov, and Judith Yanowitz. This report has been reviewed in draft form by persons chosen for

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research 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 of 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 this report: Karen S. Christopherson, Stanford University Robert D. Goldman, Northwestern University Jason Lieb, University of North Carolina at Chapel Hill Shirley M. Malcom, American Association for the Advancement of Science Ed Penhoet, Gordon and Betty Moore Foundation Maxine Singer, Carnegie Institution of Washington Paula E. Stephan, Georgia State University Charles F. Stevens, Salk Institute for Biological Studies Jack L. Strominger, Harvard University Jane Sullivan, University of Washington Michael Teitelbaum, Alfred P. Sloan Foundation Shirley M. Tilghman, Princeton University James Wells, Sunesis Pharmaceuticals, Inc. Marylynn V. Yates, University of California, Riverside Although the reviewers listed above have provided constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by Alan I. Leshner, American Association for the Advancement of Science, and Elena O. Nightingale, Scholar-in-Residence, Institute of Medicine. Appointed by the National Research Council, they were 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 carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research Contents     Summary   1 1   Introduction   15      Committee Statement of Task,   19      A Time for Action,   24      Definitions,   25      Context and Background,   27      Career Transition Awards,   28      Review of Grant Applications,   28      Sufficient Resources and Funding Policies,   29      Protected Time,   30      Feedback,   31      Career Guidance,   31      Need for Data,   32      Work of the Committee,   32      Organization of the Report,   33 2   Where Are We Now?   34      Grant Success by Age,   37      Demographic Data,   44      Grant Proposals from New Investigators,   50      Review Process,   51      Risk Taking,   56

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research      Current and Recent Opportunities for New Investigators,   57      New Investigator Awards from NIH,   60      National Science Foundation,   63      Other Federal Support for New Investigators,   65      Private Sector Programs for New Investigators,   65      European Models,   72      Conclusion,   73 3   A Vision for 2010   74      New Allocation Strategies and Funding Mechanisms for Supporting Postdoctoral Researchers,   75      Fostering Collaborative Research,   75      New Investigators and the R01 System,   76      Changes Needed in Academic Research Institutions,   77      Changing Attribution and Publication Policies,   77      Recognize and Reward Non-Tenure-Track Pathways,   78      Need for Faculty Reform,   78      Need for Data,   79 4   Optimizing Postdoctoral Training   80      Length of the Postdoctoral Appointment,   82      Reallocate NIH Resources for Postdoctoral Support,   86      Independent Funding,   92      Clarifying the Mentorship Responsibilities of PIs,   93      Broaden Educational Opportunities,   95      Need for Better Data and Program Evaluation,   99 5   Transition to First Independent Position   102      Career Transition Research Grants,   103      Program Assessment,   108      Non-Tenure-Track Scientists,   109 6   Establishing Stable Research Programs   110      R01s for New Investigators,   111      Support for Non-Tenure-Track Scientists,   114      Independent Grant Support for All Researchers,   114      Providing for Enhanced Job Security,   115      Data Collection,   117 7   Conclusion   118     References   121

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research     Appendixes     A   Committee Statement of Task   125 B   Workshop Information   127 C   Acronyms and Abbreviations   145 D   Committee Member Biographies   148

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research LIST OF FIGURES, TABLE, AND BOXES Figures 1-1   Age distribution of principal investigators receiving competing R01, R23, R29, and R37 research awards, by number of awards made to each age cohort,   16 1-2   Age distribution of principal investigators receiving competing R01, R23, R29, and R37 research awards, by percentage of awards made to each age cohort,   16 1-3   Number of NIH research awards made to PIs 35 years of age and younger,   17 1-4   NIH awards made to new investigators,   17 2-1   Complex network of current career pathways to independent investigator,   36 2-2   Success rate of competing new R01 and R29 grant application by age of principal investigator,   37 2-3   Number of R01, R23, R29, or R37 applications by age cohort,   38 2-4   Average age at time of first assistant professorship at U.S. medical schools and receipt of first R01/R29 award,   39 2-5   Instructions for PHS 398,   41 2-6   First NIH award for new investigators,   42 2-7   Entry and egress rates of NIH research project grantinvestigators,   43 2-8   Number of biomedical PhDs age 35 or younger and the number of those holding tenure-track positions,   46 2-9   Status of U.S.-earned biomedical PhDs employed at academic institutions, by gender,   48 2-10   Cohort analysis of U.S-earned biomedical PhDs employed at academic institutions,   49 2-11   Distribution of priority scores for R01 applications for new and previously funded investigators, October 2003 – May 2004 Council rounds,   54 2-12   Differences in median priority scores within study sections between new and previously funded investigators for new R01 applications,   55 2-13   Success rate for NIGMS R01 applications from new and previously funded investigators, by percentile score,   58 2-14   Success rate of R01/R23/R29 applicants with no prior support and other applicants for new R01s,   61 4-1   Sources of support for biomedical sciences postdoctoral scholars at academic institutions,   88

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Bridges to Independence: Fostering the Independence of New Investigators in Biomedical Research 4-2   Citizenship of biomedical sciences postdoctoral scholars at academic institutions,   90 7-1   Transition and career stages addressed by recommendations in the report,   120 Table 2-1   Average age for applicants and awardees for competing awards for new and previously funded investigators,   40 Boxes 1-1   Summary of the Committee Statement of Task,   20 1-2   NIH Definition of New Investigator,   25 1-3   Independence,   26 2-1   Data Sources on the Biomedical Workforce,   45 2-2   Overview of NIH Grant Review Process,   52 2-3   Guidelines for Reviewers of New Investigator R01s,   53 2-4   NIBIB New Investigator Policy,   56 2-5   NIGMS Support for New Investigators,   58 4-1   Defining the Postdoctoral Position,   82 4-2   Citizenship Eligibility Requirements for Ruth L. Kirschstein National Research Service Awards for Individual Postdoctoral Fellows (F32),   90 4-3   Career Development Programs for Postdoctoral Fellows at the University of North Carolina at Chapel Hill,   97 4-4   Office of Fellows’ Career Development at NIEHS,   98 5-1   Success of Career Transition Awards, Burroughs Wellcome Fund,   104

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