Scope and Federal Support of Scope and Federal Support of

Research and Training in Research and Training in

Biochemistry: Biochemistry:

New Challenges for ScientistsNew Challenges for Scientists

AgenciesAgencies

AcademiaAcademia

Keith R.YamamotoKeith R.YamamotoProfessor, Cellular and Molecular PharmacologyProfessor, Cellular and Molecular Pharmacology

Executive Vice Dean, School of MedicineExecutive Vice Dean, School of Medicineyamamoto@medsch.ucsf.eduyamamoto@medsch.ucsf.edu

AMGDB Annual MeetingAMGDB Annual MeetingCancun, Quintana Roo, MexicoCancun, Quintana Roo, Mexico

January 15, 2009 January 15, 2009

• Budget levels (duh…)Budget levels (duh…)• Budget levels (duh…)Budget levels (duh…)

Federal funding of research: Federal funding of research: What determinants affect ability to What determinants affect ability to

address current and future needs?address current and future needs?

• Support of early career scientistsSupport of early career scientists-- at peak of energy and creativity; training the -- at peak of energy and creativity; training the

next next generation; major investment made in their generation; major investment made in their

trainingtraining

• Support of early career scientistsSupport of early career scientists-- at peak of energy and creativity; training the -- at peak of energy and creativity; training the

next next generation; major investment made in their generation; major investment made in their

trainingtraining• Support of transformative researchSupport of transformative research -- need high-risk high reward work to drive -- need high-risk high reward work to drive

major advances major advances

• Support of transformative researchSupport of transformative research -- need high-risk high reward work to drive -- need high-risk high reward work to drive

major advances major advances ARISE: Advancing Research in Science and ARISE: Advancing Research in Science and EngineeringEngineering I. Investing in Early Career Scientists and High-RiskI. Investing in Early Career Scientists and High-Risk

High-Reward ResearchHigh-Reward ResearchFrom From The American Academy of Arts and SciencesThe American Academy of Arts and Sciences

•Recommendations to government, academia, Recommendations to government, academia, foundationsfoundations

ARISE: Advancing Research in Science and ARISE: Advancing Research in Science and EngineeringEngineering I. Investing in Early Career Scientists and High-RiskI. Investing in Early Career Scientists and High-Risk

High-Reward ResearchHigh-Reward ResearchFrom From The American Academy of Arts and SciencesThe American Academy of Arts and Sciences

•Recommendations to government, academia, Recommendations to government, academia, foundationsfoundations

Thomas R. CechThomas R. Cech Howard Hughes Medical Institute (Chair)Howard Hughes Medical Institute (Chair)David BaltimoreDavid Baltimore California Institute of TechnologyCalifornia Institute of TechnologySteven ChuSteven Chu Lawrence Berkeley National LabLawrence Berkeley National LabFrance CórdovaFrance Córdova Purdue UniversityPurdue UniversityThomas EverhartThomas Everhart California Institute of TechnologyCalifornia Institute of TechnologyRichard FreemanRichard Freeman Harvard UniversityHarvard UniversitySusan GrahamSusan Graham University of California, BerkeleyUniversity of California, BerkeleyDavid GoldstonDavid Goldston Former Staff Director, House Science CommitteeFormer Staff Director, House Science CommitteeH. Robert HorvitzH. Robert Horvitz Massachusetts Institute of TechnologyMassachusetts Institute of TechnologyLinda KatehiLinda Katehi University of Illinois, Urbana-ChampaignUniversity of Illinois, Urbana-ChampaignPeter KimPeter Kim Merck Research LaboratoriesMerck Research LaboratoriesNeal LaneNeal Lane Rice UniversityRice UniversityC. Dan Mote Jr.C. Dan Mote Jr. University of MarylandUniversity of MarylandDaphne PreussDaphne Preuss University of Chicago, and Chromatin, Inc.University of Chicago, and Chromatin, Inc.David SabatiniDavid Sabatini New York University Medical CenterNew York University Medical CenterRandy SchekmanRandy Schekman University of California, BerkeleyUniversity of California, BerkeleyRichard SchellerRichard Scheller GenentechGenentechAlbert TeichAlbert Teich American Association for the Advancement of ScienceAmerican Association for the Advancement of ScienceMark WrightonMark Wrighton Washington University in St. LouisWashington University in St. LouisKeith YamamotoKeith Yamamoto University of California, San FranciscoUniversity of California, San FranciscoHuda ZoghbiHuda Zoghbi Baylor College of MedicineBaylor College of MedicineLeslie BerlowitzLeslie Berlowitz American Academy of Arts and SciencesAmerican Academy of Arts and Sciences

Thomas R. CechThomas R. Cech Howard Hughes Medical Institute (Chair)Howard Hughes Medical Institute (Chair)David BaltimoreDavid Baltimore California Institute of TechnologyCalifornia Institute of TechnologySteven ChuSteven Chu Lawrence Berkeley National LabLawrence Berkeley National LabFrance CórdovaFrance Córdova Purdue UniversityPurdue UniversityThomas EverhartThomas Everhart California Institute of TechnologyCalifornia Institute of TechnologyRichard FreemanRichard Freeman Harvard UniversityHarvard UniversitySusan GrahamSusan Graham University of California, BerkeleyUniversity of California, BerkeleyDavid GoldstonDavid Goldston Former Staff Director, House Science CommitteeFormer Staff Director, House Science CommitteeH. Robert HorvitzH. Robert Horvitz Massachusetts Institute of TechnologyMassachusetts Institute of TechnologyLinda KatehiLinda Katehi University of Illinois, Urbana-ChampaignUniversity of Illinois, Urbana-ChampaignPeter KimPeter Kim Merck Research LaboratoriesMerck Research LaboratoriesNeal LaneNeal Lane Rice UniversityRice UniversityC. Dan Mote Jr.C. Dan Mote Jr. University of MarylandUniversity of MarylandDaphne PreussDaphne Preuss University of Chicago, and Chromatin, Inc.University of Chicago, and Chromatin, Inc.David SabatiniDavid Sabatini New York University Medical CenterNew York University Medical CenterRandy SchekmanRandy Schekman University of California, BerkeleyUniversity of California, BerkeleyRichard SchellerRichard Scheller GenentechGenentechAlbert TeichAlbert Teich American Association for the Advancement of ScienceAmerican Association for the Advancement of ScienceMark WrightonMark Wrighton Washington University in St. LouisWashington University in St. LouisKeith YamamotoKeith Yamamoto University of California, San FranciscoUniversity of California, San FranciscoHuda ZoghbiHuda Zoghbi Baylor College of MedicineBaylor College of MedicineLeslie BerlowitzLeslie Berlowitz American Academy of Arts and SciencesAmerican Academy of Arts and Sciences

ARISE: Advancing Research in Science and ARISE: Advancing Research in Science and EngineeringEngineeringhttp://www.amacad.org/arisefolder/default.aspxhttp://www.amacad.org/arisefolder/default.aspxA white paper from the American Academy of Arts and SciencesA white paper from the American Academy of Arts and Sciences

Distribution of Successful R01, R23, R29 or R37 Applicants by Age Group

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002

Fiscal Year

Percent of successful applicants

35 or less

36 to 40

41 to 45

46 to 50

51 to 55

over 55

Young investigators receiving smaller fraction of Young investigators receiving smaller fraction of awardsawards

The Perilous Postdoc-Faculty The Perilous Postdoc-Faculty TransitionTransition

• Median age, first independent position: 38Median age, first independent position: 38

• Median age, first R01: 42Median age, first R01: 42

• Percent NIH awards to new investigators: 4 Percent NIH awards to new investigators: 4

Even the most talented of our young people seem to be Even the most talented of our young people seem to be forcedforcedto endure several years of rejected grant applications to endure several years of rejected grant applications before before they finally acquire enough “preliminary data” to assure they finally acquire enough “preliminary data” to assure the the reviewers.reviewers. -- Bruce Alberts, Past President, National Academy of Sciences-- Bruce Alberts, Past President, National Academy of Sciences

It is not manageable…to have a culture where young investigatorsIt is not manageable…to have a culture where young investigatorsare discouraged from either entering a field, or…get discouragedare discouraged from either entering a field, or…get discouragedabout taking risks and bringing science into the new directions about taking risks and bringing science into the new directions that it needs to go.that it needs to go. --Elias Zerhouni, Past Director, NIH--Elias Zerhouni, Past Director, NIH

Albert Marshall Albert Marshall TomTom Einstein Nirenberg Einstein Nirenberg CechCech

First Position: 32First Position: 32 33 33 31 31

Nobel Prize: 42Nobel Prize: 42 41 41 42 42

Recommendations: Early Career FacultyRecommendations: Early Career FacultyFor federal agencies:For federal agencies:• Create or strengthen large, multi-year awardsCreate or strengthen large, multi-year awards• Early career-specific merit review, with appropriate expectationsEarly career-specific merit review, with appropriate expectations• Seed funding for early career exploration of bold ideasSeed funding for early career exploration of bold ideas• Specific policies to support needs of primary caregiversSpecific policies to support needs of primary caregivers

For private foundations:For private foundations:• Cap total number of startup and first awards per Cap total number of startup and first awards per investigatorinvestigatorFor academia:For academia:• Create or strengthen formal mentoring programsCreate or strengthen formal mentoring programs• Revise promotion and tenure policiesRevise promotion and tenure policies• Specific policies to support needs of primary caregiversSpecific policies to support needs of primary caregivers

Plus…Plus…

For Scientists:For Scientists:• Shorten and refocus graduate and postdoctoral educationShorten and refocus graduate and postdoctoral education

Graduate and postdoc education:Graduate and postdoc education:distinct missions and goalsdistinct missions and goals

Ph.D. educationPh.D. education • Broad “biological literacy” Broad “biological literacy” • Mentored acquisition of research “tools of the trade”Mentored acquisition of research “tools of the trade”• Career track decisionsCareer track decisions

Postdoctoral educationPostdoctoral education • Define and establish research focusDefine and establish research focus• Mentored acquisition of independenceMentored acquisition of independence

BScBSc

PostdocPostdoc

Independent Independent investigatorinvestigator

BusinessBusiness

CommunicationCommunication EducationEducation

LawLaw

Biotech startupBiotech startupVenture capitalVenture capital

Science policyScience policyIntellectual Intellectual propertypropertyPatentPatent

TeachingTeachingEducation Education AdminAdmin

JournalismJournalismInformation Information mediamedia

A PhD “hub” with career track “spokes”A PhD “hub” with career track “spokes”

PhDPhD

Graduate EducationGraduate Education

MissionsMissions

• Train Train experimentalists and scholarsexperimentalists and scholars in biological research in biological research• Present range of career tracksPresent range of career tracks

BenchmarksBenchmarks

Biological literacy and scholarshipBiological literacy and scholarship Mentored original researchMentored original research Career track decisionCareer track decision Completion in ~4 yearsCompletion in ~4 years

Graduate EducationGraduate Education

1. Biological literacy1. Biological literacy

Principles: chemical, biophysical, geneticPrinciples: chemical, biophysical, genetic Approaches: molecular, cellular, physiological, clinicalApproaches: molecular, cellular, physiological, clinical

2. Scholarship2. Scholarship

• Conceptual command of a field, relationship to other fieldsConceptual command of a field, relationship to other fields• Scientific judgment, interpretation of findings, perspectiveScientific judgment, interpretation of findings, perspective

3. Research skills3. Research skills

• Identify high-impact research questions/issuesIdentify high-impact research questions/issues• Develop hypothesis; plan and execute feasible experimentsDevelop hypothesis; plan and execute feasible experiments• Recognize and interpret meaningful findingsRecognize and interpret meaningful findings

Postdoctoral EducationPostdoctoral Education

MissionsMissions

•Train Train independent investigators independent investigators in biological researchin biological research• Define research focus Define research focus

BenchmarksBenchmarks

• Research achievement in specialized areaResearch achievement in specialized area• ~4 years~4 years Devise independent research plan or systemDevise independent research plan or system Acquire leadership and management skillsAcquire leadership and management skills

Transformative Research Transformative Research

Discovery and innovation are to some extent taking place in Discovery and innovation are to some extent taking place in spite of, rather than because of, the current policies and spite of, rather than because of, the current policies and practices of major funding agencies. practices of major funding agencies. -- Tom Cech -- Tom Cech

(HHMI)(HHMI)

One does not propose transformative research to NSF or NIH. One does not propose transformative research to NSF or NIH. Such proposals are dead on arrival. Such proposals are dead on arrival. -- Erich Jarvis (Duke)-- Erich Jarvis (Duke)

……potentially disruptive, paradigm-breaking, potentially disruptive, paradigm-breaking, revolutionary. Generates deep conceptual changes, revolutionary. Generates deep conceptual changes, produces new tools that extend the reach of whole produces new tools that extend the reach of whole fields, synthesizes new fields to produce new fields, synthesizes new fields to produce new insights.insights.

Recommendations: Transformative Recommendations: Transformative researchresearch

For federal agencies:For federal agencies:• Create specific programs, mechanisms, policiesCreate specific programs, mechanisms, policies• Establish metrics for evaluation of programsEstablish metrics for evaluation of programs• Strengthen application and review processesStrengthen application and review processes• Strengthen responsibilities and opportunities of program directorsStrengthen responsibilities and opportunities of program directors

For academia:For academia:• Create programs/environments that foster transformative Create programs/environments that foster transformative researchresearch• Reassess promotion and tenure policiesReassess promotion and tenure policiesPlus…Plus…

For scientists:For scientists:• Develop/maintain broad perspective and interestsDevelop/maintain broad perspective and interests• Fearlessly propose transformative ideas when they ariseFearlessly propose transformative ideas when they arise

Recommendations common to early careerRecommendations common to early careerand transformative researchand transformative research

For federal agencies:For federal agencies:

• Collect and analyze demographic data government-wideCollect and analyze demographic data government-wide

For academia:For academia:

• Accept at least partial responsibility for faculty salariesAccept at least partial responsibility for faculty salaries

• Reduce dependence on federal funds for new building Reduce dependence on federal funds for new building constructionconstruction

Securing a healthy environment for early Securing a healthy environment for early career researchers and transformative career researchers and transformative researchresearch

• Requires integrated effort from all stakeholdersRequires integrated effort from all stakeholders

Contributions from academia/scientists:Contributions from academia/scientists:• Formal mentoring for early career researchersFormal mentoring for early career researchers• Revise promotion and tenure policiesRevise promotion and tenure policies• Shorten and refocus PhD training; focus postdoc trainingShorten and refocus PhD training; focus postdoc training• Foster and nurture transformative scienceFoster and nurture transformative science• Greater cost sharing on faculty salary and building Greater cost sharing on faculty salary and building constructionconstruction• Integrate science and engineering research and educationIntegrate science and engineering research and education

A Vision of Biological Research for All A Vision of Biological Research for All StakeholdersStakeholders from the Board on Life Sciences, National Research Council, NASfrom the Board on Life Sciences, National Research Council, NAS

• The Role of the Life Sciences in Transforming The Role of the Life Sciences in Transforming America’s FutureAmerica’s Future

--Biology Summit meeting, December 3, 2008--Biology Summit meeting, December 3, 2008--White paper, release January 2009--White paper, release January 2009

• A New Biology for the 21A New Biology for the 21stst Century: Ensuring Century: Ensuring that the U.S. Leads the Coming Biology Revolutionthat the U.S. Leads the Coming Biology Revolution

--Designated committee now collecting information, --Designated committee now collecting information, adviceadvice

--Report and recommendations, release August 2009--Report and recommendations, release August 2009

Thomas ConnellyThomas Connelly Dupont Company (Co-Chair) Dupont Company (Co-Chair)Philip SharpPhilip Sharp Massachusetts Institute of Technology (Co-Chair) Massachusetts Institute of Technology (Co-Chair)Dennis AusielloDennis Ausiello MGH, Harvard Medical School MGH, Harvard Medical SchoolCori BargmannCori Bargmann The Rockefeller University The Rockefeller UniversityMarianne Bronner-Fraser Marianne Bronner-Fraser California Institute of TechnologyCalifornia Institute of TechnologyIngrid BurkeIngrid Burke University of Wyoming University of WyomingJohn BurrisJohn Burris Burroughs Wellcome Fund Burroughs Wellcome FundJonathan EisenJonathan Eisen University of California, Davis University of California, DavisAnthony JanetosAnthony Janetos The Heinz CenterThe Heinz CenterRichard KarpRichard Karp University of California, BerkeleyUniversity of California, BerkeleyPeter KimPeter Kim Merck Research Laboratories Merck Research LaboratoriesDouglas Lauffenberger Douglas Lauffenberger Massachusetts Institute of TechnologyMassachusetts Institute of Technology Wendell LimWendell Lim .. University of California, San Francisco University of California, San FranciscoMary LidstromMary Lidstrom University of Washington University of WashingtonMargaret McFall-NgaiMargaret McFall-Ngai University of Wisconsin University of WisconsinElliot MeyerowitzElliot Meyerowitz California Institute of TechnologyCalifornia Institute of Technology Shoshana WodakShoshana Wodak University of Toronto University of TorontoKeith YamamotoKeith Yamamoto University of California, San Francisco University of California, San FranciscoAnn ReidAnn Reid National Academy of Sciences National Academy of Sciences

Thomas ConnellyThomas Connelly Dupont Company (Co-Chair) Dupont Company (Co-Chair)Philip SharpPhilip Sharp Massachusetts Institute of Technology (Co-Chair) Massachusetts Institute of Technology (Co-Chair)Dennis AusielloDennis Ausiello MGH, Harvard Medical School MGH, Harvard Medical SchoolCori BargmannCori Bargmann The Rockefeller University The Rockefeller UniversityMarianne Bronner-Fraser Marianne Bronner-Fraser California Institute of TechnologyCalifornia Institute of TechnologyIngrid BurkeIngrid Burke University of Wyoming University of WyomingJohn BurrisJohn Burris Burroughs Wellcome Fund Burroughs Wellcome FundJonathan EisenJonathan Eisen University of California, Davis University of California, DavisAnthony JanetosAnthony Janetos The Heinz CenterThe Heinz CenterRichard KarpRichard Karp University of California, BerkeleyUniversity of California, BerkeleyPeter KimPeter Kim Merck Research Laboratories Merck Research LaboratoriesDouglas Lauffenberger Douglas Lauffenberger Massachusetts Institute of TechnologyMassachusetts Institute of Technology Wendell LimWendell Lim .. University of California, San Francisco University of California, San FranciscoMary LidstromMary Lidstrom University of Washington University of WashingtonMargaret McFall-NgaiMargaret McFall-Ngai University of Wisconsin University of WisconsinElliot MeyerowitzElliot Meyerowitz California Institute of TechnologyCalifornia Institute of Technology Shoshana WodakShoshana Wodak University of Toronto University of TorontoKeith YamamotoKeith Yamamoto University of California, San Francisco University of California, San FranciscoAnn ReidAnn Reid National Academy of Sciences National Academy of Sciences

A New Biology for the 21A New Biology for the 21stst Century: Ensuring that Century: Ensuring that the U.S. Leads the Coming Biology Revolutionthe U.S. Leads the Coming Biology Revolutionhttp://www8.nationalacademies.org/cp/projectview.aspx?key=48967http://www8.nationalacademies.org/cp/projectview.aspx?key=48967A project of the Board on Life Sciences, National Research Council, The National A project of the Board on Life Sciences, National Research Council, The National AcademiesAcademies

Thinking Ahead: A New Biology for the 21Thinking Ahead: A New Biology for the 21stst CenturyCentury

• What fundamental biological questions are ready for major advances? What would be the impact of answering them?What fundamental biological questions are ready for major advances? What would be the impact of answering them?  

• What are the barriers to achieving a newly integrated biology?What are the barriers to achieving a newly integrated biology?

• What are the implications of a newly integrated biology for infrastructure? What are the implications of a newly integrated biology for infrastructure?

• What are the implications of a newly integrated biology for the life sciences research culture and education? What are the implications of a newly integrated biology for the life sciences research culture and education?

• How can federal agencies best invest in biological research and education to address complex problems? How can federal agencies best invest in biological research and education to address complex problems?