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FRONTIER SCIENCE AND GRAND CHALLENGES: INVESTING IN HIGH-

POTENTIAL INDIVIDUALS AND HIGH-PAYOFF SCIENTIFIC FIELDS

Gilbert S. Omenn

University of Michigan

French Presidency of the EU

Symposium Celebrating Frontier Science

Paris, 7 October, 2008

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Europe: Investing in Intelligence

“Research and innovation are the main keys to Europe’s development. They are also the most efficient way to respond to the challenges set by Asia’s large emerging economies and to lay the foundation for sustainable development for the entire planet.”

---Nicolas Sarkozy 14 May, 2008

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Kudos to the EU on the Launch of the Frontiers of Science Program

• Investments in young scientists and their individual investigator-initiated projects

• Sufficient funding to make a difference

• High standards

• The “Ideas Program”, complementary to the 7th Framework cooperative networks

• Congratulations to those honored today

• The rest of the world has noticed!

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This morning’s headline:French, German Scientists Win Nobel for HIV, Cervical Cancer

France's Francoise Barre-Sinoussi and Luc Montagnier and German virologist Harald zur Hausen have won the Nobel Prize in Physiology and Medicine for 2008, for identifying viruses that cause AIDS and cervical cancer.

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Aims for the ERC in 2005 HLEG Report• Create a globally competitive European

Research Area (Lisbon 2000 Strategy), with international benchmarks

• Attract and support the very best talent• Channel funds into new, highly promising

research areas with agility and focus—with ICT, biotech, and nano mentioned

• Confer status and visibility on European frontier research and teams for institutional and national investment

• Generate economic and societal benefits

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Investing in Frontier Science• Identify exceptional individuals with a passion for discovery and innovation• Take risk for big payoffs, based on excellence• Pose true grand challenge questions• Stimulate over-the-horizon ideasAlso:• Provide special resources and standards--instruments

(LHC), databases (GenBank), animal models, computational models

• Create/incentivize teams for needed scale• Build institutional strengths, while facilitating mobility• Set milestones, track results, test policies: the “science of science management”

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International Approaches to Frontier Science

1. Identifying Compelling Questions, Grand Challenges, Emerging Fields

Approaches: (a) what outstanding investigators propose as individuals;

(b) using a group process to stimulate proposals in highlighted areas

2. Investing in individual researchers –

NSF, NIH, HHMI, Keck, DARPA

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Categories of Grand Challenges

1. By scientific or engineering field

2. By multidisciplinary R&D domain

3. As part of a larger societal need

2006 AAAS Presidential Address: Omenn GS. Grand challenges and great opportunities

in science, technology, and public policy. Science Dec 15, 2006; 314:1696-1704

“A mathematical problem should be difficult in order to entice us, yet not completely inaccessible, lest it mock at our efforts. It should be to us a guide post on the mazy paths to hidden truths, and ultimately a reminder of our pleasure in the successful solution.” --David Hilbert, Paris, 1900

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HILBERT’S 23 PUZZLESClasses of problems:• 1-6: mathematical foundations/logic; solutions to 4 and 5 were geometrical.• 7-13 and 17: number theoretical.• 14: algebra• 15-16, 18: geometry and topology• 19-20, 22-23: analysis and differential equations (tied to physics)#21: both analytical and algebraic geometry, solved relatively recently#8: Riemann hypothesis still incompletely solved/part of the Clay Challenge

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Grand Challenges in Physics & Astronomy: Connecting Quarks with the Cosmos

What is dark matter?What is the nature of dark energy?How did the universe begin?Did Einstein have the last word on gravity? What are neutrino masses/how have they

shaped the universe? How do cosmic accelerators work/what are

they accelerating?

U.S. National Academy of Sciences (2001)

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--David Schramm

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title

Popular Sculpture at NAS, Near Lincoln Memorial

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Hubble Telescope

The importance of instruments---synergiesbetween technologies and science

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François-Marie Arouet de Voltaire 1694-1778

On ne peut désirer ce qu'on ne connaît pas.

You can only desire what you do not

yet know.

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Sustainability in the Chemical Industry

Grand Challenges and Research Needs A Workshop Report

NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES

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Chemistry and Chemical Engineering for Sustainability

Green chemistry, replacing solvents, improving catalysts

Life cycle analysis tools and modelsToxicologic characterization of all chemical inputs

and outputsRenewable chemical feedstocks from various

biomass Renewable fuel sources More efficient chemical processingSeparation, sequestration, and utilization of carbon

dioxideScience literacy at all levels

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Grand Challenges in Environmental Sciences

National Research CouncilNATIONAL ACADEMY PRESS

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• Biogeochemical Cycles

• *Biodiversity and Ecosystem Functioning

• Climate Variability

• *Hydrologic Forecasting

• *Infectious Disease and the Environment

• Institutions and Resource Use

• *Land-Use Dynamics

• Reinventing the Use of Materials

Grand Challenges in Environmental Sciences

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“OUR NATION’S ENERGY FUTURE”Project Independence, December 1973

Priorities, in order:• Create technologies for much more efficient

combustion of fuels• Enhance recovery from existing oil fields• Create clean coal technologies• Improve efficiency and safety of nuclear fission

reactor operations and waste management• Accelerate development of long-term sources---

solar, wind, geothermal, nuclear fusion

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THE NATIONAL ACADEMIES

CREATING A DISASTERRESILIENT AMERICA

________________________________________________________________

GRAND CHALLENGES IN SCIENCEAND TECHNOLOGY

SUMMARY OF A WORKSHOPOF THE DISASTERS ROUNDTABLE

By Patricia Jones Kershaw, National Research Council

OCTOBER 28, 2004WASHINGTON, DC

Disaster RoundtableDivision of Earth and Life Studies

THE NATIONAL ACADEMIES PRESSWashington, D.C.

www.nap.edu

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U.N. MILLENIUM DEVELOPMENT GOALS

These goals for peace, security, development, human rights and fundamental freedoms (1990 to 2015) are people-centered, time-bound, and measurable.

1. Eradicate extreme poverty (<$1/day; 1 billion people) and hunger--by 50%2. Achieve universal primary education for boys and girls3. Promote gender equality and empower women4. Reduce child mortality rate before age 5 by 67% 5. Improve maternal health--reduce mortality ratio by 75%6. Combat HIV/AIDS, malaria and other diseases---begin to reverse incidence and spread7. Ensure environmental sustainabiity--50% reduction in those without safe drinking water8. Develop a global partnership for development

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GRAND CHALLENGES IN GLOBAL INFECTIOUS DISEASES (7 Goals, 14 Challenges)—Gates Foundation

• Improve childhood vaccines (3)

• Create new vaccines (3)

• Control insects that transmit agents of disease (2)

• Improve nutrition to promote health (1)

• Improve drug treatment of infectious diseases (1)

• Cure latent and chronic infection (2)

• Measure health status accurately and economically (2)

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It’s a New World in Life Sciences• New Biology---New Technology• Genome Expression Microarrays• Comparative Genomics, Epigenetics, miRNA Gene Regulation• Proteomics• Bioinformatics• Systems Biology Path to predictive, personalized, preventive (P3) healthcare

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The DNA Pioneers

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The Historic Weekend of Feb 15-16, 2001

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Eric Lander

Ari Patrinos

J. Craig Venter and Francis Collins

U.S. Leaders of the Human Genome Project

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Matthias Ruedi MathiasMann Aebersold UhlenMax Planck Institute of Royal InstituteInstitute of Molecular of Technology,Biochemistry Systems Biology Stockholm Munich Zurich

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NIH ROADMAP: National Centers for Biomedical Computing

Informatics for IntegratingBiology and the Bedside (i2b2)Isaac Kohane, PI

Center for Computational Biology(CCB)Arthur Toga, PI

Multiscale Analysis of Genomicand Cellular Networks (MAGNet)Andrea Califano, PI

National Alliance for MedicalImaging Computing (NA-MIC)Ron Kikinis, PI

The National Center ForBiomedical Ontology (NCBO)Mark Musen, PI

Physics-Based Simulation ofBiological Structures (SIMBIOS)Russ Altman, PI

National Center for Integrative Biomedical Informatics (NCIBI) Brian D. Athey, PI

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Multi- and Interdisciplinary Research will be Required to Solve the “Puzzle” of Complex

Diseases and Conditions

GenesBehaviorDiet/NutritionInfectious agentsEnvironment Society???

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Synthetic Biology, an Emerging Field

Interdisciplinary science and engineering to design and build novel biological functions and systems to:

• Gain insights into what makes life tick, constructing genetic circuits to achieve what nature evolved over eons

• Develop powerful biotechnologies by integrating biological components, circuits and replicating organisms

Applications:• Engineered microorganisms that produce drugs• Biosensors for detecting abnormalities and diseases• Microorganisms that convert renewable resources into

energy carriers• Microorganisms to remediate hazardous material

contaminated sitesSafety regimens will be critical.

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Presidential Young Investigators Awards—National Science Foundation

• The NSF is the broadest and most basic research agency in the United States

• Individual investigator grants are the bedrock• The Presidential Young Investigators (PYI) Award was a

five-year, no-strings-attached research grant to outstanding young scientists and engineers who showed exceptional potential for leadership at the frontiers of knowledge. The cornerstone of the program was that NSF funds be matched by private or industrial sources.

• One of its influences was the establishment of academic departments of computer sciences and engineering.

• PECASE, Presidential Early Career Awards for Scientists and Engineers at the frontiers of knowledge (20/yr)

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Howard Hughes Medical Institute Investigators• Emphasis on individuals, not projects• Encouraged to “pursue the science”, be bold & daring• In “emerging fields” of genetics, immunology, structural

biology, neuro and visual sciences; systems/ computational biology recently added

• Multi-year awards with renewal, HHMI mentoring, and spectacular peer group

• 340 HHMI researchers currently employed at 64 universities, including 12 Nobel laureates and 124 members of the National Academy of Sciences

• 56 new in 2008, from >1000 applications• Build a group of 10-25 students, post-docs, technicians• 2008 niches: Early Career Scientists (own labs 2-6 yrs) International Research Scholars

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NIH Director’s Pioneer and Innovator Awards, part of the NIH Roadmap for Medical Research

In response to increasingly conservative peer review for the 47,000 current research grants, the NIH has experimented with special grant competitions that seek unusually innovative and/or cross-disciplinary proposals

• In 5 years, 63 Pioneer Awards ($2.5M over 5 yrs): “bold ideas and inventive technologies”• In 2 years, 61 New Innovator Awards ($1.5M over 5 yrs)• Pan-NIH review group; thousands of applicants, as with

ERC competition• 38 “Exceptional, Unconventional Research Enabling

Knowledge Acceleration” (EUREKA) grants, Sept 2008

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Keck Futures Initiative Program

• 15 yr program administered by National Academies of Science, Eng’g, Medicine

• Annual multidisciplinary topic chosen for high potential to spark discovery

• About 100 outstanding researchers invited for 3 day conference after extensive preparation and tutorials

• Grants available to pursue ideas and collaborations generated at the conference

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Keck Futures Conference Themes

2003: Signals, Decision, and Meaning in Biology, Chemistry, Physics, Engineering

2004: Designing Nanostructures at the Interface of Biomedical and Physical Systems

2005: The Genomic Revolution—Implications for Treatment and Control of Infectious Disease

2006: Smart Prosthetics: Exploring Assistive Devices for Body and Mind

2007: The Future of the Human Healthspan: Demography, Evolution, Medicine, BioEng’g

2008: Complexity

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Defense Advanced Research Projects Agency (DARPA)

• Top-down program manager model for innovative goal-oriented R&D: free-wheeling zealots, technically outstanding, 3-5 yr rotations

• Admirable record since 1958 leading to Internet, graphical user interfaces, global positioning systems, and many other outputs of long-term university-based work

• Complete acceptance of failure if payoff high• Model for E-ARPA and H-ARPA• Complaints recently of more short-term and

more classified research at DARPA

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“The Quiet Crisis”---Shirley Ann Jackson,

2005 AAAS Presidential Address

• Projected extreme shortages of well-prepared women and men to pursue careers in science and engineering, just as the knowledge-based world economy demands high skills

• Broad investments are needed, not just for the most exceptional individuals

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The Global Scientific Community• People are mobile, seek opportunities• “The World is Flat”—Tom Friedman• Academies of Science around the world• EU-US Agreement for S&T Cooperation• Innocentive Inc---problems for scientists or

engineers to solve, with payoffs from $5K to $100K, through the Internet for companies, Rockefeller Foundation, others

• Grainger Challenge Prize for Sustainability

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Prizes can stimulatediscovery---and cause controversy

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Louis Pasteur1822-1995

Let me tell you the secret that has led me to my goal.

My strength lies solely in my tenacity.

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Human Frontier Science Program

• Launched by Japanese scientists and government in mid-1980s

• Proposed at Venice Economic Summit, 1987 by PM Nakasone

• Implemented in 1989 in Strasbourg by G7, EU, Switzerland, Austria, Korea, NZ

• Global collaboration and post-doc training in new fields and new labs/countries

• In 15 yrs, 59 nationalities supported

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The Instructive Case of Richard Muller, of Lawrence-Berkeley National Lab

• NSF Waterman Award for outstanding scientific achievements before age 35 (1978)

• Groundbreaking work in three areas—astrophysics, optics, radio-dating

The projects were so far beyond conventional wisdom and methods that his peer-reviewed proposals had been rejected that year by four agencies!

Supported by his National Laboratory chief.Recommended to Congress that divergent peer

reviews be given special emphasis.

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Summary of Challenges for the ERC • To sustain the career progress of Starter Grant

recipients • To take risks in peer review• To be a “learning organization”• To generate benefit for those not awarded grants• To make the whole > the sum of parts by

stimulating coalescence in emerging fields and productive interdisciplinary interactions

• To attract scientists from around the world to European laboratories

• To translate the passion for discovery in all fields into societal benefits

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“There are those who look at things the way they are, and ask, why?...

I dream of things that never were, and ask, why not?”

--Robert F. Kennedy

(1968)

Pierre Teilhard de Chardin

1881-1955

The future belongs to those who give the

next generation hope.