Trends in Biomedical Research and Neurology

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Trends in Biomedical Research and
Neurology Elias A. Zerhouni, M.D. Director Nation
al Institutes of Health
2
William A. Hammond, M.D.,Founder of the ANA
(1875)
As Civil War Surgeon General, questioning
untested, if popular, medicinessuch as calomel,
or mercurous chloride
3
Annualized Growth of the NIH Budget, 1971 to 2005
25
20
15
10
Growth ()
5
0
-
5
-
10
1970 1975 1980 1985 1990 1995 2000 2005
Fiscal Year
Source
Loscalzo
, NEJM (2006)
4
Science, vol. 314 17 November 2006
Science, vol. 314 8 December 2006
www.sciencemag.org/
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What Is Really Happening?

• Facilities building and faculty growth throughout
  U.S. research institutions
• 100 growth in applications and 85 growth in
  applicants per year by 2007
• Budget appropriations below inflation since 2003
• Budget cycling phenomenon

6
National Research Capacity and Demand for Grants
Surges at End of Doubling Period, Success Rates
Fall
35
60
31
30
50
51,007
25
40
Number of Applications/Applicants (in thousands)
20
Success Rate of Grants Funded
19
30
8,359
15
24,154
20
8,303
10
10
5
Applications
Success Rate
0
0
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
7
NIH Appropriations
19652007, adjusted for inflation in biomedical
research 2008 Presidents Request beyond 2008,
projected
From SJ Heinig et al., Sustaining the Engine of
U.S. Biomedical Discovery, NEJM 357, September
6, 2007
8
What are My Chances of Being Funded? Success Rate
per Application Understates Funding Rate per
Applicant
25.4
20.0
Success Rate files as of January 2007. Program
srf_indiv_060103_rfm Individuals are determined
using the pi_profile_person_id in IMPAC-II
9
Better educate the public and policy makers about
the value of the NIH investment
10
Due to Advances of Past 30 YearsAmericans are
Living Longer and Healthier

• Hospital case-fatality rates for stroke have
  declined appreciably since 1971.

• Over 60 drop in mortality for heart disease
  and stroke in 2004, drop in deaths of women
  from Heart Disease from 1/3 to 1/4 reported

• Chronic disability among older Americans has
  dropped by 30 in the past 2 decades, and the
  rate of decline is accelerating
• Life expectancy rises to 78 years, up 6 years
  since 1974

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Clearly spell out the core challenges facing our
society in regard to health and medicine
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Major Factors Will Force a Transformation of
Medicine and Health

• Socio-economics
• Demographics
• Landscape of disease
• Global health
• Scientific challenges and opportunities

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Challenge of Rising U.S. Health
Expenditures Biomedical Research Must Deliver
4.1 trillion
20
National Health Expenditures as a Percent of GDP
Actual Projected
18
16
14
Percent of U.S. GDP
Direct and indirect costs of stroke in 2007
62.7 billion
12
10
8
2012
2009
2006
2003
2000
1997
1994
1991
1988
1985
1982
1980
2015
Source http//new.cms.hhs.gov/NationalHealthExpen
dData/downloads/nheprojections2004-2014.pdf
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Evolving Public Health Challenges

• Shift from Acute to Chronic Conditions

Aging Population
Health Disparities
Emerging and Re-emerging Infectious Diseases
Emerging Non-communicable Diseases - Obesity
Biodefense
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The Shape of Things to Come
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Provide an accurate assessment of the challenges
facing biomedical and behavioral sciences
researchProvide a compelling vision for the
future
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Need to Transform Medicine and Healthcare in the
21st Century
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Today, a fundamental scientific barrier is our
limited ability to study complex and dynamic
biological systems in health or disease!
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Complexity of Biological Networks

• Multiple levels of cross-talk between molecular
  pathways
• Many molecular targets part of intricate
  signaling networks
• Novel experimental and theoretical concepts needed

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Scientific Challenge Tackling Biological
Complexity
Cells Response to Damage
Electronic Diagram
Image courtesy of UCSD
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The Future Paradigm The 4 PsTransform Medicine
from Curative to Preemptive
Personalized
Predictive
Preemptive
Participatory
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Define the general strategies and research
directions of the NIH and its community of
scientists in as simple and direct a way as
possible!
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Roadmap for Medical Research
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The greatest risk in science is to stop taking
risks!
http//artfiles.art.com/images/-/Null/Cliff-Jump-N
ote-Card-C11763337.jpeg
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NIH Directors Pioneer AwardsSupport Potentially
Groundbreaking Ideas

• Support individuals with untested, potentially
  groundbreaking ideas in many areas of science,
  from neuroscience to chemistry to behavioral
  science
• Highly competitive
• Unique review
• Short application concentrating on investigator
• Emphasis on problem selected, evidence for
  innovation
• Utilizes interview

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2005 Pioneer Award RecipientKarl Deisseroth,
M.D., Ph.D.Stanford University
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Pioneer Awards in Neuroscience, 20052007

• 2005
• Hollis T. Cline, PhD, Cold Spring Harbor
• Karl Deisseroth, MD, PhD, Stanford
• Erich D. Jarvis, PhD, Duke
• Thomas A. Rando, MD, PhD, Stanford
• Giulio Tononi, MD, PhD, University of
  Wisconsin-Madison
• Junying Yuan, PhD, Harvard
• 2006
• Kwabena A. Boahen, PhD, Stanford
• Gary J. Pielak, PhD, UNC Chapel Hill
• Rosalind A. Segal, MD, PhD, Dana-Farber
• 2007
• Peter Bearman, PhD, Columbia
• Emery N. Brown, MD, PhD, Mass. General and MIT
• Takao K. Hensch, PhD, Harvard
• Frances E. Jensen, MD, Childrens Hospital,
  Harvard
• Gina Turrigiano, PhD, Brandeis

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NIH Funding New Scientists and Novel Ideas

• NIH Directors Pioneer Award
• NIH Pathway to IndependenceAward Program
• NIH Directors New Innovator Award
• EUREKA (Exceptional, Unconventional Research
  Enabling Knowledge Acceleration)

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Directors New Innovator Award

• Award will support new investigators who have not
  yet obtained a traditional NIH R01 grant
• Goal to support highly innovative research
  projects with potential for exceptionally great
  impact on biomedical or behavioral science
• Each grant will be for five years and up to a
  total of 1.5 million in direct costs
• This year, NIH received 2100 applications
  awarded grants to 29 young innovators

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New Innovator Awards in Neuroscience

• Mark Johnson, MD, PhD, Brigham and Womens
  Hospital
• Defective microRNA biogenesis and brain cancer
• Edward Boyden, PhD, MIT
• Novel tools and principles for precisely
  controlling brain activity
• Pedro Fernandez-Funez, PhD, UT Galveston
• Mechanisms of prion misfolding
• Joanna Jankowsky, PhD, CalTech
• Selective neuronal silencing to study cognitive
  decline in Alzheimer's disease
• Alan Jasanoff, PhD, MIT
• Genetically-controlled MRI contrast agents for
  functional brain imaging
• James Shorter, PhD, U Penn
• Amyloid elimination by Hsp104 and
  substrate-optimized variants

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Top Ten Advances in Clinical Neurology Today

• Stroke prevention and acute treatment
• Deep brain stimulation for basal ganglia
  disorders
• Genes for neurological disorders
• Brain and spinal cord imaging technology
• Enzyme replacement therapy
• New medications and refined surgical planning for
  epilepsy
• Improved classification and treatment for some
  brain tumors
• New treatments for multiple sclerosis
• Improved neurological treatment for premature
  infants
• New treatments for migraine

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Primary Topics of Research
Themes
600 disorders

• Stroke
• Multiple Sclerosis
• Brain and spinal cord tumors
• Traumatic Injury
• Parkinson's
• Epilepsy
• Autism
• Pain
• Peripheral neuropathy
• Muscle disease

• Neurodegeneration
• Neurogenetics
• Neurodevelopment
• Neural plasticity and repair
• Brain and behavior

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Imaging in Neurology Research
Pittsburgh Compound B visualizes amyloid plaques
in patients with vascular amyloid as well as
Alzheimers.
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GWAS Consortium Successes

• First genes associated with MS since HLA in the
  1970s
• Both encode interleukin receptors (IL-Rs),
  validating immunomodulatory treatments, and
  suggesting new targets
• IL-Rs and related genes link a growing number of
  autoimmune diseases

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Exciting Times Acceleration of Gene Discoveries
for Common Complex Diseases
Autism Multiple Sclerosis Stroke Depression Bipol
ar Disorder Diabetes Restless leg
syndrome Hypertension Depression Drug
Addiction Breast Cancer Rheumatoid
Arthritis Lupus Colorectal Cancer ALS
Type 2 Diabetes Prostate Cancer Systemic Lupus
Erythematosus Myocardial Infarction Inflammatory
Bowel Disease Macular Degeneration
Macular Degeneration
Breast Cancer Alzheimer's Disease
Colon Cancer
90 91
92 93
94 95
96 97
98 99
00 01
02 03 04
05
06
07
YR
Encyclopedia of DNA Elements Launched
HapMap Project Initiated
Genome Wide Association Studies Launched
The Cancer Genome Atlas Launched
HapMap Project Completed
Genes and Environment Initiative Launched
Human Genome Project Completed
Human Genome Project Begins
Genetic Association Information Network Launched
NIH Research Initiatives
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Initial Genome-Wide Association Study
Data Analysis
Additional populations/health disparities
Sequencing interesting regions to find causative
variants
Functional analysis
Translation Diagnostics Therapeutics
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Re-engineering the Clinical Research Enterprise
NIH Clinical and Translational Science Awards

• Lower barriers between disciplines
• Encourage creative, innovative approaches in
  solving complex medical problems
• Catalyze change break silos, break barriers, and
  break conventions
• Train next generation of Clinical Scientists

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Building A National CTSA ConsortiumFY2006 FY
2007 CTSA Awards
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NIH Neuroscience Research FY 2007 Estimate 4.8
Billion
OTHER 6
NIDDK 2
NHLBI 2
NCRR 3
NCI 3
NIAAA 3
NIDCD 3
NICHD 6
NINDS 30
NIA 8
NIDA 9
NIMH 16
NEI 9
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NIH BlueprintSupporting Basic and Clinical
Neuroscience
A cooperative effort between the Office of the
Director and the 15 Institutes and Centers that
support neuroscience research

• Providing neuroscientists and neurologists with
• Tools
• Resources
• Training
• Funding opportunities

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Balanced National Biomedical Research Portfolio
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Transforming medicine and health through discovery
NIH