CAN WE DEVELOP A COHERENT STRATEGIC FRAMEWORK FOR BIOMEDICAL RESEARCH?

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CAN WE DEVELOP A COHERENT STRATEGIC FRAMEWORK FOR
BIOMEDICAL RESEARCH?
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GLOBAL Public Health Challenges

• Acute to Chronic Conditions

Aging Population
Health Disparities
Emerging and Re-emerging infectious Diseases
Emerging Non communicable diseases
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Need to Transform Medical Research in the 21st
Century
21st Century
20th Century
Intervene before symptoms appear and preserve
normal function for as long as possible
Treat disease when symptoms appear and normal
function is lost
Understanding preclinical molecular events and
ability to detect patients at risk
Did not understand the molecular and cellular
events that lead to disease
Orders of magnitude more effective
Expensive in financial and disability costs
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Fundamental Roadblocks in Research and
Development
Basic Research
Biology
Chemistry
Development
Ind.Discov.
Target ID
Target Valid.
Screening
Optimization
Pre-clinical
Clinical
Examples of key roadblocks
Validation of complex diseases
Insufficient read-out on safety and toxicology
Lack of standardization and efficiency of
clinical trials
Some opportunities for improvement
Biomarkers, Animal models, Systems
biology, Chemical genomics
Biomarkers, Clinical training, Regulatory
harmonization, Informatics
Biomarkers, Animal models, Data sharing
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What is the NIH Roadmap for Medical Research?

• A framework of scientific priorities that the NIH
  as a whole must address in order to optimize its
  entire research portfolio.
• A vision for a more efficient, innovative and
  productive system of research into health,
  mechanisms of disease, and related behaviors.

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The NIH Roadmap for Medical Research
New Pathways to Discovery
Re-engineering the Clinical Research Enterprise
Research Teams of the Future
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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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Complexity of Biological Networks
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• All molecules are created equal, but some are
  more equal than others.
• Animal Pharm

Adapted from George Orwells Animal Farm
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Biological Data of the Future
Current Future
Destructive Non-Destructive
Qualitative Quantitative
Uni-Dimensional Multi-Dimensional
Low Temporal Resolution High Temporal Resolution
Non-localized Spatially resolved
Low data density High data density
Variable standards Common standards
Non-Cumulative Cumulative
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Combining Functional Imaging with GFP Linked Gene
Expression
230 ml/gm
6.2 ml/gm.min
c
c
0
0
Permeability
Vascular volume
MatLyLu tumor (430 mm3), capillary marked by c
Pre-ICMIC Program at JHU-RADIOLOGY
NCI P20 CA86346
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MOLECULAR NANOMACHINES Architecture of an 11,000
kDa Pyruvate Dehydrogenase Complex
475 Å
J. Milne and S. Subramaniam, National Cancer
Institute, NIH
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High Field MRI of White Matter Tract Development
in Mouse Embryos
st
ic
White matter reconstruction studies of a mouse
brain at embryonic day 16 (ex vivo)
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Solving the Puzzle of Complex Diseases and
Conditions
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Obesity A Worldwide Issue
Cancer
Athero- scleroris
Hyper- tension
Obesity Health Risks
Gall- bladder Disease
Kidney Failure
Heart Failure
Stroke
Diabetes
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New Discoveries in Obesity Research Using RNA
Interference (RNAi)
Thin Worm
Source Ashrafi et. al., Nature, Vol. 421, pp.
268-272.
305 genes
112 genes
Obese Worm
Normal Worm
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Human Genome Project and HapMap Are Complete
Where Do We Go From Here?

• Plummeting cost of DNA sequencing
• New discoveries accelerating revolution of the
  practice of medicine
• Genes, Environment, and Health Initiative
• Identify roots of 10 most common diseases
• Devise new ways of monitoring personal
  environmental exposures

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Advances in Age-related Macular Degeneration (AMD)

• AMD is the leading cause of blindness in people
  over age 60
• Variations in certain genes involved in
  inflammation can predict the risk of developing
  AMD
• 56 of the unaffected individuals had a variant
  that conferred protection to AMD
• 74 of those with AMD had no protective variants

Normal vision
Vision affected by AMD
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New Discoveries Make it Possible to Personalize
Cancer Treatment

• Impact
• 100,000 women each year can make a more informed
  choice
• 70,000 women do not have to undergo chemotherapy
• Reduces routine cost of treating these patients
• For each patient year of life gained, we save
  8,000

Identified 16 informative genes
Test tumor samples for mutations in these genes
Predict which patients need chemotherapy
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Pharmaco-Genomics Managing Human Variability

• Pharmaco-Genetics Research Network (PGRN)
• National collaboration of scientists studying the
  effect of genes on people's responses to a wide
  variety of medicines
• Pharmaco-Genetics Pharmaco-Genomics Knowedge
  Database (PharmGKB)
• Integrated knowledge base for pharmacogenetics
  linking phenotypes and genotypes

http//www.nigms.nih.gov/Initiatives
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SCIENTIFIC FOCUS AREAS
Target ID Validation
Fundamental
R D
Practice
Phases I-III
Preclinical
Screening/Optimization
Systems biology
New Pathways to Discovery
Iterative chemistry
Predictive toxicology
Translational Centers
Animal models
Target identification and validation
Biomarkers
Pharmacogenetics
Networks NECTAR
Training
Harmonization of policies and regulations
Research Teams of the Future
Harmonization
Public Trust
Strong Bioethics and Privacy regulations
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The Future Paradigm Transform Medicine from
Curative to Preemptive
Predictive
Preemptive
Personalized
NIH research initiatives and programs are
aiming to transform the practice of medicine as
we know it.
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Meeting World Health Problems The Need for
Sound Program Planning
With the true spirit of cooperation, with the
basic understanding of needs, and with the
efforts of enlightened groups everywhere, we can
push forward to new frontiers of world health and
well-being.
Dr. Joseph W. Mountin (1952) Founder of CDC
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Transforming medicine through discovery
NIH