Transcript Donald Burke - The National Academies of Sciences, Engineering

National Academies Workshop on STEM Workforce
Needs for the DoD and the Defense Industrial Base
Emerging Science and Technol0gy
in the Life Sciences
Donald S. Burke, MD
UPMC-Jonas Salk Chair Global Health
Dean, Graduate School of Public Health
University of Pittsburgh
1 August 2011
1
Defense S&T Priorities for 2013-2017
• Data to Decisions
Reduce cycle time and manpower for analysis of large data sets
• Engineered Resilient Systems
Protect weapons systems against malicious compromise
• Cyber Science and Technology
Efficient cyber capabilities for joint operations
• Electronic Warfare / Protections
Protect systems across the electro-magnetic spectrum
• Counter Weapons of Mass Destruction
Locate, interdict, eliminate WMD
• Autonomy
Autonomous systems for all environments
• Human Systems
Enhance human-machine interfaces across a broad range of missions2
High Interest Basic Science Areas
• Synthetic Biology
• Modeling Human Behavior
• Engineered Materials
• Cognitive Neuroscience
• Quantum Systems
• Nano Science and Engineering
3
Outline
1. Observations on the spatial and temporal scales of
life sciences research
2. Examples of emerging life science research at
dimensions smaller than a human being
3. Examples of emerging life science research at
dimensions greater than a human being
4. The key role of computational thinking in the future
of life science research
4
Spatial Scales (meters)
“Human
Population
Systems”
5
Time Scales (seconds)
10^12 Dawn of civilization
10^9
One human lifespan
10^6
Influenza illness
10^3
This lecture
10^0
One Second (heart rate)
10^-3 One neuron potential spike
10^-6 Protein folding
“ Human
Population
Systems”
“Systems
Biology”
10^-9 Photoreceptor intermediates
6
Meters (log 10)
Scales of Health Science Research
Population
Health:
Behavior
Clinical
Medicine
Cognitive
Neuroscience
Synthetic
Biology
Nano Biology
Seconds (log 10)
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Nanoscience
• The study of materials and associated
physical, biophysical, and biochemical
phenomena on the scale of ~1 to 100
nanometers
Nanoscience: Potential Applications
• Vaccines: Interbilayer-crosslinked multilamellar
vesicles as synthetic vaccines for potent
humoral and cellular immune responses
-
Use nanotech to fuse liposomes together, building thicker “walls” to
become stronger and more stable in blood (less likely to breakdown after
injection). Once inside the cell, the liposomes release synthetic viral parts
and elicit strong T-cell response.
Nanoscience: Potential Applications
Vaccine Delivery: Potent Immunity to Low
Doses of Influenza Vaccine by Probabilistic
Guided Micro-Targeted Skin Delivery
10
Synthetic Biology
• View cells as programmable entities
• Primarily an engineering discipline
– Creating new functions, compounds, or properties
using biological processes.
– Extends principles of hardware engineering to
genetic engineering
• Essential to develop effective strategies for
assembling engineered devices and modules
into intricate, customizable larger scale systems.
Synthetic Biology: Malaria drugs
• Production of novel
compounds
– Artemisinin, produced from
the plant Artemisia annua is
highly effective against malarial
parasite P. falciparum, but is in
short supply.
– Researchers inserted genes
from A. annua into simple
yeast (S. cerevisiae) to produce
large quantities of artemisinic
acid, the precursor of
artemisinin.
Red circle= normal FPP (farnesyl pyrophostphate) production in yeast.
Green arrows= processes introduced in the yeast biochemical pathway from A. annua to
produce artemisinic acid from FPP.
Synthetic Biology:
Other Potential Applications
Biofuel production:
Producing alcohols from E. coli
Bioremediation:
Degrading toxic substances
that are resistant to
degradation by natual
organisms, such as
organophosphates (used in
pesticides)
Cognitive Neuroscience
• Understanding the nature of cognition from a neural perspective
• Neurophysiological advances in detecting and measuring indicators of
psychological states and intentions of individuals
• Development of drugs or technologies that can alter human physical or
cognitive abilities
• Advances in real-time brain imaging
• Development of computational systems which mimic functions of the
human brain
• 2008 NRC Report on Emerging Cognitive Neuroscience and
Related Technologies
Cognitive Neuroscience:
Potential Applications
2009 NRC Report on Opportunities in Neuroscience for
Future Army Applications
• Field Deployable Biomarkers of Neural State
• EEG Based Brain-Computer Interfaces
• Haptic Feedback Technology for Virtual Reality
Training
• Informational Workload Management to Heighten
Situational Awareness
• Technologies to Optimize Sensor-Shooter Latency
and Target Discrimination
But what about STEM at scales
larger than a human being?
16
A Forefront of Health Research:
Computation and Population Health
S&T Priorities
High Interest Basic Science Areas
17
Population Health: Socio-behavioral illnesses
• Obesity
• Drug addiction
• Violence
• Mental health
18
Scales of Health Science Research
Meters (log 10)
Public Health Dynamics
Population
Health:
Behavior
Clinical
Medicine
Cognitive
Neuroscience
Synthetic
Biology
Nano Biology
Seconds (log 10)
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The University of Pittsburgh
Graduate School of Public Health
“Public Health Dynamics Laboratory”
Core Team
• AI / Computer Scientist (Director)
• Statistical Physicist
• Quantum Chemist
• Applied Mathematician / Game Theorist
• MD/MBA
• Epidemiologist
Active participation by Industrial Engineers, Nuclear
Physicist, Astronomer, Computational Linguist,
Lawyers, Philosophers (and Public Health Experts)
Pitt Public Health Dynamics Laboratory
Computational Projects
• FRED: Simulation of pandemic spread through
USA society
• TYCHO: Historical disease data acquisition
and analysis
• FRANCIS: Modeling of human health behaviors
• TBN: Measurement of population-level immunity
21
Computational Project 1: FRED
Simulation of pandemics
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FRED: Framework for Reconstruction of
Epidemic Dynamics
Simulation Information
Management System
(FRED SIMS)
FRED
Web
Page
FRED
Interface
Synthetic
Population
Request
Queue
Request
DB
FRED
Web
Service
FRED
Core
FRED
Core
Pittsburgh
SuperComputing
Center
FRED
Client
Pathogen
Parameters
FRED
Simulation
Engine
Intervention
Policies
Analysis and
Visualization
Tools
Results
DB
Natural History, Viral Evolution
Vaccination
Antivirals
School Closure
Preventive
Behaviors
Health Belief
Model
Behavior
Change
Model
Social Network
Influences
FRANCIS
GAIA
23
H1N1 pandemic decision support using
large scale agent based simulations
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Computational Project 2: TYCHO
Acquisition and analysis of historical disease data
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A project to digitize and render computable all the data in the US
weekly National Notifiable Disease Surveillance System
• 1888 to present ( more than 120 years)
• 50 states and 1500 cities and towns
• 55 reportable infectious diseases
• 6,300 weekly reports
• 100 million cases and 4 million deaths
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Endangered public health data: USA and world-wide
USA
Laos
India
Nigeria
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Availability of hard copy historical data
Number of weekly counts per location (state or city)
- All weekly US reports from 1888 to 2009
- All states, > 1500 cities
- 55 diseases
- Total of 100 million reported cases
- Total of 4 million reported deaths
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Data entry by “Digital Divide Data” in Phnom Penh
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History of disease reporting in the US
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Example: Measles control in the US
Weekly incidence rates (/100,000) for US states: 1928-1980
- Vaccine licensed in 1963 (red line)
States
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Computational Project 3: FRANCIS
Modeling of human health behaviors
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Growing Artificial Societies
Joshua M. Epstein
Robert Axtell
Brookings Institution 1996
Generative Social Science
Joshua M. Epstein
Princeton Univ Press 2007
“If you can’t grow it, you
don’t understand it.”
Josh
Behavior Change Theories
•
•
•
•
•
Health Belief Model
Trans-Theoretical Model
Social Cognitive Theory
Theory of Planned Behavior
Social Ecological Model
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THE “TWO CULTURES” PROBLEM
35
Decision
To Get Vaccine
Cases
Cases
Gets Vaccine
36
Modeling of Human Behavior:
Francis Agent Model
Demographics:
Age
Sex
Occupation
Health:
Immune Status
Perceptions:
News Reports,
Illness among
contacts
Behavior:
Baseline Trust,
Gets Vaccine
Modeling of Human Behavior:
FRED w every agent a FRANCIS
Population-level Vaccine Compliance
Computational Project 4: Measurement of
population level immunity
High-throughput peptoid (“shape-oid” )
libraries as predictive disease biomarkers
O
NH2 +
Synthesis of Peptoids
HO
Br
PEG-coated
polystyrene
O
Br
N
H
O
H
N
R
Peptides
O
Split
R
N
H2N R1
O
n
n
Peptoids
N
H
H2N R2
R1
O
NH
N
H
H2N R3
O
R2
NH
NH
N
H
Pool
O
N
H O
N
H O
N
H
R3
R1
NH
R2
NH
R3
NH
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The Current Peptoid “ Shape-oid” Library
NH2
O
O
H
N
NH
NH
N
O
Polystyrene
HS
bead
R 8
O
NH2
NH2
HO
H2N
COOH
O
Nser
Npip
NH2
NH2
NH2
Nmba
Nasp
Nall
Nleu
NH2
H2N
Nlys
41
Peptoid Microarray Biomarker Discovery
Add serum antibodies
One bead
One peptoid
384 well plate
Compare binding patterns of
patients with the disease and
normals without the disease
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Serum Antibody Binding to Alzheimer’s Disease-specific Peptoids
Tom Kokdadek, Cell Jan 2011
80
Intensity (X103)
60
40
NC9
NC11
AD12
20
0
AD
NC
Training Set
PD
AD
NC
Test Set
43
Department of Defense Serum Repository ( est 1986 )
50,000,000 human serum specimens, collected primarily from applicants
to and members of the United States Uniformed Services
The Defense Medical Surveillance System links specimens in the repository to
individuals and to select medical outcomes data available through the Military
Health System and to other pertinent administrative data
44
Identify and deploy peptoid markers for:
Dementia
Cancers
Immunity to infectious diseases
Conduct multiple screens simultaneously
45
CONCLUSIONS
46
Meters (log 10)
Scales of Health Science Research
“Data tsunami” + ready
availability of computation
is now driving a similar
computational (systems)
approach in the sociobehavioral sciences
Sociobehavioral
Dynamics
Clinical
Medicine
Cognitive
Neuroscience
Synthetic
Biology
Nano Biology
Seconds (log 10)
A “systems approach”
was driven by the deluge
of genome sequence
data (and a concomitant
failure of classical
reductionism)
47
Computational Thinking
Jeannette M. Wing
Carnegie Mellon University
Communications of the ACM (2006)
• Conceptualizing (not programming) and thinking at multiple levels of
abstraction;
• A way that humans, not computers, think;
• Complements and combines mathematical and engineering thinking;
• Ideas, not artifacts. It’s not just the software and hardware artifacts
we produce;
• Complements and combines mathematical and engineering thinking
Report of a Workshop on The Scope
and Nature of Computational Thinking
(2010)
48
“Computer Science is the new Liberal Arts”
If Public Health is becoming a STEM discipline,
what does this say about STEM workforce
planning?
More generally, if traditional boundaries of
STEM versus the population-level
“humanities” (sociology, history, anthropology)
are becoming blurred, what opportunities
does this present for STEM workforce
planning?
49
50
Thank you for your attention
51
Defense S&T Priorities for 2013-2017
• Data to Decisions
Reduce cycle time and manpower for analysis of large data sets
• Engineered Resilient Systems
Protect weapons systems against malicious compromise
• Cyber Science and Technology
Efficient cyber capabilities for joint operations
• Electronic Warfare / Protections
Protect systems across the electro-magnetic spectrum
• Counter Weapons of Mass Destruction
Locate, interdict, eliminate WMD
• Autonomy
Autonomous systems for all environments
• Human Systems
Enhance human-machine interfaces across a broad range of missions
52
High Interest Basic Science Areas
• Synthetic Biology
• Modeling Human Behavior
• Engineered Materials
• Cognitive Neuroscience
• Quantum Systems
• Nano Science and Engineering
53
National Biosurveillance Advisory Subcommittee (NBAS)
Report issued in April 2011
Biosurveillance Workforce & New Professions
• CDC response to Homeland Security Presidential Directive 21 “Public
Health and Medical Preparedness” (HSPD-21, 2007)
• Workforce subcommittee chaired by Don Burke
• Findings of insufficient workforce and expertise in
- public health data acquisition, management, and analysis
- social / behavioral / mental health epidemiology
• Recommendation #1: New workforce requirements in public health
informatics
• Recommendation #2: New workforce requirements in social, behavioral
and mental health
54
National Biosurveillance Advisory Subcommittee (NBAS)
Report issued in April 2011
Biosurveillance Workforce & New Professions
• CDC response to Homeland Security Presidential Directive 21 “Public
Health and Medical Preparedness” (HSPD-21, 2007)
• Workforce subcommittee chaired by Don Burke
• Findings of insufficient workforce and expertise in
- public health data acquisition, management, and analysis
- social / behavioral / mental health epidemiology
• Recommendation #1: New workforce requirements in public health
informatics ( = Data to Decisions )
• Recommendation #2: New workforce requirements in social, behavioral
and mental health ( = Humans Systems & Modeling of Human Behavior )
55
USE OF HEALTH DATA FOR DECISION-MAKING
Scientific literature
Media
Resource allocation
Disease eradication
Pandemic alert
School closures
Expert opinion
Vaccination
Health regulations
Health Data
Modeling &
Simulation
Quarantine
Medication
stockpiling
56
Nanoscience: Potential Applications
• Health
– Blood Glucose Monitor “tattoos”
Nanoparticles fluoresce when exposed to a
target molecule, such as sodiumor glucose. A
modified iPhone then tracks changes in the level
of fluorescence, which indicates the amount of
sodium or glucose present
– Nano-gels that help regenerate
damaged spinal cords
Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation
after Spinal Cord Injury