National Academies Workshop on STEM Workforce Needs for the DoD and the Defense Industrial Base Emerging Science and Technol0gy in the Life Sciences Donald.
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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) 7 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) 19 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 22 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 24 Computational Project 2: TYCHO Acquisition and analysis of historical disease data 25 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 26 Endangered public health data: USA and world-wide USA Laos India Nigeria 27 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 28 Data entry by “Digital Divide Data” in Phnom Penh 29 History of disease reporting in the US 30 Example: Measles control in the US Weekly incidence rates (/100,000) for US states: 1928-1980 - Vaccine licensed in 1963 (red line) States 31 Computational Project 3: FRANCIS Modeling of human health behaviors 32 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 34 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 40 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 42 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