Jack Smith, Director S&T Foresight

1. APEC-CTF Emerging Infectious Diseases December 13, 2007 Jack Smith, Director S&T Foresight

2. What is Foresight? A set of strategic tools that support government and industry decisions with adequate lead time for societal preparation and strategic response. • Anticipates multiple, plausible futures • 5 – 25 year time horizon • A rehearsal for potential futures • Accommodates uncertainty & diversity • Highlights emerging opportunities & threats

3. Macro Shaping Trends • Ambient Intelligence – progress toward the Singularity • Miniaturization of Technology • Globalization of Capital, Terror , Disease, Environment • Anti-globalization of Biodiversity, Culture, Sustainability • De-Carbonization of Energy Economy • Harmonization - Standardization for Trade • Migration, Multi-Culturalism of Populations • Intensification, Differentiation, of Wealth • Bi-polarization of religious Values and Secular Evolution • Transformation, of Infrastructure Systems • Virtualization, Digitization & Integration of: Business-Professions, Manufacturing & Production, Communications, Entertainment, Education • Acceleration of Knowledge Services as Economic Driver • Proliferation of Surveillance - Security

4. Foresight Outcomes & Benefits Engages:multiplestakeholders Removes:currentconstraints Activates:early-warningradar Identifies:critical S&T Prepares:for change Educates:leaders &public Better decisions … more robust policy, targeted research and insightful analysis

5. UK Foresight Evaluation • Successful in mobilizing high-calibre specialists to collaborate on future societal issues and opportunities; • Engaged senior policymakers with science and scientists, and influenced government wide policy formulation in complex domains; • Directly informed national priorities and programmes, and increased public visibility; • There is scope for greater engagement with the government’s wealth creation agenda

6. Virus SARS (Severe acute respiratory syndrome) West Nile Influenza Eastern Equine Encephalitis Hantavirus Ebola Bacteria and Rickettsiae Plaque E. coli O157 Rickettsial pox (Rocky Mountain Spotted Fever) Cholera Protozoa Malaria Cryptosporidium parvum Trypanosomiasis (African) Leshmaniasis Since 1973 : Rotavirus – 1973 Parvovirus – 1975 Cryptosporidium parvum– 1976 Ebola virus – 1977 Legionella pneumophila– 1977 Hantavirus – 1977 Campylobacter jejuni– 1977 Escherichia coli O157– 1982 Borelia burgdorferi– 1982 Helicobacter pylori– 1983 Cyclospora cayatanensis– 1986 Hepatitis E – 1988 Vibrio cholerae O 139 -- 1992 Emerging & Re-Emerging Infectious Diseases

7. Sources of EID • Dam building • Traditional agriculture • Urbanization • De-forestation • Irrigation • Political unrest and open warfare • National disasters and unusual patterns

8. SARS • The initial symptoms are non-specific and common. • Incubation period of 2~10 days allowing the infectious agent to be transported, unsuspected and undetected, in an air traveller from one city in the world to anyother city having an international airport. The concentration of cases in previously healthy adults and the proportion of patients requiring intensive care are particularly alarming.Intra-hospital transmission amplified regional outbreaks and augmented spread of the illness into the community.

9. In-silico Mutagenesis of H5N1 Hemagglutinin Principle Investigator CHAK SANGMA, Cheminformatics Research Unit, Chemistry Department, Faculty of Science, Kasetsart University, THAILAND Problem Up to now, HA of H5 prefers avian receptor to human receptor but mutated HA found. Can mutation on HA cause the pandemic outbreak? Objective Structure and binding affinity prediction of mutated HA by molecular dynamic simulation using Benefit • Need for H5 mutation monitoring and provide a high throughput prediction Challenges Estimated 240 selected mutations on 24 residues. Estimated computing time: one month per mutant (AMBER9 on 8 nodes cluster) Or 60 months for 240 mutations (32 nodes) Reference: 1.Sangma C., Nunrium P., Hannongbua S. (2006) J. Theor. and Comp. Chem. 5, 1–16. Sponsor • The National Science and Technology Development Agency (NSTDA) • The National Center for Genetic Engineering and Biotechnology • The Thailand Research Fund • Kasetsart University Research and Development Institute

10. Foresight EID Insights Essential interdisciplinarity; Combine Public Health R&D with Animal Health Practices; Identify, Connect and Test Region + Global Stakeholders; Discuss, Share, Jointly Imagine the Innovative Best Practices and Technologies; Mutually Leverage the Diverse Regional Strengths for Disease Prevention-Mitigation

11. EID Scenarios 2017 • Malaria in Miami • 20 K Mystery Deaths • Jurassic Virus • Emerging Rainforest Syndrome

12. Taipei OutcomesModeling

13. Vaccine Strategies

14. Animal Tracking Strategies

15. Key Organizing Principles Integrated Trust Networks; Knowledge Management; Joint Risk Assessments; Innovative, Shared Training; Expand Stakeholders; Develop & Use Technology Emphasize Speed, Integrity & Traceability Adopt Shared Standards; Rehearse Emergency Preparedness

16. Trends in Infotechnology &Ambient Intelligence (ICT) • Progress toward ubiquitous access and embededness; • Open source collaborative tools and deeper peer- to peer functionality; • Continued migration towards device and functional convergence; • Infobased manufacturing, claytronics for distributed fabrication; • Broader object based nodes and networks so everything can be smart and connected; • Pervasive E Science and dynamic simulation and modelling; • Gaming for personal and organizational decisions, learning; • Emerging horizons for faster, exponentially more powerful encryption, quantum information • Sustained info markets growth for surveillance, sensor networks, tracking capacities, nano-electromechanics • Wearable, implantable personalized micro-nano-bio info sensors with data and communications capabilities

17. Trends in Biotechnology • Control, improvements in living organisms • Bio-sensing at the micro and nano level, micro and nano electromechanics • Integration with wireless, RFID, photonics-molecular level cameras • Tissue engineering, artificial organs, implants and protheses • Targeted drug delivery and use of in vitro capacities • Rapid scaleable bio-assays for molecule ID, medical diagnosis and forensics • Personalized medicine using large data sets of patient information, disease statistics, gene sequences and genotypes • Genetically modified insects to counter pathogen carriers • In silico- computer testing and comprehensive modelling for drug characteristics, side effects and receptor simulation – lab on chip • Molecular recognition –targeted drug delivery to organs, tumours

18. Trends in Nanotechnology • Smart materials with nano films, structures • Integration of functions and structure in membranes, fabrics, fibers, self powered entities, biomimetic materials • New environmental leaps in performance: e.g water filtration and purification, biocidals, bioremediation and decontamination • Nano sensor networks, tracking capacities – nano-electro-mechanics (eg HVAC embedded) • Wearable personalized nano sensors with data and communications capabilities • Energy and power efficiencies improvements, battery power management • Smart dust capability for widespread human , environments surveillance • Computational devices embedded in consumer, commercial goods • Functional, programmable nanostructures for controlled drug delivery, performance of implants, protheses • New devices, building materials and fabrics that incorporate nano film solar power and are climate responsive

19. EID Ubiquitous Computing by 2012 Key user requirement is for integrated, smart systems that provide powerful, instantaneous networked information; Networks need to enable early detection from distributed sources, sensors and institutional data; Early alert elements for bio-terror, pandemic and avoidance-management of social panic potential are required.

20. EID Computing 2012 Elements • Global sensing of patterns & situations; • E Science & GRIDs for massive • data mining and collection; • Distributed access & processing; • Robust regional climate and disease incidence model; • Pervasive RFID monitoring of animals; • Review of long term climate models; • Detection-correlation of target populations and climate oscillations • Global intelligence networks aligned with WHO-CDC & regional partners; • Smart sensor systems at traffic points.

21. CCUC: Biomolecular modeling and simulations .....Understand basic properties of known drug-target interaction..... ......design new compounds which fit better to the catalytic site of both Wild and Mutant types..... Put your material in and we’ll serve the calculation Bird Flu Neuraminidase (NA) Hemaglutinin (HA) M2 channel • Computer-aided molecular modeling on Influenza virus H5N1 and HIV-1 enzymes. • To study the structural properties of the enzyme. • To explore the dynamical behavior of the enzyme as well as the inhibitors/drugs. • To investigate the interaction between enzyme and inhibitor.

22. EID Technology & Training Needs • Affordable RFID tags + procedures for wildlife & domestic animals; • Cost-effective vaccines & easy distribution for major threats; • Very small aperture terminals, simple mobile data collection & entry systems; • EID consistent, easy, multilingual KM systems for diverse user interfaces; • Automated easy reporting systems using cell phones or similar; • Regional EID go data system maps and resource call networks; • 911 type alert system for hospitals to manage loads and sort emergency cases.

23. 2018 Needs for Smart EID Networks • LAMP – SMAP – RAPID type solutions for developing countries; • Real time network and data analysis disease spread models and patterns; • Border-arrivals smart detection devices connected to networks; • Prediction models from long term data analyses & climate; • Real time RFID systems, linked to global analysis capacities.

24. 2018 Technology Solutions – AIS-UC • Vector pattern migration analyses; • Pervasive marking delivery for sensors; • Cheap & easy diagnostic kits; • Traditional herb-remedies solutions for rural users; • Advanced gaming, a-life models and simulations; • Open access data base for easy access to relevant information-continuous update; • Traceability systems widely deployed.

25. 2025 Plausible EID & Ubiquitous Computing Horizons… • Smart dust for easy tracking and analysis; • Globally integrated modeling-gaming and risk models, including genomic health profiles; • Rapid characterization of pathogens and automated alerts diagnosed for threats; • Context-aware KM, linked to human response models; • Emergency societal communications and control if required for containment.

26. Convergent Technologies for Health and Life Sciences 2020 Anticipated Market Size Anticipated Feasibility

27. New Technologies for Diagnosis Simple, inexpensive and quick LAMP Useful to monitor point mutations SMAP Useful to identify unknown pathogens RAPID

28. Comparison of Three Methods for Diagnosis PCR (Polymerase Chain Reaction) LAMP (Loop-Mediated Isothermal Amplification) SMAP (Smart Amplification Process) Developed by Roche Diagnostics, Co. Ltd. Eiken Chem. Co. Ltd. RIKEN and Dnaform Co. Ltd. Amplification temperature Thermal cycling (4℃～95℃) Isothermal (65℃ ) Isothermal (60℃ ) Sensitivity High High High Cost for Equipments High Very Low Low Feature Conventional method Low cost Fast detection Fastest detection High fidelity (useful for SNPs analysis) Disadvantage Time (1.5hr) Difficult primer design Difficult primer design Source: Yoshiyuki Nagai and Yoshiko Okamoto

29. Templates 6000 copies 600 copies 60 copies 6 copies 0 copies No primers SYBR Green I→ Features of SMAP　 • Fastest detection within15-30 min • Amplification = detection (No background) • Sensitivity • Low energy requirements (isothermal amplification) Real-time　detection by measuring fluorescence intensity of SYBR Green I More compact (mobile) device is under developing

30. RAPID Robotics-Assisted Pathogen Identification Database An outbreak! 454 sequencer Extract nucleic acids from blood, airway swab, feces etc, and subtract cellular nucleic acids. Determine nucleotide sequences (20 Mb in 24hrs) with a high throughput 454 sequencer. Search their homologies with registered, known sequences. What is the causative agent? ～1 Week Question: Is it a known pathogen, unknown but related to some known one, or completely new one? Answer：It is smallpox; completely unknown; related to human/ animal corona viruses but new. Identify the agent or narrow the candidates down

31. RAPID: New DNA Sequencing Technology(454 life sciences) Features 20Mb sequencing within 24 hr No need of specific primer nor probe No need of pathogen containment facility Problems to be solved Elimination of DNA/RNA from human materials High cost (machine; appx.$1 million, running cost; $8300 per run) Speed up information processing Source: Yoshiyuki Nagai and Yoshiko Okamoto

32. BioSense Electronic Laboratory Exchange Network (eLEXNET) A geographic information system Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE) Epidemic Information Exchange (Epi-X) List of EID Projects and Emerging Technologies

33. Foodborne Disease Active Surveillance Network (FoodNet) Global Outbreak Alert and Response Network (GOARN) Global Public Health Intelligence Network (GPHIN) Health Alert Network(HAN) Infectious Diseases Society of America Emerging Infections Network (IDSAEIN Laboratory Response Network (LRN) PulseNet List of EID Projects and Emerging Technologies

34. APEC CTF EID Foresight Summary Build & Maintain Vibrant Networks – Frequent Events; Collaborate Globally on Disease Tracking, Public Health and Technology; Prepare for Threats & Contingencies Continuously; Regional EID Networks are Global Innovation Systems Assets