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From Discovery Research to Translational Innovation Interplay of Chemistry and Biology

From Discovery Research to Translational Innovation Interplay of Chemistry and Biology. Chi-Huey Wong Academia Sinica chwong@gate.sinica.edu.tw. 人類永續發展的問題. 解決人類永續發展的問題，需國際社會共同合作. 人類活動. 全球變遷. 永續發展. 如何在法律及教育等面向，制訂政策、改變人類活動. 社會 經濟 工業 …. 現象：臭氧層破洞、全球

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From Discovery Research to Translational Innovation Interplay of Chemistry and Biology

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  1. From Discovery Research to Translational InnovationInterplay of Chemistry and Biology Chi-Huey Wong Academia Sinica chwong@gate.sinica.edu.tw

  2. 人類永續發展的問題 解決人類永續發展的問題，需國際社會共同合作

  3. 人類活動 全球變遷 永續發展 如何在法律及教育等面向，制訂政策、改變人類活動 社會 經濟 工業 … 現象：臭氧層破洞、全球 暖化、極端氣候、生 物多樣性、災害、生 態、糧食、健康、水 資源、人口問題…… 研究：觀測、模式與預測能力的建立、 災害緩減及適應方式的探討、 新科技的開發(新綠能等)、 歷史探討及相關人文社會科學的研究 永續發展的歷程 策 略

  4. 台灣永續發展面臨的挑戰 • 能源自主性, 效率與 新綠能. • 農業政策與糧食自主. • 人口老化與低出生率. • 教育與人口政策, 科技與 經濟發展策略 • 水資源之利用與管理. (水旱與河川水庫整治, 地層下陷) • 山坡地與海岸土地之利用與管理. • 都市發展與人口分佈, 城鄉差距, 南北差距. • 文化價值的建立.

  5. 永續發展的主要內涵 地球環境 社會公平正義 經濟發展

  6. 前瞻的定義 • 前瞻活動納入政策決策機制是全球發展趨勢 前瞻目的在管理未來不確定性。系統性評估可能對競爭力、生活品質、財富創造等層面造成重大影響趨勢。 前瞻本質乃以調查社會的意見來預測及勾勒未來情景需求。並藉調查過程形成共識目標，掌握長期科技發展脈絡，引導政策與策略的形成，建構完善的基礎建設與有利於創新的環境，使經濟與社會獲得最大效益。 前瞻

  7. 前瞻議題 科技的前瞻 教育的前瞻 科技投資效益回饋的時程需十至二十年，且技術發展變化快速；如何掌握先機與發展方向是提升競爭力必要條件。 教育政策及方法應探討如何培育創新理性思考之人才及建立終身學習的環境，並持續且有策略的爭取國際人才。教育前瞻已是刻不容緩的公共政策基礎。

  8. 前瞻議題 資源的前瞻 人文的前瞻 人口、能源、環境、水源、土地、海洋、物種等資源，需有長遠的策略規劃，以落實永續發展。 社會的價值觀及生活方式，應從人文及環境的關懷出發，由產業、學界及社會共同塑造提倡，透過知識闡明及宣導，引導社會朝創新及永續發展，同時培養正確的生活態度及社會責任。

  9. 五、結論與建議 前瞻決策與永續發展 以推測並型塑長期社會,經濟,技術發展與需求為基礎，廣邀各界進行探索,討論與分析,形成願景與共識.其過程實踐決策科學化與意見多元化，同時配合新的法規與教育政策,以因應未來的挑戰,是提升國家競爭力與永續發展所迫切需要之機制.

  10. 50 Year Growth History of Taiwan/ MOEA Manufacture Oriented Investment Oriented Innovation Oriented Capital-based Industry Technology-based Industry Knowledge-based Industry Labor-based Industry Emerging High-Tech industry takes off. Foster the foundation for high-tech industry High-Tech industry sprouts Research-based and high added-value manufacturing Agriculture Labor-intensive industry 1990 1960 1980 1970 2010(d) 1952 2006(f) 2000

  11. Taiwan’s Innovation in the High-tech Industry World Leader of Many Electronic Products Chip foundry services Notebook PCs LCD monitors PDAs, Cell phones, iPhones

  12. 2009 STAG: General Observations Since the 1980’s, Taiwan has successfully developed the semiconductor, information and communication technology (ICT) industry. However, to meet new challenges and improve the economy, Taiwan has recognized the need for diversification and development of new knowledge-based economy through investment in six emerging industries(SEI) to ensure the long-term sustainability and high quality of life.

  13. Strategy • Some emerging industries, e.g. green energy and biotechnology, require development of key technologieswhile others require adequate business models. The government should provide incentives and infrastructure to facilitate their development. • Some emerging industries, e.g. green energy, are being aggressively pursued by other countries, Taiwan must make choices and focus on the areas whichcan become a world leader.

  14. Academic Institutions in Taiwan Innovations in research continue to accelerate in Taiwan and have built a strong foundation of knowledge for applications, but academic institutions need to have more flexibility to modify their programs to insure their graduates to have the knowledge and skills required for emerging industries and new challenges.

  15. Discovery Invention Translational Research Basic Research Products Innovation Curiosity or Problem Driven Usable Technology or Early Product Candidate Value Creation from Innovation. Manufacturing and Marketing Discovery and Innovation Bridging the Gap between Academia and Industry discovery driven, not improvement based

  16. Development of research project Problem-driven 1. Identify an important scientific or technical problem - design research – solution (tools, methods, composition). 2. Identify a significant disease problem – design research – solution (disease treatment, cure). 3. ---- Other areas problems B. Curiosity-driven Initiate a curiosity-based question - design research – result (knowledge, tools)

  17. Scientific Research and Accountability: Push and Pull Academic freedom vs social responsibility Curiosity driven vs problem solving research Intellectual property protection vs public access to knowledge Financial return vs social return Policy making vs knowledge uncertainty Participation and reward vs ethics and conflict of interest

  18. Trends in Healthcare and Biotechnology Industry From disease treatment to personalized and preventive medicine. Due to aging populations, the healthcare economy will reach US$ ~ 6 trillion in 5 years (~ 3 trillion will be from the biotech and pharmaceutical industry). Asia will soon have 1/3 of the world market.

  19. The Human Genomeand Post-Translational Glycosylation • 46 Chromosomes • Three billion nucleotides • Only 1.5% encode genes • ~25,000 genes • >90% proteins glycosylated Based on AsnXThr/Ser sequon Nature, 2001, vol. 409, no. 6822.

  20. Type A Type B Type O Red Blood Cell Red Blood Cell Red Blood Cell

  21. Influenza A Pandemic Subtype: H, Hemagglutinin; N, Neuraminidase Netherlands, Belgium etc. H7N7 H1N1 H2N2 H3N2 H1N1 H5N1 H5N1 H1N1 H9N2 H1N1 2009 Swine-origin flu Modified from Biol Pharm Bull. 2005, 3, 399-408.

  22. Effect of HA glycosylation on receptor binding and immune response: New direction for flu detection and universal vaccine design Host receptor binding site • 18 N-glycosylation sites (6 per monomer) • N-glycosylation site: N-X-(S/T) is labeled in red. • The glycans are labeled in green. • Sequences around glycosylation sites are highly conserved 20nm PNAS (2006),103,19123 Steven et al.

  23. Optimer Programmable One-Pot Synthesis Science,2001, 291, 2344

  24. Glycan Array for Detection and Differentiation of Influenza HAsJ. Am. Chem. Soc. 2010, 132, 14849-56

  25. Glycan Chips for Detection of Virus and Cancer

  26. image of an assay The High-throughput Screening System Collection: 2.2 million compounds (synthetic and natural compounds). Miniaturization: 1536-well microplate (assay volume 5uL ~ 10uL). Detection: luminescence or fluorescence(FI, FP, FRET, TRF etc ). Throughput: ~ 1 M per day for target or cell-based assay.

  27. Major Resistance Problems • Bacteria: • Methicillin- and Vancomycin resistant staphylococci (MRSA) • Penicillin-resistant pneumococci • Macrolide-resistant group-A streptococci • Vancomycin resistant enterococci (VRE) • Corynebacterium jeikeium • Mycobacterium tuberculosis • Clostridium difficile • Enterobacteriaceae • ESBLs, notably in Klebsiella • Chromosomal b-lactamases • Enterobacter, Citrobacter, etc…. • Salmonella typhi • Shigella dysenteriae • Pseudomonas aeruginosa • Burkholderia cepacia • Stentrophomonas maltophilia • Acinetobacter sp. Viruses:Hepatitis,Influenza,Dengue,Enterovirus,HIV

  28. Top 10 Causes of Death in Taiwan • Cancer Top 10 Cancers • Heart Disease 1. Lung Cancer • Cerebrovascular Disease 2. Liver Cancer • Diabetes 3. Colorectal Cancer • Pneumonia 4. Breast Cancer • Accident 5. Oral Cancer • Chronic Lower Respiratory Disease 6. Stomach Cancer • Chronic Liver Disease 7. Prostate Cancer • Hypertension 8. Pancreatic Cancer • Kidney Disease 9. Esophageal Cancer 10. Cervical Cancer

  29. Value Chain of Drug Discovery and Development Cost in US$: Preclinical ~2m; Phase 1 ~2m; Phase 2 ~10m; Phase 3 >80m Manufacturing and marketing >100m (total cost: 120m to 1b) Development Discovery Drug Discovery Animal Studies Phase I Phase II Phase III Production & Marketing Clinical Trial, 3 phases Drug Lead CandidateIND BioactiveSubstance NDA ~ 2 Years 5 Years or More Duration SuccessRate <1 / 10 1 / 5 6 / 10

  30. Changes of Glycans on Cancer-cell Surface State 1 State 2 (Healthy) (Disease)

  31. Specific Glycan Markers for Development of Diagnostics and Vaccines Angew. Chem. Int. Ed. 2001, 40, 1274; PNAS 2008, 105, 11661-6 More than 70% of breast cancer cells have Globo H. It is also on prostate, lung, ovarian, pancreatic, brain, endometrium, gastric and colon cancers. • Globo H-based vaccine for breast cancer (phase 2&3 trials) • (GloboH-KLH-QS21) • Globo H array for antibody detection

  32. From Discovery Research to Translational Medicine

  33. End Thank You

  34. End Thank You

  35. Programmable One-Pot Synthesis of OligosaccharidesZhang, Ollman, Bassov, Wong, J. Am. Chem. Soc. 121, 734 (1999)Sears & Wong, Science 291,2344 (2001) One-Pot 9 monosaccharides 1.5 x 107 possible tetrasaccharides

  36. AS Report: Enhancing Technology Competitiveness Report on Foresight Taiwan by Eugene Wong (Emeritus Professor, UC-Berkeley & Academician of AS) • Need for disruptive change – two sources: • New industries based on early stage technologies- discovery driven, not improvement based • High value services- technology based transformation of services • Goal of Foresight Taiwan - Catalyze development of new innovative industries

  37. Global Challenges Require Global Cooperation Challenges: 1. Global warming and climate change. 2. Non-carbon energy source. 3. Environment protection and biodiversity conservation 4. Natural disaster: prevention and management. 5. Population growth and food/water supply. 6. Aging and health care. 7. Emerging infectious diseases 8. Preventive and personalized medicine.

  38. 資料來源：內政部戶政司、行政院經濟建設委員會資料來源：內政部戶政司、行政院經濟建設委員會 臺灣人口結構的變遷 40

  39. 老化、醫療科技對醫療費用影響 科技發展與人口老化：人口衝擊下社會負擔 圖片來源：鄭文輝&陳孝平，老化、醫療科技、及經濟成長對醫療費用總額之影響，中央健康保險局委託研究案，2004 圖片來源：行政院經建會，2010年至2060台灣人口推計，2011 41

  40. 前瞻的內涵 資料來源:修正自 forera.jrc.ec.europa.eu/ ■結構化型塑、推測長期社會、經濟、技術發展與需求，廣邀各方相關人士進行探索性討論及分析。透過嚴謹科學互動式方法形成策略性願景及共識。 43

  41. 永續發展的主要內涵 地球環境 社會公平正義 經濟發展

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