From discovery research to translational innovation interplay of chemistry and biology
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From Discovery Research to Translational Innovation Interplay of Chemistry and Biology. Chi-Huey Wong Academia Sinica [email protected] 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

From Discovery Research to Translational InnovationInterplay of Chemistry and Biology

Chi-Huey Wong

Academia Sinica

[email protected]


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

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.


From discovery research to translational innovation interplay of chemistry and biology

永續發展的主要內涵

地球環境

社會公平正義

經濟發展


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

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。


From discovery research to translational innovation interplay of chemistry and biology

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。


From discovery research to translational innovation interplay of chemistry and biology

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.


From discovery research to translational innovation interplay of chemistry and biology

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


Taiwan s innovation in the high tech industry

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


2009 stag general observations

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.


Strategy

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.


Academic institutions in taiwan

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.


From discovery research to translational innovation interplay of chemistry and biology

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


Development of research project

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)


Scientific research and accountability push and pull

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


Trends in healthcare and biotechnology industry

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.


The human genome and post translational glycosylation

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.


From discovery research to translational innovation interplay of chemistry and biology

Type A Type B Type O

Red Blood

Cell

Red Blood

Cell

Red Blood

Cell


From discovery research to translational innovation interplay of chemistry and biology

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.


From discovery research to translational innovation interplay of chemistry and biology

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.


Optimer programmable one pot synthesis

Optimer Programmable One-Pot Synthesis

Science,2001, 291, 2344


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

Glycan Chips for Detection of Virus and Cancer


From discovery research to translational innovation interplay of chemistry and biology

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.


Major resistance problems

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


Top 10 causes of death in taiwan

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


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

Changes of Glycans on Cancer-cell Surface

State 1

State 2

(Healthy)

(Disease)


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational medicine

From Discovery Research to Translational Medicine


From discovery research to translational innovation interplay of chemistry and biology

End

Thank You


From discovery research to translational innovation interplay of chemistry and biology

End

Thank You


From discovery research to translational innovation interplay of chemistry and biology

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


As report enhancing technology competitiveness

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


Global challenges require global cooperation

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.


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

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


From discovery research to translational innovation interplay of chemistry and biology

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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