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

永續發展的歷程策 略人類活動 全球變遷 永續發展

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

如何在法律及教育等面向，制訂政策、改變人類活動

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 .

永續發展的主要內涵

地球環境

社會公平正義 經濟發展

前瞻

前瞻的定義

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。

前瞻活動納入政策決策機制是全球發展趨勢

前瞻議題教育的前瞻

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。

科技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。

前瞻議題資源的前瞻

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。

人文的前瞻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。

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 .

五、結論與建議前瞻決策與永續發展

50 Year Growth History of Taiwan/ MOEA

-3.0

2.0

7.0

12.0

Labor-based

Industry Capital-based

Industry Technology-based

Industry Knowledge-based

Industry

Agriculture Labor-intensive industry

Foster the foundation for high-tech industry

High-Tech industry sprouts

Emerging High-Tech industry takes off.

Research-based and high added-value manufacturing

1952 1960 1970 1980 1990 2000 2010(d) 2006(f)

Manufacture Oriented

Investment Oriented

InnovationOriented

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

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 • Some emerging industries, e.g. green energy

and biotechnology, require development of key technologies while 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 which can become a world leader.

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.

Discovery and InnovationBridging the Gap between Academia and Industry

discovery driven, not improvement based

DiscoveryInvention

Basic Research

Curiosity orProblem Driven

InnovationTranslational Research Products

Usable Technology

or Early Product Candidate

Value Creation from Innovation.Manufacturing and Marketing

Development of research projectA. 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 problemsB. Curiosity-driven Initiate a curiosity-based question - design research

– result (knowledge, tools)

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

財團法人生物技術開發中心DEVELOPMENT CENTER FOR BIOTECHNOLOGY

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 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.

O

OH

HO

OH

AcHN OO

OH

OO

O OHHO

OH

OH O

OH

HO

OH

HO OO

OH

OO

O OHHO

OH

OH HOO

OH

OO

O OHHO

OH

OH

Type-A Type-B Type-C

* Type-A persons contain antibodies against Type-B sugars

* Type-B persons contain antibodies against Type-A sugars

Sugars on Red Blood Cells Define Blood Type

Red BloodCell

Red BloodCell

Red BloodCell

Type A Type B Type O

Modified from Biol Pharm Bull. 2005, 3, 399-408.

H1N1 H2N2 H3N2

H1N1H1N1

H7N7

H5N1H9N2

H1N1

H5N1

Netherlands, Belgium etc.

Subtype: H, Hemagglutinin; N, Neuraminidase

Influenza A Pandemic

2009

Swine-origin flu

Effect of HA glycosylation on receptor binding and immune response: New direction for flu detection and universal vaccine design

• 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

Host receptor binding site

PNAS (2006),103,19123Steven et al.

20nm

Optimer Programmable One-Pot Synthesis

Science, 2001, 291, 2344

Glycan Array for Detection and Differentiation of Influenza HAs

J. Am. Chem. Soc. 2010, 132, 14849-56

Glycan Chips for Detection of Virus and Cancer

The High-throughput Screening SystemCollection: 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.

image of an assay

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

Major Resistance ProblemsEnterobacteriaceae

ESBLs, notably in KlebsiellaChromosomal b-lactamases

Enterobacter, Citrobacter, etc….

Salmonella typhiShigella dysenteriae

Pseudomonas aeruginosaBurkholderia cepaciaStentrophomonas maltophiliaAcinetobacter sp.

Viruses: Hepatitis, Influenza, Dengue, Enterovirus, HIV

Top 10 Causes of Death in Taiwan1. Cancer Top 10 Cancers 2. Heart Disease 1. Lung Cancer3. Cerebrovascular Disease 2. Liver Cancer4. Diabetes 3. Colorectal Cancer5. Pneumonia 4. Breast Cancer6. Accident 5. Oral Cancer7. Chronic Lower Respiratory Disease 6. Stomach Cancer8. Chronic Liver Disease 7. Prostate Cancer9. Hypertension 8. Pancreatic Cancer10. Kidney Disease 9. Esophageal Cancer 10. Cervical Cancer

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)

Discovery Development

Production &

Marketing Phase III Phase II Phase IAnimal Studies

Drug Discovery

BioactiveSubstance

Drug Lead

CandidateIND NDA

Duration

SuccessRate

~ 2 Years 5 Years or More

<1 / 10 1 / 5 6 / 10

Clinical Trial, 3 phases

State 1(Healthy)

State 2(Disease)

Changes of Glycans on Cancer-cell Surface

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

OHOO

OH

OHO

HOOH

OHO

OO

OH

OHOHO

ONHAc

OHOHO

HOO

OHOH

OOH

OHHO

H3C

OR

FucT

From Discovery Research to Translational Medicine

End Thank You

End Thank You

Programmable One-Pot Synthesis of Oligosaccharides

Zhang, Ollman, Bassov, Wong, J. Am. Chem. Soc. 121, 734 (1999)Sears & Wong, Science 291,2344 (2001)

One-Pot

9 monosaccharides

1.5 x 107 possibletetrasaccharides

AS Report: Enhancing Technology Competitiveness

Report on Foresight Taiwanby 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

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.

• 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

老化、醫療科技對醫療費用影響

圖片來源：行政院經建會， 2010年至 2060台灣人口推計， 2011 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

科技發展與人口老化：人口衝擊下社會負擔

41

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

永續發展的主要內涵

地球環境

社會公平正義 經濟發展