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
人類活動
全球變遷
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……
策
略
如何在法律及
教育等面向，
制訂政策、改
變人類活動
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
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.
 水資源之利用與管理.
(水旱與河川水庫整治,
地層下陷)
 人口老化與低出生率.
 山坡地與海岸土地之利用與
管理.
 教育與人口政策, 科技與
 都市發展與人口分佈, 城鄉差
距, 南北差距.
經濟發展策略
 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
前瞻的定義
 前瞻活動納入政策決策機制是全球發展趨勢
前瞻
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。
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.
50 Year Growth History of Taiwan/ MOEA
Manufacture
Oriented
Investment
Oriented
Capital-based
Industry
Labor-based
Industry
Agriculture
Laborintensive
industry
Foster the
foundation
for high-tech
industry
Innovation
Oriented
Technology-based
Industry
High-Tech
industry
sprouts
Emerging
High-Tech
industry
takes off.
Knowledge-based
Industry
Research-based
and high addedvalue
manufacturing
12.0
7.0
2.0
-3.0
1952
1960
1970
1980
1990
2000
2006(f) 2010(d)
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 Innovation
Bridging the Gap between Academia and Industry
discovery driven, not improvement based
Basic Research
Curiosity or
Problem
Driven
Discovery
Invention
Translational
Research
Usable
Technology
or Early Product
Candidate
Innovation
Products
Value Creation
from Innovation.
Manufacturing
and Marketing
Development of research project
A. 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
• 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
 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
• 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.
Sugars on Red Blood Cells Define Blood Type
OH OH
OH OH
O
OH
HO
AcHN
O
OH
OH
HO
O
O
O
OH
HO
O
OH
O
O
O
O
O
OH
O
OH
HO
OH
HO
OH
Type-A
Type A
Type-B
Type
B
Red Blood
Cell
O
HO
O
O
O
OH
Red Blood
Cell
* Type-A persons contain antibodies against Type-B sugars
* Type-B persons contain antibodies against Type-A sugars
OH
HO
OH
Type-C
Type
O
Red Blood
Cell
Influenza A Pandemic
Subtype: H, Hemagglutinin; N, Neuraminidase
Netherlands, Belgium etc.
H7N7
H1N1 H2N2 H3N2
H1N1
H1N1
H1N1
H5N1
H9N2
H5N1
2009
Swineorigin flu
Modified from Biol Pharm Bull. 2005, 3, 399-408.
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)
20nm
•N-glycosylation site:
N-X-(S/T) is labeled in
red.
•The glycans are
labeled in green.
PNAS (2006),103,19123
Steven et al.
•Sequences around
glycosylation sites are
highly conserved
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 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.
image of an assay
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
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
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
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
Bioactive
Substance
Duration
Success
Rate
Animal
Studies
Drug
Lead
Clinical Trial, 3 phases
Phase I Phase II
Phase III
Candidate
IND
~ 2 Years
<1 / 10
NDA
5 Years or More
1/5
Production
&
Marketing
6 / 10
Changes of Glycans on Cancer-cell Surface
State 1
(Healthy)
State 2
(Disease)
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
OH OH
OH OH
O
HO
O
O
O
HO
O
OH
O
O
NHAc
FucT
H3C
OH OH
OH
O
OH
OH
O
OH
HO
OH
O
HO
O
OR
OH
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 possible
tetrasaccharides
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
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.
臺灣人口結構的變遷
•
資料來源：內政部戶政司、行政院經濟建設委員會
40
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：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
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