1. Translational Medicine （橋渡し研究） : Bridge Over the Valley of Death （死の 谷に掛ける橋） Edward W. Holmes, MD Vice Chancellor Emeritus, Health Sciences University of California San Diego President, Sanford Consortium for Regenerative Medicine

2. Goals of Translational Medicine （ TR の ゴール） Advance our insight and understanding of human disease （ヒト疾患の洞察と理解の進 歩させる） Use these advances to improve the health of individuals and populations （個人および人 口全体の健康の改善にこれらの進歩を使 う） Enhance economic well being of society （社 会経済の健全性を増進する）

3. Translational Medicine Has a Broad Remit （ TR は広いレミットを有する） TransMed Starts and Ends with the Patient TR は患者で始まり患者で終わる Clinical Medicine Basic Research Patient studies: Therapeutic Intervention Patient studies: Disease Pathogenesis

4. What is Translational Research Translation does not end with the ribosome, and it does not begin with a clinical trial （ TR はリボソームで終わるのではなく臨 床研究で終わるのでもない） Broad enterprise that spans disease pathogenesis to discovery of therapeutic targets to demonstration of clinical effectiveness （ TR は病気の病態から治療標的の発見と臨 床効果の実証にまでわたる広範な企画である）

5. The Translational Continuum :TR の連続性 From Discovery to Delivery （発見から配送まで） Lead Optimization Drug Target Lead Optimiz- ation Target Validat- ion GMP Clinical Trials Clinical Delivery The Enablers Discovery Research High Throughput and Design Medicinal Chemistry Models: Mice Primates ManufacturingPatients G l o b a l H e a l t h Ph.D. MD Industry Chemist Translational Ph.D. Physician-Scientist Physician Scientist Clinical Investigator Clinicians The Human Capital

6. Translational Medicine （橋渡し医 学） Fundamental Medical Discovery Potential New Drug Approved New Theraupetic The Valley of Death TranslateIntoCommercializeInto 基盤的な医学の発見 死の谷を橋渡しして 可能性のある 新薬剤を開発し 承認された新規治療へと 商業化してゆく

7. Causes of the Valley of Death Too few well trained Physician Scientists （よ く鍛えられた MD,PhD が非常に少ない） Lack of adequate infrastructure （適切な下部 組織が欠如） Funding to support the people and infrastructure （人と下部組織を支持する資 金）

8. Human and Physical Capital ( 人的物理的資本） : Translational Medicine Program （ TR プログラ ム） Basic Disease- Investigative Clinical Trials Clinical Research Oriented Medicine Epidemiology Practice of Research Health Svcs Rsch Medicine Physician Scientists （ MD PhD) TCR Project Teams （研究チーム） Regulatory Experts （レギュラトリーサイエンス の専門家） Infrastructure （下部組織）

9. Human Capital （人的資本） : Translational Medicine Program Basic Disease- Investigative Clinical Trials Clinical Research Oriented Medicine Epidemiology Practice of Research Health Svcs Rsch Medicine Physician Scientists TCR

10. Bridge over the Valley of Death （死の谷に掛ける 橋） : (1) Physician Scientists （ MD, Ph.D) Training （訓練） - dual training; clinical and scientific （臨床と科学の二重の訓練） Protected time （時間の保護） - 80% research （研究） ; 20% clinical （臨床） Environment- Leadership respects and supports dual mission （統率力で２重の指名 を尊重し支持する） Endangered species （絶滅危惧種） - international shortage （国際的に欠乏）

11. Facilities( 施設） : Translational Medicine Program （ TM プログラ ム） Basic Disease- Investigative Clinical Trials Clinical Research Oriented Medicine Epidemiology Practice of Research Health Svcs Rsch Medicine TCR Infrastructure （下部組織）

12. Bridge over the Valley of Death （死の谷に掛ける 橋） : (2) Infrastructure （下部組織） Clinical Research Facilities for Patient Studies （患者研究のために臨床研究施設） Access to development technologies （進歩す る技術へアクセスする） : High Through Put Screening, Medicinal Chemistry, Mab production, device prototype production Access to GMP facilities, Toxicology assessment （ GMP に準拠した施設）、毒物学的評 価へのアクセス）

13. Team Members （チームメンバー） : Translational Medicine Program Basic Disease- Investigative Clinical Trials Clinical Research Oriented Medicine Epidemiology Practice of Research Health Svcs Rsch Medicine TCR Team Specialists （チームの専門家集団） Project Teams( プロジェクトチーム） Regulatory Experts （レギュラトリーサイエンスの専門家）

14. Bridge over the Valley of Death （死の谷に掛ける 橋） : (3) Team Members Nurses and Study Coordinators （看護師と研 究のコーディネーター） Project Team （研究チーム） Regulatory Expertise （レギュラトリーサイ エンスの専門家） Advisory Panel with industry and business expertise in addition to scientific expertise （企業やビジネスの専門家と関連を持っ た相談役の審査団）

15. Bridge over the Valley of Death （死の谷に掛ける 橋） : (4) Business Development Office （ビジネスを発展させるオ フィス） Intellectual Property and Technology Transfer （知的財産と技術移転） Legal support for contract services （契約のた めの法的な支持）, etc Industrial Partnership Office （産業連携オフィ ス）

16. Key Recommendations INDUSTRY BENCH Key performers: A*STAR BMRC RIs, universities BEDSIDE Key performers: MOH (viz. hospitals, specialist centres) >> Grow health services, public health research >> Build critical mass of human capital, supernumerary to clinical service needs >> Establish flagship programmes from bench-to-bedside (heart/ metabolic, neuro, cancer, eye, infectious disease) Driven by A*, EDB, Bio*One Driven by EDB, Bio*One >> Develop best enabling resources in Asia for translational research >> Strengthen regulatory framework for translational and clinical research. Driven by multi- agency BMS Exco Interaction strengthened by new entities arising from hospital- medical school partnerships >> Develop strong investigational med capability >> Be preferred site for early phase clinical trials in Asia

17. Research Scholarships （研究奨 学金） Masters of Clinical Investigation MD- PhD MBA-MD Research Fellowships ________________

18. Talent Development Programmes （才能育成プログラム） Singapore Translational Research Investigator Awards (STaR) Clinician Scientist Awards (CSA) Transition Awards

19. Talent Development Programmes （才能育成プログラム） 100% of academic salary provided （ 100% のアカデ ミアとしての給料を供給） Guarantee of 70-80% of time protected for research （ 70 ～ 80% の研究 時間を保証する） Variable laboratory support （種々の実験室で の支持）

20. Clinical Research Institute （臨床研究施 設） One-stop centre providing infrastructure support, to conduct clinical trials （ One-stop centre が臨床 試験を実施する下部組織の支持を供給する）

21. Translational and Clinical Research (TCR) Flagship Programmes Disease AreasAwardeesHost Institution Gastric Cancer - Genomics and biomarkers trials A/Prof Yeoh Khay Guan National University of Singapore Neuroscience - Schizophrenia and related psychoses A/Prof Chong Siow Ann Institute of Mental Health Eye Diseases - Glaucoma and corneal disorders Prof Donald TanSingapore Eye Research Institute Infectious Disease - Dengue treatment and prevention A/Prof Leo Yee SinTan Tock Seng Hospital Metabolic Diseases - Developmental pathways A/Prof Chong Yap Seng National University of Singapore Five TCR Programmes awarded - S$25mil each

22. Other TCR Initiatives （他の TCR 主導 権） Experimental Therapeutics Centre (ETC) –Established to fill the gap between identification of therapeutic targets and synthesis of lead compounds or biologics for clinical trials （治療標的の決定とリード化 合物の合成や臨床試験のための生物学との間のギャッ プを埋める） Singapore Institute for Clinical Sciences (SICS) –Research institute to bridge basic scientists at Bioplois with clinical investigators in AMCs （バイオポリスの基 礎研究者と AMCc の臨床研究者との懸け橋となる研究 施設） Restructured IRBs –Domain specific IRBs that cover all public hospitals （す べての公立病院を包括する領域に特化した IRB)

23. Other TCR Initiatives Singapore Consortium for Cohort Studies (SCCS) –Common infrastructure for coordination of cohort studies and collection of phenotypic data( コホート研究のコーディ ネートと特性データの収集のための共通下部組織） Singapore Tissue Network (STN) –National resource for collection, storage, and retrieval of human tissue samples to support translational and clinical research （ TR や CR を支持するためのヒト組織サンプルの 収集保管検索のための国立資源 Clinical Research Imaging Center (CIRC) –Advanced imaging technologies dedicated to human research studies （ヒト研究の特化した最新のイメージン グ技術）

24. Singapore’s Niche in Translational and Clinical Research （ TR と CR でのシンガ ポールの相応しい位置） Asian Phenotype （アジア人の特性） Focus on Diseases of Interest to Singapore or Special Ability to Study in Singapore （シンガポールにとって興味の ある病気またはシンガポールでの特徴的な 研究能力） Investigational Medicine and POC Studies （研究医学や POC 研究）

25. 20072008 Mid 2006 2000 Nov 07 Kent Ridge Campus Joint NUHS established Mar 08 STaR Daniel Tenen, David Virchup, Michael Chee, Wong Tien Yin Feb 07 CSI 2 Snr Inv Award 4 Inv Award Jul 07 TCR Flagship $25M for Gastric Cancer (led by NUS) Aug 07 Outram Campus GMS launched; inaugural batch of 26 students Mar 08 Training pipeline 2 AST- PhD MCI launched Jul 08 TCR Flagship $25M each for Eye & Neurosciences Oct 08 TCR Flagship $25M to be awarded for CV/metabolism, and ID Mar 08 Strategic Research Infra Proposed i) Research space (RBF, ARF, IMU):16,000sqm at KR, 23,000sqm at Outram; ii) IMUs: 24 beds in KR, 30 beds in Outram Strengthening TCR Jan 08 Academic Clinical Research Orgn Duke to establish SCRI in 08 2006 Multi-Agency BMS Exco reconstituted; co-chaired by MOH & A*STAR BMS Phase 1 (2000-2005) Jul 06 Launch of BMS Phase 2 $1.55B for TCR 2007: Establishment of SICS, SIgN, ETC Mar 08 CSA 4 Senior Inv &1 Inv Feb 08 Established CBME

26. Clinical Imaging Research Centre (CIRC) In Apr 08, Ministry of Trade & Industry approved S$31.8mil from S&T2010 to fund CIRC activities for 5 years. Construction of CIRC Phase 1 facility at the NUS Centre for Life Sciences began in early March 2008 and completed on 18 September 2008. The Siemens 3 Tesla clinical whole body MRI installed in Phase 1 facility in July 2008. Construction for CIRC Phase 2 facility at the new NUS Centre for Translational Medicine has begun and will be completed in March 2011. Ongoing exploration of partnerships with MOH, Duke-NUS GMS etc to develop CIRC's clinical programmes and advancing imaging techniques such as PET-MR.