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Julio Licinio John Curtin School of Medical Research

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1 The Pathway from Fundamental Discovery and Translational Medicine to Global Health
Julio Licinio John Curtin School of Medical Research The Australian National University




5 Smallpox V. major: more serious disease – mortality: 30–35%
V. minor: milder form of disease: kills 1% Long-term complications of V. major infection: characteristic scars, commonly on face (65–85%) Blindness: from corneal ulceration and scarring Limb deformities due to arthritis and osteomyelitis Emerged in human populations about 10,000 BC Earliest physical evidence of smallpox: pustular rash on the mummified body of Ramses V, Pharaoh of Egypt, who died in 1157 BC.

6 Ramesses V, Pharaoh of Egypt, 1149–1145 BCE

7 Smallpox 18th century: killed 400,000 Europeans per year (including five reigning monarchs) Was responsible for a third of all blindness. Of all those infected, 20–60%—and over 80% of infected children—died from the disease. 20th century alone: 300–500 million deaths Early 1950’s: 50 million in the world per year. 1967: (WHO) 15 million people contracted the disease and that two million died in that year.

8 Variola virus Genus Orthopoxvirus Family Poxviridae
Subfamily chordopoxvirinae. Large brick-shaped virus measuring approximately 302 to 350 nanometers by 244 to 270 nm Single linear double stranded DNA genome 186 kilobase pairs (kbp) in size containing a hairpin loop at each end. Unique among DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus.

9 Smallpox Africa – Europe – Asia – Americas – Australia
Japan: epidemic of killed 1/3 of population Decimated native America empires: 80-90% death Australia: introduced in 1789 and again in 1829 Devastation among aborigines Died out on both occasions Only continent without endemic smallpox Successful vaccination campaigns: 19th & 20th centuries WHO certified the eradication of smallpox in 1980 Only human infectious disease to have been eradicated


11 Smallpox vaccination Live virus Smallpox virus Cowpox virus:
Used for centuries in China and Turkey Dangerous: Person gets sick Is infectious Cowpox virus: No major illness Live vaccinia virus PROCESS STARTED 14 May 1796 ENDED 8 May 1980 Professor Frank Fenner Chairman, Global Commission for Certification of Smallpox Eradication

12 Accelerating translation
Moving away from a cottage industry of individual efforts To a systematic, cross-disciplinary effort Instead of being a side-activity TM must become a bona-fide academic discipline in its own right Process analogous to pharmacology Drugs used by different specialties for centuries An organized discipline of pharmacology led to enormous progress in therapeutics An organized discipline of TM should likewise lead to enormous progress in translation

13 Creation of a new discipline
Body of work Development of specific methods and approaches Workforce development Community engagement Academic community Community at large

14 TM as Academic Discipline
Development of specific methods and approaches (creative infrastructure that nurtures growth and progress). For translational medicine, this consists of the following: Novel translational methods. This involves cross disciplinary innovation with contributions from the following non-healthcare academic areas: Architecture: city and housing planning guided by translational health outcomes Population health and epidemiology: applying genomics to population health and epidemiology to develop and validate in large cohorts novel translational approaches towards personalised medicine. Chemistry: translational chemistry

15 TM as Academic Discipline
Mathematics: novel approaches towards modelling and data analysis. Engineering: translational biomedical engineering. Physics: novel robotics and imaging capacities. Law: new legal approaches to translational issues. Philosophy: bioethics approaches to new technologies, such as large scale genomics. Sociology and anthropology: approaches to include minority, indigenous and underrepresented rural and economically disadvantaged communities in research in a manner that is inclusive and participatory, but not coercive. Earth sciences: the impact of climate change on health.

16 TM as Academic Discipline
Asia and Pacific studies: approaches to global health outcomes Arts and communication sciences: novel outreach strategies Translational cores that facilitate the work developed in the areas listed above Research ethics, research design, and data analysis: Translational protocols must be ethical, of sound design, and interpretable Informatics capacity to support TM within institutions and for cross-institutional collaboration on compatible platforms Translational clinical research spaces

17 TM as Academic Discipline
Creation of a specialized workforce that did not exist before. Novel curricula Courses Postgraduate training programs Dedicated career development Clinical programs that incorporate translational medicine, including the offering of dual degrees, one of them being in translational medicine

18 TM as Academic Discipline
Community engagement. Two levels: Engagement within the scientific community. International programs. Specialized journals. Scientific meetings. Professional outreach programs to promote awareness and cross-disciplinary outreach and collaboration. Engagement with the community at large. Government. Business communities. Foundations and other philanthropic bodies. The public at large.

19 TM as an Academic Discipline
Development of a specific body of knowledge Vocabulary Jargon Ontogenies Databases

20 A conceptually novel structure for TM as an academic discipline
We have created a new conceptual framework for translational medicine, in 6 steps, Translation zero (Tzero) through Translation 5 (T5)

21 T0 (T zero) Refers to the fundamental process of discovery, which is sometimes forgotten in the discussion of translational science Translation cannot be a pipeline only, or a bridge from nowhere It is not the case that all fundamental discovery has occurred and if we bring to the clinic all the advances of recent years, disease will be conquered Much fundamental discovery work still needs to be done so that proper translation can occur One could have the best translation pipeline, but without translatable new fundamental science such pipeline becomes meaningless This step is also critical if we are to distinguish translational science from purely applied science or from commercialisation.

22 T1 This refers to the now "classical" step of bench to bedside – first in human studies 

23 T2 This refers to the now "classical" step of research from bedside to clinical care - clinical trials studies for example are in this domain

24 T3 This term has been emerging but needs further definition
This could be best defined as translation of new evidence into health care guidelines and health policy

25 T4 Defined as research on outcomes assessment of translation
Once translation occurs from T0 to T3, from novel fundamental discovery to health policy, the outcomes of such changes in practice need to be meticulously and critically evaluated Not all new guidelines and policies will work out Careful research is needed to determine what works out and what does not in order to guide the healthcare of the future

26 T5 = Global Health Global implementation of new guidelines that emerge as the outcome of translation after research at the T4 level. Further validates effectiveness and utility. An example of T5 would be the worldwide eradication of smallpox: After all steps of translation listed above occurred in terms of smallpox vaccine development and testing: Initial concept (T0) First in human (T1) Clinical trials (T2) After the vaccine's effectiveness became health policy in many countries (T3) And it was systematically demonstrated to be safe and effective (T4) A concerted global effort led to the final eradication of the disease (T5)

27 TM: Summary TM must evolve away from isolated efforts in academic silos to become an endeavor that in increasingly: Systematic Academically rigorous Cross-disciplinary Cross-institutional Cross-national THIS CONFERENCE WAS SPECIFICALLY DESIGNED FROM AN INITIAL PLAN BY JULIO LICINIO AND STEFAN BORNSTEIN TO JUMP START SUCH CROSS- NATIONAL EFFORTS The German-Australian Institute for Translational Medicine (GAITM) Making translational medicine a bona-fide academic discipline This conference will be instrumental in establishing Translational Medicine as an internationally recognized academic discipline Welcome to The John Curtin School of Medical Research, to The Australian National University, to Canberra and to Australia!




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