5Smallpox 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 scarringLimb deformities due to arthritis and osteomyelitisEmerged in human populations about 10,000 BCEarliest physical evidence of smallpox: pustular rash on the mummified body of Ramses V, Pharaoh of Egypt, who died in 1157 BC.
7Smallpox18th 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 deathsEarly 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.
8Variola virus Genus Orthopoxvirus Family Poxviridae Subfamily chordopoxvirinae.Large brick-shaped virus measuring approximately 302 to 350 nanometers by 244 to 270 nmSingle linear double stranded DNA genome186 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.
9Smallpox Africa – Europe – Asia – Americas – Australia Japan: epidemic of killed 1/3 of populationDecimated native America empires: 80-90% deathAustralia: introduced in 1789 and again in 1829Devastation among aboriginesDied out on both occasionsOnly continent without endemic smallpoxSuccessful vaccination campaigns: 19th & 20th centuriesWHO certified the eradication of smallpox in 1980Only human infectious disease to have been eradicated
11Smallpox vaccination Live virus Smallpox virus Cowpox virus: Used for centuries in China and TurkeyDangerous:Person gets sickIs infectiousCowpox virus:No major illnessLive vaccinia virusPROCESS STARTED 14 May 1796ENDED 8 May 1980Professor Frank FennerChairman, Global Commission for Certification of Smallpox Eradication
12Accelerating translation Moving away from a cottage industry of individual effortsTo a systematic, cross-disciplinary effortInstead of being a side-activityTM must become a bona-fide academic discipline in its own rightProcess analogous to pharmacologyDrugs used by different specialties for centuriesAn organized discipline of pharmacology led to enormous progress in therapeuticsAn organized discipline of TM should likewise lead to enormous progress in translation
13Creation of a new discipline Body of workDevelopment of specific methods and approachesWorkforce developmentCommunity engagementAcademic communityCommunity at large
14TM 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 outcomesPopulation 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
15TM 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.
16TM as Academic Discipline Asia and Pacific studies: approaches to global health outcomesArts and communication sciences: novel outreach strategiesTranslational cores that facilitate the work developed in the areas listed aboveResearch ethics, research design, and data analysis: Translational protocols must be ethical, of sound design, and interpretableInformatics capacity to support TM within institutions and for cross-institutional collaboration on compatible platformsTranslational clinical research spaces
17TM as Academic Discipline Creation of a specialized workforce that did not exist before.Novel curriculaCoursesPostgraduate training programsDedicated career developmentClinical programs that incorporate translational medicine, including the offering of dual degrees, one of them being in translational medicine
18TM 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.
19TM as an Academic Discipline Development of a specific body of knowledgeVocabularyJargonOntogeniesDatabases
20A 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)
21T0 (T zero)Refers to the fundamental process of discovery, which is sometimes forgotten in the discussion of translational scienceTranslation cannot be a pipeline only, or a bridge from nowhereIt 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 conqueredMuch fundamental discovery work still needs to be done so that proper translation can occurOne could have the best translation pipeline, but without translatable new fundamental science such pipeline becomes meaninglessThis step is also critical if we are to distinguish translational science from purely applied science or from commercialisation.
22T1This refers to the now "classical" step of bench to bedside – first in human studies
23T2This refers to the now "classical" step of research from bedside to clinical care - clinical trials studies for example are in this domain
24T3 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
25T4 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 evaluatedNot all new guidelines and policies will work outCareful research is needed to determine what works out and what does not in order to guide the healthcare of the future
26T5 = Global HealthGlobal 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)
27TM: SummaryTM must evolve away from isolated efforts in academic silos to become an endeavor that in increasingly:SystematicAcademically rigorousCross-disciplinaryCross-institutionalCross-national THIS CONFERENCE WAS SPECIFICALLY DESIGNED FROM AN INITIAL PLAN BY JULIO LICINIO AND STEFAN BORNSTEIN TO JUMP START SUCH CROSS- NATIONAL EFFORTSThe German-Australian Institute for Translational Medicine (GAITM)Making translational medicine a bona-fide academic disciplineThis conference will be instrumental in establishing Translational Medicine as an internationally recognized academic disciplineWelcome to The John Curtin School of Medical Research, to The Australian National University, to Canberra and to Australia!