António Rendas Reitor da Universidade NOVA de Lisboa

1. Mudança de paradigma na investigação biomédica?JoinedintranslationMesa Redonda: Estudos e Experimentação em Saúde António Rendas Reitor da Universidade NOVA de Lisboa XIV Encontro de Reitores GrupoTordesillas 10 – 12 novembro 2013 Universidade Federal do Paraná, Curitiba

2. Sumário • Razões da mudança de paradigmanainvestigaçãobiomédica: da investigação de translaçãoàmedicinapersonalizada. • Sistemasbiológicos e sistemasfisiológicos, joined in translation

3. Razões da mudança de paradigmanainvestigaçãobiomédica:da investigação de translaçãoàmedicinaPersonalizada

4. Lister adopts antiseptic technique in surgery Koch proves Germ Theory with discovery of B. anthracis Semmelweis proposes handwashing to prevent spread of disease 1670 1720 1770 1820 1870 1920 Reed proves mosquitoes are vector for yellow fever Pasteur explores Germ Theory of Disease Leeuwenhoek observes “little animals” under microscope Ehrlich introduces the acid-fast staining technique Jenner administers smallpox vaccine Fleming discovers Penicillin It took centuries of significant events to get us to this point The cost of diagnosing and treating infectious diseases has declined 5% per year since 1940 Source: Christensen/Hwang

5. Today, Cancer is experiencing a similar shift toward precision medicine Farber develops 1st chemotherapy for leukemia Novartis launches Gleevec, the 1st molecular targeted drug, to treat myeloid leukemia 2 types: leukemia & lymphoma 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 Disease of the blood 38 types of leukemia; 51 types of lymphoma 3 types of leukemia (acute, chronic, preleukemia) and 2 types of lymphoma (indolent, aggressive) Source: Mara Aspinall, Genzyme

6. Rapid innovation in the biomedical industry is driven by a continuous flow of scientific and technological advances

8. Signs & Symptoms In vivo Imaging Techniques In vitro Laboratory Tests Molecular diagnostics is at the core of the personalized medicine vision Diseases will be diagnosed long before the patient begins to manifest any evidence using traditional tools Molecular Diagnostics …and biomarkers will be a primary tool

9. Current capabilities of personalized medicine

10. Conceptual model for timing the arrival of personalized medicine

11. SISTEMAS BIOLÓGICOS E SISTEMAS FISIOLÓGICOS, JOINED IN TRANSLATION

12. ”Ben Franklin and open heart surgery” Comroe JH and Dripps RD, Circ. Res. 1974;35;661-669

13. Pharma, 2020

14. Claude Bernard, the first systems biologist, and the future of physiology Denis Noble, ExpPhysiol93.1 pp 16–26, 2007

15. Claude Bernard, the first systems biologist, and the future of physiology Denis Noble, ExpPhysiol93.1 pp 16–26, 2007

16. “In conclusion, I return to the theme with which this article began. Claude Bernard’s concept of the constancy of the internal environment was the first example of multilevel functionality. It was critical in defining physiology as a subject distinct from the applications of physics and chemistry.(…)” Claude Bernard, the first systems biologist, and the future of physiology Denis Noble, ExpPhysiol93.1 pp 16–26, 2007

17. “(…) The challenge we face today resembles that faced by Bernard in the mid-nineteenth century, but the chemistry involved is that of the molecule DNA. The answer though should be much the same. Higher-level control cannot be reduced to lower-level databases like the genome. A major part of the future of physiology surely lies in returning to our roots. Higherlevel systems biology is, I suggest, classical physiology by another name. Claude Bernard, the first systems biologist, and the future of physiology Denis Noble, ExpPhysiol93.1 pp 16–26, 2007

18. CONCLUSÃO “Plus ça change, plus çadevient la même chose”