4. Behaviour Diseases Environment Genetics Infectious diseases

5. Drug Discovery and BioMedical research in the 21 st century? The third revolution

6. The first revolution: The era of incidental discoveries 1930s-1960s

7. Aspirin Felix Hoffman

8. Penicillin

9. The second revolution 1970s-2000s High throughput – brute force screening of large libraries of chemical compounds

10. Statins Akira Endo

11. Future medicine- Targeted and Personally “fitted” medicine – Personalized Medicine

12. Medicine of the 21 st Century – The 4P’s Medicine (Leroy Hood) Personalized, Predictive, Preventive, and Participatory Medicine Stem cell-based therapies

15. Breast Cancer – Estrogen Receptor Negative and Positive (predicts sensitivity to Tamoxifen) Future medicine- Targeted and Personally “fitted” and medicine - Personalized Medicine

16. Herceptin (targeted)

17.  Fatal ADRs appear to be between the fourth and sixth leading cause of death in the USA Prevalence rate of ADR

18. Age elderly children neonates Sex High/Body Weight Concomitant Disease Disease Process Organ Function Liver, Kidney, Cardiac Environmental Factors diet / smoking / comedications Inter-individual Variability in Drug Response Genetic polymorphisms Factors determining inter-individual variations in drug response

19. To understand it by pharmacogenomics

20. Size of the entire Human Genome = 3 Billion Bases The Human Genome

22. Central dogma of flow of genetic information DNA (the human genome) RNA (the human transcriptome) Proteins (the human proteome) Multiple post-translational modifications: phosphorylations, acetylations, amidations, glycosylations, ubiquitinations, etc. Epigenetic control of gene expression Control by small RNAS Is the development of personalized drugs going to be straightforward? Here are some major obstacles

23. What are the obstacles – they appear to be broader and more complicated than just target identification and validation : 1.Many diseases (metabolic, psychiatric) are multi- genic, and the causative connection between the genes products is not clear. We are still missing a whole body of basic knowledge. 2.Malignancies are characterized by genomic instability and therefore targets are not stable 3.Human experimentation is complicated (HRT, stents) 4.Lack of faithful animal models (neurodegeneration, cancer, metabolic diseases) 5.Cost of developing new drugs - legal liability (Vioxx/Celebrex), markets (new antibiotics), and patents protection (AIDS - South Africa, India) 6.End of blockbuster drugs era 7.Bioethical problems of availability of genetic information