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The Evolution of Medicine: From Incidental Discoveries to Personalized Treatments

This overview examines the three revolutions in medicine from the 20th century to the present, focusing on how drug discovery has evolved through various eras. Beginning with the incidental discoveries in the 1930s to 1960s, such as aspirin and penicillin, we transition to high-throughput screening from the 1970s to 2000s, revealing landmark drugs like statins. The future promises personalized medicine focused on predictive, preventive, and participatory health strategies. However, it also faces substantial challenges, including complex disease mechanisms and ethical concerns over genetic information.

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The Evolution of Medicine: From Incidental Discoveries to Personalized Treatments

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  1. Diseases Environment Infectious diseases Behaviour Genetics

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

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

  4. Felix Hoffman Aspirin

  5. Penicillin

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

  7. Statins Akira Endo

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

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

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

  11. Herceptin (targeted)

  12. Prevalence rate of ADR • Fatal ADRs appear to be between the fourthandsixth leading cause of death in the USA

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

  14. To understand it by pharmacogenomics

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

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

  17. What are the obstacles – they appear to be broader and more complicated than just target identification and validation : • 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) • Cost of developing new drugs - legal liability (Vioxx/Celebrex), markets (new antibiotics), and patents protection (AIDS - South Africa, India) • End of blockbuster drugs era • 7. Bioethical problems of availability of genetic information

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