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- 4. Animals in Research Animationof Drug Development Process
- 5. z Animal Models •Mice • Rats • Zebrafish (3 month generation time, 200 progeny, complete embryogenesis in 120 hrs) • Dogs (lungs and cardiovascular system) • Cats • Pigs (PPL Therapeutics- delete a gene which causes hyperacute rejection of pig-to-human organ transplantation) • Primates (HIV and AIDs research, geriatric research) Animals in Research
- 6. z Alternatives toAnimal Models • Cell culture devices • Researchers use cell cultures and computer-generated models whenever possible, but this doesn’t work for looking at an organ or entire animal Animals in Research
- 7. z Regulation ofAnimal Research • The “Three Rs” • Reduce the number of higher species (cats, dogs, primates) used • Replace animals with alternative models whenever possible • Refine tests and experiments to ensure the most humane conditions possible Animals in Research
- 8. z Veterinary Medicineas Clinical Trials • Treatments for humans may also be useful for treatments with animals (e.g. the BRCA1 gene found in 65% of human breast tumors is similar to the BRCA1 gene in dogs) • Hyperthermia + radiation = more effective at killing tumors • Stimulation of cytokines for curing skin cancers Animals in Research
- 9. z Bioengineering Mosquitoesto Prevent Malaria • Cloned in a gene that prevents the parasite from traversing the midgut; blocking the continuation of its life cycle • Developed an antibody that prevents the parasite from entering the mosquito’s salivary gland Animals in Research
- 10. Clones z Cloning • CreatingDolly • Limits to Cloning: The donor cell must come from a living organism • An organism is also shaped by its environment • The success rate for cloning is very low • Clones may be old before their time • The future of cloning: preservation of endangered animals, studying the effect of drugs etc on duplicates, improve agricultural production
- 11. Transgenic Animals z Retrovirus-mediatedtransgenesis z Pronuclear microinjection z Embronyic stem cell method z Sperm-mediated transfer
- 12. z Improving AgriculturalProducts with Transgenics • Faster growth rates or leaner growth patterns (improve the product), more product • Increase nutritional content- lactoferrin • Turning the animals into efficient grazers • Transfer antimicrobial genes to farm animals Transgenic Animals
- 13. z Transgenic Animalsas Bioreactors • Biosteel otherwise known as spider silk, cloned into goat milk (“silkmilk” goats) • Goats reproduce faster than cows and are cheaper than cows • Hens also make good bioreactors in that they are cheap and a lot of eggs are produced at one time Transgenic Animals
- 14. z Knock-outs: ASpecial Case of Transgenesis • A specific gene is disrupted or removed such that it is not expressed • Procedure: DNA is modified, it is added to embryonic stem cells, where it undergoes homologous recombination. The modified ES cells are then introduced into normal embryo. The embryo is implanted in an incubator mother. The offspring is a chimera. It may take several generations of crossbreeding are required to produce animals that are complete knock-outs. • Breast cancer mouse Transgenic Animals
- 16. Producing Human Antibodiesin Animals z Production of Monoclonal antibodies (Mabs) • Used to treat cancer, heart disease, and transplant rejection • HUMANIZED monoclonal antibodies were developed to prevent the human anti- mouse antibody (HAMA) response