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LECTURE 19: BIOETHICS AND THE BRAVE NEW WORLD

LECTURE 19: BIOETHICS AND THE BRAVE NEW WORLD. Future-Shaping Techologies. Genetic Screening - Marfan Case Gene Replacement - Bubble Babies Stem Cells Cloning - Dolly the Sheep Agriculture - Crop Modification. SCID “Bubble” Baby. Cloned Sheep. Dolly and Kid. Stem Cells.

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LECTURE 19: BIOETHICS AND THE BRAVE NEW WORLD

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  1. LECTURE 19: BIOETHICS AND THE BRAVE NEW WORLD

  2. Future-Shaping Techologies Genetic Screening - Marfan Case Gene Replacement - Bubble Babies Stem Cells Cloning - Dolly the Sheep Agriculture - Crop Modification

  3. SCID “Bubble” Baby

  4. Cloned Sheep Dolly and Kid

  5. Stem Cells Stem cells divide to give rise to a copy of them selves and another cells that can differentiate into various cell types. Early embryonic cells can give rise to all cell types in the body Embryonic cells can be used to create cell lines that can also differentiate into all cells in the body (Totipotent). - These cells are called Embryonic Stem Cells (ES cells)

  6. Stem Cells Potential Uses of Stem Cells: - Generate pancreatic b-cells: Treat diabetes - Generate red blood cells: Treat sickle cell anemia - Generate white blood cells: Treat B and T-cell leukemias - Generate all blood cells: Treat bubble babies - Generate heart or muscle cells: Repair heart/muscles - Generate neuronal cells: Repair neurological damage Stem cells are also found in the adult body that have more limited potential to give rise to other cells (Pluripotent). - Blood stem cells (replace red and white cells) - Neuronal stem cells (repair brain damage) - Reproductive stem cells (generate sperm and eggs)

  7. A possible picture of the most recent common ancestor of vertebrate and invertebrates Eyespot? Sensory Appendages? Head Abdomen Tail Anus/ Genitals Mouth Gills? D/V Axis A/P Axis Non-neural Ectoderm Photosensitive Protrusions or Nervous System organs appendages

  8. Human Disease Genes in Flies • >3,100 of 5,000 Human disease genes identified • Many disease genes have fly counterparts • 75% disease genes related to a fly gene • 30% disease genes highly similar to a fly gene • Disease genes with counterparts in flies fall into all major categories of disorders

  9. Appropriate Disease Genes to Study in Flies • Human Disease Gene Function Poorly Understood • Fly Counterpart Highly Related to Human Gene • Facility of Genetic Analysis in Fly • Identified Loci Subject to Explicit Test in Humans: “Closing-the-Loop”

  10. Closing-the-Loop in Humans • Identify New Candidate Disease Genes • Alzheimer Disease (FAD) • Identify Human Modifier Loci • Primary Congenital Glaucoma (PCG) • Dissect Complex Polygenic Trait • Cardiac Defects in Down syndrome (DS) • Place Disease Gene in a Pathway • Dyggve-Melchoir-Clausen syndrome (DMC) • Identify Candidate Protein Targets • Angelman Syndrome (AS) • Study host-pathogen interactions • Bacterial toxin function

  11. Anthrax Toxins: Lethal Factor (LF) and Edema Factor (EF)

  12. Anthrax Toxins: Lethal Factor (LF) and Edema Factor (EF)

  13. Anthrax Toxins: Lethal Factor (LF) and Edema Factor (EF) • Do LF and EF act the same way in flies? • Are there new activities of LF or EF? • Is there evidence for synergy between LF and EF?

  14. EF Toxin

  15. Notch & Wg M L2 L2 BMP L3 L3 Hh L4 L4 L4 L5 L5 BMP Normal Wing BMP Pathway Mutant L2 L2 L3 L3 L4 L4 L5 L5 Hh Pathway Mutant Notch Pathway Mutant The fly wing as genetic assay system

  16. En -> Hh -> Diffuses -> Reduced hh function dpp in A/P Organizer A A dpp L3 ptc, dpp P P L3 L4 L4 hh dpp dpp En hh En WT Reduced hh function L2 L2 L3 L3 L4 L4 L5 L5 Hh determines the positions of the L3 and L4 Veins

  17. LF expression LF and EF also have unexpected effects EF expression

  18. Wk-GAL4>EF Wk-GAL4>LF+EF Synergy between LF and EF toxins Wk-GAL4>LF

  19. Hes1 RT-PCR UI WT pXO1 dLF dEF dLF/EF HBMEC B.a EF B.a B.a PBS B.a LF B.a Infected with wt B. anthracis Infected with mutant B. anthracis lacking EF toxin

  20. New CovenantJesse Bier • Nobody tells the flowers what to do, • they grow the way they please. • They don't take orders from me and you— • nor do the grasses or trees. • But that was long ago, • before the age of science. • Now that we know what we know, • we splice them to compliance. • Soon trees must do what they are told, • according to special genes. • Nothing the same as of old— • and grasses, flowers know what that means. • Next to come are you and me • after the flowers, trees and grasses. • But: Who will decide and oversee • newfounded families, permanent classes?

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