1. 412162024283236408 100% 80% 60% 40% 20% 0 Weeks after conception Embryo in uterus Embryo implants First missed period Movement first felt Delivery at Term Baby viable if born

2. Human embryo  Clump of undifferentiated cells  No organs  No brain life  Not implanted  18% chance of viability  Not an individual Human fetus   Most cell types   Organs developing or formed   Consciousness by ≥ 20 weeks   Implanted   84% chance of viability   An individual

3. Human embryos  Conception a continuum - no finite start  Most embryos lost naturally before 1st menstrual period  Destroyed by various contraceptive methods eg minipill, low-dose progesterone, IUCD, post-coital pill  Mostly surplus during IVF  Most IVF patients happy to donate them

4. The Perfect Baby?

5. Source of stem cells Immature cells from patient –Site specific (somatic) –Bone marrow –?Testis Immature cells from donor Fetal cells –Cord blood –Gametes Embryonic stem cells –IVF patients –Created specifically –Tumours

6. 1. Blastocyst in culture dish 2. Remove outer cells 3. Disaggregate 4. Transfer embryoid clumps 5. Form colonies 6. Add differentiation factors to colonies Bone cells Heart muscle Pancreas islets 5 day human embryo Layer of feeder cells in culture dish

7. Embryonic stem cells Overcoming rejection Immune suppressive drugs – Getting more effective – Lifelong administration –Serious side effects eg cancer, DM –Major expense Nuclear transfer Genetic manipulation

8. 1 kb 123456789 236 bp 173 bp63 bp ApaI M P E RT-ve Uncut DNA Cut DNA 236 173 63 M P E RT-ve Uncut DNA Cut DNA Imprinting of IGF2 in human preimplantation embryos 4-cell embryoPooled 8-cell + 400 300 200 100 Lighten, Hardy, Winston, Moore: Nature Genetics. 1997

9. Biopsy of somatic cellMature egg Enucleated egg Somatic cell nucleus Nuclear transfer Liver Heart BloodNerveIslets Patient Add growth factors Immunologically compatible transplant Therapeutic “cloning” Embryonal stem cells

10. Hello, Dolly…….. Embryo loss Abortion Fetal death Obesity Neonatal mortality Gross abnormality

11. Adult’s stem cells Advantages No serious ethical concerns Reduced problems with tissue compatibility Disadvantages Sparse, irregular distribution Difficult to harvest Restricted potential for growth, differentiation Potential declines with ageing May differentiate into unwanted cell type Delay between harvest and treatment