1. Stem Cells & Cloning 3/23/05 Stem Cells, Cloning & Bioethics Bioethics as a basis for decision-making Bellevue High School March 23, 2005 Steven G. Gilbert, PhD, DABT www.asmalldoseof.org

2. Stem Cells & Cloning 3/23/05 Why Bioethics?

3. Stem Cells & Cloning 3/23/05 Current Bioethical Issues  Check the local news paper  Stem cells (state, national, international)  Genetically Engineered Organisms  Knowing your genes  In vetro fertilization – choosing your child's genes and characteristics  Global warming  Chemicals exposures – human health  Environmental health

4. Stem Cells & Cloning 3/23/05 "A thing is right when it tends to preserve the integrity, stability, and beauty of the biotic community. It is wrong when it tends otherwise." - Aldo Leopold, 1949, A Sand County Almanac The First Bioethicist ---------- 1887 - 1948 ---------- Aldo Leopold

5. Stem Cells & Cloning 3/23/05 “An ethic, ecologically, is a limitation on freedom of action in the struggle for existence” Aldo Leopold Limits on Freedom

6. Stem Cells & Cloning 3/23/05 “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

7. Stem Cells & Cloning 3/23/05 Technical Solutions “It is our considered professional judgment that this dilemma has no technical solution.” The Tragedy of the Commons By Garrett Hardin, Science, 1968

8. Stem Cells & Cloning 3/23/05 Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

9. Stem Cells & Cloning 3/23/05 "Biology combined with diverse humanistic knowledge forging a science that sets a system of medical and environmental priorities for acceptable survival.“ Global Bioethics (1988) Bioethics -------- 1911 - 2001 -------- Van Rensselaer Potter

10. Stem Cells & Cloning 3/23/05 1860’s - Scientific method in medicine, Gregor Mendel 1928 - Penicillin discovered – widely used WWII 1920’s - Lead in gasoline, lead in paint 1931 - 30 states had sterilization laws on books 1932 - Tuskegee syphilis study initiated 1947 - Nuremberg - The Doctors Trial 1952 - First open heart surgery & Chlorpromazine 1953 - Structure of DNA – Watson & Crick Ethics and Science

11. Stem Cells & Cloning 3/23/05 60’s - Thalidomide, mercury, chronic hemodialysis, amniocentesis, informed consent, IRB’s 70’s - Hastings Center founded, bioethics defined, Tuskegee noticed, Belmont Report (3 principles), Genentech Inc. founded, awareness of FAS, sensitivity of developing CNS 80’s - Recombinant microorganism could be patented, lead is harmful to developing brain 90’s - molecular biology, sequencing of human genome (other species), Jurassic Park 00’s - US stem cell research restricted 03 - Human cloned? Ethics and Science

12. Stem Cells & Cloning 3/23/05 Question?? Who were the most influential people of the past century? James Watson (L) and Francis Crick (R), and the model they built of the structure of DNA (and Rosalind Franklin).

13. Stem Cells & Cloning 3/23/05 ELSI  Ethical  Legal / Regulatory  Social  Implications or Issues  What is unsaid or missing?  Science  Values  Politics

14. Stem Cells & Cloning 3/23/05 Topics  Why this is topic important  DNA to RNA to Proteins  Stem Cells  Cloning – Therapeutic and Human

15. Stem Cells & Cloning 3/23/05 Stem Cell History 1998 - Researchers first extract stem cells from human embryos 1999 - First Successful human transplant of insulin-making cells from cadavers 2001 - President Bush restricts federal funding for embryonic stem-cell research 2002 - Juvenile Diabetes Research Foundation International creates $20 million fund-raising effort to support stem-cell research 2003?? - California ok stem cell research 2004 - Harvard researchers grow stem cells from embryos using private funding 2004 - Ballot measure for $3 Billion bond for stem cells

16. Stem Cells & Cloning 3/23/05 Importance  Disease Diabetes, Spinal cord injury, Parkinson’s disease, heart disease  Genetic based Disease Cystic fibrosis, Huntington’s

17. Stem Cells & Cloning 3/23/05 DNA – T-A C-G Thymine (T) Adenine (A) Cytosine (C) Guanine (G) Over 3 billion base pairs, 30,000 genes Humans are over 99.9% identical

18. Stem Cells & Cloning 3/23/05 Central Dogma of Molecular Biology DNA RNA Protein Transcription Translation

19. Stem Cells & Cloning 3/23/05 RNA TranscriptionProtein Translation DNA  RNA  Protein Gene Expression

20. Stem Cells & Cloning 3/23/05 Human Variability in DNA SNPs (single nucleotide polymorphisms) Many examples directly cause disease –Huntington’s, Cystic Fibrosis, Muscular Dystrophy, etc. The ‘environment’ also plays a big role

21. Stem Cells & Cloning 3/23/05...AUC AUC UUU GGU......Ile Ile Phe Gly......AUC AU- --U GGU......Ile Il e Gly... Normal CF Common Cystic Fibrosis Mutation

22. Stem Cells & Cloning 3/23/05 Parents to Children Mother & Father both Carriers Children? 1 – Not a carrier (25%) 2 – Carrier (50%) 1 – With CF (25%)

23. Stem Cells & Cloning 3/23/05 Gene Environment Interactions PKU and consumption of phenylalanine Malaria and Sickle Cell gene HIV infection and CCR5 receptor variant Alcohol intolerance and aldehyde dehydrogenase Beryllium disease (exposure to beryllium)

24. Stem Cells & Cloning 3/23/05 Sexual Reproduction The Association of Reproductive Health Professionals

25. Stem Cells & Cloning 3/23/05 Stem Cell Differentiation Princeton University

26. Stem Cells & Cloning 3/23/05 Stem Cell Cultivation University of Wisconsin-Madison

27. Stem Cells & Cloning 3/23/05 Embryonic Stem Cells (ESCs)  August 9, 2001 - President Bush restricted federal funding of human embryonic stem cell research to 70 lines thought to be in existence  Only 11 now available and useable  Many researchers calling for change Science and Politics of ESCs research

28. Stem Cells & Cloning 3/23/05 Blastocyst Diagram Princeton University

29. Stem Cells & Cloning 3/23/05 Human Clones? Are there human clones? Yes – Identical Twins (Time 2.19.01)

30. Stem Cells & Cloning 3/23/05 Cloning Defined What is cloning? Asexual reproduction Examples? Bacteria, fungus Plants – cutting – potato Farm animals

31. Stem Cells & Cloning 3/23/05 Asexual Reproduction The Association of Reproductive Health Professionals

32. Stem Cells & Cloning 3/23/05 Cloning Dolly 1997 - 2003 (Roslin Institute http://www.roslin.ac.uk/library/)

33. Stem Cells & Cloning 3/23/05 Cloning A Sheep (Roslin Institute http://www.roslin.ac.uk/library/)

34. Stem Cells & Cloning 3/23/05 Human Stem Cell Production

35. Stem Cells & Cloning 3/23/05 Removing Nucleus Removing the maternal nucleus before nuclear transfer (Roslin Institute http://www.roslin.ac.uk/library/)

36. Stem Cells & Cloning 3/23/05 Nuclear transfer Nuclear transfer embryo about to be activated (Roslin Institute http://www.roslin.ac.uk/library/)

37. Stem Cells & Cloning 3/23/05 Coning for use in Stem Cells Cloning techniques for creating stem cells Therapeutic cloning Reproductive cloning

38. Stem Cells & Cloning 3/23/05 IVF – In Vitro Fertilization  Available since 1986  About 100,000 IVF kids in U.S.  Often creates extra embryos  U.S. - About 400,000 frozen embryos (unregulated)  England – 52,000 (regulated by government)

39. Stem Cells & Cloning 3/23/05 Stem Cells and Cloning Questions or Comments?

40. Stem Cells & Cloning 3/23/05 Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT Director, INND sgilbert@innd.org smdose@asmalldoseof.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”