1. Cloning and stem cells: facts and opinions A/Prof David Turner School of Medicine Flinders University david.turner@flinders.edu.au

2. the core issue Debate about stem cells focuses on the production of embryonic stem cells and their potential therapeutic use (they have other uses also). Currently the production of human embryonic stem cells requires the generation and subsequent destruction of a cloned human embryo. There is little debate about the appropriateness of using adult stem cells for therapeutic uses.

3. Reproductive and therapeutic cloning

4. Reproductive cloning is universally banned Therapeutic cloning is permissible in several countries

5. Reproductive and therapeutic cloning Reproductive cloning is universally banned Therapeutic cloning is permissible in several countries It is the creation and fate of the embryo which is at the centre of debate

6. Understanding how therapeutic cloning* works requires an understanding of what stem cells are…… *therapeutic cloning is also called “somatic cell nuclear transfer” or “SCNT”

7. Stem Cells Stem cells have the capacity for self- renewal and differentiation

8. Concept of a stem cell Stem cells have the capacity to “self renew” AND produce differentiated progeny. “Differentiated” means having a restricted and specialised function

9. Stem Cells Stem cells have the capacity for self- renewal and differentiation FACT

10. Stem Cells Stem cells have the capacity for self- renewal and differentiation What’s special about embryonic stem cells? To answer this question we need to know something about how embryos develop…. FACT

11. How does an embryo develop? In the first week……. from Moore and Persaud "Before we are born: Essentials of Embryology and Birth Defects"

12. How does an embryo develop? In the first week……. totipotent cells from Moore and Persaud "Before we are born: Essentials of Embryology and Birth Defects"

13. Embryonic stem cells Early embryonic stem cells are totipotent – they can produce any type of cell (in normal development). Not only cells of the embryo but extra-embryonic tissue (eg. the placenta) They can make a whole person……. FACT

14. How does an embryo develop? In the first week……. totipotent cells from Moore and Persaud "Before we are born: Essentials of Embryology and Birth Defects"

15. How does an embryo develop? In the first week……. totipotent cellspluripotent cells from Moore and Persaud "Before we are born: Essentials of Embryology and Birth Defects"

16. By day 4 after fertilization cells of the “inner cell mass” are pluripotent – during normal development they can differentiate into any type of cell except for the cells which will form the “extra-embryonic” tissue (placenta, amnion etc). Thus they can form any type of body tissue. FACT Embryonic stem cells

17. How does an embryo develop? In the second week ……. at day 14 the embryo is an undifferentiated single layer of epiblast cells…. THEN!....... from Moore and Persaud "Before we are born: Essentials of Embryology and Birth Defects"

18. …….the first cells form that determine the body axes… …..which is why experimentation is permitted only up to day 14….. from Moore and Persaud "Before we are born: Essentials of Embryology and Birth Defects"

19. If pluripotent cells are taken from the “inner cell mass” (destroying the embryo) they can be grown in culture in the laboratory. Such cultured cells are called embryonic stem cell lines. Embryonic stem cell lines (some) are “immortal” – they can divide indefinitely without differentiating. Embryonic stem cell lines

20. Stem cells have the capacity for self- renewal and differentiation Early embryonic stem cells are totipotent – they can produce any type of cell (in normal development) By day 4 after fertilization embryonic stem cells are pluripotent – during normal development they can differentiate into any type of cell except extra-embryonic tissue Cells from an embryonic stem cell line can be used to make any cell type…. FACT Embryonic stem cells FACT OPINION

21. Cloning cells for treating disease (therapeutic cloning) ? Grow organs in vitro 4 ~ 5 days somatic cell nuclear transfer embryonic stem cell line cell from patient with Parkinson’s disease transplant into brain genetic control of differentiation ovum with genetic material removed + embryo

22. To many people this sounds wonderful …….will it work?! Doing ethical research is the only way to answer this question. Majority scientific opinion is that therapeutic cloning is feasible and may provide treatment for a wide variety of disorders including: –neurodegenerative diseases –spinal injuries –chronic diseases such as diabetes –organ failures (eg heart disease, kidney disease)

23. There are several barriers to successful therapeutic cloning and its subsequent use Legal barriers ( Australia permits therapeutic cloning (December 2006 )) Availability of donor eggs ( should “cybrids” (animal oocytes) be used? ) Need for improved efficiency in establishing embryonic stem cell lines ( no human ESC line has been reported following SCNT) Control of differentiation prior to therapeutic use Many disease and organ specific factors

24. Normal tissues contain somatic stem cells - also called “adult stem cells”

25. Can adult stem cells do the same job as embryonic stem cells?

26. Normal tissues contain somatic stem cells - also called “adult stem cells” Can adult stem cells do the same job as embryonic stem cells? Answer: adult stem cells are already are used in special settings such as the treatment of various haematological cancers (certain leukaemias), in skin grafts and corneal grafts. But……

27. Adult stem cells Adult stem cells are multipotent. Adult stem cells are found in small numbers in most tissues and have limited division capacity Adult stem cells can help regenerate a limited range of tissues Adult stem cells may have the capacity to be made pluripotent ( e.g. Yamanaka et al., Atala et al. ) FACT OPINION

30. The rate of human evolution has effectively stopped Will future generations seek human enhancement?

31. nuclear transfer Human enhancement sequentially genetically modify stem cells one week culture embryonic stem cells enucleated ovum modified nucleus nuclear transfer surrogate “mother” START FINISH

32. Reproductive cloning It is not logical to say that the use of therapeutic cloning technology will necessarily lead to reproductive cloning. Ethics are the outcomes of what principled people do in the public domain We are only the guardians of our society and not the owners of the future. A future civil society may sanction cloning or human enhancement.

34. Human evolution is a work in progress Humans are moral beings who create societies with changing ethics Ethics will remain the outcomes of what principled people do in the public domain There is nothing that justifies attempting to arrest human evolution Striving for human enhancement and seeking to arrest human evolution are incompatible