The Brave New World of Cloning and Stem Cells

1. The Brave New World of Cloning and Stem Cells Daniel P. Sulmasy, OFM, MD, PhD Department of Medicine & Divinity School The University of Chicago

2. Back to High School:Developmental Biology Zygote Morula 3d Blastocyst 5 d Implantation 6-7 d 14 d Embryo 21 d Embryo 28 d Embryo 8 weeks -- Fetus

3. In Vitro Fertilization • Egg retrieval • Sperm collection • Fertilization “in glass” • Maturation to embryo stage • Embryo transfer • Inefficiency • Pregnancy “reduction” • “Spare” embryos

4. In Vitro Fertilization Zygote Morula 3d Blastocyst 5 d

5. As cells divide and the embryo grows • Chemical changes in DNA • Genes turned on and off • “Telomeres” and aging

6. Three basic kinds of cells (layers of the embryo) • Ectoderm: • skin, brain nerves • Endoderm: • gut, digestive organs • Mesoderm: • muscle, bone, blood

7. Development continues in adults: cells “turn over” • Blood cells last 120 days • Skin cells • Lining of the gut

8. Some tissues do not regenerate naturally • Brain and spinal cord • Heart muscle

9. Stem Cells • “Rookie” cells • Good young players • Can become shortstop, third baseman, or outfielder • Not yet “committed” • Can be “trained”

10. Development and regeneration depend on stem cells! • Embryo • Regenerating tissues • e.g. blood “juvenile” cells Red cell Red stem cell Platelet Platelet stem cell Lymphocyte Hematopoetic stem cell Monocyte White stem cell Polymorphoncuclear white cell

11. “Plasticity” of stem cells • “Totipotent” – can develop into any kind of cell, even a new individual organism (i.e., a twin) • “Pluripotent” – can develop into a variety of tissue types • “Committed” – can develop only into one tissue type

12. Stem Cells • Embryonic – “totipotent” • Adult – “pluripotent” • A misnomer • Umbilical cord blood • Bone marrow • Brain • Other tissues

13. “Somatic cell nuclear transfer” Even less efficient than IVF Developmental problems Process Cloning Egg + Somatic Cell Clonal zygote

14. “Reproductive” vs. “Non-Reproductive” • Begs the question – • Assumes that making embryos is not reproduction unless gestated • But a major point of contention is whether or not making a human embryo is reproducing a human being • So…..

15. “Research cloning” vs. “Cloning to bring babies to birth” Awkward but Accurate

16. Why Cloning? • To bring babies to birth • Total infertility • Gays and lesbians • “Reproductive freedom” • Research • Run out of spare embryos for stem cells • Immuno-compatible stem cells or fetal tissue • Pure basic research

17. Scientific problems with cloning • Not yet done in human beings (?) • Hwang was a fraud • Poor success rate in other animals • 1 in 277 for Wilmut to make Dolly • Not enough animal experiments • Genetic abnormalities: “old wine in new wineskins” • Premature aging

18. Moral problems with cloning to bring babies to birth • “Offense to Human Dignity” • Blurs the line between natural kind & artifact • Role problems: my twin or my son? • Begetting vs. manufacture • Threat to human freedom

19. Banning only cloning to make babies won’t work: • Once research cloning is allowed, cloning to bring babies to birth will follow • All it takes is implantation, as in IVF • Once in the freezer, how tell if cloned?

20. Why Stem Cells? • Not all body parts repair themselves • Repair of injury due to myocardial infarction and stroke • Degenerative diseases (e.g. diabetes; Parkinson’s) • Immune rejection

21. Possible sources of stem cells • “Adult” stem cells (e.g. blood stem cells for chemotherapy) • Umbilical cord blood (e.g. Krabbe or Hinter-Hurler) • Amniotic fluid • Fetal tissue (e.g. Parkinson) • “Spare” embryos • Cloned embryos

22. Moral issues • Stem cells per se are not problematic • Everyone wants to help treat disabling human conditions • No one is seriously opposed to all stem cell research and therapy • Moral status of the human embryo • Practically speaking, the clinical use of embryonic stem cells entails cloning

24. Basic objection to embryonic stem cells • Develop (or create de novo) a new human being for the express purpose of killing that human being in order to extract cells • Violates the Kantian principle that every human being is an end in him/herself and ought never be treated as a means only

25. Major counter-arguments • Before 14 days twinning can occur. Therefore there really isn’t an individual person before that time. • Embryo is so small you can’t see it without a microscope. How could that be a person? • IVF embryos will die anyway. Why not make the best of a bad job? • If we can help people, then not using stem cells will kill even more people. • What will all those people with so-called principles do once it has been proven that embryonic stem cells can cure people.

26. Twinning • Since it can twin, isn’t an individual • Reply: • One ameba  two amebas • If a legitimate argument, then internally contradictory: • none of us would be persons, since we could also potentially be twinned through cloning

27. Size shouldn’t matter • As cogent as teenage boys in a locker room • Societal prejudice against the small • Growth hormone • Dr. Seuss – Horton Hears a Who • “A person’s a person no matter how small”

28. Against Orin Hatch • “Embryo wastage” – many will die anyway • Reply: • Infant mortality in developing nations • Death row • Jack Kevorkian

29. Leftover IVF embryos • There aren’t enough! • 400,000 in U.S. • Not all are viable • Need informed consent (< 3%) • Won’t “match” recipients

30. “If we don’t pursue stem cells we’re killing all the people who could be cured using them” • Confuses the basic distinction between killing and allowing to die • All the money we’re spending on all stem cell research could provide clean water in the developing world • Ignores the fundamental principle that the end ought not justify the means • Philippa Foot – serum for five

31. What will become of their principles? • If the moral basis for public policy is that people will abandon their principles whenever it is in their self-interest, then there is no moral basis for public policy.

32. Problems with embryonic stem cells • “First do no harm” • Numerous genetic abnormalities in clones • Potentially harmful to a recipient of stem cells derived from clones • Embryonic stem cells tend to form tumors -- teratomas

33. Slippery slope: • Eugenics • Egg donors: • 17 million US diabetics (type 1 + type 2) • 250 eggs per stem cell line (if as easy as sheep) • 4.2 billion eggs for all US diabetics • Where will these eggs come from?

34. Moral status of the embryo: what’s in the dish? • Property? • Commodification and human dignity • Just a tiny bit of “tissue,” not a person • Further than Roe v. Wade • No “privacy” argument • Individual member of the human natural kind in the initial stages of development

35. • Only natural kinds have intrinsic value• Artifacts always have attributed value

36. Intrinsic Human Dignity • The value we have by virtue of being the kind of thing that we are – i.e. – a human being • The foundation of all human rights • The basis for all interpersonal morality

37. What’s at stake, then? • The fundamental basis of human morality

41. A phase sortal is not a kind sortal… zygote  embryo  fetus  neonate  infant  toddler  child  adolescent  young adult  middle-aged  older adult  very old

42. What’s in the dish? • An individual member of the human natural kind at the earliest stages of development

43. The intrinsic value of the kind of thing that is in the dish: • Whatever is in the dish is the same kind of thing, whether it is to be brought to birth or disaggregated for its stem cells • Therefore it must have the same intrinsic value regardless of the purposes for which it is used

44. Dignity and Embryonic Stem Cells • Troubling because obtaining these cells by the destruction of embryos tends to blur the distinction between an artifact and a natural kind • To the extent that human beings are created de novo, especially for the benefit of others, they tend to be considered artifacts and this explains our worries about dignity • Explains “begetting vs. manufacture”

45. Is the disaggregation of a cloned human embryo compatible with respect? • To clone a human embryo (or create through IVF) with the premeditated plan of taking it apart, killing it, and using its parts, even for a noble cause, cannot conceivably be considered ‘respectful’

46. Alternatives: • Hematologic stem cells  malignancy • Stem cells in brain, liver, elsewhere • Umbilical cord stem cells  sickle cell, Krabbe, Hurler’s • Bone marrow  heart cells • Amniotic fluid • Biochemically “de-differentiating” adult stem cells (iPS cells)

47. Alternatives • Adult stem cells • Induced pluripotent stem cells (iPS cells)

48. Adult stem cells • Proven successes • Problem of de-differentiation • Problem of immortalization

49. iPS cells: “de-differentiating Embryonic Ectodermal Cutaneous Dermal stem cell Dermal skin cell Totipotent Pluripotent Committed

50. iPS cells • First accomplished in humans 2 years ago • “Toggling” no more than 4 genes with transcription factors (Oct3/4; Sox2 critical) • Appear to be immortalized • Can be “re-differentiated” into retinal cells, heart muscle cells • The problem of viral vectors • Has been overcome in mice (valproic acid) • Still, all the problems of embryonic stem cells (e.g. tumors) if pushed back to the embryonic stage