The Brave New World of Cloning and Stem Cells Daniel P. Sulmasy, OFM, MD, PhD Department of Medicine & Divinity School The University of Chicago Back to High School: Developmental Biology Zygote 21 d Embryo Morula 3d Blastocyst 5d 28 d Embryo Implantation 6-7 d 14 d Embryo 8 weeks -- Fetus In Vitro Fertilization • • • • • • • • Egg retrieval Sperm collection Fertilization “in glass” Maturation to embryo stage Embryo transfer Inefficiency Pregnancy “reduction” “Spare” embryos Zygote Morula 3d Blastocyst 5d In Vitro Fertilization As cells divide and the embryo grows • Chemical changes in DNA • Genes turned on and off • “Telomeres” and aging Three basic kinds of cells (layers of the embryo) • Ectoderm: – skin, brain nerves • Endoderm: – gut, digestive organs • Mesoderm: – muscle, bone, blood Development continues in adults: cells “turn over” • Blood cells last 120 days • Skin cells • Lining of the gut Some tissues do not regenerate naturally • Brain and spinal cord • Heart muscle Stem Cells • “Rookie” cells • Good young players • Can become shortstop, third baseman, or outfielder • Not yet “committed” • Can be “trained” 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 “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 Stem Cells • Embryonic – “totipotent” • Adult – “pluripotent” – A misnomer – Umbilical cord blood – Bone marrow – Brain – Other tissues Cloning • “Somatic cell nuclear transfer” • Even less efficient than IVF • Developmental problems Process Egg + Somatic Cell Clonal zygote “Reproductive” vs. “NonReproductive” • 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….. Awkward but Accurate “Research cloning” vs. “Cloning to bring babies to birth” 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 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 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 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? 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 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 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 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 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. 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 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” Against Orin Hatch • “Embryo wastage” – many will die anyway • Reply: – Infant mortality in developing nations – Death row • Jack Kevorkian Leftover IVF embryos • • • • • There aren’t enough! 400,000 in U.S. Not all are viable Need informed consent (< 3%) Won’t “match” recipients “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 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. 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 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? 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 • Only natural kinds have intrinsic value • Artifacts always have attributed value 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 What’s at stake, then? • The fundamental basis of human morality A phase sortal is not a kind sortal… zygote embryo fetus neonate infant toddler child adolescent young adult middle-aged older adult very old What’s in the dish? • An individual member of the human natural kind at the earliest stages of development 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 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” 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’ 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) Alternatives • Adult stem cells • Induced pluripotent stem cells (iPS cells) Adult stem cells • Proven successes • Problem of de-differentiation • Problem of immortalization iPS cells: “de-differentiating Embryonic Totipotent Ectodermal Cutaneous Pluripotent Dermal stem cell Committed Dermal skin cell 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 Prudence • Even if unconvinced by my arguments: • When faced with two alternatives – One that raises profound moral questions (embryonic) – Another that is morally unobjectionable (adult stem cells or iPS cells) • Prudence dictates choosing the morally unobjectionable means Picasso, “Ciencia y Caridad,” 1897 The Major Driving Force Dignity is the intrinsic value of the members of any natural kind that is (as a kind): • • • • • • • • • • Rational Affective Mutually interdependent/social Aesthetic Worshipping Free willing Capable of love A sense of humor Able to grasp the finite and the infinite Practically moral • Independent deliberation • Coordinated action • Mutual binding of wills Anti-speciesist • All members of any kind that has these qualities have dignity • E.T., angels, arguably other known species Conclusions • Stem cell therapies have great promise • Cloning, even for stem cells, is deeply morally problematic and impractical as therapy • Human embryonic stem cells for therapy also raise deep moral problems • Adult stem cells and iPS cells appear able to fill clinical needs without raising moral problems