Ethical questions of stem cell research Jozsef Kovacs MD. PhD Semmelweis University-Budapest Institute of Behavioral Sciences Department of Bioethics

Historical remarks 1978—The first infant (Louise Brown) was born following in vitro fertilization (IVF) 1978—The first infant (Louise Brown) was born following in vitro fertilization (IVF) 1997—First successful Somatic Cell Nuclear Transfer (SCNT) (cloning) in a mammal 1997—First successful Somatic Cell Nuclear Transfer (SCNT) (cloning) in a mammal 1998—Isolation and culturing of the first human pluripotent embryonic stem cell lines 1998—Isolation and culturing of the first human pluripotent embryonic stem cell lines To drive stem cells to differentiate into a desired cell type is still not a solved problem To drive stem cells to differentiate into a desired cell type is still not a solved problem

The types of stem cells Human Embryonic Stem Cells (hESC) (pluripotent) Human Embryonic Stem Cells (hESC) (pluripotent) Pluripotent stem cells: they cannot form a whole organism, but they can specialize into almost all forms of adult cell types Pluripotent stem cells: they cannot form a whole organism, but they can specialize into almost all forms of adult cell types Umbilical cord stem cells (multipotent) Umbilical cord stem cells (multipotent) Adult-derived stem cells (multipotent) Adult-derived stem cells (multipotent) –Multipotent stem cells: can give rise only to some specialized cells

The source of human embryonic stem cells (hESC-s) 1. They can be isolated from the inner cell mass of human embryos (blastocyst)—these embryos can be found in IVF (in vitro fertilization) clinics 1. They can be isolated from the inner cell mass of human embryos (blastocyst)—these embryos can be found in IVF (in vitro fertilization) clinics 2.Primordial germ cells retrieved from first- trimester aborted fetuses 2.Primordial germ cells retrieved from first- trimester aborted fetuses 3. To use somatic cell nuclear transfer (SCNT)=cloning to produce embryos, and then the same as 1. (therapeutic cloning) 3. To use somatic cell nuclear transfer (SCNT)=cloning to produce embryos, and then the same as 1. (therapeutic cloning) 4. To transform multipotent adult stem cells? 4. To transform multipotent adult stem cells?

The promise of stem cells To cure diseases like To cure diseases like –Diabetes –Heart disease –Parkinson disease –Alzheimer disease –Neurodegenerative disorders –Spinal cord injury –Replace cells injured by trauma

The advent of regenerative medicine Therapeutic cloning Therapeutic cloning Regenerative medicine will transform our conception of Regenerative medicine will transform our conception of –Aging –Personal identity

The ethical dilemma of hESC- therapy Extracting the stem cells kills the embryo (which is in the blastocyst stage of development) Extracting the stem cells kills the embryo (which is in the blastocyst stage of development) Is destroying the embryo killing a human person? Is destroying the embryo killing a human person? If a 4-5 days old embryo is a person, then healing a person with stem cells is performed by killing an other one If a 4-5 days old embryo is a person, then healing a person with stem cells is performed by killing an other one

The moral status of the blastocyst The basic question The basic question –At what stage of embryonic development does the life of the embryo deserve the same respect and protection due a newborn infant? The main answers The main answers –Conservative: at conception –Liberal: at birth –Moderate: at some stage during embryonic development

The conservative position All human beings have the same value All human beings have the same value Human life begins at conception Human life begins at conception Killing an embryo is just as bad as killing adults Killing an embryo is just as bad as killing adults Problems: Problems: –Theoretical:  It uses the term „human life” in two different meanings: (human life at a cellular level and human life as the life of an organism)  „But the zygote is a potential human being”—then it only potentially has a right to life  The potentiality argument leads too far—it would prohibit contraception as well

The liberal position It takes into account women’s right to self-determination over their bodies, which is relevant in case of abortion It takes into account women’s right to self-determination over their bodies, which is relevant in case of abortion It is, however, irrelevant, when the status of the embryo, outside the woman’s body is considered It is, however, irrelevant, when the status of the embryo, outside the woman’s body is considered

The moderate positions Common in them: development is relevant to attain full moral status Common in them: development is relevant to attain full moral status The gradualist position: human life is valuable at all stages of its development, but it becomes more and more valuable during development until it reaches full moral status The gradualist position: human life is valuable at all stages of its development, but it becomes more and more valuable during development until it reaches full moral status At what point is personhood reached? At what point is personhood reached?

The symmetry between brain death and brain birth I. Human life (morally and legally) comes to an end by brain death Human life (morally and legally) comes to an end by brain death The brain dead is biological still alive (its organs can be used for transplantation purposes) The brain dead is biological still alive (its organs can be used for transplantation purposes) The end of biological life and the end of personal life do not coincide—personal human life ends earlier, than biological life The end of biological life and the end of personal life do not coincide—personal human life ends earlier, than biological life

The symmetry between brain death and brain birth II. Similarly: human life (morally and legally) begins by brain birth (at 10th week of gestation, at the end of embryonic development) (Goldenring, 1982) Similarly: human life (morally and legally) begins by brain birth (at 10th week of gestation, at the end of embryonic development) (Goldenring, 1982) Embryos (before the 10th week of gestation) are biologically humans, but are still not persons Embryos (before the 10th week of gestation) are biologically humans, but are still not persons Fetuses (after 10th week of gestation) have functioning brains Fetuses (after 10th week of gestation) have functioning brains

The symmetry between brain death and brain birth III. Human biological life is longer, than the life of the human person Human biological life is longer, than the life of the human person –It begins earlier (at conception) than personal life, and ends later (at biological death, the death of the last living cell of the organism) The life of the human person begins later, than biological life (at brain birth), and ends earlier (at brain death) The life of the human person begins later, than biological life (at brain birth), and ends earlier (at brain death)

Conclusion Embryos do not have a right to life, fetuses do have Embryos do not have a right to life, fetuses do have This moderate position is reflected in some widespread practices This moderate position is reflected in some widespread practices

Some basis for convergence Few accept the full implications of the view, that the embryo is a person with full moral status (Ronald Dworkin) Few accept the full implications of the view, that the embryo is a person with full moral status (Ronald Dworkin) These implications would be These implications would be –Abortion would not be permitted  to save the mother’s life  even in case of rape or incest Conclusion: this in practice favors some form of the moderate positions

If the blastocyst is a person, is stem cell research necessarily unethical? We could use organs for transplantation purposes, even if they resulted from a homicide We could use organs for transplantation purposes, even if they resulted from a homicide Similarly, if IVF technology involves discarding the surplus (spare) embryos, using their cells before discarding them could be acceptable, if the user did not contribute to the creation of the embryo? Similarly, if IVF technology involves discarding the surplus (spare) embryos, using their cells before discarding them could be acceptable, if the user did not contribute to the creation of the embryo?

Is discarding the embryo better than deriving ES cells from it? IVF programs necessarily entail discarding spare embryos IVF programs necessarily entail discarding spare embryos Deriving ES cells from spare embryos before discarding them will lend permanence to the embryo (McGee—Caplan, 1999) Deriving ES cells from spare embryos before discarding them will lend permanence to the embryo (McGee—Caplan, 1999) Conclusion: destructive embryo research destroys the embryo less, than discarding it Conclusion: destructive embryo research destroys the embryo less, than discarding it If IVF programs are permitted, it is inconsistent to prohibit derivation of ES cells from spare embryos If IVF programs are permitted, it is inconsistent to prohibit derivation of ES cells from spare embryos

The relevant questions Is destructive embryo research on donated spare embryos of IVF programs ethically acceptable? Is destructive embryo research on donated spare embryos of IVF programs ethically acceptable? Is the creation of embryos for research purposes ethically acceptable? Is the creation of embryos for research purposes ethically acceptable?

The major policy positions regarding human embryo and hESC research I. (Walters, 2004) Total prohibition: Total prohibition: – embryo research and research on existing hESC lines is forbidden Almost total prohibition: Almost total prohibition: –Embryo research is forbidden but research on existing hESC lines is permitted Moderate view: Moderate view: –Research is permitted only on surplus (spare) embryos of IVF programs

The major policy positions regarding human embryo and hESC research II. The liberal view: The liberal view: –The creation of embryos specifically for research purposes is permitted The radical view The radical view –Cloning of human embryos for research purposes is permitted The ultra radical view The ultra radical view –The transfer of human somatic cell nuclei into animal eggs is permitted

„Radical” and „ultra radical” countries from the point of view of hESC research UK; Belgium; Sweden UK; Belgium; Sweden India; China India; China Israel; South Korea; Singapore Israel; South Korea; Singapore USA (2 states: California and New Jersey) USA (2 states: California and New Jersey) Controversial research that can be carried out there: The creation of embryos specifically for research purposes The creation of embryos specifically for research purposes Cloning of human embryos for research Cloning of human embryos for research The transfer of human somatic cell nuclei into animal eggs The transfer of human somatic cell nuclei into animal eggs

Evaluation of consistency in various positions Total prohibition--consistent Total prohibition--consistent Almost total prohibition (USA, Germany) Almost total prohibition (USA, Germany) –Reason: the prevention of future embryo destruction –But: IVF program (accepted in these countries) involve embryo destruction –Conclusion: this position is inconsistent The moderate position—consistent The moderate position—consistent

The superiority of the liberal position to the moderate one Moderate position—allows only the use of spare embryos from IVF programs Moderate position—allows only the use of spare embryos from IVF programs –Implicit presumption—treating infertility is a goal that justifies the destruction of some embryos Liberal position—allows to create embryos for research purposes Liberal position—allows to create embryos for research purposes If a non-life saving treatment (treating infertility) justifies the destruction of embryos, why the promise of a life-saving treatment does not? (Clarke, 2006) If a non-life saving treatment (treating infertility) justifies the destruction of embryos, why the promise of a life-saving treatment does not? (Clarke, 2006) The answer depends on the acceptability of the principle of double effect The answer depends on the acceptability of the principle of double effect

The separation of state and church The difference between opponents and proponents of destructive embryo research proved to be intractable The difference between opponents and proponents of destructive embryo research proved to be intractable Imputing full moral status to the embryo is mostly based on religious premises Imputing full moral status to the embryo is mostly based on religious premises Can the health needs of persons submitted to the religious views of others? Can the health needs of persons submitted to the religious views of others? The constitutional principle of separation of church and state should be followed The constitutional principle of separation of church and state should be followed