How Physicians and Scientists Should Respond to Controversy about the Ethics of Human Embryonic Stem Cell Research

1. How Physicians and Scientists Should Respond to Controversy about the Ethics of Human Embryonic Stem Cell Research Laurence B. McCullough, Ph.D. Professor of Medicine and Medical Ethics Associate Director for Education Center for Medical Ethics and Health Policy Baylor College of Medicine Houston, Texas

2. Objectives -1 • Identify potential applications of stem cells for urology • Define key terms and concepts: • Molecular medicine and regenerative medicine • Ethics • Moral status • Moral consensus • Moral controversy • Public policy

3. Objectives -2 • Explain why human embryonic stem cell research involves intractable moral controversy • Identify a strategy for responsibly managing intractable moral controversy in science • Identify a strategy for responsibly managing intractable moral controversy in public policy

4. Urological Applications • Mouse model for the derivation of male and female gametes from embryonic stem cells in culture • Potential new tool for studying molecular basis of germ-line establishment • Opens the door to research on reproductive engineering such as nuclear transfer and other genetic manipulation of germ lines • However: • No viable embryo yet produced • Very few cell lines available • Human embryonic stem cell research “stymied by ethical and technical obstacles” • Kirk, Whirledge, Lamb 2005 • Potential for regenerative medicine • Atala 2006

5. Molecular Medicine and Regenerative Medicine • Molecular medicine understands health and disease to be functions of the interaction of genes, proteins, and the environment • “Environment” includes the immediate biochemical environment of cells, through organs and organ systems organized into bodies, to the larger biosphere in which these life forms function • Cell engineering is emerging as a major clinical tool of molecular medicine, leading to regenerative medicine

6. Ethics • Ethics is the disciplined study of morality, aiming to improve current morality through careful and sustained reflection and discourse • Morality concerns both right and wrong conduct and good and bad character • Morality can always be improved • Religious and theological ethics vs. philosophical ethics in a pluralistic society • Secular, philosophical ethics as one of the main legacies of the British, European, and North and South American enlightenments of the eighteenth and nineteenth centuries

7. Moral Status • Moral status means that the rest of us have an obligation to protect and promote the interests of an entity • Self-generated or independent moral status • Dependent moral status • Legal status means that moral status should be enforced with the power of the state

8. Moral Consensus • There is clear, consistent, coherent, applicable, and adequate argument that establishes a conclusion that withstands vigorous criticism • For example: Invasive medical treatment may not be provided to a competent, adult patient who, as a result of the informed consent process, refuses that intervention, except in cases of life-threatening emergency in which the patient does not have an applicable advance directive refusing such treatment • Ethical challenges concern how to reach consensus when there are obstacles to doing so

9. Moral Controversy • There are competing consistent, coherent, applicable, and adequate arguments that establish diverse conclusions that appear to withstand vigorous criticism • For example: Coerced cesarean delivery for intrapartum complications in a term pregnancy • Fetal distress • Cephalo-pelvic disproportion • Well documented, complete placenta previa • Ethical challenges concern sorting out claims that meet standards of argument-based ethics from claims that do not, eliminating the latter from ongoing reflection and serious consideration, and managing ongoing controversy in disciplined fashion

10. Public Policy • Public policy concerns whether and how we we, as a society, will use the instruments and power of self-government to prohibit, permit, allow, encourage, and support activities • Statutory law • Common law • Administrative and regulatory law • The absence of these is a major public policy tool for what we will permit, if only by default

11. Moral Controversy about Human Embryonic Stem Cells -1 • Over more than 2,500 years of reflection and discourse in global intellectual traditions, both religious and secular, no consensus on the moral status of prenatal human life forms – from in vivo and in vitro embryos to at-term fetuses – has emerged • Disagreement among and within major world religions on both independent and dependent moral status of these human life forms • Including Buddhism, Christianity, Confucianism, Hinduism, Islam, Judaism, and Pantheism (as well as their many, often incompatible varieties) • Disagreement in the philosophical literature

12. Moral Controversy about Human Embryonic Stem Cells -2 • Resolution of this moral controversy would require acceptance of a single perspective that would be authoritative for all because all would be compelled intellectually to accept and therefore submit to it once and for all • Such an intellectual event is inconceivable • We should therefore give up expecting it to occur or acting as if what appears to be such a compelling argument actually is one

13. Moral Controversy about Human Embryonic Stem Cells -3 • Current techniques for obtaining human embryonic stem cells require the destruction of the embryo • Currently, embryonic stem cells obtained from “therapeutic cloning” will involve the creation of human embryos for the express purpose of destroying them

14. Managing Intractable Moral Controversy in Science -1 • Eliminate enthusiasm, as Francis Bacon (1561-1626) already taught and we should not have to keep re-learning • Replace enthusiasm with the intellectual discipline required of scientists • Currently, no animal models of embryonic stem cell interventions • Currently, no human models and few of stem cell interventions (which seem to be empiric, e.g., stem cells to “treat” heart disease) • Take seriously the persistent lessons of the history of basic science and clinical research • Medicine rarely has the power to cure disease, i.e., completely eliminate pathology with no or few serious complications • By fits and starts, research results in marginally and sometimes steadily improved clinical management and prevention of disease and injury • Improved clinical management is a very good thing and usually worth the investment required to produce it

15. Managing Intractable Moral Controversy in Science -2 • Beware the trap of “ex cathedra” statements • Asserting the conclusion of an argument without presenting and warranting its premises fails to meet the requirements of argument-based ethics • “There’s nothing unethical about what we’re doing here. We think that embryonic stem cells can be made to become pancreatic beta cells and that they will be able to help diabetics produce their own insulin. I’ve never once doubted the morality of this work.” • Douglas Melton, Harvard Stem Cell Institute, New York Times, January 24, 2006 • Beware the trap of attempting to remove moral controversy though definitional maneuvers • For example: Pregnancy does not exist until implantation in the uterine wall has occurred so in vitro embryo has no moral status and therefore destroying it is permissible

16. Managing Intractable Moral Controversy in Science -3 • Scientists and clinicians need to recognize that there are significant, unavoidable moral burdens of their research for others • Especially those who find such burdens to be burdens because the science involves things that are morally abhorrent and therefore intolerable • Tolerating the morally abhorrent must be shown to be ethically justified and therefore consistent with good public policy

17. Managing Intractable Moral Controversy in Public Policy -1 • President Bush’s public policy on embryonic human stem cell research • Does not universally ban such research because its opponents find it to be morally abhorrent • Implicit, unargued tolerance for moral evil, provided that those opposed to it do not have to support it directly through taxation and the public treasury • Does ban federal funding to create embryos to be destroyed as morally abhorrent and therefore a morally unacceptable association with evil • Allows federal funding for research on a limited number of existing cell lines as not unbearably morally intolerable and therefore a bearable, not intolerable, association with evil

18. Managing Intractable Moral Controversy in Public Policy -2 • President’s Bush’s policy is incomplete because it fails to address three unavoidable ethical considerations • The burden of diseases and injuries for which current clinical management is reliably judged to be inadequate or only barely adequate and therefore in need of considerable improvement • The burden of disease and injuries for which current clinical management is adequate but needs improvement • The biopsychosocial benefit to the sick and injured of improvements in clinical molecular medicine (not to mention likely overall cost savings)

19. Managing Intractable Moral Controversy in Public Policy -3 • Ethically justified public policy needs to meet the requirements of justice • Justice in general requires us to treat like cases alike • Justice requires us to distribute the benefits and burdens of public policy fairly • When burdens accrue to many and benefits to only a few, who do not have an opportunity to gain offsetting benefit, justice is violated • When benefits accrue to many and burdens accrue to many and those burdened do not have an opportunity for offsetting benefit, justice is strained • When benefits accrue to many and burdens accrue to many and those burdened do have an opportunity for offsetting benefit, justice is satisfied

20. Managing Intractable Moral Controversy in Public Policy -4 • Reproductive cloning violates justice • Benefit accrues only to a very few, burden accrues to many, and those burdened have no opportunity for offsetting benefit

21. Managing Intractable Moral Controversy in Public Policy -5 • Therapeutic cloning to obtain embryonic stem cells for research satisfies justice • Significant benefit may accrue to many, significant burden will accrue to many, but those burdened will have the opportunity to obtain offsetting benefit • Is the burden of inadequately managed disease or injury a greater burden than having to live in a society that requires one to tolerate the morally intolerable? • Relevant cases: The American Catholic Bishops’ letter on the morality of mutually assured destruction in the early 1980s and current taxation of those who find the war in Iraq morally abhorrent • Embryonic stem cell research from cloned embryos therefore satisfies justice • President Bush’s ban on funding for creation of embryos for obtaining stem cells does not satisfy justice, because his reasoning is demonstrably incomplete • President Bush’s policy invokes only the moral burdens of research (which are real and must be taken into account) and fails to consider the full requirements of justice, including especially the burdens of not doing the research and its potential offsetting benefits to those morally burdened by it

22. Managing Intractable Moral Controversy in Public Policy -6 • President’s Bush’s restriction on the number of cell lines that can be used in federally funded research • Does not violate justice if existing cell lines are sufficient for research to move forward that would have the prospect of significant clinical benefit, the opportunity for which offsets the moral burden involved in such research • Will violate justice if existing cell lines are not adequate to achieve scientific goal of generating significant clinical benefit, because moral burden will be imposed without opportunity for offsetting benefit

23. Conclusions -1 • Beware enthusiastic and self-serving scientists • Beware enthusiastic and self-serving bioethicists • Embryonic human stem cell research involves new, unprecedented ethical challenges that threaten to outstrip our moral capacities to deal with them responsibly

24. Conclusions -2 • Some moral controversies are intractable • Their ethical challenge becomes how to live civilly and therefore successfully with them in a pluralistic society • The legacy of the national enlightenments of the eighteenth and nineteenth centuries: abjure violence for tolerance, taking into account intolerable tolerance and reaching well argued judgments about whether it is nonetheless required as a matter of justice • The discourse of justice allows us to formulate and test public policy for acceptable moral abhorrence and the morally intolerable that are experienced by many in response to advances in biomedical science and its clinical applications • Taking our pluralism seriously and submitting to the intellectual discipline of justice-based discourse and judgments

25. References Lo KC, Whirledge S, Lamb DJ. Stem cells: implications for urology. Curr Urol Rep 2005; 6: 49-54. Atala A. Recent applications of regenerative medicine to urologic structures and related tissues. Curr Opin Urol 2006; 16: 305-309.

26. How Physicians and Scientists Should Respond to Controversy about the Ethics of Human Embryonic Stem Cell Research Laurence B. McCullough, Ph.D. Professor of Medicine and Medical Ethics Associate Director for Education Center for Medical Ethics and Health Policy Baylor College of Medicine Houston, Texas