oxford handbook of bioethics

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Its theoretical supposition is elegant, intriguing to investigators, and inviting to prospective patients. Even if the link to the destruction of embryos becomes moot if investigators learn how to produce genetically compatible ES cells without first having to create a potentially viable embryo, the broader issue of making science policy in the presence of heightened politics will not. Other technologies with problematic connotations and evocative labels, such as animal – human hybrids, parthenotes, or chimeras, are waiting to be vetted in the policy arenas. Therapeutic SCNT, in other words, is a case study of how to incorporate ‘new scientific findings . . . into a policy framework that is developing under intense political pressure’ (Kennedy 2004).

Academics and policy advisory groups, among others, have contributed to an expansive literature exploring the ethical and moral dimensions of ES cell research and therapeutic SCNT (e.g. American Association for the Advancement of Science/Institute for Civil Society 1999; Committee on the Biological and Biomedical Applications 2002; FitzPatrick 2003; Juengst and Fossel 2000; Holland et al. 2001; National Bioethics Advisory Commission 1999; National Institutes of Health 1999; Nuffield Council on Bioethics 2000; President’s Council on Bioethics 2002, 2004). Some themes and areas of agreement emerge from the literature. For example, it is widely agreed that matters relating to SCNT are of societal interest, touch on deeply felt values that must be acknowledged, and warrant public deliberation. It is also expected that ethical dimensions should be discussed before rather than in reaction to scientific developments (Parens and Knowles 2003; Cohen 2001). This includes ethical issues raised by ES cell clinical trials and eventual medical therapies (Faden et al. 2003; Dawson et al. 2003). There is some agreement that discussion should be comprehensive (President’s Council on Bioethics 2002) and include a range of reprogenetic techniques, defined as ‘all interventions involved in the creation, use, manipulation, or storage of gametes and embryos’. These techniques raise ‘complex and sometimes profound ethical questions that call out for informed policy, publicly and transparently developed’ (Parens and Knowles 2003, S4, S6).

A number of commentators in the United States advocate the establishment of a national-level body to deliberate and ensure the responsible development of reprogenetics. Proposals range from a narrow body, such as the Recombinant DNA Advisory Committee (Committee on the Biological and Biomedical Applications 2002) to a more comprehensive body such as the United Kingdom’s Human Fertilisation and Embryology Authority (Parens and Knowles 2003). Others believe institutional review boards (IRBs) and local oversight are sufficient (American Medical Association 1999). Commentators also recommend federal funding of the research as a way of securing federal oversight (Committee on the Biological and Biomedical Applications 2002). Yet the distinct possibility exists that no body will be developed, or that the body will be less effective than hoped, or that federal funding will never reach the level needed for thoughtful deliberation and careful oversight.

In the current situation, three things are intersecting at once. First, an area of contentious biomedical research is proceeding, although the scope of that research is difficult to assess. Second, although there is no legal impediment to this research, significant guidance is lacking at the national level given the refusal of the government to fund research in which embryos are injured or destroyed. Third, the issue touches on fundamental values and is highly salient to supporters, who see it as a possible aid to illness and a reflection of scientific liberty, and to opponents, who see it as an immoral act in which human life is destroyed. It is this saliency and intensity of feeling that makes scientific prospects distinct from many other areas of biomedical research. Concern about the societal nature of the issues generates calls for guiding policy, which might include voluntary acceptance of ethical principles and/or legally binding regulations.

Much of the literature on therapeutic SCNT covers the moral arguments for and against proceeding and the policy stall occasioned by conflicts over the moral status of embryos. Yet it is also worthwhile to view policy from the standpoint of the resources available as well as of deficiencies in those resources. This chapter uses the idea of a policy community to examine policy making from a starting point that focuses not on what divides, but rather on the groups and individuals committed to enabling ES cell research and therapeutic SCNT. Although written with international dimensions in mind, the chapter focuses on the United States, where the politics are particularly volatile and the likelihood of policy leadership at the national level is remote.

A policy community is a set of academics, policy analysts, interest group members, and others who share an interest in the same set of policies, although they do not necessarily agree on all matters (Majone 1989: 161; Kingdon 1984: 123). Of interest in this chapter is the narrower policy community of advocates of ES cell research, including therapeutic SCNT. This community of advocates has a distinct bias, to be sure, but its members share a commitment, a sense of mission, and a personal interest in the outcome that positions them to be creative problem solvers. Given the prospect of continued research without governmental guidance at the national level, it is instructive to examine their potential contributions to policy development.

This chapter identifies groups within the community of advocates and discusses roles they might play in policy development. As background, it first reviews reasons for a policy stall over therapeutic SCNT at the national level and suggests roles the US Congress has played short of rule making. It then identifies seven groups or agencies in the community of advocates: national legislature, private funding agencies, state governments, international policy, corporations, professional associations, and policy advisory groups. It pursues the theme that these sources serve as a forum for policy development. While a comprehensive and enforceable policy is unlikely to develop from their activities, members of the community contribute to the lengthy ‘softening up’ of policy proposals requisite for the emergence of policy (Kingdon 1984: 123).

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POLIT ICAL DIMENSIONS OF THERAPEUT IC

SCNT

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Politics connotes scarcity, competition, and struggle over desired resources. Within this meaning, in the year or so after the announced birth of Dolly the lamb, reproductive SCNT was not particularly political because desired goals were not highly threatened. On the contrary, a key goal was shared: advisory groups and commissions around the world expressed concerns about cloning’s implications for children, family, and society, and surveys revealed widespread consensus about not proceeding with humans (e.g. Eiseman 1997; National Bioethics Advisory Commission 1997). These concerns ranged from the societal level, such as reduced heterogeneity in the gene pool, to the individual level, such as whether women would be exploited in the rush to secure eggs for reproductive SCNT. Most of the commentary was critical, and particular attention centered on the physical and psychological risks cloning might pose to the child. Some commentators challenged unsupported suppositions about the risks of cloning (Brock 1997; Robertson 1998; Steinbock 2000) and others advocated reproductive SCNT (Eibert 2003; Pence 1998). The early sense of urgency by critics to study the issues dissipated as it became clear that low success rates with animal cloning meant reproductive SCNT with humans would not take place in the near future even if the will existed to do so.

Although the debate was not intensely political in the sense of competition over values, it did elicit more intense reactions nationally and internationally than perhaps any scientific biomedical development to date. Reproductive SCNT had a fantastical element to it; it has long provoked creative scenarios among filmmakers (e.g. The Boys from Brazil (1978), Multiplicity (1996), Godsend (2004) ), fiction writers (Huxley 1932; Nussbaum 1998); political cartoonists, and essayists. It also tapped an intuitive element, reflected in Kass’s admonition to listen to the ‘wisdom of repugnance’ (Kass 1997). The political struggle over reproductive SCNT revolved more around the means than the end as fault lines arose over what mechanisms could best ensure that no one attempt to clone a human (National Bioethics Advisory Commission 1997). Some nations had already banned it before Dolly’s birth and others enacted new prohibitions after her birth. In the United States the National Bioethics Advisory Commission recommended that Congress enact a five-year moratorium on efforts to clone a human. Others advocated postponing decisions until more was known and, in the meantime, relying on voluntary moratoriums urged by professional associations on their members. Numerous bills were introduced to ban reproductive SCNT in the US Congress (Bonnicksen 2002).

An effort to bring to a vote a bill banning reproductive SCNT failed in the US Senate in early 1998, and the issue receded (Bonnicksen 2002). Intense politics

through most of 1998 were kept in check by a basic consensus about the folly of pursuing cloning when so many ethical reservations existed, a realization that human reproductive SCNT was remote, and a notice by the Food and Drug Administration (FDA) that it would not let reproductive SCNT proceed. Nevertheless, a precedent for policy in biomedical research had been set by the extensive debate in Congress over whether to ban a particular biomedical technology and, if so, to do so before it was even imminent. Heretofore, Congress had expressed approval or disapproval over developments in biomedical research by its control over appropriations, not by a prior restraint on a whole category of research.

Politics in the US Congress escalated in late 1998 when scientists announced that they had derived and isolated human ES cells from the inner cell mass of seven to nine day embryos ( Thomson et al. 1998). This announcement fostered visions of a limitless source of versatile cells that could be coaxed to differentiate for medical therapy. For this research, the investigators used embryos that had been donated by patients in fertility programs who no longer needed or wanted the embryos for their reproductive efforts. This had the ethical advantage of avoiding the destruction of embryos beyond those certain to be destroyed anyway, and it gave couples the opportunity to feel they had contributed to the research effort. On the other hand, reliance on donated embryos from persons struggling with infertility could skew research findings if couples had genetic reasons for the infertility, hinder the growth of cell lines from genetically diverse embryos, and deprive investigators of the opportunity to control all aspects of the derivation and return to the original embryo to secure more ES cells if necessary.

To circumvent these problems, investigators proposed creating embryos for ES cell derivation with gametes donated for the purpose. Furthermore, with an eye to eventual medical therapy, researchers proposed creating embryos through SCNT, using the nucleus from a patient’s somatic cell and an enucleated donor egg. From the inner cell mass of this embryo, technicians could generate cells for therapy that would carry the ‘genetic blueprint’ of the intended patient and thereby circumvent the need for immunosuppressive drugs (Daley 2003; Hochedlinger and Jaenisch 2003).

The idea of using SCNT for nonreproductive use generated a distinction for ethical and policy deliberations between reproductive SCNT (creating an embryo for transfer to a uterus for a possible pregnancy) and therapeutic SCNT (creating customized cell lines for medical therapy). These two were linked by technique but distinguished by intended outcome. From one perspective, the intended outcome is determinative, and therapeutic SCNT can be distinguished from reproductive SCNT for policy purposes, with the most likely option of allowing the former while banning the latter. The United Kingdom has adopted this perspective inasmuch as its Human Fertilization and Embryology Authority allows research licenses for therapeutic SCNT but prohibits reproductive SCNT. Similarly, the Republic of South Korea allows therapeutic SCNT under guidelines of its National Ethics

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Committee but forbids reproductive SCNT (Asia 2004), Singapore permits the first on a case by case basis with approval of the relevant governmental body but forbids the second (Asia 2004), and Finland’s Medical Research Act No. 488/1999 has been interpreted as allowing therapeutic but forbidding reproductive SCNT (Europe 2004).

From another perspective, technique is determinative and both forms of SCNT should be banned. Some nations, such as Italy (Europe 2004) and Australia (Oceania 2004), forbid both. One survey revealed that approximately seven nations allow therapeutic SCNT in some form, approximately thirty-three do not, and in twelve nations the status is unknown ( Jones and Cohen 2004). Different arguments defend the perspective of banning both forms. Among other things, it is argued that the creation of any embryo for research purposes is immoral; the embryo has the moral status of a person, so creating an embryo through SCNT is the same as creating a child through SCNT; if SCNT works to create a dividing embryo for therapy, the temptation to try to create an embryo for reproduction will be too much to resist; and it will be too difficult to police facilities to guard against the one but not the other.

In the US Congress, policy options gravitated to two main possibilities outside of doing nothing: making reproductive SCNT a crime (narrow ban) or making therapeutic and reproductive SCNT criminal (broad ban). It was around this time that the issue of SCNT became highly political, because opponents of SCNT were willing to sacrifice a ban on reproductive SCNT only, a proposal for which there was widespread agreement, in order to hold out for a ban on both reproductive and therapeutic SCNT. The House passed a broad ban on 31 July 2001, by a 265 – 162 vote, the Human Cloning Prohibition Act of 2001 (H.R. 2505). It passed the same bill, now renumbered, on 27 February 2003, by a 241 – 155 vote (H.R. 534). The Senate has not at the time of writing voted on the issue, and those holding out for a broad ban cannot gather the requisite sixty votes needed to overcome a motion to close debate. The administration of George W. Bush pursued the same strategy of holding out for a broad ban at the United Nations (Walters 2004).

Human ES cell research (and therapeutic SCNT as a subset) provokes heightened politics for several reasons. First, because it involves the destruction of human embryos it has been swept into the ‘intractable’, ‘vitriolic’, and ‘polarizing’ abortion debate in the United States (Annas et al. 1996; Parens and Knowles 2003). As the President’s Council on Bioethics observed about the inability to forge a consensus on ES cell research in the United States,

One side believes that what is involved is morally abhorrent in the extreme, while the other believes embryo research is noble or even morally obligatory and worthy of praise and support. It would be very difficult for the government to find a middle ground between these two positions, since the two sides differ not only on what should or should not be done, but also on the moral premises from which the activity should be approached. (President’s Council on Bioethics 2004: 39)

Second, ES cell research is highly personal and salient. In contrast to reproductive SCNT, which is abstract and saddled with intuitions, therapeutic SCNT has been paired in the public debate with living people in need of therapy. The number of people with chronic and untreatable conditions who could potentially benefit from ES cell research runs in the millions, but research proponents personalize these numbers by bringing human faces to them. Michael J. Fox and the late Christopher Reeve are two of the celebrities who have promoted the research, and Nancy Reagan and Orrin Hatch are two political figures who moved outside their pro-life positions to advocate federal funding for ES cell research. The research has been recast as regenerative medicine, a category removed from a label of embryos or procreation. Proponents mobilize patient advocacy groups, garner petitions signed by stellar scientists, and bring together coalitions of scientists, health care workers, researchers, and prospective patients and their families.

Third, therapeutic SCNT involves funding, which raises issues about public moneys for activities deemed immoral by some. In the United States this led to months of lobbying President Bush in anticipation of his decision on ES cell funding. A parallel example of the politics of funding comes from the efforts of the European Union (EU) to find common ground for funding research involving human embryos. Members of the EU in 2003 were unable to agree, after months of discussion, on a policy for funding human ES cell research as part of the 6th Framework Program for science funding in 2002 (Vogel 2003).

Fourth, the debate over SCNT is punctuated by colorful and sensational announcements that roil the public. For reproductive SCNT, Richard Seed, a physicist, announced in 1998 that he would open a cloning clinic in Chicago. In 2001 Panos Zavos announced that he and two other physicians would attempt to clone a human in an unnamed country. Also in 2001 Clonaid, through its spokesman, Rael, said that it had fifty women ready to act as surrogates for embryos created through cloning. Each announcement precipitated hearings in Congress and calls for legislation.

An early destabilizing announcement for therapeutic SCNT came in late 2001, when personnel at Advanced Cell Technologies, Inc. (ACT), a Massachusetts-based firm, announced that their scientists had created three early-stage human embryos through SCNT, two of which divided to four cells and one divided to six cells. A triad of press releases announced this: a scientific article in e-biomed: The Journal of Regenerative Medicine (Cibelli et al. 2001), a cover story in U.S. News and World Report entitled ‘The First Clone’ (Fischer 2001), and a story in Scientific American with additional coverage on the magazine’s website (Cibelli et al. 2002). Special efforts had been taken to ensure a news blackout until all three articles came out at once.

Two years later ACT announced, in a press release that coincided with a cover article entitled ‘The Making of a Human Clone’ in WIRED, that it had created ten human embryos through SCNT and eight parthenotes (Rohm 2004). According to

Policy making itself has been described as a long process of ‘softening up’ in which ‘ideas are floated, bills introduced, speeches made; proposals are drafted, then amended in response to reaction and floated again’ (Kingdon 1984: 123). Proposals are made and discussed in policy communities comprised of groups and individuals willing to invest ‘time, energy, reputation, and sometimes money’ in order to meet personal interests and promote policies and values (Kingdon 1984: 129 – 30).

Among the voices in the policy community of advocates for therapeutic SCNT are scientists, researchers, and a significant grass roots element made up of patient advocacy groups and coalitions. Techniques involving petitions by Nobel laureates, testimony by celebrities, and supportive letters and speeches by persons usually associated with anti-abortion positions are among the methods used to keep proposals to expand funding for ES cell research on the public agenda. Interest in ES cell research has prompted corporations, professional associations, funding agencies, and even state governments to lay out research plans with minimal leadership from the US legislative and executive branches. The following sections identify some players in the policy community of advocates and ask about the capacities of each to contribute to the emergence of guiding policies. It starts with the US Congress, where the pluralist interests honed their voice.

National Legislature

The US Congress is generally viewed as a barrier to reprogenetic policies through its long-standing refusal to authorize federal spending for research that involves injury to or destruction of human embryos. This provision stops policy in its tracks, and it causes observers to look elsewhere for policy direction. Yet Congress’s refusal to authorize money for research on reprogenetics does not preclude it from playing a multidimensional role in the matter of SCNT and ES cell research. On the contrary, Congress has asserted influence in its traditional roles of representing constituencies and clarifying policy options. Congress was the place where the struggle over SCNT took shape. The announcements of Dolly’s birth and of ES cell derivation provoked Congress between 1997 and 2003 to hold a total of twenty-two hearings on reproductive cloning and/or stem cell research in both chambers: the House of Representatives held eight and the Senate held fourteen. The hearings were held in five different committees in the Senate (Appropriations; Commerce, Science, and Transportation; Judiciary, Health, Education, and Pensions; and Labor and Human Resources) and four in the House (Commerce and Energy; Judiciary Government Reform; and Science). Hearings were the primary avenues for gathering information and educating the public and members of Congress.

Some hearings were convened in response to news headlines. While most were relatively staid, others, as when the Raelians testified, had a more sensational tone. Well over fifty witnesses representing a variety of interests testified in ES cell and/or

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cloning hearings from 1997 to 2004. A review of witness lists indicates that scientists and physicians testified most frequently; representatives of interest groups and organizations came in second; and ethical, legal, and policy commentators made up the third largest category. As time passed, a policy community took shape, with some legislators more active than others and some witnesses testifying two or more times. These hearings provided a forum for the emergence of repeated themes and arguments. Congress also clarified policy options by the introduction of numerous bills that in the beginning were diverse. Over time, however, key provisions kept reappearing to produce what was like a model narrow ban (to bar the transfer of an embryo created through SCNT to a woman’s uterus) and a model broad ban (to bar any creation of an embryo through SCNT). The preambles of the bills revealed ideological underpinnings, as did debate by members of Congress printed in the

Congressional Record.

While some are critical of Congress for not passing substantive legislation, the merits of a non-lawmaking role can also be argued. Law passed in this area would not necessarily establish a good precedent given the sense of headline-driven impulse that periodically puts SCNT on the Congressional agenda. In addition, political strategy permeates actions. For example, in 1998 Senate proponents of a broad ban attempted to use parliamentary maneuvers to rush the bill to the chamber floor for a vote, bypassing hearings on the bill in the process (Bonnicksen 2002). Later the broad ban bill that passed the House in July 2001 ‘received little serious debate’ (Maienschein 2003: 288). It is not unusual for House members to be ‘quick to pass what they see as politically useful legislation that they know the Senate will not support’ (Maienschein 2003: 290).

In addition, passing an SCNT law in Congress, even a protective law, would establish precedent by involving Congress substantively in biomedical research and doing so in a technique-specific way. If more contentious techniques are in sight, this could set the stage for future technique-based laws that are brittle and unresponsive to scientific change. More normally, Congress delegates technical policy making to administrative agencies, where administrative discretion allows more flexibility and responsiveness to changing technologies. The absence of a body such as the Office of Technology Assessment, which wrote informative reports for Congress before it was disbanded in 1995, also argues against narrow technique-driven legislation.

Moreover, a disparity exists between the technical nature of science policy and the political needs and interests of members of Congress. Congressional decisions involve ‘bargains and compromises and . . . strategies’ (Morgan and Peha 2003a: 8). This attention to ‘synthesis and balancing of interest’ is removed from the ‘systematic analysis’ needed for science and technology (Morgan and Peha 2003b: 173). Members of Congress, writes one observer, ‘seek agreement, not truth’ (Smith and Stine 2003: 25), a goal hampered by deep-seated differences about the moral status of the embryo. Even the President’s Council on Bioethics, which identified seven main policy options for ES cell research, produced a divided vote on the

question of funding (President’s Council on Bioethics 2002). As a consequence, the federal government retreats: it ‘does not explicitly prohibit embryo research but also does not officially condone it, encourage it, or support it with public funds’ (President’s Council on Bioethics 2004: 39).

In summary, it helps to look expansively at Congress’s functions when evaluating its impact on the development of cloning policy. Although the body has not, at the time of writing, passed a law directed at reproductive or therapeutic SCNT, it has helped defuse the sense of urgency, gather information, perform representation functions, and clarify policy options. It has also served as a forum in which a policy community of advocates and opponents has emerged. If, indeed, policy options need to be discussed over time in a process of ‘softening up’, Congress plays a role in keeping deliberation alive.

Funding Agencies

Ideally, the federal government funds promising research, which brings studies to the open, asserts quality control through peer review, enables sustained investment, and invites oversight. After intense lobbying of the executive branch between 1999 and 2001, President Bush presented a compromise agreement to allow funding of a narrow range of studies using ES cell lines derived by 9 August 2001. At the time the administration believed around sixty usable lines existed, but the number turned out to be fewer than twenty. Even with a limited role, however, the National Institutes of Health (NIH) became part of the community of advocates for ES cell research using cell lines derived before 9 August 2001. To spur more research proposals, it set up a Human Embryonic Stem Cell Registry to list (but not distribute) cell lines as they become available, an NIH Stem Cell Task Force to coordinate NIH programs and identify problems in funded research, an NIH Characterization Unit to provide data from assays on ES cell lines, and an award program to train mid-career investigators to use the cells (Zerhouni 2003a, b). The Department of Health and Human Services also announced an initiative to create a National Embryonic Stem Cell Bank (Holden 2004a). In one year of funding, sixty investigators at forty-eight institutions received money, with most (forty-four) receiving supplements to existing research and others (fourteen) receiving funds for newly initiated research (Zerhouni 2003b). Research involving therapeutic SCNT is not funded.

The uncertain outlook for expanded federal funding has propelled institutes, foundations, and even state governments to make available alternative sources of support. For example, on the west coast, Stanford University received a $12 million donation to set up a privately funded Institute for Cancer/Stem Cell Biology. Because therapeutic SCNT research is explicitly legal in California, this leaves open the possibility that such studies will be conducted. On the east coast the Howard Hughes