Embryo Stem Cell Research: Ten Years of Controversy (2010) - AQA

Embryo Stem E mbryonic stem cell (ESC) research has been a source of ethical, legal, and social controversy...

Embryo Stem E mbryonic stem cell (ESC) research has been a source of ethical, legal, and social controversy since the first successful culturing of human Cell Research: ESCs in the laboratory in 1998. The controversy has slowed the pace of stem cell science and shaped many Ten Years of aspects of its subsequent development. This paper assesses the main issues that have bedeviled stem cell progress and identifies the ethical fault lines that are Controversy likely to continue. The time is appropriate for such an assessment because the field is poised for a period of rapid devel- opment. President Obama has removed the Bush John A. Robertson administration’s restrictions on federal funding. A huge influx of federal research funds is in the offing and presumably a more rapid maturing of the science will take place. Stem cell science is also moving into the clinical realm. In March 2009, the Food and Drug Administration (FDA) approved the first clinical trial with an ESC-derived therapy for spinal cord injuries, an important first step — though by no means a final or a sure one — in moving ESC research out of the laboratory into clinical medicine.1 Finally, recent work with induced pluripotent stem (IPS) cells suggests that non-embryonic sources of pluripotent stem cells may one day be routinely available. Such a develop- ment will lessen the temperature of the ethical debate while raising other issues. Together these factors show how complicated the trajectory of innovation can be. The scientific chal- lenges are great enough, but they must be overcome in a political and social world of ethical battling and regulatory response. They are another reason why the stem cell experience is so illustrative of how law and policy affect scientific innovation. I. Why ESCs Are Controversial ESCs are the first differentiation after fertilization of cells of the embryo proper. They are not totipotent (capable of forming a new embryo), but they are pluri- potent (capable of forming all other cells in the body). John A. Robertson, J.D., holds the Vinson & Elkins Chair at the University of Texas School of Law at Austin. A graduate of Dartmouth College and Harvard Law School, he has writ- ten and lectured widely on law and bioethical issues. He is the author of two books in bioethics, The Rights of the Critically Ill (1983) and Children of Choice: Freedom and the New Reproductive Technologies (1994), and numerous articles on reproductive rights, assisted reproduction, embryo screening, organ transplantation, and other bioethical issues. He has served on or been a consultant to many national bioethics advisory bodies, including advisory bodies on organ trans- plantation, assisted reproduction, and fetal tissue and stem cell transplantation. He is a Fellow of the Hastings Center, Chair of the Ethics Committee of the American Society for Reproductive Medicine. law, science, and innovation: the embryonic stem cell controversy summer 2010 191  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SYMPO SIUM Because they are the earliest stage of all later cell lin- the neurologic capacity to feel pain and be sentient. eages, they offer a research platform for studying how To them it is clear enough that unimplanted embryos, the subsequent development of tissues arise and for which are a collection of undifferentiated cells, lack fashioning treatments to cure or prevent disease. They the physical characteristics to have the attributes were first cultured in mice in 1981, but not in humans which they view as essential for moral status.6 How- until 1998, when James Thomson at Wisconsin and ever, they are willing to acknowledge that embryos John Gearhardt at Johns Hopkins managed to do so.2 have status greater than other tissue because of the The ability to culture human ESCs in the laboratory chance that they could implant and come to term, and was an important breakthrough because it opened the thus deserve special respect. Such special respect for door to understanding and controlling human devel- embryos requires good reasons to create, discard, and opment and thus to cell replacement or regenerative experiment on them, such as the need to treat infertil- therapies in humans. ity or carry out legitimate scientific research. There is a fervent battle over the ethical acceptability of destroying early embryos to derive pluripotent ESCs, which is necessary to do to obtain ESCs. Stem cell science is thus drawn into the ongoing, highly divisive wars over abortion and the culture of life that have occupied a central stage in American law and politics over the last 30 years. Knives have been drawn about ESC research from Although the gap between these positions will its inception. Few quarrel over the aim of the research never be bridged, several things might be said about to treat illness and disease. Yet there is a fervent bat- it. The first is that the right to life position is based tle over the ethical acceptability of destroying early on an essentialist argument with a consequentialist embryos to derive pluripotent ESCs, which is neces- tinge about the importance of human DNA and the sary to do to obtain them.3 Stem cell science is thus potential to become a person. Its proponents stress drawn into the ongoing, highly divisive wars over the equality of all human beings and the dangers of abortion and the culture of life that have occupied a treating some differently from others. The fact that central stage in American law and politics over the the embryo is not conscious and cannot feel pain does last 30 years.4 I will focus on that battle in the United not matter nor that it may never acquire those char- States, but a version of it has played out in many coun- acteristics or even placed in a uterus for the chance tries. This is a moral divide that has to be managed or to implant. It must be treated as if it were because it accommodated because it is unlikely ever to be com- is living, has unique human DNA, and if transferred pletely removed from political and policy discourse. to a uterus might develop those characteristics. This The embryo status debate has been well-rehearsed is a religious-type belief, and there is no way to argue in many places, so I address its merits here only briefly. around it. On one side are persons who think that a fertilized egg Interestingly, there is also a consequentialist fla- in the laboratory is a new human being or individual vor to the embryo-protection argument: bad conse- with all the rights and moral and legal status of fully quences will happen if we do not respect human life at born persons. They see destruction of embryos, like the earliest preimplantation stages. All persons, they abortion of fetuses, as murder — as a sacrifice of the assert, will be at risk for baleful judgments about their weakest among us for the interests of others.5 They worth and status based on mental characteristics. Yet oppose destroying embryos to obtain stem cells even 30 years of experience with abortion and removing if those embryos will be discarded because they are no life-sustaining treatments for incompetent patients longer wanted by the couples who produced them to clearly belie that claim. treat infertility. A second point is to note that many persons who The other side sees the embryo as too rudimentary profess to hold pro-life views are not totally consistent. in development to have interests or rights, and thus The staunchest adherents do get prizes for consistency should not be protected at the cost of legitimate and in the fervor with which they oppose any action that important scientific research. To take this position they harms an embryo or fetus. Presumably they would need not agree on the point at which fetuses develop oppose the fertilization and discard practices in 192 journal of law, medicine & ethics  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License John A. Robertson assisted reproduction as well, though they have been without a dissenting voice that fetuses are not persons less focused on them.7 But many people who oppose within the meaning of the 14th Amendment, and thus abortion do see the matter differently when embryos do not have constitutional rights as such. Presumably involved are going to be discarded anyway, and life- that ruling would extend to embryos as well. The ques- saving research could occur. Senators John McCain tion left open, however, is whether state or federal and Orrin Hatch have taken this position, as have oth- government may choose to invest them with rights, ers who claim right to life credentials. When impor- for example, making it a crime to create embryos for tant research is at stake, they simply do not recog- research and then destroy them. This question, which nize the early embryo as having the same status as a is at the heart of the constitutional debate over abor- fetus, though they may be hard-pressed to reconcile tion, was settled in Roe v. Wade12 and Planned Parent- the difference. Such views help explain the poll results hood v. Casey.13 The Court has said that the state has a consistently showing that 60% or more of Americans legitimate interest in protecting potential life and may favor stem cell research.8 take steps to demonstrate that respect prior to viabil- The support for stem cell research involving embryos ity only when doing so would not create a substantial that will otherwise be discarded does not necessarily obstacle — an undue burden — on a woman’s obtain- extend to creating embryos solely for research. This ing an abortion. After viability government may ban marks another fault line in the ethical debate and an abortion altogether, except where the mother’s life or apparent inconsistency in some persons on the pro- health is threatened by continuing the pregnancy. research side. Persons who have strong right to life Under this approach a state could argue that it could views oppose research regardless of how the embryo restrict the use of embryos in research, for example, was created. But some persons who think embryos are preventing their destruction for research or banning too rudimentary to have interests or rights still find creating them for research, or perhaps even prohib- it objectionable to create embryos solely for research iting fertilization of more eggs than are needed for a and then destroy or discard them.9 If the embryos are successful pregnancy because of its interest in showing at the same stage of development in each case, then respect for the earliest stages of human life. It might how can one set of embryos deserve protection and also argue that since the embryos are outside of the the other set not? The distinction seems fallacious body, Roe v. Wade and Planned Parenthood v. Casey, because those same persons accept fertilizing all the which strictly speaking concern only abortion, do not eggs retrieved from a stimulation cycle as part of IVF apply. Such a law would certainly meet a rational basis treatment even though doing so will inevitably lead to test because restricting destruction of embryos is a some of them being discarded.10 Despite the lack of a rational way to show respect for early human life. The clear difference between the importance of research question, however, would be whether a more compel- and reproduction, the purpose for which embryos ling standard must be met because of the importance have been created has become a central part of fed- of embryos to ESC research and to ESC researchers eral funding policy, even though creating embryos and to the protection of life and health. If so, it is for research by either method is legal in most states. unlikely that a rational basis justification alone would Future battles over this line are likely. do. A key distinction here is the purpose or impact of II. Legal and Constitutional Issues the state restriction. If it is pitched to the creation of The ESC debate over the last decade has been a debate embryos for treatment of infertility, such laws would about funding and ethics, and only to a lesser extent most likely be unconstitutional because they would about positive law. True, a few states have banned interfere with a constitutionally protected interest in embryo research and SCNT, but much of the battle has reproducing. Any restriction on creating, preserving, been about funding and administrative policy.11 Unlike or discarding embryos that substantially interferes debates over abortion, however, the courts have had a with a decision to have or not have offspring would relatively small role in these battles. Still, the Supreme have to meet a higher standard than that of rational Court’s abortion cases hover in the background, lead- basis.14 The state’s moral concern with demonstrating ing one to wonder whether constitutional rights could respect for human life without more would not justify come into play if government tried to prohibit stem infringing a person’s right to engage in IVF or avoid cell research on a broader scale or otherwise stop the reproduction by discarding unwanted embryos.15 use of ESC-based therapies. Whether direct restrictions on embryo research are The Supreme Court has never ruled on the constitu- constitutional would depend on whether that research tional status of embryos outside of the body and most is part of a constitutionally protected right to research states have no law on the matter. But the Court has ruled or is otherwise required as part of a negative right to law, science, and innovation: the embryonic stem cell controversy summer 2010 193  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SYMPO SIUM obtain needed medical treatment. I have analyzed targeted late-stage research might be protected under those issues elsewhere and will not repeat them here such a right, earlier stage research might not be. in detail.16 The validity of a First Amendment right to Despite these difficulties with finding a constitu- research turns on whether the restriction is aimed at tional right to research or treatment, courts never- the content of the ideas or knowledge sought in the theless might carve out a constitutional role in arbi- research and whether it is a content-neutral restric- trating ESC controversies in the future. This would tion based on the means used in the research to gener- be more likely if ESC therapies were established as ate knowledge. If content-based, the First Amendment safe and effective and a state tried to block their use, is implicated and the restriction is most likely invalid. or prevented a person from objecting to their use on On the other hand, if the restriction is aimed at the grounds of conscience. As we have more experience methods used without regard to the subject-matter of with ESC research and therapy and the Supreme the research, then there is a greater chance that the Court is pushed to deal with other issues at the begin- restriction is constitutionally valid. ning of life, we may see in future years a greater role There is a plausible case that restrictions on the for judicial scrutiny over ESC research and access to use of embryos in research are method-based and not medical care generally. aimed at any particular ideas that would be generated. If so, it may be that only a rational basis for the meth- III. Funding Issues ods-based restriction is needed, as is the case with The main battles of the last decade over ESC research research restrictions requiring informed consent or have been about federal funding policy, not restric- avoiding cruelty to animals. Whether such restrictions tions on private investment in ESC research. Federal are constitutional then will depend on how stringent funding has been the focus of debate because it is and demanding the courts will be in applying a rational necessary for early-stage science, like ESC research, basis test when important interests such as research which is too far upstream from marketable products to and treatment are at stake. If a more demanding test draw much private investment. Because private inves- is applied, one more akin to the intermediate scrutiny tors cannot capture for themselves alone the benefits standard sometimes used in evaluating non-content of such investments, they have no incentive to invest based restrictions on speech, then state restrictions on to produce that knowledge. The burden thus falls on embryo research might be struck down.17 the government to do so, as it does with other public Another basis for constitutional protection for ESC goods, such as national defense and highways. research could arise from its connection with devel- Ethical controversy, however, may plug the federal oping effective treatments for illness and disease. One funding spigot. It did so with regard to fetal tissue could argue that there is a fundamental negative right transplantation research in the late 1980s. It took the to have and use effective medical treatments as part of election of Bill Clinton in 1992 to unplug it. A parallel a person’s due process right to life or liberty. If so, gov- story has unfolded with federal funding of ESC research ernment could not prohibit the use of a safe and effec- and George W. Bush’s highly restrictive funding policy. tive therapy because it used ESCs or was derived from The story of federal funding for embryo research has research based on the destruction of human embryos. a long history, going back to 1975 and the views of the Because research with ESCs is necessary to test and Ethics Advisory Board (EAB) — the first federal review develop such therapies, it too must be protected as body in this area — about funding research into IVF.19 part of the negative right to receive necessary medical The Reagan and Bush administrations disbanded the care. EAB, so no IVF or embryo research was ever funded. At present such an approach has several problems. President Clinton in 1992 asked Harold Varmus, his One is that the courts have not yet recognized a nega- new head of NIH, to develop guidelines for embryo tive right to receive necessary medical care. A federal research. The NIH Human Embryo Research Panel appeals court panel so held in the context of terminal in 1994 recommended several instances in which patients seeking access to Phase II experimental drugs embryo research should be funded, including some but that decision was reversed en banc and further cases in which creating embryos solely for research review denied by the Supreme Court.18 Even if there was justified.20 In 1994 Congress had become Repub- were a negative right to use established therapies, it lican. A rider attached to the 1995 appropriation bill does not follow that bans on the research necessary banned the use of federal money to create embryos for to develop those therapies are invalid. If the research research or for destructive embryo research.21 Known ban has independent justification, it may be that the as the Dickey-Wicker amendment, it has been attached research is too far removed from establishing a safe to every appropriations bill since. and effective therapy to be protected. While some very 194 journal of law, medicine & ethics  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License John A. Robertson These developments formed the backdrop for the The limitations of the August 2001 cut-off date debate over federal funding of ESC research. The issue quickly became apparent. Only a few of the lines were arose in 1998 when Thompson and Gearhart reported easily available, they provided little genetic diver- the first successful culturing of human embryos in sity, and had been cultured with mouse feeder cells, the laboratory. A key question was whether the gov- which raised the risk of infection and contamination. ernment could fund such research given the Dickey- Many additional lines would be needed for the field to Wicker ban on funding destructive embryo research. progress. Banning federal funding for new privately Secretary Donna Shalala of HHS asked Harriet Raab, derived lines would greatly slow the field, in part the General Counsel of HHS, to advise as to the legal- because of the hoops it required of institutions and The conclusion of the funding saga is that federal funding will inject new resources and energy into stem cell science. No funding is available for the destruction of human embryos or for research with lines derived from embryos created for research purposes, but it may be provided for research on the hundreds of ESC lines created from leftover embryos since 2001 and which will be created in the future. ity of such funding. Raab’s legal opinion was that investigators who received federal funding for other embryonic stem cells were not organisms and thus not projects to jump through.28 Institutions could not get embryos within the meaning of Dickey-Wicker. As a involved with hESCs unless they were in a position result, although ESCs are derived from embryos, they to physically separate laboratories receiving federal are not themselves embryos, and thus not covered by and non-federal funds. Even Bush’s own head of NIH the federal ban on funding research with embryos.22 eventually agreed that the limits on federal funding Research opponents argued that funding violated the had hampered ESC research.29 spirit of the amendment, if not its letter, but Raab’s Several states jumped into the breach, most nota- opinion has carried the day, and neither President bly California with the $3 billion commitment it made Bush nor Congress sought to change it.23 in 2004 with passage of Proposition 71.30 Pressure The NIH then developed guidelines for funding mounted in Congress to loosen the screws on federal ESC research and was ready to make grants when the funding. A bipartisan bill, Castle/DeGrette, passed new Bush administration in 2001 halted such efforts.24 the House in 2004. Stem cell funding was an issue in Although George W. Bush professed right to life the 2004 presidential race and again in 2008, with beliefs, it was unclear whether he would find the sci- the question debated by the candidates in nationally entific arguments for proceeding with research more televised presidential debates each year. A bipartisan persuasive than the right to life arguments against bill to lift the federal ban on new lines passed both doing so. His decision was announced in an August 9, houses of Congress 2005, but was vetoed by the presi- 2001 speech nationally televised in those halcyon days dent. The 2006 Congress re-enacted it, only to have it before 9/11.25 It was Bush’s first public policy address vetoed again.31 to the nation and generally won good marks, though it The 2008 election of Barack Obama has radically pleased neither side in the stem cell wars. shifted the federal funding situation. In March 2009, For the scientists Bush allowed NIH funding to go President Obama ordered the lifting of the morato- forward, but only for research with ESC lines that had rium on funding of ESC research with new lines. In already been derived.26 For the embryo protection- his statement accompanying the lifting of the funding ists, no federal funding would be available for deriving moratorium, President Obama said: new lines or for research with ESC lines derived after his August 9 speech. There would thus be no direct  hen it comes to stem cell research…our govern- W federal funding or encouragement of the destruction ment has forced…a false choice between sound of additional embryos. While each side had problems science and moral values. In this case…the two are with the Solomonic qualities of this position, it did not inconsistent. As a person of faith, I believe we allow research to go forward, albeit in a limited way.27 are called to care for each other and work to ease law, science, and innovation: the embryonic stem cell controversy summer 2010 195  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SYMPO SIUM human suffering. I believe we have been given the ton’s NIH, which reappear now in the Obama rules. capacity and will to pursue this research and the California developed its own set of rules for research humanity and conscience to do so responsibly... carried out under grants from the California Institute  The majority of Americans — from across the of Regenerative Medicine (CIRM), which share many political spectrum, and of all backgrounds and of those features, as do the rules adopted in other beliefs — have come to a consensus that we should states that have independently funded ESC research. pursue this research. That the potential it offers is Scientific organizations such as the National Academy great, and with proper guidelines and strict over- of Sciences (NAS) and the International Society for sight, the perils can be avoided.32 Stem Cell Research (ISSCR) have played an important role, and professional groups of doctors involved with The Obama policy did not, however, do away with all IVF, such as the American Society of Reproductive limits on federal funding. There would be no funding Medicine and the American College of Obstetrics and of derivation of cells or of ESCs derived from embryos Gynecology, have issued guidelines for some aspects of created for research purposes, by nuclear transfer or ESC donation. parthenogenesis, and no funding of research in which Because some regulation is needed to guide scientists ESCs or induced pluripotent cells are introduced into and reassure the public at large that science is not out of non-human primate blastocysts or involving animals control, it often falls to scientists themselves to develop in which ESCs may have contributed to the germ line. those rules.35 Indeed, professionals who see a looming In addition, federally funded research must comply threat of government regulation are usually quick to with regulations to assure donor voluntariness and preempt outside regulation with their own guidelines. understanding. Professional efforts are of course self-serving, and for The conclusion of the funding saga is that federal that reason may require close scrutiny. However, they funding will inject new resources and energy into stem may also provide some degree of normative certainty cell science. No funding is available for the destruction and signal to the public and lawmakers that scientists of human embryos or for research with lines derived are acting responsibly as they seek to go forward, even from embryos created for research purposes, but it may as funding and other issues are fought out. be provided for research on the hundreds of ESC lines The United States in 2003 was faced with a regu- created from leftover embryos since 2001 and which latory vacuum that could stifle the ESC science even will be created in the future.33 At least for a while the further than the lack of federal funds. The National Obama decision has thus removed stem cell research Academy of Sciences stepped into this breach with a from the national political debate. This will provide an committee to develop guidelines so that the field could important impetus to the field, and should spur much move forward despite the lack of federal support. 36 research and a quicker translation to clinical studies. That committee operated publicly, was not dominated Future controversies over Dickey-Wicker and funding by scientists, took input from many affected actors, research with cell-lines derived from embryos created and found a consensus on what was ethically accept- for research will still arise, but Obama has opened a able at that time and for the foreseeable future. new chapter in the stem cell wars. Such a move was important for the field to move forward. First, it assured the public and scientists that IV. Regulatory Issues there was an ethically acceptable framework for ESC Although federal funding of ESC research has been research, with attention to the rights of those donat- controversial, no controversy exists over the need for ing embryos and oversight of practices that were more regulation of ESC research. The federal common rule controversial. Second, it provided scientists, institu- applies to all institutions that receive federal research tions, states, and other countries a model to follow in funds, even if a particular research project occurring the research they conducted or sponsored. Third, it there has not been federally funded. But research on provided a sound basis both for private funding and ESCs may not itself qualify as research with “a human for donation by families of embryos and gametes for subject,” even though interactions with persons who ESC research. As a result, the NAS guidelines became provide the gametes or embryos may still require IRB the “industry standard” for both institutions and stem review.34 Also, IRBs may not be well-situated or have cell scientists.37 Of course, some may disagree with the expertise to handle the special ethical issues that particular portions, and other stem cell organizations arise in ESC research. may develop competing versions.38 Particular details A set of guidelines specifically for ESC research has become less important than the guidelines and over- emerged during this period. The Bush funding guide- sight that an authoritative set of professionally derived lines took main elements from those drafted by Clin- guidelines provide. The NAS now has a standing com- 196 journal of law, medicine & ethics  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License John A. Robertson mittee on ESC research to monitor the field and rec- the issue should be revisited with experience, which in ommend changes in guidelines.39 some states may not be easy to do. California and Mas- There is a wide degree of consensus about the sachusetts, two pro-ESC research states, also included main substantive elements of a regulatory approach. bans in payment to egg donors for research in their The cardinal principle here is the autonomy of the enabling legislation. gamete and embryo donor. No gametes or embryos The result of such a politically driven position is the should be donated for ESC research unless the person anomaly that human subjects in research generally is fully aware of all relevant aspects of the donation are paid as are egg donors to infertile couples, but not and makes the donation free of untoward influence or egg donors for research. This ban has created a bar- unacceptable inducement. With regard to informed rier to obtaining eggs for SCNT and creating embryos consent, for example, the donor must sign a written for research, and may need to be changed for the field consent form that states the following: that the dona- to progress. The ethics committees of the two main tion is voluntary; that the donor has been informed of professional organizations of physicians involved in alternative uses of embryos; what will happen to the stimulating ovaries and removing eggs have come embryos in derivation of ESCs; that the ESCs might out in favor of payment for donation for research on be maintained for years; that there is not restriction the same terms as paying for infertility donation. The on who might benefit from the donation; that there ISSCR guidelines leave it up to the law of the particu- will be no direct medical benefit to the donor; that the lar jurisdiction. The New York state board responsible research results may have commercial value in which for regulating this area has now concluded that pay- the donor will not share; and that information might ments of up to $10,000 may be made to egg donors be retained that could identify the donor’s identity.40 for research, which is comparable to the going rate in In cases where donor sperm or egg has been used to New York for infertility donors.44 It is likely that other create the embryo donated to research, Bernard Lo states will follow suit, and that payment to egg donors and others have argued that gamete donors should for research will eventually be permitted on a wider be informed that their gamete donation could lead to basis than now occurs. destructive ESC research.41 The emerging consensus about ESC regulation has To guard couples going through IVF against intru- also found common ground over the need for a special sion or pressure from their doctor, someone other review body beyond IRBs to review individual ESC than the doctor treating them must ask for consent projects because of the specialized nature of the sci- “whenever practicable.” No more stimulation should entific and ethical questions posed by ESC research. be imposed or eggs retrieved than they would want for The NAS guidelines were a key step in this direction. their own treatment. Also, they must make the deci- It called for the creation of a new institutional struc- sion to donate at the time they remove their embryos ture that gave a more expert and specialized review for storage, and cannot do so by advance directive. Nor than the familiar institutional review boards (IRBs) may any “inducements” be offered for the donation. in place to review human subjects research.45 The Persons might debate the need for particular ele- ESCs themselves were not persons, and the research ments of this regulatory regime, for example, why con- was not being done on the persons who provided the sent to embryo donation for ESC research should not gametes or embryos. Yet they would have ethical and occur at the time one creates the embryos or has them legal interests that needed protection that IRBS could frozen.42 The most significant area of disagreement, not provide. however, is whether a ban on inducements is justified To have the field adequately guided, some entity in in the case of women who donate eggs for research. addition to IRBS would be needed. This new entity Eggs are a scarce resource and a limit on the creation body was called an Embryonic Stem Cells Research of new ESC lines, whether by SCNT or for research Organizations (ESCROs).46 In addition to any required generally. Women who donate eggs undergo signifi- IRB review, an ESC researcher would also need cant bodily intrusion and deserve to be paid for their ESCRO approval to proceed with ESC research. While efforts. Indeed, there is a well-developed system for some persons have argued that another layer of review paying egg donors for infertility services. Logically, in addition to an IRB is costly and delaying, the argu- it should be extended to paying donors for eggs to be ment for them was the need to assure that there was used in research as well, yet there is great resistance adequate expertise about the ESC research and the to doing so.43 The NAS in 2005 took a cautious posi- special ethical problems which it posed, which an IRB tion and recommended against any payments beyond might lack. It would also assure the public that careful transportation expenses without argument or analysis review of ESC research was occurring. The idea quickly of why that position was chosen. But it did state that caught on in most places doing ESC research and in the law, science, and innovation: the embryonic stem cell controversy summer 2010 197  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SYMPO SIUM state and professional guidelines, e.g., ISSCR. Surpris- V. Translation into the Clinic ingly, the Obama regulations for ESC research do not The ESC research field has been marked by often require it. However, most institutions receiving federal extravagant claims about the likely curative power ESC research funds may still require it. of ESC research (also by claims by opponents about A final area of regulatory concern has been the cre- the curative power of adult stem cells, which are not ation of human-nonhuman chimeras to test the safety as pluripotent as ESCs). Theoretically, ESC research of ESC differentiation and proliferation. Neurologic could lead to treatment or cures for diabetes, cancer, researchers have been prominent in using such models heart disease, spinal cord injuries, macular degen- because of the difficulty of testing in patients the safety eration, and neurodegenerative diseases such as Par- of ESC-derived progenitor cells for treating spinal cord kinson’s and Alzheimer’s. But we are a long way from injuries, Parkinson’s disease, and other central nervous doing so. Getting there will require “translation” of system disorders in humans. While objections against ESC research into clinical research and eventually any interspecies mixing are easily overcome (think pig clinical medicine. The translation process poses its sources for insulin and heart valves), the more nagging own set of ethical and regulatory issues. question is the fear that nonhuman animals will have As with other regulatory issues for ESC research, human brains and related mental capacities ordinarily much work has been done by ethicists on the ethical found in humans, thus raising knotty questions about principles that should guide translational research. In their moral status. Do they then deserve the rights and some respects the ethical challenge is no different than respect accorded human subjects? How many cells with other new therapies. It is essential that random- must be infused to give them some human standing? ized clinical trials be held so that the safety and effi- How can one measure the presence of the characteris- cacy of treatments can be established. Clear outcome tics that confer moral status? The NAS took the posi- measures of improvement, such as survival, disease- tion that infusing hESCs into nonhumans at any stage free survival, or improvements in objective measures of development requires ESCRO and animal care of disease-related function, are needed to determine committee review. They specifically prohibit the trans- whether there is evidence to change prevailing medi- fer of hESCs to nonhuman primate blastocysts, but cal practice, as well as justify the imposition of the they do not prohibit transferring them into primate risks on research subjects. In some cases, such as Par- fetuses or primates at later stages of development or kinson’s and other neurologic diseases, defining and into other large mammals at the embryonic stage.47 In testing for benefit may be difficult.49 addition they prohibit any breeding of animals into Generally, participants in a clinical trial should which hESCs have been introduced. Later revisions of receive all interventions that are known to be safe, the guidelines cure some of these problems, but there effective, and commonly prescribed by physicians.50 is still room for improvement.48 Working out the rules Yet trials should also be designed in a way that will for human-nonhuman chimeric research will require provide reliable information from the study. Usually more debate than has yet occurred. this will mean some form of a randomized trial, often The 10-year battle over ESC research has thus with the placebo as a control for the new therapy. To yielded a wide consensus on the need to protect the ensure that patients get established therapy, the inves- interests and autonomy of those being asked to con- tigational agent can be given as an “add on,” with half tribute gametes or embryos for ESC research. Special of subjects getting the new therapy in addition to the committees to oversee the protection of donor inter- old and half getting a placebo.51 est and the need for the research add an additional Doing clinical research with ESCs poses additional layer of protection. The consensus about regulation is safety challenges because ESCs are cellular products a further sign of the ethical and legal infrastructure which are more difficult to manufacture and purify in a that is now in place for further developments in ESC standard way than the small molecule drugs produced science. A remaining problem, however, is the lack of by pharmaceutical companies. As an ethics advisory one central regulatory body. With so many jurisdic- group at Johns Hopkins noted: tions and advisory bodies having weighed in on the topic, there is a risk of redundancy and confusion, [ T]he manufacture of a drug or device and the with some ESC research receiving multiple reviews. generation, growth, and maintenance of a cell line For example, ESC lines established in one jurisdiction are quite different processes. While new drugs may have to undergo another ethical review if those used in U.S. clinical trials must meet rigorous FDA lines are used in an institution in another jurisdiction. standards for production, the process of deriving Ways to minimize the multiplicity of review will have cell lines does not map neatly to concepts of good to be devised. manufacturing practices. For example, hESCs 198 journal of law, medicine & ethics  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License John A. Robertson are derived following fertilization (involving cells involved at each step along the translational research of varying genetic make-up), manipulation and process. Other commentators, such as Bernard Lo, destruction of the blastocyst, and subsequent cell stress the importance of integrated scientific and eth- culture, all of which have less predictability than ics review. This will require coordination among the combining precise quantities of known chemical several oversight bodies that have some say in whether products.52 research should go forward — IRBs, SCROs, the FDA, A major problem for researchers, IRBs, and other oversight bodies in translational research is to ensure voluntary informed consent. Patients who desperately want a cure or improvement may jump at the chance to take part in a new study, especially one with the sexy cachet of “stem cell.” The problems here are familiar ones, but the political and scientific stakes are likely to be higher because of the great interest in stem cells generally. Stem cells pose additional risks because they are and national level review bodies. Since SCROs have often grown in culture for some time before differenti- been constituted primarily to review the ethical issues ated to produce the progenitor cells that may then be peculiar to stem cell research, such as the derivation of infused into a patient in a clinical trial. As the Hopkins ESCs and donation of gametes and embryos, they may group noted, “The longer cells are grown in culture, the not have the scientific expertise to review the scientific more likely they are to acquire genetic and epigenetic and design aspects of clinical trials. Lo suggests that changes, such that later passages may not be geneti- an integrated scientific and ethical review such as that cally identical to earlier passages.”53 Some stem cell conducted by the Recombinant DNA Advisory Com- preparations may lack immunogenicity while others mittee (RAC) for gene transfer research be followed not. Systematic assessment of integrity and potency here as well.55 of cell products is essential for minimizing risks to A major problem for researchers, IRBs, and other patients, but it is unclear what tests will serve this pur- oversight bodies in translational research is to ensure pose (e.g., DNA sequencing, expression analysis) and voluntary informed consent. Patients who desperately provide meaningful data about risks to researchers, want a cure or improvement may jump at the chance human subjects, and review committees.54 The risk of to take part in a new study, especially one with the sexy transferring the cell donor’s own genetic disease must cachet of “stem cell.”56 The problems here are familiar also be considered. ones, but the political and scientific stakes are likely Rigorous preclinical testing in animal models to be higher because of the great interest in stem cells whenever possible is especially important because generally. The science is complex, the risk of therapeu- stem cells can act through multiple mechanisms. Yet tic misconception is high, and the patient’s condition, animal models may not exist for many diseases sought especially in neurologic research may be grave. Con- to be treated with ESCs or may not be comparable in sider what must be done to make sure that the subject important ways. Take central nervous system disor- understands that the risks “include sensitivities sur- ders — from spinal cord injuries to Parkinson’s dis- rounding the source of cellular products, tumor forma- ease and Alzheimer’s. Pharmacologic agents that have tion, immunological reactions, unexpected behavior shown promise in nonhuman animal models of stroke, of the cells, and unknown long-term health effects.”57 for example, have not been successful in humans. The Subjects must also be educated about the realistic predictive utility of animal models for human diseases potential for therapeutic benefit so that they may is often unknown even when risks, such as tumorge- have recourse to reasonable therapeutic alternatives. nicity and the need for immunosuppression, can be If there are not alternatives, they may harbor mis- evaluated in nonhuman animal models. conceptions about the potential for therapeutic effect These limitations on animal studies show the impor- (“the therapeutic misconception”).58 Given the com- tance of expertly qualified oversight bodies for assessing plex issues involved, formalized methods of assessing preclinical data. The ISSCR has emphasized the need understanding, such as interviews, questionnaires, or for individuals with stem-cell-specific expertise to be law, science, and innovation: the embryonic stem cell controversy summer 2010 199  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SYMPO SIUM consent monitors, may be needed.59 A long and time- steam of the debate should lessen. The problems fac- consuming consent process seems inevitable. ing researchers and clinicians will then be the standard The selection of subjects for early stem cell trials ones of context-driven risks, benefits, alternatives, and must also be ethically defensible. It is now standard showing whether new interventions work or not. to use the sickest patients for Phase I safety studies because they are not as likely to be harmed as less sick VI. Future Issues patients. Yet they are more likely to be prey to the ther- This survey of the ethical, legal, funding, regulatory, and apeutic misconception and least able to give a valid translational landscape shows that we have made great informed consent. On the other hand, they may not progress during the last decade in coming to terms be as appropriate for Phase II studies because they are with the issues that this novel research platform raises. the least likely to benefit, which could lead to the false Despite the ethical debate and controversies that have conclusion that the intervention provides no benefit roiled the field, the science has made much progress, when it might work in healthier patients. Oversight though it undoubtedly has been slowed by the reluc- bodies must also consider when it is acceptable to tance in the United States to fund research with new include children in early human trials. cell lines. With the ethical and legal landscape now well Risks to research participants should be further defined, the field is poised to move forward at a more minimized through careful patient-subject monitoring rapid pace. The hard work will be doing the science so and timely adverse event reporting. Subjects’ health is that the nature of stem cells and their differentiation is of utmost importance and should be carefully moni- better understood and the clinical safety and efficacy of tored throughout the clinical trial. A data monitoring treatments derived from them is established. plan with aggregate updates to peer review commit- New challenges will arise as ESC-based treatments tees should be required. A commitment to publica- are tested on a wider basis and come to be accepted as tion of both positive and negative results and adverse safe and effective treatments for many medical situa- events is needed to prevent others from being sub- tions. A major challenge will be to ensure that they are jected to unnecessary risk in future clinical research available to patients of all means. This is a question and to ensure the development of clinically effective of the payment system for health care. Persons with stem-cell based therapies.60 means may be able to obtain experimental treatments Questions will also arise about providing innova- before others. But if ESC-based treatments are shown tive therapy outside of the context of a formal clinical to be safe and effective, then they will be part of ordi- trial 61 The ISSCR guidelines recognize that there may nary care and covered to the same extent and with the be exceptional circumstances that allow clinicians to same limitations as are other treatments. There will be attempt medically innovative care in a very small num- nothing here to distinguish ESC therapies from other ber of seriously ill patients, subject to the stringent treatments. Indeed, for many indications, they may oversight of others. These criteria include indepen- have significant cost advantages. They will be available dent peer review of the proposed innovative procedure to persons who have health insurance or who qualify and its scientific rationale, institutional accountability, for Medicare or Medicaid or other public health pro- rigorous informed consent and close patient monitor- grams to the extent that they are seen as standard ing, transparency, timely adverse-event reporting, and therapy for particular conditions.62 a commitment to move to a formal clinical trial after Another issue will be to respect the views of persons experience with at most a few patients. Many clinics who morally object to destroying embryos in research that tout stem cell therapies for a profit in Eastern or using them in treatment. Strict right-to-lifers may Europe and Asia would not meet those standards. object to receiving treatments using ESCs or their While the general principles for ethical translational derivatives. ESC-derived treatments should be labeled research are known, the specifics can be resolved only as such so that persons with conscientious objections in specific clinical contexts, which include the underly- to their use may decline them for themselves. It would ing disease, alternatives therapies for it, the site where not follow, however, that they should have a legal right stem cells are injected, the amount and purity of cells, to decline them for minor children or incompetent per- and the intended function of the transplanted cells. sons over whom they have decisional authority because The resolution of these issues for Parkinson’s disease the best interests of those patients would take prior- will differ from other neurologic conditions, which ity. Limits will also need to be set on the right of doc- will differ in turn from treatments for macular degen- tors, nurses, and other health care providers to refuse eration, diabetes, heart disease, and the many other to deliver or participate in treatments because they conditions for which stem cell interventions may be involve ESCs or have been derived from them. Some tried. As translation issues come to the fore, the ethical treatments may be so far removed from direct use of 200 journal of law, medicine & ethics  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License John A. Robertson stem cells that their right of refusal does not come into lessen the need for female donors and the controversy play. In other cases the obligations as doctors, nurses, over paying women to produce eggs for research. The and health care providers must give way to the needs ethical concern is that pluripotent cell-derived gam- of patients dependent on their services. This conflict is etes would then be used for in vitro reproduction, not unique to stem cells. Rules developed for objection either with male or female gametes provided by one’s to participation in abortion will have to be adapted to partner or or with both sets of gametes derived from deal with objections to use of stem cells as well.63 the somatic cells used to derive germ cells. Persons who Finally, we should consider the issues that will arise lack gametes due to chemotherapy, disease, or trauma if non-embryonic sources of pluripotent cells become might welcome the availability of gametes derived available. The experience to date with induced pluripo- from their own somatic tissue. In addition to signifi- tent stem cells (iPS) is very promising. Shinya Yamanaka cant concerns about the health of resulting children, and then Thomson have discovered ways to reprogram such a practice would raise kinship and family issues somatic cells to a primordial state and then redifferenti- as daunting as any that have arisen in assisted repro- ate them to tissues of choice.64 Initally done with viral vec- duction.68 Somatic cell donors would be the biologic tors that carry their own risks, progress has been made in parent of such offspring, and in some cases could be using non-viral factors to recreate stemness. Much work the genetic father and mother of the child. These ques- is needed to show that they have the same characteristics tions take us outside of stem cell research and therapy as embryonic sources of pluripotent cells and will work into the outer reaches of human reproduction. They as well in therapy. Because of the need to compare them are a vivid preview of issues to come from progress in to ESCs, they will not supplant them for some time, if perfecting the ability to induce gametes from induced they ever do. But if they do become as safe and effective, pluripotent stem cells or from ESCs themselves. it will remove a major source of conflict from cell repro- gramming and regeneration therapies. VII. Ethical Conflict and the Pace of It is important to note, as Yamanaka does, that Innovation though iPS technology has enormous potential, it This survey of the main ethical conflicts that have shaped is still at its infancy, and certainly does not do away the field of ESC research show that ethics and law can with the need for ESCs.65 Patient or disease-specific have a major impact on the pace of a science. Science iPS cells should provide unprecedented cell sources does not happen in a vacuum, but is embedded in the soil for better understanding the pathogenesis of diseases of the societies in which it occurs. The ESC experience and for developing safer and more effective drugs, shows how important law and ethics are at early stages and may even one day make it possible to perform cell of a science, and how they can encourage, facilitate, or transplantation therapies for a wide variety of diseases retard the development of new science and technology. and injuries, while circumventing ethical issues and In some cases, ethical roadblocks can lead to “inventing” immune rejection. But that day is not yet here. To real- around them, a frequent practice when existing patents ize the clinical applications, he emphasizes the need block a firm’s forward path. Opponents of ESC research have argued that the Bush restrictions on federal research t o achieve complete and uniform reprogramming funding led directly to the emergence of iPS cells and the in iPS cells. Failure to do this would result in resis- opportunities which they offer. tance to differentiation and increase the risk of After 10 years of debate and controversy with ESCs, teratoma formation. The stochastic model predicts the ethical issues have now been thoroughly aired that iPS cells can be generated from a variety of and the path is open to rapid development. Ethical somatic cells with a variety of methods. We have issues will remain, but they are the issues that arise in to evaluate different original cells and induction bringing any new discovery out of the lab into clinical methods to determine the best combination to research and then clinical use. Differing perceptions allow us to generate the safest iPS cells for clinical of the moral status of the early embryo will still be application.66 important, but they appear no longer to be the major stumbling block that they have been. One can be more iPS cells will raise their own unique ethical issues. Of optimistic than earlier that the long-awaited payoffs particular concern would be the ability to derive human from ESC discoveries may eventually come to pass. gametes from them, as appears possible with human ESCs.67 Such a feat might lead to easy production of the eggs needed to carry out some important forms of ESC research, such as SCNT or tailoring the stem cell line sought to a particular genotype. If so, this would law, science, and innovation: the embryonic stem cell controversy summer 2010 201  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License SYMPO SIUM 14. J. A. Robertson, “Assisting Reproduction, Choosing Genes, and References the Scope of Reproductive Freedom,” George Washington Law 1. The FDA has also approved Phase I stem cell clinical trials Review 76, no. 6 (2008): 1490-1513. for Batten Disease and Pelizaeus-Merzbacher Disease, which 15. Id. are much rarer than spinal cord injury. B. Lo, “Case-Based 16. J. A. Robertson, “Embryo Culture and the Culture of Life: Con- Reasoning in Stem Cell Clinical Trials: The Case of Parkin- stitutional Issues in the Embryonic Stem Cell Debate,” Univer- son’s Disease,” Journal of Law Medicine & Ethics 38, no. 2 sity of Chicago Legal Forum 2006 (2006): 1-40, at 31-38. (2010). Since approving Geron’s clinical trial, the FDA has 17. Id. A relevant case here is Turner Broadcasting, Inc. v. FCC, 512 put the study on hold pending more data on cyst formation U.S. 662 (1994) (more than minimal rational basis required and immunosuppression in the animal studies used to support for First Amendment restriction). Geron’s application. P. F. Dimond, “Special Report, Geron’s 18. Abigail Alliance for Better Access to Developmental Drugs and Setback with Testing Its hESC Therapy in Humans Points to Washington Legal Foundation v. Eschenbach, 445 F.3rd 470 FDA’s Continued Cautionary Stance,” August 28, 2009, avail- (D.C. Cir. 2006); reversed en banc, 495 F.3d 695 (C.A.D.C. able at (last visited April 7, 2010). 19. The EAB recommended that IVF research go forward and then 2. J. A. Thomson et al., “Embryonic Stem Cell Lines Derived no embryo research occur without EAB approval. R. M. Green, from Human Blastocysts,” Science 282, no. 5391 (1998): 1145- Political Interventions in U.S. Human Embryo Research: An 1147; M. J. Shamblott et al., “Derivation of Pluripotent Stem Ethical Assessment,” Journal of Law, Medicine & Ethicis 38, Cells from Cultured Human Primordial Germ Cells,” Proceed- no. 2 (2010). ings of the National Academy of Sciences of the United States 20. President Clinton immediately said he would not permit fund- of America 95, no. 23 (1998): 13726-13731. ing of research embryos. See Green, id. 3. This is a conflict over the methods used to obtain the cells 21. The first version of it was Pub. L. No. 104-99, 110 Stat. 26 used in research. Concerns about research methods, however, (1996). For later cites, see President’s Bioethics Council, Moni- can arise at any stage of a science. Research methods can be toring Stem Cell Research, 2004, at note 8, page 49. directly harmful, as with the release of toxic agents or microbes 22. See H. Raab, Memorandum to Harold Varmus, M.D., Director, into the biosphere. Or they could use animals in cruel ways NIH, Federal Funding for Research Involving Human Pluripo- or human subjects without consent. The creation of chimeras tent Stem Cells, January 15, 1999. may also be contentious. See infra note 47. 23. L. Guenin has argued that ESC research is research in which 4. Debates over embryo status and ESC research are compli- embryos are destroyed because it is necessary to destroy them cated further by their connection with cloning, assisted repro- to get the ESCs, but has failed to convince lawmakers of his duction, and other technologies at the beginning of life. The position. L. M. Guenin, The Morality of Embryo Use (New announcement of lab culture of human ESCs came a year after York: Cambridge University Press, 2008); L. M. Guenin, Ian Wilmut’s announcement of nuclear transfer cloning of a “A Proposed Stem Cell Research Policy,” Stem Cells 23, no. sheep had roiled the world with the possibility of reproductive 8 (2005): 1023-1027. If the Dickey-Wicker rider had said cloning and genetic control over progeny. Somatic cell nuclear “research involving embryos,” there might have been a differ- transfer (SCNT) cloning has been thought necessary to gen- ent outcome. erate ESCs with particular genomes to model disease and to 24. National Institutes of Health Guidelines for Research Involv- produce histocompatible replacement tissue, and has played a ing Human Pluripotent Stem Cells, Federal Register 65 central role in ESC policy debates. (August 25, 2000): 51975-51981. The National Bioethics Advi- 5. R. P. George and C. Tollefsen, Embryo: A Defense of Human sory Commission, Ethical Issues in Human Stem Cell Research Life (New York: Doubleday, 2008). (Rockville, MD: U.S. Government Printing Office, 1999). 6. For an analysis of this issue, See D. W. Brock, “Creating 25. Remarks by President George W. Bush on Stem Cell Research, Embryos for Use in Stem Cell Research,” Journal of Law, Med- August 9, 2001, reprinted in President’s Bioethics Council, icine & Ethics 38, no. 2 (2010). Monitoring Stem Cell Research, Appendix B, 181-185, 2004. 7. Efforts at state constitutional amendments or legislation pro- 26. His administration claimed that more than 60 lines fit that tecting all fertilized eggs and embryos have usually failed. In bill, but in time only between 15-20 lines were available. Some Colorado such an amendment made it to the ballot but failed. could not be verified. Some had onerous licensing restrictions, See Amendment 48 (2008), available at (last visited April 8, 2010). trial with ESC therapy. 8. Gallup Poll, “Six in 10 Americans Favor Easing Restrictions on 27. Germany also used a cut-off time. ESC lines cannot be legally Stem Cell Research,” 2007, available at (last visited April 8, 2010). January 1, 2002. See J. A. Robertson, “Assisted Reproduction 9. Sometimes they distinguish research embryos created by in Germany and the United States: An Essay in Comparative fertilization from those created by SCNT. In Massachusetts Bioethics,” Columbia Journal of Transnational Law 43, no. 1 and Missouri, for example, it is illegal to create embryos for (2004): 189-227, at 212. See also J. A. Robertson, “Causative research by fertilization but not by SCNT. vs. Beneficial Complicity in the Embryonic Stem Cell Debate,” 10. I have argued that the difference is a symbolic one – the line Connecticut Law Review 36, no. 4 (2004): 1099-1113 (argu- is a place to symbolize or mark a person’s firm commitment ing that Bush’s complicity standard would also support federal to respect for human life. The benefits of that symbolic posi- funding of those lines that had been derived in the private sec- tion, however, should be weighed against the loss in knowledge tor after the Bush announcement). that results by not having this method of obtaining embryos for 28. This required separate equipment, accounting, and even build- research available. J. A. Robertson, “Symbolic Issues in Embryo ings for use of cell lines outside the Bush cut-off. If frozen embryos Research,” Hastings Center Report 25, no. 1 (1995): 37-38. being stored for use to derive new lines in a separate facility had 11. J. A. Robertson, “Embryo Culture and the Culture of Life: a freezer shutdown, they could not switch them to the federally Constitutional Issues in the Embryonic Stem Cell Debate,” funded freezer without disqualifying any embryos there stored. University of Chicago Legal Forum 2006 (2006): 1-40. 29. The Director of the NIH actually testified before Congress that 12. 410 U.S. 113 (1973). the Bush administration funding policy was hurting the progress 13. 505 U.S. 833 (1992). of ESC science. R. Weiss, “Stem Cell Policy Hampering Research, NIH Official Reports,” Washington Post, January 20, 2007. 202 journal of law, medicine & ethics  1748720x, 2010, 2, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1748-720X.2010.00479.x by University Of Toledo, Wiley Online Library on [20/09/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License John A. Robertson 30. See note 31 for an account of Prop 71. New Jersey, Illinois, tion for Stem Cell Research,” Science 308, no. 5729 (2005): Wisconsin, Maryland, and New York also made significant 1747-1748. commitments, though none as great at that of California. 46. See NAS Guidelines, supra note 36, at 100. 31. R. Korobkin, “Embryonic Histrionics: A Critical Evaluation 47. See Cohen and Majumder, supra note 42, at 91. of the Bush Stem Cell Funding Policy and the Congressional 48. Id. The Obama guidelines also deny funding for such research. Alternative,” Jurimetrics 47, no. 1 (2006): 1-29. See Federal Register 74 (2009): 32170-32175, at 32175 (“Chi- 32. President Barack Obama, “Removing Barriers to Responsible mera ban”). Scientific Research Involving Human Stem Cells,” Execu- 49. See Lo, supra note 1; B. Lo, A. Kriegstein, and D. Grady, tive Order No. 13,505, Federal Register 74 (March 11, 2009): “Clinical Trials in Stem Cell Transplantation: Guidelines for 10667-10668. Scientific and Ethical Review,” Clinical Trials 5, no. 5 (2008): 33. Those lines will still have to meet the strict standards for con- 517-522. sent of donors, including their consent to use in the particular 50. Id. (Lo). kind of research in which they will be used. While this will 51. Special problems may arise here that require sham surgery, so disqualify some lines from federal funding, enough other lines that all patients will think that they are getting the new ther- have been created to meet the needs of researchers. See Federal apy. See Lo, supra note 49. Register 74 (July 7, 2009): 32170-32175; Editorial, “Consent 52. D. J. H. Mathews et al., “Cell-Based Interventions for Neuro- Issue Dogs Stem Cell Approval,” Nature 462, no. 7275 (Decem- logic Conditions,” Neurology 71, no. 4 (2008): 288-293. ber 17, 2009): 837 (embryos donated for diabetes research may 53. Id. not be used for other purposes). 54. ISSCR 608 commentary. 34. 45 CFR 46.101 et seq. 55. See Lo, supra note 49. 35. This was the classic case with the Berg letter that led to Asi- 56. T he willingness to travel abroad to uncertified clinics for lomar and the NIH’s Recombinant DNA rules. P. Berg et al., untested but highly touted and expensive treatments is an Letter, “Potential Biohazards of Recombinant DNA Molecules,” example of the ease with which consent can be obtained. See Science 185, no. 4148 (1974): 303. Hyun, infra note 61. 36. National Research Council, “Guidelines for Human Embry- 57. International Society for Stem Cell Research, Guidelines for onic Stem Cell Research,” 2005, available at (last visited April 8, 2010) 58. See discussion of therapeutic misconception in D. Magnus, [hereinafter “NAS Guidelines”]. “Translating Stem Cell Research: Challenges at the Research 37. Critics may question whether such guidelines have enough Frontier,” Journal of Law, Medicine & Ethics 38, no. 2 (2010). bite to get the job done. Sometimes professionally developed 59. The Johns Hopkins group argues that researcher and over- guidelines are window-dressing. But this does not appear to sight bodies should ensure that the consent process is above be the case with the NAS stem cell rules. With the ESC field reproach, and that it provides few opportunities for even mis- so eager to move forward and the source so authoritative (the guided criticism because of the sensitivity and political ramifi- NAS is not merely another professional interest group), they cations of ESC research. See Mathews et al., supra note 51, at have earned widespread respect and support. 291. 38. T he guidelines of the International Society of Stem Cell 60. Bernard Lo and Jeremy Sugarman also make these points. See Researchers (ISSCR) overlap substantially with those of the Lo, supra note 49 and J. Sugarman, “Reflections on Gover- NAS, but there are differences. Some ISSCR members have nance Models for the Clinical Translation of Stem Cells,” Jour- pointed out that the NAS guidelines were drafted without nal of Law, Medicine & Ethics 38, no. 2 (2010). international representation: “To hold that the U.S. guidelines 61. Several papers in this symposium address the issue of innova- can simply be lifted and imported to other international set- tive therapy. See I. Hyun, “Allowing Innovative Stem Cell-Based tings ignores the differing political, cultural, and religious per- Therapies Outside of Clinical Trials: Ethical and Policy Chal- spectives that shape research policy.” I. Hyun, P. Taylor, and G. lenges,” Journal of Law, Medicine & Ethics 38, no. 2 (2010) Q. Daley, “Letter,” San Jose Mercury News, February 8, 2007. (page numbers coming); P. L. Taylor, “Overseeing Innovative 39. Human Embryonic Stem Cell Research Advisory Commit- Therapy Without Mistaking It for Research: A Function-Based tee, National Research Council, 2007 Amendments to the Model Based on Old Truths, New Capacities, and Lessons National Academies’ Guidelines for Human Embryonic Stem from Stem Cells,” Journal of Law, Medicine & Ethics 38, no. 2 Cell Research, 2007. The changes to the guidelines involved (2010). clarifying the phrase “provenance of the cell lines” (changes 62. I do not mean to underestimate the problems that even people to Section 1.2); use of the hESCs approved for use in feder- with insurance have in getting standard care. Some of those ally funded research (addition to Section 1.4); importation of same problems could prevent access to stem cell therapies just hESC lines into an institution or jurisdiction (addition of Sec- as they do to other treatments. tion 1.5); and allowing ESCRO committees to serve multiple 63. Department of Health and Human Services, “Ensuring that institutions (changes to Section 2.0 and addition of Section Department of Health and Human Services Funds Do Not 2.1). Id., at 3-4. Support Coercive or Discriminatory Policies or Practices in 40. Department of Health and Human Services, “National Insti- Violation of Federal Law; Final Rule,” Federal Register 73, no. tutes of Health Guidelines for Human Stem Cell Research,” 425 (December 19, 2008): 78072-78101, CFR version at 45 Federal Register 74, no. 128 (July 7, 2009): 321470. CFR 88. 41. B. Lo, L. Parham, and M. Cedars et al., “NIH Guidelines for 64. K. Takahashi and S. Yamanaka, “Induction of Pluripotent Stem Cell Research and Gamete Donors,” Science 327, no. 5968 Stem Cells from Mouse Embryonic and Adult Fibroblast Cul- (February 19, 2010): 962-963. tures by Defined Factors,” Cell 126, no. 4 (2006): 663-676; J. 42. C. B. Cohen and M. A. Majumder, “Future Directions for Over- Gearhardt, E. Pashos, and M. Prasad, “Pluripotentcy Redux sight of Stem Cell Research in the United States,” Kennedy – Advances in Stem-Cell Research,” New England Journal of Institute of Ethics Journal 19, no. 1 (2009): 79-103. Medicine 357, no. 15 (2007): 69-72; J. Shaw, “Tools and Tests: 43. J. A. Robertson, “Compensation and Egg Donation for The Evolution of Stem-Cell Research,” Harvard Magazine 112, Research,” Fertility and Sterility 86, no. 6 (2006): 1573-1575. no. 3 (January-February 2010): 24-29. 44. Statement of the Empire State Stem Cell Board on the Compen- 65. S. Yamanaka, “Elite and Stochastic Models for Induced Pluripo- sation of Oocyte Donors, June 11, 2009. L. Nelson, “New York tent Stem Cell Generation,” Nature 460, no. 7251 (2009): 49-52. State Allows Compensation in Egg Donations for Research,” 66. Id., at 51. New York Times, June 26, 2009, at A18. 67. See references listed in Cohen and Majumder, supra note 42, 45. Strictly speaking the research occurring was not “research with at 94-95. a human subject” under the HHS guidelines. 45 CFR 46.101 et 68. Id. seq. See also M. Cho and D. Magnus, “Issues in Oocyte Dona- law, science, and innovation: the embryonic stem cell controversy summer 2010 203