Stem Cells: Ethics, Law and Politics

20 Biotechnology Law Report 678 Number 5 (October 2001) Mary Ann Liebert, Inc.

Stem Cells: Ethics, Law and Politics ALEXANDER MORGAN CAPRON*

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ver the past three years, human stem cells have moved from being something of esoteric interest for basic researchers and of therapeutic value for clinicians to being a highly visible source of distress in the relationship between right-to-life advocates and their traditional political allies. In recent decades, countless biomedical developments have become entangled in—and disrupted or even derailed by—the fallout from abortion-related political debates. For a while, human stem cell research seemed to be headed for the same fate. But for once the reverse appears to be true, for in this case, science has disrupted politics rather than the other way around: during the spring and summer of 2001, some prominent Republican right-to-life loyalists publicly urged federal funding of research with human embryonic stem cells, even as others warned President George W. Bush that such funding would make him complicit in “an industry of death.”1 Finally, on August 9, in his first televised address to the nation since becoming President, Mr. Bush announced a compromise that allowed him to keep to the letter of a campaign pledge not to finance the destruction of live embryos while also providing some opportunity for federally funded researchers to use human embryonic stem cells.2 It is too soon to know whether the compromise will work in scientific terms, much less whether it will provide the results that the President sought politically, but the importance of the field now seems firmly established in the mind of the public. This article examines the scientific aspects of the field and how the science came to be entangled with politics (with a look at the policy options that were before the President and that remain before Congress), the ethical debate (which is almost certainly not been resolved *University Professor of Law and Medicine, University of Southern California.

by the President’s decision), and the resulting legal problems (which have their own complexities). Stem cells have only recently entered public consciousness but—media commentaries notwithstanding—they are nothing new to scientists and physicians. Stem cells have long been understood (as their name implies) as the foundation of organisms, the stalk from which everything buds and branches. In developmental terms, the first cells of a new organism are totipotent, that is, each one has the ability to develop into an entire organism—indeed, when the cells of a two-celled zygote separate, identical twins are produced. After several days of cell division, the next developmental step is these cells to begin differentiation. Some will form the trophoblast and placental layers that will support the growing fetus; these cells form into the outside of the blastocyst, a hollow sphere, like a tiny beach ball, that will become attached and take sustenance from the lining of the uterus. The remaining stem cells—those clumped together inside the blastocyst, which are known as the inner cell mass—become the basis for the fetus itself. The latter cells are pluripotent; this means that they no longer possess a totipotent cell’s ability to become an entire organism but they are able to develop into the more than 200 cell types present in a mature organism. In the words of Caltech biology professor David Anderson, “They are infant cells that have not yet chosen a profession.”3 Under stim1 David

Boyer, Stem cell research divides the GOP; Centrists, leaders try to sway Bush, WASHINGTON TIMES, July 4, 2001, at A6 (quoting letter to President Bush from Reps. Dick Armey [House majority leader], Tom DeLay [House majority whip], and J.C. Watts, Jr. [House Republican Conference chairman]). 2 Frank Bruni, Bush Gives His Backing for Limited Research on Existing Stem Cells, N.Y. TIMES , Aug. 10, 2001, at A1, col. 1. 3 David J. Anderson, The Alchemy of Stem Cell Research, N.Y. TIMES , July 15, 2001, Sec.4, p. 15.

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uli that are not yet fully understood, these cells differentiate in an unfolding process which, when it operates according to plan, produces a viable, healthy organism made up of many distinct types of cells. For example, some of the pluripotent stem cells become neural stem cells, which then produce the variety of cells that make up the neurological system. As Professor Anderson puts it, the tissuespecific stem cells “even though not yet adult, are like young professionals already embarked on a career: they still have options, but fewer of them.”4 Until recently, this process has been thought of as unidirectional, with each pluripotent cell establishing a line of daughter cells destined to a particular “fate” (as bone, blood, muscle, skin, and the like), like the members of a family in feudal society, destined to do the work of smiths or bakers generation after generation. Among the differentiated cells that make up mature organisms are some stem cells associated with each particular tissue or organ—skin stem cells, blood stem cells, and so forth. These cells are important for continuous tissue homeostasis (e.g., maintaining the skin and blood) and for the normal repair processes of adult organisms. Physicians have long exploited this regenerative capacity, for example, in using bone marrow transplants (which contain stromal cells and hematopoietic stem cells) to repopulate the cells in the blood and immune system following irradiation of patients with neoplastic disease.5 Stems cells became matters of intense scientific and public interest when, in November 1998, researchers at the University of Wisconsin announced success in deriving and culturing human embryonic stem cells, just as Johns Hopkins University scientists published their success with embryonic germ cells. The cell lines established by these research groups from the inner cell mass of days-old blastocysts and from the gonadal ridge of five-to-nine week-old aborted fetuses, respectively, are both pluripotent (having the capacity to give rise to all types of cells) and stably self-replicating (perpetuating themselves indefinitely in culture without either mutating or progressing into different cell fates). The creation of these cell lines represents a substantial step towards generating a renewable source of stem cells for research, and, in the future, for clinical treatment. Without lines of cultured pluripotent cells, prospects for research and therapy using stem cells are severely hampered by having repeatedly to harvest stem cells from embryos. Yet

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the public’s great interest in these cells has not arisen solely because scientists have proclaimed them research tools of unparalleled value and the basis for the emerging field of “regenerative medicine.” What has made embryonic stem cells matters of intense interest is that to derive them scientists must destroy early-stage embryos or harvest tissue from aborted fetuses, two processes that stir up intense opposition in certain quarters. I. STEM CELLS AND POLITICS Based on the clash between moral objections to destroying potential human life and biomedical researchers’ interest in human stem cells’ possible value as tools in embryological and pharmacological research and clinicians’ hopes for their therapeutic potential, particularly in organ and tissue transplantation, research with these cells has moved to the front page of the paper and the top of the evening news, as scientists, politicians, lawyers, theologians, and members of the general public6 debate how—and even whether—they should be derived and used. The political battle over stem cell research has received a tremendous amount of news coverage.7 The issue before the President was whether to reject or modify rules adopted in 2000 by NIH, but suspended by HHS Secretary Tommy Thompson in April 2001, under which federal funds could be spent on research using stem cells derived from human embryos and aborted fetuses by private laboratories which followed specified ethical safeguards. Whereas President Bush’s usual “CEO style” of delegation would mean that such a decision would be left to Secretary Thompson, it was taken into the White House. Spokesmen kept the public informed about how deeply the President was 4

Id. Eugene H. Kaji & Jeffrey M. Leiden, Gene and Stem Cell Therapies, 285 JAMA 545, 545–550 (2001). 6 See Stem Cell Research Compromise Misguided, LOS ANGE LES TIMES, July 10, 2001, at Part 2 Page 10. See also Letters to The Editor, SAN FRANCISCO CHRONICLE, July 10, 2001, at A16 (“Doesn’t the decision about stem cell research come down to this: Are adults with debilitating or lethal diseases, like Parkinson’s or Alzheimer’s, as human as a fertilized egg?”). 7 A LexisNexis™ search produced 548 news articles discussing stem cells during the single week of July 7–13, 2001; during the seven days following the President’s speech (August 10–16, 2001), the tide of articles swelled to 1137 and has only slowly abated. 5

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immersed in the issue and how preoccupied he had become with it.8 In the weeks before the decision, commentators (with the usual hyperbole) described the decision as one “that could define his presidency” 9 and as a “lose-lose situation that would confound King Solomon.”10 And once the decision had been made, reporters emphasized how the staging of the announcement aimed “to portray Mr. Bush as profoundly ruminative, deeply serious and indisputably presidential.”11 While the President’s decision seems to have achieved his political objectives, the issue is not one that he would likely have chosen to play a defining role in the first year of his presidency.** But the convoluted politics of stem cell research virtually guaranteed it would become a high profile issue. While polls showed that a majority of Americans, includ-

ing Catholics, supported federal funding of embryonic stem cell research,12 hard-line opponents of abortion argued that the President would pay a political price if he permitted the Department of Health and Human Services to fund such research.13 Well into the spring, President Bush was sticking to the anti-embryonic stem cell position he took during the presidential campaign. As recently as May 18, 2001, the President reiterated that position to the Culture of Life Foundation, a pro-life group: “I oppose Federal funding for stem-cell research that involves destroying living human embryos.”14 Matters were made worse by a slew of letters written to the President—and then publicly released—by various factions within the Republican party, including prominent pro-life legislators, that pulled President Bush in opposite directions.15 The

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white Catholics favor stem-cell research); Representative J.C. Watts and John Podesta discuss stem cell research and other topics before the Bush White House, Meet the Press (NBC), July 8, 2001 (Citing a Wall Street Journal-NBC News poll as showing “overwhelming public support”: 69% in favor, 23% opposed); CNN-USA Today-Gallup poll, July 10–11, “Do you think the federal government should or should not fund this type of research, or don’t you know enough to say?” Should, 30%; Should not, 13%; Don’t know enough, 57%. “Which comes closest to your view of this kind of stem cell research?” Morally wrong and is unnecessary, 20%; Morally wrong, may be necessary, 34%; Not morally wrong, may be necessary, 35%; Not morally wrong but is unnecessary, 4%; No opinion, 7%. Associated Press, Stem Cells Polls at a Glance, July 12, 2001. 13 Evan Thomas et al., Battle for Bush’s Soul, NEWSWEEK, July 9, 2001, at 28. (Roman Catholic Church hierarchy has vigorously opposed the procedure as a violation of the sanctity of life, and at urging of Karl Rove, the President’s top political advisor, President Bush has been avidly and visibly courting Catholics). 14 Robert Pear, G.O.P. Leaders in the House Fight Stem-Call Aid, N.Y. TIMES , July 3, 2001, at A1. 15 See Ramesh Ponnuru, Cells, Fetuses, and Logic: Who is being sentimental, who rational, in this debate?, NATIONAL RE VIEW , July 23, 2001, at LIII. (Quoting Sen. Orrin Hatch (R-UT): “I just cannot equate a child living in the womb, with moving toes and fingers and a beating heart, with an embryo in a freezer.”); Evan Thomas et al., Battle for Bush’s Soul, NEWSWEEK July 9, 2001, at 28 (Rep. Jennifer Dunn (R-WA) sent Bush a letter, signed by 30 House Republicans, urging him to allow stem cell research; Sen. Trent Lott (R-MI, the Senate Minority Leader) has hinted his support for research; Sen. John McCain (R-AZ) has reversed his campaign stand against it); Stem-cell Research must Proceed, THE SEATTLE TIMES July 8, 2001, at B6 (Republican Main Street Partnership, an alliance of 60 GOP House and Senate members, sent a letter to the White House expressing support for research using human embryonic stem cells); Centrists, leaders try to sway Bush, WASHINGTON TIMES , July 04, 2001, at A6 (quoting letter to President Bush from Reps. Dick Armey [House majority leader], Tom DeLay [House majority whip], and J.C. Watts, Jr. [House Republican Conference chairman] declaring that supporters of the research were agents of “an industry of death.”).

“Bush is famous for his quick executive decisions and abhorrence of long briefings or memos. But as he confronts the most politically sensitive decision of his presidency thus far, Bush is agonizing to an unusual degree. *** With little fanfare, Bush is consulting widely. He is soaking up information, opinions and advice—and, above all, taking his time trying to forge a compromise.” Edwin Chen & Aaron Zitner, Bush Deep Into Cell Study, LOS ANGELES TIMES , July 13, 2001, at A7. See also Ceci Connolly, President ‘Agonizing’ on Embryo Question, WASHINGTON POST , July 15, at A1. 9 See William Safire, Stem Cell Hard Sell, NEW YORK TIMES , July 5, 2001 at A17. 10 Elaine S. Povich, Middle of the Road; Bush faces a lose-lose situation with stem cell research, NEWSDAY (New York, NY), July 10, 2001, at A7 (Quoting conservative Hudson Institute analyst Marshall Wittmann, “It’s a lose-lose situation. This is a decision that would confound King Solomon.”); See also Mimi Hall, Stem-cell issue splits Republicans Both sides lobby Bush in debate, USA TODAY, July 6, 2001, at A6 (President bombarded by opponents and supporters from within his own party on whether to fund an activity that one side calls murder and the other side hails as life-saving). 11 Frank Bruni, note 2 supra. **[Editor’s note: obviously the tragic events of September 11, 2001, completely changed all previous efforts to characterize the first year of George W. Bush’s presidency.] 12 See Elaine S. Povich, Middle of the Road; Bush faces a loselose situation with stem cell research, NEWSDAY (New York, NY), July 10, 2001, at A7 (ABC News/Beliefnet poll, June 20–24 [margin of error 1/2 3%] showed 60 percent of respondents supported “funding for stem cell research.”); Fred Rosen, Stem-cell research of vast benefit, THE BALTIMORE SUN July 9, 2001, at 9A (Jan. 2001 poll commissioned by the Juvenile Diabetes Research Foundation revealed that more than twice as many Americans [65%] support federal funding of stem-cell research than oppose it [26%]); Evan Thomas et al, Battle for Bush’s Soul, N EWSWEEK July 9, 2001, at 28 (According to a new Wall Street Journal/NBC News poll, 72% of


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public division over stem cell research within the Republican party upset the President,16 though some of the pressure also generated “cover” for any decision. For example, the “discrete” (yet still disclosed) lobbying in favor of embryonic stem cell research by Nancy Reagan and other aides to the ex-President, who suffers from Alzheimer’s disease, left some right-to-life advocates more sympathetic to the decision.17 As part of a process of looking for allies and testing the waters, various compromise positions were floated, though many commentators doubted that any compromise would succeed in placating opponents, all of whom seemed to have strongly held moral convictions .18 But compromise can some-

times do the political trick. The Clinton administration’s position on human embryonic stem cell research, which was also a compromise, might be labeled hypocritical but it survived intense lobbying from both sides; likewise, the position of legislators who insist they are “pro-life” in supporting the destruction of human embryos in the service of developing means of saving patients’ lives seemed inconsistent to some but apparently was accepted by most of the public.19 While topics like this—where the tugs on the opposite ends of the ideological rope are very strong—often seem to leave policymakers tied up in knots, a deft slice may sometimes cut the knot. It is too soon to say whether that will prove true of the President’s August 9th decision. 20

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cent human life is sacrosanct and on this we will not compromise”; Richard Doerflinger, of the United States Conference of Catholic Bishops: “It has no convincing stopping point once you begin funding some of this research. And I think it gives up the moral argument at its core.”); Evan Thomas et al., Battle for Bush’s Soul, NEWSWEEK July 9, 2001, at 28 (Dr. David Stevens [executive director of the Christian Medical Association] comparing stem-cell research to using the results of Nazi medical experiments: “This is really a life-and-death issue. . . . It’s hard to compromise on that kind of thing.”). Moreover, most scientists are equally unhappy—though for practical rather than moral reasons—with the proposed compromise. Larry Soler [chair of the Coalition for the Advancement of Medical Research]: “[the compromise is] seriously inadequate. Limiting research to a few existing cell lines . . . would not allow enough diversity to treat people with widely varying immunologies”). Id. See also Rick Weiss, For President, No Easy Solution to Stem Cell Debate, WASHINGTON POST, July 13, 2001, at A1(Richard Doerflinger: “Any of these so-called compromises are going to greatly displease people with moral principles and also displease the scientists who want to hold to their scientific principles.”). 19 “The (asterisked) pro-lifers who favor the research have to understand that in principle what they support on behalf of those they love is pretty much what they oppose for those they don’t care about. For what ails them—an affliction as old as mankind—no cure is in sight. It’s called hypocrisy” Richard Cohen, Pro-Life With an Asterisk, THE WASHINGTON POST, July 10, 2001 at A21. 20 Columnist Frank Rich gave the President a backhand salute for his “act of self-serving political Houdinism”:

Letter By Armey, DeLay and Watts On Stem-Cell Issue Infuriates White House, THE BULLETIN ’S FRONTRUNNER , July 9, 2001 (White House officials were furious after House GOP leaders issued a statement warning President George W. Bush not to lift a ban on federal funding for research using stem cells derived from human embryos; meanwhile, other House Republicans, even some who oppose federal funding for stem-cell research, castigated Reps. Armey, DeLay, and Watts for the letter: “I think you want to be very careful with the tone unless you want to say that Connie Mack and Orrin Hatch are shills for the industry of death,” said Rep. Peter King [R-NY], referring to two staunchly pro-life Republicans who have urged Bush to back stem-cell research funding.”). After the draft of a report being prepared by NIH scientists at the direction of HHS Secretary Thompson—which points to a ‘dazzling array’ of treatment possibilities and concludes that ‘all avenues of research should be exhaustively investigated, including both adult and embryonic sources of tissue’—was leaked to the press, it emerged that the White House was unaware not only that the report was about to be published, but that it was being researched at all. Ed Vulliamy, Focus: Medicine and ethics: The cell struggle: Stem cell research is President Bush’s new battleground. It could save lives and make money—but it pits man against God and divides Republicans, THE OBSERVER, July 8, 2001, at 18. 17 Frank Bruni, From Nancy Reagan, a Nod Toward Embryonic Stem Cell Research, N.Y. TIMES, July 13, 2001, at A14—and the President mentioned her views in his speech. Conversely, the decision to hold back on embryonic cell work was made more reasonable in light of the President having heard advice on the evening of July 10 from two prominent bioethicists to “go slow” on embryonic stem cell research which has been “oversold,” especially since one of them, Daniel Callahan a founder of the Hastings Center, is described as “a Democrat who did not vote for Bush.” Ceci Connolly, President ‘Agonizing’ on Embryo Question, WASHINGTON POST, July 15, 2001, at A1. 18 Leaders in the anti-abortion movement say they expect the President to abide by his campaign promises that federal funds will “not underwrite research that involves the destruction of live human embryos.” Robin Toner, Conservatives Pressure Bush in Cell Debate, N.Y. TIMES , July 12, 2001, at A1. (Ken Connor, president of the conservative Family Research Council: “There should be a nonnegotiable principle that says inno-

Denigrated as a lightweight and a slacker, he seized on the stem cell debate to transform his image into that of our philosopher king—grappling mightily with the science and ethics of an issue he and his handlers hyped as “one of the most profound of our time—even as he induced religiousright leaders to sell out their principles and sent Alzheimer’s, Parkinson’s and juvenile diabetes patients to the back of the medical research bus. Frank Rich, The Genius of George W. Bush, N.Y. Times, August 18, 2001, B-15.

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II. HOW STEM CELLS FIT INTO FEDERAL FUNDING RULES A. Three Sources of Pluripotent Stem Cells The problems now faced by politicians, the public, and scientists themselves began in one week in November 1998 when three research announcements in rapid succession greatly elevated the importance of human embryonic stem cells in both scientific and policy terms. The November 6 issue of the journal Science carried a report from the laboratory of James A. Thomson at the University of Wisconsin describing the derivation of pluripotent stem cells from human embryos.21 These cells, called human embryonic stem cells (hESCs), were isolated by culturing cleavage-stage human embryos in vitro to the blastocyst stage and then isolating the inner cell mass (ICM) which normally develops into the fetus during embryogenesis. The embryos from which the researchers derived the cell lines were originally created in fertility clinics through in vitro fertilization (IVF) and subsequently donated to research. The researchers were able to keep the ES cell lines in a pluripotent state by treating them with a cocktail of growth factors, including mouse “feeder” cells from embryos and bovine serum. Analysis of these cultures revealed that the cells expressed proteins characteristic of stem cells in other species. Furthermore, the cells could be stimulated to form tissue derivatives of all three embryonic germ layers, which indicates that they are pluripotent. Thomson’s method of deriving hESCs by extracting the ICM necessarily destroys the blastocyst and thus the developing organism. By contrast, the method described by John Gearhart and his colleagues from Johns Hopkins University in the Proceedings of the National Academy of Sciences on November 10 utilizes fetuses that have died in the process of abortion.22 The pluripotent cell lines established by Gearhart’s group are referred to as human embryonic germ cells (hEGCs) because the are generated from primordial germ cells extracted from the gonadal ridge of five to nine week-old abortuses. The isolated cells are called germ cells because their ultimate developmental fate in the organism is to form the eggs or sperm. These cells derived from the gonadal ridge apparently behave very much like the stem cells derived from the ICM though not identically. The third and most controversial derivation of

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embryonic stem cell lines, reported in the New York Times on November 12, 1998, but never published in a peer-reviewed journal, described researchers at a private company having obtained stem cells from an embryo that had been created clonally.23 A researcher had inserted the nucleus of his own somatic cell into an enucleated cow egg to form a hybrid embryo from which ICM cells were derived, in a process analogous to that used by Thomson’s laboratory. In culture, the cells expressed markers and behaved similarly to pluripotent stem cells. On July 12, 2001, the Washington Post revealed that the private biotechnology company which had performed this experiment—Advanced Cell Technology (ACT) of Worcester, Massachusetts—had, after “more than a year of quiet and careful preparation” with human rather than cow eggs, “started a series of experiments aimed at creating cloned human embryos or embryo-like entities from which embryonic stem cells could be derived.”24 Their method is doubly controversial, because it involves both the creation of human embryos solely for the purpose of destroying them during research and generating the embryos through somatic cell nuclear transfer (SCNT)—the method used to create Dolly, the first cloned mammal, in 1996. (While a number of groups have recently announced their intention to try cloning a human being, the only previously reported attempt to use SCNT to create a human embryo reportedly occurred in 1999 in Korea; those scientists told reporters that they destroyed the cloned embryo at a very early stage but have never published a report of their research in a peer-reviewed journal.) B. How Certain Research Came to be Ineligible For more than twenty-five years, the federal government has placed restrictions on the use of research funds for studies in which fetuses or embryos could be harmed. These restrictions, apply to all DHHS grants and contracts, originated in Subpart

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J.A. Thomson et al., Embryonic Stem Cell Lines Derived from Human Blastocysts, 282 SCIENCE 1145, 1145–1147 (1998). 22 M.J. Shamblott et al., Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells, 95 PROCEEDING NAT ’L ACAD. SCI. 13726, 13726–13731 (1998). 23 Nicholas Wade, Researchers Claim Embryonic Cell Mix of Human and Cow, N.Y. TIMES , Nov. 12, 1998, at A1. 24 Rick Weiss, Mass. Firm Aims to Clone Embryos for Stem Cells, WASHINGTON POST, July 12, 2001 at A1.


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B of 45 CFR 46, which covers research on “1) the fetus, 2) pregnant women, and 3) human in vitro fertilization.” These rules have implications first for federal support of research involving hEGCs derived from aborted fetuses and second for research involving hESCs derived from IVF embryos.25 By the mid-1980s, initial research had suggested that tissue taken from the brains of aborted fetuses might offer a means of treating Parkinson’s and other neurological diseases. When a protocol does not expose a living fetus to risk but involves only tissues from a dead fetus, Subpart B requires only that the research be conducted in accordance with applicable state or local laws; nonetheless, NIH Director James Wyngaarden decided that the “scientific and ethical implications” of fetal tissue transplantation were so great that he ought to obtain approval from Assistant Secretary of Health Robert E. Windom before allowing NIH physicians or grantees to proceed.26 In March 1988, Dr. Windom declared a moratorium on federal support for fetal tissue transplantation research and asked NIH to establish an advisory panel. In the fall, the panel (by a margin of 19-2) recommended continued funding for this research, under guidelines designed to ensure its ethical integrity.27 After the transition from the Reagan to the Bush administrations, DHHS Secretary Louis Sullivan extended the moratorium, on the basis of the concerns expressed by the minority members of the panel that the proposed protections were insufficient to ensure either that women would not be induced to become pregnant or have abortions in order to make donations or that the women freely consented to use of the fetal tissue. Congressional attempts to override this decision were not enacted or were vetoed by President Bush. On January 22, 1993, in one of his first official acts, President Clinton instructed the incoming DHHS Secretary to lift the moratorium.28 In March 1993, NIH published guidelines based on the 1988 advisory panel’s safeguards as limits on permissible research, and Congress promptly incorporated them into the NIH Revitalization Act of 1993.29 Specifically, these rules seek not only to ensure full disclosure of information and voluntary consent of donors but also to remove any incentives for women to conceive fetuses or to abort them, such as forbidding researchers to pay for fetal tissues or to promise that donated tissue will be transplanted into a particular person. While Dr. Gearhart’s work actually adhered to the federal rules,30 he chose to

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steer clear of any potential problems by not using public funds in deriving hEGCs from the gonadal ridge cells of aborted fetuses; indeed, the concluding stages of his research were supported by the Geron Corporation of Menlo Park, California. Other restrictions in federal law made the work done by Dr. Thomson’s group ineligible for federal funding, however, and he went to great lengths to separate that work, which was also supported by Geron,31 from his other research at the University, which did have federal support. Prof. Thomson’s research falls under a ban on funding embryo research contained in a rider—the Dickey Amendment—that Congress first attached to the funds appropriated for the Department of Health and Human Services (DHHS) in 1996.32 Yet the effective prohibition on such research goes back to the late 1970s and the debates about research to create “test tube babies.” In 1977, a university investigator applied for federal funds for research involving laboratory-created

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45 C.F.R. §46.201(a)(2000). Kenneth J. Ryan, Tissue Transplantation from Aborted Fetuses, Organ Transplantation from Anencephalic Infants, and Keeping Brain-Dead Pregnant Women Alive Until Fetal Viability, 65 SO . CAL . L. REV . 683, 697 (1991). 27 K.F. Duguay, Fetal Tissue Transplantation: Ethical and Legal Considerations, 1 CIRCLES: BUFFALO WOMEN’S JOURNAL OF LAW AND SOCIAL POLICY 36 (1992). 28 See 58 Fed. Reg. 7457 (1993). 29 By deleting the requirement in the DHHS regulations on human subjects research that IVF research undergo review by an Ethics Advisory Board appointed by the Secretary, 45 C.F.R. §§46.203(g) and 46.204(d), the Act ended the de facto bar on funding of such research. Pub. L. No. 103–43, June 10, 1993. 30 Since the Act applies only to fetal tissue obtained for transplantation, Dr. Gearhart’s work 26

arguably is not covered . . . because [the hEGCs in his research] were intended to be cultured and used in laboratory experiments, not transplanted. Nevertheless, if such research were federally supported, it could be subject to the requirements of Subpart B of 45 C.F.R. 46—both the general limitations of §46.206 (separating the investigators from the abortion process and forbidding payments for pregnancy termination) and the special requirements of §46.210 for activities involving cells and tissues from dead fetuses. National Bioethics Advisory Commission, ETHICAL ISSUES IN HUMAN STEM CELL RESEARCH 31 (Vol. 1, Sept. 1999). 31 Anne McLaren, Cloning: Pathways to a Pluripotent Future, SCIENCE, June 9, 2000, at 1775. Geron has received licensing agreements for the hESC and hEGC lines developed by Thomson’s and Gearhart’s groups (respectively). 32 The rider preempted a decision, announced by NIH Director Harold Varmus, to fund research involving “surplus” IVF embryos from fertility centers. Pub. L. No. 104–99, Title I, § 128, 110 Stat. 26, 34 (1996).

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embryos and the following year, stimulated by the great media attention to IVF arising from the birth in England of Louise Brown, the Secretary of the Department of Health, Education and Welfare (DHEW) charged the Ethics Advisory Board (EAB) with studying the social, legal and ethical issues raised by IVF. On May 4, 1979, the EAB reported to the Secretary it had concluded that federal support for IVF research was ethically acceptable under certain conditions .33 Specifically, the board recommended that federally funded research should occur only until the time at which the embryos would normally be implanted (14 days after fertilization) and that research involving human IVF without embryo transfer be designed primarily to establish the safety and efficacy of embryo transfer and to obtain important scientific information toward that end not reasonably attainable by other means. 34 Furthermore, the board recommended that the human gametes used in IVF research must be obtained from persons who have been fully informed of the nature of the research and freely consented to the use of their gametes in the research. Neither the Secretary at the time nor any of her successors have ever acted either to accept or reject the EAB’s recommendations, and no experiments involving human embryos have been funded pursuant to the conditions set forth in the report.35 Shortly thereafter, the EAB was dissolved, making consideration of further proposals to fund research involving embryos impossible .36 The requirement for EAB review was removed by §121(c) of the 1993 NIH Revitalization Act, which should have ended the prohibition on federal funding of research on human embryos.37 Indeed in 1994, NIH Director Harold Varmus appointed a Human Embryo Research Panel to establish guidelines for federally funded embryo research. The panel made several recommendations including allowing the use in research of embryos left over from IVF provided they were donated to research with the informed consent of the progenitors; the panel also concluded (with dissents) that under certain circumstances investigators should be allowed to create human embryos using IVF with the intent to use them solely in research.38 However, on the day these recommendations were unanimously accepted by the Advisory Council to the Director of NIH, President Clinton directed that no federal funds were to be used to create human embryos for research.39 In order to ensure this directive was not modified, Congress


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adopted the Dickey Amendment to the Fiscal Year 1996 DHHS appropriation and has included a comparable provision in every subsequent appropriations bill prohibiting federal funding for research in which human embryos are created for research purposes through any means, including IVF and cloning, or are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed by Federal regulations for research on fetuses in utero (which is essentially zero risk not justified by a benefit to that fetus). It is clear from the phrasing of the rider that the method used by Thomson to derive human stem cells could not be federally funded; likewise, for research of the type carried out by ACT using cloned embryos. The ban on federal funding does not, of course, prohibit the activity itself; other than laws in a few states that attempt to restrict or outlaw human embryo research (which have been successfully challenged for burdening the reproductive rights of infertile couples who claim such research might benefit them40 ), both 33

Ronald M. Green, Stopping Embryo Research, 9 H EALTH MA -

TRIX 235, 238 (1999). 34 Ethics Advisory Board,

Department of Health, Education, and Welfare, REPORT AND CONCLUSIONS : HEW SUPPORT OF RE SEARCH INVOLVING H UMAN IN VITRO FERTILIZATION AND EM BRYO TRANSFER (May 4, 1979). 35 One result of the effective moratorium on federal support has been the removal to private fertility clinics of most research involving human IVF, which is essentially supported by patientcare dollars; unlike other cutting-edge fields of medicine, research in fertility has not taken place within the context of the NIH Clinical Center or federally funded units at academic health centers and hence has lacked the visibility, ethical oversight, and careful research design that characterizes most of experimental medicine in the United States. 36 Ronald M. Green, Stopping Embryo Research, 9 H EALTH MA TRIX 235, 238 (1999). 37 NIH Revitalization Act of 1993, Pub. L. No. 103–43, §121(c), 107 Stat. 122, 133 (1993) (nullifying 45 C.F.R. 45.204(d) as it pertains to the EAB). 38 Ronald M. Green, Stopping Embryo Research, 9 H EALTH MA TRIX 235, 238 (1999). 39 Id. 40 See generally Lifchez V. Hartigan, 735 F. Supp. 1361 (permanently enjoining the enforcement of Ill.Rev.Stat., Ch. 38 para. 81–26, § 6(7) (1989), which barred fetal experimentation, as unconstitutionally vague because classification of a particular procedure as either “experimental” or “routine” could easily be outof-date within six months given rapid development of reproductive endocrinology, leaving physicians unsure whether certain procedures are illegal, and because statute impermissibly intruded on a “cluster of constitutionally protected choices,” which include medical procedures that may bring about, rather than prevent, pregnancy). See also Forbes v. Napolitano, 247 F.3d 903, 904 (9th Cir. 2000) (A.R.S. §§ 36–2302, subpart (A), which criminalized any “medical experimentation or investigation involving fetal tissue,” held void for vagueness).


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the creation of embryos and their use to create colonies of pluripotent stem cells is largely unregulated. Twenty-four states and the District of Columbia do not restrict research on fetuses or embryos, and the restrictions in most of the remaining jurisdictions are aimed principally at fetal research and only 10 prohibit or restrict embryological research.41 III. THE POTENTIAL CONTRIBUTIONS OF STEM CELL RESEARCH If federal law has imposed barriers to the pursuit of human embryonic stem cell research—at least on a par with other areas of comparable biomedical importance—policymakers want to know: what’s at stake? What are the potential contributions of this field, both to basic science and to medical treatment? A. Basic Research It seems to be widely agreed in scientific circles that hESC research will be invaluable to basic science. First, the availability of these cells greatly enhances the experimental tools to study the biology of normal human development and the developmental problems that lead to diseases and disabilities. Second, hESC research will increase understanding of the specific process of cellular differentiation and tissue specification. Research on early human development is currently relatively difficult because of the restrictions involved in working with live human beings. Current research is limited to experiments that are not harmful to the fetus as well as those involving the embryology of other species. The knowledge derived from such studies could be greatly enhanced by experimentation on hESC lines. For example, mouse embryology is often used as a model for early mammalian development and mouse ES cell lines are a characterized part of mouse embryology. Comparisons between human and mouse ES cell lines may provide powerful insights into early human development. Furthermore, a better understanding of human development may lead to insight into the interplay between development and the cell cycle, which is important in understanding how a normal cell becomes a cancer cell. Finally, a better understanding of human development will help illuminate the processes behind developmental defects, and in turn, may lead to new therapies to combat these defects.

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A specific area of basic research that will benefit from hESC research is the understanding of cellular differentiation.42 A significant part of understandin g development is identifying the signals that lead to certain cell fates, especially since this choice of fates is rarely as simple as a cell receiving a single signal. For example, in forming a limb, cells receive multiple signals organized in spatially defined patterns and gradients.43 The position of the cell within this pattern then determines its ultimate cell fate. ES cell lines are an important tool in the very difficult and complex process of properly characterizing the signals required to adopt specific cell fates. Currently, most of the information about differentiation cues comes from work performed in other organisms and then analogized to humans. Once a signal is identified in another organism, it may be possible to identify and clone a human homolog to that gene, though this does not assure that the human gene performs the same function. Unless the researcher is especially fortunate and the gene happens to be identified with a genetically defined trait, further research will be needed to determine whether the gene performs the same function in humans as in the organism where it was first identified. Short of human experimentation, the options for establishing gene function include biochemical studies of the gene product and in vivo assays using transgenic animals. These methods all suffer from the caveat that the experiments are not being performed within the proper context, so that crucial elements may be missing and thus result in misleading and erroneous findings. One method to try and get around these problems is to test the role of the gene in the context of a human cell line. Unfortunately, most cell lines consist of differentiated cells which have become “immortal” as a result of chromosomal or genetic changes that allow them to divide indefinitely. Though such cell lines have been partially changed in order to 41

C.L. Feiler, Human Embryo Experimentation: Regulation and Relative Rights, 66 FORDHAM L. REV . 2435 (1998). “All ten states that prohibit embryological research have vaguely worded statutes which could encompass cell line development if the statutes were interpreted broadly.” J. Coleman, Playing God or Playing Scientist: A Constitutional Analysis of State Laws Banning Embryological Procedures, 27 PACIFIC L.J.1331, 1358 (1996). 42 K. Sue O’Shea, Embryonic Stem Cell Models of Development, 257 ANAT . REC . (NEW ANAT .) 32, 32–41 (1999). 43 Randy L. Johnson & Cliff Tabin, 90 CELL 979, 979–990 (1997).

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make them useful for scientific inquiry and are no longer identical to the specialized cells from which they are derived, they are sometimes useful to assay the function of a new gene. Although adult cell lines can be useful, pluripotent stem cell lines are a far superior context in which to perform experiments studying cellular specialization because this is the type of cell that actually differentiates within the human body, because they are already able to divide indefinitely, without the need to be mutated to become immortal, and because they posses a normal diploid karyotype, indicating that they are genetically analogous to the stem cells from which they were derived. Once the proper signaling cues are identified, the specialized cells derived from hESC lines can be used to identify new genes involved in cell fate specification. For example, researchers will be able to use the differentiated cells to identify tissue-specific genes that are activated in response to the signal to differentiate. Ultimately, hESC lines could provide an unlimited source of tissue-specific material for biochemical experiments. Obviously, the contribution of hESC research to basic science has a secondary effect on clinical research. For example, cell differentiation and development must be understood if stem cells— including adult stem cells—are to provide a source of specialized tissue for transplantation. Absent some means of directly obtaining neural stem cells for transplantation, for instance, a clinician must first differentiate the hESCs into neural stem cells, or transdifferentiate a non-neuronal stem cell into a neural stem cell; this requires knowledge of the proper cell signals and how to use them. If such research is left to the private sector, it will probably only be pursued if it is likely to culminate in a viable product; the basic steps required to understand a rare neural degenerative disease might be ignored because the cost of investigation far outweighs any potential monetary benefit from developing a therapy. Thus, leaving the choice of what basic research is performed to private groups will almost certainly result in an uneven patchwork of basic research that covers some developmental steps in great detail and leaves others relatively obscure. B. Clinical Applications The potential application of hESC research that has received the greatest attention is transplantatio n of cells and tissue created in the lab. This applica-


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tion of stem cell research—the regeneration of a diseased or defective organ—is easy for the average person to understand and obviously of significant benefit. If successful, transplantation from hESC sources could overcome several major problems that now plague this field, namely the inadequate number of donated organs and the inability to treat certain conditions (such as spinal cord injuries) by transplantation of donor organs. Pluripotent stem cell lines could provide a plentiful supply of transplantable cells and could be used to regenerate damaged heart and neural tissue. An indication of the clinical potential can be seen in research in rats, which has shown that precursors of specialized neural cells derived from ES cells can myelinate axons of the brain and muscle44 The researchers differentiated ES cells in culture using combinations of growth factors known to stimulate differentiation of the cell population into oligodendrocytes and astrocytes. They then transplanted these cells into myelin-deficient rats which constitute an animal model for Pelizaeus-Merzbacher disease (PMD) a hereditary myelin disorder. The transplanted cells spread in six of nine rats and successfully myelinated axons. These results indicate that the technique of differentiating ES cells to specific cell types and using those cells to repair damaged tissue is viable. Similarly successful experiments have been carried out in mice whose myelin deficiency causes them to shiver45 and in rats with mechanically created spinal injuries.46 While such experiments strongly suggest that stem cell transplantation may eventually prove useful in treating neural tissue damage, the experimental transplants did not completely restore neural function but merely improved the performance of transplanted animals versus untreated animals. The potential of ES cell research is not limited to neural tissues. Stem cell transplantation has a broad variety of potential applications. For example, stem cells could be used to treat Type I (insulin-depen -

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O. Brustle et al, Embryonic Stem Cell-Derived Glial Precursors: A Source of Myelinating Transplants, 285 SCIENCE 754, 754–756 (1999). 45 B.D. Yandava et al., “Global” cell replacement is feasible via neural stem cell transplantation: Evidence from dysmyelinated shiverer mouse brain, 96 PROCEEDING NAT ’L ACAD. SCI. 7029, 7029–34 (1999). 46 John W. McDonald et al., Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord, 5 NATURE MEDICINE 1410, 1410–12 (1999).


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dent) diabetes,47 to repair cardiac damage after a heart attack, or to treat victims of stroke, burns and arthritis. The potential of hESCs lies in their ability to form a wide variety of tissues. Ideally, such cells would function as a reservoir from which the appropriate cells for treatment could be collected. If this technique is perfected, it would ultimately affect virtually all modern medicine. Despite this potential, several caveats must be kept in mind. First, to perfect ES cell transplantation, researchers need to overcome the problem of host rejection of transplanted tissues. One way to overcome this problem is to maintain large libraries of stem cells with different major histocompatibility (MHC) alleles. The cell line used for transplantation could be selected based on recipient compatibility. A related possibility would be to manipulate the antigenic markers on hESC lines to make them evade or coexist with the recipient’s immune system. A second way to get around the problem of host rejection is to use adult stem cells derived from the person needing the transplant. For example, current bone marrow transplantation techniques involve removing a sample of bone marrow from the patient, isolating in vitro hematopoietic stem cells within the marrow sample, irradiating the patients remaining bone marrow and finally transplanting back into the patient the bone marrow stem cells. The use of cultured stem cells to generate hematopoietic cells could make this procedure even more robust because the hematopoietic stem cells that are now extracted from bone marrow do not grow well in culture. Comparable results have already been achieved in irradiated mice by inducing skeletal muscle stem cells to produce hematopoietic stem cells.48 A third way around rejection would be to use SCNT from the patient to create an embryo from which hESCs could be derived, which is an objective that ACT has identified for its current attempts to clone human embryos. The difficulties that now exist in generating viable mammals through cloning and the developmental problems that many of the surviving clones manifest suggest that, ethical and prudential issues aside,49 success in this line of transplantation lies many years in the future. Furthermore, the generation of cells identical to the patient’s would not be a useful treatment for conditions that occur because of a gene defect. Another area in which hESC research may be beneficial is in drug discovery and drug safety testing. A number of cell lines are currently used this way, but

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the potential to generate any cell line at will from pluiripotent stem cells would greatly facilitate specific testing of drug and tissue interactions as well as allow research into areas that were previously infeasible due to the lack of appropriate cell lines. IV. ETHICAL OBJECTIONS TO STEM CELL RESEARCH Opponents of hESC research raise two main objections: that the destruction of human embryos amounts to the taking of a human life, and that creation of human embryos for research renders them objects of utility rather than of inherent value. Neither of these objections apply to adult stem cell research, which is why it proceeds and will likely continue without ethical objection. A. Objections to Destroying Embryos The objection to the destruction of embryos is essentially the same as the “right-to-life ” objection to abortion, namely that life begins at conception and hence killing an embryo is equivalent to the killing of any other human being. For example, during a recent Senate Labor-HHS Appropriations Subcommittee hearing, Senator Brownback (R-KS) analogized hESC research to the experiments conducted on Nazi camp inmates to underline his view that the inherent value of the embryo outweighed any utility that might be gained from ES cell research.50 While some right-to-life advocates object to hEGC research as well,51 many argue that deriving 47

Vijayakumar K. Ramiya et al., Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells, 6 NATURE MEDICINE 278, 278–82 (2000). 48 Kathyjo A. Jackson et al., Hematopoietic potential of stem cells isolated from murine skeletal muscle, 96 PROCEEDING NAT ’L ACAD. SCI. 14482, 14482–86 (1999). 49 See Alexander M. Capron, Statement, Hearing on H.R. 1644 and H.R. 2124 before the Subcomm. on Crime, House Judiciary Committee, 107th Cong., 1st Sess., June 19, 2001. 50 Labor HHS Appropriations Subcommittee hearing on April 26, 2000. 51 President George W. Bush has frequently stated his own opposition to the use of tissue from aborted fetuses in research generally. For example, shortly after assuming office in January, the President said federal money should not be used because he does “not support research from aborted fetuses.” Alissa J. Rubin & Aaron Zitner, Bush Opposes Use of Aborted Tissue; Science: Reviving the Abortion Debate for the Second Time This Week, the President didn’t say Whether he’d Fight Federal Funding for Promising, Yet Problematic, Medical Research, L.A. TIMES , Jan. 27, 2001, at A6.

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stem cells from embryos is more objectionable than from fetal tissue because the scientist in the former case is involved in the act that destroys the living being. A scientist isolating fetal tissue, such as EG cells, works with an already aborted, dead fetus, whereas hESC researchers end an embryo’s viability by removing stem cells from its ICM. While “discarded” embryos from fertility clinics would otherwise die, the time and method of destruction is determined by the needs of the hESC researcher. By analogy, hESC opponents argue this act is no more moral than it would be to harvest organs from an individual, such as a condemned prisoner, because he will die soon. The response of scientists to these criticisms has been limited. Proponents of ES cell research have tried hard to make clear that ES cell lines themselves are not equivalent to embryos, so that research with the cells, as opposed to their derivation, is not problematic.52 (In fact, NIH leaders and many other scientists refer to these cells only as “pluripotent stem cells” to avoid the word “embryo.”) Beyond this, scientists favoring hESC research have tended to argue that a blastocyst in a laboratory cannot be compared with a person after birth, or even with a living fetus in the uterus, especially post-viability, and that the enormous scientific potential of stem cell research justifies the destruction of embryos, especially those that are being discarded anyway.53 Recently, some pro-life legislators have spoken up in favor of funding embryonic stem cell research. For example, at the beginning of July 2001, Sen. Orrin G. Hatch (R-Utah) disclosed that he had urged the Bush Administration to allow such funding because “The most pro-life position would be to help people who suffer from these maladies . . . That is far more ethical than just abandoning or discarding these embryonic stem cells.”54 Yet Hatch’s position is not simply utilitarian (that the good for these many existing patients justifies the loss of a few potential lives in research). Instead, Hatch squared research funding with his pro-life views on the ground that an embryo in a Petri dish has no capacity to develop into a person in the laboratory. That capacity is attained only after an embryo is transferred to a woman’s womb, and Hatch concluded that the government’s interest in protecting the embryo only arises at that point. His position resembles the view that ensoulment occurs not at conception but sometime later, variously put at 40 days or at quickening. This view goes back to Aristotle and continued to be held by the Catholic Church until 1869 when Pope Pius IX reasserted a position first adopted


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in the Sixteenth Century forbidding abortion at any stage of pregnancy. More recent philosophers have distinguished between the embryo as a “possible” person when in a petri dish, and as a “potential” person (and hence deserving of protection) once it has been transferred to a uterus where it can develop on its own.55 The Catholic hierarchy and many other religious conservatives reject this attempt to resurrect “delayed ensoulment” (at least for IVF embryos), and some secular critics have tagged the pro-life/pro-embryonic-stem-cell -research legislators hypocrites.56 B. Objections to Commodifying Embryos The second objection commonly associated with stem cell research is that it encourages the commodification of human life. This objection has two facets. The broader version objects to any use of human embryos as a research tool. Since such use nec-

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In a recent New York Times op-ed article, Princeton molecular biologist Lee M. Silver probably did not endear himself to the scientists trying to make such a sharp distinction when he extrapolated to human beings research first performed eight years ago by embryologist Janet Rossant in which mouse ES cells, wrapped in an artificial placental layer and implanted in a mouse uterus, developed into mice: Because of their versatility, ES cells are the darlings of biomedical research. All scientists need to do is to identify the molecular signals and cellular environment required to generate any tissue or organ of choice. But if lab-grown ES cells can be coaxed to develop into any one tissue, might there be an environment in which they could be coaxed into making a whole human body? The answer is yes. Acknowledging that “with the political debate at fever pitch” other scientists will challenge his interpretation, Prof. Silver argued that for biologists, “words like ‘destruction,’ ‘creation,’ ‘embryo’ and even ‘life’ and ‘death’ are ambiguous.” Lee M. Silver, Just Whom Are You Calling an Embryo?, NY TIMES , Aug. 19, 2001, at B4, col. 1. 53 See, e.g., David Baltimore, Stem Cell Research: A Debate— Don’t Impede Medical Progress, WALL STREET JOURNAL , July 30, 2001, at A18. 54 Ceci Connolly, Conservative Pressure for Stem Cell Funds Builds; Key Antiabortionists Join Push for Embryo Research, THE WASHINGTON POST , July 02, 2001, at A01 (other conservative supporters of funding hESC research include Sens. Strom Thurmond [R-SC] and Gordon Smith [R-OR] and former Sen. Connie Mack [R-FL], a Roman Catholic and a cancer survivor who claims to hold firm to the view that life begins at conception, though his thinking has evolved to take into account new scientific discoveries such as test tube fertilization). 55 See Rick Weiss, Changing Conceptions, WASHINGTON POST , July 15, 2001, at B1 (quoting philosopher Carol Tauer of the Minnesota Center for Health Care Ethics). 56 See, e.g., Richard Cohen, Pro-Life With an Asterisk, WASH INGTON POST, July 10, 2001, at A21.


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essarily occurs without the embryos’ consent and not for their benefit, it treats them differently than any other living human entity in research, instead rendering them things, commodities to be used. The second version of this objection is directed at the creation of embryos solely for research, as was recently announced by one leading fertility center.57 Plainly, creating embryos solely for the purpose of extracting stem cells runs afoul of the first commodification argument as well. But it creates a separate concern—even for persons who do not object to the use of embryos that have been discarded and that would disintegrate if not used in research—that allowing the creation of embryos for research reduces embryos to objects that possess only instrumental and not inherent worth, and that it may lead to their commercialization, that is, the uncontrolled production and marketing of “human research embryos.” 58 Unlike the objection that stem cell research is wrong because it rests on the killing of a human being, both the broad and the narrow versions of the commodification objection do not depend for their force on assigning human embryos the same moral status as persons, though they do presuppose that embryos deserve greater respect and concern than other bunches of human cells that have no potential to become a person. It is sufficient to conclude, as the National Bioethics Advisory Commission did in its 1999 report on stem cell research and as many ethics panels have since the 1970s (such as the 1979 report of the DHEW Ethics Advisory Board, described previously, and the 1984 Warnock Committee report in the U.K., discussed below), that “the embryo merits respect as a form of human life, but not the same level of respect accorded persons.”59 Several consequences could follow from this view. First, the use of embryos should be restricted to research offering a prospect of preventing or relieving human suffering in a way not otherwise reasonably attainable. This position draws on Ronald Dworkin’s argument that many who object to abortion make an exception for rape or incest; since the moral status of a fetus arising from such wrongful acts does not differ from that of a fetus conceived without rape or incest, the willingness to allow abortion in such cases reflects a judgment that the protection usually accorded to unborn human life should yield before others’ very strong interests.60 Second, in order to avoid the slippery slope down

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in which the human body would be treated like merchandise, and more broadly, human beings would be objectified, commerce in embryos should be forbidden. 61 V. FEDERAL FUNDING OPTIONS: ALIGNING POLICY WITH LAW AND ETHICS Even if stem cell research delivers fewer or less far-reaching benefits than its sometimes fevered proponents now predict, this field will certainly produce much of value both to basic biological knowledge and to medical treatment. Not surprisingly , cries are not heard to halt funding of research using stem cells from laboratory animals or human stem cells from tissues other than embryos and fetuses. Furthermore, notwithstanding the ethical objections that still emanate from some quarters regarding federal support for research involving the extraction of hEGCs from dead fetuses, the acceptability of such research under existing law means that the focus of the debate in ethical as well as policy terms is on hESC research and whether any aspect of it should be eligible for federal funding. Four policy options have been advocated for federal support of hESC research: no funding, funding only of research using the hESCs that have already been produced, funding of research using hESCs but not their derivation from embryos, and funding of research to derive as well as to use hESCs from em-

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Susan E. Lanzendorf et al., Use of Human Gametes Obtained from Anonymous Donors for the Production of Human Embryonic Stem Cell Lines, 76 FERTILITY & STERILITY 132 (2001). See also Aaron Zitner, Embryos Created for Stem Cell Research, LOS ANGELES TIMES, July 11, 2001, at A1 (research criticized as scientifically unnecessary, ethically questionable, and politically inflammatory). 58 Persons concerned about commerce in embryos also point out that the creation of research embryos would largely rely on purchased eggs and sperm, accelerating market forces that already are at work in the context of assisted reproduction. Ultimately, the situation in which human precursors are for sale contributes to regarding human beings in themselves (particularly children) as objects of commerce. 59 National Bioethics Advisory Commission, ETHICAL ISSUES IN HUMAN STEM CELL RESEARCH 50 (Vol. 1, Sept. 1999). 60 See Ronald Dworkin, LIFE ’S DOMINION : AN ARGUMENT ABOUT ABORTION, EUTHANASIA , AND INDIVIDUAL FREEDOM (1994). 61 Were a market of buying and selling made-for-use human embryos to emerge, it would almost certainly classify embryos by genotype and other measures of utility.

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bryos. A further issue complicating each of the latter three options is whether restrictions should be placed on the source of the embryos involved—discarded, donated IVF embryos from fertility clinics versus embryos created through IVF for research purposes versus embryos created (presumably for research purposes) through SCNT. A. No Federal Support for Human Embryonic Stem Cell Research Those who argue against federal support for hESC research advance two reasons why such support is unnecessary and ought not to be provided given that a large portion (albeit not a majority) of the population believes such research is morally illicit and would be offended with the use of their taxes to support it. First, they argue that nothing will be lost because research can go forward with nonfederal funding.62 Second they claim that the same research results can be obtained by supporting research that uses differentiated (adult) human stem cells and hEGCs. 1. Leave the Field to Private Funding: The first argument has a certain plausibility, given our society’s general predilection to leave matters to “the private sector” when possible. Yet given the potential importance of this field of research such a sanguine view of the effective ban on federal funding hardly seems justifiable. Not only would researchers at such premier federal institutions as the National Institutes of Health be prohibited from working with hESCs but all investigators in other settings—including academic health centers and medical schools, where a majority of the most important research is federally supported—would have to contort their work to ensure that any which involves hESCs (which could at any point become quite a large proportion) is conducted separately from their federally supported work, in terms not only of laboratory space and supplies and the work hours of themselves and all employees charged to their federal grants and contracts but also the basic infrastructure of the laboratory that receives “indirect” support under federal grants and contracts. Moreover, to the extent that university researchers turn to private rather than federal funds, their work may fall under restrictions that for-profit companies often place on the use and dissemination of intellectual property whose creation they have


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supported. Indeed, researchers obtaining hESCs from Wi-Cell (the not-for-profit subsidiary of the Wisconsin Alumni Research Foundation that is marketing Prof. Thomson’s cell lines) must agree to restrictions and licensing requirements imposed by the Geron Corp., which funded Thomson’s work and holds patents and other intellectual property rights for most of the significant stem cell and SCNT techniques. A further effect of leaving hESC research to be developed with private rather than governmental support is that the choice of scientific areas—both basic and applied—to pursue will, of necessity, be guided by private companies’ estimate of the profits likely to be made rather than by the decisions that scientists proposing so-called R0-1 projects would choose on their own. Finally, if the federal government leaves the field to private industry, the likelihood of strong, consistent, and transparent ethical standards and review of the processes by which stem cells are derived and used will be undermined by differences among companies and among state regulatory standards (which are mostly nonexistent ) and by trade secrecy policies.63 2. Adult Stem Cells as an Alternative Means: The second argument against supporting hESC research—that other lines of research will yield the same result using means that do not generate the same controversy—remains the principal defense of conservatives responding to disease-advocacy groups and others in biomedicine who view stem cell research as the key to important thera-

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See, e.g., Robert Oldham, Stem Cells: Private Sector Can Do It Better, WALL STREET JOURNAL , Aug. 28, 2001, at A14, col. 6 (drawing analogy to the boost that the private company Celera gave to the previously publicly funded effort to map the human genome). 63 “Federal funding guarantees that the broadest array of cogent scientific questions are asked in a public arena and subject to federal oversight and ethical standards. This, in turn, will result in the greatest benefit as opportunities will be pursued for their scientific potential not their expected commercial value.” Laura Lyman Rodriguez, Why Adult Stem Cell Research is Not Sufficient?, FASEB Office of Public Affairs (Aug. 14, 2000) [http://fasb.org]. See also Andrea Knox, Bioethicist’s Resignation in Pennsylvania Sparks Debate About Ethics, Cloning, PHILADELPHIA INQUIRER , July 17, 2001, at (university bioethicist resigned in protest from ACT’s advisory body when what he hoped would be a “a ringside seat to exciting research that needed ethical evaluation” proved to be merely “an ethics stamp of approval” which the company was free to use or ignore).


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peutic advances. There is no question that research with stem cells from laboratory animals will play an essential role in developing both basic knowledge and new therapies in this as in every biomedical field, but as is always the case, eventually researchers must use human materials (and even human subjects) especially in order to develop the tools of regenerative medicine which potentially involve inserting stem-cell-derived cells and tissues into patients. Opponents of hESC research argue that this human material can come from adult stem cells that are being found in an increasing number of bodily tissues and that have proven in recent years to be more malleable than scientists had previously thought. Indeed, recent findings have overthrown the older view that adult stem cells are terminally tissue-spe cific and that the process of differentiation of stem cells is linear and irreversible. In the past several years, for example, bone marrow-derived cells have been shown to give rise to muscle, liver, heart, and brain cells, central nervous system stems cells can produce blood cells, and cells from the dermal layer of the human scalp were coaxed to become nerve, muscle and fat cells.64 The discovery that stem cells in adults can first reside in one tissue and then contribute to another suggests a previously unrecognized degree of plasticity in stem cell function. Indeed, it now appears that cell fate changes are a natural property of stem cells and may be involved in ongoing physiological repair of tissue damage throughout life. [R]ather than referring to a discrete cellular entity, a stem cell most accurately refers to a biological function that can be induced in many distinct types of cells, even differentiated cells.65 For adult stem cells to play the role envisioned for hESCs, scientists need to perfect methods to induce the adult stem cells to dedifferentiate or transdifferentiate. 66 In the process of dedifferentiation, a tissue-specific stem cell—say a neural stem cell—exposed to molecular signals would be caused to travel in reverse down the developmental path that led it to become a neural cell in the first place. If the process worked, the cell would revert to a less specialized state, perhaps all the way back to pluripotency. (Once pluripotent, the cell could be used for basic research or caused to

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differentiate into a desired type.) In transdifferentiation, a stem cell of one tissue type is exposed to signals that provoke a change of characteristics to those of another stem cell type. Essentially the stem cell reaches its destination without going back to the starting gate. Despite the promise of this research, it is too soon to assume that adult stem cells are equivalent in potential to hESCs. First, the fact that adult stem cells have some of the characteristics of pluripotent stem cells does not mean that they will be identical. Only by studying both embryonic and adult stem cells can a proper assessment be made of the potential of the latter in transplant therapies or in other branches of research. Second, it now appears that research using hESCs—which are naturally responsive to a variety of differentiating stimuli—will be needed to identify the chemical triggers for transdifferentia tion and dedifferentiation in adult stem cells.67 Indeed, adult stem cells are not likely to provide the same information about development and differentiation that will come out of hESC research regarding problems as diverse as developmental disorders and cancer. Moreover, unanticipated problems may arise in applying either ES cells or adult stem cells to actual medical therapies and it is impossible to know before which will be successful in any particular circumstance. Thus, adult stem cell research should not be viewed as a substitute for hESC research but as a complementary area of scientific inquiry. As a recent NIH report concludes, “it is impossible to predict which stem cells—those derived from the embryo, the fetus, or the adult—or which methods for manipulating the cells, will best meet the needs of basic research and clinical applications. ”68 By vig-

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Jean G. Toma, Mahnaz Akhavan, Karl J. L. Fernandes, Fanie Barnabé-Heider, Abbas Sadikot, David R. Kaplan and Freda D. Miller, Isolation of multipotent adult stem cells from the dermis of mammalian skin, 3 N ATURE CELL BIOLOGY 778–784 (Sept. 2001). 65 H.M. Blau et al., The Evolving Concept of a Stem Cell: Entity or Function?, 105 CELL 829 (2001). 66 See Irving L. Weissman, Stem Cells: Units of Development, Units of Regeneration and Units in Evolution, 100 CELL 160, 160–62 (2000). 67 Stephen Jay Gould, What Only the Embryo Knows, N.Y. TIMES , Aug. 27, 2001, at A21, col. 1. 68 Ceci Connolly, Embryo Cells’ Promise Cited in NIH Study; Call for More Research Toughens Bush Choice, WASHINGTON POST, July 18, 2001, at A1.

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orously pursuing research with cells from embryonic as well as adult sources, proponents of hESC research argue that scientists will greatly increase the likelihood that the benefits—especially new therapies—of this new field will be realized. If the eventual ability to manipulate adult stem cells proves to be as great as its boosters now predict, adult stem cells can replace embryonic ones as research and therapeutic tools.69 In the meanwhile, betting on only one horse (and one with some obvious handicaps in the race) will almost certainly delay—and may even prevent—achieving results that are important to science and perhaps vital to the lives of some patients.70


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ter (but not the former) involves destruction of embryos. To prepare standards for grants, NIH appointed a panel of experts who designed a system to ensure that although federally supported researchers were limited to embryonic stem cells derived by private parties, those parties would adhere to appropriate ethical strictures in the manner in which they derived the cells. In December 1999, NIH released a draft of guidelines for funding research involving human pluripotent stem cells.73 After an extended period of debate the final NIH guidelines were released on August 25, 2000.74 The guidelines retain the distinction between use and derivation and add a requirement that the stem cell lines be derived

B. Federal Support Only for Using Privately Derived Cells In increasing degree of liberality, the next two of the four policy options would be federal funding only for research using the hESCs that have already been produced, and federal funding for research using all appropriately derived hESCs but not for the derivation of hESCs from embryos. But the order in which these are best considered is the reverse because the second option—which was first floated as a compromise by White House insiders in July 2001—is a modification of the third option, which was the compromise struck by the Clinton Administration. 1. Funding Use But Not Derivation: The NIH procedures that were suspended by Secretary Thompson in April 2001 represented a compromise designed by the Clinton Administration to allow federal support for stem cell research without violating the Dickey Amendment. As relevant here, that appropriations rider essentially forbids funds going toward the creation or destruction of human embryos. 71 In response to a request that NIH Director Varmus made once the potential of human stem cell research became apparent in the winter of 1998, HHS General Counsel Harriet Rabb issued an opinion memorandum on January 15, 1999, in which she concluded that since stem cells are pluripotent (rather than totipotent) they are not in themselves embryos so that research with them is eligible for federal funding.72 In shorthand, federal funds could go for “use” but not for “derivation,” since the lat-

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Much of the same reasoning applies to research with hEGCs as an alternative to hESC research. While research of the former type is definitely worth pursuing, at this point, not enough is known about the differences between hEGCs and hESCs to justify funding only germ cell research. It would be premature to assume that the two types of cell lines are essentially identical and not pursue research on both. 70 As one commentator rather rhetorically pointed out recently: Even if . . . adult stem cells turn out to be almost as good as embryonic ones, which many politicians are hoping will spare them a tough decision, that “almost” will lead to unnecessary suffering and death if adult cells become an excuse to restrict embryonic ones. So, if that’s what you think justice for embryos requires, you had better be sure you’re right. Michael Kinsley, If You Believe Embryos Are Humans . . . then curbing research on stem cells is an odd place to start protecting them, TIME , June 25, 2001, at 80. 71 Pub. L. No. 105–277, § 511 (1998). 72 Harriet Rabb, Memorandum to Harold Varmus M.D., Director, NIH, Federal Funding for Research Involving Human Pluripotent Stem Cells, January 15, 1999. 73 National Institutes of Health Draft Guidelines for Research Using Human Pluripotent Stem Cells, 64 Fed. Reg. 67576. (December 2, 1999). NIH responded to the complaint that these were guidelines rather than regulations, by pointing out that the guidelines prescribe the documentation and assurances that must accompany requests for NIH funding for research utilizing pluripotent stem cells, and concluded that: “Compliance with the Guidelines will be imposed as a condition of grant award” (see note 74 infra). 74 National Institutes of Health Guidelines for Research Using Human Pluripotent Stem Cells, 65 FED . REG . 51976 (Aug. 25, 2000), corrected 65 FED . REG . 69951 (Nov. 21, 2000). The original 60 day comment period was extended an additional 28 days, in response to public interest, and approximately 50,000 comments were received.


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from frozen embryos left over from IVF.75 Research with hESC lines derived from cloned embryos created through SCNT or embryos created specifically for research could not be funded.76 The guidelines also require that (a) the embryos used for derivation be donated voluntarily,77 with no inducements, monetary or otherwise; (b) the decision to create the embryos and the decision to donate the embryos are kept separate78; and (c) the decisions to discard the embryos and to donate them to science must be kept distinct. Through such requirements, NIH officials expected to exert pressure on the procedures for deriving stem cells even though HHS-funding would not flow directly on those carrying out such procedures. As a legal matter, the General Counsel’s memorandum (and hence the NIH guidelines based on it) is at the least defensible; it exploits the failure of the statute’s drafters to express their intention in the language of the law as clearly as they have expressed it in reaction to the NIH policy.79 Strictly speaking, the acts that are ineligible for research funding under the appropriations statute do not include the manipulation of human cells unless those cells constitute an embryo, and a sound scientific basis exists for concluding that hESCs are not in themselves (that is, without being modified, such as being inserted into an ovum) capable of functioning as embryos nor developing into a fetus. The arrangements that flow from this attempt to separate funding for use (permissible) and funding for derivation (forbidden) are harder to defend on logical, ethical, or practical grounds, however. In the first place, the distinction between paying for use of stem cells and paying for their derivation is merely a bookkeeping fiction. The funding provided for studies using hESCs would of course flow directly to researchers deriving those cells, perhaps even in an adjacent laboratory. The only true difference would be that the federal funds would not go directly as salary and laboratory expenses for the derivation process but indirectly as funds to purchase hESCs, which funds would then pay the salaries, laboratory expenses, and so forth. In effect, NIH would be supporting ES cell derivation through an intermediary. Given this connection, support for research using the cells is acceptable only to the extent that the process of derivation is acceptable. Plainly, for the drafters of the NIH policy, that is the case: they did not agree with the premise of the appropriation s

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rider and hence felt it was legitimate to find a means of complying with the letter of the law while going ahead with what they regard as very important research to the extent possible. If they had regarded the underlying activity as immoral or illegal, one has to believe that they would have given greater weight to the “ complicity” argument, namely that 75

In publishing its rules, NIH answered comments on the draft regulations addressed to the question of made-for-research embryos: Some respondents were concerned that embryos might be created for research purposes. Other respondents stated there should be no distinction between embryos created for research purposes and those created for fertility treatment. Investigators seeking NIH funds for research using hPSCs [human pluripotent stem cells, the term used by NIH for hESCs] are required to provide documentation, prior to the award of any NIH funds, that embryos were created for the purposes of fertility treatment. President Clinton, many members of Congress, the NIH Human Embryo Research Panel, and the NBAC have all embraced the distinction between embryos created for research purposes and those created for reproductive purposes. National Institutes of Health Guidelines for Research Using Human Pluripotent Stem Cells, 65 Fed. Reg. 51976, 61976–79 (Aug. 25, 2000). 76 Id. 77 The NIH guidelines specify that informed consent for stem cell derivation must be obtained from the individual(s) who were part of the decision to create the embryos for reproductive purposes, who would be the couple seeking fertility treatment rather than the gamete donors, if any. 78 Section A2c of the NIH Guidelines imposes two requirements aim to ensure this separation of the two decisions: To ensure that human embryos donated for research were in excess of the clinical need of the individuals seeking fertility treatment and to allow potential donors time between the creation of the embryos for fertility treatment and the decision to donate for research purposes, only frozen human embryos should have been used to derive human pluripotent stem cells. In addition, individuals undergoing fertility treatment should have been approached about consent for donation of human embryos to derive pluripotent stem cells only at the time of deciding the disposition of embryos in excess of the clinical need. 79

“Relying on a single deeply flawed legal analysis by the General Counsel of the Department of Health and Human Services, the NIH guidelines mangle the plain meaning of the federal law, narrowing it to ban only funding of the specific act of destroying the embryo.” The National Conference of Catholic Bishops/United States Catholic Conference-Pro-Life Activities, Talking Points: “Draft National Institutes of Health Guidelines for Research Involving Human Pluripotent Stem Cells,” June 14, 2000. Some senators were also “deeply concerned with what appears to be a unilateral attempt on the part [DHHS’s] part to effectively undermine congressional intent, by circumventing the current federal funding ban on embryo research.” Ida Chow, Update on Human Pluripotent Embryonic Stem Cell Research, Society for Developmental Biology, Feb. 1999.

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anyone who profits from a wrong is morally implicated in it.80 At the same time, the position taken in the NIH funding rules is unsatisfactory (on scientific and ethical/regulatory grounds) from the opposite perspective: not because it in effect violates the appropriations law but because the system it adopts in order to comply with the statute is untenable. Stem cell research—especially hESC research—is still a young field; its methods are still evolving. Indeed, absent the legal proscriptions, many researchers using hESCs would be involved in deriving the cells or in working closely with colleagues who do so, and their experience in using the cells, including the problems they encounter, would help guide the development and modification of the derivation process. Yet the whole idea behind the General Counsel’s memo and the NIH policy is that derivation and use are two distinct processes that can be wholly separated. Some researchers may be able to conduct their work simply by ordering batches of stem cells from Wi-Cell or another supplier the way they would any other reagent or biologic. For them, the distinction between use and derivation may reflect reality. 81 But for the field as a whole, the imposition of an artificial restraint on the methods of science that separates the process of derivation from research utilizing the stem cell lines is likely to inhibit progress in this field.82 Besides distorting science, the NIH policy undermines the federal government’s ability to shape the ethics of stem cell research or, at the least, the legitimacy of its efforts to exert control over the derivation process. One need not agree with all the details in the NIH rules on the manner in which stem cells used in federally funded research must have been derived (I for one am skeptical about either the practical ability or the desirability of keeping the issue of the eventual donation of some embryos to research out of the discussions and decisions that couples make when beginning the IVF process) to applaud the existence of these ethical standards. But NIH’s moral leverage to insist that these rules be followed is undercut by its own rationale. By claiming that federal funding of research using hESCs does not implicate federal sponsors in the derivation of those stem cells, it would seem to have cut itself off from the derivation process. A usual rule is that the government cannot achieve indirectly what it is precluded from doing directly. The question of legitimacy is particularly pro-


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nounced regarding the very points on which the federal rules are most needed, namely in setting boundaries, such as the prohibition on using stem cells from made-for-research embryos or cloned embryos. The appropriations rider bans federal support for research that creates or destroys human embryos, which means that a federal agency cannot claim to be implementing federal policy were it to limit funding to research that uses only those ES cells that were derived from discarded embryos but not from embryos created for the purpose of deriving ES cells. Thus, under the Clinton-era rules NIH would be hard pressed to justify differentiation based on the type of embryos from which ES cells are derived, thereby losing an opportunity to oversee the derivation process directly and to enforce an important ethical distinction .83

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With rhetorical flourish, one commentator made this point from the viewpoint of someone opposed to the destruction of embryos: [U]nder the rules that Bush is blocking, stem-cell research would not actually take the life of a single embryo. Researchers would use embryos that are being discarded anyway. To anyone who actually believes that new embryos are just as human as you or me, this is like saying, “Well, the Holocaust is going on anyway, so we might as well turn a few dead Jews into lampshades.” Accommodating to evil is evil. Michael Kinsley, If You Believe Embryos Are Humans . . . then curbing research on stem cells is an odd place to start protecting them, TIME , June 25, 2001, at 80. 81 Even when the stem cells used in a research project most clearly resemble any other biologic or reagent purchased from a vendor’s pre-existing stock, one could say that the prospect that scientists would want to purchase the cells may have motivated the derivation of the cells, in which case, paying for the use of the cells is still indirectly paying for their destruction. 82 Alexander M. Capron, End Hypocrisy on Stem Cell Tests, LOS ANGELES TIMES, May 2, 2000, at B9. (“By banning federal funding and hence federal oversight of stem cell research we are actually encouraging unregulated and profit-driven research.”). 83 The desire that limits be placed on the manner in which stem cells are derived is so strong that some proponents of hESC research argued that the recent disclosure that the Jones Institute had created embryos solely for the purpose of harvesting stem cells provided one further reason for the federal government to fund derivation from discarded embryos because doing so provided a means for the NIH to exercise oversight over the way in which the research would be conducted. Earl Lane, Stem Cell Advances Fuel Funding Debate; Some say federal money will promote oversight, NEWSDAY (New York, NY), July 13, 2001, at A24.


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2. Funding Research that Uses Only Existing Stem Cell Lines: To achieve even greater distance from the act of destroying embryos to obtain stem cells, some of the President’s advisors let it be known in July that consideration was being given to limiting federal funding to research that would use already existing hESC lines. This position was presented as a compromise that would allow funding of some research while still literally adhering to the President’s pledge not to support destruction of embryos for research. Just as the Clinton rules—of which this was a modification, rather than a rejection—were crafted to comply with the letter (though not the spirit) of the Dickey Amendment, this proposal struck some right-to-life advocates as adhering literally to the President’s campaign promise by adding “beyond those embryos already destroyed,” while not living up to the meaning of that promise. Nonetheless, some leading Catholic intellectuals apparently gave their blessing to such a compromise.84 It was explicitly discussed by the President when he met informally on July 9 with bioethicists Leon Kass and Daniel Callahan, and it “crystallized” on August 2

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derivation, since such use was the very thing contemplated by the derivers. To fight this conclusion, the Bush administration insists that the President will not in the future extend federal funding beyond the cell lines available as of his August 9th address, although some—including Dr. Kass, whom Bush announced would head a new President’s Council on Bioethics, indicated that if a pressing need arose, the decision could be “revisited.”88 Just as the President’s decision was accepted by some who had opposed federal funding of hESC research (not the least because they had feared he might make a worse decision), it was endorsed by some who favor the research and were relieved to find him making any compromise. In some ways, the reaction among scientists resembled the “stages of dying” popularized years ago by Elisabeth Kübler-Ross, as they grieved, raged, bargained, and came to acceptance. For two weeks after the announcement, as the scientific community awaited information on the cell lines mentioned by the President, skepticism and disappointment were the ma84

when [Bush] talked to scientists at the National Institutes of Health and was told that there were perhaps more than 60 genetically diverse stem cell lines already in existence, far more than anyone had known.85 A week later, the President announced in a televised speech to the nation that he had “concluded that we should allow federal funds to be used for research on these existing stem cell lines, where the life-anddeath decision has already been made.”86 While “some of the leading anti-abortion voices on the Christian right . . . praise [Bush] for a Solomonic decision,” others who oppose federal support are vocally upset with the decision.87 In their view, the moral separation from complicity in the destruction of embryos achieved by the Bush policy is small: profiting from evil is still wrong. Supporters of the decision point to the Catholic Church’s acquiescence in the use of vaccines that are grown on tissue taken from aborted fetus, yet the Catholic hierarchy remains among the religious groups most critical of the decision. Yet the stem cell lines were not created simply to be there as objects of curiosity but to be used in research. Thus, those who use them seem at least indirectly implicated in the act of

“Spokesmen for the U.S. Conference of Catholic Bishops, which represents the church in the United States, specifically have rejected this idea, saying it would make the government complicit in embryo destruction. But one of the nation’s leading Catholic thinkers on abortion issues now is offering a different view. “I can imagine circumstances in which this would not only be politically acceptable but could be a morally justified policy,” said Robert P. George, a moral philosopher at Princeton University who participates in a weekly telephone conference of Catholic intellectuals that often includes White House staff. Another participant in the weekly calls, Rev. Robert A. Sirico, who leads a Michigan-based ethics think tank, said he has told the White House that the compromise might be regarded as acceptable and consistent with church teachings if it ensures that the government never pays for the destruction of another embryo. . . . If Bush moves in any way to support embryo cell research, it will be crucial that he win the support of at least some conservative Catholic leaders, George said. “Then they could say there’s a range of opinion and that this issue is not like abortion or euthanasia,” which are uniformly condemned by church leaders and ethicists.” Aaron Zitner, Possible Stem Cell Compromise Cited by Bush Catholic Advisors, LOS ANGELES TIMES, July 8, 2001, at A1. 85 Katharine Q. Sellye with Frank Bruni, A Long Process Led Bush to His Decision, N.Y. TIMES, Aug. 11, 2001, at A1. 86 Bush’s Address on Federal Financing for Research With Embryonic Stem Cells, N.Y. TIMES, Aug. 10, 2001, at A16 (transcript of speech in Crawford, Texas, prepared by the newspaper). 87 Laurie Goodstein, Abortion Foes Split Over Bush’s Plan on Stem Cells, N.Y. Times, Aug. 12, 2001 (division over President’s decision is not Catholic versus Protestant but “pragmatist versus purist”). 88 Sharon Theimer, Thompson: Bush Firm on Stem Cells, Associated Press, Aug. 12, 2001.

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jor emotions: 60 viable, distinct cell lines did not exist; if they did, they were encumbered by patents and licensing restrictions that would make it difficult to obtain them and burdensome to use them; the method by which the cells had been derived (using bovine serum and mouse embryonic cells) meant they would not be suitable for human therapy because of the risk of transmitting animal viruses; and in any case 60 cell lines were not enough for the full range of research because some of the lines either now or in the future would not be able to be coaxed into becoming the full range of cell types, because they would not cover the full range of human genetic diversity, and because the cells would eventually “wear out” in various ways. Many of those concerns were addressed on August 27, when the NIH issued an “Update.” NIH stated that ten laboratories in the U.S., Australia, India, Israel, and Sweden have derived stem cells from 64 individual, genetically diverse blastocysts that will be included on a “Human Embryonic Stem Cell Registry” provided that the labs certify that they meet the President’s criteria for use in federally funded research, namely: [T]he derivation process (which begins with the destruction of the embryo) was initiated prior to 9:00 p.m. EDT on August 9, 2001. These stem cells must have been derived from an embryo that was created for reproductive purposes and was no longer needed. In addition, informed consent must have been obtained for the donation of the embryo and that donation must not have involved financial inducements.89 As information about the cells and how to obtain them becomes available, it will be included in the Registry, which will “be operational as soon as possible” though not all the cell lines will be available soon, since time may be needed for the labs “to expand to reach larger numbers for the purpose of distribution” and since some lines “are still in the early stages of characterization.” Indeed, the leader of the laboratory in Sweden listed as having 30% of the total cell lines states that only 3 of the 19 lines are established, 4 are being studied, and 12 are still in early stages and may yield far fewer usable lines.90 The NIH, noting that hESC research “is still in its initial stages,” admits that “to date no universally accepted standard [exists] for determining what characteristics will predict the ability of such cells to be, for example, differentiated or, ultimately, useful for the development of therapies.” Addressing


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concerns that patents may impede research, the NIH reported that it had begun negotiating a material transfer agreement on behalf of NIH’s intramural researchers with the owners of the stem cell lines who “have publicly stated that they are very interested in making their cells available for use,” and it expected that such an agreement “may serve as a blueprint for separate agreements by NIH-funded investigators , should their institutions choose to use it.”91 Plainly, many doubts remain about whether the President’s policy will allow American scientists to participate fully in the development of a new field that was launched in 1998 by the announcement that hESC and hEGC had been successfully derived and cultured at two U.S. universities. While it is apparent that the Bush administration overstated what it was offering—for example, in describing the sixtyplus lines as “robust and viable for research”—many commentators apparently believe that the time has come to step back from politics and begin trying to work with the cell lines, testing not only their util-

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N ATIONAL INSTITUTES OF HEALTH (NIH) UPDATE ON EXIST HUMAN EMBRYONIC STEM CELLS, http://www.nih.gov/ news/stemcell/082701list.htm (accessed 8/31/01). Interestingly, these criteria are much less detailed and restrictive than those adopted under the Clinton administration (in terms of informed consent procedures, sources of the embryos, etc); furthermore, since a Registry of accepted cell lines will be established, a researcher receiving federal support need only ensure that any hESCs being used come from such a cell line, whereas under the policy that NIH was about to implement, research that proposed the use of human pluripotent stem cells, had to be formally reviewed by the Human Pluripotent Stem Cell Review Group (HPSCRG), a working group of the Center for Scientific Review Advisory Council (CSRAC) to ensure that the hESCs used were produced in compliance with NIH guidelines. http://grants.nih.gov/grants/guide/notice-files/NOT-OD01–003.html (accessed Aug. 29, 2001). 90 Donald G. McNeil, Small Lab in Sweden Holds a Huge Trove of Stem Cells, N.Y. TIMES , Aug. 29, 2001. (“Those 12 perhaps ought to be called potential cell lines,” said Professor Lars Hamberger, a group leader. “If we get 3 good lines out of them we’ll be satisfied.”) Similarly, the small U.S. company that is second on the list in terms of cell lines, CyThera of San Diego, CA, reports that its 9 lines are still being studied and will not be ready for research use for months. Andrew Pollack, Obscure Biotech Company Becomes Big Player in Stem Cell World, N. Y. TIMES, Aug. 28, 2001. 91 The holder of the principal patent in the field, the Wisconsin Alumni Research Foundation (WARF), in order to be able to facilitate use of stem cell lines created using its method, recently sued the Geron Corporation, which holds exclusive rights to develop six, potentially therapeutic types of tissue from stem cells; WARF is contesting Geron’s claim to an additional 12 tissue types, which it wants to be able to license to other researchers. Sheryl Gay Stolberg, Suit Seeks to Expand Access to Stem Cells, N.Y. TIMES, Aug. 14, 2001, at C2. ING


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ity but also the ability and willingness of the laboratories that have produced them to make them available on reasonable terms. Only such steps will determine the point at which—as researchers argued even before the President’s decisions92—more cell lines are needed for research.93 Of course, not all scientists or those who favor expanding hESC research have accepted the “proceedand-then-reconsider ” stance. Some American researchers—most publicly Roger Pederson who recently left the University of California San Francisco for the University of Cambridge in the U.K.— have gotten fed up with the barriers to stem cell and related biological studies and worry that the more liberal rules applicable in other countries will allow researchers there to outstrip their U.S. competitors.94 Carrying that one step further—and debunking the notion that private funds will ensure that the research is not unduly impeded here—Jim Clark, founder of several Silicon Valley companies, has decided to withhold $60 million of the $150 million he had pledged to Stanford University for a center for biomedical engineering and science because he has concluded that the politicization of stem cell research in the United States means that the “new future for med-

icine and biology and for resulting entrepreneurship ” that he had intended to stimulate at Stanford will instead occur abroad, especially in the U.K.95

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“If human embryonic stem cells prove to be as variable in this way as their mouse counterparts apparently are, then a political compromise floated by the Bush administration in the stem cell debate may not be as practical as some had hoped. That possible compromise would limit the number of embryonic stem cell lines, or colonies, that scientists could work on, thus limiting the number of embryos destroyed. But if seemingly identical cell lines are subtly different from each other, then some may have particular promise for certain uses—such as to make new brain cells for Parkinson’s patients—and others may excel at other tasks, such as becoming cardiac tissue for heart attack patients. ‘You may have to establish hundreds of lines to get the few you’d want to have,’ said John Gearhart, a stem cell researcher at Johns Hopkins University.” Rick Weiss, Clone Study Casts Doubt On Stem Cells; Variations in Mice Raise Human Research Issues, WASHINGTON POST, July 06, 2001, at A1. 93 The short-term effects of Mr. Bush’s policy will be that a lot of important research gets funded using these lines. And that’s all for the good. The long-term fate of stem cell research remains a potentially serious problem. . . . Mr. Bush’s compromise policy will be a reasonable one only as long as the existing cell lines are capable of supporting the research scientists need to perform. Editorial, How Many Lines? WASHINGTON POST, Aug. 31, 2001, at A22. 94 See, e.g., Nicholas Wade, Clearer Guidelines Help Britain to Advance Stem Cell Work, N.Y. TIMES, Aug. 14, 2001, at A1; Edward Epstein, Senator Wants Stem Cell Limit Revised; Boxer asks Bush to Loosen Restriction, SAN FRANCISCO CHRONICLE , Aug. 24, 2001, at A2.

C. Federal Support for Deriving as well as Using Stem Cells In the wake of the media attention to the three new ways of deriving and culturing human pluripotent stem cell lines, President Clinton asked the National Bioethics Advisory Commission (NBAC) to consider the issues involved in this field of research. In a report to the President in September 1999, NBAC made thirteen recommendations.96 The heart of the report is the Commission’s conclusion that an exception should be made in current law specifically to allow federal funding for research involving both the use and derivation of stem cells from embryos. NBAC concluded that at this time only embryos left over from IVF procedures—and not those created for research or through cloning—should be used as a source.97 NBAC’s recommendation that a couple’s decision to discard IVF embryos should be separate from the decision to donate the embryos to research,98 was then reflected, and made more elaborate, in the draft regulations that NIH published three

“[W]ith no prospect of federal support, significant scientific inquiry in a field like stem cell research will stop. No research leader can forgo federal money. Denying financing for this biomedical research will drive the formation of a new pharmaceutical industry outside the United States. Federally funded research helped create America’s economic leadership in the Internet and computer technology. . . . Restricting stem cell research for even a few years simply means that scientists in the United States will not be pioneers. Others will own the patents and claims, and a new pharmaceutical industry will thrive elsewhere. I believe our country risks being thrown into a dark age of medical research. Biologists are at the threshold of the most important set of discoveries in history, and rather than teach and lead, our politicians react and follow a conservative few. This legislative action will cause the United States to miss a revolution in biology. Meanwhile, in the United Kingdom a new industry will be born. It is futile to think that private funding can make up what is being lost to laws driven by conservative politics. I therefore have reluctantly decided to suspend further contributions until our lawmakers decide to pursue what I believe to be a rational course in this vital part of our national future.” Jim Clark, Squandering Our Technological Future, N.Y. TIMES , Aug. 30, 2001, at A19, col. 2. 96 National Bioethics Advisory Commission, ETHICAL ISSUES IN HUMAN STEM CELL RESEARCH, VOL . 1: REPORT AND RECOM MENDATIONS (1999). 97 Id. 98 Id. at 72.

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months later. In order to reinforce the voluntariness of the decision and to diminish the risk of commodification, NBAC also recommended that the sale of embryos be prohibited.99 Finally, NBAC urged the creation of a National Oversight and Review Panel to ensure that federally funded stem cell research is conducted according to ethical principles.100 This Panel would also certify hESC and hEGC lines and maintain public registries and databases to ensure that research in this field is orderly. The following year, Senators Arlen Specter (R-PA) and Tom Harkin (D-IA) introduced the Stem Cell Research Act of 2000, which largely embodied NBAC’s recommendations.101 Section 2 of this act would amend the law regarding stem cell research to allow funding of research that involved the derivation of stem cells from excess embryos created for IVF that would otherwise be discarded.102 The bill also restricts the sale of human gametes and embryos by federal researchers. 103 Finally, the bill requires that all federally funded research on human ES cells be reviewed and approved by an institutiona l review board which will follow guidelines issued by NIH.104 Having not been allowed by the Senate leadership to come to the floor for debate and a vote during 2000, the bill was re-introduced as S. 723 in the Senate on April 5, 2001 and as H.R. 2059 in the House on June 5, 2001. VI. CONCLUSION: THE NEED FOR OVERSIGHT Behind the controversy over hESCs lies the overarching issue of whether public support for research 99

Id. at 74. Id. at 76. 101 Reintroduced this year as S. 723, The Stem Cell Research Act of 2001, 107th Cong. (2001)(amending Part H of the Title IV of the Public Health Service Act, 42 U.S.C. §289 et seq.). 102 Id. 103 Id. 104 Id. 105 See John A. Robertson, Ethics and Policy in Embryonic Stem Cell Research, 9 KENNEDY INSTITUTE OF ETHICS JOURNAL 109, 131 (1999): “Precisely because people differ so sharply over personal spiritual and value commitments, one group should not erect its own view into public policy. Indeed, doing so exacts a high cost from those who would benefit from such research.” 106 Recommendation 8 of the NBAC report urges DHHS to create a “National Stem Cell Oversight and Review Panel to ensure that all federally funded research involving the derivation and/or use of human ES or EG cells is conducted in conformance with the ethical principles and recommendations contained in this report.” NBAC Report, p. 76. The panel, which would have “a broad, multidisciplinary membership, including members of the general public,” would not only review protocols for the derivation of ES and EG cells but also maintain a public registry of approved protocols and certified cell lines as well as a database of 100

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involving human embryos is appropriate when a large number of taxpayers find such work immoral.105 In a democracy based both on majority rule and on the protection of minority rights, are rules against supporting such research too deferential to the minority, or would federal funding of the research constitute too insensitive an involvement of all taxpayers in actions that some of them find deeply offensive? At the moment, several of the policy options regarding public support of embryonic stem cell research are put forward explicitly as compromises. Yet, they are rather unsatisfactory compromises in philosophical as well as practical terms, as they fail to come to grips with the question: are the scientific and clinical benefits reasonably expected from hESC research sufficiently great to justify federal funding of this particular activity in which some human embryos will be destroyed in the first week of their existence? The central lesson of the controversy that has simmered and boiled since three groups of scientists showed in 1998 that human pluripotent stem cell lines could be established from embryonic and fetal cells is that what is most needed is a mechanism for deciding the “justification ” issue in a visible and accountable fashion. The framework for such a process was one of NBAC’s central recommendations106 and was likewise included among the 10 conditions that Sen. Tommy Frist (RTN) placed on his support for stem cell research which he announced at a Senate hearing on July 18, 2001. 107 the results of the protocols, which would permit the “justification” question to be reassessed in light of experience. 107 Rick Weiss & Amy Goldstein, Frist Backs Stem Cell Funding: Senate’s Only Doctor Supports Research, WASHINGTON POST, July 19, 2001, at A1 (among ten “principles” are restrictions on the number of embryo cell lines created with federal money, a preliminary limit of five years of funding, and creation of an independent presidential advisory committee to keep tabs on the research); Sheryl Gay Stolberg, Key Bush Ally Backs Studies of Stem Cells, With Limits, N.Y. TIMES, July 19, 2000(supports federal financing for hESC research “within a very carefully regulated, fully transparent framework”). See also John A. Robertson, Ethics and Policy in Embryonic Stem Cell Research, 9 KENNEDY INST. ETHICS J. 109, 131 (1999). A more fruitful approach to research issues at the beginning of life is to recognize that for most persons the ethical or normative questions that arise are less about duties intrinsically owed to embryos or fetuses than they are about symbolizing or expressing the high respect that most persons have for human life generally. This respect is shown, not by banning all research with embryos or aborted fetuses, but by allowing such research only when good reason exists for engaging in it and an institutional, or even national, review process to assess those reasons has been implemented.


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The U.K. has such an oversight body, the Human Fertilisation and Embryology Authority (HFEA), which also covers the more commonplace matters of IVF and other fertility-related techniques through its system of licensing fertility centers and researchers. That system goes back to the well-known Committee of Inquiry into Human Fertilisation and Embryology, chaired by philosopher Mary Warnock, created in 1983 by the government in response to criticism of Medical Research Council regulations that allowed research on pre-implantation human embryos in the lab. The Warnock Committee reached conclusions very similar to those the EAB had reached five years earlier in its 1979 report on IVF research. The central conclusion was to approve as ethically acceptable research with IVF embryos up to 15 days. That is the point when implantation occurs under normal circumstances and when such differentiation has occurred in the zygote that twinning is no longer possible.108 Whereas the EAB’s report produced no official response and was followed in the United States by heated political debates about IVF and now stem cell research, the Warnock Report led to the establishment of the HFEA, first as a voluntary and later as a mandatory licensing authority in the U.K.109 When controversial issues arise, the HFEA appoints a panel to review the issue and attempt to reconcile the technical concerns of scientists with the moral and social concerns of society.110 Although, the HFEA has not always been able to reach harmonious outcomes, the effect of the HFEA on IVF research in Britain is to provide a normalizing influence that reassures the public that IVF research is conducted as ethically as possible. In contrast, in the U.S., with a prohibition on federal funding for IVF-related research, and no central authority to regulate it, all embryo research is in private hands. Not only is scientific inquiry primarily directed towards developing commercially viable products, but active

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markets have developed for gametes with desirable traits. Ironically, one of the objections to funding IVF research was that it might lead to the creation of markets for human reproductive materials. If the IVF story foretells anything for the unfolding stem cell story, it is that the withdrawal of the federal government from an arena may only add to the process of commodification, commercialization, and exploitation of the vulnerable. As the President’s policy is implemented by researchers and scrutinized by the public, Congress ought to be willing to ask whether a better policy cannot be crafted. Full authority for federal agencies to fund research deriving and using hESCs would build a better scientific base, with the fruits accessible to all investigators, and would give federally supported scientists full access to this important new tool. But such a policy must also provide ethics oversight and guidance that should deter commercialization and encourage respect for all involved in stem cell research, including the donated embryos. 111

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In Professor (later Dame) Warnock’s words, “It is therefore difficult for me . . . to trace my origin as an individual beyond the 14-day stage to the stage when I might have been two.” MARY WARNOCK , AN INTELLIGENT PERSON’S GUIDE TO ETHICS 43 (1998). 109 The Human Fertilisation and Embryology Act 1990 creates the Authority as a licensing and regulatory body (Schedule 2 §3). Furthermore, the Act allows research on embryos to continue until the formation of the primitive streak (Section 3(3)(a)). Finally, the Act forbids payment for human gametes. 110 For example, the process of sex selection of embryos used in IVF became possible in 1989. When the Authority reviewed these issues, they had no problem allowing sex selection against detrimental genetic traits. However, sex selection based on preference was found to not be socially acceptable and forbade all centers licensed under the Act from performing sex selection techniques for personal preference. 111 I thank Michael Albrecht, Ph.D., USC Law Class of 2002, and Houman Ehsan, M.D., USC Law Class of 2004, for their invaluable research assistance.