Sci. Aging Knowl. Environ., 1 September 2004
The history of in vitro fertilization could offer insights into how the controversy over the use of human embryos for stem cell research might play out
Abstract: Embryonic stem cells have the potential to turn into any type of cell, perhaps someday providing a way to replace tissues harmed by age-related and other diseases. But the complex ethical questions that swirl around this area of research--which requires the destruction of early embryos--are not new. The moral and philosophical issues in the stem cell debate trace their roots to the controversy over in vitro fertilization in the years surrounding the birth of the first "test tube baby" in 1978.
"When in the course of development does a living human embryo acquire protectable humanity? ... Here, nascent lives are being deliberately created despite certain knowledge that many of them will be destroyed or discarded." Leon Kass, chair of the President's Council on Bioethics, wrote these words more than 3 decades ago. The year was 1972, the article was "Making babies--the new biology and the 'old' morality" in Public Interest, and the target of Kass's 39-page analysis was the radical, disquieting technology of in vitro fertilization (IVF). But virtually the same sentences could be written today to summarize a central question in the controversy over embryonic stem cell research.
Back then, human embryonic stem cells weren't even a gleam in the eye of the scientific community. No one foresaw the current furor over these cells that, plucked from an embryo just days after fertilization, are like unmolded clay: Research suggests that they can be sculpted into any specialized cell, perhaps someday providing a healing bounty of cells to replace those in the heart, pancreas, or other organs impaired by age-related or other afflictions. But extracting stem cells from an early embryo destroys it--a fact that has rekindled the battle over human embryo research that first appeared on the public radar with IVF.
Embryonic stem cell technology is new, but the ethical questions roiling around it are not. Is a week-old embryo, a cluster of a couple hundred cells, a human being? Is it a callous violation of human dignity or even murder, as some accuse, to use this early embryo, or blastocyst, for research that critics say might not even yield therapeutic medicines? Will it usher in human cloning? The moral and philosophical issues surrounding stem cell science trace their roots to the achievement that made IVF possible: combining eggs and sperm and growing the resulting human embryos in a petri dish. "We've been through these arguments before," says bioethicist Arthur Caplan of the University of Pennsylvania in Philadelphia.
The debates then and now aren't perfectly parallel, but how society at first recoiled from and then embraced IVF foreshadowed the negative reaction to stem cells--and might well portend the future outcome of the controversy. Some observers, among them Harvard government professor Michael Sandel, a member of Kass's bioethics council, have noted that if one opposes embryonic stem cells, one should also oppose IVF, because the arguments for or against the two technologies stand and fall together.
Today, IVF raises few eyebrows. Even Kass, a leading opponent of the technology in its early days, changed his stance after the 1978 birth of Louise Brown, the first "test tube baby." He recognized the joy it could confer by blessing infertile couples with children. Still, he remains apprehensive about the broader implications of assisted reproduction and its associated innovations. "If anybody thinks that the controversies that were started by IVF have been settled and gone away," he says, "they should rethink."
From Sci-Fi Horror to Family Blessing Back to TopIn the public perception, IVF evolved from a nightmarish contrivance into a routine fixture, the same evolution that many a scientific advance has undergone. "The first time you hear about it creates worries, concerns, and perhaps some opposition," says bioethicist Ruth Macklin of the Albert Einstein College of Medicine in New York City. "But then people just tend to become more comfortable once it becomes established."
IVF pioneers often met with skepticism because colleagues doubted they'd succeed--and with repugnance because critics, including the Catholic Church, viewed the act of initiating life in the lab as unnatural and immoral. In 1969, University of Cambridge embryologist Robert Edwards, Oldham General Hospital surgical gynecologist Patrick Steptoe, and a colleague reported that they had fertilized a human egg in a petri dish. Commentators conjured Brave New World scenarios. One British newspaper reporter warned, "The test tube time-bomb is ticking away." The research, he wrote, brought scientists closer to someday cloning "a cohort of super-astronauts or dustmen, soldiers or senators."
But the predominant anxiety was that IVF would beget deformed monstrosities. Kass, then a member of the life sciences committee of the National Academy of Sciences, wrote a 1971 article entitled "Babies by Means of in vitro Fertilization: Unethical Experiments on the Unborn?" At a Washington, D.C., bioethics symposium, Edwards faced off against Kass and Princeton University theologian Paul Ramsey. Ramsey delivered "a denunciation of our work as if from some nineteenth-century pulpit," Edwards later recounted in A Matter of Life. "... Our work was, he thundered, 'unethical medical experimentation on possible future human beings and therefore it is subject to absolute moral prohibition.' " Another speaker, James Watson, who co-discovered DNA's double-helical structure, said that attempting IVF would necessitate "infanticide" to get rid of the "mistakes."
Edwards and Steptoe were convinced that the technique was safe, based partly on IVF experiments in animals. On 25 July 1978, Louise Brown was born. Apparently perfect, she silenced the criticisms about birth defects, says Caplan. Since then, more than a million births worldwide have confirmed that IVF and related assisted reproductive technologies, although not risk-free, are largely safe.
The debate shifted focus toward religious and moral concerns: The technique was a societal threat, conservatives said, for it would unravel the ties that bind marriage, procreation, and family. The fate of lab-manufactured human embryos drew increasing attention, foreshadowing entanglement in abortion politics. Writing in the New York Times, Georgetown University ethicist Richard McCormick noted that the British researchers had gone through roughly 200 fertilized eggs before their first IVF success. Were these discards "mini-abortions?" McCormick asked. He wasn't sure, but "the only thing standing between an eight-cell zygote and Louise Brown is a uterine home for nine months. Being a zygote is a part of the history of all of us. ... [W]e should not close our eyes."
Kass meanwhile had been arguing since his 1972 essay that creating human life in the laboratory was "a degradation of parenthood" and an assault upon marriage and family. He also worried that IVF would lead to egg and embryo donation, babymaking by single women or lesbians, surrogate pregnancy, commercialization of reproduction, and the potential exploitation of women and their bodies. Furthermore, the technology would pave the way toward troubling innovations such as genetic engineering and human cloning. Turning procreation into manufacture and regarding children as products of one's will would violate human dignity, he said. Although he came to judge IVF acceptable (for married infertile couples) by the time he spoke before a federal ethics advisory panel in fall 1978, Kass still claimed that "the humanness of our human life" was at stake.
Three decades later, many of the technological procedures that Kass and others wrote of have come to pass. But generally, says Caplan, the feared ills of an undermining of family, a cheapening of respect for human life, and exploitation of women haven't materialized. One prediction, however, has borne out: the rise of a commercial market in IVF services. Because of the maelstrom surrounding test tube babies and human-embryo research, from the mid-1970s until 2001--when restricted federal support for embryonic stem cell work became available under the Bush Administration--no scientist received federal money to do studies in those areas. As a result, Caplan says, assisted reproduction rapidly turned into a "Wild Wild West" private industry--with no clinical trials and little oversight on matters such as disclosure of health risks to egg donors and recipients. No one regulates how many embryos clinics can implant into a woman's uterus, resulting in high-risk, multiple pregnancies. In a controversial endeavor, one IVF center used genetic diagnosis of embryos to create a baby who could provide a compatible cord blood transplant for a sick sister. Donor eggs have been sold over the Internet to the highest bidder, Caplan says. And assisted reproductive technologies are mostly available only to the rich. The commercialization of babymaking that critics had warned about came true--in large part, ironically, because of their opposition, says Caplan. "Because it was so controversial, the federal government stayed out of it," he says, "and that made it next to impossible to regulate it."
The IVF Legacy Back to TopAlthough virtually all would now agree that IVF has, on the whole, been positive for society, bioethicist Daniel Callahan of the Hastings Center in Garrison, New York, says, "The research did open the way to more meddling with embryos." But where Callahan sees "meddling," scientists see progress. Such is the case with human embryonic stem cell research, which would have remained out of reach without the technique of IVF. Edwards was already dabbling with rabbit embryonic stem cells in the 1960s; today, he advocates efforts to develop stem cells' therapeutic promise.
In 1998, two U.S. laboratories isolated human embryonic stem cells for the first time, from spare embryos stored in IVF clinics and from aborted fetal tissue. Stem cells can also be cultivated from adult tissue, and although they are considered less pliable because they are already partly specialized, such cells are another source of promise for regenerative medicine (see "Lucky or Good? Stem cells' all-around talent disputed" and Edelberg Perspective). But embryonic stem cells draw the most political fire. As a result, under the restricted policy that President George W. Bush announced in August 2001, federal grants will fund only studies using the 78 stem cell lines that had already been derived from leftover IVF embryos. As Bush explained, "the life and death decision has already been made."
The week-old blastocyst is a blackberry-like cluster of cells that has no organs, no brain, and no capacity to feel pain. "This group of cells has no ability to develop into anything if it isn't implanted," says biochemist Maxine Singer, chair of the National Academy of Sciences' Committee on Science, Engineering, and Public Policy. Singer, like most scientists, does not regard the cells as a person.
But others see the embryo as a full-fledged human being, or at least as nascent life that deserves some respect and protection. A blastocyst is "exactly what a human being is like in 5 days," says Kass, echoing McCormick's caveat about IVF from more than 25 years earlier. "That doesn't mean that you have to insist that it's fully one of us, but you can't treat it as just a bag of cells." He opposes the creation and destruction of embryos for research and supports the Bush policy.
Some observers point out an inconsistency in the stance against embryonic stem cell research. Viewing the embryo as a person, Sandel argues, rules out not only stem cell research but IVF, which also involves creation and destruction of excess embryos.
"[I]f it is immoral to sacrifice embryos for the sake of curing or treating devastating diseases, it is also immoral to sacrifice them for the sake of treating infertility," he writes in the 15 July 2004 issue of the New England Journal of Medicine. In U.S. IVF clinics, 400,000 spare embryos were frozen in storage as of 2002; most will be destroyed. Yet, Sandel notes, stem cell foes have not urged banning IVF. Their objections to the research, he concludes, "cannot rest on the principle that embryos are inviolable."
Kass counters: In IVF clinics, embryos are made with "reproductive intent." Every one was produced in the hope that it might become a child, although with the knowledge that some of them will be discarded--similar to how, when a couple tries to conceive the traditional way, several eggs are fertilized over a period of months yet naturally fail to implant. "You are not deliberately creating embryos to destroy them," he says. But manufacturing embryos for stem cell studies requires generating them with the intent of destroying all of them for research purposes, he says. To manufacture and treat life as a natural resource for experimentation, he says, is to cross a major moral boundary.
But Macklin, who doesn't believe a blastocyst has a right to life, says "intention has nothing to do with the morality of killing embryos"; the end result is the same. And there is no ethical distinction, she says, between deliberately destroying an embryo and allowing it to sit around indefinitely in a tank of liquid nitrogen.
Other stem cell fears echo those that originally encircled IVF, including trepidation over the commodification of the human embryo and potential exploitation of women as egg factories. Some members of Kass's bioethics council have warned that society would suffer a "coarsening" of moral sensibilities toward human life and slide down the slippery slope toward genetically engineering babies and growing embryos to later stages for harvesting tissues and organs. And once again the threat of carbon-copying people--or reproductive cloning--has been cited, this time by observers who point to Dolly the cloned sheep as proof that the technology is imminent.
The creation of embryonic stem cells has been conflated with reproductive cloning because of a technical connection. What's known as therapeutic or research cloning is a means for producing stem cells with a genetic makeup known to predispose a person to, say, Parkinson's disease, in order to unravel how the disease develops. These stem cells would result from a process called somatic cell nuclear transfer (SCNT): taking a woman's egg, removing the nucleus, replacing it with one from an adult cell from a person with Parkinson's, and then harvesting cells from the resulting embryo after about a week's growth in a petri dish. Alternatively, if SCNT were used to create neural stem cells that carry a Parkinson's patient's genetic background but function properly, it might permit cell replacement therapy without the problems of immune-system rejection.
Embryos generated by SCNT could, in principle, be implanted into a woman's uterus, which could theoretically result in the birth of a cloned person. This line of reasoning has smeared the technique's reputation by association. A major reason Kass opposes therapeutic cloning, for instance, is because it would crack open the door to reproductive cloning. The president's bioethics panel voted in 2002 to recommend banning the latter procedure and placing a 4-year moratorium on the former. During the committee's discussions, member Charles Krauthammer warned in a memo that the way research cloning confers "thingness" on the human embryo "is the ultimate in desensitization. ... [O]nce cloning has changed us, it will inevitably enable further assaults on human dignity." Still, despite his cautions, Krauthammer supports stem cell studies with spare IVF embryos.
Talk of preventing dehumanization and protecting human dignity sounds lofty. But one might ask what it means in the context of any human embryo research, including that which led to IVF. When Louise Brown arrived as the first lab-generated baby, surely most people did not feel less human and begin treating their family, friends, and strangers with less regard. "The fears of disrespect, loss of dignity, I don't think have ever proven true," says Caplan. No one has documented any stigma, for instance, to being born through IVF. "I never heard any schoolkid say, 'Well I really feel terrible, Mom. They taunted me at school and said that I was an IVF baby.' " And IVF doctors don't seem less respectful of embryos or gametes than anyone else, says Caplan, who recently surveyed clinicians at fertility clinics about the disposal of embryos.
Winds of Politics Back to TopThe heated ethical debate has led to a stalemate over federal funding. Human embryonic stem cells stand to become a core biomedical technology, says Ronald McKay, a neuroscientist at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland. To take the research into clinical reality will require a coordinated investment in a series of supporting technologies. Federal funding could play a central role in achieving that goal, as it has in developing emerging areas of biomedical research in the past, he says.
But bioethicist Callahan says that the National Institutes of Health is already pouring millions into curing every major disease that stem cells are supposed to remedy: "I think we can get the same results by far more acceptable means of research." The lifesaving promise of stem cells has been "overblown," Callahan says. Like gene therapy, which was widely hyped but hasn't panned out, he adds, stem cell treatments "may not work at all."
Moreover, defenders of the Bush policy say it provides sufficient support for the new field, allowing research to advance on the 78 eligible stem cell lines but not encouraging destruction of more embryos. No ceiling is set on the amount of money available for such work, and stem cell science has not been banned in the private sector, they point out. Kass views the policy as "a principled solution to a genuinely difficult moral dilemma." Given that a large fraction of citizens regard the destruction of human embryos "as the equivalent of gratuitous homicide," he says, the government shouldn't insist that their tax dollars pay for it.
Yet scientists, saying that the only way to find out whether stem cells can successfully fight disease is to study them, chafe at the White House for stymieing the field, because only 21 of the approved stem cell lines are available for research. Furthermore, the lines wouldn't be appropriate for therapeutic purposes because they are grown in cultures with mouse "feeder" cells, raising the possibility of contamination by mouse viruses. Critics of the Bush policy regard the funding roadblock as déjà vu. "The federal government should be in here trying to keep an eye on this technology," says Caplan. "Leaving it to the private sector and saying, 'Well, do what you want there, just don't do it with federal funds,' is a mistake. And the history of in vitro fertilization shows that."
Kass says he'd like to see the academic scientific community propose limits on its use of human embryos for stem cell studies: "Are they willing to say, No more beyond this stage?" Researchers should develop "the kinds of boundaries, guidelines, institutional mechanisms that would give reassurance to the most serious [moral] concerns. And do this as a condition for getting the funding. ... When the scientific community is willing to do that first, then I will take seriously [its] remarks that, 'Only if they turned it over to us can it be morally regulated.' "
McKay and Singer agree that scientists must step up to the plate. "People need to be confident that the biomedical research community will act in a way that's sensitive to the ethical concerns of the majority of the population," McKay says. What the stem cell field needs, Singer and others say, is an effort similar to the Asilomar Conference: the meeting in central California in 1975 at which scientific leaders drew up voluntary guidelines for the new field of recombinant DNA technology.
Such a move is under way: The National Academy of Sciences has convened a committee to craft voluntary guidelines for responsible practices in human embryonic stem cell experiments. The panel will hold its first public workshop in Washington, D.C., 12 and 13 October. But no one expects it to easily break the impasse. For real change, all scientists' eyes are on the November presidential election. Meanwhile, work in the field is proceeding unfettered abroad, at U.S. companies, and at universities such as Stanford and Harvard, which have set up privately funded institutes for the research. Even opponents of the enterprise acknowledge that, in the same way Louise Brown's birth transformed the IVF debate, embryonic stem cell technology will be unstoppable if scientists make a major breakthrough that establishes its therapeutic potential.
September 1, 2004
Freelance writer Ingfei Chen could use a dose of neural stem cells to repair the stresses sustained while summarizing the thorny issues of this debate.
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