Déjà Vu

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.

"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 in Public Interest. The year was 1972, 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 one of the central questions 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 bounty of cells to replace those in the heart, pancreas, or other organs impaired by age-related or other afflictions (see "A Rush to Judgement?). But extracting stem cells from an early embryo destroys it--a fact that has rekindled the battle about human embryo research that first hit the public radar with IVF.

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 outcome of the controversy. 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 IVF 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."

In the public perception, IVF initially looked like a nightmarish contrivance. 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. But the predominant anxiety was that the technique would beget deformed monstrosities. Nobel Laureate James Watson said that attempting IVF would necessitate "infanticide" to get rid of the "mistakes."

But on 25 July 1978, Louise Brown was born. Apparently perfect, she silenced the criticisms about birth defects, says Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia and a member of SAGE Crossroads' editorial board. Since then, more than a million births worldwide have confirmed that IVF and related assisted reproductive techniques, although not risk-free, are largely safe.

The debate subsequently 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. Writing in the New York Times, Georgetown University ethicist Richard McCormick noted that the researchers who developed the technique had gone through roughly 200 fertilized eggs before their first IVF success. Were these discards "mini-abortions?" McCormick asked. He wasn't sure, but he wrote, "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 on marriage, family, and human dignity. 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. Although he came to judge IVF acceptable (for married infertile couples) after Louise Brown's birth, 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--such as egg donation--have come to pass. But generally, says Caplan, the feared social ramifications--undermining family, cheapening the respect for human life, exploitation of women--haven't materialized.

One prediction, however, has been 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--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. 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 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."

Although virtually all would now agree that IVF has, on the whole, been positive for society, bioethicist Daniel Callahan of the Hastings Center 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.

Stem cells can also be cultivated from adult tissue; and although adult stem cells are considered less pliable because they are already partly specialized, they are another source of promise for regenerative medicine. But embryonic stem cells, which were first isolated in 1998 from spare embryos stored in IVF clinics, draw the most political fire. Some critics of the work view the destruction of an early embryo, or blastocyst, as tantamount to murder. So 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."

Scientists, however, note that 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 Science's Committee on Science, Engineering, and Public Policy. Singer, like most researchers, does not regard the ball of 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 in 1978. "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,” Kass says.

However, Harvard government professor Michael Sandel, a member of Kass's bioethics council, points out that viewing the embryo as a person 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, every embryo 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 bioethicist Ruth Macklin of the Albert Einstein College of Medicine in New York City, 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. In addition to harvesting cells from embryos created through routine IVF, researchers would like to generate cells of a known genetic makeup by therapeutic or research cloning--known technically as somatic cell nuclear transfer (SCNT). For example, using SCNT, researchers could grow neurons from a person with Parkinson's disease. To do so, scientists would take a woman's egg, remove the nucleus, replace it with one from an adult cell from a person with Parkinson's, and harvest stem cells from the resulting embryo after about a week's growth in a petri dish; then the researchers would stimulate the cells to specialize into neurons. Having these cells could help researchers unravel how the disorder develops. And in the long term, SCNT might boost efforts to bring new cell-replacement therapies to the clinic. If SCNT were used to create neural stem cells that carry a Parkinson's patient's genetic background but function properly, it might permit such treatment 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.

The heated ethical debate has yielded 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. But 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. " And 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 that 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.

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 to address the most serious moral concerns; and it should do so as a condition for getting more federal 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. 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. Embryonic stem cell science has become a hot campaign issue since former president Ronald Reagan's family began advocating it after his death from Alzheimer's disease last summer. 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.

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.