The Niche

Stem cell research: persistence pays off

Here is a preview of an article that will be on the site next month.

Sermons railed against the creation of monsters. Headlines invoked the spectres of “frankenbunny” and “mootants”. Scientists were branded as Nazis — or worse.

And yet the research community in the United Kingdom won over a majority of the public and convinced Parliament to approve some of the most permissive embryonic stem (ES) cell research provisions in the world, expected to be finalized this autumn. So British stem cell scientists might be forgiven for being a mite critical of the low profile adopted by their counterparts in countries such as the United States and Germany.

“In other countries, scientists just keep their heads down,” says Stephen Minger, director of the Stem Cell Biology Laboratory at King’s College London. “Even with the approved lines, they don’t admit to doing embryonic stem cell research”.

For Minger, an American ex-pat, that’s the wrong way to go. He and other UK researchers speaking this July at the European Science Open Forum in Barcelona, Spain, said they had overcome fierce opposition by being at the front of the national debate over legislation governing human stem cell research. Once passed into law, the updated Human Fertilisation and Embryology Bill will expand the existing regulatory framework to include four new types of human–animal hybrid embryos.

Far less ambitious efforts in both the US Congress and Germany’s Bundestag to bolster research on human ES cells have met with scant success. The obvious question is whether Britain’s expansionist strategy can be tailored to fit the cultural realities elsewhere.

In the United Kingdom, a largely secular public has had decades to get used to the idea of scientific tinkering with human embryos. Researchers point to the first successes of in vitro fertilization (IVF) in humans and the birth of Louise Brown 30 years ago as a watershed. The visceral reactions and vigorous debate that this event engendered led to the passing of the first Human Fertilisation and Embryology Act in 1990 and the creation of the well-respected Human Fertilisation and Embryology Authority (HFEA) in the same year — and an expectation of open, if sometimes heated, discussion over the fate of human embryos.

In Germany, on the other hand, the country’s deeply conflicted views over the ethics of ES cell research are routinely attributed to revulsion over the inhumane experiments on humans carried out under the Nazi regime. In a 2006 interview with the New York Times, German Nobel laureate Christiane Nüsslein-Volhard said the “horrible” pseudoscience had contributed to the public’s “deep distrust in science and also a fear that you open Pandora’s box and you don’t know what’s coming out”. Some objectors to the UK’s new law, in fact, claim it violates the Nuremberg Code of 1947, a ten-point set of guidelines for research on humans drawn up in response to Nazi atrocities.

And in the United States, researchers and politicians cite the 1973 Roe v. Wade Supreme Court decision legalizing abortion, and the ensuing pro-choice versus pro-life cultural war, as the lens framing nearly all public discussions of embryos and human ES cells.

Nonetheless, the battle to win over British hearts and minds suggests that acceptance of ES cell research derives in large part from humdrum persistence by scientists: properly defining the science and explaining the goals; emphasizing a commitment to appropriate regulations; and reaching out to receptive audiences.

Advancing step by step

Giving the process time has perhaps been most important of all, say British policy-watchers. Under the auspices of the HFEA, researchers were first permitted to use discarded IVF embryos for research in 1991. The range of acceptable research was gradually widened, until Britain issued the first licences to derive human ES cells from IVF embryos in 2002, the same year that it outlawed reproductive cloning.

In 2006, scientists said they needed to construct a new type of embryo. A shortage of donated human eggs was curtailing the ability to create disease- and patient-specific cells by nuclear transfer. Researchers argued that this bottleneck could be overcome by inserting human DNA into enucleated fertilized cow’s eggs to create hybrid embryos (the ‘mootants’ of the tabloids and blogosphere) suitable for deriving essentially human ES cells. The result: more basic research that might lead to cures. But would the resulting embryos be classified as cows or humans? No one knew, said Minger, but existing UK regulations clearly didn’t apply. “So the science community went to the regulators and said ‘regulate us’,” he says. “Kind of weird, huh?”

But the researchers had a game plan, staking their chances on public respect for the HFEA’s regulatory role, the tradition of open debate over embryo-related science, and the continuing prohibition on reproductive cloning. Although a UK government ‘white paper’ (a policy document for consultation) proposed an outright ban on hybrid embryos, a parliamentary committee sided with the scientists in concluding that the embryos were technically human and could be used for tightly controlled research. The HFEA agreed, clearing the way for the new Human Fertilisation and Embryology Bill, now awaiting only pro forma finalization.

Of the four new categories of embryos included in the bill, true hybrids formed by the union of human and non-human gametes proved even more contentious than the cow embryo–human DNA hybrids. Researchers, though, argued that including true hybrid embryos under the HFEA’s jurisdiction would ensure that such research was strongly regulated.

Speaking in Barcelona, Norman Warner, a former health minister in the UK government, recalled denunciations from the nation’s pulpits and said the bill’s final stages were delayed to avoid upsetting Catholic voters before a series of important by-elections. Nevertheless, he said, a clear majority of the public — once they were aware of the bill’s aims — backed the government against attacks by organized religion and what he called “dialogues of the deaf”. An open letter to the government supporting the bill was signed by representatives of 223 medical organizations and charities. “They were quite happy to meddle with nature because they weren’t happy about what nature was doing to afflict those near and dear to them,” Warner said.

Policy meets history

In Germany, scientists have had to tread more carefully. Lingering unease over meddling with nature has led to an unlikely alliance of conservative parties, the liberal Green Party and the Catholic Church arguing that unlimited protection of human life from its biological beginning is non-negotiable, along with human dignity and human rights. The alliance pushed through one of Europe’s most restrictive policies against human ES cell research, enacted 10 May, 2002. The new law imposed a blanket ban on any derivation of the cells within Germany’s borders and limited their importation only to ES cells derived before 2002 from embryos not created for scientific purposes. In more recent deliberations, lawmakers dropped a provision to punish citizens who conduct ES cell research abroad only after it was deemed unconstitutional. In April, however, a divided Bundestag voted to move the cut-off date for derived ES cell imports to 1 May 2007, increasing the number of available cell lines by an order of magnitude.

Unlike the United States, the debate in Germany has not followed the battle lines over abortion: that is legal in Germany within the first trimester of pregnancy, and throughout its duration if a woman’s health is at risk. IUDs and the ‘morning after’ pill are both allowed.

When thousands of embryos are killed each year through the use of IUDs, there is no convincing reason for Germany approving only 20 research projects with imported ES cells over a five-year period, complains Urban Wiesing of the University of Tübingen’s Institute for Ethics and History of Medicine. At the Barcelona conference, Wiesing said Germany’s views are best summed up by the saying: “Wash me, but don’t make me wet”. Ultimately, he said, the country must ask itself whether a pluralistic state can accept varying positions on the rights of an embryo and whether states that allow ES cell research are still in accordance with human dignity and rights.

Nevertheless, polls suggest that a majority of Germans are uncomfortable with the morality of ES cell research. An international survey conducted by the BBVA Foundation, based in Bilbao, Spain, earlier this year found that German respondents were more likely to agree that research with human embryos to obtain stem cells is “immoral” rather than “very useful”. Out of respondents polled in 15 countries, Germans were also the most likely to agree that “research with human embryos that are a few days old is an unacceptable interference into the natural processes of life”.

Perhaps nowhere is the moral divide more pronounced than in the United States, a polarization reflected by the same international poll and in the vastly different legislative and funding positions of individual states. Congresswoman Diana DeGette (Democrat, Colorado), an outspoken supporter of ES cell research, defends the gun-shy mentality of some scientists. “I think that researchers in this country have been frustrated and felt powerless because they didn’t really understand how they could affect the political process,” she says.

DeGette said some researchers have retreated to the lab after seeing their positions distorted in the press. Nevertheless, she hails the 2008 amendments to the National Academies’ Guidelines for Human Embryonic Stem Cell Research, which stress the need for continued experiments with human ES cells as part of a comprehensive strategy. More scientists are becoming directly involved with the legislative process, she said, helping the bipartisan Stem Cell Research Enhancement Act co-sponsored win approval in the House of Representatives and the Senate in 2006, only to be vetoed by President George W. Bush. A similarly-worded bill that would have relaxed federal restrictions met the same fate in 2007.

Support for expanding ES cell research is solid, said DeGette. “What has happened, though, is that we have one stubborn person in the White House who refuses to even talk to us,” she says. That could change. Presidential candidates Sen. Barack Obama (Democrat, Illinois) and Sen. John McCain (Republican, Arizona) both voted in favor of the 2006 and 2007 bills, though McCain has since modified his stance. Unlike Obama, McCain has not explicitly pledged to lift the ban on federal funding of research on ES cell lines created after August 9, 2001.

Good visibility

Visibility and open dialogue have helped defuse the controversy for most people in the United Kingdom, says Alison Murdoch, who, like Minger, received one of the country’s first licences to clone human embryos in order to create ES cell lines. A fertility expert at the Centre for Life in Newcastle upon Tyne, her IVF clinic borders one of the city’s main squares and a major thoroughfare. “There’s a circus in the square at the moment, and yet we’ve got all this work going on, on the third floor,” Murdoch says. “The danger, sometimes, is to put barbed wire around it. That scares people. Not putting barriers up has to be beneficial”.

Murdoch has her limits, though. “I’ve rather lost any will to talk to people who are already entrenched in their views,” she says. “I think we need to talk to people who are the next generation”. In the end, though, a “very healthy” national debate led to a majority of members of parliament signing the bill, she says.

Which isn’t to say that scientific input always matches governmental output. Murdoch, for instance, says the new bill misses a chance to do away with emotion-laden descriptions. The legal language, she says, defines embryos so loosely that even an unfertilized egg and sperm in a Petri dish would qualify. And Minger recalls sitting in a parliamentary session with another scientist when they first heard a proposal for a fifth class of regulated embryo. “We looked at each other in horror because we couldn’t understand what this fifth class of embryos was,” he said. They still can’t, although much to Minger’s relief, the proposal was ultimately scrapped.


Comments are closed.