Under the lens: the US Congress may ban therapeutic cloning. Credit: SPL

“Driven by ignorance, conservative thinking and fear of the unknown, our political leaders have undertaken to make laws that suppress this type of research ... I believe our country risks being thrown into a dark age of medical research.”

With these words, delivered in an opinion article in The New York Times on 31 August, software mogul Jim Clark announced that he was suspending $60 million of a $150-million donation to Stanford University in California (see Nature 413, 5; 2001). He attacked restrictions imposed on federal funding for research on human embryonic stem (ES) cells, and legislation before Congress that would ban human therapeutic cloning — a technique that could generate ES cells genetically matched to individual patients.

These arguments echoed statements made in July by stem-cell researcher Roger Pedersen, when he announced that he was leaving the University of California, San Francisco, for the University of Cambridge (see Nature 412, 262; 2001), citing Britain's political support for ES-cell research.

Dark age: Jim Clark warns that US biomedicine will fall behind.

Meanwhile, Geron of Menlo Park, California, the leading company in the field, began telling reporters that the bill before Congress opposing therapeutic cloning might force it to shift investment to its British-based subsidiary Geron BioMed. In its 10 September issue, Business Week summed up the worries about US competitiveness with an article under the headline: “At risk: a golden opportunity in biotech”.

Despite the gloomy headlines, most experts interviewed by Nature do not believe that there is an imminent danger of a brain drain of top ES-cell scientists from the United States to countries that have taken a more permissive attitude to the research, nor of an immediate threat to US competitiveness in biomedicine more generally.

First, they stress the need to put the threats into perspective. Clark's money, for instance, is being used to construct an interdisciplinary research centre called Bio-X, but its construction had already been scaled back in the face of opposition from local residents. And the generous salaries and enviable working conditions available for US biomedical scientists mean that a significant brain drain is unlikely.

Making a start

More importantly, federally funded US researchers can now at least make a start on human ES-cell research, thanks to the compromise, announced by President George W. Bush on 9 August, that allows researchers to seek grants from the National Institutes of Health (NIH) to work on 64 human ES-cell lines isolated before then (see Nature 412, 665; 2001). Work on human ES cells is at such an early stage that US researchers will for now have plenty to do characterizing these lines and trying to determine whether any of them have clinical potential.

“I don't think there will be a large-scale migration of top US researchers to the UK, Singapore, Sweden and Australia,” says Alan Trounson of the Institute of Reproduction and Development at Monash University near Melbourne, Australia, where six of the these cell lines were derived. The main concern, however, is whether controls on federal funding will restrict the number of US researchers entering the ES-cell field.

Bated breath: a Parkinson's disease patient listens to Bush's stem-cell announcement. Credit: AP

Much will depend upon how the entire field of regenerative medicine develops. From 1988 to 1993, the administrations of Presidents Ronald Reagan and George Bush Sr imposed a moratorium on federal funding for research on therapies involving tissues from aborted fetuses. But because trials using fetal tissue grafts to treat conditions such as Parkinson's disease have yielded disappointing results, that ban is, in retrospect, not felt to have kept US researchers out of a crucial area of biomedicine.

Most experts believe that stem-cell therapies hold much greater promise — in theory, it should be possible to use them to repair a wide range of the body's tissues. But, at present, it is unclear whether ES cells will emerge as the main clinical contenders, or whether they will be eclipsed by therapies that exploit the adult stem cells found in many of our tissues. The prospects for therapeutic cloning, which may be too expensive and cumbersome for routine use, are even more uncertain (see Nature 410, 622–625; 2001).

Attention will now focus on practical questions surrounding the approved human ES-cell lines. Experience with mouse ES cells suggests that labs will, over time, zero in on a handful of lines that remain stable and viable, and retain their ability to differentiate into each of the body's tissues. If those are all on the list approved by President Bush, US researchers may be able to compete effectively in the initial stages of basic research.

“I think most will watch closely and give the situation another year to mature,” says Tom Cech, president of the Howard Hughes Medical Institute (HHMI), based in Chevy Chase, Maryland, the largest US source of philanthropic funding for biomedical research.

But there is a strong possibility that new cell lines may emerge that are clearly superior to those currently approved for US federal funding. “At this stage, we cannot predict where discoveries will come from,” says Chris Juttner, vice-president for clinical affairs with BresaGen of Adelaide, Australia, which developed four of the ES-cell lines on Bush's list. He notes that several companies are trying to establish human ES cells that can grow in the absence of a layer of mouse 'feeder' cells, making them more suitable for use in human patients. “It is only a matter of time that scientists figure out a better way to derive stem cells,” says Lawrence Soler, chair of the Coalition for the Advancement of Medical Research in Washington, which lobbies in favour of ES-cell research. “As time goes on, there will be more and more frustration among American scientists.”

Twin track

US academics can work on other human ES-cell lines if they obtain private funds. Harvard University and the HHMI recently announced that they will jointly fund a team to isolate further lines of human ES cells. But such arrangements create severe administrative and logistical problems — the Harvard scientists will have to ensure that no federal money is used to pay for any reagents or overhead costs.

Geron has supported the work of academic groups for several years, including the team led by James Thomson of the University of Wisconsin in Madison who isolated the first human ES-cell lines three years ago. To deal with the problem of keeping Geron-sponsored research separate from federally funded projects, the University of Wisconsin set up a separate non-profit facility called the WiCell Research Institute.

This twin-track approach contrasts with the situation in Britain, where both private and government-funded research fall under a single regulatory framework, with no restrictions limiting researchers to certain cell lines. “The UK has, I believe, sensible regulations,” says Anne McLaren of the Wellcome/CRC Institute of Cancer and Developmental Biology in Cambridge, who is a member of the Human Fertilisation and Embryology Authority, the body responsible for granting research licenses.

Forbidden fruit: will US researchers be denied access to the best cell lines? Credit: SPL

If ES cells do show clinical promise, and US researchers start falling behind because of restrictions on their access to the leading cell lines, Bush will come under pressure from researchers and patients' groups to amend the regulations. “As soon as we have some evidence of the potential of ES cells, the whole issue can be revisited,” says Ron McKay, who works on stem-cell therapies for Parkinson's disease at the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

In that regard, researchers are encouraged by recent polls showing that US public opinion is strongly in favour of ES-cell research. Many attribute this to media coverage of the subject — most of which has stressed the potential benefits of the research. “I think it is great that the debate brought ES-cell research to public attention,” says Peter Mombaerts, who works on mouse ES cells at Rockefeller University in New York.

But any future extensions to the list of cell lines available to federally funded US researchers would require Bush to break a pledge made to his supporters on the religious right of the Republican Party — he has said that he will not change the terms of the announcement he made on 9 August. “If the line is to be moved it will be moved by another president,” says C. Ben Mitchell, senior fellow of the Center for Bioethics and Human Dignity in Bannockburn, Illinois, which opposes human ES-cell research.

So, the stage may be set for further debate and lobbying. In the long run, say stem-cell researchers, ensuring the availability of US federal funds for cutting-edge ES-cell research is about more than promoting the competitiveness of US biomedicine. Given the huge investment that may be necessary to bring ES-cell therapies to the clinic, the involvement of the NIH, with its multibillion-dollar budget, may be crucial. “It is absolutely important that NIH researchers work on any cell lines that are developed,” concludes Juttner of BresaGen.