Human embryonic stem (ES) cells can give rise to specialized cell types of any kind, such as neurons or insulin-producing 
cells. As such, many claims have been made about the potential benefits of research involving human ES cells and their use to treat conditions such as Parkinson's disease, spinal-cord injury and diabetes. In reality, researchers are only just beginning to scratch the surface. But legal, political and ethical questions surround work on stem cells derived from human embryos, leaving researchers with an uncertain future.
Many observers predicted that there would be a wholesale exodus of US scientific talent following the decision by President George W. Bush to ban the use of federal funds for research on human ES-cell lines derived after August 2001. But with states such as California enacting legislation in support of the research and rolling out the red carpet to researchers, investors and companies alike, such an exodus has not occurred — at least not for now.
Legislation governing human ES-cell research varies widely from country to country, even within the European Union (EU). If an EU vote on 10 April to restrict research involving human ES cells was to become law, then this avenue of research might be closed down — even in countries such as the United Kingdom, which currently has one of the more liberal and favourable research environments for the field. It is joined in this position by Australia, China, India, Israel, Singapore and Sweden.
The government in Singapore, for example, sees human ES-cell research as having considerable commercial potential, and is actively promoting and funding work in this area. It matches well with a recent mandate to train more Singaporeans in the life sciences, says Ariff Bongso, an in vitro fertilization (IVF) specialist at the country's National University Hospital. "Human ES-cell research in Singapore is progressive, enthusiastic and encouraging," he says.
Bongso, who trained in North America, notes that he has recently been on the receiving end of increased interest from US scientists who are seeking collaborations outside the United States to gain access to cell lines and technical know-how.
Austin Smith says that over the past year he has received more approaches for work than ever before from postdocs in other countries.
Austin Smith, head of the Institute for Stem Cell Research at the University of Edinburgh, UK, says that he too has received more approaches over the past year from postdocs in other countries. "They feel that things are more open here," he says.
That may be true, but there is still UK bureaucracy to cope with in order to secure a licence from the Human Fertilisation and Embryology Authority to derive new human ES-cell lines for research, says Stephen Minger of the GKT Centre for Neuroscience Research at King's College London. Although it is legal in Britain to create human embryos for stem-cell research using nuclear transplantation, the three projects that have been granted licences so far all use surplus embryos from IVF clinics.
Securing a licence can be an onerous and lengthy procedure, and you have to be willing to put yourself under regulatory and administrative scrutiny, says Minger. But it is the right way to go about it, he says. "The policies here are very clear-cut; it doesn't hinder us in any way," he explains. Minger came to Britain from the United States as a postdoc about seven years ago and now runs a neural stem-cell group that is increasingly moving into human ES-cell research.
Lack of a steady supply of embryos is another issue, says Minger. Moreover, he says, the work itself is technically demanding and labour-intensive. The field is still in its infancy and no one has really mastered it, so there is little technical experience to draw upon (see 'Education, education, education').
THROUGH THE LOOPHOLE
Despite the restrictions within the United States — and the looming threat of an outright ban on all forms of human cloning, including for 'therapeutic' use — there are regions that offer a favourable climate for stem-cell research. California, for example, has passed legislation in support of human ES-cell research in the hope that this will allow it to recruit and retain high-flying scientists, as well as helping to attract investors and biotechnology companies.
Some US institutions are also exploiting a loophole in the current Bush policy. Although new human ES-cell lines cannot be derived using federal funding, the policy does not preclude the use of private or state funds. Several foundations have already stepped up their involvement. Last June, for instance, the Juvenile Diabetes Research Foundation International in New York launched a US$20-million fundraising effort in support of human ES-cell research worldwide.
Evan Snyder is certain that California will attract talented researchers for stem-cell work.
Many Californian institutions are now seeking creative ways to fund human ES-cell research from non-federal sources, in particular by setting up independent programmes. Evan Snyder, who recently left Harvard Medical School to join the Burnham Institute in La Jolla as director of its new stem cell and regeneration programme, believes that the conditions in California will attract talented individuals. Mark Mercola, who studies cardiac development in Xenopus embryos and is also ex-Harvard, has already joined him there. Snyder says that he is seeking researchers with a firm grasp of developmental biology, particularly cellular and molecular developmental biology of any system, to staff the new programme.
But he may have competition. Last August, the University of California, San Francisco, announced plans to establish a Developmental and Stem Cell Biology Program using a $5-million grant from Andy Grove, the chairman of Intel. In December, Stanford University followed suit, revealing plans for an Institute for Cancer/Stem Cell Biology and Medicine to be set up with $12 million in seed money from an anonymous donor. Other states, including Massachusetts and New Jersey, are now considering legislation similar to that in California to authorize stem-cell research.
In contrast to the United States, the federal parliament in Australia voted last year to allow ES-cell research using excess IVF embryos. The government is providing A$43.5 million (US$26.3 million) in federal funding to establish a Centre for Stem Cells and Tissue Repair at Monash University in Victoria. The centre will consolidate efforts in stem-cell research across Australia and will be headed by Alan Trounson.
With a staff of nearly 140 when it opens later this year — two-thirds of whom will be PhDs — Trounson says that the centre will offer great opportunities for established and young scientists interested in adult and ES-cell development and differentiation, tissue engineering and transplantation biology. Already it is proving attractive — Stephen Livesey is returning to Australia after a 14-year stint in the United States to become the centre's director of tissue regeneration.
For researchers elsewhere, such opportunities must seem slightly galling. Oliver Brüstle, a neuroscientist at the University of Bonn in Germany, works under much tougher conditions. German law prohibits the use of funds — public or private — to derive new human ES-cell lines, and researchers can only work on cell lines created before January 2002. Even so, Brüstle says it took him more than two years to get permission to import human ES-cell lines from Israel as part of a collaboration with the Rambam Medical Center in Haifa.
Brüstle worries that such restrictions will prevent German researchers from participating fully in international programmes or taking advantage of new technological developments. They could also make it harder to stimulate biotech interest in this area, leaving Germany at an economic disadvantage.
Admitting that he seriously considered leaving his country for Britain 18 months ago, Brüstle says that he stayed partly because his grant application to use human ES cells made him something of a "test case". Brüstle believes the ball is now in the scientists' court to demonstrate the therapeutic potential of these unique cells. "The more data are accumulated, the easier it will be to convince the politicians," he says, which will lead to fewer restrictions on who can do what and where.
