Fundamentalist Christians want it stopped; scientists believe it could save millions of lives and be worth billions of dollars. Stephen Phillips reports on the stem-cell dilemma facing President Bush

After months of heated debate, the future of stem-cell research in the United States rests in the hands of President Bush. The White House views its deliberations on whether to permit public funding for human embryonic stem-cell research in US universities as an ethical dilemma. According to his spokespeople, the president must weigh the best interests of potentially life-saving medical research against the moral considerations necessitated by the use of proto-human tissue.

But scientists and bioethicists contend that the US government is confusing the issues. "If you want ethical oversight, then the way to ensure that this does not happen is to shut off public funds," says Larry Goldstein, professor of cellular and molecular medicine at the University of California, San Diego. Goldstein fears that upholding the public-funding ban will drive human embryonic stem-cell research behind closed doors in the private sector, beyond the reach of peer review and governed by the quickest path to profit. "We will not know who is doing what or be able to verify claims - it is a horrible scenario," he says.

The fact that private-sector regulation is not under consideration "makes it impossible for (the US government) to take the moral high ground on protecting the rights of embryos", says Suzanne Holland, assistant professor of religious and social ethics at the University of Puget Sound.

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Stem cells offer scientists a biological blank slate - self-replicating undifferentiated cells that they hope may be coaxed into forming, for instance, healthy heart or liver cells. The goal is to use these to replace cells and tissues damaged and destroyed in medical conditions ranging from diabetes to Parkinson's disease. Stem cells harvested from early (four to five-day-old) embryos are deemed particularly promising, compared with stem cells from foetuses or adults, because at this stage they appear capable of developing into almost any specialised cell and have an infinite capacity for self-renewal.

But reflecting the US's unique political climate, in which science must co-exist with widespread fundamentalist Christian beliefs, human embryonic stem-cell research has run into implacable opposition from pro-life groups. Such opponents, who wield powerful influence, say harvesting stem cells requires the death of nascent life.

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Stem cells fall under a blanket ban on public funding for human embryo research enacted by Congress in 1996. The door was opened in 1999 with a ruling by the Clinton administration exempting stem cells from the ban. But it was slammed shut again this April when President Bush suspended the funding process and instigated a review on whether to permanently outlaw public human embryonic stem-cell studies.

Private funding has allowed US universities to stay in front of stem-cell research. James Thomson of the University of Wisconsin pioneered the isolation of human embryonic stem cells in 1998 using funds from biotechnology firm Geron. But as the support of companies such as Geron for publicly funded research shows, the private sector is not equipped to bankroll the long-term work needed to explore the possibilities of stem cells fully.

"This requires a mass commitment from the biomedical community," says Robert Lanza, a former associate professor of surgery at Harvard and now medical director of Advanced Cell Technology. "Therapies will take hundreds of millions of dollars to develop." Investors are unwilling to part with much money without the prospect of near-term returns, Lanza says.

The federal funding framework, proposed last week by Republican senator Bill Frist, plots one possible path to making the US government's more-than $20 billion (?14 billion) medical research budget available to human embryonic stem-cell scientists. The ten-point plan from the Senate's only physician and President Bush's closest on medical issues is seen by many to presage the White House's ruling, which is expected in the next few days or weeks. It backs federal support for research, but under tight restrictions. For example, it bars the creation of embryos for research.

Many scientists are concerned that this would leave private firms in charge of stem-cell supply, handing them a charter for abuse. "Private groups could, for proprietary reasons, withhold information on the genetic background of cell lines from researchers, and form cartels to charge unfair prices," says Mary Hendrix, professor of anatomy and cell biology at the University of Iowa. "They could also demand reach-through agreements, requiring a portion of intellectual property from researchers' discoveries."

This funding caveat militates against the Frist plan's stated aim of a "transparent" framework for research, says Hendrix, ex-president of the Federation of American Societies for Experimental Biology and a witness at last week's Senate hearings. She proposes publicly funding researchers to extract stem cells from frozen embryos (which would otherwise be discarded by fertility clinics) and share them with their academic peers, or engaging independent contractors to provide additional derived cell lines.

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Scientists are also opposed to Frist's proposed limit on the number of stem-cell lines that publicly funded research may be conducted on. While human embryonic stem cells have shown a limitless capacity to propagate themselves and an ability to mutate into almost all known cell types, results from existing cell lines have been varied.

"Embryonic stem cells have a mind of their own," Lanza says. "Sometimes they develop into a whole dish of beating heart cells, other times they become neurons. No-one is quite sure what is going on." Limiting the number of research lines would hinder efforts to systemise stem-cell development.

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Most scientists estimate that at least 100 human embryo-derived stem-cell lines are needed as a genetically diverse platform for research. It is reckoned that there are currently about 30 lines worldwide.

The highest hopes of the US scientific community are carried by Democrat senator Tom Harkin and Republican senator Arlen Specter's Stem Cell Research Bill, 2001 . The bill, which would permit researchers to extract fresh cell lines using government funds, might be employed to try to overrule the president if he bans public funding outright or issues conditional approval. According to its sponsors, it commands majority Senate support at committee stage.

The current situation is certainly wearing on scientists. "Morale is pretty low," Goldstein says. The announcement last week that one of the US's leading human embryonic stem-cell researchers, Roger Pedersen, is leaving for Britain raised the spectre of a brain drain to countries with more liberal public research environments. Pedersen, a professor of reproductive genetics at the University of California, San Francisco, cited the desire to continue his research "with public support" as a factor in his move to Cambridge.

According to Tony Mazzaschi, of the Association of American Medical Colleges, scientists face a "bureaucratic and regulatory minefield" if they want to conduct human embryonic stem-cell research at US universities. New rules adopted by the National Institutes of Health under the Bush administration mean that stem-cell programmes may not so much as use a light bulb that has been partly paid for with a government grant. The need to move his ten-person lab off UCSF's campus is thought to have been one of the deciding factors in Pedersen's decision to quit the US for Britain, where the study of human embryos and stem cells gained public funding approval in January.

Another factor that clouds the issue is the federal structure of the US, which means that whatever the overall US government position on stem-cell research, individual universities and private firms might also have to contend with state laws on the issue. According to The New York Times , nearly two dozen states have laws on research on embryos and foetuses and at least nine ban any experiments with human embryos.

In the Pedersen case, and possible future brain drain cases, the US's loss is Britain's gain. But the overall blow to stem-cell research, if the largest single funding source declines to participate, will be felt across the world. Scientists fear that such a setback could be measurable in years, during which millions of people who might otherwise have been treated using stem cells will die.

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