Stem cell scientists have a message for those who propose ethically friendly methods to alter human embryos: come on down and give it a shot.

“The ethicists seem to imagine that they can sit around a table and dream up these experiments,” says Doug Melton, co-director of the Harvard Stem Cell Institute. “They don't seem to be cognizant of the enormous effort involved in proving even a small effect.”

In December, William Hurlbut, a Stanford University ethicist and a member of the President's Council on Bioethics, generated a buzz when he suggested genetically or chemically altering human embryos so they cannot develop beyond the blastocyst stage. By doing so, Hurlbut said, scientists could pursue research without violating federal rules on embryonic stem cell research.

Hurlbut told the council that a process called 'altered nuclear transfer' may be able to generate functional cells from a blastocyte that cannot form a trophectoderm, the outer layer of cells that eventually forms the placenta. He suggested that scientists might be able to do this by deleting or blocking the action of the Cdx2 gene from the somatic cell nucleus before transfer and reinstalling it into the resulting embryonic stem cells.

Animal studies indicate that without Cdx2, a blastocyte can form an inner mass but cannot grow. Since the genetically altered embryo has no potential for life, Hurlbut notes, the process might mollify those who believe life begins at conception.

Melton says that it is not known whether Cdx2-deficient embryos die at the same stage as mice, and whether they could be used to produce stem cells. Research on these ideas would only divert energy and funding from more promising avenues, he says, and still might not satisfy opponents of stem cell research. “I am completely open to alternative approaches,” Melton says. “I just think this one is flawed.”

I am completely open to alternative approaches. I just think this one is flawed. Doug Melton,, Harvard University

Proponents of Hurlbut's idea may be underestimating the potential scientific obstacles, but the idea is worth a try, says Irving Weissman, director of the Cancer and Stem Cell Institute at Stanford Univeristy in California. The preliminary research is not complicated or costly, he adds, but it may yield nothing.

“I say go ahead and do the experiments, compete for funds,” he says. “But don't think that you can use this politically to slow down even for a minute the kind of research we are going to do in California, Korea, Japan, Israel and elsewhere.”

Meanwhile, Hurlbut and Burnham Institute's Evan Snyder plan to seek funds from California's new stem cell research fund (See News, page 107). Snyder says their research will also explore targets other than Cdx2.

“We've just put out feet on the Plymouth Rock, we have a whole continent to explore,” Hurlbut says. “Why are we pretending we're prophets, why not just go out and see what's there?”