Future of Stem Cell Tests May Hang on Defining Embryo Harm

By Rick Weiss
Washington Post Staff Writer
Sunday, July 29, 2007

With the active encouragement of the Bush administration, U.S. scientists in the past year have developed several methods for creating embryonic stem cells without having to destroy human embryos.

But some who now wish to test their alternatively derived cells have found themselves stymied by an unexpected barrier: President Bush's stem cell policy.

The 2001 policy says that federal funds may not be used to study embryonic stem cells created after Aug. 9 of that year. It is based on the assumption that the only way to make the cells is by destroying human embryos -- a truism in 2001 but not any longer.

As a result, the National Institutes of Health recently refused to consider a grant application for what would have been the first federal study to compare several of the new, less politically contentious stem cell lines.

"This is not the way to make good health policy," said Robert Lanza, the frustrated vice president for research and scientific development at Advanced Cell Technology (ACT) in Worcester, Mass. Lanza submitted the study proposal with stem cell experts from several major research labs.

Upcoming changes in the NIH's stem cell funding rules may eventually help resolve that problem. But agency officials and others say the policy tangle is more complicated than that. Although Lanza's technique and other new approaches do not destroy embryos, they may run afoul of a long-standing congressional ban on studies that "harm" human embryos.

That vague language raises the perplexing question of how one would know whether an embryo had been harmed.

At the center of the debate is a new technique, pioneered by ACT, that obtains stem cells from human embryos while leaving the embryos functionally intact. A single cell, called a blastomere, is removed from an eight-cell human embryo, then coaxed to multiply into a colony of stem cells in a dish.

Fertility doctors have been performing these blastomere biopsies for years to identify embryos that harbor genetic defects. Since a single cell is representative of the entire embryo, doctors transfer to a mother-to-be's womb only those embryos whose plucked cells pass genetic muster. The loss of a single cell -- or even two -- at that stage is not known to cause developmental problems in children born by this procedure, doctors say.

In unpublished research, ACT has made several colonies of stem cells this way, Lanza said. The seven-cell embryos developed normally and were frozen after the procedure a couple of days later, as embryos typically are until used by infertile couples.

The question is whether stem cells made this way are as versatile as those harvested from destroyed embryos. And what about stem cells created by other means, such as those of Anthony Atala, the Wake Forest University scientist who in January announced he had isolated embryonic stem cell equivalents from amniotic fluid?

To find out, Lanza joined with Atala and a team of others to compare stem cells made by various means. The group submitted a proposal to the NIH in February, then waited. And waited.

Eventually, the NIH told the team that it had referred the proposal to a different review group. Then, in a series of e-mails, the agency backed off further, first encouraging the applicants to drop Lanza's cells from the proposal and, finally, when the team refused to do so, informing them that the application was being sidelined indefinitely for "administrative review."

Story Landis, who heads the NIH's stem cell task force, said the main issue is Bush's Aug. 9, 2001, stem cell policy. It called upon the NIH to make a list of all embryonic stem cell lines known as of that date and blocked funding for research on any cells but those on the list.

"Currently, there are no cell lines derived from single blastomeres listed on the stem cell registry as eligible for funding," Landis said.

Sean Tipton, president of the Coalition for the Advancement of Medical Research, a stem cell research advocacy group, said the policy amounts to a Catch-22.

"On the one hand, they're saying, 'Find this out,' " Tipton said, referring to the Bush administration's repeated call for scientists to find ways to make and study stem cells without destroying embryos. "On the other hand, they're saying, 'You're not allowed to do the research to answer these questions.' "

A little-noted executive order issued by Bush last month, when he vetoed legislation that would have expanded embryonic stem cell funding, could eventually help resolve the problem, Landis said.

It instructs the NIH to rewrite the rules for funding stem cell research, with the emphasis not on whether the cells came from embryos but on whether any embryos were harmed.

Bush, in an interview this week with The Washington Post, reiterated his belief that "there are ways to develop stem cell lines without the destruction of human life. There's a myriad of ways to advance good science without crossing an ethical line."

It is unclear whether ACT's blastomere-derived lines, or those obtained from embryos by other means, might be deemed eligible. A 2005 report by President Bush's Council on Bioethics concluded that the blastomere approach (still theoretical at that time) "might be eligible for funding" under the do-no-harm-to-an-embryo standard. But the report raises a concern.

"[E]ven if development proceeds in a healthy manner, it may be that the child born is somehow a different child than the one that would have resulted from an undisturbed embryo," the report said, without opining on whether such a shift of fate would constitute harm.

The legal standard of allowable harm to an embryo is spelled out in 1995 congressional language and is reiterated in Bush's June 2007 executive order. It bans federal funding of research that subjects an embryo to more than "minimal" risk, although greater risk is allowed if the research is anticipated to benefit the embryo.

For now, Lanza has suggested limiting his technique to embryos that are already due to be biopsied at a fertility clinic. The plucked cell could divide for a day, providing enough cells for both the genetic testing and to start a line of stem cells. That way the embryo would not be subjected to any new or additional risk.

Still, for funding, that risk would have to be "minimal" -- a standard open to "interpretative discretion," said R. Alta Charo, a professor of law and bioethics at the University of Wisconsin at Madison.

From one perspective, she said, fertility clinic testing can be seen as a risk because if the embryo "fails" its genetic test, it will not be given an opportunity to grow into a child.

But some couples who know they harbor genes that can cause a fatal childhood disease might never risk having children unless they could test their embryos and select those not affected. For those embryos, the test poses an opportunity for life that would not otherwise exist.

Charo said that she is uncomfortable with both ideas, because they "suggest the embryo has an active interest in being born" -- a philosophical notion that imputes a level of personhood to embryos that many stem cell supporters do not accept.

Landis, of the NIH, would not say how the agency will decide which cell lines involve risks small enough to be eligible for funding, nor would she say what role, if any, the White House will have in those decisions.

Agency insiders, however, said the NIH is likely to convene workshops and fund animal tests to study the degree of harm various procedures pose to embryos -- a meticulous approach that strengthens suspicions among research proponents that real stem cell policy changes are unlikely while Bush is in office.

"I think they're trying to ride the clock out," Lanza said.

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