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Sticking points for stem cells

A technique for developing stem cell lines from a single cell plucked from a human embryo is unlikely to pass muster with the Bush administration, even though the latest experiments indicate that the embryo can survive the procedure. At least that's how the initial reactions to last week's research revelations are shaping up.

The technique, described in the journal Cell Stem Cell, involves removing one or two cells from the embryo at the eight-cell stage, then allowing the embryo to continue developing to a point where it can be frozen for later implantation. It's a procedure very much like the one currently used to check test-tube embryos for genetic flaws before they're implanted - a technique known as preimplantation genetic diagnosis, or PGD.

Usually, the removed cells are analyzed, then discarded. But researchers have found a way to grow those cells in a special chemical brew so that they take on the characteristics of an embryonic stem cell - that is, they can transform themselves into virtually any type of cell in the body, a property called pluripotency.

If the cells are truly pluripotent, they could theoretically offer another route to new therapies to boost ailing hearts, mend broken spinal cords and regenerate other broken-down tissues.

The research follows up on an earlier study that was somewhat less than fully successful a couple of years ago. This time around, about 80 percent of the embryos survived to be "frozen down" for safekeeping - which the researchers said was the normal survival rate for test-tube embryos.That led Advanced Cell Technology's Robert Lanza, the principal author of both studies, to call upon the White House to approve the resulting cell lines for federal funding as soon as possible.

Will the White House do so? A couple of years ago, the technique used by Lanza merited a mention from the President's Council on Bioethics as one of the alternatives to the usual methods for generating embryonic stem cells - which involve destroying the embryo. But even at that time, Chairman Leon Kass said the council had reservations about the method. Here's how Kass explained it to me in a July 2005 interview

"No one has yet converted a single blastomere from an eight-cell embryo into a stem cell line. That's a scientific challenge. But the council was quite concerned about the ethics of this. We didn't think that one could justify putting a child-to-be at additional risk, not for its own benefit. Until it could be proved by animal studies, or by much longer studies of preimplantation genetic diagnosis, that embryo biopsy is really risk-free to the child who results from all of this, the council is unprepared to pronounce this particular approach as ethically acceptable at this time."

Have opinions changed, now that someone actually has converted a single blastomere into what appears to be a stem cell line? Not really. Stanford neuroscientist William Hurlbut, a member of the bioethics panel, told me last week that the doubts about the procedure persist:

"We really don't know what it does long-term. It's not a foolish concern to think that when you take one-eighth or one-fourth of the embryo out, such an intervention might have some unrecognized long-term consequences."

The way Hurlbut sees it, researchers would have to show that the procedure poses no additional risk to the embryo (and one recent study raises questions). For the time being, federal funds cannot be used to pay for preimplantation genetic diagnosis - and unless there's a sudden change of heart (or a legal opinion that clarifies the matter), they're not likely to go toward research using the resulting stem cells, either. At least that seems to be the case for the final year of the Bush administration.

Of course, the next administration may well take a different view toward embryonic stem cell research. But even then, questions about the PGD-based procedure would remain, said Arthur Caplan, director of the Penn Center for Bioethics (and an msnbc.com columnist). Here's how he laid out the issues in an e-mail to me:

"Four issues arise from PGD-created stem cells:

"1. Will the isolated cell really act like a human embryonic stem cell? It's still early days to answer that.

"2. Is PGD really safe for embryos? Parents accept the risk when trying to prevent the birth of a child with a serious condition like Fanconi's anemia - but is the risk to the embryo worth it just to generate stem cells?

"3. Where are the embryos coming from that Lanza proposes be used? Who is going to want their embryo biopsied, other than people who want biopsies to prevent the use of embryos with odd diseases?

"4. If a cell from an embryo in early stages is really acting like an embryo, then why won't critics of embryonic stem cell research say it is an embryo and demand that it not be used for research?"

On the last point, Lanza told me that he's not aware of any case where a single cell from an eight-cell-stage embryo could develop into a viable embryo itself:

"No one I've ever spoken with knows of any pregnancy or any child who was born from a single cell that was removed from an embryo. That argument is very weak, and not only is it weak, but with all the new technologies, with reprogramming, even a skin cell could in theory have the potential to become a human being. The real issue here is that no embryo is destroyed, and we're only talking about a single cell that's being turned directly into an embryonic stem cell."

Lanza suggested that the cells removed for preimplantation genetic diagnosis could be routinely allowed to divide a couple of times to yield a stem cell line that would be a perfect match for the person who might eventually develop from that embryo - yielding a medical benefit with no extra risk (that is, beyond the risk of the PGD procedure).

That seems like the likeliest scenario for using Lanza's procedure. But will the concept catch on? Harvard researcher George Daley, the current president of the International Society for Stem Cell Research, suggested a more mainstream route in his congressional testimony back in 2005:

"Far preferable to spending limited research dollars on these speculative proposals, in my opinion, is support for research on additional embryonic stem cell lines that are available today—lines that are similar to those already approved under the Bush policy."

Will a new administration ease the limits on  federally funded research, essentially bypassing PGD-created stem cells? How long will it take for scientists to perfect new methods for reprogramming ordinary skin cells so that they act like embryonic stem cells?

Science vs. politics ... embryo ethics vs. the moral imperative to find cures ... timelines and bottom lines: All those factors can enter the picture when you're talking about stem cell research - as illustrated by the reactions to Lanza's latest findings. For a sampling of other reactions, check out the reports from Wired Science, TechNewsWorld, LifeNews.com and The Scientist.