Bush’s bioethicist on stem cell alternatives

In Australia, a scientist named Alan Trounson reported at a meeting also earlier this spring that he has, by a process of fusing mouse body cells with mouse embryonic stem cells, produced cells that carry the properties of the adult cell but have reverted to pluripotency — have reverted to having the functional properties of stem cells. There are differences between what he’s reporting in the mouse and what Verlinsky is reporting in the humans, but this also suggests that there is something in the embryonic stem cell that is capable of influencing the nucleus of an adult cell to run backwards.

MSNBC: Is that 'something' in the stem cell's cytoplasm?

Kass: Verlinsky’s report suggests that it’s in the cytoplasm, but the striking thing out of the Australian study was that it seemed to be in the nucleus. Trounson takes stem cells and he subjects them to centrifugation, and he separates little spherical things that are bags of pure cytoplasm, and other spherical things which are basically all nucleus, with a little membrane around it. And what he’s shown, in his experiments, is that it’s the nucleoplasts, not the cytoplasts, that carry the capacity to revert the donor nucleus, the donor cells.

So there’s this difference in the studies. It may have to do with the differences between the mouse and the human, or the differences between the techniques the two men are using.

A report out of Harvard: Dr. Kevin Eggan has reported, also using cell fusion experiments with human cells, the production of a hybrid which shows the reversion of the adult nucleus to stem cell characteristics. But at the moment he’s got a tetraploid — he’s got cells that have the nuclei of both, and he’s not yet figured out how to get the stem cell nucleus out of there, but he’s managed to revert certain properties of the adult cell back to "stemness."

So here are three independent reports. Also, Jamie Thomson, who is one of the co-discoverers of human embryonic stem cells, has indicated that he too is at work on this process of dedifferentiation. And so I think this is the most exciting new development.

Other alternatives:

Along the lines of the other alternatives discussed in the council’s report: The first alternative, namely, deriving still-living cells from organismally dead embryos … That proposal has been somewhat pooh-poohed by scientists — but, I think, unfairly. Many embryos have arrested development. There is arrested cell cleavage. In a good number of these cases, it’s because there are genetic abnormalities in the embryo that simply preclude further development. But because a fair number of embryos are genetically mosaic, not all the cells turn out to be abnormal. People have shown that it’s possible to rescue viable cells from embryos that are, as organisms, arrested.

In other words, while many of the cells might be aneuploid — having an abnormal chromosome number — nevertheless the whole may contain cells which are chromosomally normal, and if you take them out of the no longer dividing embryo and put them into a different environment, those cells show that they’re still functional. That means that even dead embryos, embryos that can’t go any further, contain individual cells that are still viable and can perhaps be coaxed to develop into stem cells.

The people who have proposed this — Drs. Zucker and Landry at Columbia University — have put a proposal in to the institutional review board at Columbia to proceed with this research. I think ethically it’s relatively unproblematic. It’s on the analogy with organ donation from cadavers.

This is different from saying, “Well, they’re embryos that nobody wants any more, so why don’t we then disaggregate them.” We’re not talking about embryos that are doomed, but embryos that are really dead — that have died a natural death, so to speak. Let people try this and see whether it works. It can be attempted in humans right now, and the people who propose this are setting out to try it.

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