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Bigger than Dolly?

by Jesse ReynoldsGenetic Crossroads
June 29th, 2007

Bush vetoing the Stem Cell Research Enhancement Act

Here in the United States, political maneuverings around embryonic stem cell research made headlines throughout June. But this was little more than rehearsed political theatre, reenacting a well-known script. The Democratic-controlled Congress once again passed a bill that would have undone restrictions on the federal funding of embryonic stem cell research, but the Republican President again vetoed it. Despite last year's electoral shift in Congress, the bill's advocates are still far short of the super-majority needed to override the veto.

Though the debate remains polarized and deadlocked, supporters of President Bush's restrictions - including many Republicans up for reelection next year - are no doubt looking for ways to extricate themselves from their increasingly unpopular position. To date, they've largely gambled on the emergence of alternative sources of stem cells that are just as powerful as those derived from embryos, but that can be produced without destroying embryos.

Until now, this strategy has been largely rhetorical. But it appears that scientific developments - including one that was heralded by several researchers as being as important as the birth of Dolly, the first cloned mammal - may be coming to their rescue.

The same day that President Bush vetoed the stem cell bill, he issued an executive order directing the National Institutes of Health to investigate such potential alternative sources, and renaming the list of federally-approved lines from the "Human Embryonic Stem Cell Registry" to the "Human Pluripotent Stem Cell Registry."

Technical developments

Recently, a number of research teams have reported significant steps towards the ability to produce stem cells that are pluripotent (that is, with full functional flexibility) - without destroying embryos, and in some cases without using human eggs. If these efforts are successful, supporters of President Bush's restrictions - including many Republicans up for re-election next year - would be able to point to progress in stem cell research that would not have been likely to occur in the restrictions' absence.

In the most important of the recent scientific announcements, three separate labs replicated and improved the work of a Japanese team that was reported last year. The groups were able to reprogram the normal skin cells of mice into fully pluripotent stem cells, whose genomes would match those of the skin cell donor. If this work can be translated to humans - a very big "if" - then it would allow custom stem cell lines to be derived without the need for either embryos or eggs. What's more, unlike the cloning procedure of somatic cell nuclear transfer (SCNT), this technique would not need the tools, expertise, and materials that are also the basis of human reproductive cloning and other widely rejected applications.

In an announcement with similar potential implications, a group at Harvard University made steps in understanding the derivation of stem cell lines via cloning in mice. Although such lines have been derived from mice before, in this case the cloning procedure used a fertilized but nonviable egg as the recipient instead of a normal egg. This particular cause of nonviability, in which the egg is fertilized by two sperm cells, occurs in about four percent of in vitro fertilizations in humans. As with the reprogramming method, if this works with human cells, neither egg retrieval specifically for research purposes nor the use of viable embryos would be necessary to derive custom stem cell lines.

Meanwhile, researchers from Advanced Cell Technology (ACT) claimed to have derived a stem cell line by extracting a single cell from an early-stage human embryo without destroying it. The announcement received little media attention - an understandable reaction given ACT's track record of exaggerated claims and questionable practices. But if this can be replicated, and the federal government approves ACT's new stem cell line for funding, then those who oppose embryonic stem cell research may win some political advantage in the ongoing controversy.

Finally, a team of Belgian researchers published a paper describing the development of early-stage human clonal embryos that were created using in vitro-matured human eggs. Although this method does not address concerns regarding the moral status of the embryo, it is another path towards custom stem cell lines that would not require women to undergo egg extraction specifically for research, as immature eggs are available from ovarectomies, cadavers, and fetuses.

But these developments do not seem to be slowing down the push for cloning-based stem cell research, which would require fresh eggs. One prominent stem cell researcher, Irving Weissman of Stanford University, reacted to the new technical developments by asserting that society has an imperative to undertake the research cloning endeavor: "I would find it immoral to delay the research to see if egg nuclear transfer or this method [skin reprogramming] gets to our goals first."

Despite an overall dearth of progress in cloning-based stem cell research, last month witnessed two significant steps. Workers at Lifeline Cell Technology, a private company in Maryland, claim to have derived a stem cell line via an alternate cloning technique called parthenogenesis. In this, an unfertilized egg, which retains its full genome, is coaxed into dividing as if it had been fertilized. When stem cells are isolated from the resulting clonal embryo, they genetically match the woman who provided the egg. And at the annual meeting of the International Society for Stem Cell Research, scientists from the Oregon National Primate Research Center claimed to have isolated the first pluripotent stem cell line via SCNT cloning in a primate.


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