The Stem Cell-Cloning Plot Thickens

Add this to the pot of stem cell sources creating a political stir: parthenogenesis, creating embryos from unfertilized eggs. Unlike the cloning issue, which has a defined division, the ethical question regarding parthenogenesis may have all the earmarks of being ambivalent. So far, the US government has already placed restrictions on federal funding for new stem cell lines derived from in vitro fertilized embryos, and the Senate is deliberating over a ban on cloning that may block stem cells derived from somatic cell nuclear transfer. But, last month parthenogenesis as a stem cell source was suggested briefly in Science,1 which may add a new wrinkle to the debate. Researchers from Wake Forest University School of Medicine in North Carolina teamed up with the oft-controversial Worcester, Mass., biotech firm Advanced Cell Technology2,3 to create embryos from the unfertilized eggs of Macaca fascicularis, the crab-eating or long-tailed macaque. Some feel that the ambiguous nature of these virginally derived stem cells could help such research escape scorn. Ruth Faden, executive director at the Bioethics Institute, Johns Hopkins University, says, "For some people, parthenogenesis, as a source of potential stem cells, is being mulled over as a way to square the circle—as a way to get around the personal moral objections and political considerations that many find deeply troubling." The researchers proposed it—if applied to humans—as, "an alternative to human therapeutic cloning," that, "may circumvent the ethical concerns voiced by some, positively impacting the debate in stem cell research."1 One researcher calls such claims, "a bit disingenuous," but says that the process does add another important tool to biomedical research, even if it is one that may only benefit women. A Different Kind of Stem Cell Kent E. Vrana, professor, department of physiology and pharmacology at Wake Forest, simplifies the process: "You take an egg. Inhibit a protein kinase, add a little salt, and give it an electric shock. This is a mature metaphase II egg, and it recruits the polar body—the haploid part of the genome it was going to throw away. It recruits that back in, becomes diploid and begins to divide." The cells grow to the ball-shaped blastocyst stage where the inner cell mass can be harvested, and stem cells that may be genetically identical to the egg donor can be grown and prompted to differentiate into a number of different tissue types. Not created by the union of a man and woman, Vrana says that the embryos, which he prefers to call "parthenodes," are self-limiting. "They konk out at the blastocyst stage. They fail to implant correctly so they don't become a fetus and go to term." And, while the egg cell contains the same genetic material as its donor, further experiments will hopefully determine the effects of crossing over and gene imprinting events that might occur during gametogenesis. Food for Thought Parthenogenesis was not addressed in the bill, authored by US Rep. Dave Weldon (R-Fla), banning all human cloning. Weldon says parthenogenesis would not fall under the restrictions because the bill pertains only to cloning by somatic cell nuclear transfer. "If they produced a live monkey I might consider amending the language in my bill, or introducing a bill barring it from being done in humans," he says. Regardless of legality, right-to-life groups may still be opposed. Speaking on her own behalf, Elizabeth Blackburn, cell biologist and member of the President's Council on Bioethics, says that these blastocysts are really no different from those made by therapeutic cloning or in vitro fertilization. "This is another wrinkle that I don't think profoundly, in any way, changes the nature of the debate." Vrana agrees that this will not end the conflicts over such research. "I don't think it solves the problem. It just produces another alternative. It expands the discussion." And that discussion saw a lot of action in January, arguably a big month for unpublished results involving stem cell research.4,5 Those vehemently opposed to stem cell and cloning research hitched their wagon to a so-called "Ultimate Stem Cell" derived from adult bone marrow. Opponents to embryonic research heralded it as mounting proof that embryos need not be destroyed much to the chagrin of the researchers involved. Although parthenogenesis is deemed acceptable by pending cloning bans, scientists face a Pyrrhic victory. "I think what we're at risk of here is when somebody latches on and says, 'oh we don't need embryo research.' I should certainly hope that doesn't happen with us," says Vrana. In addition to unforeseeable limitations in the research, parthenogenesis-derived stem cells may only benefit potential egg donors. "Remember too that parthenogenesis is only going to work for women in terms, at least, of our technology right now if we're talking about autologous transplantation," says Faden. "It is an intrusion of a profound nature into women's bodies to retrieve eggs. So, it raises issues of concern to people who are worried that women could be exploited." Regardless of the merit and meaning that ethicists and legislators alike will attach to parthenodes, scientists view them as a tool that could advance the understanding of human development and the true potential of stem cells to human health. Blackburn says, "The whole science is in an ignorant state. Where can we go with all of this? Not enough is known. How do you find out? You do the experiments and you do the work and find out. You can't just make a prejudging guess about what would work and not work. In the end, the cells are going to tell us. The cells have the last word." Brendan A. Maher can be contacted at bmaher@the-scientist.com. References 1. J.B. Cibelli et al., "Parthenogenetic stem cells in nonhuman primates," Science, 295:819, Feb.1, 2002. 2. E. Russo, "Bypassing peer review," The Scientist, 14[5]:1, March 6, 2000. 3. T. Agres, E. Russo, "Cloning controversy re-emerges in US," The Scientist, 16[1]:29, Jan. 7, 2002. 4. S.P. Westphal, "Is this the one?" New Scientist, 173:4, Jan. 26, 2002. 5. R. Weiss, "Scientists claim an advance in therapeutic cloning," The Washington Post, Jan. 30, 2002, pg. A4.

The Stem Cell-Cloning Plot Thickens

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