Getting to the root of stem cell science
If it weren't for limitations on human embryonic stem cell research, "I think that there could be children being cured of type 1 diabetes today," says Dartmouth's Ronald M. Green, Ph.D. "I think that there could be cardiac patients being brought back to functioning. And I think Christopher Reeve may not have had to die."
Many scientists and physicians hope that human embryonic stem cells (hESCs)—which can develop into any of the 200-plus types of cells that make up the body—may one day be used to treat such diseases as Parkinson's, Alzheimer's, heart disease, and type 1 diabetes, as well as spinal-cord injuries like Reeve's. Some even hope they could be grown into new organs. But the political and ethical controversy swirling around hESCs has led to limits on federal funding for such research and thus the amount of it being conducted in the U.S. So scientists have begun exploring alternative approaches to deriving hESCs.
Panel: Green, the director of Dartmouth's Ethics Institute and an adjunct professor at DMS, served on a 1994 National Institutes of Health panel on human embryo research and has studied stem cell ethics for many years. In the June issue of Nature Reviews Genetics, he explored the ethical and scientific aspects of six current alternatives—single-cell blastomere biopsy, parthenogenesis, somatic-cell dedifferentiation, altered nuclear transfer, dead embryos, and chromosomally abnormal embryos.
The source of hESCs is typically eggs discarded or unused after in vitro fertilization. When an egg is allowed to develop, by day three it's an 8- to 16-cell ball called a morula. By day five or six it's a blastocyst, which is about the size of a period. Embryonic stem cells form the inner cell layer of a blastocyst, which becomes an embryo only if it implants in the uterine wall 7 to 10 days after fertilization.
Lines: While hESC research is not prohibited in the U.S., federal funding is allowed only for studies on cell lines in existence prior to August 2001. But the 21 approved lines have been contaminated with nonhuman molecules. So scientists have been seeking expanded federal funding—as well as corporate, foundation, and state monies—to support the development of new stem cell lines and to explore alternatives.
The most promising alternative, Green says, is single-cell blastomere biopsy (SBB). SBB is an adaptation of preimplantation genetic diagnosis (PGD), in which a single blastomere is removed from the morula and allowed to divide into two cells. One cell can be used for genetic diagnosis and the other for the creation of the hESC line. Scientists at a biotech firm called Advanced Cell Technologies (ACT) reported in Nature in 2006 that they had successfully derived hESCs from SBBs using donated human embryos. Green chairs ACT's ethics advisory board but has no financial interest in nor is paid by ACT.
Embryo: SBB and PGD do not harm embryos, says Green, citing a 2004 report indicating that more than 1,000 children born as a result of PGD had suffered no ill effects. But there is debate on the matter; others point to studies showing an embryo survival rate after PGD of only around 3%.With SBB, "you just can't know that you're not bringing harm to the embryo," feels Father Thomas Berg, executive director of the Westchester Institute for Ethics and the Human Person, a Catholic think tank. But Berg does agree with Green that parthenogenesis and somatic-cell dedifferentiation merit more investigation. The former involves deriving stem cells from an embryo that has developed from an unfertilized egg, while the latter involves reprogramming body cells to an embryonic-stem-cell-like stage.
Remote: Several stem-cell scientists reported success this summer in reprogramming mouse cells to act like embryonic stem cells. But Green cautions that "in terms of clinical application, cellular reprogramming . . . is really the most remote of all the possibilities." And he feels the three other alternatives—altered nuclear transfer, dead embryos, and chromosomally abnormal embryos—are least likely to be ethically acceptable.
Many are frustrated that resources—money and scientific brainpower—are being devoted to the search for alternatives, says Anthony Mazzaschi, a senior associate vice president at the Association of American Medical Colleges. He predicts that interest in alternatives may wane quickly once there is a new administration in Washington and federal limitations are lifted. "Researchers are more likely to want to use well-defined stem-cell sources," he says.
In the meantime, although Green argues for putting funding into developing alternatives, he agrees that none of the options "should be regarded as an alternative in the sense of being a replacement for existing methods of generating hESC lines."
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