Cloning-Derived Stem Cells Raise Policy Questions
Shoukhrat Mitalipov and his research team at Oregon Health and Science University (OHSU) are back in the news with a big announcement: They have become the first scientists to create human embryonic stem cells using a cloning technique called somatic cell nuclear transfer or SCNT. Scientists have been unsuccessfully attempting this feat for over a decade; indeed, many had given up in favor of work with induced pluripotent stem (iPS) cells. The success raises questions about which kind of stem cells will drive research on regenerative medicine, as well as significant concern about human reproductive cloning and the use of women’s eggs that cloning requires.
Mitalipov and his team were recently in the news for their research on mitochondria replacement techniques, which raises serious concerns because it involves a form of inheritable human genetic modification. The media however paid more attention to yesterday's announcement. The cloning paper, published in Cell on Wednesday, prompted a range of assessments. It was called a “landmark” discovery here and here, but scientists quoted here and here were far more restrained.
A stem-cell showdown
Much of the news coverage reflects surprise that scientists are still investigating cloning techniques at all, since iPS cells appear to provide disease-specific and patient-specific lines while avoiding many of the technical difficulties and ethical quandaries of SCNT. Unlike cloning-derived ESCs, iPS cells don’t necessitate the retrieval of eggs from women, or the production of cloned embryos that could be misused in efforts at reproductive cloning. Understandably, many comparisons are now being made between the two methods (Nature called it a “showdown”).
New Scientist reported that tissues made with iPS cells have tended “to accumulate mutations and suffer abnormal patterns of gene activation.” But not everyone is convinced that making stem cells through cloning will soon – if ever – become medically useful. Carolyn Johnson at the Boston Globe commented that “the discovery would no doubt be a bigger deal if in 2007, scientists had not discovered that there was a different, simpler way to create stem cells that bear a patient’s own genome and are pluripotent, possessing the capacity to develop into any of the myriad cells and tissues in the body.” David Brown of the Washington Post also noted that “few experts think that production of stem cells through cloning is likely to be medically useful soon, or possibly ever,” and quoted MIT biologist Rudolf Jaenisch’s opinion that the study “has no clinical relevance.”
George Daley, a stem cell expert at Children’s Hospital Boston, notes that, “it’s essential to compare the cells from the two methods.” According to Nature, Mitalipov and his team are already doing exactly that – conducting a study of comparisons between iPS and SCNT cells derived from the same donor cell. There will certainly be ongoing updates on this front.
Reproductive human cloning?
The Center for Genetics and Society raised the issue of human reproductive cloning in a press statement, and pointed out that the United States – unlike some 60 other countries – still has no federal prohibition against it. “If we're going to be having cloned embryos in laboratories around the country, said CGS’s Marcy Darnovsky, “we really need to get our act together and have a law that prohibits human reproductive cloning.” GenomeWeb picked up this argument here, and NPR looks at the prospects on the policy landscape here.
Many other news outlets also voiced concern that the SCNT work could be used to attempt reproductive human cloning. Paul Knoepfler provides a useful diagram that illustrates the “elephant in the room” of the close relationship between research and reproductive cloning. He acknowledges that cloned babies will not “be bouncing out all over the place anytime now,” but says that “yesterday’s story does of course relate to human reproductive cloning and it is a real, deeply serious concern longer term. Some crazy person will try to clone humans.” Dr David King of Human Genetics Alert raises similar points and says that the OHSU research is an "irresponsible" project that has created "the baby that would-be human cloners have been waiting for: a method for reliably creating cloned human embryos".
Mitalipov’s team is understandably eager to dissociate their work from the possibility of reproductive cloning. Nature reports, “Mitalipov has tried without success for more than a decade to produce a monkey by cloning. [Co-author] Tachibana says that an upcoming publication will explain why reproductive cloning of humans is not possible using their SCNT technique.” Professor Robin Lovell-Badge, head of developmental genetics at the National Institute for Medical Research, similarly reiterates that years of cloning work with animals has affirmed that it would be unsafe to try in humans, so: “For this reason alone it should not be attempted."
More demand for women’s eggs?
Relatively few news stories explored how the SCNT success might affect the demand for women’s eggs and the health of the women who undergo invasive procedures to provide them, though a number mentioned that Mitalipov’s work used fewer eggs than previous cloning experiments. As Chris Mason of University College London told New Scientist, "Mitalipov clearly has very high efficiency ... However, it still boils down to needing to get human eggs."
Payments to women who provide eggs for research are controversial because of concerns that they encourage women to overlook the significant health risks of egg retrieval. Many women’s health advocates point out that because follow-up studies on egg retrieval have been so inadequate, getting “informed consent” to take the risks is challenging if not impossible.
Another troubling aspect of the OHSU study is that at least five of the authors of the Cell article work as practicing reproductive endocrinologists, raising concern that some may have themselves overseen the egg retrieval procedures. It is therefore unclear whether the study followed the recommendations of the International Society for Stem Cell Research that in order to avoid conflicts of interest, “wherever possible, the treating physician or infertility clinician should not also be the investigator who is proposing to perform research on the donated materials” [pdf].
The OHSU study reports some troubling findings about egg retrieval protocols, including the fact that one of the hormonal drugs typically used for ovarian stimulation results in “sub-optimal quality oocytes,” and that “premium quality” eggs are produced when fewer are retrieved in a stimulated cycle. This suggests that the hyper-stimulation protocols frequently used in fertility procedures are not only dangerous for the women who undergo them, but may also be hazardous to the health of their prospective children.
As the CGS press statement points out, these adjustments to standard IVF protocols “were made in order to obtain ‘optimized’ eggs for research, not to protect women from adverse effects” of egg retrieval. The focus, ironically, is “on the quality of the eggs, not on the well-being of the women.”
Previously on Biopolitical Times: