In an essay here last week, Greg Kaebnick proposed that induced pluripotent stem (iPS) cells are akin to the “clonotes” that result from somatic cell nuclear transfer, since both involve reprogramming the nucleus of a human somatic cell. To develop an iPS cell, one must reprogram a somatic cell, such as a skin cell, by inserting new genes into its genome, whereas to develop a “clonote,” one must reprogram that cell by inserting it into an egg, where the gene products residing in the cytoplasm of the egg do the job. Kaebnick suggests that the “clonote” “looks much like a zygote,” and maintains that just as a “clonote” appears to be a new kind of embryo, so an iPS cell may also be a new kind of embryo. Therefore, he argues, those who hail the development of iPS cells as a way to get around the moral difficulties associated with the destruction of human embryos entailed by the derivation of embryonic stem cells (ES cells) will need to rethink their critique of cloning.
This is fascinating speculation until one considers the features of iPS cells. These cells are akin to ES cells rather than to “clonotes,” and neither ES cells nor iPS cells have been shown, or are expected to be shown, to be equivalent to embryos.
Let’s compare ES cells and iPS cells. Human ES cells will not develop into newborn humans if transferred to the bodies of women for implantation because (1) they lack the extracellular layer required prior to implantation, (2) they are too small and lack the internal organization needed to function as zygotes, and (3) they are not totipotent. They can produce all the cells of the embryo proper when implanted into an embryo host, but not the extraembryonic tissues required for the development of the fetus. According to the preliminary studies carried out by those who developed them, iPS cells appear to have the same features as ES cells: they, too, (1) lack the extracellular layers required by embryos, (2) are too small and lack egg-like organization, and (3) are not totipotent, by all evidence.
Kaebnick is struck by the fact that in tests of their pluripotency these new iPS cells produce the embryoid bodies of teratomas. He appears to take this to mean that they therefore have the same capacities as embryos. While these embryoid bodies consist of tissues derived from all three embryonic germ layers (indicating pluripotency), they are not organized like an embryo and would not develop like an embryo if implanted in a woman’s uterus; they would continue to be a tumor. Teratocarcinoma tumors can also form embryoid bodies, but they are clearly not embryos. Thus, a pluripotent stem cell can divide and aggregate to form an embryoid body, but this does not make it, nor the embryoid body it may form, an embryo.
Kaebnick suggests that what might really be going on among those who object morally to the development of “clonotes” but who accept as ethical the development and use of iPS cells is that they revere the human egg as a natural entity that is “expected” to try to become a human individual because it has a “natural potential” to do so. Yet surely it is difficult to explain the moral repulsion that some experience toward cloning as grounded in a concern about the “unnatural” destruction of the human egg. There is no movement among them to freeze all “left-over” eggs in order to fertilize them and develop “Snowflake” babies from them. The basic objection of many critics of reproductive cloning is that a “clonote,” if transferred to the uterus of a woman, could well grow into a living individual human being, but with a high probability of having serious gene-based conditions. The self-indulgent creation of duplicates of living persons or the use of “clonotes” as disposable sources of spare body parts hardly justify the huge risk of damage to, or even destruction of, cloned children. Concern about the fate of the eggs destroyed in somatic cell nuclear transfer has not been a significant feature of the objections to the production of “clonotes.”
The iPS cells provide another form of pluripotent stem cell that, if developed in a way that did not call for the insertion of genes causing random mutagenesis, could become a safe and effective source of stem cells. If this were done successfully, there would be little or no need to transfer somatic cell nuclei into eggs to clone ES cells for individualized therapy or for research on patient-specific diseases.
There would also be no special need for human ES cells if the reprogramming of somatic cells to pluripotency (or useful multipotency) and high proliferative capacity could be performed so that the resulting iPS cells were safe for therapeutic uses. However, we are a long way from that. Much more research on human iPS cells is required before we know that they do indeed have the same desirable properties as human ES cells and are safe to use for any therapy. In the meantime, it is important to continue to do research on human ES cells and to produce new ES cell lines in order to learn how these cells develop, proliferate, and function and to find new, more comprehensive treatments for those who suffer from serious diseases.
Cynthia B. Cohen is a faculty affiliate at the Kennedy Institute of Ethics, Georgetown University. She is also the author of Renewing the Stuff of Life: Stem Cells, Ethics, and Public Policy. Bruce P. Brandhorst chairs the Department of Molecular Biology and Biochemistry at Simon Fraser University, in Canada.