Abstract
Ethical controversy in stem cell research arises because current methods to produce embryonic stem cell lines require the destruction of living human embryos. For this reason, there is increasing interest in developing alternative, non-embryonic sources of pluripotent stem cells. This effort is especially important in the US due to the prevailing policy against federal funding of embryo-destructive research.
Altered nuclear transfer (ANT) is one of several potential methods to develop alternative sources of pluripotent stem cells. This approach employs the technique of somatic cell nuclear transfer, but the somatic cell nucleus or egg cytoplasm (or both) are first altered before the somatic cell nucleus is transferred into the oocyte. This alteration precludes the coordinated organization and developmental potential that is necessary for the resulting biological entity to be an embryo, but it still allows the entity to generate pluripotent stem cells.
Proof-of-principle for one variant of ANT has been established in mice by silencing the functional expression of the gene Cdx2 in the somatic cell nucleus prior to its transfer into an enucleated egg. From the resulting non-embryonic laboratory construct, fully functional pluripotent stem cells were procured. Other more recent studies have suggested the possibility of achieving the same results by preemptively silencing maternally derived Cdx2 messenger RNA in the egg before the act of nuclear transfer. The procedure would produce the equivalent of a tissue culture of pluripotent stem cells.
In contrast to the use of embryos ‘left over’ from clinical in vitro fertilization, ANT could produce pluripotent stem cell lines with an unlimited range of specifically selected and controlled genotypes. Such flexibility would greatly facilitate the study of disease, drug development, and toxicology testing, and may allow the production of therapeutically useful pluripotent stem cells that are immune-compatible. If developed to the point of scientific reliability, ANT would be a valuable research tool for the study of other aspects of cell development and differentiation, including gene expression patterns, imprinting, and cell-cell signaling. ANT would also help to clarify definitions and boundaries that distinguish true organisms from ‘biological artifacts’ and, thereby, provide moral precedent to guide future progress in developmental biology.
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Notes
According to one recent poll, 56% of Americans express a distrust of science.[3] Depending on how the questions are asked, generally between 35–50% of Americans object to research in which embryos are destroyed to obtain ES cells; that figure jumps to 60–80% when the research involves the intentional creation and destruction of cloned human embryos to get patient-specific ES cell lines.[4,5] The newly elected congress may override the President’s policy regarding IVF embryos, but this would still leave no support for patient-specific ES cell lines of predetermined genotypes. If there is to be federal funding for a full range of stem cell research, there will need to be alternative sources of cell lines that do not involve the destruction of human embryos.
Some may raise the objection that such a procedure carries moral concerns because it prevents a life from coming into being. However, this is a mere abstraction; there is not and never will be an actual embryo against whom there can be a destructive act. Others may object that it is morally wrong to ‘meddle’ with the basic elements of human life, but such a limitation could equally well be applied to a wide range of biomedical research, including studies in human genetics. To open avenues for progress in developmental biology, we will need to draw a clear scientific and moral distinction between what is reasonably considered a human being and what is rightly recognized as a biomolecular or cellular process lacking the integrated unity and developmental potential that characterize a living organism.
Roberts cautions that this work needs to be confirmed by others and in other strains of mouse. Due to problems associated with some of the images, the article reporting these results may be withdrawn or clarified. However, the findings described above have been replicated and appear to be as reported (Roberts RM, personal communication).
The one remaining link with IVF, the procurement of oocytes, is a subject of intense scientific research and there appears to be several prospects for obtaining eggs without the expensive, morally dubious, and medically dangerous procedure of super-ovulation of female patients.
References
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No sources of funding were used to assist in the preparation of this article. The author has no conflicts of interest that are directly relevant to the content of this article.
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Hurlbut, W.B. Ethics and Embryonic Stem Cell Research. BioDrugs 21, 79–83 (2007). https://doi.org/10.2165/00063030-200721020-00002
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DOI: https://doi.org/10.2165/00063030-200721020-00002