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Altered Nuclear Transfer Chapter 9 A Contested Case: Altered Nuclear Transfer How to Evaluate Entities Produced by Experimenters U p till now our focus has been either on relatively clear experimental manipulations (e.g., cellular reprogramming) or on entities that are the product of natural mutation or error (e.g., hydatidiform moles, triploid embryos, and parthenotes). But the three criteria of organization are equally helpful in assessing more difficult cases of entities created through direct manipulation, for example, the entities created by Altered Nuclear Transfer, or ANT. ANT was initially proposed as a means of obtaining, from an entity that was not an embryo, pluripotent stem cells that were a perfect genetic match to a patient.1 Since ANT was proposed, the reprogram1 . William B. Hurlbut, M.D., “Altered Nuclear Transfer as a Morally Acceptable Means for the Procurement of Human Embryonic Stem Cells,” President’s Council for Bioethics, 2004, accessed November 12, 2015, .html. 223 224 Altered Nuclear Transfer ming technique pioneered by Yamanaka has provided an elegant (and far simpler) way of achieving these same goals. Yet the ANT proposal still merits a detailed discussion, because it raises a number of important questions regarding experimental manipulations of human gametes and illustrates the difficulty of accurately determining the ontological nature of entities produced in the laboratory. In its general form, ANT builds on the established technology of somatic cell nuclear transfer (SCNT), or what is commonly referred to as “cloning.” In SCNT, an adult (“somatic”) cell is fused to an enucleated oocyte. Because of the large difference in cell size (an oocyte has a volume roughly a thousand times greater than a typical somatic cell), the most significant contribution of the somatic cell is the nucleus, and therefore the technique is loosely referred to as “nuclear transfer.” Following fusion, the newly created cell is then stimulated to begin cell division. Somatic nuclei from specific tissues (e.g., liver and skin) differ significantly from each other and from the nuclei of germ cells in that the gene sequences of somatic cells are restricted so that only those genes associated with the mature state of the cell are expressed. Liver cells express only those genes associated with being a liver cell; fibroblast cells express only the genes of mature fibroblasts, and so on. This restriction is largely due to modifications in the regulatory proteins associated with the DNA (i.e., the “epigenetic state” of the nucleus). The genes that are not needed (or are indeed counterproductive to the proper functioning of the cell) are blocked by the addition of a methyl molecule to the DNA, or through other molecular mechanisms. Fascinatingly, however, the cytoplasm of an oocyte can sometimes successfully modify or “reprogram” the epigenetic state of the transferred nucleus and “reset” it to a state similar to that of a normal zygote. Hence, when the nucleus is transferred, the reprogramming begins and, if successful, the somatic nucleus is reset and the hybrid cell is now in a totipotent state from which the development process can (hopefully) begin.2 If successful, the product of SCNT will continue development 2. As has been alluded to, this process is far from foolproof. Nuclei are not always reset, which can lead to a wide variety of severe or even fatal defects. The actual success rate of the SCNT process in producing live births (e.g., “Dolly” the cloned sheep) varies by species, but in all cases is low (typically in the range of 0.1% to 3%). In addition, even “successful” SCNT (i.e., Altered Nuclear Transfer 225 and can result in a live birth of the animal in question, including—theoretically —a human. ANT proposes to use the SCNT technology, but rather than constructing a hybrid totipotent cell, it would instead aim to produce only a pluripotent one. Totipotent cells are not only capable of differentiating into every cell of the body, including extra-embryonic tissues, they also possess the internal power (potentia) to self-direct the developmental process toward the production of a complete animal.3 In contrast, pluripotent cells can produce only the cells of the ex utero body and cannot of themselves self-direct development. When not part of an actual embryo, such cells will produce only tissues, not complete animals. Though a totipotent cell will ultimately produce pluripotent cells in the normal course of self-development, pluripotent cells make up part of the embryonic body. Accordingly, the normal procedure for procuring pluripotent...


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