Somatic Cell Nuclear Transfer Cloning

Somatic nuclear transfer is a process by which the nucleus of a somatic (nongerm cell) is transferred into the cytoplasm of an enucleated oocyte to create a clone that is genetically identical to the organism from which the somatic cell nucleus was derived. The transfer can be done using a technique called electrofusion, where the enucleated oocyte and the specially treated somatic cell are forced to fuse with a jolt of electricity. The chimeric oocyte is then placed in a surrogatewomb for embryonic development. Nuclear transfer was pioneered over 40 years ago in the frog, but was not successfully realized in mammals until 1996 with the cloning of a sheep named Dolly. Since the cloning of Dolly, somatic cell clones of cattle, goats, mice, and pigs have also been accomplished. The potential benefits of this technology is that cloned animals may be used for the production of therapeutic proteins or human-compatible tissues and organs. The production of therapeutic proteins would be accomplished by first creating a recombinant somatic cell nucleus (i.e., one that contains the gene encoding the desired therapeutic), then transferring this nucleus into the enucleated oocyte. This results in a transgenic animal clone.

EXAMPLE 13.23 The gene for human coagulation factor IX, missing in hemophiliacs, has been cloned into somatic sheep cells with genetic controls for expression in sheep milk. These somatic cells were used to create somatic cell sheep clones that expressed the protein in their milk. Current treatment for hemophiliacs is primarily by purifying factor IX from human blood. This is problematic in that it is expensive and has inherent disease risks (e.g., AIDS). Cloning proponents suggest that production of recombinant proteins in livestock milk may be cheaper and more easily regulated.

Human-compatible organs and tissues can potentially be created from a complicated technology involving either (1) genetic engineering of animals, such as pigs, to destroy problematic transplantation antigens on animal organs, or (2) by using embryonic stem cells to create human organs in vitro or in other species. The process of transferring an organ from one species into another is called xenotransplantation. Stem cells are pluripotent (i.e., have the potential to develop as multiple cell types) cells that are derived from various tissues; very early embryonic tissue yields totipotent embryonic stem cells. Currently, the ethics of stem cell research is a hot topic of debate and it is outlawed in many countries. The major controversy is centered on the creation of human embryos for research purposes. If the stem cells are used to help create organs, the embryo is destroyed. It should be emphasized that neither of these technologies is yet fully realized nor have the ethical ramifications been resolved. In addition, there are potential problems with cross-species diseases coming from the recombinant animal into humans. These issues will need to be resolved before any of this technology is applied.

Practice problems for these concepts can be found at:

Somatic Cell Nuclear Transfer Cloning