Stemming the tide of cloning.

Author:Burke, William J.
Position::Correspondence - Letter to the Editor

In her article "Stem Cells and Babies" (August/September), Maureen Condic outlines a variation of cloning that she and her colleagues hope will produce the equivalent of embryonic stem cells--while by-passing the production of an actual human embryo, thus overcoming intrinsic moral problems entailed in embryonic stem cells for research.

Condic and her colleagues propose a procedure, called "oocyte-assisted reprogramming" (OAR), which they claim will produce a pluripotent cell without first producing a totipotent zygote, the single-cell embryo. The details, however, show that OAR would produce an embryo--albeit one that would be incapable of developing normally.

Condic's definition of the pluripotent embryonic stem cell is not fully accurate. She states that such cells are "specialized cells that have limited developmental capabilities." According to the National Institutes of Health's definition, however, pluripotent embryonic stem cells are "the embryonic source of all cells of the body." The NIH defines totipotent cells as the source of both embryonic stem cells and of trophoblast cells which give rise to extra-embryonic tissues such as the placenta. Thus the only difference between totipotent and pluripotent cells is that totipotent cells divide and differentiate into both embryonic stem cells and trophoblast cells. Pluripotent cells divide into more embryonic stem cells until they are ready to differentiate, later on in embryonic development.

OAR produces a crippled embryo--one whose cells can divide and differentiate to a certain stage in embryonic development and no further. The OAR proposal uses a variation of therapeutic cloning called altered nuclear transfer (ANT) in which the nucleus of a donor cell (a skin cell, for example), containing the 30,000 genes of the genetic code, is altered in such a way that it produces an epigenetic factor, a protein called nanog.

OAR proponents claim that when the altered donor-cell nucleus with its activated nanog gene is transferred to the enucleated oocyte (egg cell), the presence of nanog will immediately convert the enucleated egg cell to a pluripotent cell, without ever forming a zygote.

The conclusion that no zygote is formed is not correct. Nanog appears in both the morula (12-cell stage) and in high concentration at an advanced stage of normal embryonic development, the blastocyst (150-cell stage). The blastocyst contains both embryonic stem cells and trophoblast cells. Because a pluripotent embryonic stem cell cannot differentiate into a trophoblast cell, the blastocyst must have differentiated into these two cell types from a totipotent cell (the zygote). Therefore nanog does not block the early embryonic development of the zygote. Nanog is said to act at a later stage of development to keep cells in an undifferentiated state. But a short-lived embryo is still an embryo.

Another serious flaw in the OAR proponents'...

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