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Are totipotent cells really embryos?

Major developments in stem cell science tend to revive scruples about whether the new pluripotent cell is or could become an embryo. This happened with embryonic stem cells, with Yamanaka’s induced pluripotent stem (iPS) cells, and now with stimulus-triggered acquisition of pluripotency (STAP) cells. Unhappily, a cloud hangs over STAP cells because it appears that the original paper in Nature was peppered with mistakes. But the question remains: if scientists create cells which can develop into any cell in the body (and into the placenta as well), are they not what we would otherwise call embryos?

Maureen Condic, of the University of Utah, a redoubtable opponent of human embryonic stem cell research, debunks this idea in the journal Stem Cells and Development: stem cells, she insists, are not embryos.

The problem begins with terminology, she says. The National Institutes of Health defines “totipotent” in two different ways: “capable of developing into a complete organism” or “differentiating into any of its cells or tissues”. The first kind of totipotency is an embryo; the second is a stem cell.

The difference between these two definitions is not trivial. Producing a mature organism requires the ability to both generate all the cells of the body and to organize them in a specific temporal and spatial sequence, that is, to undergo a coordinated process of development. Totipotency in this strict sense is demonstrated by the ability of an isolated cell to produce a fertile, adult individual. Consequently, a cell that is totipotent is also a one-cell embryo; that is, a cell that is capable of generating a globally coordinated developmental sequence.

Only the fate of an organism which is capable of developing into an adult is ethically controversial.

Rather, ethical consideration is given to human embryos based on the status they already possess; that is, their unique and fully operative ability to function as a human organism. Therefore, ethical controversy regarding totipotent human cells only concerns cells that are totipotent in the strict, organismal sense; that is, a cell that is a human embryo.

 

Condic suggests that the term “totipotent” should be confined to organisms, ie, embryos. She coins the term “plenipotent” for cells which are capable of developing into all cells in the body.

What accounts for the difference? Condic explains that research shows that factors in the cytoplasm of the egg are necesssary for the existence of true totipotency. “At this time, the only known totipotent cytoplasm is produced by an oocyte and contributed to the embryo at fertilization. The fact that oocytes produce the cytoplasmic factors that are required for an embryo to be totipotent is the reason oocytes are used for cloning.” Without these factors, a “plenipotent” cell can never become an embryo.

Language matters. If people do not grasp the difference, they can create artificial controversies “over areas of research that are ethically unproblematic”, Condic writes.

Note: the article in Stem Cells and Development is behind a pay wall. Dr Condic has summarised her paper in Public Discourse, which is readily available.



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