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February 16, 2014

The ambiguities of the term "totipotent"

Via Wesley J. Smith I learned of this incredibly important recent article by embryologist Maureen Condic. If you are at all interested in the issues of the right to life of early embryos and in the science behind it, go and download a copy of the article immediately. Though I cannot see that Condic actually refers in her article (perhaps it's in the massive footnotes, which I didn't read) to recent research purporting to have created totipotent mouse cells by an extremely simple method of adult cell reprogramming (called the creation of STAP cells), what she has to say is relevant to those claims and is extremely timely.

I had not yet posted about that research for a number of reasons. For one thing, I was waiting for more information. For another, the claimed results had not (as far as I know) been duplicated. (See here for some generalized skepticism about the STAP claims, questioning whether the results will be able to be replicated at all and whether they are even scientifically accurate in their own terms.) For a third, the claims of totipotency in the cells created by the simple method of exposing differentiated cells to stress (such as an acid bath) seemed to rest on the rather shaky evidence that the cells, when subsequently injected into a mouse embryo, migrated all over the embryo including to the placenta. What, precisely, they were doing in the placenta, what sort of placental cells they became, and so forth, remained unanalyzed.

During that time the question was asked in a private Facebook forum, probably apropos of this research, whether, if human cells were de-differentiated to the point of being totipotent, it would be wrong to use them in research. I answered carefully that it would depend on the meaning of "totipotency" and, most crucially, on whether the "cells" were actually human embryos. If human embryos are created in a lab, by whatever method, then it is always wrong to use them in destructive research. In fact, it's wrong to create human embryos in the lab at all. If this process can be carried out in humans and produces embryos, then it is in effect a cloning process, and using it in humans is unethical, however convenient. However, I was extremely dubious that this process was creating mammalian embryos. There were a number of reasons for being dubious. First of all, it seemed implausible that merely subjecting adult cells to stress turns them into embryos! Relatedly, the researchers conjecture that they may be mimicking a process that occurs routinely in the adult body in response to cellular damage as a method of repair. But is human reproduction occurring routinely in, say, men's bodies? Is even mouse reproduction occurring routinely in male mouse bodies? That was enormously implausible. If so, why do we not have virgin conceptions popping up by natural causes from time to time if a virginal female's body responds to cellular stress by producing an "accidentally created embryo"? (Even if the cells produced were not embryos but merely plenipotent, a term I will discuss below, it seems that we would expect a lot more cancers, called teratomas, turning up in adult bodies--for example, in the acidic environment of the stomach. See here. This is a reason to question what is being claimed in this research.) Human reproduction is difficult, even in vitro. That's why human cloning has been so long in coming and has always required an egg. So I was skeptical. Oh, one other thing: Buried in one of the articles is a statement that an unnamed researcher had attempted to insert these allegedly totipotent cells directly into a mouse uterus to see if they would develop as baby mice, with negative results.

Into this atmosphere of uncertainty, Condic's paper comes as a useful and highly informative model of scientific rigor and thoroughness. Though Condic doesn't discuss or question the STAP research directly, she does give us important information about various types of human stem cells and the confusing terminology that surrounds them. If the STAP claims hold up to attempts by other scientists to reproduce the results, Condic's scientific work here will be indispensable to discussion of the ethical implications.

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