Stem Cell Semantics

It's been six years since human embryonic stem cells appeared on the public radar screen, and we still don't know what to call them. Take the word "embryo," which means different things to different people. In the 1980s, an embryo wasn't an embryo until it 1) had a primitive streak, 2) sported three layers, and 3) could no longer split to yield twins. Then somehow an inner cell mass became a full-fledged embryo, although it is only a mere smear of undifferentiated cells hugging the interior of a blastocyst.The problem is apples-and-oranges dichotomies and definitions. The "intent" dichotomy distinguishes reproductive from therapeutic efforts, and the "nuclear source" dichotomy introduces DNA from in vitro fertilization (IVF) leftovers or somatic cells, both routed through an inner cell mass. And the "developmental timeframe" dichotomy of embryonic vs. adult makes no biological sense. What do you call a fibroblast, busy pumping out its collagen and elastin, which is in an embryo? Or what about a hematopoietic stem cell in an 83-year-old?To attempt to get us all on the same page, the International Society for Stem Cell Research (ISSCR) on Sept. 2 released a nomenclature statement.1 It makes two main points. First, cloning is not the same as nuclear transfer, because the resulting first cell also receives mitochondrial DNA and maternal mRNAs from the vacated oocyte. Second, scientists should ditch the use of the word therapeutic, because a technique should not be named for its anticipated outcome.I agree with the statement of the problems, but not with the ISSCR's suggested solutions. It advocates that the two sources of stem cells be called hESCs for human embryonic stem cells (which I find acceptable), and NTSCs for nuclear transfer stem cells. My brain, imprinted on SCNT (somatic cell nuclear transfer) from amphibian work in the 1960s, cannot easily switch to NTSC. I prefer the term "somatic stem cells," with the nuclear transfer step inferred. (How else would a mammary gland cell's nucleus have jumped into the oocyte to make Dolly?) "Somatic stem cell" also avoids the nonsensical "adult stem cell." Said cell need not be from an adult human, nor even differentiated, just diploid.Bioethicists tackle the semantic problem, too. Harvard's Louis Guenin introduces the "unenabled embryo," which is an inner cell mass that will never enter a uterus.2 This avoids saying whether its genetic headquarters came from a fertilized ovum or an adipocyte in a 50-year-old's abdomen. But what will happen if Brave New World's ectogenesis (gestation in vitro) ever becomes fact? Embryos could then grow up sans uterus. Guenin further delineates the "epidosembryo," donated for use in experimentation or therapy, and therefore not a person.At the Dec. 3 meeting of the President's Council on Bioethics, Columbia University's Donald Landry and Howard Zucker compared a nonviable IVF embryo to a newly-deceased person whose organs are transplanted: Why not pluck healthy cells from an otherwise stagnant and destined-for-dumping blastocyst? They distinguish the nonviable embryo that can't develop to be born, from the organismically dead embryo, whose cells do not divide or interact.3 The distinction, I think, is that a nonviable embryo might not be dead, but all dead embryos are nonviable. At the meeting, William Hurlbut also presented a proposal to tap teratomas for healthy cells among the tumorigenic tissue, which is hardly a new idea in developmental biology circles.Alas, despite these noble attempts at clarity, the terms "cloning" or, worse, "therapeutic cloning," may be here to stay. For example, a two-page news release on efforts to clone primates, dated Dec. 6, from the University of Pittsburgh, uses "clone" 26 times and "therapeutic cloning" four times, twice from the researchers.4 The Pittsburgh work, according to the release, "further illuminates the science of cloning."Moreover, attempts by others in the stem cell debate to educate the public only add to the confusion. A pamphlet written by J.C. Willke, president of the National Right to Life Committee and self-described radio personality explains: "Embryonic stem cells are obtained from 5-day-old living human embryos. This tiny human is cut open and embryonic stem cells are extracted from him or her. The process directly kills a five-day-old human."5What's needed in stem cell semantics is a return to scientific precision, with explanatory phrases such as "human stem cells derived from somatic tissue." "Neural stem cells" is a nice, clear term, too, although researchers keep refining the distinctions between stem cells and their immediate progenitors. But that's another story.

Stem Cell Semantics

It's been six years since human embryonic stem cells appeared on the public radar screen, and we still don't know what to call them.

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