Politics & Policy

The Grail Searchers

Despite endless efforts to prove the contrary, science shows that an embryo is a human being.

“The development of a human being begins with fertilization, a process by which the spermatozoon from the male and the oocyte from the female unite to give rise to a new organism, the zygote.Langman’s Medical Embryology, 7th edition, 1995

For people who advocate the killing of embryonic human beings in the cause of biomedical research, the Holy Grail is an argument that would definitively establish that the human embryo, at least early in its development, is not a living human organism and therefore not a human being at all. The problem for these advocates is that all the scientific evidence points in precisely the opposite direction. Modern human embryology and developmental biology have shown that fertilization produces a new and distinct organism: a living individual of the human species in the embryonic stage of his or her development.

Some proponents of embryo-destructive research are willing to face up to these biological facts. They concede that human embryos are living individuals of the human species, but deny that this gives them the moral status of being persons. According to this argument, not all human beings are equal; not all possess inherent dignity and a right to life. Some, including those at early developmental stages, are not (or are not yet) “persons,” and they may therefore (at least in some circumstances, or in the pursuit of some goals) legitimately be killed.

#ad#There is much to be said against this position, but its defects are philosophical, not scientific. Its proponents recognize that there is no Holy Grail out there to find, and they are willing to defend the killing of human embryos while facing up to the biological facts. But then there are the Grail searchers. These people are determined to prove that what modern human embryology has been telling us is wrong, and to this end they scavenge the fields of molecular biology and human genetics.

Among the Grail searchers, there is none more determined than Ronald Bailey, science writer for the libertarian magazine Reason. Every now and then Bailey pops up to make a dramatic announcement: The Grail has been found! A few years ago, for example, he used a reductio ad absurdum that employed an analogy to cloning. Bailey offered to prove that every cell in the human body has as much potential for development as a human embryo. Therefore, he wrote, human embryos are the biological and moral equivalent of body (“somatic”) cells; they have no greater dignity than, for example, the skin cells that we rub or wash off our bodies every day.

Here is how the argument went: Each cell in the human body possesses the entire DNA code; each has become specialized (as muscle, skin, etc.) by having most of that code turned off. In the scientific process known as cloning, the portions of the code that were previously deactivated are reactivated. So, Bailey concluded, quoting bioethicist Julian Savulescu: “If all our cells could be persons, then we cannot appeal to the fact that an embryo could be a person to justify the special treatment we give it.” Since plainly we are not prepared to regard all our cells as human beings, we shouldn’t regard embryos as human beings.

Unfortunately for Bailey, his analogy between somatic cells and human embryos collapses under scrutiny. The somatic cell is something from which a new organism can be generated; it is not itself, however, a distinct organism. On its own, it remains just what it is (a constituent cell of muscle, skin, etc.). For it to contribute to the generation of a complete living being, significant interventions are needed, including the addition of critical molecular factors provided by a human egg cell.

A human embryo doesn’t need that. It already is a distinct, self-developing, complete (though immature) human organism. If someone tried to implant a somatic cell in the prepared uterus of a woman, nothing would happen — just as nothing would happen if someone tried to implant a sperm or an unfertilized egg. But a human embryo implanted in the prepared uterus of a woman will, barring some defect or accident, grow and develop, emerge from the womb some months later, soon begin walking and talking, and in a few years be asking mom and dad for the car keys.

So Bailey hadn’t discovered the Holy Grail after all. But now he’s back, claiming once again that it has been found. His claim comes in an online post criticizing an argument we made in response to some other Grail searchers.

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Those searchers are William Neaves and Gerard Magill. Their candidate for the Holy Grail is an argument purporting to show that human embryos are the ontological and moral equivalent of induced pluripotent stem cells (iPSCs). Again the form of the argument is reductio ad absurdum. No one supposes that iPSCs are human organisms, so if it can be shown that iPSCs are the equivalent of embryos, then embryos cannot be human organisms either.

What are iPSCs? They are a widely touted class of cells that have been produced by Shinya Yamanaka in Japan and James Thomson in the United States. They are made by reprogramming (or “de-differentiating”) ordinary somatic cells to the pluripotent state — the state from which they can be coaxed to become virtually any type of tissue: heart, liver, nerve, you name it. What is exciting about these cells is that they have the medically useful features of embryonic stem cells, yet they can be produced without killing (or even using) embryos.

According to Neaves and Magill, however, iPSCs are not merely the biological equivalent of embryonic stem cells; they are the equivalent of the embryos that are destroyed to produce embryonic stem cells. On what basis do they advance this idiosyncratic view? (It is, incidentally, a view plainly rejected by Yamanaka and Thomson, who have explained that the significance of iPSCs is that they do not raise the ethical problems associated with killing human embryos.) Neaves and Magill claim that an iPS cell, though obviously not an organism, is the biological equivalent of an embryo because it can develop into a human organism.

#ad#How is that? Well, when joined to a tetraploid “embryo” (an entity created by fusing the first two cells of a normal embryo into a single cell that contains twice the normal amount of DNA), an iPS cell will contribute to the development of a mature organism of its species (as has been shown with mice). In this procedure, according to Magill and Neaves, the iPS cells are merely being provided with a placenta — which they view as a “component of a supportive environment for development,” like a uterus, rather than as an integral part of the developing organism. Just as a human embryo needs only a suitable environment to develop itself to a mature stage, so does an iPS cell need only the suitable environment supplied by a tetraploid “embryo.”

Replying to Neaves and Magill, we demonstrated that their claim that iPS cells develop into a complete embryo is scientifically inaccurate. Rather, they become part of a distinct, developing organism, consisting of structures derived from both the iPS cells and the tetraploid cells. The key question is whether a placenta is just a “component of a supportive environment” or an actual organ of the embryo, and anyone familiar with human embryology will recognize that it is a mistake to classify a placenta as a mere “environmental requirement.”

Here’s why: The developing organism requires information provided by both inner cell mass cells and trophectoderm cells (the precursors to the placenta). So in the prenatal stage of development, the placenta is an integral part of the developing human, functioning as a vital organ and even sharing a common blood circulation with the rest of the developing embryonic body. In contrast, the uterus of the mother is clearly part of a distinct organism that is not integral to the embryo itself, but merely provides a supportive environment and a source of nutrition. Hence a placenta is an organ of the embryo, albeit a transitory one. This means that together, the iPS cells and the tetraploid cells constitute an entire, integrated whole — an organism. In stark contrast, at no point does an iPS cell function as a whole organism by itself. So any argument resting on the claim that an iPS cell is the biological equivalent of an embryo simply won’t fly. The Grail searchers will have to search on.

But Ronald Bailey just doesn’t want to give this one up. In “Do Skin Cells Have Souls?” he deploys the tedious and shopworn strategy of writing as if only religious zealots think human embryos are human organisms — thus his reference to souls in the title and a reference to angels on the head of a pin in the concluding sentence of his essay. But as he well knows, biology and human-embryology texts have for a long time been quite clear that a new human organism comes into existence at fertilization. That is, in human reproduction, when sperm joins ovum, these two individual cells cease to be, and their union generates a new and distinct organism. This organism is a whole, though in the beginning developmentally immature, member of the human species. Readers need not take our word for this: They can consult any of the standard human-embryology texts, such as Moore and Persaud’s The Developing Human, Larsen’s Human Embryology, Carlson’s Human Embryology & Developmental Biology, and O’Rahilly and Mueller’s Human Embryology & Teratology.

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Bailey characterizes our argument in the exchange with Neaves and Magill as “convoluted.” At one point he even calls it “desperate.” But one would be hard put to decipher from Bailey’s account of that exchange what the basic issue was. In various places we have made explicit what is generally assumed in biology: If an organism has all the internal resources, along with an active tendency or disposition, to develop itself to the stage where it performs the functions specific to an organism of a certain kind, requiring only a suitable environment and nutrition for that development, then it is an organism of that kind, at an immature stage of its life cycle. Only thus can one recognize a chrysalis as an immature member of Lepidoptera, or a tadpole as an immature member of a frog species. Human embryos, whether they are formed by fertilization (natural or in vitro) or by successful somatic-cell nuclear transfer (SCNT — i.e., cloning), do have the internal resources and active disposition to develop themselves to the mature stage of a human organism, requiring only a suitable environment and nutrition. In fact, scientists distinguish embryos from other cells or clusters of cells precisely by their self-directed, integral functioning — their organismal behavior. Thus, human embryos are what the embryology textbooks say they are, namely, human organisms — living individuals of the human species — at the earliest developmental stage.

Neaves and Magill attempted to refute this argument by pointing to “tetraploid complementation.” But in this process, the iPS cells function as part of a distinct, developing organism, consisting of structures derived from both the iPS cells and the tetraploid cells. It is plain that the iPS cells do not survive the tetraploid complementation procedure, any more than sperm and egg cells survive the process of fertilization. Like the sperm or the ovum, the iPS cells function only as part of a larger whole.

#ad#Near the end of his comments, Bailey discusses “induced totipotent cells,” but in the course of his remarks, he reveals a failure to grasp the central question about them. We do not have to wait for scientists to produce such “induced totipotent cells” and speculate about whether they would be considered embryos; such cells already exist. By Bailey’s definition of totipotency (i.e., the ability to produce all cell types, including those of the placenta), many human tumors and all human embryonic stem cells and human iPS cells are “totipotent.” But although human iPS cells are able to produce all cell types, they are not able to organize these cells into a coherent body, and therefore they are not the biological, moral, or ontological equivalent of embryos.

The truth is that iPSCs are not “totipotent” in the same sense that embryos are totipotent. Embryos not only make all cell types; they also orchestrate all the complex events of development needed to generate a coherent, integrated living body. And therein lies the characteristic that distinguishes embryos from non-organismal cells, including iPSCs. The artificial production of a totipotent cell capable of such an integrated developmental sequence has, of course, already occurred in cloning. Our point was that, so far, biology indicates that the production of a totipotent cell (a new embryo) requires factors derived from the oocyte (an egg cell). If those factors could be derived in some other fashion, their combination would generate a new entity, rather than allowing an already existing entity (such as a stem cell) to actualize an innate capacity. Yet even if that could be done, it would not negate our view of what constitutes an embryonic human organism; it would merely confirm, as cloning already proves, that there is more than one way to produce an embryo. So the Grail searchers would even then have to remain on their never-ending quest.

– Maureen Condic is an associate professor of neurobiology and anatomy at the University of Utah School of Medicine; Patrick Lee is the John N. and Jamie D. McAleer Professor of Bioethics and director of the Institute of Bioethics at the Franciscan University of Steubenville; Robert P. George is McCormick Professor of Jurisprudence at Princeton University.

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