Why Easy Stem Cells Raise Hard Ethical Questions

Late last month, Haruko Obokata and her colleagues at the RIKEN Center for Developmental Biology in Kobe, Japan reported that they had discovered a surprising new technique for making stem cells. In a pair of articles published in the journal Nature, they claimed that ordinary mouse cells could be made pluripotent (that is, having the ability to develop into any of the body’s tissue types) by exposing them to various forms of stress, such as acidic conditions.

The most obvious practical application of this new technique is that it could serve as a new source of pluripotent stem cells for regenerative medicine or for research. Initial results suggest that the technique is not only simpler than the genetic engineering techniques developed in 2006 to create induced pluripotent stem (iPS) cells, but also much more efficient at transforming cells to a pluripotent state.

There is still more work to be done before we know whether this procedure will work on the cells of adult humans. There are many differences between the stem cells of mice and humans, and the researchers reported that even in the mice they worked with, using the cells of one-month-old animals was as much as ten times less efficient than using the cells of one-week-old mice. But if it is possible to use this technique on human cells, then it seems to hold real promise as a source of pluripotent stem cells formed without destroying embryos.

The Troubling Potential of STAP Cells

Yet these cells have a troubling potential. One of the surprising features of these cells, which Obokata has called “stimulus-triggered acquisition of pluripotency” cells, or STAP cells, is that they are not only able to develop into all embryonic tissue types—they can also contribute to the development of a placenta. Neither embryonic stem cells nor iPS cells can develop into placental tissue. In fact, this has often been seen as a defining difference between embryonic stem cells and actual embryos: embryonic stem cells cannot, on their own, develop into adult organisms the way an actual embryo can, in part because they cannot grow the extra-embryonic placental tissues needed for fetal development in the womb. If STAP cells can indeed support fetal development, clusters of these cells may actually be embryos. If so, the creation of these cells would be tantamount to human cloning.

Some scientists speculate that these STAP cells could be used for reproductive purposes. In today’s in vitro fertilization (IVF) procedures, egg cells are collected from women, fertilized, and then those embryos are transferred to the mother’s (or a surrogate’s) womb. But in this theoretical new technique, a man or woman could simply have his or her skin cells transformed into STAP cells, which could then be transferred to a surrogate.

If this were possible—and I must stress that it is not clear that it ever will be—then human cloning could become a simple and practical option. One of the most difficult parts of current IVF procedures is acquiring human egg cells, which involves exposing women to potentially dangerous hormones. Even the methods of cloning used to produce Dolly, which have recently been used to clone human embryos, require the collection of egg cells. But this new technique might allow for cloned embryos to be created from just a handful of skin cells, which could be easily and safely collected from either men or women.

The Need for Further Research

Right now, the published evidence that these STAP cells might be actual embryos is fairly scant. In a shorter article accompanying their paper, Obokata and her colleagues reported that when they injected STAP cells into ten early-stage mouse embryos, descendants of the STAP cells were found in the placenta and embryo in six cases. Embryonic stem cells or iPS cells almost never contribute to the development of the placenta, so this was a striking finding.

But the wide range of developmental potential these cells have does not necessarily make them embryos. There’s an old motto in biology, attributed to the great seventeenth-century anatomist William Harvey: “omne vivum ex ovo,” or “all life from eggs.” In the animal kingdom, this doctrine still holds true; embryos are fertilized egg cells, and the egg cell provides a great deal of material necessary for the embryo’s early development. Just because an adult cell has been “reprogrammed” to a state of developmental immaturity that allows it to branch off into any of the different cell lineages, that does not mean that it will be able to undergo the highly coordinated development of an embryo on its own, or even together with other such reprogrammed cells.

We should still take the possibility seriously, however, that this new method of reprogramming might make embryos. Rumors are already circulating that scientists have attempted this in mice. According to a story in the New Scientist, one of the co-authors of the study, Charles Vacanti, said that he asked an unnamed collaborator to transfer a spherical cluster of STAP cells to a mouse. Vacanti reports that the cells began to develop as a fetus, but that halfway through the pregnancy, the fetus stopped developing normally. According to Vacanti, “There was some sort of glitch—which is probably a good thing due to the ethical issues that would occur if we were able to create a live clone.” But if it is true that these cells are able to develop as embryos, then the fact they develop defectively is not reassuring. Okotaba, for her part, said that her team was interested in regenerative medicine, not human cloning.

Scientific and Ethical Questions

Although the research has not been published, Vacanti has claimed that he has already applied the technique to human cells, and has even sent images of what he says are clusters of human STAP cells to the magazine the New Scientist. Until Vacanti’s results are published in a peer-reviewed journal, it is difficult to know much with certainty about whether the human cells he created were totipotent cells—embryos—or simply pluripotent cells. It is possible that, as research develops, boundaries might be discovered that would set ethical limits on how STAP cells are created and used.

The most serious ethical concern raised by the possibility that STAP cells have the characteristics of embryos is not that the new technology could be misused by unscrupulous parties, but that the very act of creating and experimenting on these cells would be an unethical exploitation of human life. To determine whether this is so, we must answer a question that is at once scientific and ethical: Just what is an embryo? Or, put somewhat differently, what is that makes something an individual organism, as opposed to a mere “clump of cells?”

Moral seriousness demands that we take this scientific question seriously before we embark on the use of this new technology with human cells. It would perhaps be convenient for our society to ignore the instrumentalization and destruction of human life by pretending that developments in biotechnology render the distinction between organisms and their parts meaningless. But such willful ignorance is no excuse, especially for a civilization that prides itself on scientific sophistication. Biologists should take confusion over how to determine when the life of an individual human (or for that matter, any other animal) begins not as a license for experimentation on beings whose organic unity is ambiguous, but as an embarrassment for their discipline, and as a scientific puzzle worth solving.

It is sometimes said that modern science is simply about the acquisition of power over nature, not theoretical inquiry into the nature of the world. If this were true, modern scientists would view problems whose answers will not yield new technologies—such as the question “what is an embryo?”—as vain or meaningless. But this description does not do justice to the passion for theoretical inquiry and wonder about nature that animates the work of many scientists today.

The late Carl Woese, an evolutionary microbiologist whose own important discoveries were perhaps more theoretical than practical, warned biologists in a 2004 essay that it is dangerous to allow “science to slip into the role of changing the world without trying to understand it.” Discovering a way to distinguish clusters of pluripotent cells from embryos is part of trying to understand the world. It is likely to constrain the use of new technology rather than enable scientists to “change the world,” but in a time when our biotechnological power seems to constantly outstrip our wisdom, such constraining knowledge is just what we need.

Renewing the Public Debate

Practically speaking, in the United States, the Dickey-Wicker amendment to appropriations legislation for the Department of Health and Human Services prohibits federal funding for research in which embryos are created or destroyed. The language of the law is sufficiently broad to include even such novel methods of embryo creation as those used to create STAP cells. For the National Institutes of Health to conscientiously observe the provisions of the Dickey-Wicker amendment, it would behoove them to sponsor studies in mice to determine when and how these STAP cells might be thought to constitute embryos before they provide funding for research on STAP cells in humans.

Some of the research that Obokata and her colleagues have already reported may shed some light on how scientists can create STAP cells without inadvertently creating embryos. For instance, the scientists have already found that STAP cells grown under certain conditions do not have the ability contribute to the placenta and behave more like normal iPS cells or ES cells. If scientists can identify the conditions under which STAP cells acquire different states of pluripotency, they can use this knowledge to set limits on how human cells can be grown. It will be important for scientists to attempt reproductive cloning in mice (and perhaps non-human primates as well) using STAP cells, and to publish the results of their attempts, whether they are successful or not.

One risk of doing the kind of research necessary to determine the conditions under which these STAP cells become real embryos is that the knowledge gained will not be used to limit the use of the new cells, but actually to extend their use into the realm of reproductive cloning. In a commentary accompanying their story about the new technique, the editors of New Scientist expressed their concern that some “maverick” scientists might use the method for reproductive cloning:

Such antics would poison the promise of this advance before it even begins. This is an area where passions run high, and consensus will be hard to find. So the time is ripe for renewed discussion of the uses of stem cell technologies. We should make a clear-eyed start on it now.

While the debates over cloning and stem cell research have languished since the election of President Obama, who overturned President Bush’s compromise on federal funding for embryonic stem cell research, developments like this one, and like the cloning of human embryos by scientists in Oregon last May, should remind us that the issues raised by the stem cell debate have not gone away.

Finding a way to make good on the promise of this new advance without having it poisoned by immoral applications will require a strong stance against cloning and embryo experimentation. If we can draw bright moral lines separating what is acceptable from what is immoral, then we can perform the research necessary to break new ground in biotechnology without fearing that such research will be used for dehumanizing ends.