"When Mrs. Frederick C. Little's second son arrived, everybody noticed that he was not much bigger than a mouse. The truth of the matter was, the baby looked very much like a mouse in every way. He was only two inches high; and he had a mouse's sharp nose, a mouse's tail, a mouse's whiskers, and the pleasant, shy manner of a mouse."

Thus begins E. B. White's classic tale of Stuart Little, the intrepid mouse-son of Mr. and Mrs. Frederick C. Little of New York City. I couldn't help thinking of Stuart Little as I read the recent report of the National Academies of Sciences (NAS), titled, "Guidelines for Human Embryonic Stem Cell Research."

If this seems like a peculiar claim, consider the section of the NAS report on "Interspecies Mixing," which highlights the fact that stem-cell research will inevitably require the creation of so-called chimeras. Taken from Greek mythology, the term chimera refers to the interspecies mixing of cells or tissues.

Although the mixing of human and nonhuman cells and tissue is common in research and medicine-think of heart valve replacement surgery in humans where pig heart valves are used-the NAS sought to draw attention to a little-discussed reality: stem-cell research will require the creation of chimeras because it will be necessary to test treatments developed through stem cells to ensure that they do not produce inappropriate cell types or tumors. Such testing, the report states, "will inevitably be required by the Food and Drug Administration (FDA) en route to any application of [human embryonic stem] cells or their derivatives or, indeed of adult stem cells in therapeutic applications."

The report notes that interspecies mixing is common in animal stem-cell research and cites the transfer of mouse embryonic stem cells into chicken embryos as an example. Then comes a passage that concentrates the mind: Transferring human stem cells, for example, human neural cells, into mouse embryos, the report states, "raises other [moral] issues because potentially the inner cell mass, the progenitor of the fetus, would consist of a mixture of human and mouse cells. It is not now possible to predict the extent of human contribution to such chimeras."

The idea that we will soon have a lot of Stuart Littles running around retrieving rings out of drains and unsticking piano keys is far-fetched. Still, it is worth asking what we should make morally of the creation of human-nonhuman chimeras that stem-cell research will inescapably involve.

The first thing to note about this concern over the creation of chimeras is that it is mostly something new. The moral and public-policy debate about stem-cell research has been so focused on the moral status of the early embryo that other issues related to stem-cell research have gone largely undiscussed. For example, almost all of the concern raised about the recent announcement that a lab in South Korea has developed a technique for producing stem cells through cloning has been focused on the creation and destruction of embryos. The fact that all of the reports have stressed that much work remains to be done before producing therapies from these stem cells and that the research is going to involve the creation of chimeras has been given little attention.

This is a general point I raised in a report on the ethics of stem-cell research that I wrote for the President's Council on Bioethics several years ago. Because stem-cell research has been debated primarily in terms dictated by the abortion controversy, the discussion of the ethics of stem-cell research has been too narrowly cast.

For example, much of the religious opposition to stem-cell research has focused almost exclusively on the fact that the derivation of human embryonic stem cells involves the destruction of early embryos, something that pro-life advocates consider equivalent to murder. For that reason, the rhetoric used by religious leaders who have condemned embryonic stem-cell research has closely paralleled that used to condemn abortion. Yet, because religious critics of embryonic research have not wanted to be perceived as anti-science, they have also repeatedly and uncritically praised adult stem-cell research, even though, as the question of the morality of creating chimeras shows, there are good reasons to be concerned about the pursuit of adult stem-cell research.

Thinking about the creation of cross-species chimeras forces us to confront the fact that the moral issues are not confined to the destruction of human embryos. Consider, for example, the kind of reductionistic attitude toward the natural world that the creation of cross-species organisms seems to embody, namely, a view of the world that reduces everything in nature, including sentient beings, to the status of an object to be manipulated. Such a view reduces organisms to artifacts.

It is such a view that C.S. Lewis criticizes in his essay, "The Abolition of Man." Lewis writes: "When we understand a thing analytically and then dominate and use it for our own convenience we reduce it to the level of `Nature' in the sense that we suspend our judgements of value about it, ignore its final cause (if any), and treat it in terms of quantity. The repression of elements in what would otherwise be our total reaction to it is sometimes very noticeable and even painful: something has to be overcome before we can cut up a dead man or a live animal in a dissecting room." Although it is perhaps justifiable occasionally to dominate the world analytically, as Lewis puts it, I am inclined to agree with him that something is lost when we do so.

Sometimes, however, in order to appreciate what is lost when biotechnology reduces the world around us to the status of an artifact, we need to view such technology through a different lens. Thus, in addition to using traditional moral or religious categories to think about cross-species hybrids, I have found that it can be useful to attend to the way some contemporary artists have wrestled with this issue.

Take the work of the Australian artist, Patricia Piccinini, whose work grapples with how the relationship between human and non-human animals is mediated by biotechnology. Her work, "Protein Lattice," is clearly designed to provoke discussion about the possibility of using non-human animals to grow tissue and organs for transplant to humans.

"Protein Lattice" takes as its point of departure the work of a group of scientists in Boston who sought a way to re-grow human ears for accident victims by placing a mold in the shape of an ear on the back of hairless mice. Blood from the mouse feeds the growth of the human cartilage, and eventually you have an ear that can be transplanted to a person who has lost an ear.

Piccinini's installation plays off this scientific initiative and is quite complex. It involves television monitors on which the viewer sees rats trapped in a maze. At the same time, large images of young digitally enhanced human female models are juxtaposed with rats that have human ears on their backs. In some of the images the rats surround a model; in others, rats sit perched on the shoulders of the models.

Although Piccinini's work should certainly be taken on its own aesthetic terms, it is also useful to view her work in relation to what ethicists sometimes refer to as the "wisdom of repugnance" or the "yuck" factor, for the images in her art are simultaneously beautiful and repulsive. Indeed, the artist makes clear her own ambivalence about biotechnology and sees her work partly as a vehicle for reflecting on how human manipulation of "nature" is both inspirational and frightening.

I find it instructive, for example, to reflect on the contrast between the beautiful models and the ugly rodents in "Protein Lattice." Why do we recoil from hairless mice with ears grown on their backs but not from models with breast and lip implants? Why are the mice deemed "unnatural" and repulsive but not the contestants of the television show "Extreme Makeover," whose bodies are arguably more "unnatural" than those of the mice.

Or consider the issue of crossing species boundaries as it has been depicted and explored in the "transgenic art" of Eduardo Kac. Several years ago, Kac made national and international headlines with a public art installation that centered on Alba, an Albino rabbit-jellyfish chimera that Kac had created to glow green under certain light conditions that could be manipulated by museum-goers. As Kac put it, he was making "a new art form based on the use of genetic engineering to transfer natural or synthetic genes to an organism, to create unique living beings."

Many people were outraged at Kac's creation, but, in fact, part of the point of the Alba project was to generate a public conversation on the cultural and ethical implications of genetic engineering. Kac's work thus invites us to reflect on the implications of turning nonhuman animals into artifacts. To be sure, we have been doing that for a very long time. Still, it is worth asking whether creating unique living beings for our amusement or philosophical edification is morally justifiable.

Unfortunately, that sort of question has rarely been asked in the mainstream bioethics literature. Yet animal rights advocates are surely right that non-human animals have natural capacities and needs and that they suffer when those capacities are thwarted and their needs are unmet. If we fail to notice this suffering, one reason is that we have ceased thinking of nonhuman animals as sentient beings and instead see them as machine-like. As we move toward the creation of human-nonhuman chimeras, it is worth asking whether we are not also beginning to reduce humans to the status of machine-like artifacts.

Having focused mostly in this essay on concerns raised by stem-cell research, I need also to say that such research holds out enormous promise. We must acknowledge both the promise and potential peril of this research. This is why I find the NAS report such an encouraging document. It recognizes the possible benefits stem-cell research may bring, but it also openly discusses the dangers. More than that, it makes specific recommendations for ways of regulating stem-cell research to safeguard against the dangers.

That balance strikes me as prudent. Let's proceed with stem-cell research, but let's do so under a system of strict regulation so that we do not find ourselves confronting a mouse with a human brain. After all, few of us would welcome the prospect having, like the Little family, to change a familiar Christmas verse:

`Twas the night before Christmas, when all through the house,

Not a creature was stirring, not even a louse.

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