Discussion Group Report

There are "valid scientific reasons" for creating chimeras--living entities composed of both human and animal cells--said the guidelines for research on embryonic stem cells issued by the U.S. National Academy of Sciences this past April. The implications of the kind of research addressed in this statement were explored in an article, "I, Chimera," by Jamie Shreeve in www.newscientist.com, June 25, 2005. "As stem cell technology pushes forward, expect to hear a lot more," she says.

In Greek mythology, she points out, the chimera was a monstrous creature with the head of a lion, the body of a goat and the tail of a serpent. In real-life laboratories mildly chimerical creatures have long been commonplace--mice and other animals with human immune systems, kidneys, skin, and muscle tissue, all created for the purpose of better understanding human diseases. Today pig heart valves are routinely transplanted into heart patients. None of this research has caused any public outcry, but stem cell technology has made the creation of more potent human-animal mixtures both easier and more urgent. Researchers have created monkeys with brains that are partially human, mice with functioning human photoreceptor cells in their retinas and sheep with organs that are up to 40% human. And there's a plan to create a mouse with a brain made entirely of human neurons. Such chimeras would be hugely useful in biomedical research.

But organisms assembled by mixing humans and animals are troubling. What if such a creature turned out to have human attributes? And what new responsibilities would such an ambiguous being pose to a society accustomed to a clean moral and legal distinction between human beings and the rest of the animal world? "How do we treat these new beings?" asks bioethicist Francoise Baylis.

The reason for all of this sudden interest in chimeras is the immense medical potential of stem cells. Isolated from the inner cell mass of a very early embryo called a blastocyst, human embryonic stem cells have the ability to morph into any other kind of cell in the body. They might one day be transplanted into patients with heart disease, diabetes, and a host of other ailments to regenerate damaged tissue.

Eugene Redmond of Yale University and his colleagues have injected human neural progenitor cells--stem cells that have already taken the first developmental step towards becoming a brain cell--into the brains of velvet monkeys with the intention of exploring them as a treatment for Parkinson's disease. A team at Harvard University transplanted neuronal progenitor cells into fetal monkeys to see if they would grow, migrate and differentiate along with their monkey counterparts (they did), while still others have treated mouse brains to a similar neural dusting.

Is it possible that you could end up with a creature possessing a human-like brain--and human-like cognitive abilities, such as intelligence and self-awareness--trapped in the skull of an animal? Shreeve posits that the answer to that question seems to depend on three factors: the stage in development at which the cells are introduced (the earlier, the more effect they have) the amount of material added, and how closely related the animal is to us.

Art Brivanlou of The Rockefeller University plans to inject human embryonic stem cells into 3 to 5-day-old mouse blastocysts, and then implant the embryo in a mouse uterus. "We have to know," he says, "how many cell lines contribute to the pancreas, how many to the nervous system, and so on. If we don't know the answers to these basic questions, we will never go to the next step of using stem cells clinically."

Irving Weissman and his colleagues came up with an ingenious idea to study human brain cancers and drug therapies. He imagined transplanting human neuronal stem cells into the brains of a strain of mouse that loses its own neurons just before birth. The result would be a mouse with a brain composed almost entirely of human neurons. This has already drawn negative rhetoric from talk-show host Bill O'Reilly, anti-biotech activist Jeremy Rifkin, and numerous religious commentators and bloggers. Some scientists are uncomfortable, too. Weissman answers that these critics "must be reminded that if they succeed, it's the kind of research that could result in real and new therapies, then I personally hold them morally responsible for the suffering and death of those patients."

Mouse brains are less than one-thousandth the size of human brains in volume, and are far simpler in their organization. To create an animal with a brain possessing any human attributes you would probably have to use an animal much closer to us in evolution, and early in its development, a chimpanzee, for instance. The NAS report recommends that the transfer of human stem cells into the early embryos of apes or other primates should not be permitted at this time.

Cynthia Cohen of Georgetown University argues that the real problem is that chimeras denigrate what it means to be human. Robert Streiffer of the University of Wisconsin-Madison maintains, "I don't think that taking an individual with a lower moral status and conferring a higher moral status on it is wrong for the animal. It could even be beneficial, if it reminded us in a useful way that the categorical difference between a human being and the rest of nature is not so categorical."

Shreeve opines that a true human-animal chimera "could provide unimagined insights into the lives and minds of non-human primates, and in so doing advance our understanding of all animals. But what if it were trapped between those two worlds, able neither to realize its humanity, nor to live in peace with its animal self?...Perhaps the best argument against too potent a mix of human and animal would be the emotional torment suffered by a being so unspeakably alone in the world. But such thoughts are still safely in the realm of science fiction."

"It's always science fiction," says Streiffer, "up until the point when it happens."