In Minnesota, pigs are being born with human blood in their veins. In Nevada, there are sheep whose livers and hearts are largely human. In California, mice peer from their cages with human brain cells firing inside their skulls.
These are not outcasts from The Island of Dr. Moreau, the 1896 novel by H.G. Wells in which a rogue doctor develops creatures that are part animal and part human. They are real creations of real scientists, stretching the boundaries of stem cell research.
Biologists call these hybrid animals chimeras, after the mythical Greek creature with a lion's head, a goat's body and a serpent's tail. They are the products of experiments in which human stem cells were added to developing animal fetuses.
Chimeras are allowing scientists to watch, for the first time, how nascent human cells and organs mature and interact - not in the cold isolation of laboratory dishes but inside the bodies of living creatures. Some are already revealing deep secrets of human biology and pointing the way toward new medical treatments.
But with no federal guidelines in place, an awkward question hovers above the work: How human must a chimera be before more stringent research rules should kick in? The National Academy of Sciences, which advises the federal government, has been studying the issue and hopes to make recommendations by February.
Chimeras - meaning mixtures of two or more individuals in a single body - are not inherently unnatural. Most twins carry at least a few cells from the sibling with whom they shared a womb, and most mothers carry in their blood at least a few cells from each child they have born.
Recipients of organ transplants are also chimeras, as are the many people whose defective heart valves have been replaced with those from pigs or cows.
"Chimeras are not as strange and alien as at first blush they seem," said Henry Greely, a law professor and ethicist at Stanford University who has reviewed proposals to create human-mouse chimeras there.
But chimerism becomes a more sensitive topic when it involves growing entire human organs inside animals. And it becomes especially sensitive when it deals in brain cells, the building blocks of the organ credited with making humans human. In experiments like those, Greely told the academy last month, "there is a nontrivial risk of conferring some significant aspects of humanity" on the animal.
Greely and his colleagues did not conclude that such experiments should never be done. Indeed, he and many other philosophers have been wrestling with the question of why so many people believe it is wrong to breach the species barrier.
Many turn to the Bible's repeated invocation that animals should multiply "after their kind" as evidence that such experiments are wrong. Others, however, have concluded that the core problem is not necessarily the creation of chimeras but rather the way they are likely to be treated.
Imagine, said Robert Streiffer, a professor of philosophy and bioethics at the University of Wisconsin, a human-chimpanzee chimera endowed with speech and an enhanced potential to learn - what some have called a "humanzee."
"There's a knee-jerk reaction that enhancing the moral status of an animal is bad," Streiffer said. "But if you did it, and you gave it the protections it deserves, how could the animal complain?"
Unfortunately, said Harvard political philosopher Michael Sandel, speaking last fall at a meeting of the President's Council on Bioethics, such protections are unlikely. "Chances are we would make them perform menial jobs or dangerous jobs," Sandel said. "That would be an objection."
CHICKEN OR QUAIL?
The potential power of chimeras as research tools became clear about a decade ago in a series of dramatic experiments by Evan Balaban, now at McGill University in Montreal. Balaban took small sections of brain from developing quails and transplanted them into the developing brains of chickens.
The resulting chickens exhibited vocal trills and head bobs unique to quails, proving that the transplanted parts of the brain contained the neural circuitry for quail calls. It also offered astonishing proof that complex behaviors could be transferred across species.
The most radical experiment, still not conducted, would be to inject human stem cells into an animal embryo and then transfer that chimeric embryo into an animal's womb. Scientists suspect the proliferating human cells would spread throughout the animal embryo as it matured into a fetus and integrate themselves into every organ.
Such "humanized" animals could have countless uses. They would almost certainly provide better ways to test a new drug's efficacy and toxicity, for example, than the ordinary mice typically used today.
But few scientists are eager to do that experiment. The risk, they say, is that some human cells will find their way to the developing testes or ovaries, where they might grow into human sperm and eggs. If two such chimeras - say, mice - were to mate, a human embryo might form, trapped in a mouse.
In one ongoing set of experiments, Jeffrey Platt at the Mayo Clinic in Rochester, Minn., has created human-pig chimeras by adding human-blood-forming stem cells to pig fetuses. The resulting pigs have both pig and human blood in their vessels. And it's not just pig blood cells being swept along with human blood cells; some of the cells themselves have merged, creating hybrids.
It is important to have learned that human and pig cells can fuse, Platt said, because he and others have been considering transplanting modified pig organs into people and have been wondering if that might pose a risk of pig viruses getting into patient's cells. Now scientists know the risk is real, he said, because the viruses may gain access when the two cells fuse.
In other experiments led by Esmail Zanjani, chairman of animal biotechnology at the University of Nevada at Reno, scientists have been adding human stem cells to sheep fetuses. The team now has sheep whose livers are up to 80 percent human - and make all the compounds human livers make.
Zanjani's goal is to make the humanized livers available to people who need transplants. The sheep portions will be rejected by the immune system, he predicted, while the human part will take root. "I don't see why anyone would raise objections to our work," he said.
By RICK WEISS
The Washington Post