The famous Chimera of Arezzo is a bronze statue which was found in Arezzo, in Italy, in 1553. Of Etruscan origin, from the 6th century BC Scientists have begun blurring the line between human and animal by producing chimeras a hybrid creature that's part human, part animal   Chinese scientists at the Shanghai Second Medical University in 2003 successfully fused human cells with rabbit eggs. The embryos were reportedly the first human-animal chimeras successfully created. They were allowed to develop for several days in a laboratory dish before the scientists destroyed the embryos to harvest their stem cells.   In Minnesota last year researchers at the Mayo Clinic created pigs with human blood flowing through their bodies.   And at Stanford University in California an experiment might be done later this year to create mice with human brains.   Scientists feel that, the more humanlike the animal, the better research model it makes for testing drugs or possibly growing "spare parts," such as livers, to transplant into humans.| Watching how human cells mature and interact in a living creature may also lead to the discoveries of new medical treatments.But creating human-animal chimeras named after a monster in Greek mythology that had a lion's head, goat's body, and serpent's tail has raised troubling questions: What new subhuman combination should be produced and for what purpose? At what point would it be considered human? And what rights, if any, should it have?   There are currently no U.S. federal laws that address these issues.   Ethical Guidelines   The National Academy of Sciences, which advises the U.S. government, has been studying the issue. In March it plans to present voluntary ethical guidelines for researchers.   A chimera is a mixture of two or more species in one body. Not all are considered troubling, though.   For example, faulty human heart valves are routinely replaced with ones taken from cows and pigs. The surgery which makes the recipient a human-animal chimera is widely accepted. And for years scientists have added human genes to bacteria and farm animals.   What's caused the uproar is the mixing of human stem cells with embryonic animals to create new species.   Biotechnology activist Jeremy Rifkin is opposed to crossing species boundaries, because he believes animals have the right to exist without being tampered with or crossed with another species.   He concedes that these studies would lead to some medical breakthroughs. Still, they should not be done.   "There are other ways to advance medicine and human health besides going out into the strange, brave new world of chimeric animals," Rifkin said, adding that sophisticated computer models can substitute for experimentation on live animals.   "One doesn't have to be religious or into animal rights to think this doesn't make sense," he continued. "It's the scientists who want to do this. They've now gone over the edge into the pathological domain."   David Magnus, director of the Stanford Center for Biomedical Ethics at Stanford University, believes the real worry is whether or not chimeras will be put to uses that are problematic, risky, or dangerous.   Human Born to Mice Parents?   For example, an experiment that would raise concerns, he said, is genetically engineering mice to produce human sperm and eggs, then doing in vitro fertilization to produce a child whose parents are a pair of mice.   "Most people would find that problematic," Magnus said, "but those uses are bizarre and not, to the best of my knowledge, anything that anybody is remotely contemplating. Most uses of chimeras are actually much more relevant to practical concerns."   Last year Canada passed the Assisted Human Reproduction Act, which bans chimeras. Specifically, it prohibits transferring a nonhuman cell into a human embryo and putting human cells into a nonhuman embryo.   Cynthia Cohen is a member of Canada's Stem Cell Oversight Committee, which oversees research protocols to ensure they are in accordance with the new guidelines.   She believes a ban should also be put into place in the U.S.   Creating chimeras, she said, by mixing human and animal gametes (sperms and eggs) or transferring reproductive cells, diminishes human dignity.   "It would deny that there is something distinctive and valuable about human beings that ought to be honored and protected," said Cohen, who is also the senior research fellow at Georgetown University's Kennedy Institute of Ethics in Washington, D.C.   But, she noted, the wording on such a ban needs to be developed carefully. It shouldn't outlaw ethical and legitimate experiments such as transferring a limited number of adult human stem cells into animal embryos in order to learn how they proliferate and grow during the prenatal period.   Irv Weissman, director of Stanford University's Institute of Cancer/Stem Cell Biology and Medicine in California, is against a ban in the United States.   "Anybody who puts their own moral guidance in the way of this biomedical science, where they want to impose their will—not just be part of an argument—if that leads to a ban or moratorium. … they are stopping research that would save human lives," he said.   Mice With Human Brains   Weissman has already created mice with brains that are about one percent human.   Later this year he may conduct another experiment where the mice have 100 percent human brains. This would be done, he said, by injecting human neurons into the brains of embryonic mice.   Before being born, the mice would be killed and dissected to see if the architecture of a human brain had formed. If it did, he'd look for traces of human cognitive behavior.   Weissman said he's not a mad scientist trying to create a human in an animal body. He hopes the experiment leads to a better understanding of how the brain works, which would be useful in treating diseases like Alzheimer's or Parkinson's disease.   The test has not yet begun. Weissman is waiting to read the National Academy's report, due out in March.   William Cheshire, associate professor of neurology at the Mayo Clinic's Jacksonville, Florida, branch, feels that combining human and animal neurons is problematic.   "This is unexplored biologic territory," he said. "Whatever moral threshold of human neural development we might choose to set as the limit for such an experiment, there would be a considerable risk of exceeding that limit before it could be recognized."   Cheshire supports research that combines human and animal cells to study cellular function. As an undergraduate he participated in research that fused human and mouse cells.   But where he draws the ethical line is on research that would destroy a human embryo to obtain cells, or research that would create an organism that is partly human and partly animal.   "We must be cautious not to violate the integrity of humanity or of animal life over which we have a stewardship responsibility," said Cheshire, a member of Christian Medical and Dental Associations. "Research projects that create human-animal chimeras risk disturbing fragile ecosystems, endanger health, and affront species integrity."  Source: National Geographic Of mice, men and in-between Scientists debate blending of human, animal forms By Rick Weiss Nov 20, 2004 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.   Living test beds 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. Yet the range of opinions it has received so far suggests that reaching consensus may be difficult.    During one recent meeting, scientists disagreed on such basic issues as whether it would be unethical for a human embryo to begin its development in an animal's womb, and whether a mouse would be better or worse off with a brain made of human neurons.   "This is an area where we really need to come to a reasonable consensus," said James Battey, chairman of the National Institutes of Health's Stem Cell Task Force. "We need to establish some kind of guidelines as to what the scientific community ought to do and ought not to do."   Beyond twins and moms Chimeras (ki-MER-ahs) — 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. And scientists for years have added human genes to bacteria and even to farm animals — feats of genetic engineering that allow those critters to make human proteins such as insulin for use as medicines.   "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.   Does the repugnance reflect an understanding of an important natural law? Or is it just another cultural bias, like the once widespread rejection of interracial marriage?   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 J. 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."   A research breakthrough 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.   No one has proposed similar experiments between, say, humans and apes. But the discovery of human embryonic stem cells in 1998 allowed researchers to envision related experiments that might reveal a lot about how embryos grow.   The cells, found in 5-day-old human embryos, multiply prolifically and — unlike adult cells — have the potential to turn into any of the body's 200 or so cell types.   Scientists hope to cultivate them in laboratory dishes and grow replacement tissues for patients. But with those applications years away, the cells are gaining in popularity for basic research.   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.   Not everyone agrees that this would be a terrible result.   "What would be so dreadful?" asked Ann McLaren, a renowned developmental biologist at the University of Cambridge in England. After all, she said, no human embryo could develop successfully in a mouse womb. It would simply die, she told the academy. No harm done.   But others disagree — if for no other reason than nothing else out of fear of a public backlash.   "Certainly you'd get a negative response from people to have a human embryo trying to grow in the wrong place," said Cynthia B. Cohen, a senior research fellow at Georgetown University's Kennedy Institute of Ethics and a member of Canada's Stem Cell Oversight Committee, which supported a ban on such experiments there.   How human? But what about experiments in which scientists add human stem cells not to an animal embryo but to an animal fetus, which has already made its eggs and sperm? Then the only question is how human a creature one dares to make.   In one ongoing set of experiments, Jeffrey L. 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," Zanjani said in an interview.   Mice and men Perhaps the most ambitious efforts to make use of chimeras come from Irving Weissman, director of Stanford University's Institute of Cancer/Stem Cell Biology and Medicine. Weissman helped make the first mouse with a nearly complete human immune system — an animal that has proved invaluable for tests of new drugs against the AIDS virus, which does not infect conventional mice.   More recently his team injected human neural stem cells into mouse fetuses, creating mice whose brains are about 1 percent human. By dissecting the mice at various stages, the researchers were able to see how the added brain cells moved about as they multiplied and made connections with mouse cells.   Already, he said, they have learned things they "never would have learned had there been a bioethical ban."   Now he wants to add human brain stem cells that have the defects that cause Parkinson's disease, Lou Gehrig's disease and other brain ailments — and study how those cells make connections.   Scientists suspect that these diseases, though they manifest themselves in adulthood, begin when something goes wrong early in development. If those errors can be found, researchers would have a much better chance of designing useful drugs, Weissman said. And those drugs could be tested in the chimeras in ways not possible in patients.   Now Weissman says he is thinking about making chimeric mice whose brains are 100 percent human. He proposes keeping tabs on the mice as they develop. If the brains look as if they are taking on a distinctly human architecture — a development that could hint at a glimmer of humanness — they could be killed, he said. If they look as if they are organizing themselves in a mouse brain architecture, they could be used for research.   So far this is just a "thought experiment," Weissman said, but he asked the university's ethics group for an opinion anyway.   "Everyone said the mice would be useful," he said. "But no one was sure if it should be done."   © 2007 The Washington Post Company