The laboratory creation of chimeras — animals with mixed-species heritage — has become so advanced that scientists have drawn up regulations to prevent the production of creatures that blur the line between animal and human.

The National Academies, a body chartered by Congress to advise the government and the public on science and technology, last week outlined guidelines for scientists who want to work with certain types of chimeras.

Animals implanted with human cells, scientists say, may reveal the secrets of primordial human development and lead to novel medical treatments. But some projects, particularly those involving human embryonic stem cells, raise remote but worrisome scenarios.

Embryonic stem cells have the ability to differentiate into any type of cell in the human body. Incorporating these highly morphological cells into an animal embryo or brain opens up amazing scientific possibilities and unthinkable ethical quandaries, such as a human brain trapped in a mouse’s body, or a human baby with mice for parents.

No scientist working with chimeras apparently wishes to create such nightmarish animals. But just to be on the safe side, the National Academies made chimeras a prominent part of a larger report outlining guidelines for embryonic stem-cell research.

The guidelines, which are voluntary, say scientists should never implant human embryonic stem cells into non-human primates, such as chimpanzees.

They urge caution for similar experiments in other species. They also say that no matter what species, chimeras carrying human embryonic stem cells should never reproduce. If they did, it would present the remote possibility of a human conception resulting from an animal producing human eggs mating with an animal bearing human sperm.

Researchers should also prevent human embryonic stem cells from populating the majority of an animal’s brain. It’s unlikely, but possible, that the scenario could lead to a human trapped in an animal’s body.

Scientists want to inject human embryonic stem cells into animals so they can study how the cells develop in a living creature rather than in a Petri dish, which is where most experiments have been done to date.

“It’s a useful system to use as a research tool because in a chimera, the embryo is kind of like a test tube in which you can grow your cell of interest,” said Phillip Karpowicz, a researcher at the University of Toronto who has written several papers in defense of chimera research.

Karpowicz says this method is particularly useful when studying brain or eye development, because many of the cells that make up eye and brain tissues exist only in an embryo and cannot be found in an adult.

Scientists have already created human-animal chimeras that don’t likely fall under the categories outlined in the National Academies’ guidelines. For example, Mayo Clinic scientists implanted human blood stem cells (not taken from embryos) into fetal pigs in a study of immune rejection after organ transplant.

And scientists at Baylor Institute of Medicine developed two strains of an animal-human mouse, calling it the “humouse.” One develops human T-cells for studying immunity, and another harbors a human immune system as well as human cancer.

Other chimeras created by crossing two similar species, including a “geep” (a sheep crossed with a goat) and a quail-chick, are less controversial.

Irv Weissman, director of the stem-cell institute at the Stanford University School of Medicine, has an experiment on deck that would incorporate human neural stem cells into mice brains. Even before the National Academies released its report, Weissman asked that a panel of bioethicists and medical researchers at Stanford review the proposal to hammer out ethical concerns.

His proactive approach shows that most scientists are not averse to ethical concerns, said David Magnus, director of the Stanford Center for Biomedical Ethics.

“That’s a sign that some of the leaders in the scientific community want to have some oversight (over) what sorts of things should and should not take place,” Magnus said. “Having oversight is not bad for science, (nor does it) mean that embryonic stem-cell research should stop. It’s the way we can make sure the science proceeds quickly and as well as it can, while avoiding the landmines that might come up.”

by Kristen Philipkoski

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