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Human-Animal Chimeras

Some experiments can disquietingly blur the line between species


Stem cell science has become notorious for obliging society to consider again where it draws the line between human embryonic cells and human beings. Less well known is that it also pushes us to another border that can be surprisingly vague: the one that separates people from animals. Stem cells facilitate the production of advanced interspecies chimeras--organisms that are a living quilt of human and animal cells. The ethical issues raised by the very existence of such creatures could become deeply troubling.

In Greek mythology, the chimera was a monster that combined the parts of a goat, a lion and a serpent. With such a namesake, laboratory-bred chimeras may sound like a bad idea born of pure scientific hubris. Yet they may be unavoidable if stem cells are ever to be realised as therapies. Researchers will need to study how stem cells behave and react to chemical cues inside the body. Unless they are to do those risky first experiments in humans, they will need the freedom to test in animals and thereby make chimeras.

Irving Weissman of Stanford University and his colleagues pioneered these chimera experiments in 1988 when they created mice with fully human immune systems for the study of AIDS. Later, the Stanford group and StemCells, Inc., which Weissman co-founded, also transplanted human stem cells into the brains of newborn mice as preliminary models for neural research. And working with foetal sheep, Esmail Zanjani of the University of Nevada at Reno has created adult animals with human cells integrated throughout their body.

No one knows what the consequences will be as the proportion of human cells in an animal increases. Weissman and others, for example, have envisioned one day making a mouse with fully "humanised" brain tissue. The lawyer developmental programme and tiny size of this chimerical mouse fairly guarantee that its mental capacities would not differ greatly from those of normal mice. But what if human cells were instead put in the foetus of a chimpanzee? The birth of something less beastly could not be ruled out.

The intermingling of tissues could also make it easier for infectious animal diseases to move into humans. Diseases that hop species barriers can be particularly devastating because the immune systems of their new hosts are so unprepared for them (the flu pandemic of 1918 is widely believed to have sprung from an avian influenza virus).

There are currently no international standard governing chimera experiments. Canada's Assisted Human Reproduction Act of 2004 banned human-animal chimeras. The US has no formal restrictions, but Senator Sam Brownback of Kansas proposed legislation in March that would outlaw several kinds of chimeras, including ones with substantial human brain tissue. Some institutions that supply human stem cells set their own additional limits about what experiments are permissible.

Within the US, at least, greater uniformity may emerge from general guidelines on stem cell use recommended in late April by the National Academy of Sciences. The NAS recommended that chimeras involving most animal species generally be permitted. It urged a ban on any use of human cells in other primates, however, as well as the introduction of animal cells into human blastocysts.It also warned against allowing human-animal chimeras to breed: some human cells might have managed to infiltrate the animals' testes and ovaries. Breeding those animals could theoretically lead to the horrible (and in most cases, assuredly fatal) result of a human embryo growing inside an animal mother.

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