CHIMERAS: ANIMAL-HUMAN HYBRIDS

August 2005
		Researchers are implanting human cells in animals in order to make more human-like models for medical research, prompting heated ethics debates inside and outside of the scientific community. A scientist and an ethicist answer your questions about this so-called "chimeric" research. Special Report: Chimeras: Animal-Human Hybrids

Forum Introduction Is an animal with a human stem cell brain more intelligent than one with a normal brain? Is the President's Council on Bioethics germane to chimeric research? Is there evidence that chimeras occurs naturally in pregnancy? Are test monkeys usually injured in the experiments? Will scientists one day be able to turn off genes that control many of debilitative diseases?	Kathleen Tokunow of Birmingham, Ala. asks: Is an animal with a human stem cell brain more intelligent than one with a normal brain? Can they actually pass theses changes on to their offspring? Dr. Richard Hynes responds: To the first question: We do not yet know but in most cases probably not. The chances are that if one introduces human ES [embryonic stem] cells into a mouse, they will probably contribute very little to the mouse brain because of the differences in size, gestation period and overall brain structure between mice and humans. But the experiments needed to answer this question have not yet been done. Most probably, when such experiments are done, they will be done in a phased way -- that is, initially a few hES cells will be introduced and then the resulting chimera analyzed for human cellular contributions to the brain before birth. Then the numbers of hES cells would be increased to test whether larger numbers lead to larger human contributions to the brain. If those contributions were observed to become large and lead to neuroanatomy that looks human rather than mouse (unlikely but possible) then, most likely the experiments should be terminated without allowing animals to be born. The closer the recipient animal is to a human and the earlier in development the hES cells are introduced, the more likely it is that the hES cells could contribute to building a brain with some human characteristics. So if one were to place hES cells in an adult primate, it is unlikely they would contribute in any substantive way to the higher order functions of the primate brain. The experiments on Parkinson's require only that the human cells secrete a chemical (dopamine). Participation of the implanted cells in more complex functions (such as intelligence) would require them to "wire up" in the correct way and what we know of brain development suggests that they could only do this properly if they are there during development of the brain. But if one inserted them into an early primate embryo, they might participate. No one knows because no one has tried. However, given our lack of knowledge on the possible outcomes, the NAS committee that developed guidelines for human embryonic stem cell research recommends that such experiments should not be done until we know a lot more -- and conceivably that would mean that if we learned from mice that the hES cell contribution could be significant, then perhaps those human/primate chimera experiments should never be done. This sort of question is one the reasons for suggesting a system of review of all hES cell experiments. As for the question about passing on any changes to offspring, the bottom line is NO. There would be no mixing of genes in these experiments -- a chimera is a mixture of cells from two different species. So if one made a chimera of human ES cells into a mouse embryo, any brain cells that developed would be either human or mouse, not both. Similarly, in such a chimera, germ cells (eggs, sperm) which go to make offspring, would be either human or mouse and not some mixture. Again we do not know whether human sperm or eggs could develop within such a chimera and even if they did, they could not merge to form a hybrid. Nonetheless, the NAS committee recommended that no chimeras be allowed to breed. Dr. Jonathan Moreno responds: This experiment has never been done (growing a lower animal with a brain made up of human progenitor brain cells), Given factors like the space available in the animal's skull and the various signaling processes from the rest of the animal that tell the brain how to grow, etc., it is unlikely that the resulting animal brain would resemble a human brain in important ways. However, for an experiment involving, say, human brain cells that carry genes for diseases like Alzheimer's and to investigate the origins of the disease, this could be a useful lab tool.