Chimeras

In mythology, a chimera is a fire-breathing monster composed with a lion's head, a goat's body and a serpent's tail. In medical science, a chimera is an individual having more than one genetically-distinct population of cells that originated from more than one zygote. How is this possible, and just how fast should you run if you see one?

Chimeric cattle are not at all rare. When a cow has twins, it is almost inevitable that anastomoses (areas of joining) develop between the fetal circulatory systems early in gestation. This leads to exchange of blood between the two fetuses. Fetal blood contains hematopoietic stem cells, and each fetus is permanently "seeded" with stem cells from its twin. The result is that both animals are hematopoietic chimeras. A variable fraction of all their cells that are derived from hematopoietic stem cells (peripheral blood cells, Kupffer cells in the liver, lymphocytes and macrophages in lymph nodes and spleen, etc) are from the twin.

Major clinical signifcance is seen when one fetus is a female and one a male. In such cases, the female fetus is exposed to hormones from the male and is masculinized. Such female cattle are called freemartins. The external genital tract of a freemartin looks like a female, although usually infantile. The degree to which the internal genital tract is masculinized varies, but typically, the vagina is very short and uterine horns are rudimentary. Pretty obviously, these animals are sterile. Freemartins are seen occasionally in other species, although much less commonly than in cattle, probably because those animals do not have the propensity seen in cattle to form vascular anastomoses among fetuses early in gestation.

There are reports of naturally-occurring chimerism in a variety of species. Such individuals undoubtedly do occur, although they are quite rare. The most likely pathogenesis in such cases is fusion of two early embryos into one. This is suspected because chimeras are also produced experimentally, and have been a valuable research tool in several biomedical disciplines. The basic technique is to combine two very early embryos such that their cells intermix and the resulting conceptus has cells from both original embryos. This technique has been widely applied with mice and has also been applied to ruminants.

The chimeric animal shown below is a baby "geep", made by combining a goat and sheep embryo. Notice the chimerism evident in the skin - big patches of skin on front and rear legs are covered with wool, representing the sheep contribution of the animal, while a majority of the remainder of the body is covered with hair, being derived from goat cells.



Chimeric mice and sheep-goat chimeras have been most useful in answering fundamental questions about developmental biology and pathology. There is also some potential that this technique can be applied to problems such as rescue of endangered species. It is possible, for example to construct a goat-sheep chimera such that a goat fetus is "encased" in a sheep placenta. This enables a sheep to carry a goat to term, which will not occur if you simply transfer goat embryos into sheep (the sheep will immunologically reject the goat placenta and fetus). It may be possible to extend this procedure to allow embryos from severely endangered species to be carried by recipient mothers from another species.