Monkeys Created with Two Genetic Codes: It All Started with Visionary Experiment in Philadelphia

It's one thing to be close to your siblings, but a group of monkeys born at Oregon National Primate Research Center take it to extremes. Researchers merged genetically distinct embryos into single individuals to produce what are called chimeras.

Nature creates them occasionally from what would have been fraternal twins – essentially siblings with the same birthday. If the embryos of these would-be twins merge early enough in development, they can become one animal.

The Oregon achievement is an extension of the work of an extraordinary scientist named Beatrice Mintz. Long before anyone imagined such things were possible, she created the world's very first chimeras at Philadelphia's Fox Chase Cancer Center. She merged embryos from dark mice and white mice and the result – to her and everyone else's surprise - were striped mice. Here's something I wrote about her discovery in a profile piece:

She started questioning prevailing scientific thinking in the 1940s while in graduate school at the University of Iowa, she said.

Her ideas came from her fascination with the beginning of life - the mysterious process by which a living organism grows from the countless divisions of a single cell.

The prevailing view explaining how that happened didn't satisfy her.

``People thought the egg was fixed,'' she explained, meaning that these cells somehow held the predestined qualities of the animals they were to become. She suspected that life's earliest stages were more flexible, and she conceived of an experiment to probe the issue. If she took cells from two different, unrelated early-stage embryos and combined them, could this new combination embryo grow together into a single mouse? ``The idea ran counter to the prevailing dogma,'' she said. What she was proposing was a creature with two different types of cells and two different sets of genetic instructions. It would be a creature with four parents.

``People thought I'd get monsters out of it,'' she said. ….

It wasn't until she joined Fox Chase in 1960, at around age 40, that she tried out her idea. In a petri dish, she combined the cells of two 32-cell mouse embryos, one from a black mouse and one from a white one. The cells intermixed, forming one mass.

Mintz implanted the new commingled embryo into the womb of a surrogate mother mouse. The result: a normal-sized, normal-shaped, normal-behaving mouse. Its one outstanding trait - neat, horizontal black and white stripes. Scientists have since created many such mixed-cell creatures. The scientific term for them is chimera, after the mythological creature with a lion's head, goat's body, and serpent's tail. Mintz prefers the term mosaic.

The fact that it was striped, and not gray or randomly splotchy, had a profound biological meaning, she said: ``They showed there was order in the embryo. '' Somehow, the ordering principles did not lie within one fertilized egg, but outside it, causing the black-mouse cells and white-mouse cells to divide in an organized way.

Since then, chimeric mice have been used in all kinds of biomedical research, and they do indeed tell us something about how and when a developing embryo becomes an individual.

Though the Oregon researchers promise they are not working on human chimeras, such beings already exist. You might be a chimera and not realize it. A few years ago New Scientist reported on a case in which a woman was hospitalized and underwent genetic testing because she needed a kidney transplant. Her three sons were tested for compatibility, and it appeared they weren't hers. Further testing showed that she was a chimera – she had two kinds of cells with two different genetic codes, and one kind dominated her blood while the other kind dominated her ovaries.

Interestingly, most female mammals are partial chimeras, because one of our two X chromosomes is shut down in each cell. In some of our cells our father's X is shut off, and in others, the mother's X is off. That's an epigenetic effect and it explains why only female cats come out with that patchy calico or tortoise shell pattern. I'm saving a more thorough explanation of cat epigenetics for my co-blogger Higgs when he posts again next week. Female cats were undoubtedly a major interest of his before he had is contraceptive procedure.