The hubbub that greets each newly cloned creature—first sheep, then cows, mice, goats, pigs, a cat, and most recently, rabbits—masks a grim reality. Just one in 100 cloned embryos develops normally in the womb; many of those die immediately after birth. The survivors often suffer from obesity, liver failure, or joint problems, for little-understood reasons. The troubles, two studies suggest, arise from malfunctioning genes.
Thirteen implanted mouse eggs, extracted from the uterus at mid-gestation, yielded two normal-looking cloned fetuses; most never developed.Photograph courtesy of Hans Schöler/University of Pennsylvania
Embryologist Xiangzhong Yang and geneticist Cindy Tian of the University of Connecticut in Storrs studied X chromosomes in prematurely deceased cloned cows. Females carry two copies of the X chromosome, one of which is normally silenced. But Yang found that nine genes on the active X of the dead clones had gone silent as well. He believes the cloning process failed to reprogram the donor cell nucleus to act like that of an ordinary fertilized egg.
Meanwhile, developmental biologists Michele Boiani and Hans Schöler of the University of Pennsylvania report that in more than 90 percent of cloned mouse embryos, a crucial gene called Oct4, which controls the development and fate of early cells, is activated in the wrong place, at the wrong time, or not at all. If Oct4 is expressed inappropriately, the embryo is doomed. The findings raise a red flag for human cloning. "To obtain one normal organism, you're paving the way with a lot of dead or malformed fetuses," says Schöler.