Implanting altered stem cells in embryos was not the only possible way of creating multiple copies of genetically engineered animals. "It soon occurred to me," Wilmut wrote in The Second Creation, a book about the development of Dolly that he coauthored with fellow Roslin researcher Keith Campbell and science writer Colin Tudge, "that it would be better if we could first allow the zygote [fertilized egg] to multiply, to produce several or many cells, then add new DNA to several or many of those cells, and then produce new embryos from each of the transformed cells. Such multiplication is cloning." With cloning, each successful gene transfer could produce many embryos instead of just one.
Robert Briggs and Thomas J. King, developmental biologists at the Institute for Cancer Research (later the Fox Chase Cancer Center) in Philadelphia, had cloned frogs in 1952 through a process called somatic cell nuclear transfer, in which they removed the nucleus from a fertilized frog egg and combined the egg with a cell from a frog embryo in an early stage of development. Substances in the cytoplasm of the egg somehow reprogrammed the genes in the added nucleus so that the combined cell became able to produce a whole frog embryo and, eventually, a tadpole. All the cells in the tadpole contained the same genes as the nucleus donor, which meant that the tadpole was a clone of the frog from which the donor cell came. Davor Solter of the University of Pennsylvania and others adapted this technique for use in mice, but the resulting embryos usually did not develop to produce baby mice. By the mid-1980s, most scientists had concluded that the nuclear transfer—and probably any other cloning technique—would not work with mammals.
Ian Wilmut shared this view until a fellow researcher told him during an after-hours chat at a scientific meeting in early 1986 that
Steen Willadsen, a Danish-born scientist, had cloned calves from single cells taken from embryos in a late stage of development. This claim astounded Wilmut, since all cells in late embryos were thought to have become specialized. Had Willadsen finally found cattle stem cells—or, more thrilling still, had he discovered a way to make nuclear transfer work with specialized cells?
Willadsen had not published an account of his work, so Wilmut tracked him down in Canada, where the Danish researcher was then living, and asked him if the rumor was true. Willadsen said it was. He described his technique, which included using unfertilized rather than fertilized eggs and employing a tiny jolt of electricity to make the nucleus-free egg and the body cell fuse together. Returning to the Roslin institute, Wilmut persuaded Roger Land to let him try to duplicate and extend Willadsen's experiments.
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