Ewe Again? Cloning from Adult DNA

Udderly amazing. Scientists have for the first time used DNA from an adult mammal -- specifically, genetic material from cells in the mammary glands of a 6-year-old ewe -- to create a genetic duplicate. This clone, a healthy lamb named Dolly, was born last July, Ian Wilmut of the Roslin Institute in Edinburgh, Scotland, and his colleagues announce in the Feb. 27 Nature.

 The spectacular feat builds upon cloning research dating back to the early 1980s. At that time, scientists developed a procedure called nuclear transfer that enables them to replace the DNA-containing nucleus of an egg cell with a nucleus from another cell. Researchers soon found that the altered egg could develop into a clone of the animal that provided the nucleus -- but only if the nucleus came from a cell of a barely developed embryo. Cloning attempts using nuclei from adult animals invariably failed.

 Last year, Wilmut and his coworkers described a modified nuclear transfer method that allowed them to clone sheep from older embryonic cells . By maintaining the intended donor cells in a nutrient-deprived medium, the scientists forced the cells out of their normal growth cycle and into a quiescent stage called G0. For reasons still under study, nuclei from these cells are more readily accepted by eggs.

 With the birth of Dolly, Wilmut's group has now proved that at least some adult cells prepared in the same manner can generate a viable clone when their nuclei are transferred to eggs.

 Many biologists had concluded that this was impossible, speculating that the DNA inside the nuclei of adult cells undergoes irreversible changes as the cells mature into the specialized roles they perform -- secreting milk, for example. Yet Dolly's birth shows that the DNA in an adult nucleus either reprograms itself or is open to reprogramming by factors in the egg.

 Exactly how the adult DNA changes once inside the egg is one of many fundamental biology questions raised by the birth of Dolly. The clone may also provide insight into whether a nucleus harbors a genetic clock that determines how old an organism is.

"Our 7-month-old lamb actually has a 6-year, 7-month-old nucleus in all her cells. It's going to be interesting to see what happens with the aging of this animal," notes Grahame Bulfield, director of the Roslin Institute.

 More immediate research priorities, he says, are to determine whether other types of adult cells -- liver, muscle, or brain cells, for example -- can also generate clones, whether the same cloning process works in cattle and pigs, and whether researchers can add or delete genes from the donor cells before generating clones from them.

 The latter issue will be key to the scientists' goals of using cloning to create animals that produce valuable pharmaceuticals in their milk or whose organs can be transplanted into people without being rejected.

 Dolly's birth has also generated a predictable debate about the feasibility and morality of cloning humans. In response, President Bill Clinton has directed the new National Bioethics Advisory Commission to prepare a report examining the ramifications of the Scottish cloning technology.

"It's a pretty shocking change in the way we have to think about biology," observes Jeffrey Kahn, director of the Center for Bioethics at the University of Minnesota in Minneapolis.