Bidding bye-bye to the black sheep?

Sheep already look so much alike that counting them helps people fall asleep. Now, they may become even more uniform. For the first time, researchers have demonstrated a technique that may lead to the mass production of livestock clones created from genetically altered cells.

Although scientists can create clones of genetically engineered mice, they are far less successful with livestock.

Researchers in Roslin, Scotland, report this week that they have succeeded in cloning sheep using a technique that they improved to produce potentially hundreds of animals. Moreover, the group expects to combine the method with genetic engineering to create animals with specific traits. Called nuclear transfer, the technique replaces the nucleus of an immature egg with a nucleus from another cell.

In the past, scientists obtained the replacement nuclei directly from cells in embryos. Now, Keith H.S. Campbell and his colleagues at the Roslin Institute are using nuclei from cells grown in a laboratory culture, they report in the March 7 Nature. An embryo has no more than 30 or 40 usable cells, whereas a culture features an almost endless supply.

The new approach makes genetic engineering of these donor cells more feasible because a lab culture can supply so many of them to manipulate, says coauthor Ian Wilmut. A company could first select cells for cloning from prize animals, then improve them further with a gene that, for example, makes the animals produce milk rich in a therapeutic protein. Many labs have tried for years to clone livestock using cell lines, "and now Campbell's group has done it," asserts George E. Seidel Jr. of the Animal Reproduction and Biotechnology Laboratory at Colorado State University in Fort Collins.

The success "is cause for celebration," exclaims Davor Solter of the Max Planck Institute for Immunobiology in Freiburg, Germany, who wrote a commentary accompanying the report. The finding opens the door to cloning mammals from adult cells, he adds.

In their study, the Scottish investigators grew embryo cells of Welsh mountain sheep in the laboratory. During a relatively stable stage of the cell cycle, they transferred 244 of the nuclei to the stripped-down eggs of Scottish blackface ewes.

They didn't have to fertilize the eggs, because the new nuclei had a full set of chromosomes. By giving the eggs an electric shock, they also took over the sperm's job of initiating development.

Thirty-four of the eggs developed sufficiently for the scientists to insert them into Scottish blackface ewes. After a week, they removed them from the ewes, discarded the failures, and returned the 19 healthy ones to their surrogate mothers.

Their efforts resulted in five genetically identical Welsh mountain lambs. Two of the lambs died within 10 days of birth, probably from kidney trouble. What caused the illness remains unclear. "The more you interfere with reproduction, the more danger there is of things going wrong," Wilmut acknowledges. However, asking what failed with the procedure "is like asking what went wrong when [the Wright brothers] flew their plane and it went only 300 feet. . . . Things went remarkably well," Seidel observes. He expects the approach to be applicable to cattle and other livestock.

Might this approach work for cloning humans (SN: 2/5/94, p. 92)? Both Wilmut and Seidel agree it's theoretically possible but far from feasible. Besides, "we don't think it's something you'd want to do," says Wilmut.