THE AGE OF CLONING

(3 of 4)
An inkling that this approach might work, says Wilmut, came from the success his team experienced in producing live lambs from embryonic clones. "Could we do it again with an adult cell?" wondered Wilmut, a reserved, self-deprecating man who likes gardening, hiking in the highlands and drinking good single-malt Scotch (but who was practical enough to file for a patent before he went public).

It was a high-risk project, and in the beginning Wilmut proceeded with great secrecy, limiting his core team to four scientists. His caution proved to be justified; the scientists failed far more often than they succeeded. Out of 277 tries, the researchers eventually produced only 29 embryos that survived longer than six days. Of these, all died before birth except Dolly, whose historic entry into the world was witnessed by a handful of researchers and a veterinarian.

Rumors that something had happened in Roslin, a small village in the green, rolling hills just south of Edinburgh, started circulating in scientific circles a few weeks ago. It was only last week, when the rumors were confirmed and the details of the experiment revealed, that the real excitement erupted. Cell biologists, like everybody else, were struck by the simple boldness of the experiment. But what intrigued them even more was what it suggested about how cells work.

Many scientists had suspected that the key to getting a donor cell and egg to dance together was synchronicity--getting them started on the same foot. Normal eggs and sperm don't have that problem; they come pre-divided, ready to combine. An adult cell, though, with its full complement of genes, has to be coaxed into entering an embryonic state. That is probably what Wilmut did by putting the donor cell to sleep, says Colin Stewart, an embryologist at the National Cancer Institute. Somehow, in ways scientists have yet to understand, this procedure seems to have reprogrammed the DNA of the donor cell. Thus when reawakened by the Roslin team, it was able to orchestrate the production of all the cells needed to make up Dolly's body.

Like most scientists who score major breakthroughs, Wilmut and his colleagues have raised more questions than they have answered. Among the most pressing are questions about Dolly's health. She is seven months old and appears to be perfectly fine, but no one knows if she will develop problems later on. For one thing, it is possible that Dolly may not live as long as other sheep. After all, observes NCI's Stewart, "she came from a six-year-old cell. Will she exhibit signs of aging prematurely?" In addition, as the high rate of spontaneous abortion suggests, cloning sometimes damages DNA. As a result, Dolly could develop any number of diseases that could shorten her life.

Indeed, cloning an adult mammal is still a difficult, cumbersome business--so much so that even agricultural and biomedical applications of the technology could be years away. PPL Therapeutics, the small biotechnical firm based in Edinburgh that provided a third of the funding to create Dolly, has its eye on the pharmaceutical market. Cloning, says PPL's managing director Ron James, could provide an efficient way of creating flocks of sheep that have been genetically engineered to produce milk laced with valuable enzymes and drugs. Among the pharmaceuticals PPL is looking at is a potential treatment for cystic fibrosis.