Was Dolly a Mistake?

By J. MADELEINE NASH

Extraordinary claims, scientists like to say, require extraordinary proof, and none has been more extraordinary in recent years than Scottish embryologist Ian Wilmut's claim that he and his colleagues had cloned a sheep named Dolly from a mammary cell of a pregnant ewe. More than a year later, nobody has managed to reproduce the Dolly experiment, and Wilmut is under growing pressure to prove that his famous sheep is what he says she is. Last week at a genetics meeting at the University of Louisville, in Kentucky, he blandly conceded that there was a "remote possibility" that there could have been a mix-up--that Dolly could turn out to be the clone not of the adult ewe, but of the fetus the ewe was carrying.

So does that mean all the cloning hoopla Dolly set off was for naught? Not quite. What Wilmut is conceding is that Dolly's mom--or should we say her twin sister?--probably had some fetal cells circulating in her bloodstream, and that one of these fetal cells could conceivably have found its way into the laboratory culture from which Dolly sprang. Cloning an embryo from a fetal cell, of course, would not be as big a deal. What made the Dolly experiment so extraordinary was that Wilmut had managed to get the DNA of an adult cell to revert to its early embryonic state, opening the door to the cloning of a cell from full-grown human, say, a Michael Jordan or a Bill Gates.

Wilmut last week put the chances that Dolly was some sort of fetal-cell contamination at less than a million to one. Nonetheless, he and his colleagues are scrambling to track down any other tissue samples taken from Dolly's mom so they can perform the genetic tests that will determine, once and for all, if Dolly's DNA and her mom's DNA are identical.

Meanwhile, scientists trying to make another Dolly--or her bovine equivalent--have come intriguingly close. For example, James Robl, at the University of Massachusetts in Amherst, and his colleague Steven Stice have succeeded in cloning calf embryos from adult cells taken from a big, hoofed cow leg supplied by a local slaughterhouse. So far they've cloned hundreds of cells and nurtured dozens into embryos, but to date none of those embryos has survived past 60 days of gestation.

Why should cloning an adult cell be so hard? The cell-cloning technique scientists use offers some clues. Typically, the nucleus of the donor cell, whether fetal or full grown, is transferred to an unfertilized egg from which the nucleus has been removed. In mysterious ways scientists still do not understand, something in the cytoplasm of the egg appears to reset the donor cell's DNA. That resetting, it has been clear from the beginning, works much less reliably when adult cells are used, even when they are relatively immature fibroblast cells.

But this comes as no surprise, says Stice, the chief scientist for Advanced Cell Technology in Worcester, Mass. After all, it took Wilmut's team 400 tries to create Dolly. Others attempting to reproduce the experiment could very easily find it takes 6,000 tries. Dolly, in other words, may turn out to be a fluke, not a fake. No matter what she is, it's looking less and less likely that we're going to see clones of Bill Gates or Michael Jordan anytime soon.

--By J. Madeleine Nash