Dolly, You're History

In the year and a half since Scottish embryologist Ian Wilmut presented Dolly, the cloned sheep, to an astonished world, ethicists and policymakers have been struggling with the unsettling implications of his research. Could scientists use Wilmut's method to clone not just sheep but also billionaires, basketball players and bodies grown for spare parts? Should medical entrepreneurs be allowed to pursue cloning wherever it leads? Or should the government step in now and outlaw it before it starts?

For reproductive biologists, these issues pale in the face of two more immediate and practical questions: Is Dolly really a clone--and if so, can anybody make one? It's taken a while, but the answers are finally in. The verdict, according to a trio of reports in the current issue of Nature: yes and yes. Not only have Dolly's pedigree and her immaculate conception been established beyond all reasonable doubt, but she has been joined by litter upon litter of perfectly cloned mice. Cloning has, with a speed no one anticipated, been transformed from an astonishing technical tour de force into what seems almost a mundane laboratory procedure.

What makes Dolly and these new mice special--and distinguishes them from barnyards of previously cloned pigs, cows and sheep--is that they were cloned from adult cells or, as the scientists call them, differentiated cells. All those earlier clones were made from fetal cells, which have no specialized function but carry the potential to turn into anything and everything the body needs.

Differentiated cells, by contrast, have already become specialized, with some genes turned on and some turned off, making them into breast or liver or pancreas cells. Although a differentiated cell still contains all the genetic information needed to create a whole new creature, much of that information is suppressed. Nobody had ever succeeded in reprogramming its genes back to the comparatively undifferentiated state suitable for cloning.

Until Dolly, that is. What Dolly proved is that you don't have to take your chances with fetal cells. You can wait until the litter has grown up, see which individuals have proved themselves to be great producers of wool, milk or--a stretch, perhaps--NBA titles, and then clone the champs.

Still, Dolly would be just a laboratory curiosity if no one could repeat Wilmut's breakthrough. And that's where Teruhiko Wakayama comes in. He's a 31-year-old Japanese postdoctoral student who was studying cloning as a hobby at the University of Hawaii, where his lab director, Ryuzo Yanagimachi, was famous for telling students "not to be afraid of asking crazy questions. The crazier the better."

Wakayama's idea was truly crazy: he wanted to clone mice, long believed to be among the worst candidates for cloning because their egg cells are particularly delicate and their embryos develop so rapidly. He squeezed in the cloning work during his free time, carefully manipulating one type of mouse cell after another until, just months after Dolly was unleashed on the world, he succeeded in cloning the cumulus cells that surround the egg in the ovary. Wakayama's whimsical name for his new creation: Cumulina.