The Perils of Cloning

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It's not hard to appreciate why. Mammalian cloning is an intricate process involving at least three animals, hundreds of eggs, hundreds of more mature cells and not a single sperm. The key challenge is to undo the development of an adult cell--which, like all cells, contains in its DNA the genetic blueprint of the entire organism--that has been programmed or "differentiated" to be one kind of cell (skin or bone or nerve) and no other kind. Somehow, scientists must trick this mature, fully developed cell into resetting its genetic clock so that it can begin life anew as an embryo.

The process by which that is achieved is called nuclear transfer. The first step is to remove the nucleus from an egg and replace it with the nucleus of an adult cell (in Dolly's case, a cell from a ewe's udder). The two components are electrically fused and chemically activated to trick the hybrid cell into dividing like an embryo. Not surprisingly, the process doesn't always go right. "I call it a lottery," says Wilmut. "Even if you use the same method as consistently as you can, you may get some clones with severe abnormalities and some that have only minor ones."

The most common defect--seen across most of the species that have been cloned so far--is a condition known as large-offspring syndrome. Those clones are born larger than normal and have trouble breathing in their first few weeks. Most of the surrogates that gave birth to them experience prolonged pregnancies and sluggish, difficult labors, which may have something to do with their distended and enlarged placentas. Some of Wilmut's cloned sheep were born with incomplete body walls, with muscles and skin around their abdomen that failed to properly join. Other scientists have reported abnormalities in kidney and brain function. In still other clones, the heart does not develop normally, and the walls that are supposed to separate fresh blood from deoxygenated blood do not form.

The good news, as far as cloning's future is concerned, is that those problems seem to be limited to the clones and are not passed on to the next generation. When clones mate with ordinary animals, their offspring are created by the natural merging of egg and sperm--not by the reprogramming of a mature cell--which may erase any reprogramming errors in the clone. The proof is that Dolly gave birth to five healthy lambs. Cloned cows, pigs and mice are also bearing normal offspring. But when clones mate with other clones, all bets are off. Mice created this way appear to accumulate more abnormalities with each generation.