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A Clone in Sheep's Clothing

A sheep cloned from adult cells opens vast scientific possibilities and ethical dilemmas
SHEEP FACSIMILE
SHEEP FACSIMILE. The young lamb named Dolly (left), with her surrogate mother, was created by cloning at the Roslin Institute.
Photographs of a rather ordinary-looking lamb named Dolly made front pages around the world last week because of her startling pedigree: Dolly, unlike any other mammal that has ever lived, is an identical copy of another adult and has no father. She is a clone, the creation of a group of veterinary researchers. That work, performed by Ian Wilmut and his colleagues at the Roslin Institute in Edinburgh, Scotland, has provided an important new research tool and has shattered a belief widespread among biologists that cells from adult mammals cannot be persuaded to regenerate a whole animal. Although the Scottish researchers have made clear that they would consider it unethical to adapt their technique to clone humans (Wilmut is a member of a working group on the ethics of genetic engineering), the demonstration has raised the uncomfortable prospect that others might not be so scrupulous. Cloning humans would mean that women could in principle reproduce without any help from men.

Wilmut and his co-workers accomplished their feat by transferring the nuclei from various types of sheep cells into unfertilized sheep eggs from which the natural nuclei had been removed by microsurgery. Once the transfer was complete, the recipient eggs contained a complete set of genes, just as they would if they had been fertilized by sperm. The eggs were then cultured for a period before being implanted into sheep that carried them to term, one of which culminated in a successful birth. The resulting lamb was, as expected, an exact genetic copy, or clone, of the sheep that provided the transferred nucleus, not of those that provided the egg.

Other researchers have previously cloned animals, including mammals, by transferring nuclei from embryonic cells into such enucleated eggs. (Wilmut's group published such a result using sheep cells last year, in the March 7, 1996, issue of Nature; that earlier result also produced some heated news coverage.) The interest in the new work, published in the February 27, 1997, Nature, is that some of the transferred nuclei that gave rise to lambs came not from embryonic cells but from the mammary gland of a mature, 6-year old ewe. Other workers have failed to produce viable offspring when they attempted equivalent experiments.

The key to success at the Roslin Institute seems to have been that Wilmut starved the mammary cells for five days before extracting their nuclei. This maneuver "froze" the cells in a quiescent phase of their division cycle and may have made their chromosomes more susceptible to being reprogrammed to initiate the growth of a new organism after the nuclei were transferred into an egg.

Wilmut's work is supported by a biotechnology company, PPL Therapeutics in Edinburgh, which plans to use the patented cloning technique to produce animals that will secrete valuable drugs in their milk. Other researchers engaged in similar work note that it is unclear how much practical benefit Wilmut's technique will yield in the short term: it is very labor-intensive and it required 277 nuclear transfers to produce the single, viable cloned lamb. At present, cloning from embryonic cells and even old-fashioned animal breeding are still more efficient ways of producing large numbers of genetically-altered animals, notes William H. Velander of Virginia Polytechnic institute. Nor is it certain that the technique used to create Dolly can be applied to other species.

Even so, Wilmut's experiment provides a long-sought confirmation that adult cells do in fact contain workable versions of all the genes necessary to produce an entire organism. Moreover, the procedure will surely be refined and may become an important aid in all manner of biological and biomedical investigations. It might, for example, be used to mass-produce animals that mimic human diseases for research purposes. The technique might in time also be used to improve livestock.

As for the possible use of cloning to produce copies of humans, most ethicists' initial reaction is that such an action would be unconscionable--although in the U.S., unlike in the U.K. and many other nations, it is not explicitly illegal. And opinions may change when confronted with real-world situations. Should grieving parents be denied the opportunity to produce an identical copy of their dying baby?

President Bill Clinton, who has asked the "National Bioethics Advisory Commission" to make recommendations on what controls should be placed on human cloning research, has banned the use of federal funds for such work. He has also asked private companies to honor a "voluntary moratorium" in the area. But if cloning of humans does prove practical, it may be impossible to prevent physicians from offering it--if not in the U.S., then offshore. Wilmut's technique demands skill and patience, but the equipment required is commonplace in biology laboratories. Indeed, researchers at the Oregon Regional Primate Center in Beaverton, Ore., have announced that they have cloned monkeys from embryonic cells, and researchers have known for some years how to apply a similar technique to clone cows and rabbits. So a human in vitro fertilization facility might need only a modest extra investment to set itself up to clone patients.

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