In a feat that may be the one bit of genetic engineering that has been anticipated and dreaded more than any other, researchers in Britain are reporting that they have cloned an adult mammal for the first time.
The group, headed by Dr. Ian Wilmut, 52, an embryologist at the Roslin Institute in Edinburgh, has created a lamb using DNA from an adult sheep. Their achievement shocked leading researchers who had said it could not be done. The researchers had assumed that the DNA of adult cells would not act like the DNA formed when a sperm's genes first mingle with those of an egg.
In theory, researchers said, the same techniques could be used to take a cell from an adult human and use the DNA to create a genetically identical human -- a time-delayed twin. That prospect raises the thorniest of ethical and philosophical questions.
Wilmut's experiment was simple, in retrospect. He took a mammary cell from an adult sheep and prepared its DNA so it would be accepted by an egg from another sheep.
He then removed the egg's own DNA, replacing it with the DNA from the adult sheep by fusing the egg with the adult cell. The fused cells, carrying the adult DNA, began to grow and divide, just like a perfectly normal fertilized egg, to form an embryo.
Wilmut implanted the embryo into another ewe; in July, the ewe gave birth to a lamb, named Dolly. Though Dolly seems perfectly normal, DNA tests show that she is the clone of the adult ewe that supplied her DNA.
"What this will mostly be used for is to produce more health-care products," Wilmut told the Press Association of Britain early today, according to the Reuters news agency.
"It will enable us to study genetic diseases for which there is presently no cure and track down the mechanisms that are involved. The next step is to use the cells in culture in the lab and target genetic changes into that culture."
Biologists, ethicists stunned
Simple though it may be, the experiment, to be reported Thursday in the British journal Nature, has startled biologists and ethicists. Wilmut said he was interested in the technique primarily as a tool in animal husbandry, but other scientists said that it had opened doors to the unsettling prospect that humans could be cloned as well.
"It's unbelievable," said Dr. Lee Silver, a biology professor at Princeton University who said the announcement had come just in time for him to revise his forthcoming book so the first chapter will no longer state that such cloning is impossible.
"It basically means that there are no limits," Silver said. "It means all of science fiction is true. They said it could never be done and now here it is, done before the year 2000."
Dr. Neal First, a professor of reproductive biology and animal biotechnology at the University of Wisconsin, who has been trying to clone cattle, said the ability to clone dairy cattle could have a bigger impact on the industry than the introduction of artificial insemination in the 1950s, a procedure that revolutionized dairy farming.
Cloning could be used to make multiple copies of animals that are especially good at producing meat or milk or wool.
Frog experiments failed
Although researchers have created genetically identical animals by dividing embryos very early in their development, Silver said, no one had cloned an animal from an adult until now.
Earlier experiments, with frogs, have become a stock story in high school biology, but the experiments never produced cloned adult frogs. The frogs developed only to the tadpole stage before dying.
It was even worse with mammals. Researchers could swap DNA from one fertilized egg to another, but they could go no further. "They couldn't even put nuclei from late-stage mouse embryos into early mouse embryos," Silver said. The embryos simply failed to develop and died.
As a result, the researchers concluded that as cells developed, the proteins coating the DNA somehow masked all the important genes for embryo development. A skin cell might have all the genetic information that was present in the fertilized egg that produced the organism, for example, but almost all that information is pasted over. Now all the skin cell can do is be a skin cell.
Researchers could not even hope to strip off the proteins from an adult cell's DNA and replace them with proteins from an embryo's DNA. The DNA would shatter if anyone attempted to strip it bare, Silver said.
Last year, Wilmut showed that he could clone DNA from sheep embryo cells, but even that was not taken as proof that the animal itself could be cloned. It could just be that the embryo cells had DNA that was unusually conducive to cloning, many thought.
Wilmut, however, hit on a clever strategy. He did not bother with the proteins that coat DNA, instead focusing on getting the DNA from an adult cell into a stage in its normal cycle of replication where it could take up residence in an egg.
DNA in growing cells goes through what is known as the cell cycle: It prepares itself to divide, then replicates itself and splits in two as the cell itself divides.
The problem with earlier cloning attempts, Wilmut said, was that the DNA from the donor had been out of synchronism with that of the recipient cell. The solution, Wilmut discovered, was to, in effect, put the DNA from the adult cell to sleep, making it quiescent by depriving the adult cell of nutrients. When he then fused it with an egg cell from another sheep -- after removing the egg cell's DNA -- the donor DNA took over as though it belonged there.
Wilmut said that the method could work for any animal and that he hoped to use it next to clone cattle. He said that he could use many types of cells from adults for cloning but that the easiest to use would be stem cells, which give rise to a variety of other cells and are present throughout the body.
Pub Date: 2/23/97