February 23, 1997
Scientist Reports First Cloning Ever of Adult Mammal
By GINA KOLATA
n 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, a 52-year-old 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.
Dr. 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.
Dr. 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 who supplied her DNA.
"What this will mostly be used for is to produce more health care products," Dr. 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."
Simple though it may be, the experiment, to be reported this coming Thursday in the British journal Nature, has startled biologists and ethicists.
Dr. Wilmut said he was interested in the technique primarily as a tool in animal husbandry, but other scientists said 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," Dr. 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 1950's, 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.
Although researchers have created genetically identical animals by dividing embryos very early in their development, Dr. 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," Dr. 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 may 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 tried to strip it bare, Dr. Silver said.
Last year, Dr. 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.
Dr. Wilmut, however, hit on a clever strategy. He did not bother with the proteins that coat DNA, and instead focused 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, Dr. Wilmut said, was that the DNA from the donor had been out of synchrony with that of the recipient cell. The solution, Dr. 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.
Dr. Wilmut said in a telephone interview that he planned to breed Dolly next fall to determine whether she was fertile.
Dr. 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 so-called stem cells, which give rise to a variety of other cells and are present throughout the body. In his sheep experiment, he used mammary cells because a company that sponsored his work, PPL Therapeutics, is developing sheep that can be used to produce proteins that can be used as drugs in their milk, so it had sheep mammary cells readily available.
For Dr. Wilmut, the main interest of the experiment is to advance animal research. PPL, for example, wants to clone animals that can produce pharmacologically useful proteins, like the clotting factor needed by hemophiliacs. Scientists would grow cells in the laboratory, insert the genes for production of the desired protein, select those cells that most actively churned out the protein and use those cells to make cloned females. The cloned animals would produce immense amounts of the proteins in their milk, making the animals into living drug factories.
But that is only the beginning, Dr. Wilmut said. Researchers could use the same method to make animals with human diseases, like cystic fibrosis, and then test therapies on the cloned animals. Or they could use cloning to alter the proteins on the surfaces of pig organs, like the liver or heart, making the organs more like human organs. Then they could transplant those organs into humans.
Dr. First said the "exciting and astounding" cloning result could shake the dairy industry. It could allow the cloning of cows that are superproducers of milk, making 30,000 or even 40,000 pounds of milk a year. The average cow makes about 13,000 pounds of milk a year, he said.
"I think that if -- and it's a very big if -- cloning were highly efficient, then it could be a more significant revolution to the livestock industry than even artificial insemination," Dr. First said.
Although Dr. Wilmut said he saw no intrinsic biological reason humans, too, could not be cloned, he dismissed the idea as being ethically unacceptable. Moreover, he said, it is illegal in Britain to clone people. "I would find it offensive" to clone a human being, Dr. Wilmut said, adding that he fervently hoped that no one would try it.
But others said that it was hard to imagine enforcing a ban on cloning people when cloning got more efficient. "I could see it going on surreptitiously," said Lori Andrews, a professor at Chicago-Kent College of law who specializes in reproductive issues. For example, she said, in the early days of in vitro fertilization, Australia banned that practice. "So scientists moved to Singapore" and offered the procedure, Professor Andrews said.
"I can imagine new crimes," she said.
People might be cloned without their knowledge or consent. After all, all that would be needed would be some cells. If there is a market for a sperm bank selling semen from Nobel laureates, how much better would it be to bear a child that would actually be a clone of a great thinker or, perhaps, a great beauty or great athlete?
"The genie is out of the bottle," said Dr. Ronald Munson, a medical ethicist at the University of Missouri in St. Louis. "This technology is not, in principle, policeable."
Dr. Munson called the future possibilities incredible. For example, could researchers devise ways to add just the DNA of an adult cell, without fusing two living cells? If so, might it be possible to clone the dead?
"I had an idea for a story once," Dr. Munson said, in which a scientist obtains a spot of blood from the cross on which Jesus was crucified. He then uses it to clone a man who is Jesus Christ -- or perhaps cannot be.
On a more practical note, Dr. Munson mused over the strange twist that science has taken.
"There's something ironic" about study, he said. "Here we have this incredible technical accomplishment, and what motivated it? The desire for more sheep milk of a certain type." It is, he said, "the theater of the absurd acted out by scientists."
In his interview with the Press Association of Britain, Dr. Wilmut added early today: "We are aware that there is potential for misuse, and we have provided information to ethicists and the Human Embryology Authority. We believe that it is important that society decides how we want to use this technology and makes sure it prohibits what it wants to prohibit. It would be desperately sad if people started using this sort of technology with people."
Other Places of Interest on the Web
- "Sheep Cloned by Nuclear Transfer", report by Dr. Wilmut on an earlier experiment at the Roslin Institute
- MedWeb: Bioethics, a web directory
- Scientist Comes Out of Secrecy
- Ethical Issues Raised by Cloning
Copyright 1997 The New York Times Company