Ten years ago this month, a ewe at a quiet research facility just outside Edinburgh, Scotland, gave birth to a lamb, known then as 6LL3. Seven months later, 6LL3 stepped onto the international stage with a more personable name as the most famous sheep of all time: Dolly, the first cloned mammal. She was the product of inserting a cell from an adult sheep's udder into a sheep egg from which the nucleus had been removed, then placing it in a ewe to develop.
Dolly changed the public's idea of what biotechnology might do and immediately posed the question: Can human clones be far behind?
"Dolly was important as a symbol of science gone out of control," says Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania. "People were very afraid of cloning and what it might mean in terms of genetic engineering."
A decade later, those concerns and speculations have cooled. Cloning, it turns out, is a difficult proposition. Dolly was the sole survivor among 277 attempts to clone a sheep. Human cloning has proved elusive. Progress in cloning for research and medical purposes was hit hard late last year when an apparent breakthrough by South Korean researcher Hwang Woo-Suk, who claimed to have created human embryonic stem cells through cloning, was exposed as a fraud.
Cloning to reproduce a human being is now seen almost universally as too dangerous to consider. And animal cloning hasn't attained many of the goals expected a decade ago. Still, at least 15 mammals have been cloned (though no primates) and research continues.
What will the next 10 years bring? Here's what several close observers say:
"We spent an inordinate amount of time" arguing over human reproductive cloning 10 years ago, but "I don't think that's going to wind up being a very important issue 10 years from now." Dr. Caplan says. "I think the last 10 years have shown that cloning is a difficult process to control, often goes wrong, and that many of the reasons it goes wrong are probably inextricably tied up to the cloning process itself. I think that will pretty well seal the fate of cloning to make human beings. It will be understood that the price will be too high."
In a 2001 paper in the journal Science, Ian Wilmut, the lead researcher on the Dolly project, and Rudolf Jaenisch, a biologist and biomedical researcher at the Massachusetts Institute of Technology, wrote that human reproductive cloning was inherently dangerous and would always leave deformities in the clones.
"You cannot make normal clones. The ones that survive will just be less abnormal than the ones that die early," Dr. Jaenisch says today. "There has been no progress – none – in the last six years in making cloning more safe." For human reproduction, cloning "is totally out of the question."
Some 50 countries (though not the United States) have passed laws or issued regulations against cloning to make humans. That reproductive cloning is so widely condemned "even if only on narrow safety grounds" shows that "some lines can be drawn" past which science won't go, says Marcy Darnovsky, associate executive director of the Center for Genetics and Society in Oakland, Calif., a nonprofit interested in the public policy implications of genetic manipulation.
The goal of cloning early-stage human embryos to produce stem cells for use in research, and eventually to treat diseases, is likely to remain controversial. Those who see this research as destroying human life and those who do not regard these blastocysts (embryos in their very early stages) as human life have found little middle ground.
The battle is between "those who see this as the first step to a Brave New World and those of us who see this as a legitimate ... step toward regenerative medicine and all the benefits that can accrue" from that, says James Hughes, a sociologist and executive director of the Institute for Ethics and Emerging Technologies in Hartford, Conn. The group promotes the use of biotechnology to expand human capacities.
Bioethicist Caplan expects that one or more groups of scientists, perhaps outside the US, will do "what the Koreans said they did" and clone human stem cells. They'll be "useful in the laboratory, but we still won't be in a position to see cures coming from cloned human stem cell lines" in the next decade, he predicts.
Widespread cloning of human stem cells would create a huge demand for women's eggs and in turn create an ethical challenge, Ms. Darnovsky says. The health effects on women who donate their eggs are not well studied or well understood, but early research indicates they could be taking serious risks. How can women give their informed consent to providing eggs, she says, if the risks are unknown? Paying women to provide eggs might induce poor women to put themselves at risk for the money.
"We don't want to go down the road of a market for eggs," she says.
Beyond that, she worries that human cloning research will have a spinoff or "dual use" effect. By combining cloning technology with other genetic manipulation, it may be possible to produce enhanced "designer babies."
Dr. Wilmut and others see this as a welcome way to improve progeny and prevent inherited diseases.
Darnovsky disagrees. "That's a disturbing development," she says. "The procedures that would allow enhancing future generations are ... the hydrogen bomb of this whole set of human biotechnologies." Not the least of the concerns would be the potential social inequalities between "unenhanced" children born to the poor and those born to wealthy parents, who could afford to select the traits of their future children.
The cloning of pets is controversial, too. Physical appearance can vary slightly from the original, and it's unclear if the disposition of Fido or Fluffy will be reproduced in the copy.
Farm animals are another matter. The Food and Drug Administration (FDA) is expected to issue a risk-assessment soon on the safety of milk and meat from the progeny of cloned animals. Mark Walton, president of ViaGen Inc., an animal-cloning company in Austin, Texas, is sure the offspring of clones will be found to be completely healthy and their meat and milk products identical to those from noncloned sources. "We anticipate that cloning will be accepted as a standard technology" used to breed farm animals, Mr. Walton says.
Cloned animals will not be slaughtered for meat or give milk. They're far too valuable for that. They will be used only for breeding, Walton says. It is only their offspring born through traditional breeding techniques that will be consumed. Following the expected FDA approval, he says, in the next decade some 30 to 50 percent of breeding boars may be clones, selected for their superior traits, meaning that 30 to 50 percent of the pork on the market would come from their progeny. Perhaps 10 to 20 percent of breeding bulls could be replaced by clones as well, he says.
The question of defective clones is less crucial in farm animals, since any defects would not be passed to future generations, Walton says.
The assertion by Wilmut and Jaenisch that all clones will be defective is "wrong," Walton says, calling it an "oversimplification." "Will there be clones that are born that aren't healthy clones? Absolutely," he says. But that's true of naturally born animals too. "That's just part of life," he says.
The successful cloning of Dolly the sheep 10 years ago launched a flurry of experiments and bioethics debates. Here's a brief timeline of significant events in cloning research:
July 5, 1996
• First animal cloned from an adult cell: A sheep named Dolly is born in Scotland.
• A group of Oregon researchers create two genetically identical rhesus monkeys, but they are not considered true clones.
• US President Bill Clinton signs a five-year moratorium on federal funds for human cloning.
• University of Hawaii scientists clone three generations of mice from adult ovarian cells.
• Japanese scientists clone eight identical calves using cells from a single adult cow.
• US Food and Drug Administration declares authority to regulate human cloning.
• Several groups of researchers announce they have cloned pigs.
• Britain grants a patent for human cloning.
• Cloning firsts for mules, horses, deer, and an endangered species (the banteng, a type of ox).
• A South Korean researcher claims to have cloned a human embryo. The claim is later debunked as a fraud late in 2005.
• The first cloned pet, a kitten, is delivered to its owner in Texas for $50,000.
• The United Nations calls for a ban against all forms of human cloning.
• A dog, Snuppy, is cloned in South Korea.
Source: Biotechnology Industry Organization; Center for Bioethics, University of Minnesota