On February 22, 1997, the lead story on every TV news broadcast wasn’t about war, natural disasters or the latest political scandal. It was about a sheep.
At a small research institute in Scotland, scientists had achieved something previously thought impossible. They had cloned an adult animal by transferring its DNA into an egg cell. The result was a fluffy, white-coated lamb named Dolly that was a carbon copy of her donor “parent.”
Dolly’s birth was a major scientific achievement, but the groundbreaking implications of cloned cells in medicine and agriculture were quickly overshadowed by the specter of human cloning. The cover of TIME asked: “Will There Ever Be Another You?”
Dolly wasn’t the first cloned animal or even the first cloned mammal, but her birth sparked scientific and ethical debates that still resonate today.
Why Clone a Sheep?
In the 1990s, the goal of cloning research wasn’t to make millions of copies of farm animals or household pets—and certainly not to clone humans. Animal cloning was seen as a promising tool for developing cures and therapies for human diseases.
“The purpose of animal cloning was to do genetic engineering,” says Bruce Whitelaw, director of the Roslin Institute at the University of Edinburgh, where Dolly was cloned.
Ian Wilmut, the lead scientist on the Dolly project, wanted to edit the genes of sheep so they would produce milk containing human proteins to treat conditions like diabetes and cystic fibrosis.
“You’d engineer an animal to express a human protein that you’d then harvest from the milk, purify it, and then give it to patients,” says Whitelaw.
The existing genetic engineering technology at the time was imprecise and inefficient. With cloning, researchers hoped they could produce countless genetic copies of cells in the lab and program them to produce life-saving therapies.
Wilmut and his Edinburgh colleagues could have experimented with cloning rats or pigs, but their expertise was with breeding sheep. Whitelaw says that Wilmut didn’t choose sheep for their “wooly and fluffy” appearance, but admits that “there’s something softer about sheep that may have had something to do with the appeal of Dolly.”
How Dolly Was Cloned
Wilmut and the Roslin Institute scientists used a cloning technique called nuclear transfer. They extracted the nucleus (containing DNA) from a donor cell and implanted it into an egg cell that had its own nucleus removed. The idea was to reprogram the egg cell to grow a carbon copy of the donor.
Dolly wasn’t the first sheep that the Roslin scientists cloned using nuclear transfer. In 1995, they produced two healthy lambs, Megan and Morag, that were cloned from embryonic donor cells. And in 1996, Taffy and Tweed were cloned from fetal donor cells.
In both cases, DNA was extracted from cells in the very earliest stages of development, when they were still undifferentiated like stem cells. The challenge with Dolly was to produce a clone with DNA extracted from adult cells. The scientific consensus at the time was that it was impossible to clone from cells that had already differentiated into skin cells or liver cells.
“Biologically, there's a big difference between a stem cell and an adult cell,” says Whitelaw. “This is what made Dolly such a dogma-breaking moment.”
The trick with adult cells is that the nucleus must be extracted during the cell’s dormant or “quiescent” phase when it’s not dividing. That discovery was made by Keith Campbell, Wilmut’s colleague at Roslin.
“As Ian himself freely admitted, the real genius in the thing was Keith Campbell,” says Colin Tudge, a science journalist who co-authored a book with Wilmut and Campbell. “Keith said you have to get the cells at the right stage of their cycle in both cases—the ovum and the transferred cell—in order for cloning to work. That was Keith’s great revelation and insight.”
To clone Dolly, the Roslin scientists took a cell from the mammary gland (udder) of an adult Finn Dorset sheep. They extracted its nucleus and implanted it in an unfertilized egg stripped of its genetic material. They grew the egg cell into a blastocyst in a test tube and then implanted the growing embryo into a surrogate mother.
Since Finn Dorsets have a white coat and the surrogate—a Scottish Blackface—had a black coat, it would be easy to tell if the lambs were hers or a clone of the donor. But they still had to wait 148 days to find out.
Dolly Mania
Dolly the sheep was born on July 5, 1996. She was a healthy lamb with a white coat and a white face. Dolly was officially the first animal in the world cloned from an adult donor.
Wilmut, Campbell and the rest of the Roslin team knew they’d accomplished something historic, but they couldn’t tell anybody. In those days, Tudge says, research funding depended on publication in top-shelf scientific journals like Nature. And those journals required absolute silence before the publication date.
“All they wanted to do was discuss Dolly with their colleagues over lunch in Edinburgh, but they couldn’t even do that,” says Tudge. “If the word got out, the whole thing would be blown.”
When the news finally broke on February 22, 1997, “it was absolutely bonkers,” says Whitelaw, who was also a researcher at Roslin. “We were getting 100 calls an hour from media outlets around the world. Every phone in the building was ringing.”
With some embarrassment, Wilmut and the Roslin team explained that they named the historic sheep after Dolly Parton, since Dolly was cloned from a mammary cell.
Dolly Wrapped Up in Controversy
Almost immediately, Dolly’s birth was sensationalized as the first step toward cloning humans, something that Wilmut and his colleagues had never entertained and actively opposed. For the news media, however, it was an irresistible leap from cloned farm animals to cloned people.
Politicians took notice. Wilmut testified before the U.S. Congress and reiterated his opposition to anyone using Dolly’s technology to clone humans. In June of 1997, President Bill Clinton instructed Congress to pass a human cloning ban.
But human cloning wasn’t the only controversy that Dolly was sucked into; there was also the touchy subject of embryonic stem cells. In 1998, scientists successfully grew stem cells from donor cells extracted from a human embryo. As with cloning, the goal of stem cell research was to develop therapies for human diseases using genetic engineering.
But embryonic stem cells were controversial for two reasons. First, they were harvested from aborted embryos, which tied them to the ethical and legal debates around abortion. Second, there was concern that embryonic stem cells could be combined with cloning technology to clone humans. President George W. Bush severely restricted embryonic stem cell research in 2001.
The Roslin scientists were eager to explain the potential benefits of animal cloning in the fields of medicine and agriculture, but they often ended up fielding questions about armies of “Hitler clones” and designer babies.
“It frustrated Ian [Wilmut] a lot, because it wasn’t the direction his work was going,” says Whitelaw. “But in a way, the controversies galvanized him to want to be the spokesman for the whole field, and to become a sort of ambassador for cloning and for science in general.”
Dolly Only Lived for Six Years
As the first animal cloned from an adult, Dolly’s health was closely and carefully monitored. Dolly’s DNA came from a 6-year-old Finn Dorsett sheep, and there was some concern that Dolly would age prematurely. The average life expectancy of sheep is between 10 to 12 years.
In the first years of her life, Dolly was in good health. She gave birth to her first lamb, Bonnie, in 1998. She birthed a total of six lambs during her life with help from a Welsh Mountain ram named David.
In 2000, there was a virus outbreak at the Roslin Institute that infected Dolly and several other sheep with something called Jaagsiekte sheep retrovirus (JSRV), which can cause lung cancer in sheep. The next year, Dolly’s handlers noticed that she was walking stiffly. She was diagnosed with arthritis and treated with anti-inflammatories.
In 2003, Dolly developed a cough. When the Roslin veterinarians scanned her lungs, they found cancerous tumors. They made the difficult decision to euthanize Dolly rather than let her suffer. She died on February 14, 2003. Dolly was only six years old.
It wasn’t clear if Dolly’s arthritis or her virus-induced lung cancer had anything to do with her “genetic age.” Other animal clones have not had the same issues. The Roslin Institute donated Dolly’s taxidermied body to the National Museum of Scotland, where she’s still one of the most popular displays.
Dolly’s Scientific Legacy
“Dolly changed how the public looked at genetics, biology and reproductive technologies, and we’ve never gone back,” says Whitelaw. “As a society, we owe an awful lot to Dolly creating awareness and sparking ethical debates. She generated a huge amount of chatter and dialogue between the different types of sciences.”
The goal of Wilmut’s research at Roslin has become a reality. Researchers no longer use the “nuclear transfer” method, but advances in genetic engineering have made it possible to grow replacement cells and tissues, and to create therapies targeted to a patient’s unique DNA.
“Ian’s original dream that he could make cells that can be used therapeutically is, in essence, what is happening,” says Tudge.
The cloning techniques pioneered by the Roslin Institute are still used by some agricultural breeders. For about $20,000, a prized bull or pig can be cloned to preserve its genetic traits. However, in most countries—including the United Kingdom and the U.S.—it’s illegal to sell cloned animals for food.
After Dolly, Wilmut and the Roslin Institute moved on from cloning.
“We don’t do any cloning now,” says Whitelaw. “How can you ever have another Dolly? It was such a big thing. No matter what we do, we’re never going to do that again.”
