Dolly the Sheep (1996): First Mammal Cloned From an Adult Cell

Dolly the sheep, born on 5 July 1996 at the Roslin Institute near Edinburgh, was the first mammal cloned from a cell taken from an adult animal. Her birth, announced in February 1997, showed that a specialised adult cell could be reprogrammed to create an entire new organism, something many biologists had thought impossible. Dolly became a global celebrity and set off a fierce debate about whether humans might one day be cloned.

Background: can adult cells be reset?

Every cell in an animal’s body carries essentially the same DNA, yet a skin cell, a liver cell and a nerve cell do very different jobs. Scientists long wondered whether specialised cells permanently lose the ability to use all their genes, or whether that ability could be restored.

Early experiments used frogs. In 1952 the American scientists Robert Briggs and Thomas King cloned frogs by transferring nuclei from early embryo cells into eggs. In the late 1950s and 1960s the British biologist John Gurdon produced frogs from nuclei taken from tadpole intestinal cells, but attempts with cells from adult animals seemed to fail.

In mammals, cloning from embryonic cells had succeeded in sheep and cattle in the 1980s. In 1995 the Roslin team produced two lambs, Megan and Morag, from cells grown in the laboratory from an early embryo. Cloning from a fully adult cell remained the great challenge.

How Dolly was made

The Roslin Institute, a government-funded animal research centre, worked with the biotechnology company PPL Therapeutics. Their goal was practical: to produce genetically modified livestock that could make human proteins for medicines in their milk. Reliable cloning would make that much easier.

The team led by embryologist Ian Wilmut and cell biologist Keith Campbell used a technique called somatic cell nuclear transfer. Campbell’s key insight was to starve the donor cells of nutrients so they entered a resting state, which appeared to make their DNA easier to reprogramme.

The donor cells came from the udder of a six-year-old Finn Dorset ewe, preserved in a cell culture. The scientists removed the nucleus from unfertilised eggs taken from Scottish Blackface ewes, placed a donor cell next to each egg and used small electric pulses to fuse them and start development. The embryos were grown briefly and then implanted in surrogate Scottish Blackface mothers.

The process was highly inefficient. Of 277 fused embryos made from the adult cells, 29 developed far enough to be implanted, and only one led to a live birth. Because Dolly was a white-faced Finn Dorset born to a black-faced mother, it was clear she was not the surrogate’s own lamb.

Sheep were chosen partly because Roslin had long experience with them and partly because they suited the company’s plans. If a ewe could be engineered to carry a human gene, its milk could be used to produce valuable medical proteins, and cloning would allow a flock of identical, productive animals to be bred quickly. The same 1997 paper also reported lambs cloned from fetal and embryo-derived cells, which showed that the method worked with several cell types.

The announcement

Dolly was born on 5 July 1996, delivered with the help of the institute’s staff. The team kept her secret while their results were checked and written up. News broke on 22 February 1997, and the paper, “Viable offspring derived from fetal and adult mammalian cells”, appeared in the journal Nature later that week.

The announcement caused a media sensation. Within days, reporters from around the world crowded into Roslin, and Dolly appeared on magazine covers. Some scientists initially questioned whether she had really come from an adult cell, but DNA tests published in 1998 confirmed her origin.

The ethical debate

Much of the reaction focused on human cloning. In March 1997 US President Bill Clinton banned the use of federal funds for human cloning research and asked his bioethics advisory commission to review the issue. Many countries moved to ban human reproductive cloning, and in 1998 the Council of Europe adopted a protocol prohibiting it. The United Kingdom passed the Human Reproductive Cloning Act in 2001.

Debates also covered animal welfare, since many cloned embryos and newborns died or had health problems, and the use of cloning to create embryonic stem cells for medical research, so-called therapeutic cloning. Religious groups, ethicists and scientists disagreed sharply about where to draw the lines.

Dolly’s life and death

Dolly lived at the Roslin Institute and was mated with a Welsh Mountain ram. She gave birth to six lambs between 1998 and 2000, showing that a clone could reproduce normally.

In 2002 she was diagnosed with arthritis, prompting speculation that cloning had made her age early. Studies had also found that her telomeres, protective caps on chromosomes that shorten with age, were shorter than expected. On 14 February 2003, aged six, she was put down after developing a progressive lung disease caused by a virus that affects many sheep kept indoors. Her body was preserved and put on display at the National Museum of Scotland.

Legacy

After Dolly, scientists cloned many other mammals, including mice, cattle, cats, dogs, horses and, in 2018, monkeys. Cloning is used in some livestock breeding and in attempts to conserve endangered species, but it remains costly and inefficient.

Dolly’s deeper impact was on biology. She proved that adult cells can be reprogrammed, encouraging research that led in 2006 to Shinya Yamanaka’s discovery of how to turn adult cells into stem cells using a handful of genes, without eggs or embryos. Yamanaka and John Gurdon shared the 2012 Nobel Prize in Physiology or Medicine. Like the birth of Louise Brown, the first IVF baby, Dolly’s birth forced public discussion of how far reproductive science should go, alongside later milestones such as the Human Genome Project.

The practical goal was reached soon after Dolly. In July 1997 the Roslin and PPL team produced Polly, a cloned lamb that carried a human gene for factor IX, a blood-clotting protein needed by some people with haemophilia. This showed that cloning could be combined with genetic modification as the researchers had intended.

The two leading scientists had different later careers. Keith Campbell, whose work on the cell cycle was central to the experiment, continued research on cloning and stem cells and died in 2012. Ian Wilmut, the team’s leader and public face, acknowledged that Campbell deserved much of the credit for the scientific breakthrough. Wilmut was knighted in 2008 for services to science and died in 2023.

Myths and facts

• Myth: Dolly was the first cloned animal. Frogs and mammals had been cloned before from embryonic cells; Dolly was the first mammal cloned from an adult cell.
• Myth: Dolly died of old age caused by cloning. She died of a viral lung disease. A 2016 study of 13 cloned sheep, including four made from the same cell line as Dolly, found they had aged normally.
• Myth: Dolly was an exact copy of her “mother”. She shared her nuclear DNA, but her small amount of mitochondrial DNA came from the egg donor.

Timeline

• 1995: The Roslin team clones Megan and Morag from embryo-derived cells.
• 1996, 5 July: Dolly is born at the Roslin Institute.
• 1997, 22 February: News of Dolly’s birth is made public.
• 1997, 27 February: The Nature paper describing Dolly is published.
• 1997, March: President Clinton bans federal funding for human cloning research.
• 1998, April: Dolly gives birth to her first lamb, Bonnie.
• 2002, January: Dolly’s arthritis is announced.
• 2003, 14 February: Dolly is put down after developing lung disease.

Why it matters

Dolly overturned the belief that adult cells are permanently locked into their roles, opening new paths in stem cell research and regenerative medicine. She also made cloning a public issue, prompting laws and ethical debates that continue to shape science.