The first-ever successful cloning of an animal from an adult cell took place at the Roslin Institute near Edinburgh. A Finn Dorset lamb called Dolly, her birth marked a pivotal advance for science. Dolly’s unveiling the following spring sparked unprecedented attention, including references on The Simpsons and cover photos on magazines. She also created high anxiety among ethicists and legislators, who feared that human cloning would soon follow. Others believed that medical science was about to take a quantum leap forward in the cure of disease, while the most radical began to wonder if human cloning was such a terrible idea after all. Head of the Roslin Institute team Professor Ian Wilmut, who became known as ‘the father of Dolly’, describes one of the most remarkable pregnancies and births yet seen.
In the first tranche of experiments, we used cells from a nine-day-old embryo, differentiated skin cells from a twenty-six-day-old foetus and frozen udder cells. The first ultrasound scans, at around eight weeks, showed that only one-third of the ewes had foetuses. Much to our surprise and delight, however, one ewe was pregnant with a clone from an adult cell. Ultrasound revealed an apparently normal foetus. Karen Mycock recorded the scan on a video with maternal pride and felt a thrill of anticipation that a lamb could result from this supposedly impossible experiment.
That day, 20 March 1996, was when we first began to think seriously about clones from adult cells. Keith Campbell [pioneer of nuclear transfer in the cloning process] and I became nervous, particularly as the pregnancies continued to fail. Except, that is, the one that should not have been: Dolly. We shared a mixture of excitement and concern because we knew that a milestone would be passed if the lamb survived. We knew from previous experience that many of the foetuses die, sometimes late in pregnancy or even at birth. As we fretted over Dolly the foetus, the Princeton professor Lee Silver was writing a popular book on reproduction technology in which he was patiently explaining why cloning from adults was a biological impossibility.
That May, around 110 days into pregnancy, four foetuses were found to have perished, all clones of embryos. Of the 29 embryos that we had created from 277 udder cells, one foetus continued to thrive in her Scottish Blackface surrogate mother. We constantly monitored her wellbeing. Every time John Bracken used ultrasound, it always took a few seconds to get the whole image in view. You could usually see the head, legs and ribs at first. There would also be some movement. Most important of all was the moment when we could see a heart beating. Then we all felt a great sense of relief and satisfaction.
To ensure that our nails were bitten to the quick, Dolly’s gestation, like that of other clones, took longer than normal. In most British breeds of sheep the average duration of pregnancy is 147 days. Experience now tells us that pregnancy sometimes drags on up to 155 days for clones. They usually die if the pregnancy goes beyond day 153. The labour of the ewe carrying a clone is also slow and sluggish, as we now know also to be the case in other species. Just before the onset of labour, a ewe having a normal pregnancy will often leave the rest of the flock and make a ‘nest’ by pulling grass or straw together to form a hollow in a quiet corner of a field, an ancient reflex to create a defence against predators. For reasons we don’t understand, nesting was less likely to be triggered by a cloned embryo. The wait continued.
We did everything we could to keep the ewes and the clones safe, and placed the animals under twenty-four-hour observation. We wanted to leave nature to take its course, but if the pregnancy went beyond 153 days we would induce birth with an injection of the same hormones that the foetus normally releases to signal that it is ready for the outside world. The lambing pen at Roslin had seen great excitement and satisfaction, but more often than not with clones it has also witnessed death and deformity. But that was not the case on 5 July 1996. A healthy lamb was born that day, one that would become the talking point of paupers and presidents.
Dolly entered the world head and forelegs first in a shed on the Roslin farm late in the afternoon. Her arrival was a muted affair. She weighed 6.5 kilograms, surprisingly large for a normal lamb but not for a clone; we now know that animals cloned by nuclear transfer are often oversize. In attendance were a local vet and a few staff members from the Roslin. John Bracken was in charge. Even though I am often called the father of Dolly the sheep, I was an old-fashioned father and was not present at her birth. Her expected arrival was the cause of a great deal of excitement among the team, and I gave the instruction that only those who had to be present should be there. At the time of the birth I was digging in the vegetable garden in the grounds of the institute. One thing her mother did not need was stress brought on by too many people being present …
[After the birth] I did not hand out cigars or go for a celebratory drink in the local pub. No one took photographs. Nor could my wife remember me coming home and performing cartwheels of joy. Roslin was not painted red. Dolly’s creation had been so long coming, so protracted, so difficult and such hard work that we were too fatigued to cry ‘Eureka!’