How Dolly changed the world
The birth of the first cloned animal 20 years ago was historic. But was it the most important scientific breakthrough of the 20th Century? Or did Scots researchers create a monster?
IN the early part of 1996 she was known only as 6LL3 and hardly registered in the consciousness of anyone, even her creators. There were, after all, 276 others just like her with equally boring code names.
But there was something about 6LL3, something which, paradoxically, made her stand out from her exact copies. As, one by one, they fell by the wayside, 6LL3 endured all the way through her surrogate mother’s pregnancy.
Then, on July 5 that year, a healthy lamb was born. She was suckling within minutes. The new arrival certainly had her creators’ attention then. She – and they – had just made history.
In producing a clone of an adult Finn Dorset ewe using a single cell from its mammary gland, Ian Wilmut’s team at the Roslin Institute in Midlothian had become the authors of one of the most important biotechnological breakthroughs of the 20th century.
They did not know it yet, but they had also unleashed a monster – not the harmless lamb, but a beast born of imaginations running riot. If scientists had cloned a sheep, what next? Humans, surely; whole armies of them, probably. In fevered minds a sci-fi Doomsday scenario seemed suddenly terrifyingly real.
It is now 20 years since the birth of the sheep scientists named Dolly after singer Dolly Parton – and a little less than that since the world learned about it and panicked.
But, judging by the event organised to mark the anniversary, it is fair to say the panic has died down somewhat. On July 5, a small group of residents from the village of Roslin will have a tea party in a local pub. There will be a cake in the shape of a sheep.
Now 71 and retired, Professor Sir Ian Wilmut used to say it was impossible to predict where the biggest breakthroughs would take science.
‘One misconception is that scientists are any more farsighted than anyone else,’ he said. ‘We are not. Most of the things this technique will be used for have not yet been imagined.’
Those who imagined the arrival of human clones within a few years were mistaken.
But, two decades after the birth of a perfectly ordinary looking sheep, her legacy is both rich and vast. The placid ewe, which died of lung disease at the age of six, has become godmother to a raft of exciting new avenues in medical research. Current work on treatments for conditions such as multiple sclerosis, motor neurone disease and Parkinson’s all owe a debt to the late Dolly.
Not that, in the genetic sense, Dolly is dead. Away from the public gaze, on land belonging to Nottingham University, four clones gambol around. Known as ‘the Dollies’, the quads are exact genetic replicas of each other, of the original Dolly and of the dead ewe whose udder cells were used to make the copies. In 2010, Professor Keith Campbell, one of the key scientists behind the original research at Edinburgh University’s Roslin Institute, said: ‘Dolly is alive and well. Genetically, these are Dolly.’
They were created by defrosting the udder sample, removing more cells from it and fusing each of those with developing sheep egg cells whose DNA had been ‘switched off’. Those which ‘take’ are implanted into surrogate mothers. Dolly was the one success story out of 277 eggs but, by the time her clones were created in 2007, the success rate was much higher.
Only five embryos were required to produce each one of the Dollies.
Tragically, Professor Campbell himself is no longer here. The man Sir Ian Wilmut said ‘deserves 66 per cent of the credit for Dolly’ hanged himself in 2012 after returning home from work at Nottingham University drunk and argumentative. A coroner returned a verdict of misadventure, finding the 58-year-old had not intended to go through with the suicide.
His death casts a long shadow over a scientific endeavour which laid important groundwork for saving lives.
The team had already succeeded in producing genetic clones of sheep using embryo cells. But, in Dolly, they managed to create a clone from a single adult cell. That depended on a breakthrough which truly sounded like science fiction – turning the clock back to zero on living cells.
No one, least of all Sir Ian, was under any illusions about the occasionally controversial nature of their work. In 1991, when animal rights activists learned about his research, they set
fire to his laboratories. But even that could not have prepared him for the onslaught which followed in 1997 when the Roslin Institute went public with Dolly. In the seven months since her birth, only around a dozen people were aware of Dolly’s existence.
Now she was worldwide news. Sir Ian was giving evidence to the Commons Science and Technology Committee in London. Then he was answering questions for Congress in Washington DC. The Vatican, meanwhile, wanted to have the moral meaning of cloning clarified.
Headline writers invoked Doctors Frankenstein and Strangelove. As for the ‘monster’, one breathless scribe reported how Dolly ‘looks at you with those intense red eyes – eyes full of hate’.
Asked about using similar techniques to produce a human clone, Sir Ian said the idea was ‘repugnant’ and ‘illegal’. ‘The objectives we had with this project were to produce methods for making precise genetic change in livestock and for making copies of embryos,’ he said. ‘It is legitimate to do things in farm animals you would not do in humans.’
FORTUNATELY, perhaps, little about Sir Ian conformed to the stereotype of mad scientist immersed in morally ambiguous work. He was a balding bloke with a beard and a wife and a pet spaniel. He enjoyed real ales and single malts.
‘I am diffident Englishman,’ he commented at the time. ‘I am trying my best to get [cloning] launched without getting my own life all tangled up in it.’
As unremarkable as Dolly may have looked, her journey to life sounded like fantasy. Even experienced scientists were amazed a mammal as complex as a sheep could have been produced from a single cell taken from a frozen mammary gland sample.
And even her creators struggled with questions about the organism they had created. How old was Dolly when she was born? Was she really six, the age of the original sheep when the udder sample was taken? What were the implications for Dolly’s health and longevity? The scientists did not know.
Although for security reasons Dolly never left her pen, a small Welsh mountain ram was selected as a mate and, between 1998 and 2000, they produced six lambs.
But concerns for her health were growing. First she was diagnosed with arthritis; then, in March 2000 it emerged that Morag, a sheep cloned from cultured embryo cells had sheep pulmonary adenomatosis (SPA), a virus which causes tumours to grown in the lungs of infected animals. Since she and Dolly had been housed together it was thought likely Dolly had it too. Then one of her second litter of lambs was diagnosed with the same disease, making it certain Dolly was infected.
She lasted two more years until it was noticed she was coughing in February, 2003. A scan carried out confirmed tumours were growing in Dolly’s lung. A deliberate overdose of the anaesthetic agent was delivered and she never woke up.
‘Quite a sad day,’ reflected Sir Ian later. ‘People said she died early because she had DNA from a sixyear-old sheep. This is totally false. She was just unlucky.’
Thirteen years after Dolly’s death, the good health of ‘the Dollies’ now aged nine, appears to put it beyond doubt that their exact replica Finn Dorset Ewe was just unlucky. Yet, as Dolly’s 20th anniversary approaches, the most important research is no longer focused on producing identikit animals, even if US companies have succeeded in cloning cattle and horses and pigs for breeding on farms.
The real prize lies in ‘reprogramming’ cells to allow healthy ones to replace diseased ones.
PROFESSOR Bruce Whitelaw, deputy director of the Roslin Institute, said: ‘The whole basis of the Dolly experiment was that we could take a cell and we could change its state, we could reprogram it and, in the case of Dolly, re-program it to start from scratch if you like, from the embryonic state.’
Twenty years on, he said, the idea that a cell could be re-programmed had become a major driver in cell therapy. ‘It opens up this whole raft of still largely potential new surgical approaches based around regenerative medicine. There is a huge amount of potential there.’
Until that potential is realised, he said, Dolly’s greatest legacy lies in the public awareness that she brought to the fields of biological and medical genetics.
Next month a taxidermied Dolly will go back on show at the newly refurbished science and technology galleries of the National Museum of Scotland in Edinburgh.
Her namesake is still going strong. Sir Ian said Dolly was named after Miss Parton because the sheep came from a mammary gland ‘and we couldn’t think of a more impressive pair’ than the singer’s.
‘She gave me a lot of competition’ lamented Miss Parton some years ago. ‘I never met her, but there’s no such thing as baaad publicity.’