Dolly was the first mammal to be cloned from an adult cell, and on the 25th anniversary (Dollyversary?) this documentary by BBC Scotland tells the full story with never-before-seen archives. Dolly – The sheep that changed the world makes the story accessible to any interested viewer with no specific science knowledge needed. The emphasis is on the scientific development and medical benefits, but, as with any great scientific discovery, there is also an emotional roller coaster!
The story is woven around the Roslin Institute in Edinburgh, set up after the second world war with the aim to improve food production. However, with a change in government in 1979 and the arrival of Margaret Thatcher, institutes like Roslin were asked to prove their viability. In 1981, having just missed the axe, a conscious decision was made to 'follow the money' and ramp up its work in the emerging field of genetic engineering.
A brief review followed on the development of genetic engineering in the USA in the 1960s, and how scientists inserted a growth hormone gene from a rat into a mouse egg, which resulted in 'giant mice'. Furthermore, growth hormones were also being used in livestock, and these first advances in the field of genetic engineering led to public alarm.
While they did introduce the idea of 'playing god' with the building blocks of life, the documentary quickly moved the focus onto the potential use of genetic engineering in the fight against human suffering. With the newly found ability to pinpoint specific genetic mutations that lead to certain diseases, scientists at the Roslin Institute focused their research on genetic diseases, in particular spina bifida. Enter senior research embryologist Karen Walker, one of the original researchers, whose personal story I found particularly interesting as she was born with spina bifida.
The Roslin Institute was already researching sheep breeding and genetic engineering was the next logical next step. Sheep were very cheap, as well as easier to use than mice and rats, hence, necessity was the mother of invention, and a shoestring research budget started the programme that led to Dolly.
Genetic engineering was used to insert the gene of a human protein, alpha 1-antitrypsin, into a fertilised sheep egg with the hope that the ewe born would produce human alpha 1-antitrypsin in her milk. Failure led to persistence and finally, in 1990 a ewe was created that did produce human alpha 1-antitrypsin in her milk. The sheep was called Tracy, whom the team referred to as a 'living drug factory'. Even though this research was aimed at the development of treatments for life-threatening diseases, two animal research institutes in Scotland were burnt down, thought to be the work of animal rights activists.
However, the team was undeterred and decided to take the science further – with the aim to develop a flock of 'Tracys' – to cloning. Dolly was created by a close team in early 1996, including embryologists Walker and Dr Bill Ritchie (Dolly's mum and dad), working alongside late biologist Professor Keith Campbell. The project was led by Professor Sir Ian Wilmut, who drummed up the required four million pounds in funding.
Previously, it was believed that cloning cells was only possible from embryonic cells, however, the scientists at Roslin were not successful and made the rather bold decision to use adult differentiated cells instead. Professor Campbell believed that the adult cells could be reprogrammed and kick-started into new life.
Dr Ritchie and Walker even made their own pipettes so that they were exactly the way they wanted them to be. They then used these pipettes to remove the nucleus from a sheep's egg and replace it with an adult cell, in a process known as nuclear transfer, which Walker described as being 'tricky but very boring'. Embryos were subsequently implanted into surrogate sheep... and it took a whopping 277 fertilised eggs to make Dolly.
The story was strictly embargoed until 27 February 1997, when Nature was due to publish its success, but it leaked in the Sunday papers. A moral panic swept the world and reporters from all over the globe descended on the Roslin Institute, which they were ill-prepared for. Professor Wilmut became the face of cloning who patiently explained the details to the press.
There was much anthropomorphising of Dolly in the documentary – she loved the limelight, puffed herself up and posed for photos. It was heart-warming to listen to the scientists lovingly describing Dolly as 'a bit of diva', describing how she would rush to greet people for treats, and how she knew she was beautiful and something special.
Dolly was a game-changer, yet even though scientists at Roslin condemned human cloning, the interrogation from the media was relentless, and human cloning was subsequently banned. The project then 'caught the eye of the most important man in the world' – US President Bill Clinton, who made a speech about the use of this technology to assist humans (while banning human cloning).
On the other side of public opinion, animal rights campaigners were frequently breaking into facilities to try to halt experiments. At one point activists even tried to liberate Dolly but 'sheepishly' left empty-handed when they couldn't identify which sheep in the barn was Dolly! Yet, it was clear that the researchers did indeed love and care for the animals.
The Ministry of Agriculture shockingly cut funding at Roslin, resulting in their need to sell the technology. It was explained that the technology used to create Dolly could potentially be used to replace failing organs and failing cells in such diseases as Parkinson's disease. A deal was struck with Geron Corporation, a biotech company in San Francisco, who bought the technology for 30 million pounds.
Professor Wilmut now has Parkinson's disease, the disease that he hoped Dolly's legacy would one day cure. It seems that Dolly did not lead to either the medical treatments that were hoped for, or the cloning dystopia that was feared. But she does continue to inspire the scientists of today and tomorrow.
The scientists at Roslin continued cloning, creating sheep, Polly and Molly, that produced milk that was rich in human proteins that could fight genetic disorders. In 2001, the drug entered clinical trials yet the trials weren't successful as commercial-scale production wasn't feasible. The disappointment the scientists felt was paramount.
Dolly did produce six lambs, proving that cloning or genetic modification does not intrinsically harm reproduction. Dolly was euthanised aged six, after being diagnosed with a progressive lung disease, which the scientists determined had no link to the genetic modification. Dolly was also arthritic and overweight due to being fed too many treats by her many visitors. She is now stuffed and in the National Museum of Scotland.
I'd recommend this programme to anyone with an interest in Dolly, especially school biology students. There is no scientific jargon, as any technical terms are fully explained. Hammy imagery and dramatic music featured throughout, yet the documentary emphasised the important parts of the work while remaining entertaining. As for myself, I was glad to see the scientists celebrated, and it was interesting to see how chance, money and politics played such a big part in this defining scientific moment of the 20th century.
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