Leader of the flock: 25 years on from Dolly the Sheep

It was a story that grabbed headlines around the world, sparking a media frenzy and the unfolding of a prolonged ethical debate.   

On a Friday at the Roslin Institute in Midlothian just over 25 years ago, Dolly the sheep was born. She was the first mammal to be cloned from an adult cell in a major scientific breakthrough. The date was 5 July 1996. 

Dolly was created by replacing the nucleus in an egg cell from a Scottish Blackface sheep with that of a cell from the mammary gland of a Finn Dorset sheep. The subsequent embryo was implanted in a surrogate Blackface ewe. 

Her existence was unveiled to the public almost eight months after her birth as the Roslin team timed the announcement to coincide with the publication of the scientific paper describing the experiments that produced her. 

Hordes of photographers and reporters descended on the Institute to catch a glimpse of what was considered a scientific miracle. Dolly – named after country singer-songwriter Dolly Parton – munched at the hay in her pen unperturbed, if not oblivious, to the scenes developing around her. 

During the week that followed, the Institute received 3,000 phone calls from all over the globe. The level of hysteria caught many within the scientific community off guard. 

Professor Kevin Sinclair, an expert in developmental biology and head of the division of animal sciences at the University of Nottingham, was based in Aberdeen at the time. He was working on a separate project but had been collaborating with Sir Ian Wilmut and the team at Roslin.

“I wasn’t directly involved in the team,” he says. “But we were down at Roslin with regular meetings, and we were familiar with the programme of research that was going on at the time. And when it was released – Dolly was born in ‘96 but it became public knowledge in ‘97 – I was around at the time. 

Professor Kevin Sinclair

“I was one step removed from the actual action. It gave you quite a unique perspective in that you were close enough to really understand what was going on at the science level, but just one step removed, you could step back and see how the team were having to respond and interact with the media at that time. 

“The public reaction just took everybody by surprise – myself included. Obviously, it stemmed from extreme excitement in the scientific community for a major advancement in our understanding of what I would call developmental biology... to the kind of hysteria about human cloning and things like that. It just captured the public imagination. It ran wild.”

Dolly’s birth was so transformative because she showed that specialised cells could be used to create an exact copy of the animal they came from. Rather than having just the information to do that job, the mammary cell had all the information required to create a whole new sheep.

She was put to sleep at the age of six in 2003 after a CT scan showed tumours growing in her lungs. Because of her death at a relatively young age, concerns were raised that cloned animals might age more quickly. 

Sinclair led a team at Nottingham that was able to dispel these fears in 2016. The study, which tracked four sheep derived from the cell line that gave rise to Dolly, found they had aged normally.  

At the end of each strand of DNA, there’s a short sequence called a telomere. Every time the DNA replicates, the telomere gets shorter and once it reaches a certain point, the DNA will start to degrade as part of the ageing process. The team was worried that the telomere from an adult cell would be shorter, so that when reprogrammed to produce a new animal, it would age prematurely. 

Sinclair explains: “What we needed to do was establish if there was any long-term legacy in terms of the health. We took these animals up to about nine to 10 years of age, which is about as old as you can probably take them. Sheep can live beyond that, but not many of them do and the issue is that they start to develop age-related problems like arthritis naturally. So, allowing us to take them to the extreme end would be unethical, but we took them up to about nine or 10 years of age. 

“On two or three occasions, we assessed their health. We assessed what we call cardio metabolic health, like blood pressure, whether they were insulin resistant or predisposed to type two diabetes. We also X-rayed them and put them through an MRI and CT scanner on a couple of occasions, to establish if there was any evidence of early onset arthritis, which might be indicative of premature ageing. 

“It turns out that they were perfectly normal, that they were ageing at the same rate as sheep that were conceived normally, and there was nothing untoward about these animals. The take-home message there simply was that it is possible with these advanced breeding technologies to produce animals that can lead a perfectly normal, healthy life.”

Dolly’s birth and the work that followed undoubtedly represented a paradigm shift in science – a step change that propelled the discipline on to the front pages of newspapers. Decades on and we are once again living in an era in which science and innovation is grabbing the wider public’s focus as it provides the route out of a deadly pandemic, which has gripped the world, causing disruption and devastation in equal measure. 

We have become accustomed to seeing virologists, epidemiologists and experts in public health on the television, offering insight, commentary and advice during a period we will unlikely ever forget. 

Might the crisis we have lived through change how people perceive and appreciate the discipline? The question is put to Professor Michael Barrett, an expert in biochemical parasitology at the University of Glasgow and the director of the Scottish Universities Life Sciences Alliance (SULSA).

“I hope so,” he tells Holyrood. “As a scientist, it’s been an extraordinary thing because you do see some of the great benefits that science has brought in an incredibly short timeframe. We never thought it was possible to get a vaccine in a year and I was on the record saying forget about it. So, it’s just been extraordinary that we’ve had that. 

“Of course, the reason we could do it was because of investment in the fundamental research needed to generate the technologies that were ready to adapt when the pandemic came along.

“But other things I think we need to bear in mind as well, with respect to political exploitation of science, is perhaps look for ways whereby scientists can be given more devolved power from politics. 

“I recently read Jeremy Farrar’s book on the pandemic called Spike... One really interesting thing I got from the book – having sat through Dominic Cummings’ seven-hour extravaganza at Westminster – is just how close Cummings’ view of what was happening inside Westminster was to the scientists’ perplexed view of what on earth was going on in Westminster based on how their advice was being treated.

“I would actually just really have said that, perhaps at some point, Boris Johnson and Dominic Cummings, and I don’t know to what extent Nicola Sturgeon or others here did this, could just sit back and say, look, this is so serious, we’re not going to put too much of our own opinion into this, we will just let these guys run the show.”

Barrett, who was involved in setting up the Lighthouse Lab network of Covid-19 diagnosis laboratories, believes much has been learned from our experience during the last 18 months. 

“I never thought you could have a lockdown in countries like the United Kingdom, even if you could in China, because of opinions on civil liberties. I’m actually pleased to see that it was possible to do that. Having seen you can do that, we can refine how lockdowns work, because we will have another pandemic. This isn’t the end. I think emerging viruses are likely to keep coming and we need to work on the lessons we’ve learned from this pandemic to make sure we can respond better next time.”

He reflects on how far the country has come in terms of testing and stresses the importance of building on such networks. “The early days of testing were terrible,” he says. “We just didn’t know who had the disease. Having established these labs gives the capacity and capability to be vigilant for any forthcoming pandemics and they should be maintained. 

“It will cost money to sustain such surveillance networks, but nothing compared to the economic damage of not catching future epidemics early. It’s analogous to nuclear deterrents, where one invests in military technologies with the hope that they never have to be used.”

We cannot understate what science has achieved during the pandemic response, but neither should we lose focus on other areas where Scotland is excelling and breaking ground in the discipline.

With more than 770 life sciences organisations employing more than 41,000 people, the country is one of the largest life sciences clusters in Europe. It has a range of expertise including drug discovery, bio-manufacturing and stem cell sciences. The sector contributes £2.4bn to the Scottish economy and has seen seven per cent growth each year since 2010.

As we discuss some of the key areas Scotland is pioneering in its research, Barrett points to continued progress in understanding infectious diseases. He calls the country a “world leader” in drug discovery and raises the topic of precision medicine. 

“That’s the whole notion that instead of just throwing drugs at people with a vaguely defined condition, you go in and with genetic medicine, you can now define clearly what is the cause of a particular type of disease. Because you know exactly what the cause is of a particular type of disease, you can decide whether particular medicines are going to work or not.”

Scotland has a rich history in terms of its involvement in scientific discovery and innovation. Looking ahead, it is evident that it is in a strong place to continue that in the future, too. Not least, Barrett believes, because in many ways it is just the right size.

“We’re small enough for us to be able to be in touch with researchers across the great institutions but at the same time, we’re big enough to have a critical mass where great thinking can be shared. 

“Scotland has a sweet spot in terms of its size to enable collaborative research in the way that has allowed great discoveries going back to the 19th century, right through to Dolly, and moving ahead as well.”