Ian Wilmut, 'father' of Dolly the sheep, dies

We pay tribute to a legendary embryologist...
15 September 2023


Dolly with Professor Sir Ian Wilmut, who led the research which produced her.


This week the scientific community mourned the loss of the British biologist and cloning pioneer, Sir Ian Wilmut, who dubbed himself, "The Father of Dolly the Sheep". She was unveiled to the world via the front cover of the science journal Nature in 1997, and was the first example of anyone cloning - in other words making a genetically identical replica - of an adult mammal. The work was done at Edinburgh's Roslin Institute, where Ian Wilmut led a team that included the cell biologist Keith Campbell whose insights were crucial to making the experiments - that were inspired by science carried out on tadpoles almost a century previously - come to fruition. But the objective, when the work began in the 1980s and early 90s, wasn't simply to clone animals: it was about genetically manipulating them for therapeutic purposes, as Ian Wilmut himself explained back when he talked to the Naked Scientists in an interview marking a decade on from Dolly...

Ian - The ambition was to be able to make genetic changes in farm animals so they would produce proteins needed to treat human disease. That was the aim when we first started.

At the time, they were injecting DNA instructions into eggs to make animals with the ability to produce human gene products; one of their successes was a sheep called "Tracy" that produced in her milk the substance alpha-1-antitrypsin, which is used to treat some forms of emphysema.

Wilmut acknowledged that more valuable animals, like cows, were the ultimate animal goal for the work, but they also had long gestation periods and were expensive. Sheep, on the other hand, reproduced far more rapidly and, as Ian Wilmut put it, "you could buy one for less than the price of a bottle of mineral water at a posh hotel."

After genetically modifying Tracy, Wilmut became interested in the question of whether it might be possible to clone a mammal; presumably the idea was that once you'd made one special animal, you might want more identical ones, so being able to copy them faithfully would be beneficial. Or if you could produce new organs this way, it would be handy to have ones that were genetically identical to the donor to avoid immune rejection later.

The technique that the Roslin team refined and which ultimately resulted in Dolly's creation is called "somatic cell nuclear transfer".

Put simply, the nucleus - containing the DNA - is removed from an adult cell and injected into an unfertilised egg cell that has had its own DNA removed.

Dolly got her name - by Wilmut's own admission - from Dolly Parton because, she was cloned from a cell collected from an adult sheeps' udder. Dolly Parton, in turn upon hearing about her ovine namesake remarked that "no publicity is Baaa'd publicity!"

Crutically, the work - that was painstaking and took hundreds of attempts to perfect - showed that something about the internal environment of an unfertilised egg has the ability to reprogramme donor DNA so that it "forgets" that it was previously in a specialised adult cell and is "rebooted" as an embryo that begins to develop.

Arguably, it was this discovery - that the clock can be wound back and adult cells can be "unspecialised" - that was one of the most important to emerge from the creation of Dolly the Sheep...

Ian - We all came from a single cell of an embryo, which is smaller than a grain of salt, and almost all of our cells have exactly the same genetic information in them. The way in which the many different tissues that we have are formed is because the functioning of the gentic information is changed systematically to produce muscle, skin, bone, in them and all of the different tissues that we have. We used to believe that the mechanisms that bring that about are so complex and so rigidly fixed that it would not be possible to reverse them. The most important thing to come form the Dolly experiment was to show that's not true...

Indeed, it was this discovery - that adults cells can be reprogrammed to become stem cells again - that opened the door to the creation of what are now called iPS - induced pluripotent stem cells. These are stem cells but made from adult cells.

And this had led to work such as the announcement by scientists in Israel last week that they can now even make artificial human embryos this way.

It also means that we are a step closer to the goal of using embryology and cell biology to produce tailor-made cells to repair diseased human organs.

Equal powerfully, you can also use the technique to reproduce some aspects of a disease in the laboratory dish and test new treatments, although the pace of progress is slow, something Ian Wilmut himself reflected on ruefully towards the end of his life...

Ian - I personally have Parkinson's disease so there is a chance of the same thing happening for that disease and I think that unexpectedly the Dolly experiment has revolutionized the approach to these diseases. I really do genuinely believe that treatments will come along but it may very well be 50 years before the treatment becomes routinely available. So people like me will probably have died of Parkinson's disease before the new treatments become available which is a frustrating thing to think.

Ian Wilmut, who led the team that successfully cloned the first mammal - Dolly the Sheep - and died this week aged 79.


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