Sir Ian Wilmut: Legacy of Dolly the Sheep

23 April 2019

Interview with 

Sir Ian Wilmut, Roslin Institute & Scottish Centre for Regenerative Medicine

DOLLY-THE-SHEEP

Dolly the Sheep with her first born lamb, called Bonnie.

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Sometimes a bizarre idea quickly becomes the best idea and one experiment in particular rocked the world of genetics. On 22nd February 1997, in a world first, researchers at the Roslin Institute in Edinburgh announced that they had taken the DNA from a skin cell of an adult sheep and inserted it into a sheep's egg cell from which the DNA had first been removed. The egg was placed into the uterus of a surrogate sheep where it developed and the result was a lamb they called "Dolly". She was so-named because the adult cell used to clone her came from an udder, so naming her after singer Dolly Parton seemed apt. Chris Smith was pleased to be joined by the scientist who led that work, Sir Ian Wilmut…

Ian - It’s a point which is very very important to make. You need a crew of something like 12 or 15 people to do this sort of experiment. So to say I did it would be seriously misleading.

Chris - Why did you start with sheep though?

Ian - The Roslin Institute has always been concerned with farm animals. And if you are thinking of using cloning in a farm animal species, either to improve their performance or to increase numbers, the species with the greatest commercial interest would be the cow. But cattle are extremely expensive to buy, to maintain and they have a very long gestation, so that if you're doing an experiment where you transfer embryos as you said into a foster mother, you've got to wait 10 months or whatever it is before you know the answer to the experiment. By comparison the sheep are much easier to look after. They’re are a lot smaller for one thing, they're cheaper, and their gestation is less than half that of cattle. So it was really thinking that sheep are small, cheap cows was the reason why we chose them.

Chris - How did Dolly go down? Were you sort of celebrated and did you get a good reception to what you announced you've done or did you face quite a bit of controversy?

Ian - We've got an enormous amount of publicity of course and a lot of skepticism. Some people doubted whether Dolly was really a clone. If you explain to people the reason why you're doing this sort of thing the majority would become supportive but a small proportion would be hostile to experiments with animals.

Chris - And some people expressed concern that perhaps there would be accelerated aging and that kind of thing on the part of Dolly. Was that borne out by experimentation?

Ian - It's actually very difficult to do the experiments in sheep. It's much easier to do them in mice. You really do have a shorter generation interval and lifespan. I don't think that there is any evidence of this but it's quite a difficult and expensive experiment to do.

If you have to produce another generation and wait another generation and wait, to see if your changing lifespan or not.

Chris - Because there's a recent paper in one of the Nature journals, where they actually got the skeleton of Dolly and C.T. scanned, because one of the criticisms had been that there was premature arthritis and did they not find from these studies that actually there was no evidence really that there was an accelerated rate of arthritis. She didn't really show any signs of that compared with say a sheep born the normal way?

Ian - I think that's right. Accelerated aging was just a very slick journalistic expression to indicate that things were not quite right but I don't think there's ever been really good clear data about the aging of cloned animals.

Chris - What would you like to see the long term outcome be? If you could now wave a magic wand and we'd be in a certain position or know a certain thing, what is the final big question that you would like to see answered now?

Ian - The general understanding before Dolly was that once a cell had formed a particular type it couldn't change or be changed artificially by us. What Dolly showed was that it is possible to change cells and we had mammary cells which became equivalent to embryo cells and we got viable normal offspring. And this has created important new opportunities in medicine. What it means is that if we have somebody who let's say has motor neurone disease which reflects damage to nerves that run down the spine. If we take skin cells from them we can treat them so that they become equivalent to embryo stem cells, the cells which have the ability to form any different tissue, and then change them into the cells which are damaged in the disease and for the first time we have cells which are equivalent to those in early stages of motor neurone disease.

So if you have got a disease of the central nervous system you can't have samples from a patient like that until they've passed away. And by then there may be many secondary effects of the disease. Now in this new situation you can use them to test drugs which may be effective in slowing down or even preventing motor neurone disease. 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 inherited 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.

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