It's 20 years since Dolly the sheep was born at the Roslin Institute in Edinburgh on 16 July 1996. She was the first mammal to be cloned by the technique known as Somatic Cell Nuclear Transfer or SCNT for short.
The "somatic" bit just means a cell that is not a sex cell (a gamete i.e. an egg or a sperm) was used to provide the DNA for Dolly.
The "nuclear transfer" bit refers to the way the nucleus (including all the DNA of the sheep that was being cloned) was transferred from its original cell from the mammary gland of a Finn Dorset sheep (and so we see the derivation of the Dolly name, a little dedication to Ms Parton).
Who was Dolly's mum? At the time of her birth, the sheep that provided the original mammary cell containing Dolly's DNA had already been dead for 3 years. The cell was being grown in a cell line - millions of identical cells (clones) endlessly dividing in plastic bottles and being fed regularly with a carefully prepared soup of nutrients.
Meanwhile, the scientists removed (and disposed of) the nucleus from an egg cell taken from a different breed of sheep (the black-faced sheep) to leave an anucleate cell. In other words, an egg cell without a nucleus, an egg cell who can be made whole again by being joined with one of those cloned cells growing in the plastic bottles. So with the aid of a little electric shock, the cloned cell with a nucleus fuses with the empty egg cell and we are left with what we might call a zygote - a diploid cell, the first cell of Dolly the sheep, a cell that will divide by mitosis again and again and slowly build a new sheep, Dolly the sheep, whose every cell contains identical DNA to the 'mum', or should we say twin sister, of the sheep who provided the original mammary cell.
Dolly grew up to be a mum of six lambs, but her health could have been better. She suffered from arthritis at a relatively early age, which was the source of some interest in the media. She eventually died from the effects of a virus she caught along with some of the animals she shared accommodation with. It's an unpleasant disease called sheep pulmonary adenomatosis that results in tumours forming in the lungs. She died a few months before her seventh birthday when other Finn Dorset sheep could expect to live until twelve or so.
Speculation in the media and scientific literature were keen to put her poor health and premature death down to the cloning. One particular aspect of Dolly which remains interesting is that her telomeres were shorter that those of a sheep the same age. Telomeres are a section of nucleotides at the ends, the tops and tails, of each chromosome and they shorten just a tiny bit each time a cell replicates its DNA ready for mitotic division. This happens to cells that are part of a multicellular organism. A cell in a cell line, like those cells who are the cloned progeny of that sheep mammary cell, just divide and divide all day long, ad infinitum, with no effect on their telomeres. This is apparently due to a telomere rebuilding exercise supervised by telomerase enzyme.
It's a popular theory that telomere shortening is the key driver in ageing - imagine if every cell in your body could only divide a fixed number of times before snipping of the chromosome ends begins to impact on genes present near these ends. Gradually, the likelihood of interfering with the protein products of these damaged genes will lead to death. And you can bet there are many scientists working on ways to make and deliver telomerase enzyme in our quest for immortality.
Though it's worth pointing out that Dolly's telomeres, while not quite as long as a sheep her own age, were not that much shorter.
Another popular line of thought is that epigenetic changes in the DNA from the sheep who supplied the original mammary cell may have been a source of the health problems lived out by Dolly. The science of epigenetics is yet another relatively new area of biology that is causing great excitement. It's about the way genes are switched on an off in an organism - a process that can be carried over to offspring. So things that happen in your life can be passed on, via the genes in your sperm or egg, to your children. If only Lamark had known about this stuff, he would have had a much better chance battling out the evolution through acquired characteristics vs natural selection debate.
However, maybe Dolly just happened to be unlucky. She has several twin sisters derived from the same cell line, but born a few years later, and Debbie, Denise, Dianna and Daisy are all doing quite well at the ripe old age of 9 (around 70).
Select sources:
http://www.roslin.ed.ac.uk/public-interest/dolly-the-sheep/a-life-of-dolly/
https://www.statnews.com/2016/07/26/dolly-sheep-clone-aging/
