6LL3, better known as Dolly the Sheep, showed that mammalian cloning was possible in 1997

Why was a sheep the first choice for this ground-breaking work?

6LL3, better known as Dolly the Sheep, showed that mammalian cloning was possible in 1997
Wilmut I et al. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature. DOI: 10.1038/385810a0
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So, why was a sheep the first choice for this ground-breaking work?

Well, they’re cheap, and Ian Wilmut and his team at the Roslin Institute in Scotland were interested in creating a mammalian platform for the development of biological pharmaceuticals to treat human disease.

The first step of that pioneering vision was to show that it was possible to clone a mammal!

Dolly was created by transferring the nucleus (contains the DNA!) of a mammary epithelial cell from a 6-year old Finn Dorsett ewe into an Oocyte (fancy term for an egg) of a Scottish Black Face ewe that had been enucleated (had its nucleus removed).

The egg with the new nucleus was then implanted in a surrogate and Dolly was born!

Basically, Dolly is the 'clone' of the 6-year old Finn Dorsett sheep.

Although the authors do not use the word 'clone' anywhere at all in the original article.

But you may be wondering why this is such a big deal.

And the answer to that is because it’s really hard to clone animals!

Cells in adults have undergone differentiation – meaning, parts of their genomes have been deactivated so that the cells only produce the proteins required for their specific function within the body.

The researchers tricked these cells into removing all these deactivation marks and then inserted the 'reprogrammed' nuclei into Oocytes to see if they could create live lambs.

Technically, 8 lambs were reported in this paper, but Dolly was the only one that was derived from adult tissue.

The figure above shows the microsatellite markers of the recipient ewes (the surrogates), the cells (embryo derived – SEC1, fetal-derived – BLW1, and mammary-derived – OME), and the lambs that were born.

6LL3 shares the same microsatellite markers as the mammary cells she was derived from, but not the same microsatellite markers of any of the surrogate ewes.

Dolly is a bonafide copy!

And it should come as no surprise that the popular reporting on Dolly at the time highlighted how close humanity was to creating designer babies.

Or, that scientists should stop playing god.

But this work, along with earlier work in amphibians by John Gurdon, fueled the later discovery of induced pluripotent stem cells (iPSC) by Shinya Yamanaka and led to his subsequent Nobel Prize in 2012.

The scientific value of cellular reprogramming and proof that it could be done in mammals (Dolly!) was a tremendous first step in using this and similar techniques to help us understand the complexities of our genomes, how they function, and, ultimately, the usefulness of cloning (and stem cells!) for the development of treatments for human disease.