Dolly the Sheep was announced to the word with a paper published in 1997, in the journal Nature, succinctly titled “Viable offspring derived from fetal and adult mammalian cells”. Ian Wilmut, Keith Campbell, Jim McWhir and William Ritchie from The Roslin Institute described how they produced the first animal cloned from an adult cell.
The team wanted to know whether cloned animals could be produced from cells at different stages of development, so donor cells were collected from a recently fertilised sheep embryo, a lamb fetus and the udder of an adult sheep. The cells were collected from three different breeds of sheep, Poll Dorset, Black Welsh Mountain and Finn Dorset respectively.
In preparation for cloning, these donor cells were grown to make cell cultures. Egg cells were collected from donor Scottish Blackface sheep and the nucleus, containing the DNA, was removed. The eggs were fused with the donor cells, ‘activated’ using electrical stimulation and cultured for a week in the lab to develop into early stage embryos. The cloned embryos were transferred to surrogate Scottish Blackface ewes, eight of which gave birth to cloned lambs. Different breeds of sheep were chosen for the donor cells and the egg donor and surrogate sheep, so that the team could see straight away that the offspring were not genetically related to their surrogate mothers or the egg donors.
Eight live lambs were born to the surrogate ewes – four lambs were cloned from the embryo cells, three from the fetal cells, and only one lamb was successfully cloned from the udder cells of the adult sheep. DNA analysis of the lambs and the original cells confirmed that all of the lambs were genetically identical to their donor cells.
The lamb cloned from the udder cell was the first example of an animal cloned from an adult cell and although only referred to as “6LL3” in the Nature paper, she was later named Dolly, after the singer Dolly Parton. Dolly’s birth was a significant milestone because it proved that scientists could turn back the clock on a fully developed adult cell to make it behave like a cell from a newly fertilised embryo.
Dolly was part of a larger project to create transgenic (genetically modified) sheep that produced therapeutic proteins in their milk. Although scientists at The Roslin Institute no longer create cloned animals, their work on genetically modified livestock continues to this day. Recently, the development of genome editing technology has enabled scientists to make precise changes in the DNA of animals and plants, and is being used at The Roslin Institute in a range of research projects that aim to improve livestock health, productivity and welfare.
Written by Selene Jarrett