1996: July – Dolly, the first cloned sheep, was cloned by nuclear transfer from adult cells

On July 5, 1996, Roslin Institute in Scotland and PPL Therapeutics created the first ever organism to be cloned from adult cells, Dolly.  This ordinary-looking lamb has extraordinary origins, being not only a cloned lamb with no father, but also the world’s first clone from differentiated adult cells, a feat that was considered scientifically impossible. 

Ian Wilmut, Keith Campbell and their team cloned Dolly using adult udder cells from a mature, 6-year old Finn Dorset ewe.  They transferred the nucleus of the cell into an enucleated unfertilized sheep egg.  They were then fused together with an electric current, so that the egg contained a complete set of chromosomes.  The cells were cultured in the lab and put into a third sheep, which acted as a surrogate mother and brought it to term.  Out of the 277 trials, Dolly came as the sole survivor.  Dolly was genetically identical to the sheep which supplied the udder cells.

Nuclear transfer is not new.  It was first used in 1958 to clone frogs (by Briggs and King) and in the 1980s to clone cattle and sheep, all from embryonic cells.  Scientists before were convinced that differentiated cells are stuck to become what they are, and have lost the ability to form an embryo and all the different types of cells in a complete organism.  What made Dolly possible where others have failed? It seemed to have been the step they took in starving the mammary cells for 5 days before the nuclear transfer.  Wilmut and Campbell had learnt previously that a newly fertilized egg enters a state of suspended animation to coordinate its DNA with the new DNA from the sperm. They starved the udder cells by giving it a nutrient solution with just enough nutrients to keep it alive. This move simulated the natural suspended state, freezing the cells into a dormant phase of their division cycle, the G0 state.  They then fused the adult cells with an unfertilized, enucleated egg with an electric current. The cell cycles of the 2 cells were thus synchronized, and it made the chromosomes more susceptible to being ‘reprogrammed’ to initiate the growth of a new sheep.

The birth of Dolly proved cells in our bodies are not ‘fixed’ into becoming predefined cell types. Rather, they contain all the genes which are workable and are necessary for producing a complete organism, i.e. totipotency can be re-established. The success opened the door for introducing much more precise genetic modifications in animals. Together with gene targeting, scientists can make exact genetic changes in cloned offspring quicker, since with cloning you can be sure each animal is identical and the genes will be expressed. The new cloning technique may be used in the future to produce animals that will secrete in their milk valuable drugs. After improving the technique, it will definitely be useful in all sorts of biological investigations.  It could be used to mass-produce genetically identical animals for research on human diseases. This technique may also help xeno-transplantation, and preserve wild or endangered species.

There were also uncertainties as to the short-term practical uses of this new technique. The success rate at the time was very low.  Out of 277 nuclear transfers, only 29 came as developing embryos, and only one birth survived.

The announcement of Dolly’s birth astounded the public and sparked intense debates as to the possibilities of human cloning. This achievement was a major event in the history of cloning and has led following investigations.

Photo courtesy of the Roslin Institute