Conceiving a Clone : 1995

The Details: Timeline:
1995: A precursor to Dolly.

Scientist Profiles:
Ian Wilmut
Keith Campbell

In July 1995, Ian Wilmut and Keith Campbell of the Roslin Institute in Scotland successfully cloned two sheep, named Megan and Morag, from differentiated embryo cells. The idea to clone sheep was arrived at by Ian Wilmut as an answer to a gene insertion project he was researching. At the time, time inserting genes into embryo cells was a difficult and tedious process. Few embryos survived the insertion of a gene, even fewer incorporated the gene into their genetic code, and even fewer organisms developed properly and used the gene in all of their cells. In 1986, when Wilmut heard a rumor that Steen Willadsen had successfully cloned cattle from differentiated embryo cells, he decided to abandon traditional gene insertion methods and investigate the possibility of cloning. He knew that older cells could more easily be manipulated in a lab. If cloning from more advanced cells was possible, Wilmut knew he could manipulate these differentiated cells in the lab, and then produce a limitless number of clones from them. In 1990, Wilmut teamed up with cell cycle biologist Keith Campbell to begin the cloning study.

Building upon earlier research by Lawrence Smith of the Roslin Institute, Campbell believed that in order for cloning by nuclear transfer to work, the two cells, the differentiated embryo cell and the egg, had to be synchronized in their cell cycles. As cells duplicate, they follow a certain pattern in checking and duplicating their DNA. It was believed that if the DNA of the embryo cell was not in the same stage of the cell cycle as the egg's cell DNA, then cloning would be ineffective. Campbell also believed that directly after fertilization, the egg enters a state of suspended animation, the Gap Zero, or G0 state, while it coordinates its two sets of DNA. In this case, the embryo cell should also be in the G0 state. To solve this problem, Campbell devised the clever process of starving the embryo cell until it entered the suspended state, G0.

After synchronizing the cell cycles, Wilmut and Campbell then proceeded to fuse the differentiated embryo cell with an enucleated egg using an electric current. From the process, Wilmut and Campbell obtained two live Welsh mountain sheep, Megan and Morag, which where cloned from differentiated embryo cells.

The Roslin Technique Details.
The Birth of Dolly
The Birth of Polly

Web Links:
The Roslin Institute Online
Interview With Ian Wilmut

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