Although the cloning of Dolly the sheep in 1996 created a major furor in the media, from a scientific viewpoint it was a relatively small step in a developing technology. Cloning animals relies on the technique of nuclear transplantation . This actually dates back to 1952 when nuclei from early frog embryos were transplanted into eggs from which the nucleus had previously been removed. Some attempts gave rise to normal embryos. Although animal somatic cells differentiate and eventually become irreversibly committed to specialized roles, their nuclei nonetheless retain a complete genome. (A few exceptions, such as red blood cells, lose their nucleus.) Under some circumstances the cytoplasmic environment in the egg cell can reprogram nuclei from somatic cells. Not surprisingly, the earlier the stage of development in the nuclei, the easier they are to reprogram.
Nuclear transplantation can be used to generate a group of identical cloned animals . Several nuclei from the same donor are transplanted into a series of enucleated eggs.
Since the 1980s, nuclear transfer in a variety of mammals has been performed successfully using nuclei from early embryos (morula or blastocyst stages). Fusing a somatic cell with an empty egg cell transfers the donor nucleus into a completely nondifferentiated cytoplasm.
A brief electrical pulse fuses the two cell membranes into one embryo.
In 1995, nuclei from cultured embryonic cells of sheep were successfully transplanted.
Two lambs, Megan and Morag, were produced by this technique at the Roslin Institute in Edinburgh, Scotland.
In 1996 the same research group produced Dolly by nuclear transplantation from an adult cell line—the epithelial layer of the mammary gland. Thus Dolly was the first mammal to be produced using a nucleus from a differentiated cell line.
DOLLY THE CLONED SHEEP
Cells in an early embryo are totipotent ; that is, they possess the ability to divide and give rise to any type of body cell (liver, spleen, brain, etc.). Later on, cells lose this ability. They become committed to generating a particular tissue such as the nervous system or the digestive tract. Most cells in an adult animal can either no longer divide or else only give rise to a particular, specialized type of cell. During development, different genes are expressed in different tissues and others are shut down. So while almost all adult cells retain a complete genome, they don’t retain the ability to develop into new individuals.
The cloning of Dolly the sheep showed that it is possible to reset the clock of an adult cell to zero and start development again. In Dolly’s case, the trick was to starve cultured udder cells from the donor animal so that both the cell and the DNA stopped dividing (i.e., the cells entered the G 0 stage of the cell cycle). What exactly happens to the DNA when the cell is starved is not known. However, there is probably some modification, including demethylation, which converts the DNA back to a form resembling that of an embryonic cell. When the resting G 0 nucleus is placed in an egg cell whose own nucleus has been removed, it starts dividing again. The egg is then transplanted into a female animal, where it will develop into an embryo. If all goes well, a baby will be born.
Early in 1996, at the Roslin Institute in Scotland, the world’s first cloned animal, Dolly the sheep, was born. The donor nucleus came from a mammary gland cell (also known as the udder) from a pregnant ewe. Since Dolly’s birth, a variety of other animals, including cattle, pigs, goats, mice, and cats have been cloned. Dolly herself has been mated and gave birth to a lamb of her own—named Bonnie—during Easter 1998.
Strictly speaking, Dolly is not a complete clone. In addition to the nucleus, which contains the majority of the genetic information, animal cells contain a few genes in their