Animal cloning

8/1/03. By Richard Twyman

The production of genetically identical animals by nuclear transfer from somatic cells to unfertilised eggs.

Animal clones are genetically identical. Natural clones occur in the form of identical twins but it is also possible to produce artificial clones by nuclear transfer. The nucleus is removed from a somatic (body) cell and placed in an egg whose own nucleus has been removed. The egg is then implanted in a surrogate mother and develops to term.

Key principles

Differentiated animal cells are unable to develop into complete animals but the nuclei of most differentiated cells retain all the necessary genetic information.

It is possible to transfer such a nucleus into an egg whose own nucleus has been removed.

Transfer to the environment of the egg reprograms the nucleus (makes it forget its history) and allows the full development of a viable animal that is genetically identical to the donor of the somatic cell.

Until 1997, cloning in mammals was only possible using nuclei obtained from very early embryos. A breakthrough was made when cloning was achieved using nuclei from adult cells.

Recent research suggests that animals produced by cloning from adult cells may age prematurely, but further investigation is necessary.

How does it work?

Nuclear transfer is carried out by fusing the donor somatic cell to an egg whose own nucleus has been removed. Fusion is achieved in a culture dish by applying an electric current. The change in electrical potential also mimics the normal events of fertilisation and initiates development.

A key aspect in the success of nuclear transfer is synchronisation of the cell cycles between the donor nucleus and the egg. Before fertilisation, the egg's nucleus is quite inactive. The nucleus of the donor cell must also be made inactive otherwise it will not be reprogrammed and development will fail. Inactivation is achieved by culturing the cell but starving it of essential nutrients. The cell stops dividing and enters a quiescent state compatible with nuclear transfer.

Table 1. Fifty years of animal cloning

1952: Cloning by nuclear transfer first demonstrated in animals. Source of nuclei was the very early embryo of the frog Rana pipens.

1956: Animal cloning in toads (Xenopus laevis) achieved by nuclear transfer from tadpoles.

1989-90: Cloning first achieved in mammals (rabbits, sheep, cows) by nuclear transfer from very early embryos.

1995: Cloning first achieved by nuclear transfer from cultured mammalian cell line, resulting in the sheep Megan and Morag.

1997: Cloning first achieved using adult sheep cell, resulting in Dolly.

1997: Cloning first achieved using a transgenic sheep, Polly.

1998-2000: Cloning achieved using adult cells in mice, cows, pigs, goats and monkeys.

2001: Cloning first achieved following gene knockout in sheep.

How is it used?

Animal cloning has the potential to overcome the limitations of the normal breeding cycle. In the future, it may be used to produce elite herds by cloning the superior animals, or to rapidly produce herds of transgenic or otherwise modified animals. Transgenic farm animals make useful bioreactors, producing valuable proteins in their milk.

Another application is the use of genetically-modified pigs as a source of organs suitable for transfer to humans (xenotransplantation).