Genetic flaws hit cloned animals clones hit by flaws in genes

Steve Connor
Thursday 29 April 1999 23:02

CLONED ANIMALS have been found to suffer from serious genetic defects - a discovery that could deliver a fatal blow to hopes of ever using cloning for human reproduction.

French scientists have for the first time found unequivocal evidence that cloning inter-feres with the normal function of genes, a factor that can lead to debilitating illnesses and death. Ian Wilmut, the scientist at the Roslin Institute near Edinburgh who cloned Dolly the sheep, said the findings are the most detailed so far to explain the side-effects resulting from the cloning process.

Professor Wilmut, who cloned Dolly by transferring the nucleus of an udder cell taken from a six-year-old ewe into an unfertilised egg that had its own nucleus removed, said inherent problems with the technique may prevent it ever being applied to humans.

"It astonishes me that people would consider human reproductive cloning and this research adds further concern," he said.

"It is the most detailed information to emerge so far of the abnormalities arising from nuclear transfer and it is further evidence that we should be extremely cautious in ever applying this to humans."

Dolly, the first adult clone of a mammal, raised the prospect of scientists being able to clone identical copies of adult human beings. Although Dolly herself appears normal, evidence that other animals created by the same process suffer from genetic disorders will make human reproductive cloning less likely to receive ethical consent.

The French team, led by Jean-Paul Renard of the Institut National de la Recherche Agronomique in Jouy-en-Josas, investigated the death of a calf that was cloned from a skin cell taken from the ear of a 15-day-old calf, which was itself a clone of a bovine embryo.

The calf that died had developed normally for the first six weeks but then suffered a rapid depletion of blood cells and severe anaemia caused by the incomplete development of its lymph glands.

In a research paper published in The Lancet, the scientists say: "This is the first report of a long-lasting defect associated with somatic [adult cell] cloning."

Because the "parent" of the calf was itself an embryonic clone that had suffered no ill-effects, the scientists were able to conclude that the death of the calf must have been due to the process of nuclear transfer from an adult cell.

Professor Wilmut said the cause of the problems could be connected with the genetic "reprogramming" of the adult cell nucleus, which is necessary for it to switch on all the genes needed to create a fully grown animal from a single cell.

"What has to happen is that the adult cell's genes are switched off and the genetic reprogramming needs to be done.

"People were surprised this could happen at all, so it is not surprising that sometimes it almost happens but not quite enough," Professor Wilmut said.

Cloning by nuclear transfer is known to cause an unusually high number of deaths. Up to 50 per cent of cloned sheep foetuses die in the womb - 10 times higher than normal - and about 20 per cent of live births result in the animals dying within the first few days, about three times higher than the normal death rate immediately after birth.

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