She looks exactly like any other sheep. But the cloning method used to produce Dolly may change our lives
By Roger Highfield, Science Editor
THE possibility that an adult human can be cloned from a single blood or skin cell was raised yesterday with the announcement that scientists have produced the world's first clone of an adult animal.
The clone, a Finn Dorset sheep called Dolly, paves the way to unprecedented genetic manipulation of farmyard animals, more cheaply and more accurately than ever before.
A single cell could be taken from a prize bull, elite racehorse or award-winning pig, and hundreds of identical animals produced using the patented cloning technology developed at the Roslin Institute and PPL Therapeutics, near Edinburgh.
Introduction or deletion of genes in the cloned cells also offers the means to make animals that produce drugs in their milk, grow faster for meat production, or are resistant to diseases such as scrapie and BSE.
The first sheep altered using the method may be born later this year, though it will be several years before scientists will have developed the means to alter many genes simultaneously, which will be necessary to boost growth or make leaner beef.
But any other use of the technology, for instance to mass-produce human eggs for use in in-vitro fertilisation, is outlawed, said Dr Ron James, managing director of PPL.
Dr James said he had advised relevant regulatory committees about the development and its implications but added: "An Act of Parliament specifically forbids even doing with human eggs what we have done with sheep eggs."
And he acknowledged that there are limitations to the use of the technology at the farm - herds of identical livestock are at greater risk of disease - in addition to the inevitable qualms about mass-producing identical animals or designing animals for human use.
In earlier work, the Roslin team unveiled Megan and Morag, sheep that had been cloned by taking a cell from an early embryo, mass-producing it in the laboratory, and using these cells to "re-program" two emptied eggs.
Until now it has been thought impossible to perform the same feat using cells from an adult animal. Unlike embryo cells, which have the potential to develop into a vast range of cell types, adult cells are differentiated, that is they have turned into a liver, brain or, in this case, a cell from the udder.
Dr Ian Wilmut, Dr Keith Campbell, and Dr Jim McWhir at Edinburgh's Roslin Institute, working with Angelica Schnieke and Dr Alex Kind at PPL Therapeutics, will announce the feat this week in the journal Nature, cloning cells from the mammary gland and connective tissue.
This breakthrough, the first time that any new born mammal has been derived from adult cells, offers PPL the possibility of using the technique to alter genetically sheep much more easily than before.
Previously, scientists have used a hit-and-miss affair: injecting DNA into an embryo and hoping that it is taken up, which only happens in 10 per cent of cases or less.
Instead, genes can be introduced into large numbers of cloned cells. Then the cells where genetic engineering has been successful are selected and mass-produced, producing a herd of identical "transgenic" animals.
"We are looking at things like introducing genes for blood-clotting proteins that haemophiliacs lack," said Dr James, adding that they focused on cloning mammary cells to make it easier to ensure that human proteins will be made in the animal's milk.
Moreover, the technique also enables the team to knock out genes, raising the possibility of deleting the prion protein - one linked to BSE - from cows so they are resistant to the disease. "Cloning cattle should be possible, because the embryology is not too dissimilar to sheep," he said, adding that pigs would also be studied.
Cloning from adult animals may be more useful to agriculture than cloning from embryos, as farmers will be able to pick particularly productive and disease-resistant adult animals to copy.
In this case, the resulting lamb - Dolly - was genetically identical to the sheep from which the cell was taken. Dolly is now several months old and is showing every sign of normal development.
"Animal breeding companies are already showing interest in the use of this technology to multiply their best animals," said Roslin team leader Dr Ian Wilmut. "Genetic modification of the donor cells in culture before they are used in nuclear transfer will also allow us to introduce very precise changes in their DNA and open up the possibilities for a range of new products for the treatment of, for example, cancers and inflammation. What this will mostly be used for is to produce more health care products. It will enable us to study genetic diseases for which there is presently no cure and track down the mechanisms that are involved. The next step is to use the cells in culture in the lab and target genetic changes into that culture."
The Roslin Institute has agreed to grant PPL an exclusive licence for the use of the technology to make human protein drugs. Patents to protect the new technology have been applied for.
Previous efforts to clone Megan and Morag from embryo cells ran into a problems. Six in every 10 attempts made in the original experiments worked. Five clones were produced but three sisters died - two within minutes of birth and the third within 10 days.
Post-mortem examinations revealed kidney and cardiovascular abnormalities.
