Creator of “Dolly the sheep” discards cloning in favor of embryo-free technique

Nov 20, 2007 / 08:17 am

"Therapeutic cloning" techniques may soon become a thing of the past after their foremost inventor has decided an alternative method of developing embryonic stem cells is more promising.

Edinburgh University's Professor Ian Wilmut may not be a household name, but his 1997 cloning breakthrough, in which he and his research team revealed Dolly the cloned sheep to the world, is common knowledge.

Despite his renown, the method for making Dolly has become controversial because scientists have tried to use it to clone human embryos. The technique, called somatic cell nuclear transfer, moves the DNA contents of an adult cell into an emptied egg cell that is then stimulated with an electric shock to develop into a cloned embryo.  The embryo is then destroyed for its stem cells, which many scientists believe to have great potential for medical cures.  

The method's use on humans is opposed by pro-lifers because it relies on the destruction of a human embryo.

However, Professor Wilmut now thinks a Japanese technique, which apparently sidesteps moral objections, is the way of the future.

The research of Professor Shinya Yamanaka at Kyoto University suggests a way to create embryonic stem cells without the need to create and destroy human cloned embryos.  

Professor Yamanaka has developed a technique in mice to turn skin cells into what appear to be versatile stem cells.  After his team used a virus to add four genes to adult mouse fibroblast cells, the resulting cells were filtered to find the resulting embryo-like cells that were marked with proteins typical of embryonic stem cells.

Called "induced pluripotent stem cells," these new cells look and grow like embryonic stem cells.  

The stem cells generated by the new method have also been used to generate viable chimeras.  In this case the mice stem cells were mixed with mouse embryos.  The resulting adult was able to pass down the reprogrammed DNA to its offspring.

These stem cells could be used in future medical treatments to repair damage to muscle cells after a heart attack or to repair the effects of Parkinson's.  Since the cells are identical to the patient's, the cells would not be rejected by his or her immune system.

Theoretically, these reprogrammed cells could convert into any of the 200 other cell types in the body.  It is hoped they could be used to re-grow tissue and even whole organs.

Britain's new Nobel prize winner and pioneer of stem cell research, Sir Martin Evans of the Cardiff School of Biosciences, commented on the Japanese work: "This will be the long-term solution."

While there has been some progress with embryonic cloning, which the Church is wary about because of its likely adaptation for human experimentation, researchers have little to show for their effort.

This last week a team of researchers at Oregon Health and Science University announced it had cloned rhesus monkey embryos and derived two stem cell lines from them, though one line was chromosomally abnormal.  Dr. Shoukhrat Mitalipov, one of the researchers, used 304 eggs from 14 rhesus monkeys to develop the cell lines.  Though he presented his work as a "proof of principle" he acknowledged the method's efficiency was low, and not yet a cost effective option.

Thinking along the same lines, Professor Wilmut believes that the new Japanese technique is promising enough to abandon the method he invented to clone Dolly the sheep. He commented on the Oregon research saying "It is a nice success but a bit limited."

"Given the low efficiency, you wonder just how long nuclear transfer will have a useful life," he said.

"The odds are that by the time we make nuclear transfer work in humans, direct reprogramming will work too," he continued.  "I am anticipating that before too long we will be able to use the Yamanaka approach to achieve the same, without making human embryos. I have no doubt that in the long term, direct reprogramming will be more productive, though we can't be sure exactly when, next year or five years into the future."

Professor Wilmut now backs the direct reprogramming or "de-differentiation" method which requires no embryos, calling it "100 times more interesting."

While his concerns are mainly practical, he also recognizes that the Japanese technique is "easier to accept socially."  

Reaction to Wilmut’s Announcement

The news that Professor Wilmut is to abandon cloning was welcomed by Josephine Quintavalle on behalf of Comment on Reproductive Ethics, which is against the use of human embryos in research.

"At last scientists are starting to see reason and we are going to have fact and reality, rather than hype. It could not come at a better time with the new Human Tissue and Embryos Bill having its second reading in the [House of] Lords on Monday. It is a gift to us all. We are at last going to see some common sense coming into the debate."

She suggested this new method could mark the end of proposals to create animal human hybrid embryos too, to overcome difficulties obtaining enough human eggs, since this now seems irrelevant.

"If people are doubting the straight cloning process, what on earth are they are going to say about combining two different species."

She said she was aware of the Japanese work and said it was given a cautious welcome at a recent meeting in the Vatican.

"A lot of people who have looked at it with more scientific expertise than me said it is very convincing and very interesting."

She added that this approach would attract more investment because it is not burdened with the ethical issues of creating and destroying embryos.

The National Catholic Bioethics Center has also voiced its support for the new method saying, "such strategies should continue to be pursued and strongly promoted, as they should help to steer the entire field of stem cell research in a more explicitly ethical direction by circumventing the moral quagmire associated with destroying human embryos."

Researchers stress that further research into the Japanese technique is needed to determine if it can fulfil its considerable promise.