Dolly creator Prof Ian Wilmut shuns cloning
By Roger Highfield, Science Editor
Last Updated: 6:30pm GMT 16/11/2007Page 1 of 3
The scientist who created Dolly the sheep, a breakthrough that
provoked headlines around the world a decade ago, is to abandon the
cloning technique he pioneered to create her.
The life and death of Dolly the diva, by Ian Wilmut
Ian Wilmut: The status of the human embryo
Have you say: Can cloning ever be ethical?
Prof Ian Wilmut's decision to turn his back on "therapeutic cloning",
just days after US researchers announced a breakthrough in the
cloning of primates, will send shockwaves through the scientific
establishment.
Ian Wilmut, the creator of Dolly the Sheep
He and his team made headlines around the world in 1997 when they
unveiled Dolly, born July of the year before.
But now he has decided not to pursue a licence to clone human
embryos, which he was awarded just two years ago, as part of a drive
to find new treatments for the devastating degenerative condition,
Motor Neuron disease.
Prof Wilmut, who works at Edinburgh University, believes a rival
method pioneered in Japan has better potential for making human
embryonic cells which can be used to grow a patient's own cells and
tissues for a vast range of treatments, from treating strokes to
heart attacks and Parkinson's, and will be less controversial than
the Dolly method, known as "nuclear transfer."
His announcement could mark the beginning of the end for therapeutic
cloning, on which tens of millions of pounds have been spent
worldwide over the past decade. "I decided a few weeks ago not to
pursue nuclear transfer," Prof Wilmut said.
Most of his motivation is practical but he admits the Japanese
approach is also "easier to accept socially."
His inspiration comes from the research by Prof Shinya Yamanaka at
Kyoto University, which suggests a way to create human embryo stem
cells without the need for human eggs, which are in extremely short
supply, and without the need to create and destroy human cloned
embryos, which is bitterly opposed by the pro life movement.
advertisementProf Yamanaka has shown in mice how to turn skin cells
into what look like versatile stem cells potentially capable of
overcoming the effects of disease.
This pioneering work to revert adult cells to an embryonic state has
been reproduced by a team in America and Prof Yamanaka is, according
to one British stem cell scientist, thought to have achieved the same
feat in human cells.
This work has profound significance because it suggests that after a
heart attack, for example, skin cells from a patient might one day be
manipulated by adding a cocktail of small molecules to form muscle
cells to repair damage to the heart, or brain cells to repair the
effects of Parkinson's. Because they are the patient's own cells,
they would not be rejected.
In theory, these reprogrammed cells could be converted into any of
the 200 other type in the body, even the collections of different
cell types that make up tissues and, in the very long term, organs
too. Prof Wilmut said it was "extremely exciting and astonishing" and
that he now plans to do research in this area.
This approach, he says, represents, the future for stem cell
research, rather than the nuclear transfer method that his large team
used more than a decade ago at the Roslin Institute, near Edinburgh,
to create Dolly.
In this method, the DNA contents of an adult cell are put into an
emptied egg and stimulated with a shock of electricity to develop
into a cloned embryo, which must be then dismantled to yield the
flexible stem cells.
More than a decade ago, biologists though the mechanisms that picked
the relevant DNA code that made a cell adopt the identity of skin,
rather than muscle, brain or whatever, were so complex and so rigidly
fixed that it would not be possible to undo them.
They were amazed when this deeply-held conviction was overturned by
Dolly, the first mammal to be cloned from an adult cell, a feat with
numerous practical applications, most remarkably in stem cell science.
But although "therapeutic cloning" offers a way to get a patient's
own embryonic stem cells to generate unlimited supplies of cells and
tissue there is an intense search for alternatives because of
pressure from the pro-life lobby, the opposition of President George
W Bush and ever present concerns about cloning babies.
Prof Wilmut's decision signals the lack of progress in extending his
team's pioneering work on Dolly to humans.
The hurdles seem to have been overcome a few years ago by a team led
by Prof Hwang Woo-Suk in South Korea, with whom he set up a
collaboration.
Then it was discovered Prof Hwang's work was fraudulent. "We spent a
long time talking to him before discovering it was all a fraud," he
said. "I never really got started again after that."
advertisementAnd Prof Wilmut believes there is still a long way to go
for therapeutic cloning to work, despite the headlines greeting this
week's announcement in Nature by Dr Shoukhrat Mitalipov and
colleagues at Oregon Health & Science University, Beaverton, that
they cloned primate embryos.
In all Dr Mitalipov used 304 eggs from 14 rhesus monkeys to make two
lines of embryonic stem cells, one of which was chromosomally
abnormal. Dr Mitalipov himself admits the efficiency is low and,
though his work is a "proof of principle" and the efficiency of his
methods has improved, he admits it is not yet a cost effective
medical option.
Cloning is still too wasteful of precious human eggs, which are in
great demand for fertility treatments, to consider for creating
embryonic stem cells. "It is a nice success but a bit limited,"
commented Prof Wilmut. "Given the low efficiency, you wonder just how
long nuclear transfer will have a useful life."
Nor is it clear, he said, why the Oregon team was successful, which
will hamper attempts to improve their methods. Instead, Prof Wilmut
is backing direct reprogramming or "de-differentiation
free route pursued by Prof Yamanaka, which he finds "100 times more
interesting.
"The odds are that by the time we make nuclear transfer work in
humans, direct reprogramming will work too.
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."
Prof Yamanaka's work suggests the dream of converting adult cells
into those that can grow into many different types can be realised
remarkably easily.
When his team used a virus to add four genes (called Oct4, Sox2, c-
Myc and Klf4) into adult mouse fibroblast cells they found they could
find resulting embryo-like cells by sifting the result for the one in
10,000 cells that make proteins Nanog or Oct4, both typical markers
of embryonic cells.
When they studied how genes are used in these reprogrammed
cells, "called induced pluripotent stem (iPS) cells", they were
typical of the activity seen in an embryo. In the test tube, the new
cells look and grow like embryonic stem cells.
And they were also able to generate viable chimaeras from the cells,
where the embryo cells created by the new method could be mixed with
those of a mouse embryo to grow into a viable adult which could pass
on the DNA of the reprogrammed cells to the next generation.
None the less, there will have to be much work to establish that they
behave like embryo cells, let alone see if they are safe enough to
use in the body. Even so, in the short term they will offer an
invaluable way to create lines of cells from people with serious
diseases, such as motor neuron disease, to shed light on the
mechanisms.
Given the history of fraud in this field, the Oregon research was
reproduced by Dr David Cram and colleagues at Monash University,
Melbourne. "At this stage, nuclear transfer to create pluripotent
stem cell lines remains an inefficient process," said Dr Cram.
"De-differentiation may indeed prove to be more efficient method but
there is still much research to do to optimise nuclear transfer and
de-differentiation and demonstrate genetic normality after these
manipulations.
Prof Robin Lovell-Badge of the National Institute of Medical
Research, Mill Hill, said the overall success rate of 0.7 per cent
reported by the team Oregon "is still too low to be used in human
studies, especially given the difficulty in obtaining eggs for
research.
"I do think de-differentiation is very likely to be the future - once
this has been shown to work in humans (I hear rumours that it is) and
to work well with a reliable cell source (that is, without too many
mutations, and so on)".
advertisementBritai
cell research, Sir Martin Evans of the Cardiff School of Biosciences,
commented on the Japanese work: "This will be the long-term solution."
The news that Prof 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 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 added this work 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 is 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.
Quintavalle said that the Oregon work was much more disappointing
than suggested by newspaper headlines.
"We read that 15,000 monkey eggs were used in order to develop the
new protocol; that the current application of this protocol required
304 eggs to derive 2 embryonic stem cell lines, one of which was
chromosomally abnormal, delivering an extremely low success rate of
0.7 per cent.
"The researchers acknowledge that they have little idea of what
separates the successes from the failures, and whilst it might be
theoretically possible to repeat this research in humans it is
unlikely that anybody could obtain the number of eggs necessary for
such experiments.
"It is also noted that the embryos created were morphologically poor
and attempts at pregnancy on 77 occasions were all unsuccessful.
Shoukhrat Mitalipov, the lead scientist is quoted as saying, 'No
pregnancy made it even to day 25.'"
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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