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PARIS, Nov 14, 2007 (AFP) - Scientists said Wednesday they had created the world's first cloned embryo from a monkey, in work that could spur cloning of human cells for use in medical research.
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In a paper published online by the British journal Nature, a team in the US said they had created cloned embryos of rhesus macaques, using the same method that famously led to Dolly the Sheep and other genetically duplicated animals.

It is the first time that this technique has been successfully used to create cloned primate embryos.

The group generated two lines of embryonic stemcells from the embryos, according to the research headed by Shoukhrat Mitalipov of the Oregon Health and Science University in Beaverton, Oregon.

Dolly, the world's first cloned animal, was created in 1996, by using so-called somatic cell nuclear transfer (SCNT) in which the genetic core of an egg is removed and replaced with the nucleus of an adult cell.

The egg is then stimulated with chemicals or a jolt of electricity to prompt its division.

The list of other cloned creatures using SCNT includes mice, pigs, cats, cows and dogs.

Until now, though, there has been no cloned primate, for researchers encountered obstacles that caused cell development to be catastrophically flawed.

Work on primate cloning has also stirred controversy among ethicists, who say it could open the door to cloning human beings, not just cells. In an exceptional move, Nature said it moved forward the release of the paper because of "continuing speculation" about the research.

Researchers distinguish between "reproductive cloning" of humans, in which a cloned baby would be born and "therapeutic cloning" in which only cloned cells would be used for medical reasons and no baby would result.

Helen Wallace of Genewatch UK, a British group that monitors cloning and other activities in biotechnology, said the breakthrough announced on Wednesday would cause "a real worry" in some quarters that it would tempt a renegade scientist to create a cloned baby.

"The clear risk of an experiment [in human reproductive cloning] is of a deformed baby and maternal suffering," she told AFP in a phone interview.

"In Britain, we don't think that the technology is going to go that far because there are laws against reproductive cloning," she said. "However, in most countries around the world, there are no legal safeguards."

Stemcells are immature cells that develop into the specific tissues of the body.

Embryonic stemcells have the highest capability of all, because they can differentiate into any tissue. Scientists hope to be able to coax these cells into one day becoming replacement tissue for organs that are damaged or diseased.

Transplanted cells from a donor, however, run the risk of being attacked as intruders by the patient's immune system. By creating stemcells that are programmed with the patient's own DNA the risk of rejection would be skirted.

Mitalipov's team said they collected 304 eggs, also known as oocytes, from 14 female rhesus macaques.

The donor nucleus came from skin cells taken from an adult male monkey housed at the Oregon National Primate Research Center.

Thirty-five blastocysts, or early-stage embryos, resulted from the SCNT operation. They in turn led to two lines of self-dividing embryonic stemcells -- a success rate of 0.7 percent when compared to the number of eggs used.

"Our results represent successful nuclear reprogramming of adult somatic cells into pluripotent ES (embryonic stem) cells and demonstrate proof-of-concept for therapeutic cloning in primates," the paper said.

Wallace criticised what she said was the "very high failure rate" of SCNT.

The technique has always needed large numbers of eggs to be harvested in order to result in just a small number of cloned embryos. In addition, many cloned animals are born with genetic defects and die prematurely.

"We have concerns about the implications of using this technology because the failure rate raises questions as to whether the suffering in animals is justified," said Wallace.

The claim that the stemcells were an exact DNA copy of the donor monkey's genetic code was validated independently by a team led by David Cram of Monash University in Melbourne, Australia.

That confirmation comes on the heels of a scandal surrounding earlier claims on cloning.

In 2004, South Korean scientist Hwang Woo-suk announced he had created 30 cloned human embryos from which he derived stemcells, but his data turned out to be fake.

Cloning: a giant step
For the first time, scientists have created dozens of cloned embryos from adult primates. But what are the implications of this technical breakthrough for the future of mankind?
By Steve Connor, Science Editor
Published: 12 November 2007

A technical breakthrough has enabled scientists to create for the first time dozens of cloned embryos from adult monkeys, raising the prospect of the same procedure being used to make cloned human embryos.

Attempts to clone human embryos for research have been dogged by technical problems and controversies over fraudulent research and questionable ethics. But the new technique promises to revolutionise the efficiency by which scientists can turn human eggs into cloned embryos.

It is the first time that scientists have been able to create viable cloned embryos from an adult primate – in this case a 10-year-old male rhesus macaque monkey – and they are scheduled to report their findings later this month.

The scientists will also demonstrate that they have been able to extract stem cells from some of the cloned embryos and that they have managed to encourage these embryonic cells to develop in the laboratory into mature heart cells and brain neurons.

Scientists who know of the research said it was the breakthrough that they had all been waiting for because, until now, there was a growing feeling that there might be some insuperable barrier to creating cloned embryos from adult primates – including humans.

The development will not be welcomed in all quarters. Opponents of cloning will argue that the new technique of manipulating primate eggs to improve cloning efficiency will lead to increased attempts at creating – and destroying – cloned human embryos for research purposes.

Although it is illegal in Britain to place any such cloned embryos into the womb of a woman, many people also fear that the relative ease of being able to perform cloning using the skin cells of an adult will increase the chances of its being applied to produce a cloned baby. Scientists in South Korea reported in 2004 that they had created the first cloned human embryo but in 2006 their study was retracted after it emerged that its main author, Hwang Woo-suk , had committed fraud.

There has only been one other documented example of a human embryonic clone, but it died after a few days and did not produce stem cells. The work has so far not been replicated.

The scientists who carried out the latest primate work are believed to have tried to implant about 100 cloned embryos into the wombs of around 50 surrogate rhesus macaque mothers but have not yet succeeded with the birth of any cloned offspring.

However, one senior scientist involved in the study said that this may simply be down to bad luck – it took 277 attempts, for instance, to create Dolly the sheep, the first clone of an adult mammal.

The work was led by Shoukhrat Mitalipov, a Russian-born scientist at the Oregon National Primate Research Centre in Beaverton. Dr Mitalipov helped to pioneer a new way of handling primate eggs during the cloning process, which involved fusing each egg with a nucleus taken from a skin cell of an adult primate.

Dr Mitalipov said he was unable to comment on the study until it was published in the journal Nature. But he told colleagues at a scientific meeting this year that he had made two batches of stem cells from 20 cloned embryos and tests had shown they were true clones.

Professor Alan Trounson of Monash University in Australia said Dr Mitalipov's findings represented the long-awaited breakthrough. Despite many attempts, no one had been able to produce cloned primate embryos from adult cells, yet this had been done on dozens of other non-primate species. " This is 'proof of concept' for the primate. It has been thought by some [to be too] difficult in monkeys – and humans – but those of us who work [with] animals such as sheep and cattle thought that success rates would be much like that achieved in these species," Professor Trounson said.

"Mitalipov's data confirms this. They have the skills necessary and we can now move on to consider what might be able to be achieved in humans."

Professor Don Wolf, who led the laboratory at the Oregon National Primate Research Centre before his recent retirement, said the new procedure was based on a microscopic technique that does not use ultraviolet light and dyes, which appear to damage primate eggs.

"In the early days we tried to use that technique in the monkey and unbeknownst to us at the time that was basically damaging the egg. So one of the keys was to remove that step from the process," Dr Wolf said.

"We could now produce cloned blastocysts [embryos] in the monkey at a reasonable frequency, at least a frequency that would allow us ...to study the cloned blastocyst ," Professor Wolf said.

The Oregon team, working with a group in China, has so far produced about 100 cloned embryos that have been transferred into around 50 female macaques, but none has resulted in a full-term pregnancy, he said.

"It's possible that we're still just having bad luck. We're producing may be one in 20 or one in 30 cloned blastocysts that are 'normal' and capable of producing a pregnancy and we just haven't got them into the animal recipient at the right time to allow implantation and pregnancy to occur," Professor Wolf said.

"The focus now is going to be on therapeutic cloning and using the non-human primate as a paradigm for therapeutic cloning for what you might be able to do clinically," he said.

"We're the first to do it, although it's a tainted subject because of the fraudulent research that came out of South Korea. One can never be sure but there may be some validity to what the South Koreans did. But this would now be the first documented therapeutic cloning in a primate," he added.

A brief history of cloning

The monkey-cloning technique is the same basic procedure that resulted in Dolly the sheep. The nucleus of a healthy, unfertilised egg is removed and another nucleus from the mature skin cell of an adult animal is placed inside the egg. With careful timing and the use of electrical pulses, an embryo can be created which is a genetic clone of the skin tissue donor. It is possible to implant embryos created in this way into the womb to produce cloned animals. This so-called 'reproductive cloning' of humans is illegal in Britain and many other countries. However it has been applied to a range of animal species, including:

* Cow: Many domestic cattle have been successfully cloned. First attempt to clone an endangered species was Noah, a rare gaur ox, which was cloned in the US in 2001 but died 48 hours after birth

* Mouse: Cumulina was a common brown house mouse, cloned from adult cells at the University of Hawaii in 1997. She survived to adulthood and produced two litters, before dying in May 2000

* Horse: Called Prometea, the first cloned horse, born in Italy in May 2003

* Cat: A kitten called CopyCat was born in 2002 in Texas, and gave birth to three kittens by a natural father in September 2006

* Dog: Snuppy, born in South Korea. Doubts about its authenticity were dispelled by DNA tests. The group has also cloned two wolf cubs, called Snuwolf and Snuwolffy using the same procedure. Cloned Afghan hounds named Bona, Peace and Hope have also been born

LadyTevar wrote:7% success rate is pretty pitiful. It will be decades before they can get this to work better.