Tuesday, November 13, 2007


Leading article: Cause for excitement, hope - and also caution


Published: 12 November 2007

The news that a team at the Oregon National Primate Research Centre has created dozens of cloned embryos from a 10-year-old rhesus macaque monkey will be read with interest across the scientific world. This is the first time scientists have been able to create embryonic cloned embryos using the DNA of an adult primate.

Such research has great significance. Scientists have successfully cloned several types of animals over the past decade, ranging from sheep to dogs. But before now it had never been done successfully with primates. Scientists will be eager to study Dr Mitalipov's techniques to see if they can be applied to human embryos, which are genetically similar to those of primates.

Success in human embryo cloning has been elusive. Claims from a South Korean laboratory in 2004 proved to be fraudulent. The one other documented example of a human embryonic clone died after a few days. And the work has not so far been replicated. But this latest research, which will be published in Nature this month, seems to promise a breakthrough.

This has exciting medical implications. It could open the door to the next stage of therapeutic cloning; the creation of stem cells for tissue, muscle and nerve transplants that will not be rejected because they will be made from the same DNA as the patient. People suffering from Parkinson's, Alzheimer's, heart disease, diabetes and spinal cord injuries could all potentially benefit.

But it also raises familiar ethical questions, in particular the spectre of human reproductive cloning. Attempts by the Oregon institute to produce live cloned primate births have failed. Embryos were implanted in the womb of 50 surrogate macaque mothers with no success. But there is still optimism among scientists that reproductive cloning of primates is possible. Some point to the fact that it took 277 attempts to create Dolly, the cloned sheep. But the flip-side of this optimism is that, if proved correct, it could help a maverick scientist to produce a cloned baby.

Creating human clones would raise a whole host of difficult moral questions. But the most powerful argument against the practice is that it would be inhumane to the cloned baby. Cloned animals have not been healthy specimens, with most suffering from genetic defects. As one of the "creators" of Dolly, Professor Ian Wilmut, has argued, cloning human beings would be dangerous and irresponsible.

How can we prevent this from happening? One of the suggestions in a United Nations report released yesterday is an international ban on all human cloning. Efforts to develop an international framework of regulation would be welcome. At the moment there is a serious risk that an unscrupulous scientist could exploit the different levels of legal protection that exist in different countries. But a total ban would be going too far because it would end cloning research by reputable scientists for purely therapeutic purposes.

Britain is at the forefront of cloning technology. Here, therapeutic cloning for stem-cell research is permitted under licence, but it is illegal to implant a cloned human embryo in a woman's womb. That is a sensible balance – and one that ought to be adopted internationally.

Reproductive human cloning is certainly a worrying prospect. But that is not a reason to fear or deprecate research of the sort that is taking place in Oregon. Nor is it an excuse for panic. Rather, it reinforces the need to build legal safeguards in our societies against the unethical application of these fascinating new scientific techniques.






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





Published: 12 November 2007

Perhaps the most important question raised by the latest study into primate cloning is whether this brings us any nearer to the prospect of a cloned human baby. Many scientists would say "no" on the grounds that this is not the intention of the researchers involved, and in any case such activity is illegal. I believe they are wrong.

The technology of somatic cell nuclear transfer – cloning of an adult – is difficult. In 1996, it took 277 attempts to create Dolly the sheep, and the success rate is still far too low to make it as simple as, say, in-vitro fertilisation.

Primates – including humans – posed even greater problems than many other species. No matter how hard scientists around the world tried, they were unable to clone a monkey offspring from an adult animal. Meanwhile, attempts on human eggs were mired in scientific misconduct. It has even been suggested that there may be some inherent barrier to Dolly-style cloning for all primates. However, the latest research coming out of Oregon suggests that the barrier was due to a flawed laboratory technique rather than a fundamental biological block.

Although the Oregon scientists have not yet succeeded in producing a cloned offspring, they have managed to produce dozens of cloned embryos, and some of them have developed well enough to generate stem cells – the mother cells of the body from which all specialised tissues derive. The technique will no doubt be studied by those scientists interested in producing cloned human embryos for the same purposes.

And if it is possible to improve the efficiency at which an unfertilised human egg can be merged with an adult's skin cell, then that too would be useful for anyone contemplating reproductive cloning.

Reproductive cloning is banned in about 50 countries in the world, which means that it is still legal in the majority of nations. Attempts by the UN to formulate an international ban ground to a halt a couple of years ago because some countries wanted a total ban on all types of cloning – such as therapeutic cloning – which Britain and other nations opposed.

In a report today, the United Nations University calls for a new global consensus to outlaw reproductive cloning so that there can be no place in the world where it could be undertaken legally. The problem we all face is that science is not static and apparent technical barriers to human cloning can evaporate overnight. If the cloning of human embryos becomes straightforward and reliable, then someone, somewhere will attempt to transplant a cloned embryo into the womb of woman. We may not be able to stop such a chilling development.








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