It was a breakthrough decades ahead of its time. On 23 February, 1997, the world learnt that British scientists Ian Wilmut and Keith Campbell had created the first clone of an adult mammal. 'They have taken a cell from a sheep's udder and turned it into a lamb,' ran The Observer's front-page story. Dolly the Sheep had arrived.
The creation of Dolly - at the Roslin Institute, the agricultural research centre near Edinburgh - opened up the prospect of an era of new medicines and treatments for conditions such as Alzheimer's and Parkinson's. It also triggered a fierce debate about the prospects of cloning humans and creating armies of Saddam Hussein doppelgangers.
Yet, despite the fuss, neither medicines nor cloned dictators have materialised. For a technology that promised to transform the world, this absence is startling. Indeed, most recent headlines have focused on South Korean scientist Hwang Woo-suk. He once claimed to have cloned human embryos and extracted stem cells, which have the potential to be used as life-saving medicines. However, Hwang has since been revealed to be a fraud.
Controversy, but not results: not much of an epitaph for Dolly. She died in 2003 and her stuffed remains are now displayed in Edinburgh's National Museum of Scotland. Will we soon wonder what was so special about her? Why have we not seen more scientific breakthroughs emerging - particularly in Britain?
It is an issue that vexes Wilmut. At present the best use of cloning has been the creation of a herd of cows that can make human antibodies, he believes. 'This has really important implications,' he said in an interview with The Observer last week. 'If a virus or a cancer gets past a person's immune system, he or she is in trouble. Soon we may be able to use cattle to provide antibodies that would pick up such a tumour or microbe. It has great potential.' The trouble is that the herd is the creation of Jim Robl of Hematech, a company based in the United States.
In fact, Wilmut has moved on from the Roslin Institute, where he did his pioneering work, to become director of Edinburgh University's centre for regenerative medicine. In effect he has turned his back on agricultural research and moved into medical science. A major motivation seems to have been the failure of Roslin to take advantage of his cloning work for use in agriculture, though Wilmut is reticent on this issue.
A few years ago the companies set up by the institute to exploit his cloning techniques were sold to the US biotechnology giant, the Geron Corporation. With those companies went the rights for Wilmut and Campbell's cloning technology. As a result, if a scientist or company wants to make a cloned animal as a part of a commercial enterprise today they have to pay Geron for the privilege. Even Wilmut would have to stump up - though only if he wanted to use it for commercial purposes. Scientists doing basic research do not have to pay.
'We are not entrepreneurial in this country,' Wilmut said. 'This is another technology that has walked, which means we miss out from the point of view of return on investment, on employment and in getting good access to profits.'
Thus the rights to use cloning techniques, and the best example of its exploitation, reside on the other side of the Atlantic. It is not a healthy position.
On the other hand, Britain retains the whip hand when it comes to the use of cloning in medicine for humans. Human embryos can be made by cloning and then be used as sources of stem cells, which have great promise as treatment for diseases such as Parkinson's and Alzheimer's. However, work like this is banned in federal laboratories in the US, giving Britain a clear advantage in ground-breaking research in this field.
A classic example of the potential cloning holds for humanity is provided by one of the crippling - ultimately fatal - illnesses, motor neurone disease. Wilmut was recently given permission to create human embryos from the DNA of victims of the disease, which strikes people at an average age of 56 and affects about 1,200 people in Britain every year. The aim of his research was simple. He intended to grow embryos taken from motor neurone patients, then remove the stem cells - the cells that eventually grow into the bodies' different tissues. In this way, key insights into the development of the disease would be gained, raising hopes of developing new drugs.
However, the gods of cloning again conspired against Wilmut. He was persuaded by Woo-suk Hwang - then hailed as the world's greatest cloner - that this approach was wrong and doomed to failure. So Wilmut gave up the programme and let his licence lapse. 'I should have known better,' he said. 'We'd visited Hwang in Korea on a couple of occasions and he had all these invalids in wheelchairs lined up in the audience in front of the platform that he was speaking from. He would tell them he would have them walking in no time. It really wasn't on.'
Now Hwang has been disgraced and Wilmut's approach vindicated. However, the licence has expired, which means his research plans into motor neurone disease have been set back by about five years. However, he remains determined. Indeed, his commitment is touching. In America, he pointed out, motor neurone disease is known as Lou Gehrig's disease, after the baseball star who died of it in 1941. In this country the disease should, by the same logic, be known as Jimmy Johnstone's disease. Johnstone was the Celtic winger who helped his team win the European Cup in 1967 and whose dazzling bursts on the right earned him the Glaswegian accolade of 'Wee Jinky'. Last year Johnstone died of motor neurone disease.
'I had the privilege of meeting him and his wife a few months before he died. He and I were roughly the same age, but he was completely paralysed from the neck down.' The recollection stopped Wilmut in his tracks, and for a couple of minutes he seemed on the cusp of tears. 'I am not normally lost for words. It was extremely moving meeting someone like that. Why are we not doing what we can for them?'
As head of his university's new regenerative medicine centre, Wilmut intends to do just that and aims to regalvanise his efforts in seeking breakthroughs in the treatment of motor neurone disease: 'That would be the best possible way to celebrate Dolly's life.'
Cloning will ultimately be extremely valuable to medicine, Wilmut added. It is just proving hard to exploit. It took 270 attempts to create the embryo that resulted in Dolly. 'That represents an efficiency of 0.3 per cent. Today we have got that up to about 3 per cent. But it is still very low.'
There are other reasons for our failure to follow on swiftly from Dolly's creation, however, as Simon Best of the UK Bioindustry Association pointed out: 'Dolly's creation was simply so far ahead of its time it caught scientists out. If you had taken a poll of scientists in 1997, the vast majority would have said there was no prospect of cloning a mammal for another 15 to 20 years.
'Wilmut and Campbell caught everyone by surprise. This field was considered so uncompromising only a handful of scientists were working in it. There were therefore no promising young scientists, expert in the field, to take up this work and follow through with new breakthroughs. That is why we are still having to wait.'
Look at other great scientific discoveries and you see a similar picture, added Best. When Crick and Watson discovered the structure of DNA, it took more than 20 years for their work to be translated into biotechnology products including human growth hormone, blood clotting treatments and other drugs.
And the science behind DNA's structure was much less revolutionary than that involved in Dolly's creation. Crick and Watson indulged in a great deal of scientific detective work to make their discovery, of course. But Wilmut and Campbell carried out hundreds of highly complex biological experiments before they succeeded. To create Dolly they removed a cell from an adult sheep. Then they took an egg from another sheep, scooped out its DNA and inserted the first sheep's nucleus. After a series of chemical treatments, they then placed this artificial embryo into a third sheep and coaxed it to grow into Dolly. This is cloning or nuclear transfer technology.
'Until then, we all thought it was impossible to reprogramme an adult cell and persuade it to act like an embryo,' said Cambridge cloning expert Roger Pedersen. 'Wilmut and Campbell showed that was wrong. They turned back the arrow of time. And we are still trying to come to grips with the implications.'
Wilmut looks an unlikely scientific revolutionary. He has an amiable, avuncular demeanour and describes himself as 'a rather shy, reserved middle-aged Englishman'. It is a fair description. His casual, bearded appearance makes him look more like a Yorkshire farmer than a researcher whose work frightened the living daylights out of politicians round the world.
'I hadn't expected all that fuss,' he admitted. 'Even in the middle of it, I thought it would all die down. I remember being on holiday, walking along a beach in Scotland, six months after the story broke, thinking: "Oh, well, at least it is now all over and I can got on with my work." But of course, it wasn't all over. It has never gone away. It just shows what I knew about my work's implications.'
Stem cell timeline
1981 - Gail Martin at the University of California, San Francisco, and Martin Evans, University of Cambridge, isolate embryonic stem cells in mice for the first time.
23 Feb, 1997 - Dolly the Sheep (born at the Roslin Institute ) is revealed to the world. It is the first clone of an adult mammal.
July 1998 - Noto and Kaga, the first cloned cows, are produced by the Ishikawa Prefectural Livestock Research Centre, Japan.
2001 - The UK becomes the first country to legalise therapeutic human cloning for research.
Feb 2003 - Dolly the Sheep dies.
April 2003 - The sequencing of the human genome is completed.
Feb 2004 - South Korean scientist Hwang Woo-suk and his team claim to have created 30 cloned human embryos and extracted stem cells.
August 2005 -The first dog clone, an Afghan hound called Snuppy, is born in South Korea, also created by Dr Hwang.
Jan 2006 - Dr Hwang's work exposed as fake.
July 2006 - President Bush uses his veto in order to kill a bill to increase federal funding of stem cell research.
Luc Torres
