Scientist who cloned Dolly the sheep dies aged 79
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SIR IAN WILMUT: 1944–2023
Sir Ian Wilmut, who has died aged 79, was the English developmental biologist who led a large team that created an unlikely global superstar, a lamb named Dolly. The feat, the first mammal cloned from an adult cell, made global front-page news.
The Finn Dorset sheep, born in 1996 in the Roslin Institute, south of Edinburgh, lived a relatively long and full life (for a sheep) and would adorn magazine covers, inspire operas, adverts and more, even catching the eye of US president Bill Clinton.
Scientist and professor Ian Wilmut and Dolly, the world’s first cloned sheep, at the Roslin Institute near Edinburgh where Dolly was developed and created, 2002.Credit: Getty
The dogma of the day’s biology said that the cellular clock could not be turned back once embryonic cells had differentiated into stem cells and then hundreds of other cell types in an adult body, from brain to muscle cell. But, as Wilmut declared, Dolly revealed, rather than defied, the laws of biology. The reason Wilmut’s team created Dolly was in research to improve the genetic alteration of animals.
While American scientists were sceptical that a tight-knit group of hirsute underdogs toiling in an obscure Scottish animal research lab had snatched the cloning prize from clean-shaven, lantern-jawed scientists working in a well-funded North American powerhouse of genetics (most of whom thought cloning of adult cells was impossible), journalists expecting to meet a wild-eyed Frankenstein were confronted with the genial and softly spoken figure of Wilmut – in wool sweater, parka and, as one paper put it, with “the face of a bank clerk”.
Scottish scientist Ian Wilmut in St Paul’s Church in Frankfurt, Germany, 2005.Credit: AP
He and his colleagues had used the method of nuclear transfer, a technique conceived in 1928 by the German embryologist Hans Spemann (1869-1941), working with Hilda Mangold, which involves taking the DNA in a compartment at the heart of cells called the nucleus, and transferring it to an egg cell that has had its own nucleus removed.
In 1989 Wilmut and Lawrence Smith, a doctoral student at Roslin, generated four cloned lambs this way. It was Smith who had the idea to try nuclear transfer and who had taught Wilmut the basics of cloning. Importantly, their work suggested that the sequence or cycle through which each cell progresses from one cell division to the next was important.
Dr Ian Wilmut, leader of the team that created Dolly the sheep – the world’s first mammal cloned from an adult cell – stands next to her as she goes on display at the National Museum of Scotland in Edinburgh, 2003.Credit: Reuters
In 1991 Wilmut hired the English biologist Keith Campbell, whose knowledge of the cell cycle proved critical for the cloning of Dolly. As Wilmut said, “I conceived the project, but it was thanks to Keith’s inspiration that it succeeded.”
They focused on cloning sheep because at that time, he explained, “it was possible to buy one at the market for less than a bottle of mineral water in a posh hotel”.
They first realised it was possible to clone differentiated cells in 1995, in that case nine-day-old embryonic cells, with the generation of two cloned Welsh mountain sheep, Megan and Morag. They were the first clones from differentiated cells – and, to underline the significance of his contribution, which made the front page of The Daily Telegraph, Keith Campbell was listed as the Nature paper’s first author.
The following year the large team, working with the company PPL Therapeutics, used mammary-gland cells from a six-year-old ewe as nucleus donors for transfer into egg cells: his team made 277 embryos this way, implanting them into 13 surrogate mothers, only one of which became pregnant.
The resulting 6.6 kg lamb, born on July 5, 1996, was Dolly. As Wilmut recalled, her name was an “affectionate tribute to the buxom American singer Dolly Parton”. Dolly’s white face provided instant reassurance that she was a clone because if she had been genetically related to her surrogate mother she would have had a black face.
News of her birth leaked out in February 1997, before the Nature paper, generating lurid headlines, such as in The New York Times: “Researchers astounded … Fiction becomes true and dreaded possibilities are raised”. This was by no means the only headline that sounded the alarm: “Cloning discovery has unleashed a wolf in sheep’s clothing”, “Cloned sheep in Nazi storm”, “Dolly opens door for life after death”, “The clone rangers need to be stopped” and “Golly, Dolly! It’s the abolition of man”.
President Clinton asked experts to review the implications, as did the Vatican and the European Commission. As he articulated in his co-written book After Dolly, Wilmut was concerned by the psychological impact of cloning, but above all else he considered human cloning both impractical and unethical because, from what he knew, many embryos died following implantation, and many of those embryos that did survive and develop to term were excessively large, sometimes died immediately following birth, or were born with defects.
The interest in using cloning to make stem cells for treatments was intense. However, in 2007 Ian Wilmut decided not to pursue a licence to clone human embryos, which he had been awarded just two years earlier, as part of a drive to find new treatments for the devastating degenerative condition motor neuron disease.
This was because a rival method to genetically alter cells, developed in Japan by Shinya Yamanaka (which would earn a Nobel Prize in 2012), had more 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 without the ethical concern about creating and dismantling human embryos.
Ian Wilmut was born on July 7, 1944, at Hampton Lucy in Warwickshire, and brought up in Coventry. As a young man he wanted to go into the navy, but had to think again when he was diagnosed as colour blind. Despite what he described as an undistinguished performance at school, he attended the Agricultural College at the University of Nottingham, where he initially pursued his lifelong interest in farming.
But he soon turned his attention to basic research when in 1966, his final year, he received a scholarship to conduct research for a summer under a pioneer of animal reproductive science, Chris Polge of the Animal Research Station at the University of Cambridge.
Following his graduation from Nottingham in 1967, Wilmut returned to Cambridge, where he pursued a doctorate under the guidance of Polge, whose research was focused on improving low-temperature storage of embryos. In 1971 Wilmut was awarded a doctorate by Darwin College, Cambridge, for preserving boar semen this way.
Portrait in Sydney of Ian Wilmut in 2006.Credit: Kate Geraghty
In 1973 he successfully implanted into a surrogate mother a calf embryo that had been cryo-preserved, and the resulting red-and-white Hereford Friesian cross calf was dubbed Frostie. He also got his first experience of dealing with the media as The Daily Mail declared, “Ice-age calf weighs in”.
In 1973 Wilmut was appointed senior scientific officer at the Animal Breeding Research Organisation, which would become the Roslin Institute in 1993. His work there eventually led to the birth of a sheep in 1991 named Tracy, created from a fertilised egg that had been genetically engineered through DNA injection to produce milk containing alpha-1 antitrypsin, a human enzyme used to treat cystic fibrosis and emphysema. The sheep, which he called “a living drug factory”, is now in the collections of the Science Museum Group.
The work on Dolly was aimed at developing an efficient alternative. In 1997 Wilmut and his colleagues generated Polly, a Poll Dorset clone created by nuclear transfer using a foetal cell nucleus genetically engineered with a human gene for human factor IX, a blood clotting factor that is absent in people with haemophilia – along with two other sheep engineered to produce human factor IX that were also born in 1997.
In 2005 Wilmut accepted a position as chair of reproductive science at the University of Edinburgh but maintained his relationship with the Roslin Institute as a visiting scientist. He received several awards, was made a Fellow of the Royal Society in 2002 and was knighted in 2007. In addition to papers published in major journals such as Nature and Science, he wrote The Second Creation: Dolly and the Age of Biological Control (2000, with Keith Campbell and Colin Tudge) and After Dolly: The Uses and Misuses of Human Cloning (2006, with Roger Highfield, the former Telegraph science editor).
Five years ago he revealed he had been diagnosed with Parkinson’s and had told one interviewer that though work with Dolly would accelerate the development of treatments, “people like me will probably have died of Parkinson’s disease before the new treatments become available”.
Ian Wilmut is survived by his second wife, Sara, and by two daughters and an adopted son from his first marriage, to Vivienne, who died in 2015.
The Telegraph, London
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