The Scotsman (Scotland), Feb. 15, 2003
ALASTAIR DALTON, SCIENCE CORRESPONDENT
The death of one of the world’s scientific icons will add fuel to concerns about the safety of animal – and human – cloning.
The announcement of Dolly the sheep’s birth six years ago brought instant global fame to the Roslin Institute in Midlothian and opened up a realm of possibilities for therapeutic cloning assisting medical advances.
A spin-out firm, PPL Therapeutics, was created to reap the commercial potential of the breakthrough and the institute went on to clone pigs, and is currently attempting to clone chickens.
However, the creators of the first cloned mammal always warned about the likely risks of animal cloning, which appeared to be confirmed when Dolly was found to have aged prematurely last year.
Professor Ian Wilmut, who led the team which created Dolly, admitted at the time that current cloning techniques were “inefficient”.
When she was born in July 1996, Dolly seemed normal but researchers warned she could have hidden genetic defects. Aged two, members of the team who monitored her health published research suggesting she might be prone to premature ageing.
Arthritis is not unknown in sheep, but Dolly succumbed at an unusually young age and had the disease in two joints which are not normally affected.
However, the issue is complicated because Dolly was created using genetic material from a six-year-old ewe, so could arguably be said to be 12 years old, not six.
Prof Wilmut said the arthritis in the sheep’s left hind leg may have been the result of a genetic defect caused by cloning.
He said: “This provides one more piece of evidence that, unfortunately, the present cloning procedures are rather inefficient. What’s very important is that not only we at the institute, but others who produce cloned animals, should monitor their health throughout their entire life span.
“It is a technology with enormous promise for the treatment of degenerative diseases, but we do need to be a little bit cautious.”
However, Prof Wilmut said it would never be known if Dolly had arthritis because she was cloned or whether it was “an unfortunate accident”.
Japanese research on mice published a month after Dolly’s condition was announced showed for the first time that cloned animals die prematurely. Almost all the mice in the study died early, half of them from severe pneumonia and liver failure.
The National Institute of Infectious Diseases in Tokyo found that ten of its 12 cloned mice lived for less than 800 days, with the first deaths occurring after 311 days. By comparison, all but one of its seven normally-conceived mice outlived the clones.
Dr Atsuo Ogura, who led the research, said it was thought that faulty immune systems in the cloned mice had been unable to fight off infections.
Two weeks ago, Australia’s first cloned sheep died unexpectedly. Matilda, who was born in 2000, was reported to have appeared healthy on the day she died, but a post-mortem examination failed to establish its cause.
However, the South Australian Research and Development Institute, near Adelaide, where Matilda lived, said there was nothing to suggest that her death was linked in any way to the animal being a clone.
Dr Patrick Dixon, a human cloning expert, said the nature of Dolly’s death would have a huge impact on future cloning.
He said: “The real issue is what Dolly died from, and whether it was linked to premature ageing. There have been suspicions that Dolly had not been as healthy as has been hoped and that she had developed severe arthritis.
“She was not old – by sheep standards – to have been put down. A key question is exactly what kind of progressive lung disease she has had and whether that can be related in any way to the cloning technology which produced her.”
However, Dr Donald Bruce, the director of the Church of Scotland’s Society, Religion and Technology Project, warned against exaggerating the significance of Dolly’s death.
Dr Bruce, who is also a member of PPL Therapeutics’ ethical committee, said: “Dolly was a celebrity who attracted attention because she was a one-off, so we do not know what the implications of her death for cloning.
“Dolly rewrote the laws of biology and represented both the promise and the threat of what biotechnology might do. Her death marks the end of the era that she opened.”
Baroness Greenfield, the director of the Royal Institution, said: “One should be very careful of knee-jerk conclusions. We can’t rule out that Dolly’s death was connected to her status as a clone – but it’s important for science now to explore other factors involved, including the unusual lifestyle enjoyed by the world’s most famous sheep.”
Dolly had been living in “retirement” at the Roslin Institute after several years of tests.
She was being treated with anti-inflammatory drugs and it was thought that she could have lived until she was ten.
Dr Harry Griffin, the institute’s acting director, told The Scotsman a week ago her condition remained unchanged and she appeared healthy.
5 July 1996: Dolly is cloned from a breast cell of a six-year-old ewe and born at the Roslin Institute, near Edinburgh. Dolly, a Finn Dorset named after the country and western singer Dolly Parton, goes on to breed normally on two occasions giving birth to four lambs.
23 February 1997: Dolly’s birth is announced seven months after it took place and is heralded as one of the most significant scientific breakthroughs of the decade but it also triggers a furious debate about the ethics of cloning.
21 December 1997: The scientists who made Dolly clone two more lambs. The lambs, named Molly and Polly, have been cloned with a human gene so that their milk will contain a blood-clotting protein that can be extracted to treat human haemophilia.
22 July 1998: The production of a batch of 22 healthy cloned mice at the University of Hawaii, Honolulu is announced. Mice are considered cheaper and easier to conduct research on.
13 March 2000: Five pigs are successfully cloned by the US spin-off of the Roslin Institute in Edinburgh. The breakthrough prompts scientists to declare that the likelihood of NHS transplants of animal organs into humans within six years becomes “a real possibility”.
4 January 2003: The UFO cult, the Raelian movement, announces the birth of the world’s first human clone, named Eve and born to a 31-year-old American on 26 December, 2002. Over the following days the cult is repeatedly asked to prove its claim and is widely dismissed by the scientific community as a hoax.