Dolly, the world's first cloned sheep, has developed arthritis at the relatively early age of 5 1/2 years, stirring debate that current cloning procedures might be flawed and raising questions about the implications for cloning humans in the future. The announcement of Dolly's illness -- just days after scientists announced the apparently successful cloning of genetically modified piglets -- also casts new doubt on the feasibility of cloning animals for use in human transplantation.
Prague, 8 January 2002 (RFE/RL) -- Dolly was the first mammal to be cloned with DNA taken from an adult cell, and her arrival in 1996 made headlines around the world. Since that time, scientists have used the same technique to clone hundreds of animals, including pigs, cows, and mice.
The recent announcement by researchers at the Edinburgh-based Roslin Institute that their famous creation had developed arthritis at an early age sounded an alarm bell. Sheep can live to between 15 and 17 years, and arthritis, when it occurs, does not typically develop until age 10 or 11. But Dolly is only 5 1/2. Already in 1999, scientists noticed signs that the cells in Dolly's body -- who was cloned from a 6-year-old sheep -- had started to show signs of wear more typical of an older animal.
Does this mean that Dolly -- in physical terms -- is in fact 11 1/2 years old, her biological clock having been set at 6 years old upon birth?
Ian Wilmut, the scientist most closely associated with the Dolly experiment, admitted that there was no way to tell. Wilmut said researchers would probably never be able to determine whether Dolly's condition occurred because she was cloned or whether it was, in his words, "an unfortunate accident."
Robin Lovell-Badge heads the development genetics program at Britain's National Institute for Medical Research. He tells RFE/RL no conclusions can be drawn because Dolly has hardly led a typical sheep's existence. Lifestyle and diet, not genetics, may explain the early onset of arthritis.
"As a scientist, you just cannot base any theory on 'N-equals-1,' on a sample size of one. So Dolly is an extraordinary sheep in many ways and because, of course, she was the first one cloned she's received an awful lot of attention," Lovell-Badge said. "She's been housed in different ways from any other sheep. She's overweight, partly because she has been fed a lot of goodies by everyone over the years."
There is no doubt, however, that Dolly will be monitored closely in coming months and years for further signs of anomalies.
Pinpointing the link between cloning and health problems has become a critical issue, as scientists now move toward cloning animals for therapeutic purposes. Also last week, two rival teams of scientists announced they had cloned pigs genetically engineered to be suitable for animal-to-human transplants, a procedure known as xenotransplantation. The cloned pigs were born without a gene which normally induces the human body to reject pig tissue, leading to hopes that one day, such animals could be bred to provide livers, hearts, and other organs to human beings in need of transplants.
But here too, independent scientists warn that the risks remain great and uncertainties numerous. For one, pigs naturally have a far shorter lifespan than human beings, meaning their organs are not designed to last as long as human organs. In the case of cloned pigs, the cycle could be even shorter. Gert van Dijk is a researcher at the Rathenau Instituut, tasked with analyzing the latest scientific and technological developments on behalf of the Dutch parliament.
"Pigs don't last as long as humans, so if you want a pig organ to remain in the human body for, say, 20 years, that's going to be very tough because pigs don't live that long," van Dijk said. "So any way you turn it, you're going to have an organ that is not going to last as long as a human organ -- let alone if you use a cloned animal, it might be even older. We just don't know at the moment."
The more serious worry is that pigs are known to contain what are called porcine endogenous retroviruses (PERVs), which are viruses that evolved with the swine over millions of years and now are part of the species' genes. The viruses do not affect pigs, but no one knows what would happen if pig organs were transplanted into humans. Some studies in which humans were exposed to pig cells have suggested that PERVs do not infect human cells. But critics say there are many other examples showing that some retroviruses that are harmless in one species become virulent killers when transplanted into others.
The most notable example is HIV, the virus that causes AIDS. The retrovirus is thought by some scientists to have lived harmlessly in the African green monkey, becoming deadly only when it jumped to humans. Van Dijk explains: "If xenotransplantation is going to be a serious option for transplantation, that means thousands of transplants will be done every year; and only one of them has to go wrong and you have a big problem, because a virus that jumps the species barrier might jump to other people as well. This has happened with AIDS, for instance. That jumped from monkeys to humans and the same could happen with pig viruses. And it just has to happen once and you have a big problem, like AIDS is now. And that is the big worry at the moment."
Lovell-Badge only sees animal-to-human transplants as a stop-gap possibility for emergency situations, until a human donor becomes available: "You might be able to use these organs as temporary graft organ transplants to then help you look for a better human donor."
But as he points out, research on man-made transplants, such as the artificial heart, might soon make the devices sufficiently reliable to supplant any need for animal organs. Whether people will eventually clone copies of themselves for "spare parts" is, for now, too scientifically remote and ethically repugnant to be seriously debated by most researchers. But the day when the issue moves from the realm of science fiction to reality may be closer than many believe.
Prague, 8 January 2002 (RFE/RL) -- Dolly was the first mammal to be cloned with DNA taken from an adult cell, and her arrival in 1996 made headlines around the world. Since that time, scientists have used the same technique to clone hundreds of animals, including pigs, cows, and mice.
The recent announcement by researchers at the Edinburgh-based Roslin Institute that their famous creation had developed arthritis at an early age sounded an alarm bell. Sheep can live to between 15 and 17 years, and arthritis, when it occurs, does not typically develop until age 10 or 11. But Dolly is only 5 1/2. Already in 1999, scientists noticed signs that the cells in Dolly's body -- who was cloned from a 6-year-old sheep -- had started to show signs of wear more typical of an older animal.
Does this mean that Dolly -- in physical terms -- is in fact 11 1/2 years old, her biological clock having been set at 6 years old upon birth?
Ian Wilmut, the scientist most closely associated with the Dolly experiment, admitted that there was no way to tell. Wilmut said researchers would probably never be able to determine whether Dolly's condition occurred because she was cloned or whether it was, in his words, "an unfortunate accident."
Robin Lovell-Badge heads the development genetics program at Britain's National Institute for Medical Research. He tells RFE/RL no conclusions can be drawn because Dolly has hardly led a typical sheep's existence. Lifestyle and diet, not genetics, may explain the early onset of arthritis.
"As a scientist, you just cannot base any theory on 'N-equals-1,' on a sample size of one. So Dolly is an extraordinary sheep in many ways and because, of course, she was the first one cloned she's received an awful lot of attention," Lovell-Badge said. "She's been housed in different ways from any other sheep. She's overweight, partly because she has been fed a lot of goodies by everyone over the years."
There is no doubt, however, that Dolly will be monitored closely in coming months and years for further signs of anomalies.
Pinpointing the link between cloning and health problems has become a critical issue, as scientists now move toward cloning animals for therapeutic purposes. Also last week, two rival teams of scientists announced they had cloned pigs genetically engineered to be suitable for animal-to-human transplants, a procedure known as xenotransplantation. The cloned pigs were born without a gene which normally induces the human body to reject pig tissue, leading to hopes that one day, such animals could be bred to provide livers, hearts, and other organs to human beings in need of transplants.
But here too, independent scientists warn that the risks remain great and uncertainties numerous. For one, pigs naturally have a far shorter lifespan than human beings, meaning their organs are not designed to last as long as human organs. In the case of cloned pigs, the cycle could be even shorter. Gert van Dijk is a researcher at the Rathenau Instituut, tasked with analyzing the latest scientific and technological developments on behalf of the Dutch parliament.
"Pigs don't last as long as humans, so if you want a pig organ to remain in the human body for, say, 20 years, that's going to be very tough because pigs don't live that long," van Dijk said. "So any way you turn it, you're going to have an organ that is not going to last as long as a human organ -- let alone if you use a cloned animal, it might be even older. We just don't know at the moment."
The more serious worry is that pigs are known to contain what are called porcine endogenous retroviruses (PERVs), which are viruses that evolved with the swine over millions of years and now are part of the species' genes. The viruses do not affect pigs, but no one knows what would happen if pig organs were transplanted into humans. Some studies in which humans were exposed to pig cells have suggested that PERVs do not infect human cells. But critics say there are many other examples showing that some retroviruses that are harmless in one species become virulent killers when transplanted into others.
The most notable example is HIV, the virus that causes AIDS. The retrovirus is thought by some scientists to have lived harmlessly in the African green monkey, becoming deadly only when it jumped to humans. Van Dijk explains: "If xenotransplantation is going to be a serious option for transplantation, that means thousands of transplants will be done every year; and only one of them has to go wrong and you have a big problem, because a virus that jumps the species barrier might jump to other people as well. This has happened with AIDS, for instance. That jumped from monkeys to humans and the same could happen with pig viruses. And it just has to happen once and you have a big problem, like AIDS is now. And that is the big worry at the moment."
Lovell-Badge only sees animal-to-human transplants as a stop-gap possibility for emergency situations, until a human donor becomes available: "You might be able to use these organs as temporary graft organ transplants to then help you look for a better human donor."
But as he points out, research on man-made transplants, such as the artificial heart, might soon make the devices sufficiently reliable to supplant any need for animal organs. Whether people will eventually clone copies of themselves for "spare parts" is, for now, too scientifically remote and ethically repugnant to be seriously debated by most researchers. But the day when the issue moves from the realm of science fiction to reality may be closer than many believe.
