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While litters of cloned pigs are genetically identical both to one another and to the animal from which they were cloned, the similarities end there. Far from sharing physical traits and temperament, as might be expected, each clone develops in its own idiosyncratic fashion, differing significantly from its siblings and parent in looks, behaviour and even blood chemistry.
The degree of variability within a cloned litter, indeed, can even exceed that seen in control litters of natural pure-bred pigs, scientists have discovered.
The findings demolish the idea that it might be possible to clone favourite pets to create replacements of identical appearance and character. Animal breeders who had hoped to use cloning to replicate prize bulls or champion racehorses will also have to think again.
By the same token, they show that science fiction visions of dictators cloning themselves, or creating cloned armies with identical, pliant personalities, are always likely to remain fantasy.
Even therapeutic cloning of human embryonic stem cells, for creating “spare part” tissue for medical therapies, could be affected by the discovery. Researchers believe that the differences between pigs may reflect subtle genetic errors introduced by the cloning process, and that these could also disrupt the ability to coax human stem cells to make tissue.
The research, which overturns much of the conventional wisdom about cloning, is the first to compare the variability of cloned animals with normally bred ones. The experiments were designed by Jorge Piedrahita, Professor of Molecular Biomedical Sciences at North Carolina State University, who has worked with cloned pigs for years and became intrigued by the differing characters and appearances of the animals that he bred.
“We were very curious about clonal variation,” he said. “The theory said they should be alike, but it was so obvious in the pen that while these animals were genetically the same, they were simply not like each other.
“All the previous research has asked the question: ‘Are clones abnormal?’ That wasn’t the important question to us. We wanted to find out whether clones were alike, whether they were any more similar to one another than regular pigs.”
His team created two litters of cloned Duroc sows, one of four animals and one of five, and reared them alongside two litters of four naturally bred pigs. Environmental variables such as pen conditions, diet and temperature were similar for both sets of animals, to limit their influence as far as possible.
While tests showed that the cloned pigs had identical DNA, they showed just as much diversity as the normal litters across a range of physical and physiological traits. Attributes such as the number of teats, hair length, body size and skin thickness varied widely among the cloned animals, which ought in theory to have been similar. Even blood characteristics, such as glucose levels, fluctuated as greatly as in the normal animals.
“We found some differences that were very striking,” Professor Piedrahita said. “The clones were so different to one another that if you showed the clones and the controls to someone who didn’t know and asked them which is the clone group, 90 per cent of the time they would pick the wrong one.”
Professor Piedrahita then compared the behaviour of the two groups of pigs. The team tested food preferences, use of time over a 72-hour period, and temperament, recording the animals’ reaction when they were picked up, placed on their backs, or had their eyes covered with a towel.
“The clones are not any more alike in behaviour than any other group of pigs,” he said. “You have aggressive animals and docile animals, calm ones and neurotic ones, some who prefer fighting and some who prefer playing, some who like crackers and some who like apples. There is nothing identical about their behaviour at all.”
The study is published in the journal Applied Animal Behaviour Science, and the physiology research has been accepted for publication in Biology of Reproduction.
Although the work is the first to compare clones with control groups in systematic fashion, the results fit with evidence from other cloning research. Last year, for example, the world’s first cloned cat, cc, was born with an entirely different pattern of markings to her mother.
The variability can be explained in two ways. First, the cell nuclear transfer method of cloning was already known to introduce small genetic abnormalities, and these could easily account for some of the differences. Second, the results suggest that tiny differences in an animal’s environment, so small that scientists cannot eliminate them, can have very large developmental consequences.
“It is really clear that genes are not the whole picture, that some environmental levels are so strong that you cannot control them even if you try,” Professor Piedrahita said. “It’s impossible, for example, to control what happens in the womb, and we know that some positions in the uterus have a richer blood supply than others.
“The uterine environment is very, very important for the future behaviour and development of animals. It’s a perfect example of how genes are only one component of development. If genetics was the only factor, then all these pigs would be behaving exactly the same.”
Richard Gardner, Professor of Zoology at Oxford University and chairman of the Royal Society’s working group on cloning, said: “This shows that the effects of genes can be much more labile than many people would claim. If you look at cattle clones, and look at the patches of pigment, they can be hugely variable. With regard to human cloning, it certainly shows that those who want to create a clone to replace a dead child have hugely unrealistic expectations.”
The effect on stem cell cloning, he said, was less likely to prove a major problem than the study published last week by Gerald Schatten of the University of Pittsburgh, which suggested that it may be impossible to clone primates.
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