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The Short, Unhappy Lives of Clones

Cloned animals may die young, according to the first study of their lifespans, carried out by Japanese researchers on mice.

Cloning involves removing the nucleus from an egg and replacing it with the nucleus of a donor cell. Many of the embryos created in this way never develop or miscarry, and even after birth some clones die. But up to now, cloning scientists have insisted that the few survivors can be perfectly normal.

But Atsuo Ogura of the National Institute of Infectious Diseases in Tokyo says his work suggests that some effects of cloning are not apparent in the days, weeks or even years after birth. ?It is very probable that, at least for some populations of clones, some unpredictable defects will appear in the long run,? he says.

In November, 2001, U.S. biotech company Advanced Cell Technology (ACT) cloned two dozen apparently healthy cows. However, 20 per cent of the cloned calves died soon after birth. Rudolf Jaenisch, who clones mice at M.I.T., says the new work ?shows that to look at animals at one point in time and say they are healthy and normal is really wishful thinking.?

Evidence of severe pregnancy complications and defects caused by cloning have been reported by cattle cloners. There have been cases of dramatically oversized calves, enlarged tongues, intestinal blockages, immune deficiencies and diabetes.

In January, the first mammal cloned from an adult cell, Dolly the sheep, was reported to have developed arthritis at the relatively young age of five and a half. The scientists who created Dolly say it is impossible to know whether the cloning process is to blame for her premature aging. ?The fact that Dolly has arthritis at this comparatively young age suggests there may be problems,? says Ian Wilmut of the Roslin Institute in Scotland. But ?We cannot ever know whether this is the result of cloning or just an unhappy coincidence.? The average lifespan of a sheep is 12 to 14 years. Ogura?s team cloned 12 male mice and these were compared with seven males from natural matings and six others produced using in-vitro fertilization. The clones appeared active and healthy, gained weight normally and matched the control animals in 14 of 16 physiological measurements.

But the first cloned mouse died after only 311 days and by day 800, 10 (83 per cent) of the cloned mice were dead. In contrast, only three (23 per cent) of the controls died during the same period.

The dead clones showed high rates of pneumonia, liver disease, cancer and a lower level of antibody production, suggesting they had an immune system defect. Ogura?s team is now trying to pinpoint the precise cause of death and repeat the experiment with more animals.

Tony Perry of ACT says it?s unclear if clones from other species, such as cows or pigs, die early. And even if clones in general do prove to have shortened lifespans, he does not believe that means that clones are inherently unhealthy.

In November, ACT reported it had created the first human cloned embryos, although only one of them reached the six-cell stage. In December, ACT researcher Tanya Dominko reported that apparently healthy 32-cell monkey embryos were actually a ?gallery of horrors? deep inside, since the cells in most of them did not form distinct nuclei containing all the chromosomes. Dominko thinks the trauma of removing the nucleus from the egg might be what triggers the defects.

All the researchers agree that these new discoveries should be an warning to scientists who want to create human clones.

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The first cloned cat, now a 2-month-old kitten, has been created at Texas A&M University. The kitten joins a growing list of animals that have been cloned from adult cells, starting with Dolly the sheep and now including pigs, goats, cattle, mice and an ox-like creature called a gaur.

?The kitten was vigorous at birth and appears to be completely normal,? says Mark Westhusin, who is part of the cloning team.

The kitten is a calico-and-white shorthair named ?Cc? that does not exactly resemble her genetic parent. She looks very different from the tabby cat that gave birth to her. The scientists said her coat coloring is different because an animal?s markings are not only due to genetics, but also to conditions in the womb. ?The public, when they see this, they are going to say this is not a clone,? says Duane Kraemer. ?It?s a genetic clone.?

Especially in cats, coat color is influenced by unknown factors and by genes that are turned on and off according to unknown circumstances. ?It is even more so true in the calico cat, the tricolor cat,? Kraemer says.

Lou Hawthorne, chief executive officer of Sperling?s Genetic Savings & Clone, which supports the cloning of pets and rare animals, says he would not have chosen a calico as the first clone for this reason, since other kinds of cats would produce clones more identical to their genetic parents. ?They?ll never be identical but they?ll be a lot more similar than this,? he says.

It?s not easy to clone a cat. It took the researchers 188 tries to produce a single kitten. They cloned 87 embryos but only two cats became pregnant and only Cc was born.

The work began with Genetic Savings and Clone?s ?Missyplicity? project. Its first attempt was to clone Missy, a longhaired mutt whose owners want to duplicate her.It didn?t work because it?s much harder to clone dogs than cats because their egg cells are more difficult to work with.

The Humane Society of the United States objected to the news. ?We are very concerned about the rush toward the cloning of mammals,? says Wayne Pacelle, senior vice president of the organization. ?We are particularly concerned about cloning cats, because there are millions of cats that are killed every year for lack of suitable homes.?

But Hawthorne says cloning is good for strays and groups like the Humane Society. ?It takes eggs to make clones, hundreds if not thousands of eggs. Where do we get those eggs? From spay clinics. What do we give them in exchange for those eggs? We give then money. They will spay hundreds of times more cats with the money we give them than each single clone we make.?

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