Cloning Producing Genetic
Defects in Animals

The Sunday Times
SUN 28 APR 2002

Gene defects emerge in all animal clones
Jonathan Leake Science Editor

A REVIEW of all the world's cloned animals suggests that every one of them
is genetically and physically defective. Ian Wilmut, co-creator of Dolly the
sheep, the first mammal to be cloned from an adult cell, published his
findings this weekend.

The study coincides with claims by researchers trying to create the first
cloned human. In Italy, Dr Severino Antinori has claimed that three women
are pregnant with cloned babies; in America, Dr Panayiotis Zavos has said he
will achieve such a pregnancy within two years.

Wilmut said his latest research suggested that a cloned human would also be
at huge risk of genetic defects.

This was a clear warning that "nobody should be attempting to clone a
child". The new study surveys cloning efforts worldwide. "The widespread
problems associated with clones has led to questions as to whether any clone
was entirely normal," Wilmut said.

Dolly, the sheep cloned by Wilmut five years ago at the Roslin research
centre in Scotland, has already shown defects. She was born with chromosomes
that have shortened telomeres < the DNA tips that protect the end of
chromosomes.

In normal sheep < and humans < telomeres grow shorter with age. As they
shorten, cells seem to become more prone to disease and death. This has been
linked with diseases of ageing and cancer. Earlier this year Dolly was found
to be developing arthritis at a far younger age than is normal in sheep.

Wilmut listed defects occurring regularly in other cloned animals, including
gigantism (excessive size) in cloned sheep and cattle; placentas of up to
four times the normal size in mice; and heart defects in pigs.

Despite being given normal amounts of food, many cloned mice also become
grotesquely fat, while many cloned cows, sheep and pigs have developmental
difficulties, lung problems and malfunctioning immune systems.

Cloned animals have also shown a variety of individual defects. A calf
cloned in France appeared to be thriving but suddenly died at 51 days old
after a failure in its ability to produce white blood cells.

Similarly, scientists at Roslin had to put down a cloned lamb at 12 days old
because the muscles around its lungs were so abnormally thick that it could
hardly breathe.

Wilmut has looked at the behaviour of methyl molecules which attach
themselves to DNA in all cells and help to control many of its functions.

He found that the methylation of the DNA in adult cells differed sharply
from that of sperm and eggs. It means that when a nucleus is taken from a
cell of an adult animal and injected into an egg < the process that leads to
a clone < its DNA is formatted in radically different ways from that found
in sperm.

He believes this is why the genes of cloned animals seem to behave in
unpredictable ways and suggests that human clones are also vulnerable to
this problem.

Earlier this year Advanced Cell Technology, an American company, announced
that it had created three cloned human embryos but admitted that none had
been able to grow to more than six cells in size.

Wilmut concludes: "There is abundant evidence that cloning can and does go
wrong and no justification for believing that this will not happen with
humans."

The researchers behind the human cloning programmes said they could overcome
such problems. Zavos is seen increasingly as the more serious candidate. He
claims to have two laboratories perfecting their techniques on animals
before attempting to reproduce a human in the "near future".

[BOX] IMPERFECT COPIES

* Sheep: clones often oversized or have deformities of the heart and
lungs
* Mice: placentas up to four times normal size
* Cattle: many cloned embryos aborted
* Humans: unknown defects kill embryos. None known to have grown larger
than six celts
* All species: chromosome damage leads to premature ageing and random
genetic defects
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