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TITLE:  Human cloning currently 'almost impossible'
SOURCE: The New Scientist, UK, by Philip Cohen
        http://www.newscientist.com/news/news.jsp?id=ns99993614
DATE:   Apr 10, 2003

------------------ archive: http://www.gene.ch/genet.html ------------------


Human cloning currently 'almost impossible'

A newly discovered quirk of primate cell biology suggests that monkeys -
and humans - are nearly impossible to clone with current techniques.

"There's a molecular obstacle that stops the technology from working in
primates," says Gerald Schatten, at the University of Pittsburgh School
of Medicine in Pennsylvania. "Charlatans who claim they have cloned
humans clearly don't understand the biology."

Unlike other mammal species in which adult animals have been successfully
cloned, Schatten's team found that the eggs of rhesus monkeys are robbed
of a key set of proteins during the cloning procedure. The same appears
to be true for human cells.

That loss causes genetic chaos in cloned monkey embryos, with chromosomes
distributed almost at random. As a result, the embryos look fine at an
early stage, but are completely incapable of further development. The
finding severely undermines claims by Clonaid, a company started by a UFO
cult, to have created several cloned babies.

"It's an interesting part of the puzzle of why primates have been so
difficult to clone," says Robert Lanza of Advanced Cell Technology, a
Massachusetts-based biotech company that has cloned human embryos.

"Gallery of horrors"

Schatten's group want to clone monkeys to assist in the study of human
diseases. The key technology is called somatic cell nuclear transfer
(SCNT), where a cell from the adult animal to be cloned is fused with an
egg stripped of its own nuclear DNA.

Other researchers had cloned sheep, cows, mice, goats, pigs, rabbits and
a cat, so Schatten was confident monkeys could be cloned too. But despite
producing perfect-looking monkey embryos using SCNT, none developed further.

New Scientist reported concerns about cloned monkey embryos in December
2001, when one of Schatten's colleagues described them as a "gallery of
horrors".

The new study of 716 rhesus monkey embryos revealed the same chromosomal
chaos. Some of the embryo's cells contained double the normal number of
chromosomes, others had odd combinations and some had none at all. And
Schatten's team have now discovered why.

Lost direction

On a hunch they examined the cells' spindles, structures that guide
chromosomes into daughter cells as the embryo divides. The researchers
found that SCNT primate embryos lacked at least two proteins required for
proper spindle function, leaving the chromosomes to distribute randomly
throughout the embryo.

These proteins turn out to be tightly linked to the chromosomes in the
monkey's eggs, which are removed in one of the first steps of the nuclear
transfer process. Further, unpublished work by Schatten's group and
others has shown the same is true for human cells.

In contrast, mice and cows have extra copies of these proteins floating
around to help out the cloned embryo. Schatten jokes: "It's almost like
God in her wisdom said go ahead and clone cows and sheep, but if you
clone a human I'm going to paralyse the egg."

Embryonic cells

The discovery is important, says Lanza, but there may be other important
factors. Although attempts to clone a monkey by SCNT using adult cells
have all failed, two animals were cloned by embryonic cell nuclear
transfer, which Schatten reports also creates the damaging spindle defect.

Furthermore, even trivial differences, such as a slight changes to
reagents, can turn success into failure when cloning other species, says
Lanza.

Schatten intends to test his spindle idea by using a different cloning
technique. He will allow the egg's chromosomes to remain in the embryo
until after the donor cell has been fused, so the spindle proteins can
migrate to new locations. He already has preliminary evidence that proper
spindles then form, suggesting primate cloning could perhaps be feasible.

But he warns against any attempt at human cloning, given the high rate of
abortions, neonatal deaths and health problems that in clones. "I hope
this natural obstacle affords us time to make responsible and enforceable
legislation to prevent anyone attempting human reproductive cloning," he says.

Journal reference: Science (vol 300, p 297)