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					Cloning - The Good, The Bad and The Ugly
Good news! Cloning can cure genetic diseases! Bad News! You die younger. The
scientific press has recently thrown up both good news and bad news for those of us
interested in the field of cloning. Work from America has shown that a genetic
deficiency can be cured by using cloning techniques, while Japanese scientists tell us
that cloned animals tend to die young. So what exactly do these papers say? And
what do they mean for the future of cloning research?




                                        The success story comes from the lab of
Rudolf Jaenisch, using mice deficient in a gene called Rag2 which is important for
the immune system. Without this gene, the animals are highly susceptible to
infections. Notably, a similar condition exists in humans defective for the equivalent
gene. The American researchers took cells from the tail tips of the mutant mice, and
injected them into eggs from which the DNA had previously been removed. These
eggs were then allowed to develop to an early stage of development known as a
blastocyst. Mouse blastocysts have an intriguing property in that certain cells from
these embryos can be maintained indefinitely in culture (in plastic dishes), becoming
embryonic stem cells.

These embryonic stem cells (or ES cells, as they are more often known) can be
replaced in blastocysts and will develop into normal mice, or they can be treated
with various chemicals to turn them into a wide range of other cell types. The
researchers took the ES cells from the cloned blastocysts lacking the Rag2 gene, and
repaired the mutation using standard genetic engineering techniques. These mended
ES cells were then used in two different ways. Firstly, they generated new embryos
from the ES cells and allowed them to develop into mice.

These "healed" mice were then used as bone marrow donors, replacing the defective
immune cells in the mutant mice with functional repaired cells. Because the donors
and the mutants are derived from mice with the same genetic background (apart
from the Rag2 mutation), there are no problems with rejection of the donated cells.
Analysis of the treated mutants showed a complete restoration of the immune
system, making this method a great success.

A second approach involved growing the repaired ES cells in culture with certain
factors which convert them into specialised immune system stem cells. These
artificially generated immune stem cells could then be transplanted back into the
mutant mice. Unfortunately, the mutant mice rejected these transplanted cells,
perhaps due to changes which happen to the cells during the culturing process. The
transplants were only successful when the Rag2 mutants were given treatment to
further damage their already compromised immune systems, as it is the remaining
immune components that cause the rejection. But what does this research mean
practically? Can we transfer this knowledge to human therapies?

Sadly, it would appear not at the moment. In the successful first experiment, the
scientists used the cloned repaired ES cells to generate a whole new donor mouse. If
we translate this to humans, this would mean generating an adult clone as a "spare
part" donor, an act that most people would view as morally questionable in the
extreme. A less extreme but perhaps comparable situation might be the furore that
surrounded the announcement that a couples undergoing IVF had genetically
selected their embryos to be cell donors for their other child. Although the second
approach, growing the cells in culture, had some success when the mutant host
animals were treated with immunosuppressants, this is also a far from ideal
situation as the whole point of the therapy is to restore immune function.

Another nail in the coffin of this idea is the fact that human ES cells do not have
exactly the same properties as mouse ES cells. Indeed, the difficulty of working with
these cells (both technically and legally) has meant that researchers know very little
about the properties and potential of human ES cells. However, this research does at
least give a glimmer of hope that one day cloning and stem cell technology could be
used in this way to treat human diseases.

In the other corner of the world, both scientifically and geographically, Japanese
scientists led by Atsuo Ogura have demonstrated that cloned mice die significantly
sooner than normal mice, or mice generated by artificial injection of sperm into the
egg. Over eighty percent of the clones had died after 2 years and 2 months, while
the normal mice were still going strong. The clones were found to suffer from severe
penumonia and liver failure. Other researchers have also shown clones to have
excessive obesity, birth defects and a high rate of death immediately after birth.
This is true not just of mice, but of other animals such as cows.

The recent claim in the media by human cloning guru Severino Antinori that at least
one woman is currently pregnant with a cloned human is enough in itself to warrant
a shiver of fear in the scientific community. As the evidence grows that cloning
directly to make whole new individuals (not ES cells, as with the American
experiments) leads to defects and problems, the likelihood of generating viable
human clones recedes. The attack of the clones, at least as the science fiction
writers would have it, seems to be just as far away as ever.

				
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posted:1/21/2013
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