Documento 11234

Of all the terms coined by scientists which have entered popular vocabulary, 'clone' has become one of the
more emotive. Strictly speaking a clone refers to one or more offspring derived from a single ancestor, whose
genetic composition is identical to that of the ancestor. No sex is involved in the production of clones, and
since sex is the normal means by which new genetic material is introduced during procreation, clones have no
choice but to have the same genes as their single parent. In the same way, a clone of cells refers simply to the
descendants of a single parental cell. As such, adult organisms can be viewed as clones because all their parts
stem from the single cell, which is the fertilized egg. Likewise, many tumors are clones, derived from one
aberrant cell, which no longer obeys the normal rules of growth control. The offspring of organisms which
reproduce asexually, like corals, are also clones; as are identical twins produced by the natural, or sometimes
deliberate, splitting of a single embryo. Members of a clone are genetically identical and genetic identity has
given cloning an additional more technical meaning: namely the procedures used to create a new organism
whose genetic constitution is a replica of another existing individual. Such a feat can be achieved by
substituting the nucleus, which contains the genes, from one of the cells making up that individual's body, for
the nucleus of a fertilized egg.
Since our genes dictate to a large extent what we look like, how we behave and what we can and cannot do,
having identical genes, as identical twins do, ensures something more than mere similarity. Novelists and film
makers have not been slow to exploit the imagery afforded by cloning. Limitless numbers of identical beings
manufactured from existing or previous generations has obvious dramatic potential, although seldom of a
reassuring nature. Clones traverse the cinema screen as crowds of dehumanised humans destined for
monotonous drudgery, as invincible armies of lookalikes from outer space, as replicas of living
megalomaniacs and, in the ultimate fantasy, as the resurrected dead − troupes of little Hitlers and herds of
rampaging dinosaurs. Of course, this is science fiction. Nonetheless there is just a whiff of plausibility, a
whisker of scientific credibility; enough to plant an indelible vision of what might be, or even what could be.
So it is easy to understand why the arrival earlier this year of Dolly, the sheep developed from an egg whose
own genes had been replaced by those from an adult udder cell, was seen as the first incarnation of a sinister
future. Dolly was a clone of the sheep (her genetic mother) who provided the udder cell. The package of genes
in the nucleus of that udder cell contained exactly the same repertoire of genes as all the rest of her mother's
cells and so Dolly's genetic makeup was to all intents and purposes identical to her mother's. No sperm had
had the opportunity to add its genetic pennysworth. However, there was nothing radically new, neither
technically nor conceptually, in the way in which Dolly was made. Almost all films and documentaries on
cloning still show the same footage, produced more than twenty−five years ago during unsuccessful attempts
to clone rabbits, of a nucleus being injected into an egg. What was novel about Dolly was that she was the
first unequivocal mammalian clone. Lower vertebrates had been cloned in the early 1960s when it was shown
that a nucleus taken from an adult frog cell transplanted to a frog egg whose own nucleus had been destroyed
was able to direct the development of that egg into a swimming tadpole. Indeed, it was this experiment that
first indicated that the genetic content of all our cells, despite the profound differences between a skin cell and
kidney cell, must be more or less the same and retain all the genetic information necessary for an egg to
develop into a whole organism.
While cloning can offer the scientist important answers to fundamental questions about our genes, it has a
much older and very natural history which long precedes the sophistications of the modern
laboratory. The word 'clone' comes from the Greek klwn, meaning twig, and there is a very good
reason for this. For example, every chrysanthemum plant you buy at a Garden Centre is a clone of
some distant and probably long dead chrysanthemum which once supplied a side−shoot for rooting.
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Likewise, whenever you divide an overgrown shrub or successfully cultivate a houseplant cutting you are
cloning. In each case you are deliberately propagating a copy of the parent, and eventually over successive
years and many hours in the greenhouse, producing a multitude of plants (clones) all genetically identical to
the prized parent. Elm trees and other suckering plants clone themselves
naturally, sending out subterranean roots from which new plants, of identical genetic constitution, will sprout.
Deliberate cloning is as old as horticulture itself. Thousands of years before anyone
understood the physical nature of heredity, specific genetic constitutions were preserved through
cloning because they bestowed on the plant desirable qualities such as disease−resistance, high yield
and predictable growth. Cloning is as important to the production of fine wine, the supply of rubber
and the fruit harvest as it is to the variety of an English country garden. Furthermore, natural cloning is not
confined to plants: microbes and some insects frequently propagate themselves by producing genetically
identical offspring without recourse to sex. The toothless mammal, the armadillo, gives birth not to identical
twins but to genetically identical octuplets: every litter a batch of eight clones. There is nothing a priori
unnatural about cloning.
Apart from facilitating plant propagation what are the advantages of generating genetically identical
organisms? As with plants, a stable mixture of robustness and productivity is desirable in all agricultural and
commercially important animal stock. Centuries of selective breeding have been
applied to produce particular breeds with a highly selected genetic composition aimed at ensuring
predictable performance. This applies as much to the quest for healthy high milk−yielding cows, or
sheep with particularly luxuriant wool, as to breeding the fastest racehorse or producing the supreme
champion at Crufts. The genealogy of Derby winners is a masterpiece of human design. The very diversity of
dogs is largely attributable to human intervention. All dogs, be they Great Danes or Chihuahuas, belong to a
single species, but over the millenniums man has channelled different canine characteristics into the vastly
different strains we see today. Specific desirable features have been accentuated by persistent inbreeding,
mating close relatives who are already genetically similar such as brother and sister, or father and daughter, to
create even greater genetic homogeneity. As we know this is not always a wholly benign process. For
example, the features of Pugs so loved by their owners are without question a serious handicap to the dog
when it comes to breathing. Likewise, inbreeding to enhance desirable attributes can sometimes also increase
the likelihood of genetic disease. Genes causing hip dysplasia have been carried along with genes defining the
handsome lines of Labradors. Disadvantages aside, the huge array of dog breeds illustrates that striving for
genetic similarity and stability, contrary to popular belief, does not necessarily decrease diversity but actually
often generates greater variety.
In biological research, using genetically identical material, be it cells in a dish or whole organisms, is often
essential for standardising experiments. Only when differences in genetic effects can be ruled out can the
response to a certain drug or a particular infection be interpreted unambiguously.
Ironically, understanding the mechanisms which cause the body to reject transplants of genetically
dissimilar tissue, required generations of inbreeding to produce different inbred strains of mice each
composed of essentially genetically identical individuals. Only then could the response to foreign tissue be
scrutinised rationally. For reasons of survival, commerce, scientific endeavour and sometimes just whimsy,
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and for a very long time, selective breeding has been used to achieve slowly but surely more or less the same
ends that cloning can. However, there are two major differences between cloning and inbreeding. Firstly,
inbreeding takes a long time to ensure the requisite genetic identity. Secondly, it can only take advantage of
genes already present in the organism.
In theory cloning provides an alluring short cut to amplifying the number of animals with an
apparently desirable genetic constitution. If Dolly represents one genetic copy of her mother then
nuclei from the thousands of other udder cells could, with a sufficient supply of host eggs, produce a thousand
Dollies − a thousand genetic replicas − in a single generation. However, here theory and practice diverge.
Dolly was a single sheep produced from nearly three hundred attempts, without even counting the previous
years of failed experiments. With a single result of this kind it is not possible to evaluate the real frequency of
success. Is it one in three hundred or one in a million? Recently, the newspapers have published accounts of a
second sheep clone, although for reasons of commercial priority the provenance of this clone has not been
made available to scientific scrutiny. The existence of a second clone at least suggests that there must be a
finite chance of obtaining liveborn sheep clones. Nonetheless, cloning remains an extremely costly,
technically demanding and inefficient exercise; not one poised to replace normal methods of animal
husbandry.
The desire to clone livestock is largely allied to transgenesis: the ability to add new genes to an
animal's normal repertoire or to precisely modify one of its own genes. Why would one want to do
such a thing? One reason is that farm animals could then be used not just to provide traditional
products such as meat, milk and hide but also to produce natural proteins for pharmaceutical use, or
to serve as organ donors for human transplants. Of course, the production of drugs from animals is
not new − hundreds of thousands of pigs have been sacrificed over the years to supply diabetics with
insulin. However, transgenesis offers a more imaginative and less destructive way of producing drugs
from the farm. Transgenes have been introduced into the nucleus of cow, sheep and pig eggs and
become part of the resulting animal's genetic repertoire, indistinguishable as far as it is concerned,
from its own genes. Such genes have been designed to cause secretion of human proteins into the
milk, thereby turning the milking parlour into a drug production line. In this way, animals have been
generated whose milk contains human proteins involved in emphysema and blood clotting
deficiencies, and it has been possible subsequently to purify quite large quantities of these therapeutic
products from the milk. Such transgenic farm animals would allow patients to be treated with 'on tap'
human products, and the transgenic animals themselves would enjoy exactly the same life style as any
other dairy animal.
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However, introducing genes into eggs is a rather hit and miss affair, because there is no control over
whether the gene will land up in a position where it can be fully active, and only some of the offspring
produce reasonable amounts of human protein in their milk. If the high level producers could be
cloned then standardised herds could be established relatively quickly to facilitate efficient drug
production. Even better, if animals can be cloned from udder cells then why not introduce the
transgene into these cells first, check out that it works properly and then clone an animal from the cell
in which the gene is most active. Better still, take advantage of the animal's own mechanisms for
ensuring high levels of protein in the milk and replace the gene which codes for one of its normal milk
proteins with the gene encoding a pharmaceutical protein. Such precise replacement of one gene by
another is possible but extremely inefficient, occurring perhaps only in one of a million cells. One
cannot contemplate generating a million animals on the offchance that such a replacement might have
occurred, but it is relatively easy to grow a million udder cells in a dish and to recognise and recover
the single cell in which the desired gene replacement has happened. To be able to clone an animal
from such a cell, in which a human protein is being produced at the same high levels as a normal milk
protein, would permit a much better and more controlled means of making transgenic animals than is
practised at present. Likewise, if animals are to serve as organ donors for humans then gene
replacement combined with cloning would allow some of the animal genes most responsible for graft
rejection to be replaced with compatible human ones. Whatever one's personal views about using
animals as vehicles for human drug production or as a source for replenishing defunct human organs,
it is important to realise that it is mammalian transgenesis, which has been underway now for twenty
years, and not cloning, that has opened the way for such practices. Cloning would have little future,
and certainly be of little commercial value, without genetic engineering.
Finally, the inevitable question. Is it possible to clone humans? Actually, the question is
unanswerable. Until Dolly came along no mammal had been cloned by transferring a nucleus into an
egg. Quite considerable efforts had been made over several years to clone mice in order to
understand how gene activity changes during embryonic development. None met with success and it
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was acknowledged that cloning mice was not going to be straightforward. One reason why sheep, a
far less well understood and less used experimental animal than mice, should have proved easier to
clone may relate to differences in the very earliest stages of mouse and sheep embryonic
development. The unfertilized eggs of all mammals accumulate a supply of proteins, and the means of
making more protein, as they mature in the ovary of the mother. In this way, the egg brings with it a
larder for the embryo to make use of until the embryo's own genes become active and it can supply
these things for itself. The sheep embryo makes good use of this store and does not start to depend
on its own genes until the sixteen−cell stage, four cell divisions after fertilization. In contrast, the
mouse embryo gets off to a very quick start, becoming reliant on the activity of its own genes after
just the first division when the fertilized egg becomes two cells. Therefore, a foreign nucleus
introduced into a sheep egg has a bit of breathing space to adapt to its new role before it has to start
running the show. On the other hand, a nucleus introduced into a mouse egg has to acclimatise very
fast for its genes to be able to direct embryonic development within one cell division. Perhaps there
is just not enough time in the mouse for the extensive re−programming of gene activity that is
required. The human embryo is thought to rely on its own genes after three cell divisions, when it
comprises eight cells. This might or might not provide time enough for a foreign nucleus to feel at
home. However, were we to understand the nature of the re−programming that has to take place
then there is every likelihood that both mice and humans could be cloned, although probably still with
a very low success rate.
In order to be prepared it is probably best to assume that the cloning of humans is not impossible.
As has already been pointed out the technology has been available for decades had anyone wanted
to try, but apart from the odd bogus book claiming to be an authentic account of human cloning it
does not seem that anyone has. The great desire for vanity cloning appears to be a fiction. Are there
any arguments in favour of permitting human cloning? Not many. A handful of people who are
childless due to rare hereditary diseases would be able, if they were lucky, to produce offspring that
were genetically theirs. However, if Dolly is anything to go by then a success rate of less than one in
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a hundred poses formidable practical problems. More importantly, it is quite possible that cloned
individuals will turn out to be at risk. We do not know the long term effects of asking an 'old' adult
cell nucleus to begin life again in an egg. The nucleus of a skin cell could have accumulated many
genetic mistakes of no consequence to its role in the skin, but when asked to make a brand new
organism these could prove deleterious in other tissues, or greatly increase the probability of
developing cancer. However, if one asks what threat could cloning pose to general human health, as
opposed to the individual, then the answer has to be none. The risks are almost certainly lower than
those encountered in the effective inbreeding of consanguinous marriages. There are no scientific
grounds per se for banning cloning. Like other things which are possible, not of great consequence
to the physical well being of humanity, but generally considered undesirable on moral or social
grounds,for example cannibalism, female circumcision and polygamy, the outlawing, qualified or not,
of human cloning requires a simple pragmatic decision.
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