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surfchick
Dec 22, 2004

Cloning, Methods, Controversy, and Analysis Research Paper

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Cloning

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 fertilised egg.
Likewise, many tumours 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
fertilised 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.
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, 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.

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 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 unfertilised 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 fertilisation. 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 fertilised 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 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.