Animal pharming: transgenic and cloned animals

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Animal pharmingtransgenic and cloned animals
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The process of using transgenic or cloned
animals to produce human drugs
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Dolly made front pages around the world because
of her startling pedigree Dolly, unlike any
other mammal that has ever lived, is an identical
copy of another adult and has no father. She is
a clone, the creation of a group of veterinary
researchers. That work, performed by Ian Wilmut
and his colleagues at the Roslin Institute in
Edinburgh, Scotland, has provided an important
new research tool and has shattered a belief
widespread among biologists that cells from adult
mammals cannot be persuaded to regenerate a whole
animal. Although the Scottish researchers have
made clear that they would consider it unethical
to adapt their technique to clone humans (Wilmut
is a member of a working group on the ethics of
genetic engineering), the demonstration has
raised the uncomfortable prospect that others
might not be so scrupulous. Cloning humans
would mean that women could in principle
reproduce without any help from men.
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Scientific American, 1997
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Wilmut and his co-workers accomplished their feat
by transferring the nuclei from mature somatic
sheep cells into unfertilized sheep eggs from
which the natural nuclei had been removed by
microsurgery. Once the transfer was complete,
the recipient eggs contained a complete set of
genes, just as they would if they had been
fertilized by sperm. The eggs were then
cultured for a period before being implanted into
sheep that carried them to term, one of which
culminated in a successful birth. The resulting
lamb was, as expected, an exact genetic copy, or
clone, of the sheep that provided the transferred
nucleus, not of those that provided the egg.
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Other researchers have previously cloned animals,
including mammals, by transferring nuclei from
embryonic cells into such enucleated eggs. The
interest in the new work, published in the
February 27, 1997, Nature, is that some of the
transferred nuclei that gave rise to lambs came
not from embryonic cells but from the mammary
gland of a mature, 6-year old ewe. Other
workers have failed to produce viable offspring
when they attempted equivalent experiments.
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The key to success at the Roslin Institute seems
to have been that Wilmut starved the mammary
cells for five days before extracting their
nuclei. This maneuver "froze" the cells in a
quiescent phase of their division cycle and may
have made their chromosomes more susceptible to
being reprogrammed to initiate the growth of a
new organism after the nuclei were transferred
into an egg.
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It required 277 nuclear transfers to produce the
single, viable cloned lamb.
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Wilmut's experiment provides a long-sought
confirmation that adult cells do in fact contain
workable versions of all the genes necessary to
produce an entire organism.
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On February 14, 2003 Dolly was put to sleep. She
was 6 years old, and had been diagnosed with
progressive lung disease. Was it an early death,
was it because she was a clone? Sheep live 11-12
years Dolly came from a 6 years old ewe The
telomerases were shorter She had arthritis on her
hind legs Lung disease is common in older
sheep She had three healthy lambs before she got
sick Conclusions?
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Animal Pharming The industrialization of
Transgenic Animals Transgenic animals express
one or more human genes . The inserted genes,
when successful, enables an animal to make the
desired pharmaceutical in their milk, urine,
blood, sperm or egg, or to grow organs resistant
to rejection after transplants.
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Currently there are more than a dozen different
molecules produced by pharm animals and used for
therapeutic purposes. These include treatment
for cystic fibrosis, hemophilia,
osteoporosis, arthritis, malaria, and HIV.
Transgenic animals can also produce monoclonal
antibodies that are used for the development of
vaccines
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Transgenic animals are costly 20,000-30,000 for
one animal, and low chances of success. If
successful, one animal can produce in its life
time 200,000-300,000 million worth of drugs. A
herd of 600 transgenic cows could supply the
worldwide demand of human serum albumin (used in
the treatment of burns and traumatic injuries)
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Traditional methods to produce recombinant
proteins -Laboratory cell cultures of transgenic
bacteria, yeast, or animal cells Disadvantages
-Cultures require constant monitoring -Expression
is more costly, because substantial machinery
must be purchased and maintained -Isolating and
purifying proteins is more difficult than
purifying proteins from an animals milk or
bodily fluid. Animal bioreactors are more
cost-effective, they have the cellular
machinery to produce complex proteins,
recombinant proteins come out from milk 99
pure.
Any other advantage? Bacteria-vs mammalian cells
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The first trangenic animal produced was a mouse
(1981). A gene was inserted into this mouse that
made him susceptible to cancer. In 1985 the
first transgenic farm animal was made, a sheep
called Tracy. Tracy had a human gene that
expressed high levels of human anti-trypsin. The
protein , when missing in humans, can lead to a
rare form of enphysema.
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Most recently, the enviro pig has been
developed. This pig has a phytase gene placed in
its salivary glands to allow better utilization
of phosphorus in feedstuff. The enviro pig may
prove to be part of the solution to animal
waste issues. In Wisconsin 37 cows were cloned
in 1999, 17 of them were transgenic. The cost
is projected to go down to 5,000 per animal.
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• A human gene responsible for producing a desired
  protein
• Is isolated in a laboratory.
• 2. An animal is given hormonal treatment to
  produce a large number
• Of embryos, and the embryos are collected from
  the oviduct.
• 3. The human gene is inserted into the fertilized
  egg via microinjection
• 4. The transgenic embryo is placed in a surrogate
  host which gives
• Birth to the transgenic animal
• 5. The offspring is tested for the new gene

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