Chapter 7 Animal Biotechnology

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Chapter 7 Animal Biotechnology
BTEC 3301
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Dolly the sheep

• Dolly was created by agricultural research
  scientists, who were being funded to make the
  perfect sheep, for the purposes of more efficient
  agricultural production.
• The name "Dolly" came from a suggestion by the
  stockmen who helped in the process, in honor of
  Dolly Parton, because the cloned cell was a
  mammary cell
• After the cloning was successfully demonstrated
  by Dolly creators, many other large mammals have
  been cloned, including horses and bulls.

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• Dolly who became the first famous adult cloned
  sheep was successfully cloned in 1996, (July 1996
  to Feb 2003) was the first mammal to have been
  successfully cloned from adult cells.
• She was created at Roslin Institute Scotland and
  lived there until her death nearly seven years
  later.
• Dolly was put down on
• Feb 14 2003, due to complications from a lung
  infection.
• Refer Pg 159 Fig7.7 for the process.

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Transgenic Animals

• Animal biotechnology is the field to engineer
  transgenic animals, i.e., animals that carry
  genes from other species.
• The technology has already produced transgenic
  animals such as mice, rats, rabbits, pigs, sheep,
  and cows

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What is a transgenic animal?

• A transgenic animal is one whose genome has been
  changed to carry genes from other species.
• For example, an embryo can have an extra,
  functioning gene from another source artificially
  introduced into it, or a gene introduced which
  can knock out the functioning of another
  particular gene in the embryo

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• Animals that have their DNA manipulated in this
  way are known as transgenic animals.
• Transgenic animals are useful as disease models
  and producers of substances for human welfare

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Why are these animals being produced?

• Some transgenic animals are produced for specific
  economic traits. For example, transgenic cattle
  were created to produce milk containing
  particular human proteins, which may help in the
  treatment of human emphysema (A lung disease
  which involves damage to the air sacs (alveoli)
  in the lungs)

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• Other transgenic animals are produced as disease
  models (animals genetically manipulated to
  exhibit disease symptoms so that effective
  treatment can be studied
• The OncoMouse or the Harvard mouse, carrying a
  gene that promotes the development of various
  human cancers

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How are transgenic animals produced?

• DNA microinjection
• Introducing the transgene DNA directly into the
  zygote at an early stage of development. No
  vector required
• Retrovirus-mediated gene transfer
• Infecting mouse embryo with a retrovirus which
  carry the new gene. Using virus as a vector .

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• Embryonic stem cell-mediated gene transfer
• The blastocyst (inner layer of a fertilized egg)
  is harvested and mixed with recombinant DNA and
  inserted back in the blastocyst
• Sperm-mediated transfer
• Use of Linker protein" to attach DNA to sperm
  which transfer the new DNA during fertilization.
• Gene gun
• As described in Chapter 6.

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Embryonic stem cell-mediated gene transfer

• This method involves
• isolation of totipotent stem cells (stem cells
  that can develop into any type of specialized
  cell) from embryos
• the desired gene is inserted into these cells
• Cells containing the desired DNA are incorporated
  into the host's embryo.

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Assignment for class Stem cell Research.

• Stem cell Research

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Improving Agricultural Products with Transgenics

• Transgenic technology holds great potential in
  agriculture, medicine, and industry
• The benefits of these animals to human welfare
  can be grouped into areas
• Agriculture
• Medicine
• Industry

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1. Agricultural Applications

• A) Breeding
• Traditional cross breeding have been used for
  ages to create chickens, cows, pigs etc.
• Farmers have always used selective breeding to
  produce animals that exhibit desired traits
  (e.g., increased milk production, high growth
  rate).
• Traditional breeding is a time-consuming,
  difficult task.

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• Researchers have now used gene transfer to
  improve the productivity of livestock. Now it is
  possible to develop traits in animals in a
  shorter time and with more precision.
• It also offers farmers an easy way to increase
  yields.

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• Scientists can improve the size of livestock
  genetically.
• Transgenic cows exist that produce more milk or
  milk with less lactose or cholesterol.
• Transgenic cows have been used to produce milk
  which are richer in proteins and lower in fat.

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• B) Quality
• Herman, a transgenic bull carries a human gene
  for Lactoferrin (gene responsible for higher iron
  content)
• Pigs and cattle that have more meat on them.
• Sheep that grow more wool.
• Eggs can be made healthier with high quality
  protein.

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• C) Disease resistance
• Disease-resistant livestock is not a reality just
  yet.
• But there has been improvement in disease
  reduction in animals.
• The Foot- and- Mouth disease in England in 2000
  led to destruction of herds of cattle, sheep and
  goat.

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• Scientists are attempting to produce
  disease-resistant animals, such as
  influenza-resistant pigs, but a very limited
  number of genes are currently known to be
  responsible for resistance to diseases in farm
  animals.
• Transgenic disease protection promises a long
  term cost effective method of battling animal
  diseases.

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2. Medical Applications

• Xenotransplantation
• Transplant organs may soon come from transgenic
  animals.
• Transgenic pigs may provide the transplant organs
  needed to alleviate the shortage of organs donor

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• Xenotransplantation is hampered by a pig protein
  that can cause donor rejection but research is
  underway to remove the pig protein and replace it
  with a human protein.
• Milk-producing transgenic animals are especially
  useful for medicines.

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• B) Nutritional supplements and pharmaceuticals
• Products such as insulin, growth hormone, and
  blood anti-clotting factors may soon be or have
  already been obtained from the milk of transgenic
  cows, sheep, or goats.
• The first transgenic cow (Rosie ) produced human
  protein-enriched milk at 2.4 grams per liter.

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• This transgenic milk is a more nutritionally
  balanced product than natural milk and could be
  given to babies or the elderly with special
  nutritional or digestive needs.
• A transgenic cow exists that produces a substance
  to help human red cells grow.

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• C) Human gene therapy
• Human gene therapy involves adding a normal copy
  of a gene (transgene) to the genome of a person
  carrying defective copies of the gene.
• Finland produced a calf with a gene that makes
  the substance that promotes the growth of red
  cells in humans.

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3. Industrial Applications

• By extracting polymer strands from the milk and
  weaving them into thread, the scientists can
  create a light, tough, flexible material that
  could be used in such applications as military
  uniforms, medical microsutures, and tennis racket
  strings.
• Biosteel is an extraordinary new product that may
  be soon used in bullet proof vests and in suture
  silk for stitching wounds.
• Animals have been used as Bioreactors to
  produce proteins. Genes for desired proteins are
  introduced via transgenics to the target cells .

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• The target cells are cloned and several such
  cells are raised into adults.
• These adults may produce milk or eggs (due to the
  presence of introduced gene rich in desired
  protein).
• Toxicity-sensitive transgenic animals have been
  produced for chemical safety testing.
• Microorganisms have been engineered to produce a
  wide variety of proteins, which in turn can
  produce enzymes that can speed up industrial
  chemical reactions.

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• Transgenic animals have been used to produce
  pharmaceutical protein example a human gene
  called AT III has been transferred to goats.
• Goats milk contain this protein that prevents
  blood clotting (goats multiply faster than cows)
• Hen bioreactor eggs are used to enrich protein
  by recombinant DNA technology.

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What are the ethical concerns surrounding
transgenesis?

• Ethical concern is ever increasing as the
  technology grows, including the issue of lab
  animal welfare
• These ethical issues include questions such as
• Should there be universal protocols for
  transgenesis?
• Should such protocols demand that only the most
  promising research be permitted?

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• Is human welfare the only consideration?
• What about the welfare of other life forms?
• Should scientists focus on in vitro (cultured in
  a lab) transgenic methods rather than, or before,
  using live animals to alleviate animal suffering?

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?

• Will transgenic animals radically change the
  direction of evolution, which may result in
  drastic consequences for nature and humans alike?
• Should patents be allowed on transgenic animals,
  which may hamper the free exchange of scientific
  research? ?

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A summary of Animal Cloning

• Although there has been limited success in
  cloning some animals, it's still seen as a viable
  technology.
• Ever since the announcement of the birth of Dolly
  three years ago, additional sheep, cows, goats,
  pigs and mice have been cloned.
• So far, most cloned animals die just before or
  after birth.

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• There are still obvious problems as evidenced
  from the numerous deaths of cloned animals that
  occur just before or after birth.
• Cloning is a big first step. Genetic manipulation
  of cloned animals is the future direction of the
  cloning frontier.

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• Cloning can produce genetically identical
  laboratory animals which can be used as models
  for human disease.
• No live dog clones have yet been reported, the
  company PerPETuate, Inc. (Connecticut) is
  freezing tissue from family pets for the future.
• Cells could be harvested from early embryos to
  provide cell and tissue replacement without the
  hazards of transplantation rejection.

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• The cloning of human embryos for reproductive
  purposes is illegal at this time.
• Yet it is still important to examine the
  consequences and the likelihood of this scenario.
  
• The media may dream up and forecast robotic
  cloned armies of Hitler however, identical twins
  illustrate that being genetically identical does
  not remove their humanness.

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• At any rate, there have been significant
  difficulties with cloning primates, including an
  extremely low success rate and a high number of
  abnormalities.
• These results make it unacceptable to attempt
  human cloning at this moment in time.
• Cloning has opened many doors that could lead to
  remarkable medical advancements but, as with all
  new technologies, it will be accompanied by
  ethical and social dilemmas.

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• Today's successes will pave the road to improving
  efficiencies and help add to the basic
  understanding of our cells.
• Even Dolly's creator, Ian Wilmut, is focusing
  less on sheep and more on understanding the
  mechanism of reprogramming our genetic material!.

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What are stem cells?

• Additional reading
• Keep update with political issues on stem cells
  research including Christopher Reeves (Superman)
  idea of promoting stem cell research.

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• Stem cells can be used to grow any organ.
• Stem cells have the capacity to develop into any
  type of cell in the body.
• And therefore, they have the potential to be used
  for almost anything, organ transplants, a cure
  for Parkinson's etc.
• Fetal stem cells, once harvested, cannot become
  embryos!.

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• When a woman's egg is fertilized, the egg (or
  zygote) is totipotent -- it has the capacity to
  turn into any type of cell in the human body,
  including the placenta.
• About four days after fertilization the cells
  begin to specialize and form a blastocyst, which
  is a hollow sphere of cells with an inner cell
  mass in the center.
• The outer layer of cells becomes the placenta and
  other tissues necessary for the survival of the
  fetus

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• The inner cell mass goes on to form the fetus and
  eventually the baby. It is these inner cells that
  are so incredible because they go on to form all
  the tissues in the human body.
• If this inner cell mass was placed in a woman's
  uterus, it would not develop into a fetus and
  because of this some people claim that this
  cannot be considered an embryo

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• The controversy comes when the cells are
  harvested.
• Harvesting can be done by
• obtaining cells from the embryos of terminated
  pregnancies
• getting them from embryos from in vitro
  fertilization clinics

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The politics of stem cells

• In 1993, President Clinton banned federally
  funded research on stem cells and now President
  Bush has promised that he'll "not support
  research from aborted fetuses."
• The government's position reflects the views by
  others who oppose stem cell research. For
  example

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• Religious groups and some politicians believe
  that it's unethical to harvest these cells
  because they believe it destroys the embryo.
• One Kansas senator went as far as to say that
  it's "Nazism," saying it's "illegal, immoral, and
  unnecessary."3

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• Some religious groups also believe that "you are
  getting in the way of God's work.
• Adult stem cells have limited potential and may
  carry genetic mutations

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References

• http//www.animalbiotechnology.org/ani_bio.asp
  (List of transgenic animals)
• http//en.wikipedia.org/wiki/Human_cloning (Human
  cloning)
• http//www.gre.ac.uk/courses/under/sch/cls/biochem
  _bsc.html (Cloning)
• http//www.stemcells.ca/
• http//en.wikipedia.org/wiki/Stem_cell
• http//gslc.genetics.utah.edu/units/stemcells/
• http//www.humancloning.org/dolly.htm (Dolly
  created)
• http//news.bbc.co.uk/2/hi/science/nature/2764039.
  stm (Dolly dies)

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Animal Biotechnology

• Dolly