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Animal Cloning
Animal Clones
• Natural clones in animals are rarer than in plants,
fungi and bacteria but they do occur.
• Thus
– Hydra and Obelia will produce new organisms by
budding
– Aphids will produce large numbers of identical female
offspring by parthenogenesis in the summer
– Cleavage of a fertilised ovum to give two separate
embryos will produce identical twins
• An animation on cloning can be viewed at:
http://www.dnalc.org/resources/animations/cloning101.html
• Artificial cloning is becoming more
commonplace and use one of two methods:
– Artificial embryo splitting
– Somatic cell nuclear transfer
Artificial Embryo Splitting
• This is the equivalent of artificially producing twins.
– Cells of an early embryo are separated
– Each cell can potentially grow into an individual
– All will be genetically identical and a clone
• High value pedigree animals are used as egg and sperm
donors
– Produce a zygote which is grown onto the 8-, 16- or 32-cell
stage
– Embryo then split into single cells or groups of cells
– Allowed to develop further before implantation into
surrogate mothers – do not need to be high quality
• Cattle and sheep have been cloned in this way.
IVF
Early
embryo
with 8, 16
or 32 cells
Pedigree bull
 sperm
Embryonic
cells separated
Embryos implanted into surrogate cows
High quality
cow  eggs
Cloned cattle
produced
Q. Suggest which features might make the
donor cow and the bull ‘high quality’.
Q. Suggest why, following embryo splitting,
the groups of cells are further grown on
before implantation into the surrogates.
Q. Why do the surrogates not have to be
pedigree animals themselves to produce
quality calves?
Q. Suggest which features might make the donor cow and
the bull ‘high quality’.
• Milk yield; protein/fat content of milk; temperament;
growth rate; food conversion rate; lean meat.
Q. Suggest why, following embryo splitting, the groups of
cells are further grown on before implantation into the
surrogates.
• Check that growth and cell division are proceeding
normally; may want to further subdivide embryos.
Q. Why do the surrogates not have to be pedigree animals
themselves to produce quality calves?
• Quality comes from the pedigree cow and bull; all
embryos are genetically identical; surrogate simply acts as
a womb for embryo to grow in.
Somatic Cell Nuclear Transfer
• In this technique:
– A differentiated cell is extracted from an animal, and
– Placed into an enucleated egg cell
• i.e. an egg cell that has had the nucleus removed
• With luck, the egg develops, but uses the
instructions in the DNA from the donated nucleus
to control its growth and development.
• The resulting animal is a clone of the animal from
which the cell was removed from.
• Somatic cell nuclear transfer produced Dolly the sheep in 1996, at
the Roslin Institute, University of Edinburgh.
– Dolly was the first mammal to be cloned from an adult cell.
– Cells from the udder of a Finn Dorset ewe were fused with an
enucleated egg taken from a Scottish Blackface ewe.
• Dolly was the only success from a large number of tries
– 277 eggs were used to make 29 embryos which produced three lambs,
only one of which, Dolly, survived.
• Dolly was fertile, went on to have lambs of her own, but got
arthritis and was ‘put down’ aged six.
• Dolly also had a type of virus-induced lung cancer (sheep
pulmonary adenomatosis)
– Indoor-raised sheep are prone to it
– Other sheep in the flock also suffered from it
Nucleus
removed from
egg
Egg taken from
a Scottish
Blackface ewe
Embryo
transplanted into
uterus of Scottish
Blackface ewe
Electric shock and/or
chemicals stimulate
cell division
Udder cell and
enucleated egg
fused together
Cell taken from
udder of a Finn
Dorset ewe
Finn Dorset lamb
produced – a clone
of the original,
named ‘Dolly’
Q. Suggest why the surrogate mother was a Scottish
Blackface rather than a Finn Dorset.
• Physical characteristics very different so it would be
easy to spot lineage of the lamb; larger; known to be
capable of accepting a transferred embryo.
Q. Suggest how it might be possible to prove that Dolly
was indeed a clone of the Finn Dorset sheep that
donated the udder cells.
• Physical characteristics would confirm Finn Dorset
ancestry; genetic fingerprinting; serotyping.
Non-Reproductive Clones
• Rather than produce a whole organism, the aim
of non-reproductive cloning is to make cells,
tissues and organs to replace those that have
been damaged by disease, accident or age.
• Consequently, this is sometimes called
therapeutic cloning.
• Various sources/options for the cloned cells:
– Cancer cells
– Repair faults with gene therapy
– Stem cells
Cancer Cells
• Cancer cells are immortal
– They can divide repeatedly and indefinitely.
• The most well known is the HeLa cell line
– Taken from Henrietta Lacks in the early 1950s
• The cells have been used extensively in
research and drugs testing.
Totipotent, pluripotent, uni/multipotent
Anything, many things, several things
Totipotent
Pluripotent
Potential for storage
for future
therapeutic use
Multipotent / Unipotent
Pluripotent
Stem Cells
• Stem cells are capable of dividing and
differentiating.
• There are:
– Embryonic stem cells
• These are totipotent
– Adult stem cells
• Usually either multi/unipotent or pluripotent
• However, there are exciting developments
which may allow production of totipotent
adult stem cells.
Windpipe transplant breakthrough
Trachea is
removed from
dead donor
patient
Donor trachea "scaffold" coated with
stem cells from the patient's hip bone
marrow. Cells from the airway lining
added
It is flushed with chemicals to
remove all existing cells
Once cells have grown (after about four
days) donor trachea is inserted into
patient's bronchus
Trachea (wind-pipe)
graft ready for
transplantation
Narrowing of bronchus
to left lung
http://news.bbc.co.uk/1/hi/health/7735696.stm
Potential Uses of Stem Cells
• Potential uses of stem cells are:
–
–
–
–
–
Regeneration of heart tissue damaged by heart attack
Production of liver to replace one damaged by disease
Repair nervous tissue damaged by multiple sclerosis
Repair of nervous tissue following a broken neck
Repair brain tissue in Parkinson’s disease
• There would be definite advantages to such uses
– There would be no rejection
– There would be no donor shortage
– Stem cells are totipotent and so have great potential
Synthetic organs seeded by stem cells:
http://www.bbc.co.uk/news/health-14072829
Repair Faulty Genes in Gene Therapy
• Replace faulty gene in a cell line and then grow
the repaired cells (nuclear reprogramming)
• Example: SCID (severe combined
immunodeficiency disease)
– Caused by faulty gene coding for an essential enzyme
in T cells
– Correct gene is inserted using a retrovirus
– Repaired cells cloned before putting them back into
the body
The stem
cells should
have the same
recognition
antigens as
any other cell
from the
patient’s body
Advantages and Disadvantages of Animal Cloning
• Discuss the potential advantages and
disadvantages of cloning animals, and then
complete the summary table.
• You should consider:
– Genetic uniformity
– Desirable qualities
– Ability to produce sufficient numbers
– Specific examples of potential benefit
Advantages of Animal Cloning
Disadvantages of Animal Cloning
Cloned animals are genetically
identical – all have the good
characteristics of their ‘parent’, e.g.
milk yield, meat quality.
Transgenic animals can be cloned,
so producing a small herd that
produces specific human protein in
their milk, i.e. pharming.
Endangered animals can be
cloned, so preserving their genes
for future.
Cloned animals are all genetically
identical – may have unknown
genetic disease or susceptibility to
disease.
Quality of life of cloned animals
may be poor – smaller groups,
isolation, controlled conditions,
shorter life expectancy.*
Clones are genetically identical and
so could be problems of genetic
drift and evolutionary bottlenecks.
Rapidly improve the quality of
herds.
Success rate is low for some types
of cloning, e.g. Dolly only success
out of 277 attempts.
*Early evidence from cloning suggested lifespan may be less – thought that
starts life with a genetic age that is the same as the cell that was cloned and
that each cell/chromosome only capable of a certain number of divisions. May
not be so!
Summary • Natural plant clones are produced
• Depending upon your perspective a
clone is:
– A group of genetically identical
organisms or
– An exact copy of a:
•
•
•
•
Cell
Chromosome
Gene
DNA
• Reproductive cloning aims
to produce a whole
organism and can utilise
natural or artificial
methods.
• Non-reproductive cloning,
aka therapeutic cloning,
produces cells or tissues for
treating disease.
by vegetative propagation.
– Examples include:
• Bulbs, corms tubers, runners,
rhizomes and root suckers
• There are advantages:
– Uniformity allows colonisation of
an area that suited to
– Resist damage by grazers
– Fallback if sexual reproduction
fails
• There are also disadvantages:
– Uniformity means there is:
• Insufficient variation to cope with
change
• Increased disease susceptibility
– Takes time to colonise new areas
• It is likely that all English elms are
derived from trees introduced by
the Romans
– Only reproduces
• From root suckers
• Cuttings
– All elms are a clone
• Susceptible to Dutch elm disease
cause by the fungi
– Ophiostoma ulmi and O. novoulmi and
– Transmitted by the elm bark
beetle Scolytus scolytus
– English elm virtually wiped out
by the disease
• Traditionally many cultivated
varieties of plants have been
propagated artificially
– Cuttings
• Cut below a node and place in
gritty compost
• Roots produced from cambium
– Grafts
• Bud is grafted onto a root stock
– Cuttings and grafts are identical
to parent material
• Tissue culture is an example of
artificial propagation
– Meristem culture
• Buds are excised and grown
into plantlets
– Callus culture
• Explant material produces a
mass of undifferentiated wound
tissue (callus)
• Can be split and induced to
differentiate
– Cell suspension
• Callus grown in suspension to
obtain metabolites
• Natural clones in animals are
rarer than in plants
– Examples include:
• Identical twins
• Parthenogenesis in aphids
• Artificial cloning can be achieved
by:
– Artificial embryo splitting
• IVF using pedigree cow and bull
• Early embryo split into groups
– 2, 4 or 8 cells
– Each develops into further
identical embryo
– Somatic nuclear transfer
• Enucleated ovum has nucleus
from mature cell inserted
» Dolly the sheep is a well known
example of such a clone
» Low success rate for technique
• Non-reproductive cloning
includes:
– Use of cancer cells
• E.g. HeLa cells
• For testing drugs
– Replacing faulty gene
• Then cloning repaired cell
• As with T cells of patients
suffering from SCID
– Stem cells
• To regenerate/repair tissue
damaged by disease