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Cloning is a novel form of sexual reproduction.
OR
Cloning is a novel form of asexual reproduction.
??
??Clones are produced only in
laboratories.
OR
Clones are produced as a normal part of an organism’s biology.
1839: Theodor Schwann lays foundation for cell theory
1855: Rudolf Virchow-”All cells arise from cells”
1865: Gregor Mendel-fundamental laws of heredity
1885: August Weismann proposes that genetic information in cells diminishes as cell differentiate during development
1888: Wilhelm Roux’s work supports Weismann
1892: Hans Driesch shows that each cell of a 2-cell or 4-cell sea urchin embryo can develop into a perfectly formed embryo
1894: 1st nuclear transfer experiment by Jacques Loeb
1914: Hans Spemann performs nuclear transfer experiments with newts and in 1928 with salamanders
1938: Spemann asks what would result if a nucleus from a differentiated cell were inserted into an enucleated egg cell
1952: Robert Briggs and Thomas King report development of normal Rana pipiens tadpoles by transferring nuclei from embryonic cells to enucleated egg cells
1953: Watson and Crick report structure of DNA
1962-75: John Gurdon reports cloning frogs using donor nuclei from fully differentiated adult intestinal cells
1979: Steen Willadsen uses single cells from 8-cell sheep & cattle embryos to raise adult animals
1986: Willadsen clones a sheep from embryo cells using nuclear transfer
1990: Human Genome Project officially begins
1995: Ian Wilmot and Keith Campbell use differentiated sheep embryo cells to clone Megan and Morag, the world’s first sheep cloned from differentiated cells
1997: Wilmot and colleagues report the cloning of Dolly, the first animal to be cloned from adult cells
1997: Polly is born at the Roslin Institute-she is cloned from a fetal fibroblast into which the gene for clotting factor IX had been inserted
1998: James Thomson and colleagues report deriving human pluripotent stem cell lines from blastocysts
1998: John Gearhart and colleagues report the derivation of human embryonic germ cell lines from aborted human fetal material
Primates: 1 success in >300 attempts
Megan and Morag were only surviving fertile sheep from 244 nuclear transfers
Dolly was sole survivor from 277 transfers of adult nuclei
In experiments with cattle, goats, and mice success rate is seldom greater than 3% & many abnormalities observed
Idaho Gem, 1 of 3 from 305 transplants
Success RatesSuccess Rates
Normal Looking = Normal Clone?Normal Looking = Normal Clone?
Reported in Science, July 6, 2001
Scientists made mouse clones from ES cellsMonitored activity of imprinted genes
Found that ES cells are unstable in cultureClones made from sister stem cells had differences in gene expression
Imprinted genes important in fetal development so results are a concern for reproductive cloning
1. The Time Machine Problem
2. Imprinting
3. Physical damage
4. Extra or Missing donor molecules
5. Lack of understanding of process
Possible ReasonsPossible Reasons
Nuclear Transplantation is Nuclear Transplantation is an Epigenetic Probleman Epigenetic Problem
K. Hochedlinger et al., Reprogramming of a melanoma genome by nuclear transplantation, Genes & Development 18:1875-1885, August 1, 2004.
Embryonic stem cell line created from melanoma
Injecting ES cells into blastocysts produced chimeric mice
ES cells contributed to multiple organs, including skin, heart, and liver
Oocyte cytoplasm reprogrammed melanoma nuclei yielding pluripotent embryonic stem cells
are born to two different mothers in two different environments in utero,
develop from different eggs & thus have different mitochondrial genomes, and
experience mutations at different rates and at different places in the genome.
Mutations present in the donor’s genome are passed to the clone, and
Clone may start life with telomeres of shorter length than did donor
Clone and donorClone and donor
ScienceScience, Vol 303, 1669-1674, 12 March 2004, Vol 303, 1669-1674, 12 March 2004Hwang et al., Seoul National UniversityHwang et al., Seoul National University
Used 242 eggs from 16 women
Donor DNA from cumulus cell of egg donor
Produced 30 embryos
Derived pluripotent embryonic stem cell line from cloned blastocyst
Cell line genetically identical to donor and stable after 70 passages
Imprinting and other analyses confirm embryos derived from donor and did not arise by parthenogenetic activation
Teratomas (containing tissue representative of all three germ layers) formed by human SCNT ES cells in the testes of SCID mice at 12 weeks after injection. Neuroepithelial rosset (A), pigmented retinal epithelium (B), ostoid island showing bony differentiation (C), cartilage (D), and glandular epithelium with smooth muscle and connective tissues (E).
There are ethical, legal, There are ethical, legal, and social issues that and social issues that
must be dealt with.must be dealt with.
Is it important to evaluate Is it important to evaluate separately the issues separately the issues surrounding human surrounding human cloning and those of cloning and those of
animal cloning?animal cloning?
Is concern for Is concern for continuity of species continuity of species or fitness of single or fitness of single
individual?individual?
How does one manage the potential dangers for prospective clones when one is attempting to protect a future potential person
against harms that might be inflicted by their very existence?
Is it appropriate for a Is it appropriate for a person to be his/her person to be his/her
own parent?own parent?
Does cloning Does cloning undermine the undermine the
freedom of human freedom of human beings to construct beings to construct
his/her own life?his/her own life?