ISIS Report 28/03/11
Unacceptable Death Rates End Cloning Trials in New Zealand
Government lab announced the end to
cloning eight years after the scientist who pioneered the technique abandoned
it for precisely the same reasons Dr. Mae-Wan Ho
Please circulate widely and forward to
your political representatives
Final curtains on animal cloning?
“Unacceptable death rates” forced New Zealand national science agency AgResearch to end its trials on cloning animals . But
it will continue to create more genetically modified (GM) animals using a new
The agency has
issued reports – obtained by The Dominion Post under the Official
Information Act - documenting chronic arthritis, pneumonia, lameness and blood
poisoning among the causes of death in cattle, sheep and goats.
The reports include
trials on genetically modified (GM) animals for producing “super milk” as well cloned
animals. Cloning and genetic modification are closely linked (see  Cloned Meat
& Milk Coming, Be Very Afraid, SiS 50).
biotechnologies general manager Jimmy Suttie said that the decision was made
after 13 years of study to find out how to prevent abnormalities in cloned
animals, and “enough is enough.”
Nuclear transplant cloning causes high
rates of death and abnormalities
Cloning by nuclear transplant (NT) involves
transferring the nucleus of a cell from the adult or developing embryo into a
mature egg that has had its nucleus removed. The
reconstituted eggs are activated to develop, and the resultant embryos are
implanted into surrogate mothers. The technology is
highly inefficient and has been known to involve horrendous deaths and
deformities in clones and surrogate mothers alike.
In 2003, Ian
Wilmut, who pioneered the technology abandoned it for cloning animals  (Death Sentence on
Cloning, SiS 19), stating that he would use NT only for creating
human cells for tissue repair and for studying human diseases. However, the
discovery that ordinary human cells could be induced to become stem cells had
made NT completely redundant .
In NT cloning of
normal non-GM animals, at most 10 per cent of cloned embryos selected for
implantation survive the trials . (In terms of total embryos made by NT, it
would be about 1 percent.) The main problems were spontaneous abortions and hydrops,
where the surrogate mother’s uterus fills up with water, and the animal has to
be put down.
The New Zealand
Animal Ethics Committee reported 16 foetuses or calves from mid gestation
onwards spontaneously aborted or died in the neonatal period in 2010. Another
10 foetuses or calves had to be euthanized along with 14 cows.
Genetic modification without cloning?
Although cloning trials have been abandoned,
AgResearch would continue to develop transgenic cattle, sheep and goats. Suttie
said new technology using embryonic stem cells to create transgenic animals was
unlikely to cause the same death rates as cloning.
research has only begun four months ago. In 2010, two out of 12 kids delivered
at term in a trial to develop transgenic goats died at birth. One suffered from
chronic arthritis in its front legs. Four other animals died or had to be
euthanized in another trial to produce transgenic cattle.
AgResearch’s work would benefit New Zealand. The trials include creating
animals that will produce proteins with pharmaceutical benefits. One goal was
to produce a drug like Herceptin more cost-effectively and make it readily
available. Herceptin is a monoclonal antibody drug for treating certain breast
cancers costing $100 000 a year, but is controversially associated with a high
risk of death from heart disease .
to end cloning from AgResearch lacks credibility in view of its continuation
with developing transgenic animals. All the signs are that GM and cloning go
together, given that the original motivation for NT was to create ‘elite herds’
of GM animals to produce drugs in their milk . It is also why NT cloning is
continuing in the US.
A potential alternative
route to creating cloned transgenic animals is via genetic modification of
cells that could then be turned into induced pluripotent stem cells (iPS cells)
. The iPS cells are then injected into a tetraploid embryo made by
fusing the two cells of an ordinary embryo at the two-cell stage with an
electric current so that the resulting cell has four complements of chromosomes
(tetraploid) instead of the usual two (diploid). Such tetraploid embryos would
not develop into organisms, except when embryonic stem cells or iPS cells are implanted
into them. The embryo itself would then develop from the iPS cells while the tetraploid
cells give rise to extraembryonic tissues. This procedure has been carried out
with some success in the mouse , although it is still unclear whether it
would work in another species. So far, iPS cells have yet to be created from
Published studies confirm high death and
failure rates in NT cloning
Cloning efficiency by nuclear transfer,
measured as the proportion of selected cloned embryos transferred into
surrogate mothers that survive into adulthood, is 9 percent at AgResearch,
according to a study published from the agency in 2009 . The proportion
surviving to term is 14 percent, but further losses occur before weaning. These
figures compares unfavourably with IVF where approximately 30 percent develop
into healthy calves at weaning.
Poor survival of
cloned embryos is generally attributed to the unpredictable nature of
NT-induced reprogramming of the donor nucleus and the marked changes in
epigenetic identity and transcription pattern of the hybrid egg cell. These
reprogramming reactions are initiated in the cytoplasm of the egg cell
immediately following the transfer of the donor nucleus. Although some of the
necessary genes for reprogramming are known, it is still impossible to predict
or influence cloning efficiencies in any reliable way.
analyses showed substantial differences between the transcriptomes (the
totality of transcripts) of NT vs fertilized or artificially activated embryos.
Over 95 percent of genes were reprogrammed, but no distinct set of consistently
mis-expressed genes were found in NT embryos. Proteomes (the totally of
proteins expressed), with its many low-abundance proteins and often carrying
post-translational modifications, are more difficult and complex to analyse,
and have not been profiled comprehensively in NT clones.
No correlation between cloning
efficiency and state of differentiation of donor cell
The hypothesis that cloning efficiency is
inversely correlated with the differentiated status of donor cell could not be
confirmed. Once the zygote (fertilized egg) starts to develop, and divides into
smaller cells called blastomeres, reprogrammability declines. In the mouse,
there is a clear decline in cloning efficiency between the 4 to 8 cell stage;
as consistent with the notion that individual four- but not eight-cell mouse
blastomeres are still totipotent, i.e., able to give rise to all embryonic and
extraembryonic cell types. Thus, using nuclei from the zygote versus cumulus cells
(that surround the developing egg cell in the ovary) gives cloning efficiencies
of 34 vs 3 percent, and using nuclei from a 4-cell embryo vs foetal fibroblasts
results in cloning efficiencies of 43 vs 3 percent.
According to the same
hypothesis, stem cells, which are undifferentiated, and multipotent (capable of
giving rise to more than one cell type), should give higher cloning
efficiencies than differentiated somatic cells; but this has failed to be confirmed
by extensive experimentation. Cultured ES (embryonic stem) cells are notorious
for epigenetic instability and accumulation of chromosomal abnormalities, which
make them unreprogrammable. Patterns of DNA methylation (a common form of gene
marking) and expression of imprinted genes (genes expressed according to
whether they come from mother or father) vary widely between ES cell lines and
between subclones of a given ES cell line, and even individual cells in a
Stem cells and progenitor cells
(arising from stem cells but before they differentiate into definite cell
types) were evaluated as nuclear donors in seven different somatic lineages -
antler, adipose tissue, blood, bone marrow, muscle, brain and skin - and
four different species: mouse, cattle, pig and deer. This represented 10
percent of the total number of different mammalian cell types. There was no
substantial improvement in cloning efficiencies of stem cells over somatic
cells. The researcher summed up : No conclusive correlation [between cloning
efficiency and state of differentiation] was found, indicating that the somatic
donor cell type may not be the limiting factor for cloning success.”
Hopes pinned on new stem cells
However, considerable hope has been pinned on
a new method of creating pluripotent stem cells that are capable of producing all
the cells of the embryo except for the extraembryonic tissues.
pluripotent stem cells (iPS cells) are obtained after somatic cells are
transduced (infected) with a vector expression a set of special transcription
factors. Such iPS cells are practically indistinguishable from embryonic stem
(ES) cells in morphology, gene expression and pluripotency. The researcher
considered such cells “the most promising candidates for future somatic NT
experiments,” and stressed “the importance of deriving these cells in livestock
It is not clear
whether the new experiments mentioned by the Dominion Post  on creating
transgenic animals were done with iPS cells. If so, the high rates of death and
abnormalities have hardly diminished.
It is time to
end all attempts to create GM animals or to clone animals by nuclear
transplant. It is unacceptable in terms of animal suffering and the serious hazards
to health as .
“Animal death toll ends cloning trials”, Kiran
Chug, The Dominion Post, 21 February 2011, http://www.stuff.co.nz/national/4681283/Animal-death-toll-ends-cloning-trialshttp://www.stuff.co.nz/national/4681283/Animal-death-toll-ends-cloning-trials
Ho MW. Cloned meat & milk coming, be very
afraid. Science in Society 50
Ho MW and Cummins J. Is FDA promoting or
regulating cloned meat and milk? Science in Society 33,
Okita K, ichisaka T and Yamanaka S. Generation
of germline-competent induced pluripotent stem cells. Nature 2007, 448, 313-8.
Trastuzuma b, Wikipedia, 14 February 2011, http://en.wikipedia.org/wiki/Trastuzumab#Side_effects
Boland MJ, Hazen JL, Nazor KL, Rodriguez AR,
Gifford W, Martin G, Kupriyanov S ad Baldwin KK. Adult mice generated from
induced pluripotent stem cells. Nature 2009, 461, 91-96.
Oback B. Cloning from stem cells: different
lineages, different species, same story. Reproduction, Fertility and
Development 2009, 21, 83-94.
There are 1 comments on this article so far. Add your comment
|Rory Short Comment left 29th March 2011 17:05:29|
Natural evolution has led to humans being able to be conscious. Thus, as we are the products of nature, not its overlords, the most beneficial use of our consciousness would be to use it to work as junior partners with nature in a genuinely cooperative fashion, not as beings functioning independently from nature, which has been how the bulk of humanity has operated up until now. To me the cloning of animals is an excellent example of the misuse of our consciousness.