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Biotech century ending?
This miniseries charts the further collapse of the biotech empire, particular in the supposedly ‘highly lucrative’ biomedical sector since the latter part of 2000. It is now desperately grasping for support from the taxpayer by hyping genetics and bio-defence. Don’t be fooled.
- Genetics & Bio-Defence Research Rescue Biotech Slump
- Gene Therapy Risks Exposed
- Death Sentence on Cloning
- Pig Organ Transplants Dangerous & Costly
- Animal Pharm Folds
Death Sentence on Cloning
The final curtain is drawn over the controversial Dolly cloning. But that should
spell the death for ‘therapeutic’ human cloning as well, say Dr.
Mae-Wan Ho and Prof. Joe Cummins.
The complete document with references, is available in the ISIS members site. Full details here
Ian Wilmut, father of Dolly the cloned sheep, had effectively passed the death
sentence on cloning in a review published in Nature October 2002. The death
sentence was already overdue by then, for cloned animals had been pronounced “a gallery
of horrors” the year before.
The review said cloning by present methods is “very inefficient”, due to “inappropriate
expression of many genes”, “failure of ‘reprogramming’”. Cloning has so far been
accomplished in sheep, cattle, mice, pigs, goats, rabbits and cats; but not in rat,
rhesus monkey and dog. And only 0-4% of embryos reconstructed using adult or foetal
somatic cells develop to become live young.
In addition to failures during embryonic development, there are high rates of
foetal, perinatal and neonatal loss, and production of abnormal offspring. Some effects
are attributed to embryo culture.
Typically, at least one third of surrogate mothers confirmed pregnant lose their
foetuses during gestation. Abnormal development of the placenta, including reduction
of blood vessels is a principal contributing factor during early pregnancy in sheep
and cattle. It may also contribute to some of the defects reported in neonates. In
cattle the rate of loss is also increased in the second and third trimester (compared
with in vitro fertilisation, IVF), with greater losses when adult rather than foetal
or embryonic nuclei are used. The over-accumulation of placental fluid occurs rarely
in natural pregnancies, but can affect up to 2 and 40% of pregnancies established
with IVF and cloned embryos, respectively. In cloned mice, the placenta is often
2-3 times heavier than normal.
Many cloned offspring die within the first 24h of birth, commonly from respiratory
distress, increased birth weigh and major cardiovascular abnormalities that can result
in gross distension of the liver and dilated major vessels. Oversized offspring are
frequent in many species. Prolong gestation, fluid accumulation, enlargement of organs,
sluggish onset of labour and difficulty in breathing are also common.
Postnatal abnormalities that have been described include failure of the immune
system, structural abnormalities of the brain, digestive dysfunction, enteritis and
umbilical infections. Genetic background or donor cell type may play a part. In two
independent studies with different strains of mice, those cloned with cumulus cells
became obese in adult life, whereas those from Sertoli cells of immature mice died
at an unusually early age. By contrast, physiological studies of cloned calves suggest
normality, at least for the tests administered. But the eldest was only 4 years when
tested. Success also depends on the cell cycle stage of the donor cell.
In sheep, cattle and mice, inappropriate expression of genes, perturbations in
the expression of imprinted genes are often observed. Epigenetic instability inherent
to embryonic stem cells lines may also be a factor in the failure of cloning from
such cells.
Another top cloner Yanagimachi summarized the experience of cloning mammals: “At
present, cloning efficiency..…is low regardless of the cell type (including, embryonic
stem (ES) cells) and animal species used. In all animals, except Japanese black beef
cattle, the vast majority (97%) of cloned embryos perish before full term. Even in
the Japanese cattle, less than 20% of cloned embryos reach the adulthood. This low
efficiency of cloning seems to be due largely to faulty epigenetic reprogramming
of donor cell nuclei after transfer into recipient eggs. Cloned embryos with major
epigenetic errors die before or soon after implantation. Those with relatively ‘minor’
epigenetic errors may survive birth and reach adulthood. We found that almost all
foetuses of inbred mice die at birth from respiratory problems, while those of hybrid
mice do not, suggesting that genomic heterogeneity masks—to some extent—faulty epigenetic
errors. So far, the majority of cloned mice that survived birth, had a normal life
span and were fertile. However, these animals may not be totally free of health problems.
Post pubertal obesity in certain strains of mice is one example.”
Cloned adults show abnormalities including liver damage, tumours and impaired
immune systems. And serial cloning of mice to six generations did not improve embryo
survival, suggesting that ‘clone-ability’ could not be improved by selection. The
fundamental question is, do cloning defects arise from unsolved technical problems
or are the deaths and defective phenotypes a fundamental and irreparable consequence
of cloning?
A recent study examined the expression of 10 000 genes in developing embryos and
placenta of cloned mice, using a micro array gene-chip. Clones were derived from
embryos produced using cell nuclei from cultured embryonic stem cells or from freshly
isolated cumulus cells (cumulus cells are the maternal cells adhering to the developing
egg), and the RNA in placenta and liver cells screened. The results show that for
both donor cell types, about 4% of the expressed genes in placenta of the cloned
animals differed dramatically from normal embryos, and the majority of abnormally
expressed genes were common to both cumulus cell clones and embryonic stem cell clones.
But the expression of a smaller set of genes differed between the embryonic stem
cell clones and the cumulus cell clones. The livers of the cloned mice also showed
abnormal gene expression, although to a lesser extent than the placental cells, and
involved a different set of genes. Thus, most abnormalities were common to the cloning
operation, with the rest reflecting the particular cloned nuclei (whether from embryonic
stem cell culture or fresh cumulus cells).
It is clear that cloning animals is no longer considered a commercially viable
option, and there are those of us who have opposed it on ethical grounds long before.
However, many researchers are still arguing for ‘therapeutic’ human cloning, ie,
to clone human embryos that will be sacrificed to produce embryonic stem cells for
tissue replacement, a procedure that most people find objectionable on ethical grounds.
Of course, the abnormalities in gene expression and ‘reprogramming’ that dogs animal
cloning will still affect the embryonic stem cells, which raises serious safety concerns.
But these concerns are generally ignored.
The overriding concern of most people including ourselves, is that ‘therapeutic’
human cloning is an “unnecessary evil” when evidence dating back to 2001 already
shows that adult stem cells, readily obtainable from patients themselves, are a much
safer, more effective and affordable treatment.
Research and clinical findings since have amply confirmed the promises of adult
stem cells. A new report in the Lancet earlier this year documents
how bone marrow cells taken from patients who have suffered myocardial infarction
and injected back into the patients, were able to regenerate the damaged heart tissues.
This should spell the death also for ‘therapeutic’ human cloning and human embryonic
stem cells research.
The complete document with references, is available in the ISIS members site. Full details here
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