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Published online 3 February 2009 | Nature | doi:10.1038/457642b
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Hybrid embryos fail to live up to stem-cell hopes
Strategy for creating pluripotent cells called into question.
The creation of human–animal hybrid embryos — proposed as a way to generate embryonic stem cells without relying on scarce human eggs — has met with legislative hurdles and public outcry. But a paper published this week suggests that the approach has another, more fundamental problem: it may simply not work.
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When SCNT with nonhuman ova was proposed in the UK it was accompanied with (more or less explicit) claims that this technology would contribute to the cure of a range of diseases from Cystic Fibrosis to Parkinson's. I do not believe that it was a coincidence that media advocates mentioned a disease which affects the child of the Prime Minister. Those who questioned the ethics or the prospects of this technology had to face angry patients who had been convinced that cybrids would be the holy grail that would cure them. As a critic of these proposals I more than once had to face such anger. Every scientists hopes that his or her project will make a contribution to knowledge, but the high profile public hyping of very speculative proposals, like cybrids, is a disservice to the public and to science. What goes on in the lab, especially where it is publicly funded, needs to be accountable and accountability must start with a realistic assessment of the prospects. If the public debate about the direction and funding of science is reduced to emotional manipulation, as I think it has been in this case, then it has ceased to be a rational discourse. Scientists who use patient groups in this way can do serious harm. I should make clear that, to my knowledge, Justin St John (mentioned in the above article) is not one of those who have used the media or patient groups in this way. Nevertheless, as the difficulties of SCNT with a large species gap are more and more apparent, I hope his team will turn their attentions to more realistic avenues of research.
Since progress has been continuosly made in the field of induced pluripotent cell technology, one that turns somatic cell directly into pluripotent status, patients still can conceive hope and even more than before.
Will iPSCs live up to all the great hopes given to them? Let's us wait and see.
This is really not surprising. Successful development requires harmonious chat between the nuclear and mitochondrial genomes and we've known for years that inter-species cybrids don't function well. There was an ill-fated attempt some years back by an IVF unit in NY to 'rescue' dysfunctional oocytes by fusing them with cytoplasts donated from healthy young women. Someone likened that to fixing sour milk by adding a dollop of fresh!
Hybrid stem cells with necessarily non-matching nuclear and mitochondrial encoded proteins can never provide the promised insights or cures for the diseases listed. From diabetes to Alzheimer's to rarer metabolic disorders the pathology involves mitochondrial proteins. Non-matching mitochondrial proteins will therefore a) not correct the disease and/or b) introduce artefactual different metabolic problems. Hybrids are thus a non-starter even if they grow (as may be the case for closely related e.g. human-primate hybrids). Induced or "natural" adult stem cells may offer both a research and a therapeutic platform. Otherwise perhaps we'll have to accept that sometimes no cure is possible.
exploring the reason could help to understand embryo development