Brussels, 14 Sep 2005
Paul de Sousa of Edinburgh University has announced at the BA Science Festival in Dublin that his team has succeeded in creating 'virgin embryos', or parthenotes, by stimulating a human egg to start dividing like an embryo without the addition of any genetic material from a male sperm cell.
The announcement comes just one day after the UK Human Fertilisation and Embryology Authority (HFEA) authorised the transfer of the components of a human embryo into an unfertilised egg from another woman, further pushing back the boundaries of reproductive research
This virgin conception embryos are expected to mark a new way to grow women's cells and tissues for a vast range of experiments and treatments. The Edinburgh team, working at the Roslin Institute where Dolly the sheep was cloned, used about 300 human eggs from volunteer donors to create half a dozen parthenote blastocysts - human embryos that consist of about 50 cells, which can be used as a source of stem cells.
In normal reproduction, eggs would kick out half their genetic material in preparation to receive the male complement delivered by a sperm cell. To make parthenotes, the eggs were cultured in the lab in such a way that they retain all of their chromosomes; about half could be successfully matured and persuaded to divide with an electric shock. But only five in every hundred grew to the blastocyst stage, and then with only half the usual number of cells. Dismissing objections regarding the efficiency of the process, Dr De Sousa said: 'It's a numbers game. It's just a matter of supply of tissue to be engaged in experimentation.'
The embryos were grown by a process called parthenogenesis, which means 'virgin birth' in Greek; parthenogenesis occurs quite naturally in plants and a number of animals, such as bees and ants and even in a few lizards. Humans, like other mammals, do not undergo this process because of a gene regulation process called imprinting that ensures genes from the mother and father must both contribute if development of the embryo is to reach full term. So far, scientists have induced parthenotes artificially in creatures such as mice and monkeys, although it has very often resulted in abnormal development.
Imprinted genes are genes whose expression is determined by the parent that contributed them; imprinted genes violate the usual rule of inheritance that both sets of parental genes are equally expressed. A small number of genes in mammals, about 80 of them at the most recent count, have been found to be imprinted. Because most imprinted genes are repressed, either the maternal gene is expressed exclusively because the paternal is imprinted or vice-versa. The process begins during gamete formation when, in males, certain genes are imprinted in developing sperm, and in females, others are imprinted in the developing egg. All the cells in a resulting embryo will have the same set of imprinted genes from both its father and its mother except for those cells ('germplasm') that are destined to go on to make gametes (eggs or sperm cells), in which all imprints - both maternal and paternal - are erased.
Imprinting is a very important process: deliberate (experimental in mice) or accidental (in humans) inheritance of two copies of a particular chromosome from one parent and none from the other parent is usually fatal; also the inheritance of two copies of one of the mother's genes and no copy of the father's (or vice versa) can produce serious developmental defects. Moreover, failure of imprinting in somatic cells may lead to cancer.
This is the reason why scientists are interested in using cells from parthenotes, that could shed light on cloning, a process which disrupts imprinting, and on the links between faulty imprinting and disease. Parthenogenesis also offers the opportunity to grow cells from women suffering from serious genetic diseases, allowing a detailed study of the cellular effects of these diseases and, in theory, the stem cells obtained by this method could be used to grow replacement tissue for a women who had developed certain diseases. Dr De Sousa told the BA meeting that, 'at the moment we have not managed to get stem cells from these embryos but that continues to be our ambition.'
Some scientists had thought that the use of parthenotes in research could avoid objections from pro-life groups, Dr De Sousa does not share this view, confirmed by declarations of dismay from these groups to the press, and declared that, 'someone who has a pro-life outlook will regard any usage of eggs and embryos for non-reproductive purposes as objectionable.' Dr De Sousa also insisted that there are no plans to implant the embryos to create a pregnancy - besides, the terms of their research licence prohibit this anyway.
Others voices have expressed doubts based on technical grounds, arguing the degree of genetic manipulation required to achieve parthenogenesis makes this route to embryonic stem cells an unnecessarily complicated one, and even human embryos cloning would appear to be a more straightforward approach: Dr De Sousa believes, however, that during the early stages of stem cell research scientists have to keep different options open. 'We want these cell lines mainly for research,' he said. 'Both cloning and parthenogenesis create cells with perturbations, and it is entirely possible that these will mean cloned stem cell lines are not suitable for therapy or research models.'