scrambling human eggs : dangerous mischief or a therapeutic marvel?

An editorial and article in ‘Nature’ this week (1 & 2) is dedicated to monkey research involving modification of monkey eggs achieved by combining genetic material (maternal mitochondria or mtDNA) from two different maternal sources. The resulting eggs were fertilised in vitro and 15 of these were transferred into 9 female monkeys. 3 monkeys carried pregnancies to term, with 4 live births at the end of June this year. The offspring appear so far to be normal.

The rationale behind the research is to tackle a problem arising in human reproduction where faulty maternal mitochondria (which provide the energy source for fertilisation) can cause early or later onset serious disease.

The therapeutic objective of the monkey research is obviously virtuous, to find a therapy for mitochondrial disease, but the process involved in this specific methodology raises innumerable ethical problems which cannot be easily side-lined, and makes human application highly questionable.

Some may be concerned about experimenting with animals in this way, but our focus is on possible human application. It is extremely worrying to note how uncritical the majority of the UK media has been in assessing the acceptability of genetically modifying human eggs, when the authors of the Nature article are themselves cautious even about the animal results. They acknowledge that they are not sure whether they have indeed eliminated the faulty mitochondria, and point out that it is far too early to know what the long-term effects might be, especially given that many mitochondrial diseases do not appear until much later in development. They recommend further extensive studies to determine the safety and efficiency of the technology before it could ever be even considered for application to human subjects.

Human trials would certainly be necessary but, in CORE’s opinion, could never be justified. This is the insuperable obstacle that lies ahead for those wanting to demonstrate safety for human subjects. Consent could not be obtained from the potential offspring who would be exposed to any danger and nor could concepts of beneficence be successfully argued, both requirements of international protocols, particularly the Nuremburg Code.

Considering that this therapy would affect not just the immediate offspring but, as it is a form of germline therapy (forbidden under EU legislation), future generations as well it is extraordinary how little caution has been expressed in the media coverage of this research.

Nature has determined one egg, one sperm, in the creation of human embryos through centuries of evolution. To accept the addition of a third genetic parent to this equation, without any apparent worries, doubts, or second thoughts is at the least incredibly naïve.

Thankfully some serious scientists do have very real reservations about combining maternal mitochondria in this way. A current research project funded by the California Insitutute for Regenerative Medicine (CIRM) is addressing this very issue, and is entitled, ‘The Dangers of Miotchondrial DNA Heteroplasmy …’ (3)

The applicant, Dr Douglas Wallace, is Director of Molecular and Mitochondrial Genetics at the University of California, and he states in the research application:

‘It is universally agreed that mixing the nDNAs from two different cells would be destructive, yet the potentially disastrous effects of mixing different mtDNAs has been overlooked. In electricity, randomly mixing the components of two different integrated electrical circuits will result in short circuits. The same appears to be true for the cell. In mice in which we artificially mixed two mtDNAs, the resulting mice aged and died prematurely, had a striking increased frequency of cancer, and an increased mtDNA mutation rate.’

And a further ethical consideration. Yet again we are looking at a technology which requires egg donation in great numbers and further exploitation of women. CORE does not know how painful egg collection may be for laboratory monkeys, but we are more than aware of the invasive and potentially harmful nature of egg harvesting in humans. The cajoling of healthy women by emotive or financial means to undergo procedures not for their own benefit, is an ethical minefield in its own right, but there was little mention of that in the UK coverage of the story either.

All too often during the history of IVF we have witnessed unseemly haste in pushing through new technologies, and only later do we stop to think whether the novelties have indeed brought benefit or at what cost. ICSI (a sperm manipulation technique) and PGD (biopsy of embryos to test for abnormalities) are two such procedures which are now being seriously questioned because of their association with subsequent problems in the resulting offspring.

It is CORE’s opinion that this latest novelty, mixing maternal mitochondria, whatever is unravelled through the monkey experiments, should go no further. It should be prohibited in human application.

1. Editorial Nature 460, 1057 (27 August 2009) | doi:10.1038/4601057a; Published online 26 August 2009

2. M. Tachibana et al. Nature doi:10.1038/nature08368; 2009

3.D. Wallace ‘The Dangers of mitochondrial DNA Heteroplasmy in stem cells created by therapeutic cloning.’ (RC1-00353-1)

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