Embryos and mitochondria
Commentary on the "mitochondrial transplantation" experiment

Gonzalo Herranz, department de Humanities and Medical Ethics, University of Navarra
partnership for CiViCa, Pamplona, 4 September 2009

Nature has just published an early virtual version of work (Tachinaba et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Doi:10:1038/nature08368) is worthy of comment. The accompanying publishing house (The ethics of egg manipulation. Cell research reopens the discussion on embryo destruction, egg donation and what is natural. Nature 2009;460:1057), which heads the latest issue August 2009 issue of the journal.

The article, despite the fact that the summer holidays are almost over, has been spread with glee in recent days by many media outlets. The media have reported statements by scientists and bioethicists, which are worth mentioning.

The transfer of the mitotic spindle-chromosome complex (ST): an animal experiment without blemish

In an admirable display of technical virtuosity, Tachinaba et al have produced a flawless, seamless work which, brilliantly confirming their expectations, leads them to the conclusion that effective treatment of diseases due to mitochondrial DNA mutations is feasible.

Researchers at the National Primate Centre in Oregon research have succeeded in isolating the mitotic spindle-chromosome complex from Macaca mulatta metaphase II oocytes and then transferring and fusing them, with financial aid of a Sendai virus extract, with homologous cytoplasts (metaphase II oocytes, whose mitotic spindle-chromosome complexes had been previously extracted). The embryos thus obtained (ST embryos) proved to have a more than satisfactory capacity for development, as revealed by two different tests: on the one hand, they were able to give rise to two stable embryonic stem cell lines, with a yield of 25% (similar to that of the control embryos); and, on the other hand, they were also able to be gestated to term: from 15 ST embryos transferred into the macaque tube, four animals were born, two of them result from a twin gestation.

A convincing, if not overwhelming, amount of supplementary information is available at article . Under the heading "Supplementary Methods", it is stated that "All procedures on animals were approved by the Institutional Animal Husbandry and Use committee ". This contains all the explicit ethics of article: the ethics management assistant required for animal experimentation.

Human implications

But that is only part of the problem. Because, although we are dealing with a research on animals, and not on human beings, the human implications of the work are notorious: there is a lot of "intentional" ethics in the article. In the first paragraph, we are already told about human mitochondrial diseases and the procedures designed to treat them, which have so far been ineffective. The authors consider that the technique they offer could be applied in human clinical practice: "For this purpose, the nuclear genetic material could be extracted from a patient's oocyte containing mtDNA mutations and transplanted into an enucleated oocyte donated by a healthy woman with normal mtDNA".

Although the authors acknowledge that today's analytical procedures are not entirely reliable, they are inclined to think that their procedure appears to be free of the risk of transferring diseased mitochondria, i.e. it does not appreciably infect the recipient cytoplasm with abnormal mitochondria. deadline They note, cautiously, that long-term preclinical programs of study will be necessary before the technique can be applied to humans.

But it is precisely here, when it comes to the possible application of the technique to humans, that the ethical problems begin. Nature's editorialist, who professes a weak and sentimental ethic, laments: "Proving that this can be done safely will require research that will be contentious - and, in many countries, legally or practically impossible. The need to create human embryos exclusively for the purposes of research, which many see as a violation of the sanctity of human life, is the biggest stumbling block". But no: for the Nature editorialist, the really serious stumbling block lies in the extraordinary difficulty of obtaining human oocytes to produce experimental embryos. There are not many women willing to go through the hard test of ovarian hyperstimulation and then donate their oocytes free of charge to produce human embryos for experimental purposes. Nor does the paradoxical "paid donation" seem to offer very promising prospects for research : apart from the fact that the market for human oocytes is dominated by human assisted reproduction clinics, there is a legal difficulty: outside New York State, the sale of oocytes for research is prohibited.

Finally, the editorialist points to a dead argument, an argument from the past: the repugnance once expressed at the "unnaturalness" of being the child of three parents. The unstoppable expansion of the combination of donors, gestational parents and new family types, brought about by the reproductive revolution, has demonstrated the futility of prohibitions.

It does not seem improper to think that the ultimate message of Nature's article publishing house is that life would be better lived with simple inspection management assistant, not with ethical standards or laws.

What the media reported

Will assisted reproduction technicians be able to respect the prohibition of the Oviedo agreement to produce human embryos for experimental purposes? In order to comply with a Helsinki rule , will they wait to start their clinical trials long enough to gather the necessary, indispensable preclinical information? It does not seem likely. Oviedo and Helsinki have binding force in Spain: this is not the case in the United States.

A test: in contradiction to what he had stated in Nature's article about the need for long-term pre-clinical programs of study deadline , Shoukhrat Mitalipov, researcher the main author of work , emphasised, in a statement to the BBC, that the technology is ready to be applied to humans and that, consequently, he had already applied for authorisation to start working with human embryos. Moreover, he hopes that he will soon be able to do so with patients.

What is behind this haste? A scientific mind, eager for knowledge and proof? A compassionate heart, burning with the desire to save suffering at all costs? A very human ambition for fame and prestige? The all too human auri sacra fames? An emotivist mixture of everything, clouding ethical analysis, craving social recognition? It should not be forgotten that, in biomedical research , the art of appealing to the public's feelings, of stirring up the pity that good people feel in the face of suffering, especially that of children, is widely practised. Mitalipov told the BBC: "It is estimated that every 30 minutes a child is born with a devastating [mitochondrial] disease and I think we should prevent it. The crusade is on. But it is not easy to know whether this is true or a pious exaggeration. There is still no reliable data about the incidence of "devastating" mitochondrial mutations, which, moreover, seem to be preceded by a very high rate of second- and third-trimester miscarriages. But Mitalipov's use of a high-resolution chronology ("every 30 minutes", not "every average hour", or "more than 20 children every day") lends the data a mask of "scientific" precision that induces occasional student to acquiesce: an improper use of scientific authority.

A "dirty" comment

The BBC's report on article by Tachinaba et al. also included a statement by Professor Robin Lovell-Badge, a British embryologist, well known for his research on sex determination, in particular for having identified the SrY gene. Lovell-Badge is a great science communicator, who argues that, when addressing the public, scientists should use metaphors, and describe things in vivid colours, with simple words. It is not surprising, therefore, that he is often called upon by the media to comment on high-impact bioethical news.

Said Lovell-Badge, at purpose of the application of Tachinaba's experiment to humans: "People need not worry too much about germline alterations. After all, mitochondria do not confer specifically human qualities. It would be the same as changing the bacteria in our intestines, which, I suspect, no one cares about.

Obviously, the comparison, as shocking and original as it is, makes a strong impact. But is it appropriate, timely, ethical? I believe that in bioethics, good humour should play a more important role. It should compensate for the acrimony that so often contaminates its interminable debates. Bioethicists are chronically in need of good humour, Socratically ironic, not sophistically frivolous. But good humour must be prevented from degenerating into irreverent pique, into the vilification of things and people.

Beyond its faecal character, Lovell-Badge's metaphor is sophistic: it is telling us that there is no need to worry about human mitochondria, nor, for that matter, human embryos: there is nothing admirable about them that is worthy and respectable.

That settles the question. There is no problem, because experimenting with the germ line, which means destroying human embryos, is not a matter we have to be careful about.

This is a very typical behaviour of certain scientists. Already Chesterton, in 1910, wrote: "Some men of science pass over the difficulties by dealing only with the easy part: and so they will say of first love that it is sexual instinct, and call the fear of death an instinct of self-preservation. But that is to hide the reality [...] That there is a strong physical element in both infatuation and Memento mori makes them, if possible, more puzzling than if they were purely intellectual phenomena. [...] That these things are animal, but not wholly animal, is just the reason why the dance of difficulties begins. The materialists analyse the easy part, deny that the hard part exists, and go home to tea".