Nothing new
It is impossible to put up with a ban
Polina Loseva, N+1
Genetic editing can be used to minimize the consequences of incest, and for American women, when choosing a sperm donor, his height is almost as important as intelligence – these and other strange things were learned by the editor of N+1, listening to the broadcast of the meeting of the international commission on genetic editing. She tells what else they talked about there and how the fate of future genetically modified children was decided.
The Commission on the Clinical application of Genetic editing appeared shortly after the scandal with the Chinese Jiankui He in November 2018. It consists of scientists and physicians from all over the world, and its work is organized jointly by the British Royal Society and the National Academies of Sciences and Medicine of the USA.
The discussion of the ethics and safety of genetic editing has not stopped for almost a year – since the Chinese scandal. We have also written about him more than once, read our materials "Revised Edition" about Jianku He and "In editing mode" about Denis Rebrikov's attempts to introduce this technology in Of Russia. It would seem that during this time the pro and contra arguments should have dried up.
The same thing was said at the meeting of the Commission by a professor from Utrecht Annelien Bredenoord, remembering the first International Summit on Human Genome Editing in 2015: every decade new technologies appear in this field – in vitro fertilization, preimplantation genetic diagnostics, mitochondrial donation, now genome editing... but every time we discuss the same issues.
It is all the more surprising that something new was voiced at the Commission meeting - and even more surprising that these new arguments strengthen the positions of supporters of editing rather than opponents.
Who to cut
Jiankui He was reproached for the fact that his experiments were not justified from a medical point of view: he was trying to make people resistant to HIV, while there is a much less risky therapy for this disease. Then who needs genetic editing at all? Most of the speakers at the meeting urged not to forget about prenatal genetic diagnosis: we have long been able to choose from fertilized embryos the one that does not carry harmful mutations, and in most cases this is enough.
There are quite a few situations in the world when diagnostics cannot help. To do this, both parents must be homozygous for a recessive mutation (which manifests itself only if both copies of the gene are broken). However, such married couples are extremely rare, and homozygotes for a dominant mutation, for which one broken copy is enough, are even rarer.
But representatives of African countries who see the situation from a completely different angle also spoke at the Commission meeting. For example, Sonia Abdelhac from the Pasteur Institute in Tunisia complained that they have a lot of closely related marriages in the country. As confirmation, she told the story of a boy who suffered from a genetic kidney disease and needed a transplant. The boy's mother gave him a kidney, but after this kidney did not help, it turned out that both mother and son are homozygotes for the same mutation.
People don't see anything wrong with closely related marriages, Abdelak said. On the contrary, a woman from another family brings with her new, unfamiliar mutations and risks. And about a woman of her own kind, everything is clear and it is known what to prepare for.
However, the Commission members did not seriously discuss whether editing fetuses could solve the problem of incest. Instead, they listened to representatives of various disabled societies, who also found something to say.
Jackie Leach Skully from Newcastle University, for example, drew attention to the fact that genetic therapy of diseases leads to their stigmatization. Everyone who discusses the use of editing in the clinic agrees that it is necessary to divide the diseases into "acceptable" and "severe", and use risky treatment only in the second case. But the disabled themselves may not agree with such a list: someone will refuse to consider his condition "acceptable" and will demand to recognize him as seriously ill, and for someone, on the contrary, his "severe" condition is an integral part of identity, as is often the case with deaf people or dwarfs. In this case, they risk becoming victims of harassment: people will perceive them as those who could be "repaired" and blame them or their parents for not doing it. Scully noted that due to the spread of prenatal genetic diagnosis, this is already happening – people are beginning to perceive disabled people as those who were "wrongly chosen" at the embryo stage.
However, the discussion on how to draw a line between the two types of diseases did not turn out to be lively. It was completed by Muntaser Ibrahim from Sudan, who sharply stated: in some cases – as, for example, with Duchenne myodystrophy – it is pointless to reason, you need to take and edit. After that, the discussion came to naught, and the members of the commission probably became wary, waiting for the appearance of a new He in Sudan.
How to ban
Both the Commission on Clinical Application and the WHO Commission working in parallel with it should develop global rules for handling new technology. At the same time, no one understands how to ensure that these rules are followed everywhere. British embryologist Peter Braude recalled that even on assisted reproductive technologies, which do not cause such acute disputes, the world has not yet agreed. For example, prenatal genetic diagnosis is allowed in the vast majority of countries around the world, but is limited in Germany. Mitochondrial transfer (the so-called technology of "children from three parents") is prohibited in China and the USA, allowed in some cases in the UK, but most often it is simply not regulated in any way.
What the laws of different countries say about embryo editing: dark gray - ambiguous, light gray – limited, light pink - prohibition (recommendations), dark pink – prohibition (laws) // Araki & Ishii / BMC Reproductive Biology and Endocrinology, 2014.
In such a situation, it is useless to prohibit genetic editing: there will always be a country that will not rush to introduce restrictions, and both doctors and patients will immediately reach out to it. This has already happened with mitochondrial transfer technology. The first child of three American parents was born in Mexico, because there, unlike the United States, there were no restrictions. Last year another such a child was born in Greece, although the clinical trials were conducted by Spaniards – it's just that in Spain the legislation is stricter.
The authors of a recent review on medical tourism found 20 countries in which clinics offered their clients to carry out mitochondrial transfer abroad. Among them there are those where it is definitely prohibited – such as China, for example, and those where there is no legal prohibition, but the technology has not yet come to clinics – for example, Russia. It is likely that the same thing awaits us in the case of genome editing. It is impossible to track and limit such a multilateral flow: donors, biological samples, embryos and future parents will move from country to country independently of each other and meet in "neutral" territories. A ban here will not save anyone.
At the same time, it is also impossible to leave genetic editing without attention and regulation. Peter Braude recalled that, while mitochondrial transfer is acceptable in many countries to combat genetic mitochondrial diseases, it has also been used for other purposes – for example, for the treatment of infertility – while there are no clinical trials and evidence of the effectiveness of most such technologies. Following the transfer of the fertilized nucleus into the cytoplasm of a healthy egg – as originally planned – work began to appear on injections of cytoplasm into the egg, transfer of the dividing nucleus of the embryo and transplantation of polar bodies (these are cells that separate from the egg during its maturation). Thus, turning a blind eye to one – albeit controversial, but proven technology – we give the opportunity to bloom a lot of questionable colors.
What should we do in a situation when we are not sure about the technology, but we cannot afford to ban it or do without regulation? The answer suggests itself. Professor Bredenord drew the Commission's attention to the fact that all these stories that cause outrage among the scientific community do not occur in those countries where reproductive technologies are legally approved. At one time, the approval of mitochondrial transfer in the UK looked imprudent, but no excesses have occurred in this country since then – unlike those who have not formulated clear rules.
Who is better
The speech at the meeting, of course, also touched on eugenics, since the boundary between the cure and the "improvement" of people is still not defined. And here again I had to recall the experience of previous technologies. Catherine Racowsky from Harvard said that existing reproductive technologies – and primarily prenatal genetic diagnostics – have already brought us closer to eugenics in some way.
Despite the fact that this procedure is not a treatment, but only "diagnoses" embryos, do not forget that it is followed by a choice: which embryo to live. And doctors, together with future parents, make this choice based on genetic tests. As a rule, they pay attention only to specific parts of the genome where the mutations they are interested in are located. But what prevents you from analyzing the whole genome and relying on other factors in your choice – not only the health of the child, but also gender, height, eye color, strength of intelligence, type of character?
And while scientists are looking for a line between acceptable and unacceptable choice parameters, technologies are already getting ahead of themselves. A week and a half ago, the American company Genomic Prediction began offering such services for the first time: they are ready to diagnose the embryos of healthy parents for predisposition to heart attacks, diabetes and several types of cancer. In addition, according to the test results, the company promises to warn parents if the child risks being among the lowest inhabitants of the planet, as well as the owner of a low IQ.
But scientists are in no hurry to sound the alarm. On the one hand, as Braude reminded, genetic diagnosis carries a lot of hidden risks. At each stage, something can go wrong: obtaining germ cells, fertilization, embryo cultivation, sampling for diagnosis, interpretation of data, freezing-defrosting, planting in the uterus. There is a fairly high chance that at one of these stages the desired embryo will be eliminated and will not even live to implantation. If you add editing to this, the number of stages will increase, and the chances, accordingly, will become even smaller.
On the other hand, Rakovsky drew attention to a recent article that has so far been posted only on the bioRxiv preprint site. The authors of this study tried to understand to what extent, according to genetic sequencing, it is possible to predict, in particular, the growth and level of intelligence of a child. They managed to make a forecast for an additional 2.5 centimeters of growth and 2.5 IQ points. And if our opportunities for today are limited to this, then, according to Rakovsky, there is no reason to seriously worry about this yet.
Rakovsky also recalled a 2013 paper, the authors of which interviewed 1,700 women about which person they would like to see as a sperm donor for their child. Of these, only half said that when choosing, they would pay attention to the intelligence of the child's father. Another 42.7 percent would be interested in a person's height, and 40 percent would be interested in nationality. Perhaps this means that our fears are exaggerated, and while we worry that too smart or too aggressive people will fill the planet, women simply choose those who are taller.
Anyway, during the two days of the meeting, no one called for a final ban on embryo editing. Scientists seem to have come to terms with the fact that it will inevitably win its positions, and are only concerned about what questions need to be asked in time and what laws will best keep this editing within the framework of medicine. And despite the fact that the experience of previous technologies shows that heterogeneous legislation results in chaos, the Commission agrees that it is impossible to develop uniform rules for everyone.
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At the end of one of the discussions, the topic of cloning appeared out of nowhere. Here is another technology, the participants of the discussion suddenly remembered, which seemed taboo to everyone and required a legislative solution. Cloning people seems to have been banned all over the world, and since then nothing has been heard about it. Where did it disappear to? – the members of the commission asked themselves. And they immediately answered themselves: no one just needs it. You can't help imagining how, somewhere on the other side of the globe, in China, at this moment another researcher is giggling - like those who recently implanted a gene in monkeys that is responsible for the development of the human brain, and those who learned how to clone genetically edited macaques.
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