The embryos of two Chinese twins had been genetically modified to obtain a natural immunity against AIDS. But unexpected mutations would have affected their genome, with consequences that no one can predict.
Mutating the genome to obtain natural immunity against dangerous viruses is technically possible. This is one of the possible uses of the CRISPR-Cas9 system, also called “genetic scissors”, which makes it possible to target, cut and modify a DNA sequence.
Such manipulations on humans are impossible today in France because the legislation prohibits any intervention on a person’s genetic heritage. However, Chinese scientists ignored these ethical limits and, in 2018, announced to the world that they had, thanks to the CRISPR-Cas9 system, modified twin embryos in the context of in-vitro fertilization. The objective of this intervention: to give unborn babies a natural immunity against AIDS.
Consequences that no one can predict
But today, according to an American journalist from the MIT Technology Review cited by 20 minutes, there are serious concerns about the future of Lulu and Nana, the two twins born of this in-vitro fertilization with genetic modifications of the embryos. If the mutation has apparently succeeded – so if these babies are “naturally” immune to AIDS – the problem is that these mutations would have also affected other parts of their genome with, this time, consequences that no one can today predict today.
Explanations: the use of the CRISPR-Cas9 system makes it possible to target, cut, delete or modify and reimplant a DNA sequence. It is the principle of “copy-paste” which authorizes a rewriting of the genome in order to prevent or correct genetic disorders at the origin of certain diseases, or even to adapt the human organism to protect it from external attacks such as viruses or bacteria.
But, as Carine Giovannangeli, research director at the CNRS, points out in the program “Santé 2030” broadcast on the YouTube channel of Pourquoi Docteur, “once we have broken the DNA with the CRISPR-Cas9 system, it is the mechanisms triggered by the break that modify the cells and we have no control over these mechanisms, sometimes it works, sometimes it works less well.”
An “off-target” modification
Carine Giovannangeli explains that these are indeed, on precision and efficiency, the limits of the use of the CRISPR-Cas9 system. Indeed, beyond the uncontrollable effects of DNA breakage, there is also the fact that when a sequence of the genome is targeted, the system can identify it, but can also identify at the same time all the similar sequences and produce unwanted effects. What the researchers call an “off-target” modification.
It is this lack of precision of the CRISPR-Cas9 system that seems to be at issue in the case of the Chinese twins. According to the journalist of the MIT Technology Review, the results of their intervention written – but not published – by the Chinese scientists, would explain this kind of dissemination of the mutations on the whole genome of the two girls. With zero visibility on the effects that this can produce.
The announcement of their intervention on the embryos by the Chinese scientists had aroused great emotion linked to all the ethical questions that accompany innovations such as the CRISPR-Cas9 system. The case of the Chinese twins clearly shows that these techniques, as promising as they are, must still be secured to avoid chain reactions which could be dramatic in the event of negative effects of the mutations.
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