Genetic modification of human embryos: a gateway to eugenics?

Research on human embryos: subjects or objects of study?  

For several years now, the CRISPR-Cas9 technique has been used to modify genes by cutting the double-stranded DNA at the site of a deleterious mutation and replacing the mutated sequence with a DNA sequence that corrects the mutation. In the study in question, the researchers sought to determine whether it was possible to modify human embryos without causing the chromosomal damage commonly associated with CRISPR-Cas9 (loss of an entire chromosomal segment, chromosomal rearrangements or mosaicism, see below). To do this, they used the base-editing technique, which allows precise modifications to be made to a single base in the DNA without completely cutting the chromosome.  

To test this technique, the researchers targeted three genes for modification: the first, PCSK9, influences the production of ‘bad’ cholesterol. By deactivating it, the risk of a heart attack could be reduced. The HBG1 and HBG2 genes are involved in the production of foetal haemoglobin. Mimicking them could help alleviate conditions such as sickle cell anaemia (an inherited disorder that causes red blood cells to become misshapen, blocking blood vessels and leading to anaemia and painful crises). For each of these genes, the researchers replaced a single base (an adenine (A) with a guanine (G)). According to the results of this study, it would appear that the mutations introduced into these genes did not cause any major deletions (a chromosomal abnormality or mutation involving the irreversible loss of a segment ofDNA or a chromosome), nor any chromosomal breaks or major rearrangements.  

However, they were unable to prevent mosaicism (this affected 7 out of the 9 embryos examined). This abnormality arises because not all of the embryo’s cells have received – or have only partially received – the genetic modification. This results in a mixture of genetically different cells within the same embryo. According to the researchers, intervening at an even earlier stage in the embryo’s development could help to limit this effect. Furthermore, when editing the HBG1 and HBG2 genes, insertion errors in the DNA (off-target effects) were observed.  

Finally, the researchers discovered that when the DNA-editing tool was injected in protein form, the embryos developed normally up to the blastocyst stage (5–6-day-old embryo). However, its administration in the form of mRNA* consistently led to premature arrest of embryonic development.  

Whilst the researchers acknowledge that the clinical application of this technique is still premature at this stage, numerous ethical questions are already being raised.  

From basic research to the temptation of ‘designer babies’ 

At present, no country authorises the genetic modification of human embryos for the purpose of pregnancy (heritable germline). However, basic research on embryos modified in the laboratory (and subsequently destroyed) is legal under certain conditions in a few countries, such as the United Kingdom, Belgium, China and the United States.  

In Europe, the Oviedo Convention specifically prohibits the creation of human embryos for research purposes and germline (heritable) modifications. This binding legal instrument aims to protect the dignity, identity and integrity of human beings in the face of potential abuses in the application of biology and medicine. Whilst 29 European countries have ratified it to date, Belgium has not signed it, preferring to rely on its own, more permissive legislation on embryo research.  

Whilst gene-editing technology is primarily capable of creating precise mutations linked to a disease rather than the creation of ‘designer babies’, the risk of a gradual slide has nevertheless been highlighted by certain bioethicists such as Hank Greely (Nature): ‘You could set up an in vitro fertilisation laboratory and a genetic testing laboratory for just a few million dollars and start doing this,’ explains Greely. This would result in ‘the birth of seriously ill children’. The 2018 precedent involving the two girls whose genomes were modified at the embryonic stage shows that, once the technology exists, there is a strong temptation to use it despite bans and uncertainties regarding long-term health effects.  

 Selection rather than treatment: the risk of eugenics  

The technique of base editing ultimately raises the question of whether it is desirable to deliberately select, modify and improve the genetic traits of future generations.  Currently, pre-implantation genetic diagnosis (PGD) already involves the selection of embryos conceived in vitro to prevent the transmission of serious diseases. But such selection could extend to non-pathological traits. This is, in fact, the aim of companies such as Nucleus Genomics in the United States, which offer parents the opportunity to analyse the DNA of their embryos in order to select the ‘best embryo’ for implantation. It is no longer a question of choosing an embryo free from disease, but one whose genetic profile suggests it will have the traits desired by its parents. Or by society?  

If these techniques for selecting and modifying embryos were to become widespread, they could lead parents to choose to genetically modify their child rather than take the ‘risk’ of giving birth to an imperfect child. This could make it collectively more difficult to accept a child with a genetic condition or a disability. Parents who refuse to use these techniques and who give birth to children with ‘defects’ considered preventable could, in turn, face stigma. As for the child thus engineered to fulfil their parents’ wishes, will they still be able to feel free to become their own person?   

*mRNA is a temporary copy of a section of DNA. It carries genetic instructions from the nucleus to the cell to produce the proteins necessary for life.