How American companies reopen the race to modify the DNA of embryos

Modifying the DNA of the human embryo and changing the fate of the unborn child's entire generation: this is the new bet in Silicon Valley, where a flood of investment is flowing into start-ups that intend to use the innovative CRISPR technique of 'cutting' DNA to apply it in the field of reproductive genetics. New biotechs that, alongside the proposal of already established genetic tests to identify serious chromosomal abnormalities or rare mutations, are putting forward the idea, still largely theoretical, that this information can guide ad hoc DNA modifications already in the embryo.

However, the Americans are not the pioneers in this field: a Chinese researcher was, in 2018, the first to use CRISPR in an experiment to genetically modify human embryos intended for birth. The experiment, conducted in violation of the rules in force at the time, showed that the technology was not under control and that the outcomes of the intervention were incomplete and unpredictable, opening a global debate on the scientific, clinical and ethical limits of germline genetic editing. The stated aim of the experiment conducted in China was to make two girls resistant to HIV infection by editing the CCR5 gene. After birth, however, the limitations of the intervention became apparent: one of the twins had only one copy of the gene modified, a condition that does not guarantee resistance to infection, while in the other, off-target effects were found, i.e. unforeseen genetic alterations, the long-term consequences of which are unknown. In both cases, there was no certainty of protection against HIV. The affair provoked almost unanimous condemnation in the international scientific community and led to the imprisonment of the researcher responsible.

Maurizio Genuardi, director of the Medical Genetics Unit at Gemelli Hospital and professor at the Catholic University of Rome, had just been appointed president of the European Society of Human Genetics when, in 2019, the Chinese researcher responsible for the experiment was arrested. "It was an affair that showed how easy it is to circumvent the rules and how fragile global control over certain practices is," he notes. "Even in China this type of intervention was not allowed", but was in fact tolerated until "there was a strong scientific and international outcry". The operation, Genuardi recalls, was justified by the fact that the father was HIV-positive, 'but a gene was altered not to cure a disease in the child, but to make him resistant to an infection for which alternatives already existed'. Added to this was the absence of adequate controls: 'these were studies on embryos conducted without the protocol having been submitted to an ethics committee beforehand'. Genuardi draws a parallel with practices already in use, such as medically assisted procreation, citing the case, reported by CNN, of about two hundred children born from a single sperm donor carrying a genetic mutation associated with an increased risk of cancer. An episode that, he notes, highlighted the lack of adequate controls and the presence of economic interests in the management of these procedures. After the case of the Chinese twins, Genuardi recalls, the curtain had fallen on this field, which has risen again after seven years, in the America of Donald Trump.

The debate is already rapidly moving beyond the hypothesis of using CRISPR on embryos as an early therapy for very rare monogenic diseases, which would affect very limited numbers of cases and would be unlikely to sustain an industrial model. More likely, instead, is the development of a business model centred on the expansion of pre-implantation genetic diagnostics, with tests on embryos becoming more extensive and sophisticated, and more probabilistic, based on associations between genetic variants and future risks. In this context, genetic editing could be proposed as an additional 'corrective' service: no longer the selection of the embryo lacking a known mutation, as is the case today, but the modification of embryos with variants considered undesirable. A prospect that, as Giuseppe Novelli, a geneticist at the Policlinico Tor Vergata in Rome, warns, 'fuels promises that are difficult to keep, such as that of the 'genetically guaranteed' child', and opens the way to a clinically fragile use of the technology, with a high ethical risk, because it is based on estimates of probability and not on biological certainties. In relation to this, Genuardi recalls, the European Society of Human Genetics has published a position statement in which the use of polygenic risk scores in the prenatal period is defined as 'unethical and also not scientifically valid', warning against the use of weak genetic predictions to guide reproductive choices.

Alongside this possible direction, the debate also extends to the hypothesis of an ameliorative use of gene editing. A distant prospect? Perhaps not entirely. If genetic modification of human embryos destined for birth is illegal today, in the United States as in many other countries, and numerous researchers and scientific organisations have called for a global moratorium until the main scientific and ethical issues have been resolved, "things can change rapidly", warns Maurizio Genuardi. "The current framework is contingent, not stable," he notes, and is bound to be tested by the technological, economic and geopolitical pressure that accompanies the development of these biotechnologies. Also drawing attention to this scenario was a recent Wall Street Journal investigation, which, recalling the debate on eugenics, describes a rapidly expanding field in which embryo screening is presented as a means of controlling genetic 'quality' and, in some cases, as a first step towards deliberately improving the traits of the future born. In the United States, Genuardi notes, 'there have already been companies promoting in vitro fertilisation associated with forms of genetic selection for some years', including the selection of embryos on the basis of presumed predispositions to diseases of adulthood. Looking ahead, he adds, these same companies 'also propagate the possibility of selecting on the basis of IQ or other psycho-intellectual characteristics', explicitly placing themselves in the area of so-called human enhancement, i.e. practices that aim to 'improve' or enhance human capabilities.