Genome editing tools in research

Genome editing tools have opened new perspectives for research on embryonic development, but they do not make the birth of genetically modified children acceptable or desirable. These techniques allow for precise modification of certain letters of the DNA in human embryos, but they present risks that are still poorly controlled, and the medical situations that would justify their use are extremely rare.

Advancements in genome editing

Genome editing techniques are progressing rapidly. After the initial tools CRISPR-Cas9, newer methods allow for directly replacing a single "letter" of the genome with another. This new approach, called "base editing," has the advantage of not necessarily causing breaks in both strands of the DNA molecule, unlike previous techniques.

Recent studies on base editing

Two recent studies illustrate the potential of base editing. One examines the possibility of modifying certain genes in human embryos without causing the major chromosomal anomalies observed in previous experiments. The other uses genome editing to understand the role of the NANOG gene in the very early stages of development.

Scientific progress and ethical limits

These works constitute important scientific advances. They should not, however, be interpreted as a natural step towards the clinical use of genetically modified embryos for reproductive purposes. Because a technical possibility does not constitute a medical indication or an ethical authorization.

Distinguishing research uses

If the authors of the two publications have used genome editing, the uses they have made of it must be clearly distinguished. In the first case, the genome editing of surplus human embryos was used to measure the effectiveness and biological risks of the technique itself. The results indicate that this has allowed avoiding the damage observed with classical techniques.

Research in human and animal embryos

In the second case, genome editing was used as a tool for fundamental research: modifying a gene in mouse embryos and in surplus human embryos allowed observing its role in embryonic development. The mechanisms of human development are not always the same as those observed in mice or in other animal models. The study on NANOG shows precisely that some embryonic processes differ in humans and mice.

Ethical distinction in research

Within a strictly regulated framework, without any plan to implant the resulting embryo from such manipulations, research on human embryos can contribute to better understanding the early stages of our development, the causes of certain infertility or the mechanisms leading to embryonic anomalies. However, there is a fundamental difference between modifying an embryo to produce knowledge and modifying an embryo intended to become a child.

Safety concerns and off-target effects

It is important to understand that the absence of detectable chromosomal anomalies during the first days of development does not mean the technique is safe. Beyond the breaks and other deletions that can affect the chromosomes, genome editing techniques can have "off-target" effects: unwanted modifications can occur elsewhere in the genome.

Mosaicism and unpredictable consequences

Another problem: the modification introduced by using genome editing may not be present in all the cells of the embryo, producing what is called "mosaicism." Other effects are even more difficult to predict. A seemingly precise modification can influence the functioning of other genes, disrupt the development of an organ or produce consequences that will only become visible several years after birth.

Understanding genome complexity

We now know the DNA sequence very well and many molecular mechanisms, but we still imperfectly understand how the entire genome produces an organism and its characteristics, particularly the role of non-coding regions, of epigenetics and the interactions between genes and the environment.

Limitations of current knowledge

Genome editing techniques are progressing very quickly, but they remain recent and their technical precision does not eliminate biological uncertainty: modifying a sequence is one thing, predicting all the long-term consequences of this modification is another. If an observation reassuring during a few days of embryonic development constitutes an interesting scientific data, it by no means constitutes a "safety certificate."

Medical necessity for genome editing

Another question is often neglected: in which situations would the modification of an embryo's genome be medically essential? For many diseases caused by a mutation in a single gene, preimplantation genetic diagnosis already allows, in certain situations, to identify the embryos that do not carry the family mutation.

International guidelines and exceptional cases

The international recommendations that have considered, in a theoretical manner, a possible future use of hereditary genome editing have therefore limited it to exceptional situations: serious monogenic disease due to a clearly identified mutation, in the absence of other reasonable solution and with a very high level of safety.

Economic and social implications

Certain companies already offer embryonic selection services based on extended genetic analyses. This is, for example, the case of the Californian company Orchid Health, which offers a complete genetic screening of the embryo, or that of Nucleus Genomics, which offers "genetic optimization." Others highlight polygenic scores supposed to estimate the probability of developing common diseases or presenting certain complex characteristics.

Risks of eugenics

These technologies would also be accessible primarily to those who can afford them. Economic inequalities could thus be doubled by new biological inequalities assumed or claimed. The main danger is therefore not only that an isolated researcher crosses a red line again, as the Chinese researcher He Jiankui did in 2018.

Global governance and ethical responsibility

Beyond this type of initiative, there is another danger regarding genome editing: that of the progressive normalization of an international market for reproductive selection and optimization. The answer should not be the rejection of all research on human embryos. Such research can be legitimate when it answers an important scientific question, is authorized by law, evaluated by independent bodies, based on informed consent and conducted in transparency.

International standards and future oversight

A first step in this direction was taken after the scandal caused by the revelation of He Jiankui's work. The World Health Organization (WHO) then created an expert advisory committee on the development of global standards for the governance and oversight of human genome editing. This committee published its recommendations in 2021 and notably proposed the creation of an international registry of clinical trials using genome editing – now online.