Base Editing: Ethics and Safety Concerns

Base editing, a refined form of the widely-known CRISPR-Cas9 technique, allows precise chemical changes to be made in a single DNA letter without cutting the DNA’s double helix. Although this technical innovation broadens the horizon for correcting certain mutations, its clinical application in human embryos for reproductive purposes is associated with serious safety risks, technical inefficiencies, and profound bioethical dilemmas.

In this article, we analyze why germline modification—associated with risks such as mosaicism and unpredictable harmful effects—and the false transhumanist promise of “human enhancement” open the door to eugenic practices that directly violate human dignity. In light of the alarming trend toward biotechnological commodification, driven by the dangerous illusion of the “perfect baby” through embryo selection and disposal, there is an urgent need to call for scientific realism, prudence, and ethical reflection to safeguard developing human lives.

Base editing is a second-generation genetic engineering technique, a refinement of the CRISPR-Cas9 method, which allows precise single-base (A = adenine; T = thymine; C = cytosine; G = guanine) changes to be made in the DNA. It is a modified version of CRISPR that allows scientists to change a specific nitrogen base for another without completely cutting the double helix, thus reducing the risk of unwanted genetic changes. Using a guide RNA, the specific target DNA sequence is identified, and a Cas9 enzyme with deactivated nuclease activity is employed to prevent DNA strand cleavage while carrying an additional domain capable of converting one base into another: C → T (or G → A); A → G (or T → C). Instead of cutting the DNA and letting the cell repair it, the system performs a chemical correction directly on the desired base.^{[1, 2]} This innovation greatly expands the number of mutations that can be corrected, in addition to reducing the risk of affecting regions outside the target (off-target effects).

Despite its encouraging potential, base editing cannot correct any type of mutation and is not suitable for correcting long DNA deletions or insertions, complex chromosomal rearrangements, or polygenic systems, as explained below.

From editing monogenic systems to hereditary polygenic editing

Base editing is not applicable to polygenic traits, such as those that partially govern intelligence, height, and other characteristics, which are determined by the joint action of multiple genes with additive effects distributed throughout the genome. As we explained in a previous article on gene editing in germ cells, gene editing is unfeasible and ineffective for polygenic systems. In these systems, a so-called polygenic risk score (PRS)—the statistical calculation that aims to evaluate the likelihood of a person having or developing a medical condition or a certain phenotype—is neither possible nor accurate. Furthermore, it is not possible to assess the relative importance of the different genomic variants detected, nor are the available data sufficient.

In March 2025,   a theoretical work by Australian authors and the Uehiro Oxford Institute on gene editing in germline cells (which generate gametes) or human embryos using the CRISPR-Cas9 technique was published in Nature.^[3] In the study—led by Dr. Peter Viescher and co-authored by the transhumanist philosopher Julian Savulescu—the authors analyzed the possibilities of applying “heritable polygenic editing” (HPE) in germline tissue to reduce the risk of transmitting polygenic diseases to offspring. The calculations failed to consider other factors that are particularly involved in polygenic systems, such as intergenic interactions like pleiotropy and epistasis, and environmental factors. In the mathematical model applied by these authors, they concluded that only a small proportion of the edits could significantly reduce the risk of error, a scenario that would require no less than three decades to overcome.

Since then, there has been intense debate about the feasibility and safety of these techniques, not only for their application in polygenic systems, but for any intended genome modification in the germline or embryos.

Regarding the safety of genomic editing techniques in embryos

Although some argue that it makes sense to edit embryos rather than waiting to correct genetic abnormalities when the individual is fully developed, it should be noted that, unless the safety of the technology has been firmly established, the outcome could be disastrous for the health of genetically edited children. Consequently, current genome editing approaches using CRISPR-Cas9 or base editing should be restricted to adult somatic tissues, where these techniques can also be performed ex vivo through the in vitro culture of patient-derived cells; once the desired modification has been confirmed, the cells are re-infused via autologous transplant.

Almost from the moment these technologies emerged in the field of genetic engineering, it became apparent that there was a need to establish a moratorium on their application, especially in the germ line and human embryos. In 2015, an editorial in the journal Nature called for the creation of an international interdisciplinary observatory, and “to invite in voices and concerns that are currently inaudible to those in centres of biological innovation, and draw on the full richness of humanity’s moral imagination”.

The issue is particularly relevant in relation to human embryos, because unpredictable alterations can arise due to the imprecision of the technology, so that changes made in an early embryo can pass to the cells of the developing individual, including reproductive cells. This means that the modifications could be transmitted to subsequent generations. Beyond the risks involved, other considerations must be taken into account, such as the impossibility of obtaining informed consent from future generations who would inherit the changes, the potential use of the technology for non-medical purposes (such as the selection or enhancement of human traits), and the social inequalities that could arise if these techniques were available only to certain groups.

Base editing: difficulties for its clinical application

A study published on June 1 by cell biologist Dieter Egli and his colleagues at Columbia University in New York discusses the risks and possibilities of using base editing in embryos less than 14 days old. The article has not yet been peer-reviewed, but was announced on the bioRxiv preprint server and initially reported by The New York Times. This study consisted of applying base editing to modify three genes: PCSK9, which regulates “bad” cholesterol levels in the blood; and HBG1 and HBG2, involved in the synthesis of fetal hemoglobin as a means to replace adult hemoglobin in patients with β-thalassemia and sickle cell anemia. In all cases, the objective was to substitute an A for a G at a specific site in the gene, thereby producing the desired modification. The results revealed cases of mosaicism, as well as harmful effects on the embryos due to cell division arrest caused by the guide RNA.

Consequently, the researchers involved in this study consider that important questions remain regarding the safety, efficacy, and biological consequences of these technologies, and conclude that CRISPR-Cas9 genome editing and base editing techniques are not yet sufficiently mature to support their routine clinical use for reproductive purposes.

Nevertheless, the study represents a conceptual shift that has the potential to revitalize the field and fuel its commercialization by biotechnology companies, eager to do business based on producing babies with desired characteristics or, going even further, for human enhancement purposes, to guarantee desired physical traits, intellectual or athletic abilities, etc. Some biotechnology companies such as Nucleus Genomics are already considering the use of complex genetic models that seek to predict traits such as intelligence and height, using catchy slogans like: “Have your best baby. The modern way to plan and have a baby, driven by science, guided by love”.

However, it should be stressed that traits involving polygenic systems—such as intellectual ability, physical traits, and many of those related to human health—do not respond solely to a genetic component, or do so only to a very small degree; rather, they are largely the result of environmental factors, such as education, personal effort, nutrition, and healthy lifestyle habits. For these reasons, many in the international scientific community consider that there is insufficient evidence to support the use of base editing technologies for reproductive purposes. Many countries allow limited research on human embryos under strict conditions and ethical oversight, but prohibit the implantation of genetically modified embryos for reproductive purposes. Regulation varies considerably across jurisdictions and continues to evolve as technology advances.

Learning from mistakes

It is important to remember the Chinese biomedical scientist He Jiankui, who applied CRISPR-Cas9 technology to edit the DNA of human embryos in 2018 (two initially and a third later), which he implanted in women who subsequently gave birth to the babies. His work caused great outrage among the scientific community for ignoring all safety protocols, ethical warnings, and the international moratorium on such applications. A group of 122 Chinese researchers issued a statement calling Jiankui’s actions “crazy” and his claims “a huge blow to the global reputation and development of Chinese science”. As a result, he received a 3-year prison sentence. Despite this, Jiankui declared to The New York Times that he “was very proud of his work.” It should be recalled that, after serving his sentence and being released, he expressed his firm resolve to continue working in the same direction.

Bioethical aspects

As discussed thus far, base editing offers the possibility of correcting certain hereditary mutations with increasing precision, but its application in human embryos raises scientific, medical, ethical, and regulatory questions that continue to be the subject of intense debate.

Some researchers question whether genome editing or base editing in embryos is necessary when technologies already exist to diagnose the presence of unwanted genetic factors in embryos created from in vitro fertilization, i.e., the application of preimplantation genetic diagnosis (PGD).

Indeed, PGD is more direct and technically simple than base editing in embryos. However, it is not without technical and ethical limitations, including potential errors resulting from mosaicism and false-positive or false-negative results, as well as ethical concerns regarding its eugenic nature, which entails the selection or discarding of human lives. Regardless of which traits are intended for selection, it is equally reprehensible to select embryos that guarantee a gifted child or a child with certain traits, or to eliminate others because they are carriers of a possible disease, or simply because they fail to meet a certain standard. Eugenics—whether positive or negative, and whether applied to Mendelian or polygenic systems—is still eugenics and, as such, constitutes a direct attack on human dignity.

Furthermore, given the uncertainty surrounding the application of genome editing and base editing, PGD may ultimately need to be performed on embryos that have been subjected to these technologies as a safety measure prior to their implantation. Many human embryos would be lost in the attempt and, of those that do develop, doubts would always remain about unintended epigenetic or genetic modifications arising from such extensive manipulation.

Finally, the aforementioned technological innovations have paved the way for the pursuit of human enhancement by feeding fantasies such as the perfect baby, selection based on physical traits, body optimization, super intelligence, longevity, etc., a whole spiral of future applications that would be contrary to human dignity by turning human embryos into objects that can be manipulated, selected, or discarded.

It is urgent to appeal, first, to realism in the approach to related research, by weighing its inherent limitations; second, to prudence in its development, considering the risks associated with the lack of precision, effectiveness, and safety; and, third, to the essential ethical reflection on the nature of what is being acted upon, namely, developing human lives.