New studies on Down syndrome reopen the bioethical debate on fetal research

Two recent research papers published in Science and PNAS have reignited the debate on Down syndrome, gene editing, and the ethical limits of biomedical research. While one of the studies analyzed the molecular alterations in fetal brain development in fetuses with trisomy 21 obtained after induced abortions, the other explored silencing of the extra chromosome 21 found in this syndrome using CRISPR-Cas9 technology. Although both papers point to potential therapeutic advances, they also raise profound bioethical questions about the use of aborted fetuses in research, the dignity of human life, and the moral implications of intervening genetically in humans before birth.

In the last month, two articles have appeared in highly prestigious scientific journals discussing some aspects of Down syndrome. The first of these, co-authored by three researchers from Harvard Medical School (Boston, USA) and led by Volney Sheen, was published on April 13 in PNAS ^[1] and later reported on our Bioethics Observatory website.^[2] The second involved a multidisciplinary team of 23 authors, led by Luis de la Torre-Ubieta (University of California, Los Angeles), and was published on April 23 in the journal Science.^[3]

The study led by Sheen used iPS cells derived from individuals with Down syndrome. These cells are generated from skin fibroblasts and exhibit most of the properties of embryonic stem cells. Due to their origin, they present the characteristic trisomy 21, making them highly useful for studying the consequences of this chromosomal abnormality. Using these cells, the authors applied an elaborate variant of CRISPR-Cas9 gene editing technology,^[1] which has been detailed in an article by Jouve and Tudela.^[2]

The second study led by de la Torre-Ubieta sought to understand the prenatal development of the abnormalities in the neocortex (the region of the cerebral cortex most critical for cognitive function) that underlie the cognitive impairment observed in individuals with Down syndrome. To that end, they used brain tissue from 26 fetuses obtained from induced abortions carried out between 13 and 23 weeks of pregnancy. Thirteen of the fetuses were aborted due to a diagnosis of trisomy 21; the remaining 13 had a normal chromosomal set and were used as controls.

The results of the research, obtained via an elaborate and complex methodology, show that fetal development of the neocortex in individuals with trisomy 21 involves the acquisition of numerous abnormalities at the molecular level. For example, changes in the expression of numerous genes were detected, caused in part by alterations in the organization and accessibility of chromatin (a complex formed mainly by DNA and proteins). Although surprising at first glance, changes in gene expression affect not only the genes contained on chromosome 21, but are observed across all chromosomes. This finding can be explained by the fact that regulation of gene expression involves numerous factors encoded by multiple genes distributed throughout the genome. Consequently, the study authors demonstrated that trisomy 21 involves changes in gene regulatory circuits and in a key transcription factor that affect neurogenesis. They also observed alterations in various metabolic pathways and identified changes in neuron interactions and microglia activation.^[3]

The authors of both studies concluded that their research could facilitate the discovery of treatments for Down syndrome. However, in the case of the article published in Science, it is virtually impossible to think that these studies could lead to finding therapeutic measures to eliminate the effects of trisomy 21, given the complexity of the observed alterations. In view of the multigene nature of the condition (as demonstrated by the large number of affected genes in the fetuses analyzed), it is simply not feasible to recover a normal expression level for all of them. In contrast, silencing the extra chromosome 21 in Down syndrome attacks the root cause of the pathological alterations inherent to the condition. Nevertheless, as Jouve and Tudela caution, this approach is not expected to translate into clinical practice in the near future.^[2] Further preclinical research with animal models will first be required to identify a safe and appropriate method to perform this silencing in fetal cells. The next critical step will be to verify in these models whether the silencing of the extra chromosome is sustained after birth and whether the abnormalities observed in Down syndrome disappear, or at least decrease. Finally, the criteria for human clinical trials must be established. With respect to the latter, it should be noted that a CRISPR-Cas9-based technology was effective in correcting a genetic abnormality in a neonate, and that clinical trials are being considered to extend its use to a wider population.^[4] Moreover, the in utero correction  of a genetic abnormality has also been achieved recently, as mentioned by the Bioethics Observatory, although in this case it was not carried out using gene editing.^[5]

Bioethical assessment

The article published in Science and led by de la Torre-Ubieta^[3] raises a clear ethical issue. Presenting studies allegedly aimed at finding therapeutic solutions to trisomy 21 while using fetuses aborted voluntarily is a paradoxical endeavor. It must be taken into account that, in all likelihood, these abortions will have been performed following medical advice after detecting trisomy 21 during prenatal screening. Moreover, even if the real purpose of the research was to find potential therapeutic resources (resources that, for the reasons indicated above, are practically unfeasible), the means used are clearly illicit. In this sense, the categorical statement of the Papal Encyclical Evangelium vitæ is clear, equating as it does the destruction of human embryos with abortion itself, stating that [t]o use human embryos or foetuses as the object or instrument of experimentation constitutes a crime against their dignity as human beings having a right to the same respect that is due to the child already born and to every human person.^[6]

María de Ujué Moreno Zulategui

Department of Biochemistry and Genetics. Faculty of Sciences

University of Navarra

Luis Franco

Member of the Spanish Royal Academy of Sciences

Member of the Bioethics Observatory

References

1. Lian, G., Khabazeh, A. y Sheen, V. (2026) A modified CRISPR/Cas9 approach in silencing the triplication in Down syndrome: A treatment path XISTs. Proc. Natl. Acad. Sci. U. S. A. 21:e2517953123.
2. Jouve, N. y Tudela, J. (2026) A new breakthrough in chromosome silencing offers a potential treatment pathway for trisomy 21. UCV Bioethics Observatory, 18 April.
3. Vuong, C. K., Weber, A., Seong, P., (…) y de la Torre-Ubieta, L. (2026) A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex. Science 392:eaea1259.
4. Musunuru, K., Grandinette, S. A., Wang, X., (…) y Ahrens-Nicklas, R. C. (2025) Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N. Engl. J. Med. 392:2235-2243.
5. Franco, L. (2025) New hope for in utero treatment of spinal muscular atrophy. UCV Bioethics Observatory, 6 March.
6. John Paul II. (1995) Encyclical Letter Evangelium Vitae, no. 63: AAS 87:472-473.