A team from the Weizmann Institute of Science in Rehovot, Israel, has reported that it has differentiated naive and primed human pluripotent stem cells into trophoblast cells. The article detailing the work of Sergey Viukov and colleagues was published in an early November 2022 issue of the journal Stem Cell Reports. The authors state that their research will allow for the study of placental development and disorders in vitro. More controversially, they also aim to develop human “synthetic” embryos using these results.

When an embryo is at the blastocyst stage of development, it consists of three parts: an outer layer of trophoblast cells, a fluid-filled cavity, and an inner cell mass that is polarized to one side of the cavity. Trophoblast cells go on to significantly contribute to the development of the placenta, which provides nutrients and oxygen to the growing child. Previously it was believed that primed pluripotent stem cells (those reflecting the state of the inner cell mass of the postimplantation embryo) are not able to differentiate into trophoblast stem cells. By stimulating and inhibiting key cell-signaling pathways with their cell medium, Viukov and colleagues were able to differentiate primed pluripotent stem cells into two major trophoblast cell lines associated with nutrient exchange between mother and child, hormone secretion, and penetration of the endometrium and the mother’s blood vessels. Fittingly, the article was highlighted on the cover of the journal with art depicting a construction site assembling a mammalian embryo.

Many of these same investigators made waves in Summer 2022 with their report on culturing post-gastrulation synthetic embryos, termed sEmbryos, generated solely from mouse embryonic stem cells. After eight days of growth and time in a specially designed bioreactor, the sEmbryos displayed incredible development, with “well-formed head folds, neural tube (NT), invaginating foregut, beating heart, and up to four pairs of somites, followed by the tail.” The results were reported in international news outlets as a major achievement.

The stated ends of the research program are to study healthy and diseased human development as well as to create a platform for tissue transplantation. Biotechnology firms and investors have taken notice of the remarkable results of the Weizmann Institute and their implications. For example, RenewalBio, a startup company associated with Jacob Hanna, one of the lead authors in both studies, has been founded to harvest tissues from human sEmbryos for therapeutic transplantation to patients.

Hanna has stated that the team’s intention is to continue similar post-gastrulation work with human cells. He does not believe that human sEmbryos are now or will become human beings, stating in an interview with MIT Technology Review, “We are not trying to make human beings. That is not what we are trying to do.” Earlier in the article, Hanna associates sEmbryos’s inability to grow outside their test tubes as indicative of a lack of humanity. The pioneers of human stem-cell-derived embryo models consider the research to be an ethical alternative to the use of naturally derived human embryos. However, guidelines from the International Society of Stem Cell Research have grouped protocols involving naturally derived embryos and those involving integrated stem-cell-based embryo models into the same review and oversight category, indicating an ethical equivalence between the two groups.

The biological status of the synthetic embryo is paramount for moral analysis. In Donum vitae, the Catholic Church teaches that the human being, “from the first moment of its existence, that is to say from the moment the zygote has formed, demands the unconditional respect that is morally due to the human being in his bodily and spiritual totality” (I.1). Thus, in Dignitas personae, the Congregation for the Doctrine of the Faith reaffirms that the prohibition on abortion is also applied to experimentation on human embryos, which is a “crime against their dignity as human beings who have a right to the same respect owed to a child once born, just as to every person” (n. 34).

Unfortunately, the status of the sEmbryos created thus far is unclear. Based on the results with mouse cells, it is possible that any human sEmbryos created by Hanna’s team will be bona fide young humans, albeit stunted. Prudential caution is warranted until a broad public consensus is formed around the status of stem-cell-based, or “synthetic,” entities. Otherwise, investigators risk a grave crime against the dignity of the embryonic human.

Kevin Wilger is a research engineer in Lafayette, Indiana.

Scientists Move Closer to “Synthetic” Human Embryos