Imagine: behind closed doors in a laboratory, clusters of cells are bathed in a strange liquid. These are simple cells taken from the skin of a mammal, nothing extraordinary at this stage. But suddenly, traces of blood appear, and… a heartbeat. The resemblance to a real embryo is striking, except that its creation did not require sperm or egg. Science fiction? In recent years, research on what is wrongly called “synthetic embryos” has taken several decisive steps. And the feats are accelerating. In the spring, several teams announced spectacular – and highly publicized – advances in the development of human embryoids, which aim to reproduce the functioning and development of an embryo, but without the need for any fertilization.
Among other things, recently the teams of Magdalena Zernicka-Goetz, from the University of Cambridge (United Kingdom), by Jacob Hanna, Weizmann Institute (Israel), and Tianqing Li, from Kunming University (China) have posted results online as part of a pre-publication. Jacob Hanna explains that he cultivated this embryonic model from human embryonic stem cells, up to a stage equivalent to 14 days after fertilization. In these three cases, the scientists let their embryonic models self-assemble from human stem cells, some of which had been previously converted into cells similar to those forming the placenta. The structures formed reflect certain aspects of the embryo between 10 and 14 days. Lacking the tissues that allow attachment to the uterus, these structures would not have been able to grow into viable fetuses anyway. Several groups had already published complete mouse and human models, called blastoids. As for some partial mouse models, they have progressed to form the beginnings of the formation of the heart and the brain, even if these structures form imperfectly and inefficiently.
Many questions remain open, and caution is warranted. Claims from the latest studies, none of which have yet been peer-reviewed, need to be validated by reputable publications, and then verified by other labs. The stakes are enormous: the creation of a human embryoid would mark a scientific first of a rare magnitude. And that’s the whole challenge.
For Jacob Hannah, the goal remains to create a model human embryo “that develops and progresses dynamically through the various stages of development”, regardless of the number of days in culture. “An embryo must not simply exist, it must advance in its development while retaining its refined architecture in order to transform itself every day. There lies the mystery”, he continues. For the time being, we are approaching it step by step while remaining quite far from the expected result. Jacob Hannah anticipates the creation of models of human embryos that would reach a stage of development equivalent to forty days after fertilization. “It’s not for tomorrow, but it will certainly be possible,” says the biologist.
Drugs to increase IVF success
Faced with a rare media frenzy in the field of fundamental research, some observers fear the effects of the announcement likely to obscure an ethical reflection that promises to be complex. However, this research is of considerable interest for better understanding the first days of an embryo, a period whose mechanisms remain in fact very mysterious. “We are currently trying to send humans to Mars but, strangely enough, we do not know how human life is formed. With this research, we have an incredible opportunity to find out where we came from,” says Nicolas Rivron, who himself developed mouse blastoids in 2018 and human blastoids in 2021 at the Vienna Academy of Sciences, reproducing the blastocyst stage, just before implantation in the maternal uterus. These human blastoids are able to attach to uterine cells in vitro, thus mimicking the implantation process, and can grow up to day 13, but they gradually become disorganized.
The gains in terms of public health could be enormous, in particular to better understand and treat unexplained early pregnancy loss, reduced fertility, the development of genetic diseases or even contraception. “It will play out in the next ten to fifteen years with regard to the use of these models to discover the molecules that act at this stage of development and which can, subsequently, be prescribed in the clinic to facilitate the culture of embryos. from in vitro fertilization, he continues. In the longer term, we could eventually discover drugs to be taken at the time of the embryo transfer to help it implant and develop properly”. The researcher also imagines non-hormonal means of contraception, in order to avoid the inconvenience associated with the pill, or preventive developmental medicine. “We know that certain behaviors during pregnancy (diet, stress, etc.) can cause the appearance of certain chronic pathologies much later, continues Nicolas Rivron. We could possibly prevent them and ensure that the fetus develops as well as possible”. But for that, it will be necessary to wait several decades, he warns.
Embryoids will not fail to raise ethical questions, particularly on the status to be given to them. Controversies quickly arise when the term “synthetic embryos” is used. This expression is considered incorrect by many researchers, because these structures are in fact incapable of developing. They are not synthetic either, since they require starting from real cells. From an ethical point of view, until now, the debates have focused on natural embryos, around, in particular, the time limit for their growth outside the uterus. The International Society for Stem Cell Research (ISSCR), which publishes guidelines, has until now recommended a maximum of fourteen days as the limit for culturing human embryos, but, in its recommendations published in May 2021, it invites legislation to discuss and take charge, through their ethics committees, of this duration of in vitro culture. However, for technical reasons, we do not currently know how to correctly replicate the complexity of the human organism at a more developed stage. But research continues…
Towards the creation of a “humanoid”?
Faced with recent progress, the scientific community met again in 2018. “We have been thinking about it for five years in reality, and we anticipate what will happen, specifies Nicolas Rivron, who is part of reflection committees. The first regulations were published by the ISSCR in 2021, even before the publication of the first human blastoids, and advocate strict regulation of research and a ban on transferring these human models into wombs, whether animal or human. The next recommendations, which will be published soon, will insist on refining the definition of the embryo in order to better assess, in the future, when these models could switch and be considered as true embryos. still there, but it is important that the ethical questions are resolved upstream”.
All this in order to avoid the creation of humanoids manufactured in the laboratory? So far, we have never succeeded in developing a reintroduced blastoid in a mouse or a monkey. A beginning of pregnancy certainly takes place, but it stops less than a week after the implantation. “Scientifically we are still very far from it, tempers Nicolas Rivron. And then even so, I don’t believe it. The only legal mode of reproduction is by the fusion of an oocyte and a sperm, and that will not change. not”. “We do not want to create life in this way but simply to observe it at its beginnings”, adds Magdalena Zernicka-Goetz. Science fiction, for now, but it’s never too early to think about such odds, however low they may be. “This is a golden age for answering many fundamental and medical questions. Let’s not miss the opportunity, warns Nicolas Rivron. This research must be carried out, but always in an ethical way”.