Science is advancing in the creation of synthetic embryos: where are the limits?

Until now, a human embryo was obtained with eggs and sperm, either in a womb or in vitro. Now, cells can be taken from an adult and treated until a conglomerate is obtained that is difficult to distinguish from an embryo.

Since last June, several teams of scientists have announced the creation of artificial human embryos

The artificial embryos are promising for studying why so many pregnancies fail and the origin of serious malformations. But they are in a legal loophole: It is not clear that the rule of not making them grow is valid beyond 14 days, which applies to experimental embryos made from eggs and sperm. Could an unscrupulous scientist implant a synthetic embryo in a womb?

Artificial embryos show promise for studying pathologies, but they are in a legal loophole: Could an unscrupulous scientist implant one in a womb?

And there is more. Make a artificial belly It seems like a relatively easier challenge than manufacturing an artificial embryo. Will there come a day when these embryos can be gestated outside of a womb?

Faced with these questions, many scientists abhor the term ‘synthetic embryos’ and advocate referring to ‘stem cell-based embryo models’. However, others believe that going from a model to an exact copy is just a matter of time. Defining the line that separates the two things is not easy.

Some scientists defend non-integrated embryos as an alternative: they allow the generation of tissues, which do not completely imitate an embryo, and cannot be implanted.

Lets start by the beginning. The earthquake occurred in June, when the biologist Magdalena Żernicka-Goetz announced at a conference the obtaining of synthetic embryos in its laboratory at the University of Cambridge (United Kingdom). Shortly after, in September, Jacob Hanna, a researcher at the Weitzmann Institute in Israel, published that he had achieved the same thing with another method. While Żernicka-Goetz genetically modified the stem cells, Hanna did so without genetic modification.

In the following weeks, other laboratories quickly announced that they were also working on the same topic. “Suddenly we realized how many people were working on it around the world,” he says. Sergio Pérez Acebronbiologist at the University of Heidelberg.

Scientists seek to observe gastrulation, the phase of development in which three layers are formed that give rise to all the organs.

Żernicka takes pluripotent stem cells and genetically modifies them so that they organize like embryos. Hanna doesn’t just do genetic modification: she mixes various types of cells in a specific culture and applies a protocol that gets them structured like embryos. “The cells have genetic information to spontaneously organize themselves into structures very similar to human embryos,” he observes. Lluís Montoliuresearcher at the National Center for Biotechnology (CNB-CSIC).

“It is a technology that is not based on the complete understanding of a living system, but on guiding it to express its potential. It is more like gardening than engineering,” he explains. Ben Harlbutbioethics researcher at Arizona State University.

Observe gastrulation

The scientific motivation for developing a synthetic embryo is to remove the veil over a key moment of embryonic development: gastrulationthe phase in which three layers are formed that give rise to all the organs.

In fish and amphibians, this phase can be observed because their eggs are transparent. In mammals, it occurs under the endometrial envelope and is hidden from the gaze of scientists. Synthetic embryos allow us to see what happens in a laboratory dish.

“The question is not whether they are embryos or not, but what the limits are and who is going to establish them”

Ben Harlbut

Bioethics researcher at Arizona State University

“With this, we could improve the in vitro fertilization and study congenital diseasessuch as malformations of the spinal column,” points out Alfonso Martínez-Ariasbiologist at Pompeu Fabra University.

“The embryo models could also be used as reactors, to generate all kinds of fabrics“says Acebron. For example, healthy eggs could be generated for women who do not have them.

Alternative system

All of this could be achieved with a less controversial systemin which Martínez-Arias works, among others: the models of unintegrated embryosartifacts that can generate a variety of tissues, which do not completely imitate an embryo and cannot be implanted.

These models also pose ethical challenges. For example, they could be used to generate many eggs and select them eugenically. However, it is the integrated models (such as those of Hanna and Żernicka) that generate the most controversy. Conceivable applications include producing clones or gestating the synthetic embryo outside the womb.

Currently, the main barrier is technical. “The efficiency of the process is very poor. Only one embryo is obtained from dozens of attempts,” observes Montoliu. Implantation experiments in mice have resulted in “very damaged animals,” explains Martínez-Arias. Attempts in macaques have failed.

Conceivable applications include producing clones or gestating the synthetic embryo outside the womb, but there are still technical barriers

“What is being done has been greatly exaggerated. It is dangerous and can harm research,” says the scientist, who defends that non-integrated models are much more reliable and reproducible.

However, technical hurdles could soon fall. “Some cell models look very similar to embryos and will become more and more similar,” warns Pérez-Acebrón. “A specialist would detect differences, but the truth is that they are very similar,” Montoliu agrees. So, are they embryos like the others, or not?

“Some cell models look very similar to embryos and will become more and more similar”

Sergio Pérez Acebron

Biologist at the University of Heidelberg

Various scientists agree on one criterion: embryos must be considered if, once implanted, they can give rise to a fetus. If not, they are not. Since the viability is now doubtful, many believe that they should be called embryo models.

“It’s a way of use the language so as not to have to face certain problems,” he replies Immaculate Conception of Melo-Martín, bioethicist currently visiting the National Cancer Research Center. If the criterion is implantation and this is prescribed, then the criterion does not hold, according to Harlbut.

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“Even if they are not embryos, their resemblance can generate rejection among citizens. It may seem that we are creating people in culture,” says Acebron. Martínez-Arias believes that complex structures such as a synthetic embryo should not be generated if the same can be achieved with simpler models.

“The question is not whether they are embryos or not, but What are the limits and who will establish them?. Just because scientists created them does not mean that only scientists have to decide. There are questions about human dignity and our responsibility towards it. These are questions for the entire society,” concludes Halrbut.

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