Creating artificial human embryos in the laboratory

It is not often that the public can follow a scientific race virtually live. After developmental biologist Magdalena Zernicka-Goetz from the University of Cambridge announced last Wednesday during a lecture in Boston that her team had created synthetic human embryos from stem cells, this was first reported in the British Guardian - scientific articles had not yet been published at the time. On Thursday, the competing working group led by stem cell researcher Yaqub Hanna from the Weizmann Institute in Israel uploaded an article to the online database for biomedical pre-publications BioRxiv, in which they presented a very similar result to Zernicka-Goetz, only with a different procedure. Two other working groups also published preliminary reports on work with artificial human embryos there on Thursday. And on Friday, the paper by the team led by Zernicka-Goetz followed, in which the researchers provided details of the presentation in Boston.

None of these articles have yet been thoroughly peer-reviewed by independent experts. However, experts agree that this is an expected, yet major step forward for the field of research. Until now, such experiments had only been described in connection with animal embryos. However, the competition is not only about scientific fame, but also about property rights for the methods. Researchers from the groups led by Zernicka-Goetz and Hanna have declared that they are involved in patent applications.

A whole person could not yet grow from the cell clusters

The embryos created from stem cells in the laboratory must be imagined as clusters of cells. They may have the potential to grow into a human being, but there are no techniques for this in the laboratory. And these constructs could not be transferred into a woman's uterus because they omit a necessary developmental step.

The researchers therefore also refer to their synthetic embryos as "models" - potentially useful for regenerative medicine, reproductive medicine and developmental biology. "Furthermore, the discussion about this type of embryo production will also pose a new challenge to the legal and ethical framework in Germany and beyond," write Nils Hoppe and Sara Röttger from the Centre for Ethics and Law in the Life Sciences (CELLS) at the Gottfried Wilhelm Leibniz University of Hanover in a joint statement on the reports from England and Israel. "Are synthetic embryos less worthy of protection than, for example, embryos from fertility treatment? We will have to reorient ourselves once again in terms of society."

The team led by Zernicka-Goetz genetically modified human stem cells so that they began to develop not just individual tissue types, but a complete embryo. Instead of genetic engineering, Hanna's group used a cocktail of biochemicals to trigger this transformation. The fact that it should be possible to grow entire embryos with different cell types from individual stem cells had already been shown previously in experiments on monkeys and mice. In this respect, the transfer to human cells was only a matter of time.

It is impressive to see "how more than a decade of very fundamental research" led to this result, says Jesse Veenvliet, head of the Embryogenesis Research Group at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, who was not involved in the work. He describes the similarity between the artificial embryos and their natural equivalents as "remarkable, almost uncanny".

Do the experiments mark a renaissance of cloning?

Michele Boiani, head of the "Mouse Embryology" working group at the Max Planck Institute for Molecular Biomedicine in Münster, is also impressed by the work, "but I am critical of the linguistic nomenclature used, in which the embryonic structures created are described as mere 'models' of human embryonic development." As a mouse biologist, he sees things this way: If the function of development is given, the constructs should simply be regarded as embryos - regardless of their biological origin, he says. "Insofar as they recapitulate early human development, they should be called embryos and not treated as mere models - especially in a legal sense."

Ingrid Metzler, who works in the Department of Biomedical Ethics and Healthcare Ethics at Karl Landsteiner University of Health Sciences in Krems, agrees. The groups led by Hanna and Zernicka-Goetz "seem to suggest that work with stem cell-induced embryo models could be an ethical alternative to research on embryos," says Metzler. "From the groups' point of view, this is an understandable position. However, I think it would be premature to turn this position into a general categorisation of research on and with these new types of objects."

In principle, similar research would also be conceivable in Germany. "In Germany, the production of artificial embryo-like structures is not prohibited," says medical law expert Jochen Taupitz from the University of Mannheim. They could never develop into a born human being. He therefore also believes it is right not to apply the 14-day rule, which is sometimes applied abroad, according to which embryos should only be researched up to two weeks after fertilisation. However, if the artificial embryos are created from embryonic stem cells, as in the current case, the Stem Cell Act applies, which only allows such research under strict conditions. The situation would be different if iPS cells, reprogrammed body cells, were used: "Induced pluripotent stem cells (iPS) and entities derived from them, on the other hand, are not covered by the Stem Cell Act," says Taupitz.

From Michele Boiani's point of view, the clusters of cells created are not only embryos, but also clones that are grown from stem cells in the laboratory. Accordingly, the experiments "ultimately represent a renaissance of human embryo cloning"

Article in the "Süddeutsche Zeitung" from 17 June 2023