The next step in the development of artificial life

When controversial genetic engineering pioneer Craig Venter announced in 2010 that he had created the first organism with a completely artificial genome from the bacterium Mycoplasma capricolum, the media response was manageable. But it was a milestone in modern genetic engineering (even if important functions had been retained in the cells). Actually, it sounded quite simple: it had been possible to synthesise the complete genome from a computer data set and transplant it into an existing cell from which the DNA had been removed. Almost four years later, Jef Boeke succeeded in reconstructing a complete chromosome of yeast with a few artificial changes. Yeasts are so-called eukaryotes. The genetic material of yeast is much more extensive and complicated than that of the bacteria and viruses in Venter’s studies. Humans are also eukaryotes; basically the jump from the bacterial genome to the baker’s yeast genome is greater than that from the baker’s yeast genome to the human genome. The first steps towards the artificial generation of more complex life forms had thus been taken. Thus, after his success, Venter spoke of a new “digital era” in biology, in which DNA as the “software of life” could be programmed at will to produce microorganisms as needed. These could produce precisely desired amino acid sequences, i.e. proteins, which would make it possible, for example, to produce new medicines that were previously very difficult and expensive to get to.

But the ambition of genetic engineers goes even further: they want nothing less than to learn to use the programming language of life to produce better genomes than nature has done. This could make completely new organisms possible, and with very tangible benefits: In addition to applications in medicine, one hopes for applications in energy production, e.g. electricity or hydrocarbon-producing bacteria, breaking down oil spills in the world’s oceans, decomposing plastics, CO2 “eating” by bacteria, better and more efficient food production or improvements in agriculture.

The next step was now “real” animals. As mentioned, the step from yeasts to larger animals is not as big as intuitively assumed. But that does not mean that it is all so simple. On 26 August 2022, after more than 10 years of hard work, scientists led by Magdalena Zernicka-Goetz in Cambridge (UK) announced that they had created synthetic mouse embryos without eggs or sperm, but from stem cells – the body’s master cells that can develop into almost any cell type in the body[1]. This work could decisively shape the idea of how a human being is created in detail. While the method is far from perfect (only a very small proportion of the synthetic embryos grew as desired, and even the best result still differs in important details from the natural model), the work nevertheless allowed the researchers to observe organ development in a mammal in unprecedented detail.

Specifically, the researchers mimicked natural processes in the lab by directing the three types of stem cells found in early mammalian development, representing the three early tissue types, in the right proportions and into the right environments to promote their growth, to the point where they begin to cooperate. By inducing the expression of a specific group of genes and creating a unique environment for their interactions, the researchers were actually able to get the stem cells to communicate with each other. This allowed them to organize themselves into structures that went through the various stages of development until they had a beating heart and the foundations of the brain, as well as the yolk sac from which the embryo develops and receives nutrients in the first few weeks. Unlike other synthetic embryos, the models developed in Cambridge reached the point where the entire brain began to develop.

Such experiments and equally detailed observation of the very early stage are now planned with human stem cells. The technique could one day replace experiments on living animals in developmental biology research or be used to grow organs and tissue for transplantation into humans. By then, at the latest, it should be clear: Ethical questions arise here. In many countries, experiments on human embryos are prohibited, in many others (such as in England) the so-called 14-day rule applies, according to which embryos left over from artificial insemination may not be grown in the laboratory for longer than two weeks. However, it is unclear whether and under what conditions human synthetic embryos are considered embryos in the legal sense. When is an embryo an embryo? That remains an open question … until now.

[1] Magdalena Zernicka-Goetz et al., Stem cell-derived mouse embryos develop within an extra-embryonic yolk sac to form anterior brain regions and a beating heart, Nature (26. Aug. 2022)