Health Science Reviews

by Warwick Pitman

Both my favourite science fiction novel, Brave New World, and science fiction film Blade Runner 2049, depict a reality in which ‘humans’ can be cultured outside of the mother until the end of embryonic development. The idea stems from the allure of potentially hacking biology in a way that allows humans to create organisms with preferable capabilities. If that isn’t a recipe for a perfect science fiction novel or film, I don’t know what is! With the discovery of genetic engineering tools such as CRISPR-Cas9, the idea of introducing specific changes into the genome has indeed become a reality, but what about the culturing of embryos outside of the mother’s body? Recently a study published in Nature shows that although we are far from this reality, we are a step closer to achieving this controversial yet remarkable feat. The authors established a system that allows for the culturing of mouse embryos from an early point in embryo development, specifically known as gastrulation, through to a point at which organ development occurs.  

The purpose of developing such a culture system is to help elucidate the developmental processes of tissue and organ formation during embryo development as these processes are difficult to investigate inside the body because they occur after implantation of the embryo. An analogy for this could be a little mole that one can observe and study when it is above ground but is actually most interesting to study when it burrows itself underground where they are adapted to hunt and create tunnelling networks. The same can be said for the embryo after it embeds itself within the uterine lining of the mother, as this is when the body axes of the embryo are established and where cells change in multiple ways to form the different organs of the body.

Since the maternal environment provides the embryo with specific nutrients and availability of oxygen to aid development, the authors had to attempt to replicate this environment as accurately as possible. This was accomplished by testing different media, supplements, and pressures, before ultimately finding the goldilocks conditions that supported the growth and correct development of the cultured embryos. The authors then provided evidence that the cells of the cultured embryos expressed the same genes as those found in embryos that developed inside the mother. This suggested that the culture system was not interfering with the normal development of the embryo and therefore could be used as a tool to recapitulate what occurs within the maternal environment.

One of the major implications of the system, that the authors make mention of, is as a tool to determine the effects of different perturbations on development of the embryo. This was something Aldous Huxley, the author of Brave New World made use of, to differentiate the castes formed in his dystopian novel. For example, oxygen deprivation and alcohol treatment are used in the novel to lower the intelligence and size of individuals of the lower three castes (Gammas, Deltas and Epsilons). In contrast to this, the motives of the authors of the Nature paper are ethically superior, as they contemplate using such a system to better understand the processes leading to the formation of organs through genetic modification which can have therapeutic applications. One of which would be its use in the field of regenerative medicine, as by understanding the molecular cues that orchestrate the development of an organ can provide insight into how one could regenerate it following an injury. To better understand this idea, one could view each organ of the body as a specific building each with its own architectural plan. If you knew the exact amount of brick, wood, and glass that was used to assemble the structure, it would be much easier to rebuild it, should it ever get knocked down.  

Overall, the study established a system that prolonged the culturing of embryos outside of the mother to a point in embryo development never observed before, but also showed the current limitations in executing what was described and depicted in Brave New World and Blade Runner 2049, respectively. This may be a good thing, as with such great power comes great responsibility, and whether our society would want such a culture system to be available for use is questionable considering the dystopian worlds developed in such novels and films.

Reference:

Aguilera-Castrejon, A., Oldak, B., Shani, T. et al. Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis. Nature 593, 119–124 (2021). https://doi.org/10.1038/s41586-021-03416-3