Clumps of matter in a petri dish swim and sway like schoolkids drunk on the rush of a playground carousel spun too fast. To the casual observer, the video of these whirling motes looks a little like the sea of microorganisms you see floating in a drop of pond water under a microscope in a school science class. But to researchers, this video may represent the opening of a new chapter in biology — both technologically and philosophically.
These little peach blobs are in fact artificially engineered biorobots, caught on camera reproducing for the first time. The experiment results, published this week in the Proceedings of the National Academy of Sciences, are perhaps the strangest synthesis of artificial intelligence and biology yet.
What’s new — This disturbing and enthralling innovation is the latest advance in the emerging science of Xenobots. First created in January of 2020, these biological robots are actually globs of stem cells derived from the cells of African clawed frogs. At first, these bots had a single purpose: To move forward. Since then, the bots have developed their motor skills and gained new capabilities, including memory and the ability to interact with their surrounding environment. And now they can multiply — but how the Xenobots beget new versions of themselves isn’t the typical kind associated with biological life.
Rather, the authors of the study term this life-like behavior as “self-replication,” rather than reproduction:
“The ability of genetically unmodified cells to be reconfigured into kinematic self-replicators, a behavior previously unobserved in plants or animals, and the fact that this unique replicative strategy arises spontaneously rather than evolving by specific selection, further exemplifies the developmental plasticity available in biological design,” the authors write.
Why it matters — These bots look alive, so it is worth thinking about how we define “life.” According to NASA, life is a “self-sustaining chemical system capable of Darwinian evolution,” although some scientists might take issue with this definition (hello, viruses). Xenobots are stem cells and behave in ways we think of as “life-like” but they are not alive.
They are undifferentiated stem cells, which means they are cells without a purpose. They also don’t behave like a typical organism — which is perhaps why the way they multiply is like nothing seen in nature.
This method of self-replication, though, could tell us something about the first organisms to exist on Earth and even organisms existing elsewhere in the universe on habitable worlds. In the early days of our planet, self-assembling peptides became capable of self-replication, “and would thus represent the earliest stage in the evolution of life,” the authors write. This theoretical stage of life pre-dates the rise of RNA — the blueprint DNA uses to convert genetic information into proteins. Life as we know it today — based on DNA — arose even later in Earth’s history.
It is worth considering, however, how these bots can not only offer insight into the origins of life, but also new frontiers for biology and robotics.
How they did it — To build the Xenobots, researchers first remove stem cells from a very early stage in the development of a frog embryo, called the blastula. Stem cells are a sort of builder cell that is not yet specialized into specific cell types, like brain cells or muscle cells.
These “blank slate” cells are then placed in a saline solution, which prompts the cells to agglomerate into spheres of about 3,000 cells each.
After three days, the spheres developed cilia or hair-like appendages that allow them to interact with the surrounding environment. The researchers then place the spheroids into a petri dish along with 60,000 other stem cells. Incredibly, the spheroids sort of herd the other stem cells together into smaller structures of about 50 stem cells each.
These mini-spheres, in turn, move around, and when encountering other stem cells, start the process all over again, building “new” Xenobots as they go. In the case of this experiment, there were only enough stem cells provided to generate two new sets of spheres. Still, that means that the original spheres existed long enough to see their grandchildren, as it were.
To maximize the experimental results, the researchers paired them with a machine learning algorithm that helped guide certain features, like sphere size and shape, as well as the terrain they encountered along the way.
What’s next — The algorithm aspect matters when it comes to future applications for this weird technology. The team behind this study, for example, believes that computer modeling could enable the Xenobots to have new forms and functions — flexibility inherent in stem cells on a biological level, too. Imagine stem cell “bots” that shuttled drugs through hard-to-penetrate systems, like the blood-brain barrier, for example.
“AI design methods have been shown to be capable of exploiting this flexibility to exaggerate these behaviors and, in future, possibly guide them toward more useful forms,” the authors write.
Abstract: All living systems perpetuate themselves via growth in or on the body, followed by splitting, budding, or birth. We find that synthetic multicellular assemblies can also replicate kinematically by moving and compressing dissociated cells in their environment into functional self-copies. This form of perpetuation, previously unseen in any organism, arises spontaneously over days rather than evolving over millennia. We also show how artificial intelligence methods can design assemblies that postpone loss of replicative ability and perform useful work as a side effect of replication. This suggests other unique and useful phenotypes can be rapidly reached from wild-type organisms without selection or genetic engineering, thereby broadening our understanding of the conditions under which replication arises, phenotypic plasticity, and how useful replicative machines may be realized.