XENOBOT Gene-Edited “Packman Living Robot” Frog Cells Reproduce, Display Unanticipated Behaviors

Xenobots, hybrid frog-derived dermal cells “liberated” to a petri dish and given mouths using CRISPR gene editing technology, feed, do new things on their own, and even reproduce. As noted in the Harvard.edu/news:  In a Xenopus laevis frog, these embryonic cells would develop into skin. “They would be sitting on the outside of a tadpole, keeping out pathogens and redistributing mucus,” says Michael Levin, Ph.D., a professor of biology and director of the Allen Discovery Center at Tufts University and co-leader of the new research. “But we’re putting them into a novel context. We’re giving them a chance to reimagine their multicellularity.” Levin is also an Associate Faculty member at the Wyss Institute.

“People have thought for quite a long time that we’ve worked out all the ways that life can reproduce or replicate. But this is something that’s never been observed before,” says co-author Douglas Blackiston, Ph.D., the senior scientist at Tufts University and the Wyss Institute who assembled the Xenobot “parents” and developed the biological portion of the new study.

“This is profound,” says Levin. “These cells have the genome of a frog, but, freed from becoming tadpoles, they use their collective intelligence, a plasticity, to do something astounding.” In earlier experiments, the scientists were amazed that Xenobots could be designed to achieve simple tasks. Now they are stunned that these biological objects—a computer-designed collection of cells—will spontaneously replicate. “We have the full, unaltered frog genome,” says Levin, “but it gave no hint that these cells can work together on this new task,” of gathering and then compressing separated cells into working self-copies. “These are frog cells replicating in a way that is very different from how frogs do it. No animal or plant known to science replicates in this way,” says Sam Kriegman, Ph.D.,  the lead author on the new study, who completed his Ph.D. in Bongard’s lab at UVM and is now a post-doctoral researcher at Tuft’s Allen Center and Harvard University’s Wyss Institute for Biologically Inspired Engineering.

“We asked the supercomputer at UVM to figure out how to adjust the shape of the initial parents, and the AI came up with some strange designs after months of chugging away, including one that resembled Pac-Man,” says Kriegman. “It’s very non-intuitive. It looks very simple, but it’s not something a human engineer would come up with. Why one tiny mouth? Why not five? We sent the results to Doug and he built these Pac-Man-shaped parent Xenobots. Then those parents built children, who built grandchildren, who built great-grandchildren, who built great-great-grandchildren.” In other words, the right design greatly extended the number of generations. And the team sees promise in the research for advancements toward regenerative medicine. “If we knew how to tell collections of cells to do what we wanted them to do, ultimately, that’s regenerative medicine—that’s the solution to traumatic injury, birth defects, cancer, and aging,” says Levin. “All of these different problems are here because we don’t know how to predict and control what groups of cells are going to build. Xenobots are a new platform for teaching us.”

The Wyss Institute for Biologically Inspired Engineering at Harvard University (https://wyss.harvard.edu) uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Watch a video on xenobots here. See also this CNN report for additional information: https://www.cnn.com/2021/11/29/americas/xenobots-self-replicating-robots-scn/index.html.