AI-developed Xenobots reveal a completely new form of biological self-replication – very promising for regenerative medicine

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In order to exist, life has to reproduce. Over billions of years, organisms have evolved many types of replication, from budding plants to sexual animals to invading viruses.

Now, scientists from the University of Vermont, Tufts University, and the Wyss Institute for Biologically Inspired Engineering at Harvard University have discovered an entirely new form of biological reproduction – and applied their discovery to create the very first self-replicating living robots.

The same team that built the first living robots (“Xenobots”, composed of frog cells – reported in 2020) discovered that these computer-designed and hand-assembled organisms swim into their tiny shells, find individual cells, and collect hundreds can put them together and assemble “baby” xenobots in their Pac-Man-shaped “mouths” – which a few days later become new xenobots that look and move just like themselves.

And then these new xenobots can run out, find cells, and make copies of themselves. Again and again.

“With the right design, they’ll spontaneously replicate themselves,” says Joshua Bongard, Ph.D., a computer scientist and robotics expert at the University of Vermont who led the new research.

The results of the new research were published on November 29, 2021 in the. released Procedure of the National Academy of Sciences.

Into the unknown

In one Xenopus laevis Frog, these embryonic cells would develop into skin. “You’d sit on the outside of a tadpole, keeping pathogens out and redistributing mucus,” says Michael Levin, Ph.D., professor of biology and director of the Allen Discovery Center at Tufts University and co-director of the new research. “But we put them in a new context. We give them the chance to rethink their multicellular nature.” Levin is also an associate faculty member at the Wyss Institute.

And what they imagine is something completely different than skin. “People have long believed that we have all worked out ways in which life can reproduce or replicate. But this is something that has never been observed before, ”says co-author Douglas Blackiston, Ph.D., senior scientist at Tufts University and the Wyss Institute who compiled the Xenobot” parents “and the biological portion of the new study developed.

“That’s profound,” says Levin. “These cells have the genome of a frog, but when freed from tadpoles, they use their collective intelligence, a plasticity, to do something amazing.” In previous experiments, scientists were amazed that Xenobots can be engineered to perform simple tasks. Now they are stunned that these biological objects – a computerized collection of cells – are replicating spontaneously. “We have the full, unchanged frog genome,” says Levin, “but there was no evidence that these cells could work together in this new task,” collecting separate cells and then compressing them into functioning self-copies.

“These are frog cells that replicate very differently than frogs did his Ph.D. in Bongard’s laboratory at UVM and is now a postdoctoral fellow at the Allen Center in Tuft and the Wyss Institute for Biologically Inspired Engineering at Harvard University.

The Xenobot mother alone, which consists of around 3,000 cells, forms a sphere. “This can create children, but then the system usually dies. It’s actually very difficult to get the system to reproduce further, ”says Kriegman. But with an artificial intelligence program working on the Deep Green supercomputer cluster of the Vermont Advanced Computing Core by UVM, an evolutionary algorithm was able to test billions of body shapes in simulation – triangles, squares, pyramids, starfish – to find those which enabled cells to be more effective in the motion-based “kinematic” replication reported in the new research.

“We asked UVM’s supercomputer to figure out how to match the shape of the original parents, and after months of chugging, the AI ​​came up with some strange designs, including one that looked like Pac-Man,” says Kriegman. “It’s not intuitive. It looks very simple, but it’s not something a human engineer would come up with. Why a tiny mouth? Why not five? We sent the results to Doug, and he built these Pac-Man-shaped parent Xenobots. Then those parents built kids, who built grandchildren, who built great-grandchildren, who built great-great-grandchildren. ”In other words, the right design made the number of generations much longer.

Kinematic replication is well known at the molecular level – but it has never been observed before at the whole cell or organism level.

“We discovered that there is this previously unknown space within organisms or living systems, and it is a huge space,” says Bongard. “Then how can we explore this space? We found xenobots that are leaving. We found Xenobots swimming. And now, in this study, we’ve found Xenobots that kinematically replicate.

Or, as the scientists in the Proceedings of the National Academy of Science Study: “Life has surprising behaviors just below the surface, waiting to be discovered.”

React to risks

Some people may find this exciting. Others may react with concern or even horror at the idea of ​​self-replicating biotechnology. For the team of scientists, the goal is a deeper understanding.

“We’re working to understand this property: replication. The world and technologies are changing rapidly. For society as a whole, it is important that we investigate and understand how this works, ”says Bongard. Entirely housed in a laboratory, easy to extinguish, and vetted by federal, state, and institutional ethics experts, these millimeter-sized living machines “don’t keep me up at night. What is at risk is the next pandemic; the Accelerating ecosystem damage from pollution “. ; increasing threats from climate change, “says Bongard of UVM.” This is an ideal system for studying self-replicating systems. We have the moral imperative to understand the conditions under which we can control, direct, stun, exaggerate it. “

Bongard draws attention to the COVID epidemic and the hunt for a vaccine. “The speed at which we can produce solutions is very important. If we can develop technologies, learn from Xenobots, where we can quickly tell the AI, ‘We need a biological tool that does X and Y and suppresses Z’ – that could be very beneficial. It takes a long time now. ”The team wants to accelerate how quickly people can go from identifying a problem to developing solutions -“ like using living machines to remove microplastics from waterways or to build new drugs, ”says Bongard.

“We have to create technological solutions that grow at the same pace as the challenges we face,” says Bongard.

And the team sees great promise in research for advances in regenerative medicine. “If we knew how to tell collections of cells to do what we wanted them to do, it would ultimately be regenerative medicine – the solution to traumatic injuries, birth defects, cancer and aging,” says Levin. “All of these various problems are here because we don’t know how to predict and control which groups of cells will be formed. Xenobots are a new platform to teach us.”

Video of the world’s first self-replicating living robot: https://www.youtube.com/watch?v=aBYtBXaxsOw

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