Discovery & Innovation

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>>> Scientists Create ‘Living Machines’ With Algorithms, Frog Cells

Darpa-funded research is focused on “biobots” with potential environmental and health applications.


Bloomberg

by Matthew Hutson

December 16, 2021


https://www.bloomberg.com/news/articles/2021-12-16/scientists-design-living-machines-from-frog-cells-through-biology-and-robotics?srnd=premium


Michael Levin, a biologist at Tufts University, spends his days doing things such as coaxing flatworms to grow two heads or helping frogs regenerate lost legs. It may not seem like it, he says, but this counts as robotics research. In Levin’s view every organism is a type of machine, and he speaks with the vocabulary of a programmer, describing animals’ genomes as determining their “hardware” and explaining how he modifies living things by rewriting the “software” of their cellular communication and hacking their “bioelectric code.”

Some of Levin’s work involves biobots, small cellular blobs he and his colleagues build in a lab from the skin, muscle, and stem cells of frog embryos. His main collaborator is Josh Bongard, a computer scientist at the University of Vermont whose previous work has included building robots that could relearn to walk after, say, losing part of a leg. Although animals can recover from injury and adapt to new circumstances, robots and artificial intelligence systems still struggle to do so. The scientists are anticipating that combining elements of robotics and biology can change that.

The Defense Advanced Research Projects Agency (Darpa), the Pentagon’s moonshot arm, began funding Levin and Bongard’s work in 2018 as part of its Lifelong Learning Machines program, which seeks to apply biological mechanisms to novel computing systems. Levin uses a simulated version of natural selection to design his biobots—he calls them xenobots, for Xenopus laevis, the species of African clawed frog they’re built from—to crawl, navigate, remember, and carry cargo. Eventually biobots might be built to detect and digest pollution in waterways or clean plaque from people’s arteries. (The Pentagon’s involvement might appear to hint at more aggressive applications, but Darpa doesn’t always fund projects with specific military applications in mind.)

The development of Levin and Bongard’s biobots began when Sam Kriegman, one of Bongard’s doctoral students, made a computer simulation of evolution for robots. It first generated simulated bots resembling cubes with eight units on each side, where each unit was either one of two types of blocks or an empty space, sort of like a simplified Rubik’s Cube with holes in it. One type of block sat passively, while the other type twitched. The simulation then kept those that moved in certain ways that aligned with its objectives. It mutated and duplicated the keepers, trying different configurations over many generations until it ended up with flexing cube creatures that could crawl.

At this point in the process, the creatures exist only as software. In the next step, Douglas Blackiston, a scientist in Levin’s lab, builds physical versions of the computer-simulated cubes out of frog cells. For the passive blocks, he uses stem cells destined to become skin; the twitching ones are made out of stem cells destined to become heart muscles.

The work takes precision. Blackiston builds the biobots using a set of hand-sharpened forceps and a cauterizing filament almost too fine to see. The simulation can spit out millions of designs a day, but it takes him hours to craft only one. Once they’re deployed in a petri dish, the bots do what they evolved on the computer to do: crawl, push around pieces of detritus, carry payloads, or collaborate to sweep particles into piles. Last year the team published the results of the experiments in the prestigious journal the Proceedings of the National Academy of Sciences (PNAS), writing that the cubebots, which they referred to as “living machines,” have the potential to deliver drugs inside the human body or help with environmental remediation.

The researchers followed up with a different approach in the journal Science Robotics. They formed stem cells from frog embryos into simple spheres, each a half-millimeter in diameter. The spheres quickly self-organized—no manual molding required—into skin-covered balls coated with cilia, hairlike structures that functioned like little swimming paddles.

The biobots had no neurons but could swim through tight spaces and turn corners. They could also be engineered to have memory: When injected with messenger RNA for a light-sensitive glowing protein, they glowed green until they swam over a light of a certain wavelength, after which they glowed red, indicating the experience had changed their behavior.

The job of the bots was to work collectively to sweep debris into piles. They didn’t actively collaborate through direct communication. But coordination emerged nonetheless.

The xenobots survived 10 days without feeding and three months in a nutrient-filled solution. And even when the scientists created deep lacerations, the bots repaired themselves within 15 minutes, a feat that helps in turbulent environments and also demonstrated the prowess of cells.

The results of the lab work, Levin says, are shocking even if they illustrate what he suspected all along was possible. “My jaw’s on the floor every couple of weeks,” he says.

In their latest work, published in December in the PNAS, the scientists used digital evolution to design biobots that can self-replicate. The critters, some shaped like half-doughnuts, gather and compress stray frog cells into copies of themselves. “No known organism replicates in this manner,” Bongard says. Future versions might also do other work, such as building chip circuitry, while amassing an army of workers. The dystopian implications of self-replicating robot creatures have been explored repeatedly in science fiction, but Levin notes that runaway replication is extremely unlikely because they require a source of loose cells and a specialized kind of saltwater to reproduce.

From here the biobots team plans to automate the fabrication process, giving Blackiston a break from his forceps. They also want to refine the evolutionary algorithm and work with different types of cells or cells from different species. They’d like to control the shapes that biobots grow into by hacking their bioelectricity and to alter their genomes to code for new sensors, circuitry, and moving parts.

Any biobots serving a medical purpose would have to be made from human cells, a jump with the potential to cause more controversy than fiddling with frog cells. The process also raises other ethical questions, such as whether biobots could have unforeseen environmental consequences. But failing to pursue a line of work that could reduce human suffering, Levin says, also raises moral issues.

Biobots could be ready for environmental purposes in as few as five years, but approval for medicine will likely take a decade or more. “There’s a long way to go in this field,” says Kevin Parker, a bioengineer at Harvard who builds organic-artificial “biohybrid” robots, such as a silicone stingray powered by rat heart muscle. “But it’s fun, it’s exciting, and it’s kind of whimsical at this point.”

Biobots don’t even need to leave the lab to make life better, says Parker, who describes them as a tool for answering basic questions about science. For Levin, the living machines pose an opportunity to untangle the mystery of how cells collectively decide to work together to do things like build an arm, while also providing insight into how collective intelligence operates in areas such as swarm robotics, the internet of things, and economies. Learning to predict and control the goals of such systems, he continues, is a matter of existential importance. “And these bots are giving us a uniquely powerful new sandbox in which to play.”

BOTTOM LINE - Darpa has been funding research showing how clumps of cells can be designed to do specific tasks, a potentially useful innovation that explores how life and robotics intersect.

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