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A hundred years ago, it was easy to tell when something was a machine. The machines were “hard and clumsy, metallic and quite heavy,” as developmental biologist Michael Levin puts it. Reverse.
But lately it has become clear to Levin and his collaborator Joshua Bongard, professor of computer science at the University of Vermont, that our definitions of “machine” and “living organism” are about to get very, very fuzzy.
In January 2020, the first two made headlines after announcing that their team had succeeded in creating “completely biological machines”. Now Levin and Bongard have taken their biological machines, or “Xenobots,” to the next level – using frog cells to create life forms capable of movement, memory, and manipulation of the world around them.
These incredible results were published on Wednesday in the journal Scientific robotics.
The background – Biological Machines 2020 were designed in computer simulations, then built in Petri dishes using micro-scalpels and living biological tissue – skin and muscle cells harvested from African clawed frog embryos, Xenopus laevis. In other words, they are designed like one would design a robot, but the raw materials are 100% living cells.
Levin and Bongard landed on a design reminiscent of the dog turned beanbag The beauty and the Beast which, when sculpted, would actually contract its muscle cells and cross the plate. They named their living creations Xenobots (pronounced zenno-bot), after the frog that gave birth to its cells.
“Already in this first article, we were showing creatures whose evolutionary history took place in a computer,” says Levin, a professor at Tufts University.
“They had an evolutionary history, it just wasn’t on Earth. It is in this completely virtual world that Josh Bongard coded.
A few weeks ago, Bongard published his new theory on whether to still use the metaphor that living things are like machines (spoiler: it isn’t). In the team’s latest bot advance, no sculpting is needed. The new Xenobots are not bean bags, they are spheres. And they don’t have muscle cells, they’re all skin. But they still move very well.
What’s up – The skin of a Xenopus the frog is covered with cilia, tiny hair-like structures, which redistribute the mucus on their skin. It is an adaptation to ward off bacteria and fungi. When you put embryonic skin cells together, they clump together into small spheres with the eyelashes on the outside.
The team found that the eyelashes on this new Xenobot “work together so that things can move forward,” Levin says. “They start to row and the thing moves.”
The researchers also tested to see if they could configure the Xenobots with some rudimentary form of memory. They injected them with RNA that encodes a protein that changes color when exposed to a certain color of light. It worked: the robots were making the proteins, and it was clear which robots had “seen” the light when they returned a different color.
“It’s proof of principle that we can modify cells to add other things to them that give them new functionality,” says Levin. “Nowadays, synthetic biology is just ‘cell soups’, they are all cells in culture. Now they can be embodied – we have a body that you can put all of these types of circuits in.
The team were also interested in how the Xenobots would act as a group. Bongard ran more computer simulations to try and predict what would happen when you let robots enter an arena with a bunch of particles. How would the movement of robots redistribute the particles? Can you get them to make piles of them?
It was an iterative process, measuring the properties of the Xenobots, putting the data into the computer simulation to make predictions, then testing those predictions on the bots and measuring again. “It goes from simulation, to experimentation, to simulation, to experience and hopefully every time we’re a little smarter after every round,” Levin says.
Why this is important – In practice, Xenobots could have applications such as swimming in the bloodstream and unclogging the arteries. But Levin is more excited about the big picture.
“Most of the problems of modern medicine go away… if we understood how to make cells build what we want them to build.
As Xenobots grow during their short 10-day lifespan, they elongate and become transparent.
“They almost look like ghosts,” says Levin. “And that’s nothing you would have predicted, they don’t look like frog embryos, they don’t look like tadpoles.” They have their own new sequence of development. “
It’s a whole new type of model organism, says Levin, that will help us understand how cells build structures and how we can ‘motivate’ them to do different things besides their genetic defect – no genetic engineering is available. ‘is required.
“Most of the problems in modern medicine would go away… if we understood how to get cells to build whatever we want them to build,” he says.
When asked if it was just an accident that this configuration of hair cells could move, Levin pushed the question back. He says a lot of people don’t take evolution seriously enough.
“Our own complex cognitive properties evolved from smaller, simpler versions of these exact same properties in others. [earlier] organizations, ”he says.
“[Are the Xenobots] to use physics to reuse their mechanisms in a way that can be explained by chemistry and physics? Of course they are. There is no magic. But it’s the same for us. When we walk, we use electricity from our brain’s power grids to activate our muscles. That doesn’t mean it’s less wonderful.
“People are very binary in things. They say it’s a robot or is it an organism? Yes and yes, ”says Levin. “These binary classifications are just not good anymore.”
And after? – Levin and his team move forward with their experiments, some of which use cells from sources other than frogs. He is motivated by his curiosity about how groups of cells work together to form a kind of collective intelligence – just like our human brains.
“It’s a problem that kept me awake since I was a kid,” he says. “How does the structure of the body relate to the spirit that lives there in one way or another?”
As these living robots become more and more complex, society will have to ask what it means to be cognitive. Levin imagines a future straight out of a sci-fi movie – one that will challenge our view of cognition and what we ethically owe our creations.
“Over the course of your lifetime we are going to be surrounded by an incredible plethora of new agents which are weird hybrids, cyborgs and robots with embedded living tissue and [vice versa] – every combination under the sun is going to run somewhere, ”says Levin.
Abstract: Swarms of robots have, to this day, been constructed from man-made materials. Mobile biological constructs have been created from muscle cells grown on precisely shaped scaffolds. However, harnessing the emerging self-organization and functional plasticity into a self-directed living machine remained a major challenge. We report here a method of generating in vitro biological robots from frogs (Xenopus laevis) cells. These xenobots exhibit coordinated locomotion via cilia present on their surface. These cilia arise through normal tissue structuring and do not require complicated construction methods or genomic editing, making production suitable for high throughput projects. Biological robots are born by cellular self-organization and do not require scaffolding or microprinting; amphibian cells lend themselves very well to surgical, genetic, chemical and optical stimulation during the process of self-assembly. We show that xenobots can navigate watery environments in a variety of ways, heal from damage, and show emerging group behaviors. We built a computational model to predict useful collective behaviors that can be obtained from a swarm of xenobots. Additionally, we provide proof of principle for writable molecular memory using a photoconvertible protein that can record exposure to a specific wavelength of light. Together, these results present a platform that can be used to study many aspects of self-assembly, swarm behavior, and synthetic bioengineering, as well as to provide versatile soft-bodied living machines for research. many practical applications in biomedicine and in the environment.
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