You may or may not have heard of xenobots, a kind of Frankenfrog creation that involves researchers turning frog embryo cells into tiny bio-machines that can move around, push or carry objects, and work together. These ephemeral beings were first made by a team of scientists from Tufts University and the University of Vermont in 2020. 

The goal behind building these “bots” was to understand how cells communicate with one another. Here’s a breakdown of the hard facts behind how xenobots actually work, and what they are currently used for. 

What are xenobots?

A “living robot” can sound like a scary sci-fi term, but they are not anything like the sentient androids you may have seen on screen.

“At the most basic level, this is a platform or way to build with cells and tissues, the way we can build robots out of mechanical components,” says Douglas Blackiston, a senior scientist at Tufts University. “You can almost think of it as Legos, where you can combine different Legos together, and with the same set of blocks you can make a bunch of different things.” 

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Xenobots are tiny. Here they are against a dollar bill for size. Douglas Blackiston and Sam Kriegman

But why would someone want to build robots out of living components instead of traditional materials, like metal and plastic? One advantage is that having a bio-robot of sorts means that it is biodegradable. In environmental applications, that means if the robot breaks, it won’t contaminate the environment with garbage like metal, batteries, or plastic. Researchers can also program xenobots to fall apart naturally at the end of their lives. 

How do you make a xenobot?

The building blocks for xenobots come from the eggs laid by the female African clawed frog, which goes by the scientific name Xenopus laevis

Just like with a traditional robot, they need other essential components: a power source, a motor or actuator for movement, and sensors. But with xenobots, all of these components are biological.

A xenobot’s energy comes from the yolk that’s a part of all amphibian eggs, which can power these machines for about two weeks with no added food. To get them to move, scientists can add biological “motors” like muscle or cardiac tissue. They can arrange the motors in different configurations to get the xenobots to move in certain directions or with a certain speed.  

“We use cardiac tissue because cardiac cells pulse at a regular rate, and that gives you sort of an inchworm type of movement if you build with it,” says Blackiston. “The other types of movement we get are from cilia. These are small hair-like structures that beat on the outside of different types of tissues. And this is a type of movement that dominates the microscopic world. If you take some pond water and look, most of what you see will move around with cilia.” 

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Swimming xenobots with cilia covering their surface. Douglas Blackiston and Sam Kriegman

Scientists can also add components like optogenetic muscle tissues or chemical receptors to allow these biobots to respond to light or other stimuli in their environment. Depending on how the xenobots are programmed, they can autonomously navigate through their surroundings or researchers can add stimulus to “drive” them around. 

“There’s also a number of photosynthetic algae that have light sensors that directly hook onto the motors, and that allows them to swim towards sunlight,” says Blackiston. “There’s been a lot of work on the genetic level to modify these to respond to different types of chemicals or different types of light sources and then to tie them to specific motors.”

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Even in their primitive form, xenobots can still convey some type of memory, or relay information back to the researchers about where they went and what they did. “You can pretty easily hook activation of these different sensors into fluorescent molecules that either turn on or change color when they’re activated,” Blackiston explains. For example, when the bots swim through a blue light, they might change color from green to red permanently. As they move through mazes with blue lights in certain parts of it, they will glow different colors depending on the choices they’ve made in the maze. The researcher can walk away while the maze-solving is in progress, and still be in the know about how the xenobot navigated through it.  

They can also, for example, release a compound that changes the color of the water if they sense something.  

These sensors make the xenobot easy to manage. In theory, scientists can make a system in which the xenobots are drawn to a certain wavelength of light. They could then shine this at an area in the water to collect all of the bots. And the ones that slip through can still harmlessly break down at the end of their life. 

A xenobot simulator

Blackiston, along with collaborators at Northwestern and University of Vermont, are using an AI simulator they built to design different types of xenobots. “It looks sort of like Minecraft, and you can simulate cells in a physics environment and they will behave like cells in the real world,” he says. “The red ones are muscle cells, blue ones are skin cells, and green ones are other cells. You can give the computer a goal, like: ‘use 5,000 cells and build me a xenobot that will walk in a straight line or pick something up,’ and it will try hundreds of millions of combinations on a supercomputer and return to you blueprints that it thinks will be extremely performant.”

Most of the xenobots he’s created have come from blueprints that have been produced by this AI. He says this speeds up a process that would have taken him thousands of years otherwise. And it’s fairly accurate as well, although there is a bit of back and forth between playing with the simulator and modeling the real-world biology. 

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Xenobots of different shapes crafted using computer-simulated blueprints. Douglas Blackiston and Sam Kriegman

The xenobots that Blackiston and his colleagues use are not genetically modified. “When we see the xenobots doing kinematic self-replication and making copies of themselves, we didn’t program that in. We didn’t have to design a circuit that tells the cells how to do kinematic self replication,” says Michael Levin, a professor of biology at Tufts. “We triggered something where they learned to do this, and we’re taking advantage of the native problem-solving capacity of cells by giving it the right stimuli.” 

What can xenobots help us do?

Xenobots are not just a blob of cells congealing together—they work like an ecosystem and can be used as tools to explore new spaces, in some cases literally, like searching for cadmium contamination in water. 

“We’re jamming together cells in configurations that aren’t natural. Sometimes it works, sometimes the cells don’t cooperate,” says Blackiston. “We’ve learned about a lot of interesting disease models.”

For example, with one model of xenobot, they’ve been able to examine how cilia in lung cells may work to push particles out of the airway or spread mucus correctly, and see that if the cilia don’t work as intended, defects can arise in the system.

The deeper application is using these biobots to understand collective intelligence, says Levin. That could be a groundbreaking discovery for the space of regenerative medicine. 

“For example, cells are not hardwired to do these specific things. They can adapt to changes and form different configurations,” he adds. “Once we figure out how cells decide together what structures they’re going to form, we can take advantages of those computations and build new organs, regenerate after injury, reprogram tumors—all of that comes from using these biobots as a way to understand how collective decision-making works.”