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Xenobots: The Self-Replicating Living Robots

These living robots are redefining what it means to be a robot, trading in shiny metals and hardware for carefully configured frog cells.

xenobots populating under a microscope view
Living robots might sound like an oxymoron, but they’re here, and they’re challenging everything we know about biotechnology. Known as xenobots, these computer-generated, hand-sewn clumps of cells are made out of biocompatible materials. They also exhibit autonomous behaviors, such as self-repair and self-replication. In short, they’re alive, biodegradable, fully programmable synthetic lifeforms that are a first of their kind.

XENOBOTS DEFINITION
Xenobots are computer-generated, programmable lifeforms made out of stem cells harvested from the African frog, Xenopus laevis.

An overview of IoT, architecture, functionalities, enabling technologies, and applications.

If you think about it, most “smart” technologies are built from “dumb” parts. Things like smartphones, Internet of Everything devices and robots are made out of steel, concrete, chemicals or plastics, then wired to a computer and fitted with sensors. But with xenobots, scientists are trying to flip that script, introducing organic robots that function as living systems themselves.

What Are Xenobots?

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Xenobots are programmable organisms designed by computers and assembled from living stem cells. They’re an entirely new life form developed by researchers at the University of Vermont, Tufts University and the Wyss Institute in order to learn more about how cells communicate — and eventually control it.

These brainless blobs are less than a millimeter wide and take on a C-shape with a yellow tint, reminiscent of 1980s arcade star Pac-Man.

They’re made up of stem cells scraped from the embryos of an African clawed frog, formally known as Xenopus laevis, from which its name is derived. Researchers harvested skin cells to craft the architecture of a xenobot, and heart cells for their ability to contract and relax, acting as a sort of engine to propel the organic robot for functional mobility.

To determine how exactly these passive and active cells should be configured, researchers
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tested billions of shapes in simulation — from triangles and squares, to pyramids and starfish — on a supercomputer using an artificial intelligence program with an evolutionary algorithm. The team then used the top designs to microsurgically assemble the novel living robots.

Team Builds the First Living Robots content piece image
“What we’re very much interested in is this question of how cells work together to make specific functional structures,” Michael Levin, a biophysicist on the project, told Wired.Under a microscope, researchers studied the xenobots as they scooted around in a liquid solution.

image of the organism's group behavior

They spin in place, shoot across the petri dish in lines or circular motions. Using their “mouths,” they can carry and transport objects. They can also collectively work together to herd loose cells into heaps, move toward a target and, if cut, can self repair. 

Given the exhibited behavior, scientists from the study see xenobots as a bio-friendly answer to cleaning microplastics and toxic contamination from waterways or the next big thing in regenerative medicine.

How Do Xenobots Reproduce?

Scientists Build First Living Robots That Can Self-Replicate

In addition to performing simple tasks, xenobots can self-replicate. Following up the original study, published in 2020, the same team of researchers unveiled in a follow up report that the living robots would team up to spontaneously gather hundreds of loose, single cells dropped into the petri dish — initially supplied as feedstock — to assemble “baby” xenobots.

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“You can think about this like using the different cells [as] building blocks like you would build with LEGO or with Minecraft,” Douglas Blackiston, a co-author of the study and senior scientist at Tufts University, told NPR.

Xenobot Swarm Activity
Swimming around on hairlike cilia, parent xenobots propel themselves around hundreds of individual stem cells into a pile using a corralling motion. Over the course of about five days, the hoard of cells are compressed and constructed into offspring, then released from the parent’s wedge-shaped “mouths.”
Biobots and Xenobots (A) Four layers of body architecture for engineered artificial ray as an example of a biobot. (B and C) (B) Concept of operation and (C) phototactic control via optical stimulation that triggers muscle activation and produces undulatory locomotion and swimming. Asymmetric stimulation controls the direction (taken with permission from Park et al., 2016). (D) Ectodermal and muscle cells from Xenopus embryos are extracted, allowed to re-associate, and then micro-sculpted to remove some cells. (E-H) (E) The remaining cells self-organize a large-scale pattern (with muscle inside, shown by red fluorescent protein signal) to enable forward locomotion of the Xenobot using the available features of the structure. The sculpting is done in accordance with a simulated Xenobot evolved in a virtual computer environment (F), and many different shapes with diverse emergent movement profiles are possible (G). The movement of these synthetic organisms alters their environment by moving materials (H and I) in ways exactly as predicted by the computational model of the swarm behavior.
This next generation will metamorphose into a fully operational xenobot that can then go on to create new copies, and so on.

Three roundish objects made up of many colors, with short hair-like projections in yellow. Tiny biological multicellular bots called Anthrobots move around and help heal “wounds” created in cultured neurons
“This self-replication process is reliant on the organisms’ movement, contrasting with other animals and plants, whichgrow and shed to create new beings,” Jonathan Brennan-Badal, who, while not part of the study, builds robots for biologists as CEO at Opentrons, told Built In.

“Interestingly, this capability occurs autonomously — so it doesn’t necessitate specific evolution or an
Spontaneous kinematic self-replication. (A) Stem cells are removed from early-stage frog blastula, dissociated, and placed in a saline solution, where they cohere into spheres containing ∼3,000 cells. The spheres develop cilia on their outer surfaces after 3 d. When the resulting mature swarm is placed amid ∼60,000 dissociated stem cells in a 60-mm-diameter circular dish (B), their collective motion pushes some cells together into piles (C and D), which, if sufficiently large (at least 50 cells), develop into ciliated offspring (E) themselves capable of swimming, and, if provided additional dissociated stem cells (F), build additional offspring. In short, progenitors (p) build offspring (o), which then become progenitors. This process can be disrupted by withholding additional dissociated cells. Under these, the currently best known environmental conditions, the system naturally self-replicates for a maximum of two rounds before halting. The probability of halting (α) or replicating( 1 À α) depends on a temperature range suitable for frog embryos, the concentration of dissociated cells, the number and stochastic behavior of the mature organisms, the viscosity of the solution, the geometry of the dish's surface, and the possibility of contamination. (Scale bars, 500 μm.)

introduction through genetic manipulation.”
Researchers note that this type of reproduction — coined as kinematic self-replication — has never been observed before. In fact, since this method has only been witnessed on a molecular level exclusive of multicellular organisms, it wasn’t even thought possible.

Uses Cases for Xenobots

Aside from potentially cracking the morphogenetic code, which would offer a window into the way cells
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interpret information and organize to make up an organism, xenobots may serve as promising solutions to relevant global issues in their practical application.

Clean-Up Efforts

Inspired by the xenobots’ collective corralling capabilities, researchers concluded that the organic robots could eventually be programmed to target microplastics and assist in the clean up of the 50 to 75 trillion pieces of plastics polluting the ocean.  This same technology can be adapted to identify and eliminate radioactive elements in the environment, such as nuclear waste, or employ xenobots to monitor and maintain ecosystems. Most importantly, xenobots can “adapt to organic environments without causing any contamination,” Brennan-Badal noted.

Drug Delivery, Diagnostics and Internal Surgery

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As indicated in the study, xenobots are nontoxic and have a self-limiting lifespan of about one week.  These features, along with their potential to carry payloads, make for intelligent drug delivery vehicles that can internally travel to a specific part of the body, like treating tumors directly on site.
Furthermore, xenobots could be programmed to locate and digest toxins within the body, remove plaque from artery walls and detect deformities caused by disease, such as cancer cells.

Regenerative Medicine

Built in a petri dish, xenobots can be configured in any form desired and programmed for specific purposes — essentially providing anatomy on demand — with self-replicating and self-healing properties. In the context of regenerative medicine tomorrow, this could mean using a patient’s own cells to repair failing organs or even building transplant organs from scratch.

Risks of Xenobots 

Xenobots can have various positive applications, though the creation of these organisms could also pose risks in a few different ways. 

Environmental and Ecological Effects 

Xenobots are set to be used to clean pollution in oceans and aquatic environments, but doing so could inadvertently disrupt natural ecosystems and other habitating organisms. This may occur if they are consumed by other species in the ecosystems or cause damage to species that they aren’t previously acclimated to. With their ability to self-replicate, xenobots also have the possibility of becoming an invasive species to an ecosystem if they are unregulated and reproduce at a rapid pace. 

Manipulation and Malicious Use

Since xenobots are programmable organisms, this means they could be instructed to perform tasks for harmful purposes. Xenobots may be created to maliciously target bodily functions or deliver harmful substances inside humans, animals or plant life, making them a possible tool in crime or warfare.

Ethical Concerns

Though they are developed with no brain, xenobots are produced from living cells and exhibit autonomous behaviors. These qualities raise questions of what ethical boundaries and rights exist when working with these organisms, as they are developed with the sole purpose of performing labor under human instruction. Xenobots may also be developed in the future to include nervous systems and sensory capabilities, making the ethicality of use even more difficult to grapple with.

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