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Xenobots: Living Robots that Make Science Fiction a Reality

Designed using stem cells, these living machines open the door for exciting advances in regenerative medicine and other fields

by
Ajay P. Manuel

Ajay P. Manuel, PhD, is a scientific coordinator/writer for Lab Manager. Born in Madurai, India, Ajay completed his secondary education at Cairo American College in Egypt and Khartoum American...

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Imagine being able to clump together a bunch of cells and programming them to do as per your wishes. This may sound similar to a robot, but when we think of robots, we imagine metal-clad machines equipped with electronic circuits—not living cells. 

The process of building robots connects various fields including electronics, materials science, and engineering. But instead of building these synthetic servants out of inorganic materials, what happens if we build them using nature’s powerhouses—cells? This is exactly what a group of scientists from Tufts University and the University of Vermont accomplished in 2020, calling their creation “xenobots”. 

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What are xenobots?

Measuring less than a millimeter across, xenobots are living, self-powered robot-like beings built out of the stem cells of an African-clawed frog species called Xenopus laevis. “Xeno” is derived from that term, and “bot” refers to robot. 

Classical robots are not a great choice for work in organic environments such as the ocean or the inside of a human body. The synthetic materials in these robots pose a contamination risk, pushing scientists to develop alternatives that can capitalize on the full potential of nanobot technology without endangering the environment they occupy. 

Composed of genetically unmodified cells but designed by artificial intelligence (AI), xenobots are not normal by any means. The resulting microorganism is something between a living being and a robot, bringing together AI and biology in a unique platform for bio-robotics or adaptive engineering. Made of entirely organic material, xenobots can carry out a range of tasks beyond the reach of fully artificial organisms while minimizing environmental impact. 

How are xenobots made?

Research on xenobots originally began in 2017 with an effort to bring together computer scientists and developmental biologists to create adaptive AI systems that draw inspiration from nature’s biological systems. Much of this initial work was accomplished by the team of Josh Bongard, PhD, and Sam Kriegman, PhD, (who was at that time Bongard’s doctoral student) at the University of Vermont, using simulated models on a computer. Akin to playing with LEGO, Bongard and Kriegman designed virtual, soft robots that could be modified and deformed for various functionalities. These candidate designs were possible with the help of an AI program armed with an evolutionary algorithm allowing it to produce various cell configurations over the span of a few hours or days—a process that would have otherwise taken a human thousands of years. The host supercomputer then helped detect optimal designs that could move and perform functions.

Recognizing the similarities between these models and those that could be built using frog cells, fellow researcher Douglas Blackiston, PhD, at Tufts University, suggested a collaboration. Collecting stem cells (cells from which all other cells with specific functions are generated) from the embryo of Xenopus laevis, researchers differentiated them into skin cells and heart cells. The former was utilized to make the xenobot’s structure, and the latter’s relaxation and contraction abilities provided locomotion. Arranging the cardiac tissues in different configurations enables the xenobots to move in various directions or at specific speeds. Capitalizing on the inherent characteristic of cells being naturally sticky and using microsurgery tools such as forceps and electrodes, thousands of skin and heart cells were joined together, bringing to reality the virtual designs produced by the simulators. The result was xenobots, microorganisms capable of clumping together and moving in linear and circular directions. 

Surprisingly, the xenobots began to create piles, clumping the dye together like microscopic bulldozers.

Self-replication—“Life finds a way”

The first generation of xenobots was made in 2020. These were relatively simplistic, cardiac-driven, and moved in a single direction along the bottom of a petri dish. A switch to cilia, hair-like structures on the outside of cells, helped produce faster movement. Newer generations of xenobots could quickly swim about on the surface of the petri dish, as opposed to the slow crawl of their predecessors. To test their interactions with other materials, researchers placed dye particles on the bottom of the petri dish. Surprisingly, the xenobots began to create piles, clumping the dye together like microscopic bulldozers. 

Replacing the dye with stem cells, the same materials the xenobots were made of, researchers observed that the xenobots, with the right design, exhibited a spontaneous ability to replicate and reproduce. This was accomplished using a xenobot design reminiscent of the well-known video game character Pac-Man. The xenobotic Pac-Man would chomp around and collect the surrounding stem cells, clumping them together into piles that could form subsequent generations of progeny. These embryonic stem cells, containing the genome of the Xenopus laevis frog, would naturally develop into the tadpole’s skin and would help in redistributing mucus and protecting pathogens. However, when freed from this natural order of things, the cells used their collective intelligence and their inherent plasticity to do something completely different. 

It is important to note that, unlike other living systems, xenobots require additional building materials to enable their self-replicative behavior. So, if you are worried about self-replicating robots, rest assured as the parent xenobots can only produce progeny when they are provided access to additional free-floating cells. Otherwise, they cannot replicate at all and they gradually die in a matter of days. While the origin of the self-replicative behavior of xenobots remains unclear and is entirely alien to how natural frog cells work, researchers believe they can get the answers by continuing to explore their inherent problem-solving capacities as cells, given the right stimuli and design. 

The original xenobots were initially able to survive for seven to 10 days, but advancements and progressive research accomplished with the help of AI simulators geared toward non-intuitive xenobot designs have bestowed them the capability to heal themselves and extend their lifetime. Over many generations, xenobots can now evolve in shape, adapt different material properties, and conform to diverse control systems. The procedure of making xenobots is an active demonstration of the potential of combining biological engineering with AI, to go through billions of years of virtual evolution, and produce microorganisms of specific designs and functionalities. 

Redefining the future

The fundamental idea behind xenobots is using living cells to perform specific functions across numerous tasks with very high efficiency. Using xenobots, researchers gain a deeper understanding of the collective intelligence of cells and how it could be exploited toward specific objectives in various applications. 

This would particularly benefit the research space of regenerative medicine. Thanks to their short (and regulated) lifespan and non-toxicity, xenobots could serve as innovative vehicles for internal surgery and intelligent drug delivery. This sets the precedent for scenarios where a patient’s cells can be used to create xenobots to locate, remove, and control locations of disease events in the patient’s body while also delivering targeted immunotherapy on affected cells. The tiny nature of the xenobot alongside its naturally limited lifespan offers a safer alternative to invasive therapies in areas of the human body that may be difficult to access using traditional means while eliminating chances of patient rejection and additional complications. 

Beyond their applicability in regenerative medicine, researchers claim that xenobots can also contribute heavily toward environmental remediation. They could play the role of sentinel bots that clean out toxic materials and waste products, such as microplastics, as well as identify molecules and substances of interest in environments physically inaccessible to classical robots.

Over many generations, xenobots can now evolve in shape, adapt different material properties, and conform to diverse control systems.

By continuously augmenting the cognitive capabilities of xenobots, we gain deeper insights into the rules behind cellular assembly and how we can make a collection of cells navigate focused tasks in various application spaces. Nonetheless, beyond the amazing potential of xenobots, there are major ethical considerations to contend with surrounding their creation and use. 

Beyond mother nature

Combining AI and genetic engineering has provided researchers the creative opportunity to explore a morpho-space far more diverse than what has been witnessed naturally on our planet over several billion years of evolution. A key part of this research concerns the use of AI to help in explaining the biology of living materials. Xenobots are a direct consequence of this, and their very existence has blurred rigorous distinctions between living and synthetic organisms. 

Beyond semantics, there are several ethical issues surrounding the use of these living robots including the possibility of malfunction or development of new programming, manipulation, and misuse of the technology for nefarious purposes, the creation of organisms from human stem cells harvested from human embryos, and the incorporation of cognitive abilities leading to sentient microorganisms, etc. 

Xenobots demonstrate great potential for a variety of crucial applications surrounding medicine, environmental remediation, and many more. As living machines that fight various issues, xenobots are an invaluable tool that could be used to solve critical issues that ail our planet. Nevertheless, as researchers continue to explore advances in regenerative medicine, synthetic biology, and robotics, there remains an equal, if not greater, need to establish rules and safeguards to guide the development of this exciting frontier technology.