Last year, a team of biologists and computer scientists from Tufts University and the University of Vermont (UVM) created tiny self-healing biological machines from frog cells called “Xenobots”. These cells can move around, push a payload, and even exhibit collective behaviour in the presence of a swarm of other Xenobots.
Introducing Xenobots 2.0.
The same team has now created life forms that self-assemble a body from single cells, do not require muscle cells to move, and even demonstrate the capability of recordable memory. The new generation Xenobots also move faster, navigate different environments, and have longer lifespans than the first edition, and they still have the ability to work together in groups and heal themselves if damaged.
Compared to Xenobots 1.0, in which the millimetre-sized automatons were constructed in a “top-down” approach by manual placement of tissue and surgical shaping of frog skin and cardiac cells to produce motion, the next version of Xenobots takes a “bottom-up” approach. The biologists at Tufts took stem cells from embryos of the African frog Xenopus laevis (hence the name “Xenobots”) and allowed them to self-assemble and grow into spheroids, where some of the cells after a few days differentiated to produce cilia – tiny hair-like projections that move back and forth or rotate in a specific way. Instead of using manually sculpted cardiac cells whose natural rhythmic contractions allowed the original Xenobots to scuttle around, cilia give the new spheroidal bots “legs” to move them rapidly across a surface. In a frog, or human for that matter, cilia would normally be found on mucous surfaces, like in the lungs, to help push out pathogens and other foreign material. On the Xenobots, they are repurposed to provide rapid locomotion.
“We are witnessing the remarkable plasticity of cellular collectives, which build a rudimentary new ‘body’ that is quite distinct from their default – in this case, a frog – despite having a completely normal genome,” says Michael Levin, professor of biology and director of the Allen Discovery Center at Tufts University, and corresponding author of the study. “In a frog embryo, cells cooperate to create a tadpole. Here, removed from that context, we see that cells can re-purpose their genetically encoded hardware, like cilia, for new functions such as locomotion. It is amazing that cells can spontaneously take on new roles and create new body plans and behaviours without long periods of evolutionary selection for those features.”
“In a way, the Xenobots are constructed much like a traditional robot. Only we use cells and tissues rather than artificial components to build the shape and create predictable behaviour,” says senior scientist Doug Blackiston, who co-first authored the study with research technician Emma Lederer. “On the biology end, this approach is helping us understand how cells communicate as they interact with one another during development, and how we might better control those interactions.”
While the Tufts scientists created the physical organisms, scientists at UVM were busy running computer simulations that modelled different shapes of the Xenobots to see if they might exhibit different behaviours, both individually and in groups. Using the Deep Green supercomputer cluster at UVM’s Vermont Advanced Computing Core, the team, led by computer scientists and robotics experts Josh Bongard and under hundreds of thousands of random environmental conditions using an evolutionary algorithm. These simulations were used to identify Xenobots most able to work together in swarms to gather large piles of debris in a field of particles
“We know the task, but it’s not at all obvious — for people — what a successful design should look like,” says Bongard. “That’s where the supercomputer comes in and searches over the space of all possible Xenobot swarms to find the swarm that does the job best. We want Xenobots to do useful work. Right now we’re giving them simple tasks, but ultimately we’re aiming for a new kind of living tool that could, for example, clean up microplastics in the ocean or contaminants in soil.”
It turns out, the new Xenobots are much faster and better at tasks such as garbage collection than last year’s model, working together in a swarm to sweep through a petri dish and gather larger piles of iron oxide particles. They can also cover large flat surfaces, or travel through narrow capillaries.
These studies also suggest that the in silico simulations could in the future optimize additional features of biological bots for more complex behaviours. One important feature added in the Xenobot upgrade is the ability to record information.
Now with memory
A central feature of robotics is the ability to record memory and use that information to modify the robot’s actions and behaviour. With that in mind, the Tufts scientists engineered the Xenobots with a read/write capability to record one bit of information, using a fluorescent reporter protein called EosFP, which normally glows green. However, when exposed to light at 390nm wavelength, the protein emits red light instead.
The cells of the frog embryos were injected with messenger RNA coding for the EosFP protein before stem cells were excised to create the Xenobots. The mature Xenobots now have a built-in fluorescent switch that can record exposure to blue light around 390nm.
The researchers tested the memory function by allowing 10 Xenobots to swim around a surface on which one spot is illuminated with a beam of 390nm light. After two hours, they found that three bots emitted red light. The rest remained their original green, effectively recording the “travel experience” of the bots.
This proof of principle of molecular memory could be extended in the future to detect and record light and the presence of radioactive contamination, chemical pollutants, drugs, or a disease condition. Further engineering of the memory function could enable the recording of multiple stimuli (more bits of information) or allow the bots to release compounds or change behaviour upon the sensation of stimuli.
“When we bring in more capabilities to the bots, we can use the computer simulations to design them with more complex behaviours and the ability to carry out more elaborate tasks,” says Bongard. “We could potentially design them not only to report conditions in their environment but also to modify and repair conditions in their environment.”
Xenobot, heal thyself
“The biological materials we are using have many features we would like to someday implement in the bots – cells can act as sensors, motors for movement, communication and computation networks, and recording devices to store information,” says Levin. “One thing the Xenobots and future versions of biological bots can do that their metal and plastic counterparts have difficulty doing is constructing their own body plan as the cells grow and mature, and then repairing and restoring themselves if they become damaged. Healing is a natural feature of living organisms, and it is preserved in Xenobot biology.”
The new Xenobots were remarkably adept at healing and would close the majority of a severe full-length laceration half their thickness within 5 minutes of the injury. All injured bots were able to ultimately heal the wound, restore their shape and continue their work as before.
Another advantage of a biological robot, Levin says, is metabolism. Unlike metal and plastic robots, the cells in a biological robot can absorb and break down chemicals and work like tiny factories synthesizing and excreting chemicals and proteins. The whole field of synthetic biology – which has largely focused on reprogramming single-celled organisms to produce useful molecules – can now be exploited in these multicellular creatures
Like the original Xenobots, the upgraded bots can survive up to ten days on their embryonic energy stores and run their tasks without additional energy sources, but they can also carry on at full speed for many months if kept in a “soup” of nutrients.
What the scientists are really after
In his TED Talk, professor Levin describes the remarkable potential for tiny biological robots to carry out useful tasks in the environment or potentially in therapeutic applications, but he also points using the bots can provide a foundation for regenerative medicine.
Xenobots and their successors may also provide insight into how multicellular organisms arose from ancient single-celled organisms, and the origins of information processing, decision making and cognition in biological organisms.
Recognizing the tremendous future for this technology, Tufts University and the University of Vermont have established the Institute for Computer Designed Organisms (ICDO), to be formally launched in the coming months, which will pull together resources from each university and outside sources to create living robots with increasingly sophisticated capabilities.
The goal for the Tufts and UVM researchers is not only to explore the full scope of biological robots they can make; it is also to understand the relationship between the ‘hardware’ of the genome and the ‘software’ of cellular communications that go into creating organized tissues, organs and limbs. Then we can gain greater control of that morphogenesis for regenerative medicine, and the treatment of cancer and diseases of aging.