Tag Archives: Sam Kriegman

Moving past xenobots (living robots based on frog stem cells)

Laura Tran’s June 14, 2024 article for The Scientist gives both a brief history of Michael Levin’s and his team’s work on developing living robots using stem cells from an African clawed frog (known as Xenopus laevis) and offers an update on the team’s work into synthetic lifeforms. First, the xenobots, Note 1: This could be difficult for people with issues regarding animal experimentation Note 1: Links have been removed,

Ibegan with little pieces of embryos scooting around in a dish. In 1998, these unassuming cells caught the attention of Michael Levin, then a postdoctoral researcher studying cell biology at Harvard University. He recalled simply recording a video before tucking the memory away. Nearly two decades later, Levin, now a developmental and synthetic biologist at Tufts University, experienced a sense of déjà vu. He observed that as a student transplanted tissues from one embryo to another, some loose cells swam free in the dish. 

Levin had a keen interest in the collective intelligence of cells, tissues, organs, and artificial constructs within regenerative medicine, and he wondered if he could explore the plasticity and harness the untapped capabilities of these swirling embryonic stem cells. “At that point, I started thinking that this is probably an amazing biorobotics platform,” recalled Levin. He rushed to describe this idea to Douglas Blackiston, a developmental and synthetic biologist at Tufts University who worked alongside Levin. 

At the time, Blackiston was conducting plasticity research to restore vision in blind African clawed frog tadpoles, Xenopus laevis, a model organism used to understand development. Blackiston transplanted the eyes to unusual places, such as the back of the head or even the tail, to test the integration of transplanted sensory organs.1 The eye axons extended to either the gut or spinal cord. In a display of dynamic plasticity, transplanted eyes on the tail that extended an optic nerve into the spinal cord restored the tadpoles’ vision.2 

In a similar vein, Josh Bongard, an evolutionary roboticist at the University of Vermont and Levin’s longtime colleague, pondered how robots could evolve like animals. He wanted to apply biological evolution to a machine by tinkering with the brains and bodies of robots and explored this idea with Sam Kriegman, then a graduate student in Bongard’s group and now an assistant professor at Northwestern University. Kriegman used evolutionary algorithms and artificial intelligence (AI) to simulate biological evolution in a virtual creature before teaming up with engineers to construct a physical version. 

i have two stories about the Xenobots. I was a little late to the party, so, the June 21, 2021 posting is about xenobots 2.0 and their ability to move and the June 8, 2022 posting is about their ability to reproduce.

Tran’s June 14, 2024 article provides the latest update, Note: Links have been removed,

Evolving Beyond the Xenobot

“People thought this was a one-off froggy-specific result, but this is a very profound thing,” emphasized Levin. To demonstrate its translatability in a non-frog model, he wondered, “What’s the furthest from an embryonic frog? Well, that would be an adult human.”

He enlisted the help of Gizem Gumuskaya, a synthetic biologist with an architectural background in Levin’s group, to tackle this challenge of creating biological robots using human cells to create anthrobots.8 While Gumuskaya was not involved with the development of xenobots, she drew inspiration from their design. By using adult human tracheal cells, she found that adult cells still displayed morphologic plasticity.

There are several key differences between xenobots and anthrobots: species, cell source (embryonic or adult), and the anthrobots’ ability to self-assemble without manipulation. “When considering applications, as a rule of thumb, xenobots are better suited to the environment. They exhibit higher durability, require less maintenance, and can coexist within the environment,” said Gumuskaya.

Meanwhile, there is greater potential for the use of mammalian-derived biobots in biomedical applications. This could include localized drug delivery, deposition into the arteries to break up plaque buildup, or deploying anthrobots into tissue to act as biosensors. “[Anthrobots] are poised as a personalized agent with the same DNA but new functionality,” remarked Gumuskaya.

Here’s a link to and a citation for the team’s latest paper,

Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells by Gizem Gumuskaya, Pranjal Srivastava, Ben G. Cooper, Hannah Lesser, Ben Semegran, Simon Garnier, Michael Levin. Advanced Science Volume 11, Issue 4 January 26, 2024 2303575 DOI: https://doi.org/10.1002/advs.202303575 First published: 30 November 2023

This paper is open access.

Xenobots (living robots) that can reproduce

Xenobots (living robots made from African frog (Xenopus laevis) frog cells) can now self-replicate. First mentioned here in a June 21, 2021 posting, xenobots have captured the imagination of various media outlets including the Canadian Broadcasting Corporation’s (CBC) Quirks and Quarks radio programme and blog where Amanda Buckiewicz posted a December 3, 2021 article about the latest xenobot development (Note: Links have been removed),

In a new study, Bongard [Joshua Bongard, a computer scientist at the University of Vermont] and his colleagues from Tufts University and Harvard’s Wyss Institute for Biologically Inspired Engineering found that the xenobots would autonomously collect loose single cells in their environment, gathering hundreds of cells together until new xenobots had formed.

“This took a little bit for us to wrap our minds around,” he said. “There’s no programming here. Instead, we’re designing or shaping these xenobots, and what they do, the way they behave, is based on shape.”

“We take a couple of thousand of those frog cells and we squish them together into a ball and put that in the bottom of a petri dish,” Bongard told Quirks & Quarks host Bob McDonald. 

“If you were to look into the dish, you would see some very small, what look like specks of pepper, moving about in the bottom of the petri dish.”

The xenobots initially received no instruction from humans on how to replicate. But when researchers added extra cells to the dish containing xenobots, they observed that the xenobots would assemble them into piles.

“Cells early in development are sticky,” said Bongard. “If the pile is large enough and the cells stick together, the outer ones on the surface will grow very small hairs, which are called cilia. And eventually, after four days, those cilia will start to beat back and forth like flexible oars, and the pile will start moving.”

“And that’s a child xenobot.” 

A November 29, 2021 Wyss Institute news release by Joshua Brown describes the process a little differently,

To persist, life must reproduce. Over billions of years, organisms have evolved many ways of replicating, from budding plants to sexual animals to invading viruses.

Now scientists at the University of Vermont, Tufts University, and the Wyss Institute for Biologically Inspired Engineering at Harvard University have discovered an entirely new form of biological reproduction—and applied their discovery to create the first-ever, self-replicating living robots.

The same team that built the first living robots (“Xenobots,” assembled from frog cells—reported in 2020) has discovered that these computer-designed and hand-assembled organisms can swim out into their tiny dish, find single cells, gather hundreds of them together, and assemble “baby” Xenobots inside their Pac-Man-shaped “mouth”—that, a few days later, become new Xenobots that look and move just like themselves.

And then these new Xenobots can go out, find cells, and build copies of themselves. Again and again.

In a Xenopus laevis frog, these embryonic cells would develop into skin. “They would be sitting on the outside of a tadpole, keeping out pathogens and redistributing mucus,” says Michael Levin, Ph.D., a professor of biology and director of the Allen Discovery Center at Tufts University and co-leader of the new research. “But we’re putting them into a novel context. We’re giving them a chance to reimagine their multicellularity.” Levin is also an Associate Faculty member at the Wyss Institute.

And what they imagine is something far different than skin. “People have thought for quite a long time that we’ve worked out all the ways that life can reproduce or replicate. But this is something that’s never been observed before,” says co-author Douglas Blackiston, Ph.D., the senior scientist at Tufts University and the Wyss Institute who assembled the Xenobot “parents” and developed the biological portion of the new study.

“This is profound,” says Levin. “These cells have the genome of a frog, but, freed from becoming tadpoles, they use their collective intelligence, a plasticity, to do something astounding.” In earlier experiments, the scientists were amazed that Xenobots could be designed to achieve simple tasks. Now they are stunned that these biological objects—a computer-designed collection of cells—will spontaneously replicate. “We have the full, unaltered frog genome,” says Levin, “but it gave no hint that these cells can work together on this new task,” of gathering and then compressing separated cells into working self-copies.

“These are frog cells replicating in a way that is very different from how frogs do it. No animal or plant known to science replicates in this way,” says Sam Kriegman, Ph.D.,  the lead author on the new study, who completed his Ph.D. in Bongard’s lab at UVM and is now a post-doctoral researcher at Tuft’s Allen Center and Harvard University’s Wyss Institute for Biologically Inspired Engineering.

Both Buckiewicz’s December 3, 2021 article and Brown’s November 29, 2021 Wyss Institute news release are good reads with liberal used of embedded images. If you have time, start with Buckiewicz as she provides a good introduction and follow up with Brown who gives more detail and has an embedded video of a December 1, 2021 panel discussion with the scientists behind the xenobots.

Here’s a link to and a citation for the latest paper,

Kinematic self-replication in reconfigurable organisms by Sam Kriegman, Douglas Blackiston, Michael Levin, and Josh Bongard. PNAS [Proceedings of the National Academy of Sciences] December 7, 2021 118 (49) e2112672118; https://doi.org/10.1073/pnas.2112672118

This paper appears to be open access.

A new generation of xenobots made with frog cells

I meant to feature this work last year when it was first announced so I’m delighted a second chance has come around so soon after. From a March 31, 2021 news item on ScienceDaily,

Last year, a team of biologists and computer scientists from Tufts University and the University of Vermont (UVM) created novel, tiny self-healing biological machines from frog cells called “Xenobots” that could move around, push a payload, and even exhibit collective behavior in the presence of a swarm of other Xenobots.

Get ready for Xenobots 2.0.

Here’s a video of the Xenobot 2.0. It’s amazing but, for anyone who has problems with animal experimentation, this may be disturbing,


The next version of Xenobots have been created – they’re faster, live longer, and can now record information. (Source: Doug Blackiston & Emma Lederer)

A March 31, 2021 Tufts University news release by Mike Silver (also on EurekAlert and adapted and published as Scientists Create the Next Generation of Living Robots on the University of Vermont website as a UVM Today story),

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. The results of the new research were published today [March 31, 2021] in Science Robotics.

Compared to Xenobots 1.0, in which the millimeter-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,” said Michael Levin, Distinguished 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 behaviors 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 behavior.” said 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 modeled different shapes of the Xenobots to see if they might exhibit different behaviors, 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 Sam Kriegman, simulated the Xenbots 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. 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,” says Bongard. “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 capillary tubes.

These studies also suggest that the in silico [computer] simulations could in the future optimize additional features of biological bots for more complex behaviors. 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 behavior. 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 which 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 not only light but also 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 behavior upon sensation of stimuli. 

“When we bring in more capabilities to the bots, we can use the computer simulations to design them with more complex behaviors and the ability to carry out more elaborate tasks,” said 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 like sensors, motors for movement, communication and computation networks, and recording devices to store information,” said 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 adds, 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

An engaging description of the biological bots and what we can learn from them is presented in a TED talk by Michael Levin. In his TED Talk, professor Levin describes not only the remarkable potential for tiny biological robots to carry out useful tasks in the environment or potentially in therapeutic applications, but he also points out what may be the most valuable benefit of this research – using the bots to understand how individual cells come together, communicate, and specialize to create a larger organism, as they do in nature to create a frog or human. It’s a new model system that 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 ultimate 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.

Here’s a link to and a citation for the paper,

A cellular platform for the development of synthetic living machines by Douglas Blackiston, Emma Lederer, Sam Kriegman, Simon Garnier, Joshua Bongard, and Michael Levin. Science Robotics 31 Mar 2021: Vol. 6, Issue 52, eabf1571 DOI: 10.1126/scirobotics.abf1571

This paper is behind a paywall.