From Xenobots to Anthrobots

There were many things I could have written bout this week – e.g., in A.I., in quantum computing, even “transparent wood” -- but when I saw some news about biological robots, I knew I had my topic.

Yep, those are robots -- biological robots. Credit: Gizen Gumuskaya

The news comes from researchers at Tufts University and Harvard’s Wyss Institute. Their paper appeared in Advanced Science, introducing “a spheroid-shaped multicellular biological robot (biobot) platform” that they fondly dubbed “Anthrobots.” Importantly, the Anthrobots are made from human cells.

Let’s back up. In 2020, senior researcher Michael Levin, Ph.D., who holds positions at both Tufts and Harvard, worked with Josh Bongard, Ph.D. of the University of Vermont to create biological robots made from frog embryo cells, which they called Xenobots.  They were pretty impressive, capable of navigating passageways, collecting material, recording information, healing themselves from injury, and even replicating for a few cycles on their own, but the researchers wanted to find out if they could create biological robots from other types of cells – especially human cells.

Well, the new research showed that they could. They started with cells from adult trachea, and without genetic modification were able to demonstrate capabilities beyond those Xenobots had demonstrated. Lead author Gizem Gumuskaya, a PhD. student said: “We wanted to probe what cells can do besides create default features in the body. By reprogramming interactions between cells, new multicellular structures can be created, analogous to the way stone and brick can be arranged into different structural elements like walls, archways or columns.”   

The Anthrobots come in different shapes and sizes, and are capable of different motions. Ms. Gumuskaya is quite excited about their capabilities:

The cells can form layers, fold, make spheres, sort and separate themselves by type, fuse together, or even move. Two important differences from inanimate bricks are that cells can communicate with each other and create these structures dynamically, and each cell is programmed with many functions, like movement, secretion of molecules, detection of signals and more. We are just figuring out how to combine these elements to create new biological body plans and functions—different than those found in nature.

Even better, Ms. Gumuskaya pointed out: “Anthrobots self-assemble in the lab dish. Unlike Xenobots, they don’t require tweezers or scalpels to give them shape, and we can use adult cells – even cells from elderly patients - instead of embryonic cells. It’s fully scalable—we can produce swarms of these bots in parallel, which is a good start for developing a therapeutic tool.”

They tested Anthrobots’ healing capabilities by scratching a layer of neurons, then exposed the gap to a cluster of Anthrobots called a “superbot.”  That triggered neuron growth only in that area. The researchers noted: “Most remarkably, we found that Anthrobots induce efficient healing of defects in live human neural monolayers in vitro, causing neurites to grow into the gap and join the opposite sides of the injury.”

“The cellular assemblies we construct in the lab can have capabilities that go beyond what they do in the body,” said Dr. Levin. “It is fascinating and completely unexpected that normal patient tracheal cells, without modifying their DNA, can move on their own and encourage neuron growth across a region of damage.”

Xi “Charlie” Ren, a tissue engineer at Carnegie Mellon University who was not involved with the research, told Science that the work “is amazing, and groundbreaking,” and “opens the way to personalized medicine.” Ron Weiss, a synthetic biologist at the Massachusetts Institute of Technology who also was not involved with the work added: “Levin demonstrated that cells can be coached to do something they would never have done on their own.”

Some researchers are not yet convinced. Jamie Davies, a developmental biologist at the University of Edinburgh in Scotland, who was not involved in the 2020 study or this recent one, told Scientific American: “I cannot see how these clumps of cells with flailing cilia merit the term ‘bot.” Dr. Levin and his team, of course, don’t believe the movements are random, and that Anthrobots “could be designed to respond to their environment, and travel to and perform functions in the body, or help build engineered tissues in the lab.”

The ultimate hope is that clinicians would be able to use Anthrobots created from a patient’s own cells to perform therapeutic work. Those bots shouldn’t trigger an immune response, would be bioresorbable, and couldn’t survive outside the lab or the body (making risk of any unintended spread minimal).

The researchers see a wide variety of potential uses in health care:

…various applications can be imagined, including but not limited to clearing plaque buildup in the arteries of atherosclerosis patients, bulldozing the excess mucus from the airways of cystic fibrosis patients, and locally delivering drugs of interest in target tissues. The possible applications will represent those arising from exploiting surprising novel behaviors of cells and engineering new ones via future synthetic biology payloads, such as novel enzymes, antibodies, and other ways to manipulate the cells they traverse and interact with. They could also be used as avatars for personalized drug screening^[32] having the advantage of behavior over simple organoids, which could be used to screen for a wider range of active, dynamic phenotypes.

That’s 21^st century medicine. That’s the kind of health care I want to see.

21st century medicine in action. Credit: Bing Image Creator

The researchers have a number of research areas they want to further explore, including:

• What other cells can Anthrobots be made of?
• What other behaviors might they exhibit, and in what environments?
• What other tissue types can they repair or affect in other ways?
• Can transcriptional or physiological signatures be read out in living bots, that reflect their past and immediate interactions with surrounding cellular or molecular landscapes?
• Do they have preferences or primitive learning capacities, with respect to their traversal of richer environments?

As researchers like to say, more research is required – and, from where I’m sitting, eagerly awaited.

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OK, so these aren’t like the cute robots you see doing flips. They’re not the nanobots many of us have been waiting for. We don’t (yet) have to worry about Asimov’s Three Laws of Robotics with them. But, boy, if we’re going to have robots crawling around inside us doing therapeutic things – and we are -- what could be better than a biological robot made from your own cells?