Biological Robots May Soon Build You a Better Heart

Friday, June 4, 2021

/ by mansuralisaha

 The News Cover: I think people hear "robot" and they think Terminator or RoboCop. Your move, creep. The idea that you could build a new organism that has never existed from cells that does something we've never seen before, essentially a biological machine, has really captured the imagination. If xenobots sound like science fiction brought to life, it's because they are. They're biological machines made by humans but designed by computers. This project offers a new way to make what you might call a robot that's very different from existing robotic technologies. A machine for a new purpose, not to recapitulate biology or build a heart, but to build something that could do work for any number of tasks that you'd use a traditional robot for. So it's kind of a weird marriage between robotics and computer science and biology. These tiny specks seen here under a microscope are xenobots, made of about 5,000 living skin cells. They get their name from the African clawed frog Xenopus Laevis, which supplies their cells. 

They can't reproduce and they will only live for around 10 days, feeding on the small platelets of yolk that fill each of their cells. Really, this was the first time we thought, could you take stem cells and build something from the ground up? And the idea is really to take these stem cells very early in development, collect them, and essentially have different types of cells like you would different Lego blocks. Cells already act like little machines, some contract and expand, others capture material. By shaping these cells, you create the machine. So you could imagine a red Lego block is a heart cell and a green Lego block is a skin cell. And then really similar to building Legos where you just sort of start connecting the pieces from the bottom up, we build our robots in the same way. 

We just build cell by cell until we get to a final shape and form. Xenobiotics are designed and then evolve using artificial intelligence before they're made. Sam Kriegman is a graduate student at the University of Vermont and designed that computer program. Unlike every other organism that has ever existed before on this planet, the xenobiotics evolve inside of computer simulations and the computer simulates the physical world, but it can do so very rapidly and many worlds at once and so, it can do evolution in days instead of millennia and at the end of this evolutionary process, it prints out a blueprint that tells us how to build a new organism for some desired task from essentially scratch from existing biological materials. 

The simulated xenobots are subjected to physics engines similar to those in video games. The AI assesses how variants will perform and makes changes according to the tasks they're set. This is natural selection put on fast-forward with a computer at the controls. Evolution on Earth works as a long chain of mutations, Evolution on Earth works as a long chain of mutations, tiny revisions to existing designs, one after the other over millions or billions of years. And sometimes, we can speed this up by selectively breeding crops and livestock and dogs so that their offspring have desired characteristics. But it's very unlikely that you could select from wolves or dogs anything that you wouldn't call a dog. But with computers, we can speed up this process. So we can simulate a billion years of evolution in a day or in a week on a supercomputer. The computer selects its top candidates to build and only then do humans come back into the picture. The AI-generated blueprints are sent off to Dr. Blackiston and his wet lab at Tufts University, Massachusetts. Right, so this is the fun part, it's a bit like sculpting and some designs are not possible to be built biologically currently.

 They have features that are too difficult to shape or construct like right angles, very small gaps. But we often get five or six excellent designs that are completely buildable in the lab, which is where we port everything over into the wet lab and build them by hand manually. We then build from the ground up using those different cells the shape that new one, and it typically starts as a sphere. So the cells round off and make a roughly round shape after 24 hours and then we go in with a pair of surgical forceps that we polish with the sharpening stone manually and also a very small cautery electorate. We carve away from that sphere the design and sculpt the final shape that we would like to match the computer design and that's really sort of the amazing part in the innovation is this, this sculpting aspect to give you a very, very precise three-dimensional shape at only the scale of about half of a millimeter. Right now, xenobots are made of only about 5,000 skin and heart muscle cells, but they can perform basic tasks like moving in a straight line, carrying objects from one spot to another and behaving collectively. 

Xenobots don't need to be that sophisticated to supply some kind of social utility. We found that even the xenobots that simply swirl around in their dish, they tended to clean their dish as they moved through it. So that is, they tended spontaneously to sweep up and corral any detritus in their dish into centralized, neat little piles. Why they do that is still somewhat of a mystery. We evolve them in the computer simulation simply to move and we got something for free because they're living systems that have their own agenda and do useful things that weren't necessarily programmed, like cleaning. At the moment, all xenobots are constructed out of frog cells, but if human cells were used instead, then there's huge medical potential for these machines. Potentially, they could simply by swirling around in an artery, scrape plaque off of the walls or abrade calcium deposits in arthritic joints. or abrade calcium deposits in arthritic joints. With a little bit more bio-engineering, we can imagine targeted drug delivery, which is something that we've been thinking about even in our very simple simulations.

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