Groundbreaking! First Fully Functional Synthetic Cell Has Just Been Created

[00:00:00]Hello in person. This is Anton and today we're going to be discussing a landmark achievement in the field of synthetic biology. The creation of what seems to be the most complete artificial cell ever built. Something the scientists are now calling spud cell. And well, the thing is for a very long time this was actually one of the biggest challenges in modern biology with the challenge being trying to create something that seems to be life but by using artificial methods and by using principles from simple chemistry. In other words, for the past few decades, biologists have tried to transition simple chemistry into actual biology that mimics life.

[00:00:41]And in the last few years, we've actually explored quite a few of these achievements. Some of which you can find in the videos in the description. But every single time, there was always something missing and something that was still not working properly. Mostly because we know that living organisms are just extremely complex. They're made out of a lot of non-living components, but those components function in a very specific way. But exactly how they actually function and how they interact with each other or basically how these pieces come together to create a self- sustaining system has remained a little bit elusive. Which essentially brings us to this very recent announcement and this very recent breakthrough that possibly finally brings us closer to that eventual answer and the ability to engineer a synthetic cell entirely from ground up. And in this case, a cell that can eat, grow, replicate, and even undergo a form of evolution. But before we dive into this research and the discovery, we first need to definitively understand what an artificial cell actually is. And in pretty much most research, in general, these are usually defined as these artificial particles that try to mimic one or more functions of a biological cell. With some researchers sometimes taking a kind of a top- down approach where they essentially take an existing living cell and strip away its genes and pretty much most of its internal structure until they try to find the absolute bare minimum needed for the cell to function and to basically resemble life. And the most famous one is probably a project from approximately a decade ago. This was a creation of what's known as Cynthia, the synthesis of a minimal genome that was then put into a cell that contained nothing inside. But while Cintia could replicate, we didn't actually understand what many of his genes were physically doing. In other words, here it was not entirely clear how everything worked, even though it actually did work. But in this recent research, the team behind Spotell, led by Dr. Keta Damawa from University of Minnesota took the opposite approach referred as the bottom up approach.

[00:02:48]Instead of editing an existing cell, they wanted to build something from scratch. Essentially using a chemically defined kit of various individual parts.

[00:02:58]And this is of course a much more interesting approach because here it definitively proves to us that fundamental functions of life do not require some kind of a magical spark or some kind of an unusual force in order to suddenly become living and to start functioning. They just need the right balance of chemical components. And so what exactly is spot cell? Well, essentially this is just a microscopic water droplet wrapped in a somewhat simple fatty membrane. But inside this membrane, there's also a tiny genome containing approximately 90,000 base pairs or about 50 times smaller than inside a typical bacterium. But this genome is not a single long strand. It's split across seven to eight separate DNA plasmids with this modular design allowing scientists to program everything independently and with a lot of control with the workspot cell essentially being chosen for two reasons. first because this cell resembles a tiny potato, but also it's a kind of a nod to Sputnik or the first satellite in space. And so here this is a kind of an evocation of a new age, but in this case for the biological fields as opposed to the space age. But how exactly does any of this work and what's happening inside? Well, one of the hardest parts of creating an artificial cell is basically getting it to eat something or [clears throat] to acquire resources in order to grow. And spot cell does this through a process referred to as genetically encoded feeding. And so here the cell's genome contains instructions on how to produce a protein referred to as alphain.

[00:04:37]This protein creates tiny tiny pores in the cell's membrane with these pores serving two purposes. First, they allow the waste to leave from inside to the outside while at the same time allowing nutrients to come inside. But more importantly, researchers engineered a way for the spot cell to fuse with smaller feeder liposomes and thus absorb a lot of stuff through the membrane fusion process as well. And so when a spot cell produces a certain tag on its membrane, it attracts these feeder liposomes which then merge with spot cell providing it with more membrane material and fresh molecular machinery to keep functioning which is surprisingly not so different from how some of the more simple bacteria function as well. And by itself this is a huge achievement. This coupling of gene expression to physical growth is a major achievement for artificial life.

[00:05:31]This type of control and this type of a function has never been artificially created before. None of the previous synthetic systems could do any of this.

[00:05:40]But in order for a cell to physically be referred to as life, it also has to find a way to somehow replicate. And so basically, in order to have a life cycle, it needs to be able to produce offspring. And that means that it has to have instructions inside and has to be able to divide into something that resembles itself. And here spot cell can also do that too. It actually uses an enzyme referred to as 529 polymerase that directly copies its entire DNA in order to then give it to its offspring.

[00:06:11]And the thing is this particular process seems to be isoothermal or basically it can happen at a steady temperature without any extreme heat cycles. And that's actually important because normally in a typical lab condition in [clears throat] order to copy DNA and in order to actually make DNA do all sorts of stuff artificially it does require extreme heat cycles and basically additional temperature from somewhere else. But here this particular cell can copy everything in steady temperature conditions and does not require any external heat. But the most impressive feat is of course the division [clears throat] itself. And that's because in natural cells this is a very complex process involving internal scaffolding referred to as cytokeleton pulling the cells apart before division can start. But spot cell does not have this cytokeleton and instead uses a slightly different technique. It uses a process referred to as membrane protein crowding. So basically here researchers program the cell to produce specific proteins that cluster together on the surface of the membrane. And as more proteins crowd together, they eventually create mechanical stress and make the membrane curve, eventually causing the droplet to pinch off and split into daughter cells. So basically these proteins squeeze on the mother cell and produce two separate bubbles that then become two separate cells. And while currently this process is not particularly efficient. Apparently only about 30% of daughter cells acquire the full DNA, it still represents a massive leap forward in showing how simple physical forces can actually achieve complex biological tasks. And so even with these 30% functional daughters here, this still meets the definition for life. But on top of all of this, research has also demonstrated a kind of an artificial evolution. with researchers demonstrating that a lot of these cells could go through a form of selection that then changed them just a little bit. And specifically, they introduced a kind of a beneficial mutation or basically a stronger version of the feeding gene that allowed some cells to produce more of these feeding tags, thus acquiring more of those liposomes from outside. And over five generations, the cell with this mutation grew much faster and produced more offspring compared to the weaker cells.

[00:08:34]And when the food was scarce, the advantage of these mutated cells became even more pronounced. So this is essentially a kind of a natural selection occurring entirely in a test tube filled with non-living chemicals with this even going as far as showing multiple generations competing for resources and eventually evolving into slightly different versions. Although in this case we still have to clarify something very important. Even though spot cell can perform lielike tasks, researchers in the study and of course experts that have already commented on the study emphasize that this is still not a living being in a traditional sense. This is still a complex synthetic platform constructed from non-living chemicals. And so here it still cannot independently regulate its own metabolism, manage complex homeostasis by itself, or even dispose of waste in a much more complex and efficient way. So this is still best understood as a sophisticated programmable biological engineering platform that just mirrors fundamental features of life. But nevertheless, spot cell is still extremely important and essentially represents a kind of a pinnacle in synthetic biology and it's unique amongst all other synthetic cells because it manages to combine almost all lifelike modules in one single package.

[00:09:56]Here we have feeding, growing, copying DNA, dividing and even evolution in a single chemically defined system which is very different from previous research that essentially tried to maybe improve one or two things and never achieved all of them at once. But I guess the other question is if this is not life and if this is essentially just a bunch of chemicals pretending to be life, why exactly is this important? Or basically why spend years building a cell potato that barely works? Well, first it helps us define the minimum chemical requirements for life to actually function or basically here by building life from scratch, we can understand exactly which parts are essential and which are possibly just junk accumulated over billions of years. So essentially this is important for theoretical biology that [clears throat] tries to understand exactly what life is and of course if it can exist somewhere else out there. Second this also has a massive industrial potential because a lot of modern medicine and a lot of modern fuels are usually made using some kind of a biological cell usually a bacteria but also involving some kind of a harsh chemical. And in this case, synthetic cells can be designed in a much more efficient way and can then basically produce fertilizers, grow plastic or even create specific drugs that would be very difficult to achieve in a normal bacteria because of the operating conditions. And they can possibly even do all of this at room temperatures and with much less energy.

[00:11:28]In other words, it's essentially a kind of a biological factory that can help us create so much more with so much less.

[00:11:35]And because it's not truly alive in the way that the bacterium is, it also means that it can be controlled much easier.

[00:11:42]And that's because here it's technically a kind of a perfect heteratroof, meaning that it's completely dependent on sciences providing it with complex liposomes in order to feed and also requires very specific proteins to function. And so if you were to somehow take it outside of the lab or basically if it was somehow to escape the lab, it would not create some kind of a hazardous toxic environment. and would actually just completely stop working right away. And so here, this actually allows us to control things much easier.

[00:12:11]But this is still just the first step and the first prototype. And so the next step for the team is to try to make these cells more robust by possibly consolidating its DNA into one single chromosome instead of seven, but by also somehow finding a way for this particular cell to then produce its own ribosomes so it can then produce its own proteins. But the thing is to make this research go faster and to make it publicly accessible, researchers also have now created a public benefit institution referred to as biotic whose main purpose is to keep this research open and collaborative. You can find the link for this in the description below.

[00:12:51]So basically here the idea is to never make this private and to never fully commercialize this making sure that this remains publicly accessible and recreatable by anyone anywhere.

[00:13:02]Although, at least for now, that's essentially all we have. And so, it's definitely a really intriguing time to be alive, or in the case of Spotell, almost alive because we're actually finally achieving something that biologists have been dreaming about for decades and decades. We're finally learning to write the software of biology and to create the actual hardware from scratch. But because this is still a work in progress and because I've been following this progress for a pretty long time with videos in the description talking about previous achievements, we'll definitely come back and discuss the next part once it comes out. Until then, thank you for watching.

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