Breakthrough Synthetic Cell Has Just Reproduced - But Is It Alive?

0:00When you need to build up your team to handle the growing chaos at work, use Indeed Sponsored Jobs. It gives your job post the boost it needs to be seen and helps reach people with the right skills, certifications and more. Spend less time searching and more time actually interviewing candidates who check all your boxes. Listeners of this show will get a$75 sponsored job credit at Indeed.com slash podcast. That's Indeed.com slash podcast. Terms and conditions apply. Need a hiring hero? This is a job for Indeed Sponsored Jobs. I think this is the breakthrough of the year so far, Penny. It's a synthetic life form built from the ground up.

0:35They've called it spud cell. Spud cell.

0:38Kate Adamala:Spud cell. It's a big breakthrough. How big remains to be seen. But the news here is that an artificial cell has been created using 36 existing genes. And it's partly capable of replicating itself. But it's not a living organism. Not yet. No, I think of it like if you think of a normal living cell as a jet airliner, a modern airliner. This spud cell is like the Wright brothers first attempt at an airplane made of wood and cotton, cotton sheets that could just about get off the ground. Still big if true though. Huge if true. Huge if true. And that's what we're discussing on this episode of The World, The Universe and Us from New Scientist.

1:16Kate Adamala:I'm Dr Penny Sarsho. And I'm Dr Rowan Hooper. We're joined by Michael LePage. Michael, you've been reporting on this story and on previous synthetic life stories over the years. So we're going to get into that. This is the first synthetic cell built from non living components, that's able to complete a full cell cycle. Well, it's yes, but those non living components come from existing bacteria. So this isn't something that's been created from scratch. It's, it's, it's essentially it's an attempt to create a minimal cell, but to do it from the bottom up rather than the top down. So in the past, sort of people like Craig Fenter, so they tried to create a minimal cell by taking existing bacteria and knocking out genes one by one and getting them right down.

2:00And I think they started with sort of 900 genes and got them down to 400 and something. Yeah. This is working the other way around. So Kate Adamala has taken sort of just a few genes from bacteria. There are a couple of viral genes. There's also a jellyfish gene. That's so you can see it fluoresce and you can actually see it easily. Always need to have a jellyfish gene in these experiments. GFP, the famous glowing jellyfish gene. Yeah. And so she's taken these and put them together to create this cell. It's not quite a living cell. It sort of doesn't do any of the things it does very well, and it needs a lot of help doing them.

2:39But it's still, you know, it's a momentous sort of breakthrough, because no one's got this far before. This is way more than other people have achieved.

2:47Kate Adamala:The synthetic biology field has been ticking along for a while, and Craig Venter obviously did that work. The difference here is that rather than knocking things out, we're actually building it from the start up. Yes. So these genes were taken from other bacteria and then sort of put on these artificial pieces of DNA. And to rev it up, what the team did, the 36 genes are divided between seven pieces of DNA. So they made loads of copies of these and they put them in solution along with all the other sort of chemicals that these cells would need. And then they also added to the solution these sort of fatty molecules that will spontaneously form these cell-like bubbles.

3:26So as these bubbles formed, some of them would include the DNA in them. And a few of them had all of the necessary genes to start copying their DNA and growing and so on.

3:40Kate Adamala:Amazing. And it makes you think about the first time that happened on planet Earth as well. Well, I want to get into that. But shall we do the name first? It's quite a cool name, Spud Cell. Why is it called that? Well, so you mentioned Kate Adamala, the boss of this lab. The people in the lab were calling them Adamala cells. And she was like, oh, I don't like that. It's a bit much. She said, I'm Polish. I'm made of spuds. They look like spuds. And then the people in the lab started calling them Spud Cells. But they've also said Spud Cell is supposed to invoke Sputnik, which was the dawn of the space age.

4:17And this is the dawn of the synthetic biology age. Maybe another false dawn, but it's another dawn. Yes. But Michael, yeah, take us through a bit more detail about how they made the spud cell. So once they sort of revved them up by creating, getting these bubbles to form and solution, these bacterial genes inside them kicked in and they started copying DNA. They also started making some proteins. genes but it's important to say you know this is all dependent on lots of nutrients being supplied from the outside so these cells they can't make any of the chemicals they need and they can't make the building blocks of dna they can't make the building box of protein and they also one key thing is they can't make the protein making factories ribosome the ribosome so those had to be supplied to them from the beginning yeah and so the team was constantly sort of feeding them these nutrients.

5:08Now, a couple of the genes code for proteins that form pores on the outside of these spud cells. So they can get some small molecules into them through those pores. But a lot of the feeding had to be done by making little bubbles full of food that would fuse with the spud cells. So it's quite an involved process. I mean, I sort of thinking of it as like spoon feeding a child. This is, you know, this is, they need a lot of care and attention.

5:32Kate Adamala:But they can divide a bit, can't they? Is it up to five rounds of division? Which is impressive. Does this mean that they're alive? Well, the first thing to say is, for them to divide, what the team do is they add these large proteins to the solution. And when those proteins bind to the spud cells, they start jostling for space is how Kate described to me. And then that makes the membrane bend. And sometimes you get bits of the spud cell budding off. But it's not an equal division. It's not sort of, you know, So the spud cell isn't dividing neatly in two. And also the sort of bits of DNA inside it, they're not being equally shared.

6:09So it's quite random. So some of the cells that bud off, some of the daughter cells, have not got all the genes they need and they're dead end. But some of them, just by chance, they do have all the genes they need. And then they can go on and repeat the cycle. So, yeah, it's cell division, which is incredibly impressive. But it's a very sort of primitive, rough and ready form of cell division. We've got to start somewhere. right and you imagine cell division would have started by just a physical process the the vesicle just becomes too big and splits it apart and then what the cell has to do eventually is figure out a way or let's get dna equally into those two bits that and that's not where we're at yet but you can see that's where the next step needs to be but the challenge with this is sort of compounded

6:53Kate Adamala:with how they gave it the dna isn't it because it's very impressive and in previous attempts to do minimal cells we've been talking about bacteria with things like 900 genes or nearly 500 and this is just 36 but am I right in understanding you know you might imagine that they'd all be on one bacterial chromosome but actually they're in loads of different pieces in the cell and it's very hard to divide that up accurately yeah so that I asked Kate about that and she said that the problem is that it's very hard to make a big piece of DNA right with all the genes on it that would be the ideal so that's still a sort of technical capability that we don't have six genes though well yeah but it's it's it's because they they're using other bacteria to multiply the bits of dna that they're then put into the spud cell and these bacteria don't like to make big pieces of dna so it can be done but it takes a lot of time so to speed things up they just use these smaller pieces of dna but then that means you've got seven instead of one and they you've got problems with dividing them between the cells.

7:54So, you know, they will definitely create a single piece of DNA. They have all the genes of them in the future when they're happy with what they've got. But this is a work in progress.

8:04Kate Adamala:So then it's replicating to a degree. It's feeding. Is it alive? I would say no at the moment. And the main reason is not only does it need a lot of help doing all these things and it can't do it by itself, but they sort of fail after about five replications. They just sort of stopped doing much. The team isn't quite sure why, but the speculation is, you remember I said earlier that they have to be supplied with the protein making factories that are producing the ribosomes. And so the thinking is that those ribosomes are just gradually sort of sort of wearing out and failing. And then once the C cells, these spud cells can't make their own proteins and everything goes wrong.

8:43So I think obviously the team want to get to the point where they can make their own ribosomes that's something that they're working on already and if that enables them to keep uh dividing indefinitely then they're getting much closer to life and then the other thing that uh kate said to me is that she would want them to be capable of evolution as well so if they're dividing indefinitely and evolving she would regard them as living yeah but what what i what i think is one of the most interesting things about this work is that i i think most scientists would already know this but normal people probably don't is that life is not a binary on off thing so you hesitated when penny said is it alive you're not i don't you would say i would say no but that's so interesting like life is something that's smeared out across something that is definitely dead to something that we all would say is alive and it doesn't suddenly flip it flip when does it flip from one to the other so we're part we've gone along that road towards something living yes and we've done that artificially and that is something really amazing it is amazing so that you know there's all this debate about viruses and are they alive or not and obviously they depend on other cells but then every cell depends on other cells to some extent so uh yeah it's it's very hard to draw a line and give a clear definition this is living and

10:06Kate Adamala:this is not i wonder if the ribosome is is key because often when you talk about the origins of life we think the ribosome the ability to make your own proteins and then to make your own factories that make the proteins is really important to self-sustaining life presumably that's something they're working on yes they want to put in a cytoskeleton that's a sort of protein framework inside it that will help it divide more neatly and separate the the bits of dna properly then they want to add a ribosome and things like that so they've got this long to-do list the thing to say is these are going to be very difficult to achieve but they've made they've released this as open source so that everyone around the world can sort of chip in and help sort of make this better if they want to so this isn't just going to be one team trying i think that's something really to be applauded as well isn't it and before uh you know with the venter stuff they very famously kept it all to themselves um when they were sequencing the human genome but but also with the synthetic life stuff.

11:07So this is, I mean, it's really admirable that they've made it open source, but also it's very practical, as you say. You know, this is a very complex thing. Let's get all the help we can. And someone does the cytoskeleton, someone else does the ribosome, and you all chip in. Yeah, it'll be interesting to see how many people chip in and start working on this, but I imagine it'll be quite a few.

11:31Kate Adamala:Shall we talk about the motivations for work like this? I guess we're learning about the nuts and bolts of how, what do you actually need to build a cell? But what more is there to this sort of field of research? So the classic thing that synthetic biologists will tell you, if you take an existing living organism and try and make it do something, it's really difficult. So you sort of change one thing and you find you've broken 10 others. You didn't even know we're connected. And that's because of the way evolution works. Evolution just sort of takes what there and adapts it to do lots of different things.

12:02and so it's really hard to change some existing living cells to do what you want to do. So the idea with synthetic biologists to say, what we need, we need a cell where we understand everything. We've sort of built it ourselves. We understand everything. We can change things and make it do exactly what we want because we understand the system. I mean, that's a fair enough argument, but if you look at spud cell right now, I mean, it's very impressive, but it's not anywhere near doing anything useful. all that's a very long way away and you know my suspicion is that you're gonna have to get it to evolve a lot to really optimize it and then once it starts evolving you're going to get some of those same problems back again now i put that to kate adamler and what she said is well we're gonna you know yes we do need to evolve it but we're gonna check it mutation by mutation so make sure we understand each mutation as it happens well that's gonna really slow i mean it's gonna make it really difficult to do things fast that's going to take if you're going to do mutation by mutation as it because of course it's small now but as you add in all these extra things that they're wanting to do then you're going to have all these extra layers of complexity and it's going to get bigger and if you're going mutation one mutation at a time that's going to be very slow so i'm i mean i'm sort of maybe one day but i you know i think this is we're talking decades still before well, this does anything useful.

13:26And even then, wouldn't we just be better starting with living cells? I mean, they've already widely used to produce a whole range of chemicals now. Imagine living on the ocean floor for days at a time, stepping straight into an open moon pool into the sea. That's the dream of the scientists and engineers at DEEP who've built Vanguard, the world's first new open ocean subsea research habitat in 40 years. Join them in a New Scientist co-lab video to find out what happened when they deployed Vanguard at Tennessee Reef off the coast of Florida. Their goal is to inspire oceanographers, biologists, researchers and others to become the next generation of aquanauts.

14:07Search New Scientist Deep Vanguard to explore the blueprint for our aquatic future. Sponsored by Deep. This episode is brought to you by Google Chrome. You think you know a browser, but Gemini and Chrome? That's new. It can help you with practically anything on the web, like restoring a vintage motorcycle from a 50-page restoration block, or finally break down that long article you've had open for weeks. Gemini and Chrome is here for it. Ready to make anything online make sense? There's no place like Chrome. Check responses set up required, compatibility and availability varies 18+. i just want to bring it back to more fundamental questions because i know that we're all primed to say well what are we going to get out of it and what we're going to make out of it and when are we going to get synthetic pharmaceuticals out of this thing but but again you know it so it's telling us something about what life is but then i also like how it will start maybe telling us about how life arose so we're starting you know i just visited that lab at university college london nick lane's pathway to life they're trying to put together how living things emerge from non-living things and that's what they're doing here in a different way though putting together the different components of things that are dead on their own and then you get eventually you're going to get something alive out of it and that will shed life light on one of what is still one of the biggest questions that we've ever asked the origin of life i think it will but they are starting at a fairly i mean they're taking fairly advanced bacterial genes here and and using them as a building block so this is this is after they've skipped a few really important jumps they've skipped a billion years or so of evolution uh to get to get to this point but but obviously you know if once we start being able to do more things like this then you can try and go back and recreate those earlier steps which would be really exciting.

16:05Kate Adamala:I did find the stated aims eye-catching though even if they're decades away. One of the things that Adamana has said is that this could lead to a way to make petrochemicals with living biology so that we can stop extracting all the kinds of chemicals that we often forget come from oil. Things that we use for pharmaceuticals and cosmetics and plastics and everything, get them from bacterial cells instead of having to dig up fossil fuels. Can you see a pathway to that ultimately? Or is this like what all researchers do? You just come up with the grandest aims possible for your research? I mean, I've absolutely no doubt it's possible.

16:43I mean, we've already sort of engineered some sort of very complex systems into, I think it's yeast, if I remember, where it makes a malarial drug. and that took dozens of genes. It's definitely achievable. The question is how long it takes and how cost-efficient is that process. What Katie D 'Amolo was saying to me is, she thinks one of the issues is that a lot of these petrochemicals are toxic to living cells, and that's one of the problems you have when you try and make them in a normal bacterium where you say it kills them off. And so she thinks the synthetic approach, you can sort of make cells that are resistant to those chemicals and therefore be better at manufacturing them.

17:27And we might be seeing it coming from synthetic yeast before we get this bottom-up approach really up and running enough to scale up and work on industrial scale. But, you know, the synthetic yeast project has been a long time coming. It's always like nearly there, nearly there. So for that there, I think there's 13 chromosomes in yeast and they're having to synthesize each one from scratch and then debug it. So these are, I don't know, how many thousands of genes on each chromosome. So it's an immense job. Each different lab around the world has got its own chromosome they're working on. And then you've got to debug them all and then bring them all back together.

18:09And then that's a eukaryotic cell, though.

18:11Kate Adamala:Yes, so much more complex than a bacterium. But also much more robust and much more powerful than a bacterial cell. So let's see which one comes first. I think there will be people listening who want to know, is this dangerous? We're building cells. We want them to evolve. What could possibly go wrong? Yeah. I mean, I think at this stage, this is like if you could think of it as a Frankenstein's monster, but a Frankenstein's monster that's bedridden. There has to be spoon fed. It's not going to. At this stage, there's absolutely no danger of running amok. and then even if we can succeed in turning it into a true living cell that needs less help and can keep dividing indefinitely it's been you think of the bacteria that pose dangers to us they do so because they've evolved to sort of challenge us and to get around our immune system and things like this that's all been stripped away here so this i mean you can think this is going to be a really defenseless organism that is probably not going to be able to survive outside a sort of lab or a factory.

19:13It reminds me of when someone said I think it was about Venter's work years ago you know you're playing God and someone replied well we're not playing God very well we've made a really bad sale here it doesn't work very well. Breakthrough of the year

19:28Kate Adamala:but also really bad. No let's say it's still breakthrough absolute breakthrough of the year so far. So far. That's all for this episode thanks to our guest Michael Lepaid and thanks to you for listening. And as always do subscribe and follow wherever you get your podcasts. Bye for now.

19:52To be continued...

20:12need to help them perform under pressure. Sounds pretty good, right? Toast. Built for busy.