Hi, thanks, and very cool work (assuming it eventually holds up in peer review)!
A few things that confused me while trying to read the paper:
- There's two different methods of cell division mentioned -- mechanical extrusion and the autonomous, protein-driven division. Most of the results (e.g. the five generations) focus on the mechanically driven one, while the autonomous one is more "lifelike". Does the autonomous division have a higher failure rate, or can you get the same results with it as well?
- It's mentioned that the bottleneck for survival of many generations is ribozomes degrading, but also that ribozomes are supplied from the outside. Do the degraded ribozomes actively harm the cell? Or is there some other reason why they cannot be replenished?
- You say that after 5 generations, only 30% of the cells have the correct genome, and it's presented like a problem -- but 30% of 2^5 is more than 10, so this sounds like more than enough for continued survival. Is there something missing in this train of thought? Perhaps other failures that can kill the cell?
And some questions about the implications:
- Do you think that the genome you use is already close to minimal? AFAIK a lot of the minimal organisms found in the wild are parasites of some sort, getting most of their complex molecules from the outside, which is a similar spirit to this (a rich medium and the cell "just" self-duplicating). If the multiple plasmids are causing trouble (per the previous point), would it make sense to try and get rid of some of them?
- Are those minimal genes somehow interpretable -- as in "you need functions X, Y, and Z and cannot avoid them by using a better medium"?
- Do you think this is a plausible stage of very early life?
The current model, of a cell that cannot live on its own and cannot evolve (being too far from "edge of chaos") is what will be most useful for bio-engineering. Yes, we need the mechanism for creating cells, and the newfound division for a minimum viable cell is paramount. But, we also need for ways to control its reproduction, be it as to die out on its own after few generations due to degraded protein build-up, or (in the best case scenario) due to some other built in mechanism. Otherwise, expect (at least) some amount of scaremongering, about playing fast and loose with things that may get out of hand. The best thing is to have this kind of cell template that could somehow be augmented with whatever additional plug-in functionality (useful for us, case by case) and then get it produced in the needed quantities and not more. The research direction that makes sense is for ways to add such "mission specific" functions to this synthetic cell and ways to create the first generation as efficiently as possible, at large scale. That's it.
What are the implications for nanobots with this kind of innovation: Artificial cell division recreating itself in 2? Is this a future endeavor of this tech?
Great question - what we built isn't a "nanobot" in the Drexlerian sense (a tiny engineered machine assembling things atom by atom). It's a cell, it runs onn molecular machines like ribosomes, membranes, and enzymes. The self-replication and division you're picturing comes from that biological machinery copying and dividing, not from a mechanical device building a second copy of itself.
So on your specific question: division is very much a core goal of the synthetic cell field, and getting a built-from-defined-parts system to grow and divide reliably on its own is one of the big open problems ahead of us. What SpudCell demonstrates is assembling something cell-like from well-defined components.
Where this does connect to the "programmable matter" dream is that if you can engineer a cell from the ground up, you can in principle program what it makes and does, using biology's own manufacturing stack rather than trying to invent a mechanical one from scratch. That's a slower and messier path than the sci-fi version, but it's the one that actually runs on physics we think we understand.. hope it makes sense!
> The self-replication and division you're picturing comes from that biological machinery copying and dividing
I think it will be a missed opportunity to not foresee manufacturing applications of "biological machinery". Enzymes have long been used in manufacturing, especially in chemistry. For the first time, ribosomes and membranes could be used as well.
Hi, thanks, and very cool work (assuming it eventually holds up in peer review)!
A few things that confused me while trying to read the paper:
- There's two different methods of cell division mentioned -- mechanical extrusion and the autonomous, protein-driven division. Most of the results (e.g. the five generations) focus on the mechanically driven one, while the autonomous one is more "lifelike". Does the autonomous division have a higher failure rate, or can you get the same results with it as well?
- It's mentioned that the bottleneck for survival of many generations is ribozomes degrading, but also that ribozomes are supplied from the outside. Do the degraded ribozomes actively harm the cell? Or is there some other reason why they cannot be replenished?
- You say that after 5 generations, only 30% of the cells have the correct genome, and it's presented like a problem -- but 30% of 2^5 is more than 10, so this sounds like more than enough for continued survival. Is there something missing in this train of thought? Perhaps other failures that can kill the cell?
And some questions about the implications:
- Do you think that the genome you use is already close to minimal? AFAIK a lot of the minimal organisms found in the wild are parasites of some sort, getting most of their complex molecules from the outside, which is a similar spirit to this (a rich medium and the cell "just" self-duplicating). If the multiple plasmids are causing trouble (per the previous point), would it make sense to try and get rid of some of them?
- Are those minimal genes somehow interpretable -- as in "you need functions X, Y, and Z and cannot avoid them by using a better medium"?
- Do you think this is a plausible stage of very early life?
The current model, of a cell that cannot live on its own and cannot evolve (being too far from "edge of chaos") is what will be most useful for bio-engineering. Yes, we need the mechanism for creating cells, and the newfound division for a minimum viable cell is paramount. But, we also need for ways to control its reproduction, be it as to die out on its own after few generations due to degraded protein build-up, or (in the best case scenario) due to some other built in mechanism. Otherwise, expect (at least) some amount of scaremongering, about playing fast and loose with things that may get out of hand. The best thing is to have this kind of cell template that could somehow be augmented with whatever additional plug-in functionality (useful for us, case by case) and then get it produced in the needed quantities and not more. The research direction that makes sense is for ways to add such "mission specific" functions to this synthetic cell and ways to create the first generation as efficiently as possible, at large scale. That's it.
Is it edible? If not, why not?
What are the implications for nanobots with this kind of innovation: Artificial cell division recreating itself in 2? Is this a future endeavor of this tech?
Great question - what we built isn't a "nanobot" in the Drexlerian sense (a tiny engineered machine assembling things atom by atom). It's a cell, it runs onn molecular machines like ribosomes, membranes, and enzymes. The self-replication and division you're picturing comes from that biological machinery copying and dividing, not from a mechanical device building a second copy of itself. So on your specific question: division is very much a core goal of the synthetic cell field, and getting a built-from-defined-parts system to grow and divide reliably on its own is one of the big open problems ahead of us. What SpudCell demonstrates is assembling something cell-like from well-defined components. Where this does connect to the "programmable matter" dream is that if you can engineer a cell from the ground up, you can in principle program what it makes and does, using biology's own manufacturing stack rather than trying to invent a mechanical one from scratch. That's a slower and messier path than the sci-fi version, but it's the one that actually runs on physics we think we understand.. hope it makes sense!
> The self-replication and division you're picturing comes from that biological machinery copying and dividing
I think it will be a missed opportunity to not foresee manufacturing applications of "biological machinery". Enzymes have long been used in manufacturing, especially in chemistry. For the first time, ribosomes and membranes could be used as well.