The article is about bottom-up efforts in building a synthetic cell (i.e. assembled from molecular building blocks) as opposed to the top-down M. m. JCVI-syn1.0 you’re linking, which originates from a pared-down synthetised genome transplanted into a wild type Mycoplasma host without DNA.
M95D•4mo ago
There is no bottom-up building of a living cell. All those building blocks you speak about come from DNA and genes (edited or not) can only come from existing living cells, which makes any "new" cell not at all different than editing-out redundant DNA from an existing species.
flobosg•4mo ago
> There is no bottom-up building of a living cell.
There is currently no bottom-up building. The article proposes some potential strategies.
> All those building blocks you speak about come from DNA and genes (edited or not) can only come from existing living cells
Many of the macromolecules found in a cell can be generated abiotically. In fact, that is how the initial M. laboratorium genome cassettes were built. No living system was involved in the synthesis of their DNA (cassette recombination was done in yeast, though)[1]:
> Synthetic genome assembly strategy. The designed cassettes were generally 1080 bp with 80-bp overlaps to adjacent cassettes (11). They were all produced by assembly of chemically synthesized oligonucleotides by Blue Heron (Bothell, Washington)
> The article states otherwise and proposes some potential strategies.
The article has very low scientific value. It doesn't say anything new,which is why I provided a better article on the subject, easier to understand for most readers of this page.
> Many of the macromolecules found in a cell can be generated abiotically.
So? The result is the same and it doesn't make the cell any different than one with edited DNA. Sure, you can replace some codons with more stable equivalents (more G/C), leave out some introns, and even add a watermark, but the information encoded is the same, the function is the same, the protein is the same, the metabolic pathway is the same, etc. If looks like a duck, moves like a duck, then ...
Why go through all the trouble to get basically the same result? Contrary to their claims, it won't really help understanding how the cell works. Not adding a gene to a custom genome vs. cutting out a gene from an existing genome leads to the same understanding of that gene's function.
flobosg•4mo ago
> The article has very low scientific value.
The article is a perspective. According to Nature’s guidelines:
> Perspective articles are intended to provide a forum for authors to discuss models and ideas from a personal viewpoint. They are more forward looking and/or speculative than Reviews and may take a narrower field of view. They may be opinionated but should remain balanced and are intended to stimulate discussion and new experimental approaches.
> which is why I provided a better article on the subject
They are not mutually exclusive. Readers will profit from both, as they present the topic from different perspectives.
> So?
It directly contradicts your previous claim, namely: “All those building blocks (…) can only come from existing living cells”
> The result is the same and it doesn't make the cell any different than one with edited DNA.
Exactly. Not sure why you’re focusing on gene editing, though. The perspective doesn’t address that point at all.
> Why go through all the trouble (…)?
The article lists several reasons, …
> Contrary to their claims, it won't really help understanding how the cell works.
…which could be more difficult to achieve using existing cellular machineries, such as enabling non-canonical chemistries, alternate macromolecular architectures, and allow for more control and fine-tuning, given the minimalism that these systems could reach. “Understanding how the cell works” is only a small fraction of the potential applications presented in the perspective.
M95D•4mo ago
> Not sure why you’re focusing on gene editing, though. The perspective doesn’t address that point at all.
It's not at all useful to focus on "building blocks" directly (I really don't like that term, but let's use it anyway). With every cell division, each one gets half the quantity of initial buiding blocks the cell was initially constructed with. If DNA can't direct the creation of new buiding blocks, in max 2 generations there won't be enough for a new cell division. So, you see, it doesn't matter what building blocks (except DNA) the initial cell started with, synthetic or from an existing cell. In just a few generations the initial material is all gone.
In a living cell, all building blocks (cell structural components, functional components, metabolism, etc.) are derived directly or indirectly from DNA. DNA may directly encode ribosomal RNA (a functional component), or a cytoskeleton protein (a structural component), or a series of enzymes that process non-protein building-blocks [1]. So, in an artificial cell, the focus is always genes. The article may not focus on gene editing, but that's the 99.9% of the work - making DNA that makes building blocks.
It is very difficult to create new proteins that work for some purpose other than enzymes (current examples: synthetic antigens (vaccines), enzyme inhibitors (Imatinib), receptor blockers, receptor activators). Remember folding@home? It's an order of magnitude harder than that to create new enzymes . I can't even give you an example. And it's an order of magnitude harder still to create DNA/genes that makes enzymes. It's literally creating a molecular folding@home program [2] using folding@home.
It's not realistically possible today to create complex cellular machines such as the DNA replication enzymes [3], which are the most important parts of a living cell. There's absolutely no way to create a completely new synthetic cell without having those machines. And then, remeber folding@home? We don't need the machines - we need the DNA that makes the machines that fold the machines (no, it's not a typo, it's that complicated).
We can, at best, convince bacteria to syntesize new drugs for us. No need for a new synthetic organism for that. E.coli can do it just fine.
As reaserch only, entirely new, very simple cell components can be created, probably even convincing some host cell to make them for itself, but we're very, very, very far from bottom-up building a living cell. Cold fusion and interstellar travel are closer than that.
When you read an article like that, think "money", as in "grant money" and "investors", not "future tech".
> It is very difficult to create new proteins that work for some purpose other than enzymes (antigens, receptor blockers, receptor activators).
It’s not that difficult. Most of the work on de novo protein design has been related to protein or ligand binders and receptors, and successful examples are published frequently. But yes, enzyme design is much more challenging.
> There's absolutely no way to create a completely new synthetic cell without having those machines. (…) but we're very, very, very far from bottom-up building a living cell.
Hence the perspective.
M95D•3mo ago
> Hence the perspective.
I can see that. But why? Nobody writes a perspective on teleportation and anti-gravity generators...
M95D•4mo ago
https://en.wikipedia.org/wiki/Mycoplasma_laboratorium
flobosg•4mo ago
M95D•4mo ago
flobosg•4mo ago
There is currently no bottom-up building. The article proposes some potential strategies.
> All those building blocks you speak about come from DNA and genes (edited or not) can only come from existing living cells
Many of the macromolecules found in a cell can be generated abiotically. In fact, that is how the initial M. laboratorium genome cassettes were built. No living system was involved in the synthesis of their DNA (cassette recombination was done in yeast, though)[1]:
> Synthetic genome assembly strategy. The designed cassettes were generally 1080 bp with 80-bp overlaps to adjacent cassettes (11). They were all produced by assembly of chemically synthesized oligonucleotides by Blue Heron (Bothell, Washington)
[1]: https://www.science.org/doi/10.1126/science.1190719
M95D•4mo ago
The article has very low scientific value. It doesn't say anything new,which is why I provided a better article on the subject, easier to understand for most readers of this page.
> Many of the macromolecules found in a cell can be generated abiotically.
So? The result is the same and it doesn't make the cell any different than one with edited DNA. Sure, you can replace some codons with more stable equivalents (more G/C), leave out some introns, and even add a watermark, but the information encoded is the same, the function is the same, the protein is the same, the metabolic pathway is the same, etc. If looks like a duck, moves like a duck, then ...
Why go through all the trouble to get basically the same result? Contrary to their claims, it won't really help understanding how the cell works. Not adding a gene to a custom genome vs. cutting out a gene from an existing genome leads to the same understanding of that gene's function.
flobosg•4mo ago
The article is a perspective. According to Nature’s guidelines:
> Perspective articles are intended to provide a forum for authors to discuss models and ideas from a personal viewpoint. They are more forward looking and/or speculative than Reviews and may take a narrower field of view. They may be opinionated but should remain balanced and are intended to stimulate discussion and new experimental approaches.
> which is why I provided a better article on the subject
They are not mutually exclusive. Readers will profit from both, as they present the topic from different perspectives.
> So?
It directly contradicts your previous claim, namely: “All those building blocks (…) can only come from existing living cells”
> The result is the same and it doesn't make the cell any different than one with edited DNA.
Exactly. Not sure why you’re focusing on gene editing, though. The perspective doesn’t address that point at all.
> Why go through all the trouble (…)?
The article lists several reasons, …
> Contrary to their claims, it won't really help understanding how the cell works.
…which could be more difficult to achieve using existing cellular machineries, such as enabling non-canonical chemistries, alternate macromolecular architectures, and allow for more control and fine-tuning, given the minimalism that these systems could reach. “Understanding how the cell works” is only a small fraction of the potential applications presented in the perspective.
M95D•4mo ago
It's not at all useful to focus on "building blocks" directly (I really don't like that term, but let's use it anyway). With every cell division, each one gets half the quantity of initial buiding blocks the cell was initially constructed with. If DNA can't direct the creation of new buiding blocks, in max 2 generations there won't be enough for a new cell division. So, you see, it doesn't matter what building blocks (except DNA) the initial cell started with, synthetic or from an existing cell. In just a few generations the initial material is all gone.
In a living cell, all building blocks (cell structural components, functional components, metabolism, etc.) are derived directly or indirectly from DNA. DNA may directly encode ribosomal RNA (a functional component), or a cytoskeleton protein (a structural component), or a series of enzymes that process non-protein building-blocks [1]. So, in an artificial cell, the focus is always genes. The article may not focus on gene editing, but that's the 99.9% of the work - making DNA that makes building blocks.
> enabling non-canonical chemistries, alternate macromolecular architectures
Ah, this is the point you were trying to make!
It is very difficult to create new proteins that work for some purpose other than enzymes (current examples: synthetic antigens (vaccines), enzyme inhibitors (Imatinib), receptor blockers, receptor activators). Remember folding@home? It's an order of magnitude harder than that to create new enzymes . I can't even give you an example. And it's an order of magnitude harder still to create DNA/genes that makes enzymes. It's literally creating a molecular folding@home program [2] using folding@home.
It's not realistically possible today to create complex cellular machines such as the DNA replication enzymes [3], which are the most important parts of a living cell. There's absolutely no way to create a completely new synthetic cell without having those machines. And then, remeber folding@home? We don't need the machines - we need the DNA that makes the machines that fold the machines (no, it's not a typo, it's that complicated).
We can, at best, convince bacteria to syntesize new drugs for us. No need for a new synthetic organism for that. E.coli can do it just fine.
As reaserch only, entirely new, very simple cell components can be created, probably even convincing some host cell to make them for itself, but we're very, very, very far from bottom-up building a living cell. Cold fusion and interstellar travel are closer than that.
When you read an article like that, think "money", as in "grant money" and "investors", not "future tech".
[1] https://en.wikipedia.org/wiki/Fatty_acid_synthesis
[2] https://en.wikipedia.org/wiki/Chaperone_(protein)
[3] https://en.wikipedia.org/wiki/DNA_replication#DNA_replicatio... (you should read a bit about each one)
flobosg•4mo ago
It’s not that difficult. Most of the work on de novo protein design has been related to protein or ligand binders and receptors, and successful examples are published frequently. But yes, enzyme design is much more challenging.
> There's absolutely no way to create a completely new synthetic cell without having those machines. (…) but we're very, very, very far from bottom-up building a living cell.
Hence the perspective.
M95D•3mo ago
I can see that. But why? Nobody writes a perspective on teleportation and anti-gravity generators...
It's for the money.