11 ms·

I was astounded when I read Matt Ridley's book "Genome" at just how mechanical cellular life is. The nucleus, loaded with DNA, is functioning like a ready-progr

by kitd 2y ago

I was astounded when I read Matt Ridley's book "Genome" at just how mechanical cellular life is. The nucleus, loaded with DNA, is functioning like a ready-programmed CNC machine, or robot, or other programmable piece of hardware that interacts with the physical or chemical world.

roywiggins 2y ago
I know it's lame to link to video, but I saw this pair of videos recently which I thought made an interesting counterargument to the cell-as-machine idea: https://www.youtube.com/watch?v=zpIqQ0pGs1E https://www.youtube.com/watch?v=zpIqQ0pGs1E https://www.youtube.com/watch?v=jPhvic-eqbc https://www.youtube.com/watch?v=jPhvic-eqbc Referenced paper: https://philpapers.org/archive/NICITC.pdf https://philpapers.org/archive/NICITC.pdf The author's notes on genetics: https://www.subanima.org/mendel/ https://www.subanima.org/mendel/
- quonn 2y ago
  It‘s an evolved machine, meaning that the parts are not designed to be easily understandable or maintainable or to develop or even necessarily particularly easy to evolve. But the videos are good, thank you.
  - roywiggins 2y ago
    the thing about cells is that even labeling bits of them as discrete "parts" seems like it might be misleading, eg this from the linked paper: > recent research on the cellular architecture demands that we look more carefully at what we have previously assumed were well-defined structures and reconsider them as stabilized processes. Because processes are temporally extended, it follows that they can only be understood by giving time due consideration... The structure of a machine, after all, can be grasped in abstraction from time (as it is not constantly changing), whereas the structure of, say, a whirlpool or a stream cannot. This explains why, when we have started using techniques that allow us to examine the cellular architecture in real time, we have found that many of the cell’s compartments and organelles are not fixed machineries at all, but stable macromolecular fluxes.
    - quonn 2y ago
      Okay, „parts“ for me was just a word to refer to the machine, it is also okay if it is only a single part. It still remains a machine in the sense that it performs a task it should perform and does so using the same approach across all instances. That the „parts“ do not only perform a specific function is not really surprising, because the machine does not need to be comprehensible or understandable. I would expect single-purpose parts only if that helps the function or if it helps evolvability (in the sense of not creating dead ends).
      - roywiggins 2y ago
        The paper covers this also. Cells don't behave predictably: > The variable flickering of transcriptional activity in different cells is one of the major causes of heterogeneity in isogenic populations. But where exactly does this cell-to-cell variability in transcriptional activity come from? The answer becomes apparent when we remember that gene expression is a molecular process, and like all molecular processes, it is inherently stochastic, given that it takes place in an environment that is subject to the chaotic dynamics of Brownian motion. Each step in the process relies on fortuitous encounters between molecules that are randomly moving about as a consequence of thermal agitation. Evidently, these molecules must be at the right place and at the right time—not to mention in the right vibrational state—for them to be able to participate in the appropriate reactions. The unpredictability of the whole process is further amplified by the fact that the participating molecules in each step are present in the cell in very low copy-numbers, as this decreases the chances of successful interactions between them... > as research into the non-genetic heterogeneity of cells continues, evidence for the biological importance of this phenomenon is mounting ever-rapidly. We now know that non-genetic heterogeneity plays key roles in both microbial and eukaryotic cells, in embryonic development, and in evolution. For one thing, it is a crucial generator of phenotypic diversity, which enables cell populations to adapt rapidly to changing environmental conditions. It does so by permitting the implementation of probabilistic diversification strategies within a population, such as bet-hedging and divisions of labour, which can confer considerable fitness advantages... > One very important theoretical implication of the probabilistic nature of cellular behaviour and the observed heterogeneity of cell populations is that, quite literally, every cell (in an organism and elsewhere) is a unique entity. No two cells are identical, given that no two cells respond to a stimulus in the exact same way—even if they are genetically the same.
- wvbdmp 2y ago
  I fully believe the biological details presented in the videos, sure, but there’s a certain clickbaitiness about them that leaves a bad taste. The one about genetics seems to force conclusions that are palatable to modern sensibilities. How does Mendel accidentally fudging his results using eugenics prohibit “talk of good genes and bad genes”? There clearly are good and bad genes, this is obvious to anyone. It’s practically the whole point of the olympics to showcase people who have the best genetic prerequisites for their discipline. None of the technical minutiae of inheritance prevent us from breeding better sprinters. In fact we’ve done it with several animals. Whether or not any of this is ethical is not the field of biology’s concern. The video about cells has a similar problem, where it acts like it wants to invalidate higher levels of abstraction because reality is more complicated. Of course biology doesn’t operate like a designed and manufactured apparatus, but omitting complexities irrelevant to the question at hand is the entire point of making diagrams. Does the thing turn methane into methanol? Yes, it does. There is no problem here. These could be great educational videos if they weren’t strawmanning so hard. This is especially obvious in his carefully designed definition of a machine. Biology is just stupidly stochastic, but this stuff is akin to “nooooo, systems don’t »prefer« low energy states, they’re not conscious qq”. Like, okay, use a different verb if that makes you happy??
- FrustratedMonky 2y ago
  Had to stop watching those videos after so many errors. Saying Gene's aren't machines, because Machines are rigid bodies?? That is wrong, that seems to be the crux of his arguments, that gene's flex, and can become different shapes. Hello, machines do this.
  - roywiggins 2y ago
    Do you know any machines where single constituent parts can have hundreds of functions and will switch between them at random?
    - FrustratedMonky 2y ago
      Do you know any Proteins that do that? The examples given were for a 'few' modalities. Not thousands. My fishing rod is flexible. And I can cast over hand, or underhand, or side arm it under some trees.
      - roywiggins 2y ago
        I mean, the video says that inherently disordered proteins make up a quarter of mammalian proteins, they don't even have a small set of conformations that they switch between. They're just flopping around all the time.
        FrustratedMonky 2y ago
        Sure. But to say something is floppy, and serves multiple functions, means it is not a machine, is a stretch. They made the argument multiple times about machines not flexing, and that is just no where in the definition of a machine.
        roywiggins 2y ago
        I think the video does dwell on that a bit too much. The paper he's pulling from defines machines like this: > First, machines can be described in terms of a list of parts and a blueprint indicating how those parts fit together, meaning that someone who has never seen a particular kind of machine should in principle be able to assemble any number of copies—each virtually identical in appearance and performance—provided they can consult the machine’s design specifications. Second, as machines are designed to perform highly specific functions, their operation is tightly constrained, which is why it is possible to predict and control their behaviour. Third, machines are highly efficient in what they do because they always follow the exact same sequence of steps in every cycle of their operation. And fourth, the operation of machines is not continuous; their functioning can be interrupted and their parts examined without thereby jeopardizing their structural integrity. And argues that cells look more like this: > according to this alternative view, the cellular architecture is regarded as a fluid, self-organizing process; protein complexes are considered to be transient, pleomorphic ensembles; intracellular transport is deemed to result from the harnessing of Brownian motion; and cellular behaviour is viewed as a probabilistic affair, subject to constant stochastic fluctuations. And > Viewing the cell as a machine allows us to think of its organization in terms of modular, solid-state circuits that can be approached reductionistically, and it also gives us the confidence to expect that when we eventually work out how all of the cell’s parts fit together, we will be able to completely predict its behaviour. If, on the other hand, we view the cell as a highly integrated, self-organizing, fluid system composed of densely interconnected processes ever-subject to stochastic fluctuations, we no longer have reasons to suppose that achieving such epistemic goals is even possible, let alone feasible. The stark contrast between these two outlooks is exemplified by their strikingly different ways of understanding causation in the cell (Bizzarri et al., 2019), and it serves to explain why some researchers find it easier than others to obtain funding and publish their work. https://philpapers.org/archive/NICITC.pdf https://philpapers.org/archive/NICITC.pdf
api 2y ago
These are all very rough analogies though. Everything interacts with everything. Proteins go back and 'flag' DNA with epigenetic flags, control how DNA is transcribed, control how other proteins are folded, etc. Sometimes cells even edit their own DNA, and not just during sexual reproduction. Then there's viruses, virus-like patterns within genomes, etc. Computational or mechanical analogies are not totally wrong but they're dangerously over-reductive.
- exe34 2y ago
  > but they're dangerously over-reductive I never used to understand this position, until I saw right wing snowflakes getting triggered over a woman looking too manly at the Olympics. They confidently explained XX and XY to whomever would read their little meltdowns, and even rode back on their usual line that genitals determine gender - suddenly they care about hormone levels. So I'm having to come around to the idea that over-reductive can be a real thing. Although I'm not sure that the sort of dumdum that dive off the deep end with these things would do any better.
  - api 2y ago
    It's particularly dangerous with biology. A biology professor of mine put it this way: pretend you are reverse engineering alien technology. The stuff you are trying to understand was not designed by human minds. It was designed by evolution over billions of years, literally an alien intelligence that doesn't "think" anything like you do. A big difference between biology and human engineering is that humans like one-part-one-function and linear chains of cause and effect. Biology isn't like that at all. It's an analog causal matrix where everything affects everything else to varying degrees and most parts have multiple simultaneous functions.
    - medstrom 2y ago
      Bit like a codebase where different parts slowly accrete extra features that presume the presence of the other parts, so that you eventually have to read the whole to follow anything.
bitwize 2y ago
I was explaining mRNA vaccines to my dad, and I found myself describing the cell's ribosomes as reading RNA and 3D-printing proteins based on the instructions in the RNA. Not the best analogy, but I figure not a terrible one either.

by kitd 2y ago

roywiggins 2y ago

I know it's lame to link to video, but I saw this pair of videos recently which I thought made an interesting counterargument to the cell-as-machine idea: https://www.youtube.com/watch?v=zpIqQ0pGs1E https://www.youtube.com/watch?v=zpIqQ0pGs1E https://www.youtube.com/watch?v=jPhvic-eqbc https://www.youtube.com/watch?v=jPhvic-eqbc Referenced paper: https://philpapers.org/archive/NICITC.pdf https://philpapers.org/archive/NICITC.pdf The author's notes on genetics: https://www.subanima.org/mendel/ https://www.subanima.org/mendel/

quonn 2y ago
It‘s an evolved machine, meaning that the parts are not designed to be easily understandable or maintainable or to develop or even necessarily particularly easy to evolve. But the videos are good, thank you.
- roywiggins 2y ago
  the thing about cells is that even labeling bits of them as discrete "parts" seems like it might be misleading, eg this from the linked paper: > recent research on the cellular architecture demands that we look more carefully at what we have previously assumed were well-defined structures and reconsider them as stabilized processes. Because processes are temporally extended, it follows that they can only be understood by giving time due consideration... The structure of a machine, after all, can be grasped in abstraction from time (as it is not constantly changing), whereas the structure of, say, a whirlpool or a stream cannot. This explains why, when we have started using techniques that allow us to examine the cellular architecture in real time, we have found that many of the cell’s compartments and organelles are not fixed machineries at all, but stable macromolecular fluxes.
  - quonn 2y ago
    Okay, „parts“ for me was just a word to refer to the machine, it is also okay if it is only a single part. It still remains a machine in the sense that it performs a task it should perform and does so using the same approach across all instances. That the „parts“ do not only perform a specific function is not really surprising, because the machine does not need to be comprehensible or understandable. I would expect single-purpose parts only if that helps the function or if it helps evolvability (in the sense of not creating dead ends).
    - roywiggins 2y ago
      The paper covers this also. Cells don't behave predictably: > The variable flickering of transcriptional activity in different cells is one of the major causes of heterogeneity in isogenic populations. But where exactly does this cell-to-cell variability in transcriptional activity come from? The answer becomes apparent when we remember that gene expression is a molecular process, and like all molecular processes, it is inherently stochastic, given that it takes place in an environment that is subject to the chaotic dynamics of Brownian motion. Each step in the process relies on fortuitous encounters between molecules that are randomly moving about as a consequence of thermal agitation. Evidently, these molecules must be at the right place and at the right time—not to mention in the right vibrational state—for them to be able to participate in the appropriate reactions. The unpredictability of the whole process is further amplified by the fact that the participating molecules in each step are present in the cell in very low copy-numbers, as this decreases the chances of successful interactions between them... > as research into the non-genetic heterogeneity of cells continues, evidence for the biological importance of this phenomenon is mounting ever-rapidly. We now know that non-genetic heterogeneity plays key roles in both microbial and eukaryotic cells, in embryonic development, and in evolution. For one thing, it is a crucial generator of phenotypic diversity, which enables cell populations to adapt rapidly to changing environmental conditions. It does so by permitting the implementation of probabilistic diversification strategies within a population, such as bet-hedging and divisions of labour, which can confer considerable fitness advantages... > One very important theoretical implication of the probabilistic nature of cellular behaviour and the observed heterogeneity of cell populations is that, quite literally, every cell (in an organism and elsewhere) is a unique entity. No two cells are identical, given that no two cells respond to a stimulus in the exact same way—even if they are genetically the same.
wvbdmp 2y ago
I fully believe the biological details presented in the videos, sure, but there’s a certain clickbaitiness about them that leaves a bad taste. The one about genetics seems to force conclusions that are palatable to modern sensibilities. How does Mendel accidentally fudging his results using eugenics prohibit “talk of good genes and bad genes”? There clearly are good and bad genes, this is obvious to anyone. It’s practically the whole point of the olympics to showcase people who have the best genetic prerequisites for their discipline. None of the technical minutiae of inheritance prevent us from breeding better sprinters. In fact we’ve done it with several animals. Whether or not any of this is ethical is not the field of biology’s concern. The video about cells has a similar problem, where it acts like it wants to invalidate higher levels of abstraction because reality is more complicated. Of course biology doesn’t operate like a designed and manufactured apparatus, but omitting complexities irrelevant to the question at hand is the entire point of making diagrams. Does the thing turn methane into methanol? Yes, it does. There is no problem here. These could be great educational videos if they weren’t strawmanning so hard. This is especially obvious in his carefully designed definition of a machine. Biology is just stupidly stochastic, but this stuff is akin to “nooooo, systems don’t »prefer« low energy states, they’re not conscious qq”. Like, okay, use a different verb if that makes you happy??
FrustratedMonky 2y ago
Had to stop watching those videos after so many errors. Saying Gene's aren't machines, because Machines are rigid bodies?? That is wrong, that seems to be the crux of his arguments, that gene's flex, and can become different shapes. Hello, machines do this.
- roywiggins 2y ago
  Do you know any machines where single constituent parts can have hundreds of functions and will switch between them at random?
  - FrustratedMonky 2y ago
    Do you know any Proteins that do that? The examples given were for a 'few' modalities. Not thousands. My fishing rod is flexible. And I can cast over hand, or underhand, or side arm it under some trees.
    - roywiggins 2y ago
      I mean, the video says that inherently disordered proteins make up a quarter of mammalian proteins, they don't even have a small set of conformations that they switch between. They're just flopping around all the time.
      - FrustratedMonky 2y ago
        Sure. But to say something is floppy, and serves multiple functions, means it is not a machine, is a stretch. They made the argument multiple times about machines not flexing, and that is just no where in the definition of a machine.
        roywiggins 2y ago
        I think the video does dwell on that a bit too much. The paper he's pulling from defines machines like this: > First, machines can be described in terms of a list of parts and a blueprint indicating how those parts fit together, meaning that someone who has never seen a particular kind of machine should in principle be able to assemble any number of copies—each virtually identical in appearance and performance—provided they can consult the machine’s design specifications. Second, as machines are designed to perform highly specific functions, their operation is tightly constrained, which is why it is possible to predict and control their behaviour. Third, machines are highly efficient in what they do because they always follow the exact same sequence of steps in every cycle of their operation. And fourth, the operation of machines is not continuous; their functioning can be interrupted and their parts examined without thereby jeopardizing their structural integrity. And argues that cells look more like this: > according to this alternative view, the cellular architecture is regarded as a fluid, self-organizing process; protein complexes are considered to be transient, pleomorphic ensembles; intracellular transport is deemed to result from the harnessing of Brownian motion; and cellular behaviour is viewed as a probabilistic affair, subject to constant stochastic fluctuations. And > Viewing the cell as a machine allows us to think of its organization in terms of modular, solid-state circuits that can be approached reductionistically, and it also gives us the confidence to expect that when we eventually work out how all of the cell’s parts fit together, we will be able to completely predict its behaviour. If, on the other hand, we view the cell as a highly integrated, self-organizing, fluid system composed of densely interconnected processes ever-subject to stochastic fluctuations, we no longer have reasons to suppose that achieving such epistemic goals is even possible, let alone feasible. The stark contrast between these two outlooks is exemplified by their strikingly different ways of understanding causation in the cell (Bizzarri et al., 2019), and it serves to explain why some researchers find it easier than others to obtain funding and publish their work. https://philpapers.org/archive/NICITC.pdf https://philpapers.org/archive/NICITC.pdf

api 2y ago

These are all very rough analogies though. Everything interacts with everything. Proteins go back and 'flag' DNA with epigenetic flags, control how DNA is transcribed, control how other proteins are folded, etc. Sometimes cells even edit their own DNA, and not just during sexual reproduction. Then there's viruses, virus-like patterns within genomes, etc. Computational or mechanical analogies are not totally wrong but they're dangerously over-reductive.

exe34 2y ago
> but they're dangerously over-reductive I never used to understand this position, until I saw right wing snowflakes getting triggered over a woman looking too manly at the Olympics. They confidently explained XX and XY to whomever would read their little meltdowns, and even rode back on their usual line that genitals determine gender - suddenly they care about hormone levels. So I'm having to come around to the idea that over-reductive can be a real thing. Although I'm not sure that the sort of dumdum that dive off the deep end with these things would do any better.
- api 2y ago
  It's particularly dangerous with biology. A biology professor of mine put it this way: pretend you are reverse engineering alien technology. The stuff you are trying to understand was not designed by human minds. It was designed by evolution over billions of years, literally an alien intelligence that doesn't "think" anything like you do. A big difference between biology and human engineering is that humans like one-part-one-function and linear chains of cause and effect. Biology isn't like that at all. It's an analog causal matrix where everything affects everything else to varying degrees and most parts have multiple simultaneous functions.
  - medstrom 2y ago
    Bit like a codebase where different parts slowly accrete extra features that presume the presence of the other parts, so that you eventually have to read the whole to follow anything.

bitwize 2y ago

I was explaining mRNA vaccines to my dad, and I found myself describing the cell's ribosomes as reading RNA and 3D-printing proteins based on the instructions in the RNA. Not the best analogy, but I figure not a terrible one either.