5 ms·

Can a biologist fix a radio? What I learned while studying apoptosis (2002) [pdf]

77 points by bilsbie 2y ago

dang 2y ago
Related: Can a biologist fix a radio? Or, what I learned while studying apoptosis (2002) - https://news.ycombinator.com/item?id=31697757 https://news.ycombinator.com/item?id=31697757 - June 2022 (21 comments) Can a biologist fix a radio?–Or, what I learned while studying apoptosis (2002) [pdf] - https://news.ycombinator.com/item?id=30120457 https://news.ycombinator.com/item?id=30120457 - Jan 2022 (18 comments)
pvaldes 2y ago
If is unemployed, you can bet that can and will do it.
Micand 2y ago
As was flagged in the other discussions, see Could a neuroscientist understand a microprocessor: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005268 https://journals.plos.org/ploscompbiol/article?id=10.1371/jo... Or a recap from The Atlantic: https://www.theatlantic.com/science/archive/2016/06/can-neuroscience-understand-donkey-kong-let-alone-a-brain/485177/ https://www.theatlantic.com/science/archive/2016/06/can-neur... I saw a wonderful recording of a talk the authors gave a few years ago (which I regrettably can't find now), and it was amongst the most eye-opening talks I've ever seen.
- bee_rider 2y ago
  It is sort of interesting… I think we will all admit that brains are more complex than computer chips. But I still wonder if there’s some general underlying principle that makes brains more reasonable to study in this fashion than computer chips. For example, they talk about destroying one transistor, observing that the thing can’t play Donkey-Kong anymore, and concluding that that is the DK transistor. But computer chips are designed to have incredibly long chains of dependencies where each specific transistor does exactly the right thing, every time. For neurons, it isn’t so specific, right? They all might fire, depending on the timing, and whether or not they are… I don’t know biology, charged or whatever. The whole system works under the assumption that many complements will mis-fire or be duds are any moment. It seems (to me at least) more reasonable, to come to the conclusion that the DK neuron is really a DK neuron, if removing it causes an un-recoverable DK related failure… because the whole system is based around handling failures! It is somehow special that something can break it.
  - rcxdude 2y ago
    Yes, there's more of a degree of redundancy in brains than microprocessors, but the 'lesion' approach tends to involve affecting more than just one neuron. The main point of that section is that you've got to be careful about what you define as a 'function'. In the processor case, if you defined function in terms of a register or instruction working properly, then this approach could actually give you a pretty good map. But if you've defined it as whether a particular game runs, it doesn't give you a good map at all, because most games exercise most functions of the microprocessor, and so which small parts aren't important to that particular game is only incidental. With brains the main thing is the underlying functions are not really known, so you need to approach with care.
    - bonoboTP 2y ago
      I used to have the impression that the brain is more "mixed up" than it really is. It's quite hard to get the right impression as a layman. Experts push too hard towards the extreme that makes us think that everything is involved in everything and it's all thoroughly uniformly mixed, advising against believing those old naive brain charts etc. But really, certain functions are remarkably well localized. This kind of overcorrection is quite common if one often reads HN-like "well actually"-content, which is supposed to supplement a common perception with a small caveat. Beware of internalizing just the caveat and forgetting the main thrust.
  - jerf 2y ago
    "For neurons, it isn’t so specific, right? They all might fire, depending on the timing, and whether or not they are… I don’t know biology, charged or whatever." So we assume. And with some good reason, including both the studies done over the decades, and the fact that we've built systems based on this architecture that match this concept. However, it is important to observe that this characteristic is still in the metaphorical spotlight. It is a thing that we can discover. If, in fact, there was One Blessed Neuron that contained the most vital aspect of some critical concept in someone's brain, we currently have zero capability to discover it, zero ability to characterize it, and effectively zero ability to manipulate that neuron directly in some experimental fashion once identified. Therefore, we should be fairly suspicious of the claim that we've eliminated this as even being a possibility. I expect it is unlikely that there is a such thing as the One Blessed Neuron, even so, but there are a large number of other hypothetical organizations that could exist beyond "an amorphous neural net with nothing really located anywhere", and we have good evidence for that as well; the "regions" of the brain, the fact we can visibly see physically different organizations of neurons in certain regions and associate them with certain tasks. I would not even dream of trying to guarantee that there is no structure lying in between the gross differences we already know about and the hypothetical undifferentiated neural mass, the structures in those complexity voids between what we can currently see. We again have a lot of inductive reasons to believe that there is likely more structure there we do not even have a clue exists, on the grounds that every time we get a closer look at something for the first time ever, it is rarely only and exactly what we expected. It's such a notable outcome that it gets called out specifically when it happens, precisely because it's rare.
- stochastician 2y ago
  Author of that paper here -- What an incredibly nice comment to wake up to at 3am, thank you! This paper made me quit neuro and switch to systems that are easier to model (small molecules) which it turns out are still annoyingly difficult!
fastaguy88 2y ago
I am always puzzled when biologists make analogies between living systems (or sub-systems) and human-designed devices (even complex devices). Human designed devices have an essential property that biological systems do not -- they were designed. While radios may seem complex, they are built from a relatively small number of component types with very well understood behaviors and typically limited numbers of interactions. Biological systems have no such constraints -- they were not designed, there can be many different ways to do the same thing (in the same cell), there are at least thousands, if not hundreds of thousands of different components, many of which have lots and lots of interactions. Considering how messy the systems are, it is quite remarkable that genetics and biochemistry discovered the basis of heredity (or at least some of it), the genetic code, hundreds of signaling pathways, etc etc. But there is no missing language, because there was no design that used that language.
- doe_eyes 2y ago
  Sure, but... how often do we object when fellow techies make analogies between just about anything and their field of expertise? We feel that our knowledge makes us quite qualified to explain the economy, to chime in on microbiology, and so on. It's really pretty universal.
- minifridge 2y ago
  Biological systems have also designs that emerged through evolution. Although the complexity may seem at different scales, the main difference is the measurements you can do. Both biological and electrical circuits are dynamic systems that have designs that gives them emergent functional properties. As the article describes imagine having the list of radio components instead only instead of their topology (wiring diagram). The problem of figuring out how a radio works with this information, if youbknow little about their design, becomes quite similar with how figuring out how a biological system works. The absence of a design diagram and our inability to measure components at the molecular level without disturbing the state of a system is the main reason bilogical systems are so challenging to understand.
  - fastaguy88 2y ago
svilen_dobrev 2y ago
the two schematical views reminded me of a) the dualisms in Pirsig, and b) also of another similar one: two views of what-a-cat-consists-of - one according to the granny owner, and another according to the surgeon - but cannot remember which book was that from. Anyone?
ngcc_hk 2y ago
The evolution approach is more like throwing spaghetti on the wall not design. The key event seems to “The Cambrian Explosion of Animal Life” which nature “ Experiment” body parts etc and see what is the best. If a real biologist do it it will be like the evolution line approach which some thinks lead wu han lab created the covid funded by USA and approved by … That is debatable but the approach is not. Unless we can do evolve radio … One must note bird seems to evolve use quantum mechanics to direct their migration. Hence that is not unthinkable. The question is whether have radio communication has an evolution advantage. Ignore the issue of not science (as not refutable), that is the real question.
- wizzwizz4 2y ago
  Birds don't use quantum mechanics. Birds use reality. Quantum mechanics is a model of reality.
anthk 2y ago
Biology makes me thing if the universe/consciousness itself it's a product on information parsing itself, making that 'essence' or 'soul' (on how they defined it the Ancients) a truth beyond matter. No, not something religious, but more related to computation. But for this we should accept that 'data' it's an intrinsic part of Physics, not just matter. I would like an intro to Thermodynamics, but IDK where to start.
sundarurfriend 2y ago
> changing the colors would have only attenuating effects (the music is still playing but a trained ear of some can discern some distortion) What is this referring to? For most pieces inside the radio, the colors would be just superficial and not have any effect. There are some components (capacitors, resistors) where the colors have meaning, and changing them could lead to overcurrent and fires/damage or insufficient conduction and things not really working. I'm finding it hard to imagine what parts the author is thinking of where changing the colors would have only attenuating effects, where it would take a trained ear to hear the distortion. In the set of all outcomes from changing just colors, most would be either "nothing happened" or "radio's operation is clearly messed up". The author's scenario seems like one of the less likely ones.
- creer 2y ago
  In that section, they are not yet altering the radios. They are comparing the ones from a pile purchased. So this is about the different radios having components from different manufacturers, different tech, different quality. - Leading to (usually) minor sound differences.
dekhn 2y ago
Biologists have investigated a number of systems which, given the nature of evolution, bear eerie resemblance to the systems engineers have designed to solve similar problems. Here's an example: https://en.wikipedia.org/wiki/Flagellum#Motor https://en.wikipedia.org/wiki/Flagellum#Motor Over the decades people gradually uncovered more and more of the structure and ultimately recognized that the flagellum motor has components that correspond to engineered motors, with rotors, stators, energy sources, rings, bearings, etc. Amusingly, after all the effort, we recognized that the motor greatly resembles ATP synthase- one of the most core energy management proteins we have (which carries out a totally unrelated function). I imagine that any rationally designed human engineering product could be understood by a biophysicist with no real technical knowledge beyond basic electrical and mechanical engineering. See also "The Salvation of Doug", which gives an absolutely hilarious analogy between using scientific methods to understand biology, and reverse-engineering a car factory: """Emboldened by his successes, the next morning the geneticist tied the hands of an individual dressed in a suit and carrying a briefcase in one hand and a laser pointer in the other (he was a vice president). That evening the geneticist, and Doug (although he would not openly admit it), anxiously waited to see the effect on the cars. They speculated that the effect might be so great as to prevent the production of the cars entirely. To their surprise, however, that afternoon the cars rolled off the assembly line with no discernible effect."""

77 points by bilsbie 2y ago

dang 2y ago

Related: Can a biologist fix a radio? Or, what I learned while studying apoptosis (2002) - https://news.ycombinator.com/item?id=31697757 https://news.ycombinator.com/item?id=31697757 - June 2022 (21 comments) Can a biologist fix a radio?–Or, what I learned while studying apoptosis (2002) [pdf] - https://news.ycombinator.com/item?id=30120457 https://news.ycombinator.com/item?id=30120457 - Jan 2022 (18 comments)

pvaldes 2y ago

If is unemployed, you can bet that can and will do it.

Micand 2y ago

As was flagged in the other discussions, see Could a neuroscientist understand a microprocessor: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005268 https://journals.plos.org/ploscompbiol/article?id=10.1371/jo... Or a recap from The Atlantic: https://www.theatlantic.com/science/archive/2016/06/can-neuroscience-understand-donkey-kong-let-alone-a-brain/485177/ https://www.theatlantic.com/science/archive/2016/06/can-neur... I saw a wonderful recording of a talk the authors gave a few years ago (which I regrettably can't find now), and it was amongst the most eye-opening talks I've ever seen.

bee_rider 2y ago
It is sort of interesting… I think we will all admit that brains are more complex than computer chips. But I still wonder if there’s some general underlying principle that makes brains more reasonable to study in this fashion than computer chips. For example, they talk about destroying one transistor, observing that the thing can’t play Donkey-Kong anymore, and concluding that that is the DK transistor. But computer chips are designed to have incredibly long chains of dependencies where each specific transistor does exactly the right thing, every time. For neurons, it isn’t so specific, right? They all might fire, depending on the timing, and whether or not they are… I don’t know biology, charged or whatever. The whole system works under the assumption that many complements will mis-fire or be duds are any moment. It seems (to me at least) more reasonable, to come to the conclusion that the DK neuron is really a DK neuron, if removing it causes an un-recoverable DK related failure… because the whole system is based around handling failures! It is somehow special that something can break it.
- rcxdude 2y ago
  Yes, there's more of a degree of redundancy in brains than microprocessors, but the 'lesion' approach tends to involve affecting more than just one neuron. The main point of that section is that you've got to be careful about what you define as a 'function'. In the processor case, if you defined function in terms of a register or instruction working properly, then this approach could actually give you a pretty good map. But if you've defined it as whether a particular game runs, it doesn't give you a good map at all, because most games exercise most functions of the microprocessor, and so which small parts aren't important to that particular game is only incidental. With brains the main thing is the underlying functions are not really known, so you need to approach with care.
  - bonoboTP 2y ago
    I used to have the impression that the brain is more "mixed up" than it really is. It's quite hard to get the right impression as a layman. Experts push too hard towards the extreme that makes us think that everything is involved in everything and it's all thoroughly uniformly mixed, advising against believing those old naive brain charts etc. But really, certain functions are remarkably well localized. This kind of overcorrection is quite common if one often reads HN-like "well actually"-content, which is supposed to supplement a common perception with a small caveat. Beware of internalizing just the caveat and forgetting the main thrust.
- jerf 2y ago
  "For neurons, it isn’t so specific, right? They all might fire, depending on the timing, and whether or not they are… I don’t know biology, charged or whatever." So we assume. And with some good reason, including both the studies done over the decades, and the fact that we've built systems based on this architecture that match this concept. However, it is important to observe that this characteristic is still in the metaphorical spotlight. It is a thing that we can discover. If, in fact, there was One Blessed Neuron that contained the most vital aspect of some critical concept in someone's brain, we currently have zero capability to discover it, zero ability to characterize it, and effectively zero ability to manipulate that neuron directly in some experimental fashion once identified. Therefore, we should be fairly suspicious of the claim that we've eliminated this as even being a possibility. I expect it is unlikely that there is a such thing as the One Blessed Neuron, even so, but there are a large number of other hypothetical organizations that could exist beyond "an amorphous neural net with nothing really located anywhere", and we have good evidence for that as well; the "regions" of the brain, the fact we can visibly see physically different organizations of neurons in certain regions and associate them with certain tasks. I would not even dream of trying to guarantee that there is no structure lying in between the gross differences we already know about and the hypothetical undifferentiated neural mass, the structures in those complexity voids between what we can currently see. We again have a lot of inductive reasons to believe that there is likely more structure there we do not even have a clue exists, on the grounds that every time we get a closer look at something for the first time ever, it is rarely only and exactly what we expected. It's such a notable outcome that it gets called out specifically when it happens, precisely because it's rare.
stochastician 2y ago
Author of that paper here -- What an incredibly nice comment to wake up to at 3am, thank you! This paper made me quit neuro and switch to systems that are easier to model (small molecules) which it turns out are still annoyingly difficult!

fastaguy88 2y ago

I am always puzzled when biologists make analogies between living systems (or sub-systems) and human-designed devices (even complex devices). Human designed devices have an essential property that biological systems do not -- they were designed. While radios may seem complex, they are built from a relatively small number of component types with very well understood behaviors and typically limited numbers of interactions. Biological systems have no such constraints -- they were not designed, there can be many different ways to do the same thing (in the same cell), there are at least thousands, if not hundreds of thousands of different components, many of which have lots and lots of interactions. Considering how messy the systems are, it is quite remarkable that genetics and biochemistry discovered the basis of heredity (or at least some of it), the genetic code, hundreds of signaling pathways, etc etc. But there is no missing language, because there was no design that used that language.

doe_eyes 2y ago
Sure, but... how often do we object when fellow techies make analogies between just about anything and their field of expertise? We feel that our knowledge makes us quite qualified to explain the economy, to chime in on microbiology, and so on. It's really pretty universal.
minifridge 2y ago
Biological systems have also designs that emerged through evolution. Although the complexity may seem at different scales, the main difference is the measurements you can do. Both biological and electrical circuits are dynamic systems that have designs that gives them emergent functional properties. As the article describes imagine having the list of radio components instead only instead of their topology (wiring diagram). The problem of figuring out how a radio works with this information, if youbknow little about their design, becomes quite similar with how figuring out how a biological system works. The absence of a design diagram and our inability to measure components at the molecular level without disturbing the state of a system is the main reason bilogical systems are so challenging to understand.
- fastaguy88 2y ago

svilen_dobrev 2y ago

the two schematical views reminded me of a) the dualisms in Pirsig, and b) also of another similar one: two views of what-a-cat-consists-of - one according to the granny owner, and another according to the surgeon - but cannot remember which book was that from. Anyone?

ngcc_hk 2y ago

The evolution approach is more like throwing spaghetti on the wall not design. The key event seems to “The Cambrian Explosion of Animal Life” which nature “ Experiment” body parts etc and see what is the best. If a real biologist do it it will be like the evolution line approach which some thinks lead wu han lab created the covid funded by USA and approved by … That is debatable but the approach is not. Unless we can do evolve radio … One must note bird seems to evolve use quantum mechanics to direct their migration. Hence that is not unthinkable. The question is whether have radio communication has an evolution advantage. Ignore the issue of not science (as not refutable), that is the real question.

wizzwizz4 2y ago
Birds don't use quantum mechanics. Birds use reality. Quantum mechanics is a model of reality.

anthk 2y ago

Biology makes me thing if the universe/consciousness itself it's a product on information parsing itself, making that 'essence' or 'soul' (on how they defined it the Ancients) a truth beyond matter. No, not something religious, but more related to computation. But for this we should accept that 'data' it's an intrinsic part of Physics, not just matter. I would like an intro to Thermodynamics, but IDK where to start.

sundarurfriend 2y ago

> changing the colors would have only attenuating effects (the music is still playing but a trained ear of some can discern some distortion) What is this referring to? For most pieces inside the radio, the colors would be just superficial and not have any effect. There are some components (capacitors, resistors) where the colors have meaning, and changing them could lead to overcurrent and fires/damage or insufficient conduction and things not really working. I'm finding it hard to imagine what parts the author is thinking of where changing the colors would have only attenuating effects, where it would take a trained ear to hear the distortion. In the set of all outcomes from changing just colors, most would be either "nothing happened" or "radio's operation is clearly messed up". The author's scenario seems like one of the less likely ones.

creer 2y ago
In that section, they are not yet altering the radios. They are comparing the ones from a pile purchased. So this is about the different radios having components from different manufacturers, different tech, different quality. - Leading to (usually) minor sound differences.

dekhn 2y ago

Biologists have investigated a number of systems which, given the nature of evolution, bear eerie resemblance to the systems engineers have designed to solve similar problems. Here's an example: https://en.wikipedia.org/wiki/Flagellum#Motor https://en.wikipedia.org/wiki/Flagellum#Motor Over the decades people gradually uncovered more and more of the structure and ultimately recognized that the flagellum motor has components that correspond to engineered motors, with rotors, stators, energy sources, rings, bearings, etc. Amusingly, after all the effort, we recognized that the motor greatly resembles ATP synthase- one of the most core energy management proteins we have (which carries out a totally unrelated function). I imagine that any rationally designed human engineering product could be understood by a biophysicist with no real technical knowledge beyond basic electrical and mechanical engineering. See also "The Salvation of Doug", which gives an absolutely hilarious analogy between using scientific methods to understand biology, and reverse-engineering a car factory: """Emboldened by his successes, the next morning the geneticist tied the hands of an individual dressed in a suit and carrying a briefcase in one hand and a laser pointer in the other (he was a vice president). That evening the geneticist, and Doug (although he would not openly admit it), anxiously waited to see the effect on the cars. They speculated that the effect might be so great as to prevent the production of the cars entirely. To their surprise, however, that afternoon the cars rolled off the assembly line with no discernible effect."""