3 ms·

After long study, my iron-clad law of biology is this: every other iron-clad law of biology ends with the phrase “well, except when ...”

infogulch 6y ago
This seems to apply to your law as well.
- hprotagonist 6y ago
  isn’t it great?
nobodyknowsyoda 6y ago
I’m probably preaching to the choir, but yup that inherent uncertainty seems to distinguish biology from the other sciences. There is a huge stochasticity & serendipity in everything because there is no intentionality in the design of any biological component; any convergence toward a chemically or physically optimized component or behavior is driven by evolution by natural selection but remains imperfect. Warts, quirks, and all It also explains how the folks on HN positing “Covid is just the flu” and “long Covid isn’t real” have been so confident yet so gravely mistaken. They are used to other sciences where there is much less room for uncertainty
- hprotagonist 6y ago
  Yep. For better or worse i've been up to my eyeballs in "hey, you know, biological systems are actually insane!" since high school, and now through a few advanced degrees :) I've been working in tech more than normal for a few years now, and the endemic nature of "the andy grove fallacy" among my coworkers has ceased to startle me, but it's just kind of bothersome every time. https://blogs.sciencemag.org/pipeline/archives/2007/11/06/andy_grove_rich_famous_smart_and_wrong https://blogs.sciencemag.org/pipeline/archives/2007/11/06/an...
  - nitrogen 6y ago
    Despite the common trope that software/hardware engineers think they understand everything, automation can make exponential development possible in bio. I know someone who works at a biotech company, and the stories I hear lead me to believe that traditional thinking in e.g. medicine and insurance, and from colleagues, really is a bottleneck. Maybe exponential growth will never apply to the number of diseases cured, but it can and should apply to the hardware and software that facilitates the next iteration of biological discovery.
    - hprotagonist 6y ago
      It's not that software/hardware engineers think they understand everything, it's that the absolutely common idea "my way of thinking about understanding things is appropriate in this other domain" breaks down very fast. I'm not speaking about running hospitals or dancing with insurance companies. I'm speaking about much earlier in the pipeline: fundamental, blue-sky biological research is fundamentally different from software. The reason is that we are not studying designed systems; the effect is that there is so much that we don't know that we don't know that things that sound easy are in fact basically impossible because the prior knowledge is simply not established. (Until they aren't. When does that change? First slowly, then all at once.) As a biomedical engineer, i'm on board with hardware and software improvements: it's kind of my job. The trick is knowing what you're doing, what you aren't, and what you can expect, and to balance confidence in the value of what you _can_ tightly constrain and design versus humility in accepting that the natural world simply doesn't care.
      - natechols 6y ago
        I think what bugs me the most is the common assumption that we just need better modeling tools to make a lot of the messy lab work go away. Everyone who raises this idea seems to think it's original and revolutionary and a no-brainer, but there's at least 40 years of bitter experience in biotech and pharma development saying otherwise. Even genuinely impressive feats like AlphaFold get inflated wildly in importance (and used to retroactively bash experimentalists for all the time they wasted by not listening to software people). Actually speeding up the entire process of biomedical research requires improvements across the board in many different fields, and it's not something that is magically going to be solved by computer science wizardry alone.
grishka 6y ago
As a software developer, I find biology to be fascinating but at the same time extremely complex and counterintuitive. Everything seems to be influencing everything else in subtle ways. You can never separate an organism into distinct modules that do distinct jobs and expose distinct interfaces, like you could a program or a hardware device when reverse engineering. The fact that physics and chemistry are being exploited in most unexpected ways doesn't help either. But then the thing to remember is that biology is alien technology in the sense that it wasn't created by humans and is still ahead of our current technological progress. It's the only alien technology we've been able to get our hands onto.
- WJW 6y ago
  Mother Nature only cares about energy efficiency and evolutionary fitness. If that means every variable has to be global, so be it. She is not coding with understandability in mind.
  - O_H_E 6y ago
    That is..... a wild way to put it. Thanks for the amusing laugh.
- idrios 6y ago
  You can still expose interfaces, the tricky part is that there are multiple systems you're creating interfaces to -- whether or not you intended it. Take blood for example. Through a fluid mechanics lens, the role of blood is to maintain a certain amount of flow and pressure in different parts of the body. You can look at it with Poisseuille's Law in mind: F = (ΔP/R) where F is flow rate, ΔP is pressure, and R is (for the purposes of this example) a constant [1]. Low blood pressure = lower flow rate, which means blood spends a longer amount of time in parts of the body than necessary. So blood is depositing oxygen slower than it should. Makes sense that the resulting symptoms would be things related to lack of oxygen -- dizzyness, lethargy, etc. Meanwhile high blood pressure = higher flow rate (which is good), but that pressure is being generated from a fluid pump (your heart), which means your heart is working harder than it needs to so it makes sense that high blood pressure results in heart-related problems. So the role of blood for fluid mechanics is to maintain the right pressure & flow. Through a biomaterials lens, blood needs to flow easily when it's in the body but not when there's a leak in your pipes (a cut). Its solution is more or less that it recognizes a certain kind of surface as "self" and doesn't bind to that surface, but any other kind of surface attracts plasma which attracts blood. Through an immunology lens, the cardiovascular system represents a huge vulnerability in the human system because it provides a channel for foreign attackers to reach any of the body's many microservices -- lungs, kidneys, brain, you name it. So it makes sense that the strongest antivirus would be present in the blood stream. That, and the blood is a very convenient transport service for antibodies that need to get to a compromised area quickly, to contain the incident. Through a biochemistry lens, oxygen is a resource that every cell in the body needs for cell respiration. Blood needs to be able to pick up oxygen from the alveoli in the lungs, and drop it off in a fairly evenly distributed manner throughout the body. It'd be bad if it couldn't even pick up the oxygen (which is why Carbon Monoxide kills you -- it binds to blood and doesn't let go). It'd be bad if picked up the oxygen and dropped it off too early. It'd be bad if it picked up the oxygen and then refused to let go. So the body evolved a really clever system where it uses hemoglobin, which binds oxygen more tightly at higher Ph and more loosely at lower Ph. Conveniently, high concentrations of CO2 lower Ph, so blood naturally lets go of its Oxygen when it's in areas of high CO2 concentration. Through a bioelectricity lens, blood is electrically inert. This doesn't get talked about because it's uninteresting, but it is still a design decision that blood doesn't generate or consume electrical energy and does not interfere with the electrical activies of neurons. You can still draw the interfaces as you would in software engineering. But anything you make will have interfaces to all of the body's systems so you need to make sure you're not throwing off any other equilibriums [1] http://hyperphysics.phy-astr.gsu.edu/hbase/ppois.html http://hyperphysics.phy-astr.gsu.edu/hbase/ppois.html
tejtm 6y ago
This. Decades ago I once innocently noted Biology is a system of exceptions! still hear the echos.

infogulch 6y ago

This seems to apply to your law as well.

hprotagonist 6y ago
isn’t it great?

nobodyknowsyoda 6y ago

I’m probably preaching to the choir, but yup that inherent uncertainty seems to distinguish biology from the other sciences. There is a huge stochasticity & serendipity in everything because there is no intentionality in the design of any biological component; any convergence toward a chemically or physically optimized component or behavior is driven by evolution by natural selection but remains imperfect. Warts, quirks, and all It also explains how the folks on HN positing “Covid is just the flu” and “long Covid isn’t real” have been so confident yet so gravely mistaken. They are used to other sciences where there is much less room for uncertainty

hprotagonist 6y ago
Yep. For better or worse i've been up to my eyeballs in "hey, you know, biological systems are actually insane!" since high school, and now through a few advanced degrees :) I've been working in tech more than normal for a few years now, and the endemic nature of "the andy grove fallacy" among my coworkers has ceased to startle me, but it's just kind of bothersome every time. https://blogs.sciencemag.org/pipeline/archives/2007/11/06/andy_grove_rich_famous_smart_and_wrong https://blogs.sciencemag.org/pipeline/archives/2007/11/06/an...
- nitrogen 6y ago
  Despite the common trope that software/hardware engineers think they understand everything, automation can make exponential development possible in bio. I know someone who works at a biotech company, and the stories I hear lead me to believe that traditional thinking in e.g. medicine and insurance, and from colleagues, really is a bottleneck. Maybe exponential growth will never apply to the number of diseases cured, but it can and should apply to the hardware and software that facilitates the next iteration of biological discovery.
  - hprotagonist 6y ago
    It's not that software/hardware engineers think they understand everything, it's that the absolutely common idea "my way of thinking about understanding things is appropriate in this other domain" breaks down very fast. I'm not speaking about running hospitals or dancing with insurance companies. I'm speaking about much earlier in the pipeline: fundamental, blue-sky biological research is fundamentally different from software. The reason is that we are not studying designed systems; the effect is that there is so much that we don't know that we don't know that things that sound easy are in fact basically impossible because the prior knowledge is simply not established. (Until they aren't. When does that change? First slowly, then all at once.) As a biomedical engineer, i'm on board with hardware and software improvements: it's kind of my job. The trick is knowing what you're doing, what you aren't, and what you can expect, and to balance confidence in the value of what you _can_ tightly constrain and design versus humility in accepting that the natural world simply doesn't care.
    - natechols 6y ago
      I think what bugs me the most is the common assumption that we just need better modeling tools to make a lot of the messy lab work go away. Everyone who raises this idea seems to think it's original and revolutionary and a no-brainer, but there's at least 40 years of bitter experience in biotech and pharma development saying otherwise. Even genuinely impressive feats like AlphaFold get inflated wildly in importance (and used to retroactively bash experimentalists for all the time they wasted by not listening to software people). Actually speeding up the entire process of biomedical research requires improvements across the board in many different fields, and it's not something that is magically going to be solved by computer science wizardry alone.

grishka 6y ago

As a software developer, I find biology to be fascinating but at the same time extremely complex and counterintuitive. Everything seems to be influencing everything else in subtle ways. You can never separate an organism into distinct modules that do distinct jobs and expose distinct interfaces, like you could a program or a hardware device when reverse engineering. The fact that physics and chemistry are being exploited in most unexpected ways doesn't help either. But then the thing to remember is that biology is alien technology in the sense that it wasn't created by humans and is still ahead of our current technological progress. It's the only alien technology we've been able to get our hands onto.

WJW 6y ago
Mother Nature only cares about energy efficiency and evolutionary fitness. If that means every variable has to be global, so be it. She is not coding with understandability in mind.
- O_H_E 6y ago
  That is..... a wild way to put it. Thanks for the amusing laugh.
idrios 6y ago
You can still expose interfaces, the tricky part is that there are multiple systems you're creating interfaces to -- whether or not you intended it. Take blood for example. Through a fluid mechanics lens, the role of blood is to maintain a certain amount of flow and pressure in different parts of the body. You can look at it with Poisseuille's Law in mind: F = (ΔP/R) where F is flow rate, ΔP is pressure, and R is (for the purposes of this example) a constant [1]. Low blood pressure = lower flow rate, which means blood spends a longer amount of time in parts of the body than necessary. So blood is depositing oxygen slower than it should. Makes sense that the resulting symptoms would be things related to lack of oxygen -- dizzyness, lethargy, etc. Meanwhile high blood pressure = higher flow rate (which is good), but that pressure is being generated from a fluid pump (your heart), which means your heart is working harder than it needs to so it makes sense that high blood pressure results in heart-related problems. So the role of blood for fluid mechanics is to maintain the right pressure & flow. Through a biomaterials lens, blood needs to flow easily when it's in the body but not when there's a leak in your pipes (a cut). Its solution is more or less that it recognizes a certain kind of surface as "self" and doesn't bind to that surface, but any other kind of surface attracts plasma which attracts blood. Through an immunology lens, the cardiovascular system represents a huge vulnerability in the human system because it provides a channel for foreign attackers to reach any of the body's many microservices -- lungs, kidneys, brain, you name it. So it makes sense that the strongest antivirus would be present in the blood stream. That, and the blood is a very convenient transport service for antibodies that need to get to a compromised area quickly, to contain the incident. Through a biochemistry lens, oxygen is a resource that every cell in the body needs for cell respiration. Blood needs to be able to pick up oxygen from the alveoli in the lungs, and drop it off in a fairly evenly distributed manner throughout the body. It'd be bad if it couldn't even pick up the oxygen (which is why Carbon Monoxide kills you -- it binds to blood and doesn't let go). It'd be bad if picked up the oxygen and dropped it off too early. It'd be bad if it picked up the oxygen and then refused to let go. So the body evolved a really clever system where it uses hemoglobin, which binds oxygen more tightly at higher Ph and more loosely at lower Ph. Conveniently, high concentrations of CO2 lower Ph, so blood naturally lets go of its Oxygen when it's in areas of high CO2 concentration. Through a bioelectricity lens, blood is electrically inert. This doesn't get talked about because it's uninteresting, but it is still a design decision that blood doesn't generate or consume electrical energy and does not interfere with the electrical activies of neurons. You can still draw the interfaces as you would in software engineering. But anything you make will have interfaces to all of the body's systems so you need to make sure you're not throwing off any other equilibriums [1] http://hyperphysics.phy-astr.gsu.edu/hbase/ppois.html http://hyperphysics.phy-astr.gsu.edu/hbase/ppois.html

tejtm 6y ago

This. Decades ago I once innocently noted Biology is a system of exceptions! still hear the echos.