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We can't even simulate a single cell. At least not accurately. You'd need to be able to simulate ribosomes, gene expression, epigenetic factors. Still a lot we

We can't even simulate a single cell. At least not accurately. You'd need to be able to simulate ribosomes, gene expression, epigenetic factors. Still a lot we don't understand because even single cells are incredibly complex electrochemical machines.

typon 2y ago
I can imagine a world where you can simulate a simple organism like a worm without knowing how to simulate the cells that make it. This is because emergent behaviour of complex systems can be much simpler than the constituent parts of that system (temperature vs. knowing particle velocities).
- amelius 2y ago
  How are you going to simulate the administering of a medicinal molecule? Or the knocking out of a gene?
  - typon 2y ago
    My modelling the relevant parts of the worm that are involved in these processes. You don't need an atomistic DFT simulator to get a good enough simulation of fluid dynamics, enough to design jets or rockets that go into space.
    - amelius 2y ago
      > modelling the relevant parts of the worm that are involved in these processes. You mean cell chemistry?
- kingkawn 2y ago
  But none of that means you should take a drug bc someone’s elaborately technologized guess is that it’ll be okay
- yathern 2y ago
  I can write a program today that can simulate a worms "emergent behavior" without simulating the cells. Maybe a little 3D model that wriggles around. I can even do a human! But I think what we're looking for here is something closer to emulation. In the same way that video game console emulators seek to reproduce the exact bugs that the original hardware produced - the value here does not come from abstracting away the lowest levels of behavior.
  - JPLeRouzic 2y ago
    > the value here does not come from abstracting away the lowest levels of behavior I totally agree.
- SketchySeaBeast 2y ago
  It seems to me that if you can fully simulate a worm you're probably only an order of magnitude of difficulty away from a person, but to get there you need to have crossed dozens across many domains.
- Palomides 2y ago
  there's https://openworm.org/ https://openworm.org/ for simulating a c. elegans, but think you're underestimating the complexities
h1fra 2y ago
I agree but we also don't know what gravity is, and yet we can compute it with some degree of error. There might be a world we can just approximate enough of this cell, that the details matter less.
- awb 2y ago
  This actually illustrates the crux of the problem. Gravity is a single (highly accurate) approximation when applied to 2 objects. But when you have 3 objects interacting with each other, the system is chaotic: https://en.m.wikipedia.org/wiki/Three-body_problem https://en.m.wikipedia.org/wiki/Three-body_problem Even if we could estimate all the molecules, cells, and processes of a biological entity to a similar precision as gravity, the errors would compound exponentially.
soyeahok 2y ago
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JPLeRouzic 2y ago
Thanks for your answer, but we either don't understand the biology of the animal models that we use. I think that medicine and drug regulations do not use the same conceptual framework as biology. Medicine and drug regulations are pragmatic, hence the concept of clinical trial: They test if something works while minimizing the confounding factors. They do not try to understand the biology down to cellular force fields of the animal model. So why not have the same approach with software? Anyway, drugs authorities have already approved drugs based on software simulations [0, 1]. [0] https://www.fda.gov/media/163156/download https://www.fda.gov/media/163156/download [1] https://www.fda.gov/science-research/about-science-research-fda/modeling-simulation-fda https://www.fda.gov/science-research/about-science-research-...
- salomon812 2y ago
  > Anyway, drugs authorities have already approved drugs based on software simulations The simulations you have linked aren't on the same scale. The paper uses the phrase "are powerful tools that COMPLEMENT traditional methods for gathering evidence" And I'd argue this is more like detailed analysis rather than a simulation. It's like hoping you've found an immersive computer world like The Matrix, but it's a 2D side-scolling video game like Mario Bros. I'd also question "approved drugs based on..." and instead argue they "didn't reject drugs based on..."
- jryb 2y ago
  Yes, but while animals are a black box to some extent, the outcomes of the experiments are not. And you don't have to worry about whether your results are an artifact of your simulation. Your instincts are good - if we could simulate people in silico we could basically understand and cure every disease - but the scale of such a simulation is literally (not figuratively!) astronomical. Biological systems are way, way, way more complex than they appear and our computers are (currently) hopelessly inadequate.

typon 2y ago

I can imagine a world where you can simulate a simple organism like a worm without knowing how to simulate the cells that make it. This is because emergent behaviour of complex systems can be much simpler than the constituent parts of that system (temperature vs. knowing particle velocities).

amelius 2y ago
How are you going to simulate the administering of a medicinal molecule? Or the knocking out of a gene?
- typon 2y ago
  My modelling the relevant parts of the worm that are involved in these processes. You don't need an atomistic DFT simulator to get a good enough simulation of fluid dynamics, enough to design jets or rockets that go into space.
  - amelius 2y ago
    > modelling the relevant parts of the worm that are involved in these processes. You mean cell chemistry?
kingkawn 2y ago
But none of that means you should take a drug bc someone’s elaborately technologized guess is that it’ll be okay
yathern 2y ago
I can write a program today that can simulate a worms "emergent behavior" without simulating the cells. Maybe a little 3D model that wriggles around. I can even do a human! But I think what we're looking for here is something closer to emulation. In the same way that video game console emulators seek to reproduce the exact bugs that the original hardware produced - the value here does not come from abstracting away the lowest levels of behavior.
- JPLeRouzic 2y ago
  > the value here does not come from abstracting away the lowest levels of behavior I totally agree.
SketchySeaBeast 2y ago
It seems to me that if you can fully simulate a worm you're probably only an order of magnitude of difficulty away from a person, but to get there you need to have crossed dozens across many domains.
Palomides 2y ago
there's https://openworm.org/ https://openworm.org/ for simulating a c. elegans, but think you're underestimating the complexities

h1fra 2y ago

I agree but we also don't know what gravity is, and yet we can compute it with some degree of error. There might be a world we can just approximate enough of this cell, that the details matter less.

awb 2y ago
This actually illustrates the crux of the problem. Gravity is a single (highly accurate) approximation when applied to 2 objects. But when you have 3 objects interacting with each other, the system is chaotic: https://en.m.wikipedia.org/wiki/Three-body_problem https://en.m.wikipedia.org/wiki/Three-body_problem Even if we could estimate all the molecules, cells, and processes of a biological entity to a similar precision as gravity, the errors would compound exponentially.

soyeahok 2y ago

[dead]

JPLeRouzic 2y ago

Thanks for your answer, but we either don't understand the biology of the animal models that we use. I think that medicine and drug regulations do not use the same conceptual framework as biology. Medicine and drug regulations are pragmatic, hence the concept of clinical trial: They test if something works while minimizing the confounding factors. They do not try to understand the biology down to cellular force fields of the animal model. So why not have the same approach with software? Anyway, drugs authorities have already approved drugs based on software simulations [0, 1]. [0] https://www.fda.gov/media/163156/download https://www.fda.gov/media/163156/download [1] https://www.fda.gov/science-research/about-science-research-fda/modeling-simulation-fda https://www.fda.gov/science-research/about-science-research-...

salomon812 2y ago
> Anyway, drugs authorities have already approved drugs based on software simulations The simulations you have linked aren't on the same scale. The paper uses the phrase "are powerful tools that COMPLEMENT traditional methods for gathering evidence" And I'd argue this is more like detailed analysis rather than a simulation. It's like hoping you've found an immersive computer world like The Matrix, but it's a 2D side-scolling video game like Mario Bros. I'd also question "approved drugs based on..." and instead argue they "didn't reject drugs based on..."
jryb 2y ago
Yes, but while animals are a black box to some extent, the outcomes of the experiments are not. And you don't have to worry about whether your results are an artifact of your simulation. Your instincts are good - if we could simulate people in silico we could basically understand and cure every disease - but the scale of such a simulation is literally (not figuratively!) astronomical. Biological systems are way, way, way more complex than they appear and our computers are (currently) hopelessly inadequate.