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Ask HN: How close are we to replace animal models with software?
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Re: Ask HN: How close are we to replace animal models with software?
#12We 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.
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.
Re: Ask HN: How close are we to replace animal models with software?
#13Not even close. We don't yet have a computational model that accurately reproduces all the properties of water, the solvent where most life of interest occurs. And, if and when we have one, and are able to develop accurate models for the myriad proteins involved (an even worse problem,) and we're able to develop accurate models for all their interactions (O(huge)), and so forth, the computational cost to simulate systems that would be relevant at the scale of a whole organism would be... jaw-dropping.
Re: Ask HN: How close are we to replace animal models with software?
#14We 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.
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).
How are you going to simulate the administering of a medicinal molecule? Or the knocking out of a gene?
Re: Ask HN: How close are we to replace animal models with software?
#15Wait until we cracked protein folding, then add 20 years.
Re: Ask HN: How close are we to replace animal models with software?
#16We 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.
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Re: Ask HN: How close are we to replace animal models with software?
#17We 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.
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
[1] https://www.fda.gov/science-research/about-science-research-...
Re: Ask HN: How close are we to replace animal models with software?
#18We 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.
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).
But none of that means you should take a drug bc someone’s elaborately technologized guess is that it’ll be okay
Re: Ask HN: How close are we to replace animal models with software?
#19Biology is an organic computation that runs at the speed of existence. There may be no way to simulate this computation in silicon at the same scale, insofar as biology is already massively parallel and may very well involve quantum computation.
Put another way, if we accept for a moment that the universe is a simulation, it may be fundamentally impossible for an in-simulation simulator to ever reach the computational power of its parent simulator.
Re: Ask HN: How close are we to replace animal models with software?
#20Hi! My professional job is to write emulators, my wife is a molecular biologist, and as a kid I had dreams of writing the exact software you are referencing, so I think I have a decent handle on this question.
We are no where close. We are ludicrously far away.
Let's define the exact scenario: we want to replace clinical trials with a software simulation of the human body. If the simulation shows ill side-effects, we can deny approval of a treatment.
1. We can barely emulate other computers. It's tempting to look at something like a Nintendo emulator and think "oh this isn't that hard" but it is. Most video game emulators get about 90% of the emulation right and it's good enough for most games. But a common practice is to carry patches for all the software to patch the software. Hilariously, this is sometimes because the software is working around a hardware quirk or bug, but then it turns out difficult to emulate that quirk or bug, so we patch out the hack. If you want a perfect emulator it's really hard [0] If you're testing for bad drug interactions in a human simulation, it's exactly these quirks/bugs you want to accurately simulate!
2. The software of cells is DNA and the genes contained within. And genes encode for proteins which are amazing at doing a huge amount of varied tasks. But these are the basic building blocks, and we've only begun to scratch the surface. We made huge progress but we barely understand. [1] Imagine trying to work on an emulator of a microchip, but we don't quite understand how transistors work.
3. There's mind-body feedback loop with the endocrine system [2]. On top of everything else, we need to simulate the brain. Sure we can use a simplified model of that, but animal models are also simplification. The whole point was to try to get more accurate, and how accurate do you need to guarantee results? I know this argument is a bit absurd but it's to point out there's no finish-line, only more and more difficultly as higher accuracy is demanded.
4. How would we develop this simulator. Let's suppose I have my initial prototype. I've simulated various known drugs and got results, and I've tuned my parameters. But this is a massive complex system. Once I run a new novel drug, the point is that it's doing something new! So, if I have a bad reaction, is it a bad drug, or a simulation bug? Each scenario is new and poses to surface incorrect modeling between complex subsystems. You can argue that we'd build our confidence over time, but that means we'll see the long path to simulator development. There have been some attempts but they have appeared to not provide predictive results [3]
5. When asked to debate whether or not we could simulate the human body, the pro-simulation side invoked fantasy: "Exascale or quantum computing will enable algorithms that we are yet to conceive of" suggesting that we are very far away if it is possible. [4]
[0] https://arstechnica.com/gaming/2011/08/accuracy-takes-power-...
[1] https://www.quantamagazine.org/how-ai-revolutionized-protein...
[2] https://www.psychologytoday.com/us/blog/the-brain-body-conne...
[3] https://en.wikipedia.org/wiki/Virtual_Physiological_Human