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What if you could solve this bottom up, e.g.: Math -> Physics -> Chemistry -> Biology. I'm assuming that's how it would in theory play out.
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Nonsense. This is like when people used to say "AI will never be able to write code as good as a human!" Biology will become a solved problem.
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I don't think that's at all an accurate characterization of prior skepticism, and indeed it's quite obvious how the systems we've built to improve AI code generation work, and they were also an obvious thing to try (in parallel with the models themselves getting more capable).

Despite the improvements, though, we still see plenty of code that is "slop", because it's directed by someone with little idea of what to do, but also because it's harder to test for (or even measure) code quality than correctness. The "solved problem" rhetoric depends very strongly on your standards.

In other fields the problem is similar, and typically worse. Plenty of AI music sounds acceptable, not clearly flawed, and even mildly "interesting" to me; but I think this is much more a commentary on music than it is on AI. Prose continues to be abhorrent in nearly every application; while I've seen examples of people getting really impressive output, it takes a level of effort that defeats the purpose of almost everyone who wants AI to assist their writing (i.e., just generate a comprehensible report on some findings and get on with their day). Art is a whole different world; the quality of results clearly strongly depends on the quality of prompting, it's much better/worse in some genres than others, humans vary widely in their ability to notice "mistakes", etc.

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Eventually maybe, but the problem is hard from both directions. Answering basic questions such as "what does aspirin actually do at a biochemical level?" or "design a drug to reduce beta amalyoid plaques" are both very non trivial. Nevermind something complex like 'cure cancer'.
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it can be simulated to a very high fidelity.
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There’s no simulation you can do today that can tell you that your drug will likely make it through phase 3 trials. The best we can do is simulate reactions of a few key molecules, we’re nowhere near cell or organism scale simulations.
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Observing a faithful simulation is not at all the same thing as understanding what has been seen.
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we do have high precision microscopes that can see molecules, so it is possible to build closed system with feedback loop that feeds back into AI at very small scales
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It's often not necessarily about visibility, but real iteration time.

For instance, let's say we are doing biology on plants, which is still much easier than doing human trials. No matter how motivated claude might get, you aren't getting a corn plant to grow in 40 seconds. Real world research pipelines involve stages where even greenhouses don't do, and sacks of grain are shipped to Hawaii, or Brazil, or wherever, to try to get practical data for a given test.

If your computer simulation is so accurate you can skip a step now done with biology, great, but it gets harder the larger your problem is. I might see if a molecule kills bacteria kind of quickly, but what does a molecule do to a real human being? Not so easy.

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I don't follow how "we can see tiny stuff" = "it is possible to build closed system"?

Seeing tiny stuff doesn't magically give you enough info for Claude to reason with the system predictably (the way it can with source code).

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It can start to reason about what it seems under the microscope. You just need to train it on images and data from microscopes.
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Have you looked at cells and tissues under a microscope? There’s patterns upon patterns inside patterns under and over and through other patterns.

There’s no well-labeled dataset for all this because we don’t know everything we are looking at.

Take a neuron. You can stain it so you can tell apart an axon and a dendrite. But if you don’t it’s very possible to miss or mislabel the axon, because unlike the textbook neuron, the axon isn’t always obviously oriented in a way that promotes ID.

And that’s just one example. With more complex samples, you also have a lot of edges which AI models don’t segment very well.

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You largely explained a day in life of a SWE working in a complex codebase spanning (tens of) millions lines of code. In complex products we always deal with a great degree of uncertainty and due to the ambiguity and high complexity we usually have no simple way of proving that the thing (TM) we designed is going to be working as advertised in all cases. Because the problem space is in-exhaustive, and to increase the likeliness of the solution we designed, we run the experiments, and not on a sole machine but clusters at data-center scale. Even then you get "bug reports" and that's not because engineers were lazy but because the domain is genuinely complicated, and ever changing.

So, I'd say it's a pretty similar process, and yet we have the AI models now almost completely integrated into the SWE domain remediating significant parts of its complexity.

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What is it with SWEs thinking every problem can be addressed in terms of SWE, while at the same time being unaware of how little they understand the problem they are trying to address?
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Do you know what loading a sample into a scanning tunneling microscope involves?
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the transition is in-silico => in-vitro => in-vivo

AI already can do in-silico simulation

add microscopes and tiny precision actuators, and we can build closed feedback loop in-vitro system

once we have in-vitro, it will be easier to go in-vivo

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Why would number 2, which we’ve been able to do for decades, possible affect number 3 on your list?
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No its not, this is complete dunning kruger, please provide an example.
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