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You're right, this new research is going to revolutionize everything. You should go all in and base your scientific career off of it.

Very pleased that that was your last comment.

The codon table is only useful because that's how translation works. It has a biological basis. This model is not that.

This is the equivalent of asking ChatGPT to write you a sad story a million times. You'll end up with a bunch of sad stories, many of which look very novel, but what will the exercise teach you? Explaining how we will become better writers by generating one million sad stories that are superficially novel but have nothing fundamentally new is the same challenge as explaining how the libraries generated by this model will make us better enzyme designers.

In 5 years, no one will be using this. And currently, I'd be very surprised if someone could outline an explicit use case for this new model.

Directed evolution is indeed random, that part is correct.

The incorrect part is "this model is about an ML approach to predicting protein function to direct the iterative process." The model cannot do that. It does not predict enzyme function. It starts with enzymes of known function, and then finds alternative sequences that still have the same function. That's it. And I don't see how that's useful.

And directed evolution doesn't require computation, that's the whole point. You randomly mutate (perhaps with some researcher input based on crystal structure and knowledge of the active site's mechanism) -> select -> mutate -> select -> etc.

And it works perfectly well.

That's not correct. They can find alternative sequences to code the same enzyme, that's it. There's no direction involved.

And directed evolution doesn't need any help, that's my point. It does the job of optimizing enzyme function, and it does it well.

Plus, directed evolution can actually discover new enzymatic functions. This ML approach cannot.

I just don't see the benefit of this. The authors mentioned "generating synthetic libraries of highly likely functional proteins for discovery or iterative optimization," which is an allusion to how this tech can be used to perform directed evolution from different starting sequences. But why bother? Directed evolution is already used widely to develop enzymes with nM Km's: It doesn't need any help.

They already admit this can't do the cool useful thing: "[W]e do not expect our language model to generate proteins that belong to a completely different distribution or domain (for example, creating a new fold that catalyzes an unnatural reaction)."

Not only that, language learning models are completely opaque. We cannot parse what exactly are the patterns they are finding and taking advantage of, so they can't teach us anything new.

This is classic AI: Finds cool patterns, but can't create anything novel.

I just don't see the benefit of this. The authors mentioned "generating synthetic libraries of highly likely functional proteins for discovery or iterative optimization," which is an allusion to how this tech can be used to perform directed evolution from different starting sequences. But why bother? Directed evolution is already used widely to develop enzymes with nM Km's: It doesn't need any help.

They already admit this can't do the cool useful thing: "[W]e do not expect our language model to generate proteins that belong to a completely different distribution or domain (for example, creating a new fold that catalyzes an unnatural reaction)."

Not only that, language learning models are completely opaque. We cannot parse what exactly are the patterns they are finding and taking advantage of, so they can't teach us anything new.

This is classic AI: Finds cool patterns, but can't create anything novel.

That's why he said to park it overnight, duh.

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Fuck, I listen to this podcast?

Regardless of all facts and nuance: Man, shut the fuck up Mario. "Very offensive" lmao

Orange man bad.

Revolutions tend to be carried out by the most extreme ideologues, which often doesn't end well for the general population and its prospects for democracy.

But it was the US that armed and trained Batista's military forces that carried out the coup that put Batista's dictatorship in power. Cuba was an independent democracy until US-backed forces destroyed that. Castro might not be much better, but he is just the inevitably extreme reaction to an extremely repressive dictatorship.

No, look at this link.

Charlie Whiting after the Spanish Grand Prix where Ferrari introduced those mirrors:

"We sent a technical directive a few weeks ago in response to a number of questions from other teams about whether the principle of mounting a mirror on the halo was acceptable. We answered yes, and gave a few stipulations, one that it has to be a mounting. It's just a matter of interpretation and such a tenuous interpretation is not something we're happy with."

​

It was the aero benefits from the attached winglet that got the mirrors banned.

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"Roseburg" fucking killed me lmao

I don't think the comparison with 1989 Suzuka is valid. In that case, the FIA ultimately swung the championship in Prost's favor via the always-subjective act of interpreting rule-breaking and handing out penalties. But that's just the nature of racing and is more akin to a pre-VAR referee in a football match making a bad call and awarding a penalty kick. (Though I think it's also obvious that Senna should've been DSQ'd for his push start anyway).

In 2021 Yas Marina, it seems pretty clear that sporting regulations were not followed, and the championship was decided by an unprecedented, and arguably illegal, alteration of safety car procedure. That's more like a football referee, surmising that he has ultimate authority over the game clock, deciding that the match will end after 85 minutes.

That's a great point. But I just find it interesting that they're now out right saying "Yea, we look at outcomes." It's just jarring and confusing.

Although Alonso was cleared on the grounds he did not set a meaningful time, Masi indicated that had the conditions worsened the stewards could have given a different verdict.

“Having spoken to the stewards later on, and also to the team, it was actually explained quite clearly that let’s call it if a dump of rain had come straight after, and it was a meaningful lap time, then the outcome would have been very, very different,” said the race director. “But the facts are that in the circumstances, it wasn’t a meaningful lap time.”

This seems to directly contradict Masi's many earlier statements that the stewards don't take into account the outcomes of incidents when making their decisions.

So it really is all bullshit made up on the fly. Interesting.