Need to let loose a primal scream without collecting footnotes first? Have a sneer percolating in your system but not enough time/energy to make a whole post about it? Go forth and be mid: Welcome to the Stubsack, your first port of call for learning fresh Awful you’ll near-instantly regret.
Any awful.systems sub may be subsneered in this subthread, techtakes or no.
If your sneer seems higher quality than you thought, feel free to cut’n’paste it into its own post — there’s no quota for posting and the bar really isn’t that high.
The post Xitter web has spawned soo many “esoteric” right wing freaks, but there’s no appropriate sneer-space for them. I’m talking redscare-ish, reality challenged “culture critics” who write about everything but understand nothing. I’m talking about reply-guys who make the same 6 tweets about the same 3 subjects. They’re inescapable at this point, yet I don’t see them mocked (as much as they should be)
Like, there was one dude a while back who insisted that women couldn’t be surgeons because they didn’t believe in the moon or in stars? I think each and every one of these guys is uniquely fucked up and if I can’t escape them, I would love to sneer at them.
(Credit and/or blame to David Gerard for starting this.)
Derek Lowe comes in with another sneer at techbro-optimism of collection of AI startup talking points wearing skins of people saying that definitely all medicine is solved, just throw more compute at it https://www.science.org/content/blog-post/end-disease (it's two weeks old, but it's not like any of you read him regularly). more relevantly he also links all his previous writing on this topic, starting with 2007 piece about techbros wondering why didn't anyone brought SV Disruption™ to pharma: https://www.science.org/content/blog-post/andy-grove-rich-famous-smart-and-wrong
interesting to see that he reaches some of pretty much compsci-flavoured conclusions despite not having compsci background. still not exactly there yet as he leaves some possibility of AGI
Of course not he is a capitalist pigdog! A traitor to the cause! Bla bla. ;)
I posted his work here before, despite thinking he isnt totally correct about his stance on capitalism stuff. He seems to be a good source on the whole medical chemistry science field. And quite skeptical and hype resistance. (Prob also why he I could make de self deprecating joke above). He wrote also negatively about the hackers who do homemade meds thing.
i've heard about them before and got reminded of their existence against my will recently. (do you know that somebody made a recommendation engine for peertube? can you guess which CCC talk from last winter was on top of pile in their example?)
you know, i think they have a bit of that techbro urge to turn every human activity into series of marketable ESP32 IOT-enabled widgets, except that they don't do that to woo VCs, they say they do that for betterment of humanity, but i think they're doing it for clout. because lemmy has only communist programmers and no one else, not much later i stumbled upon an essay on how trying to make programming languages easier in some ways is doomed to fail, because the task of programming itself is complex and much more than just writing code, and if you try, you get monstrosities like COBOL. i'm not in IT but it seems to me that this take is more common among fans of C and has little overlap with type of techbros from above.
so in some way, they are trying to cobolify backyard chemistry. the thing that is stupid about it is that it has been done before, and it's a very useful tool, and also it does something completely opposite than what they wanted to do. it's called solid phase peptide synthesis, and it replaces synthetic process that previously has been used in liquid phase (that is, like you do usually in normal solutions in normal flasks). (there's also a way to make synthetic DNA/RNA in similar way. both have a limitation that only a certain number of aminoacids/bases is actually practical). the thing about SPPS is that it can be automated, and you can just type in sequence of a peptide you want to get, and machine handles part of the rest.
what you gotta give it to them is that automated synthesis allows for a rapid output of many compounds. but it's also hideously expensive, uses equally expensive reagents, and requires constant attention and maintenance from two, ideally more, highly trained professionals in order to keep it running, and even then syntheses still can fail. in order to figure out what got wrong you need to use analytical equipment that costs about as much as that first machine, and then you have to unfuck up that failed synthesis in the first place, which is something that non-chemist won't be able to do. and even when everything goes right, product is still dirty and has to be purified using some other equipment. and even when it works, scaleup requires completely different approach (the older one) because it just doesn't scale well above early phase research amounts.
what i meant to say is that while automation of this kind is good because it allows humans to skip mind-numbingly repetitive steps (and allows to focus on "the everything else" aspect of research, like experiment planning, or parts of synthesis that machine can't do - which tend to be harder and so more rewarding problems) this all absolutely does not lead to deskilling of synthesis like this bozo in camo vest wanted to, i'd say it's exactly the opposite. there's also the entire aspect of how they don't do analysis or purification of anything, and this alone i guess will kill people at some point
This is prob right, but the 'in some ways' part does a lot of work here. Think the issue is that some complexity can be removed without problem, and some absolutely cannot. And the problem of figuring out which is which is hard. (Which if you squint, seems to be similar to the chemistry stuff you describe here). With software it (as far as I can tell) is also quickly that bigger projects need bigger teams, and that adds a lot of communication problems, and as a non-stacking process you can't just add more programmers to make stuff go faster (compared to for example building a building, which can be sped up a lot more with just more workers) as these communication problems remain. From what I heard is that this, and the problem of maintaining software on a large scale is what Java was trying to fix. Which is why all programmers love Java. It is a language for enterprise scale projects. (On that note, which is also why a lot of reason people hate Java for the wrong reasons, a lot of the hated stuff makes sense if you recall it is made for enterprise scale projects/teams etc. It is an attempt to make those projects easier (lets leave it in the middle if that attempt worked or not (Do think it is amusing that Minecraft of all things was coded in Java by a single person (initially))).
Interesting our community seems to attract a few outspoken chemistry people. Not something I know much about, know somebody who does something with crystal chemistry machines, and when he technically talks about it I'm happy I understand about 30% :).
@Soyweiser @fullsquare
"With software it (as far as I can tell) is also quickly that bigger projects need bigger teams, and that adds a lot of communication problems, and as a non-stacking process you can’t just add more programmers to make stuff go faster"
I bought two copies of that Fred Brooks book so I could read it twice as fast
@pikesley @Soyweiser @fullsquare IIRC the coordination problem afflicts all engineering disciplines: with large tech projects like the LHC and ITER, costs scale as something like the fourth power of the energies they're working with, and a large part of the reason is that managing the project is insanely difficult. I'd love to see some numbers for how the management complexity of large software projects (eg. operating systems, LLMs) compares to this.
Well, i'm not exactly sure about it, but what i can do is describe how this process works in terms of operations and you can draw your own conclusions. There's not that much complexity in peptides in the first place, because synthetically, all you have to do is to make a lot of amide bonds, and this is a solved problem. Slightly bigger problem is to make it in controlled way, which is reason why protecting groups are used, but this is also a thing that has been around for decades.
The trick is to bind the thing you want to get to resin, which makes it always insoluble and therefore your product always stays in reactor. This can be an actual dedicated automated reactor or a syringe with a filter. We start with
Resin-NH-Fmoc
Fmoc is a protecting group that falls off when flushed with a base, so we do so, wash resin, and get
Resin-NH2
Then we can add coupling agent and protected aminoacid, for example leucine, then wash again, and this gets us
Resin-NH-Leu-Fmoc
then repeat. All operations are add reagent or wash solvent, stir, wait, drain, repeat. Deprotection, solvent, coupling, solvent, repeat. It's all very amenable to automation and it was explicitly designed this way. When all is done, resin is treated with acid which releases peptide, and because resin can be washed there are no leftover reagents.
Of course it can be all done by hand, and this allows for doing things like putting a couple of aminoacids on resin on a big scale, then splitting it into a couple of batches and attaching different things on top of that in parallel. Machine can't do this (at least machine like we have). Machine can instead run all of this while hot and this makes it fast, but sometimes things break this way, and also machine can run unattended for more than one shift (when it's not broken). Sometimes things fail to work anyway and it's a job of specialist to figure it out and unfuck it up. Sometimes peptide folds on itself in such a way that -NH2 end is hidden inside and next residue can't be attached. This can be fixed by gluing two aminoacids in flask and then using a pair instead of a single one in machine, bypassing that problematic step. Or in a couple of other different ways, and picking the right one requires knowing what are you doing.
Solution phase synthesis looks different because every step requires purification after it, which is sometimes a thing you can wing and sometimes not. The advantage is that when you need lots of product, you can just use bigger flasks, while bigger machine (and large amounts of resin) gets prohibitively expensive. Ozempic was made in solution (at least once) for example. Again, doing things by hand gets you extra flexibility, because machine can only make peptide from start to finish in single run, but if it's done in solution instead, you can start from, say, five points and then put pieces together (which starts to look like convergent synthesis, and this also makes it better for large scale). Machine can't do that (unless these pieces are provided, but at this point most of the work is done)
Looking back at these people, even when operations are simplified, there's no deskilling of operators that they aimed for, it's just throughput that increases. They also don't have the benefit of that "keeping the important things always in reactor" thing
i can't find that essay now, but i think it was written in latex, and also complained on top of cobol about java, ada (in military context) and a kind of non-programming where block diagram made by non-programmers was turned into executable
Of course it was. (I enjoy LaTeX myself but still, it is a type of person)