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Cake day: March 31st, 2025

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  • their original promise was that: you will be able to plug a jar to a controller, download instructions and it will make medicine for you, no knowledge of chemistry needed. i think it was one talk before this one where they claimed to make an antiviral (still under patent) and gave away some pills of it for free. i don’t think they made it in a way that matters, they didn’t show their pathway, they didn’t show analyses they say they made, they don’t say what they used as a starting material and how they got it, and they didn’t provide anything in way of formulation or other three drugs needed in that treatment (iirc). it might be very well that their costs are even higher per pill than what usual distribution will charge, but they don’t say any of that, and it might be just as possible that if more people did that starting material supply would dry out. (or they might be just lying) worse than that, while they might do some analyses, it’s not included or expected in jar and controller scenario, so there’s no real quality control and if released, this alone can be reasonably expected to kill people. i’m not sure if they even released anything workable in this capacity (they also claim that they made pyrimethamine, but it’s also after nilered made it, so they might just copy his process. it’s simpler thing)

    what they’re doing later: there’s this horse medicine that you can use as (more dangerous, less effective) ersatz plan B, or this estradiol thing, it’s much less sketchy because they don’t cook anything, they “just” formulate an API they get from somewhere else, but it’s still a fair bit sketchier than using fish antibiotics in humans because for example massive accidental overdose is still quite likely


  • 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).

    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



  • 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









  • Now, this is clearly a repugnant market. Repugnant market is a market where some people would like to engage in it and other people think they shouldn’t. (Think market in human kidneys. Or prostitution. Or the market in abortions. […])
    

    i consent/i consent/ i don’t!!

    lol who asked them? stop the presses, homegrown techbro has an Opinion! also when you use up drones it’s only natural that you’ll need new ones. even observation drones go down all the time, and rewarding certain targets is just making sure that drones don’t get blown up on stupid shit, so this is government specifically incentivizing what would be most important targets to them, on top of regular rules of engagement and more specific orders. this one seems to be meant as supplementary program that also, or even primarily, makes nice videos for propaganda

    Introducing a market system, on the other hand, allows the lower-level units to take calculated risks. Destroy that many enemy units and you can buy, say, an armored vehicle, that improves your safety. Friction gets greatly reduced.

    these are drones for drone kills, nothing else. biggest thing i’ve seen is that some units get donations from their drone videos, and used these to get a car or jammer or more drones, but never APC or anything like that, it’s too big deal and too expensive, and drone operator is unlikely to benefit from APC anyway

    No side gets an advantage when both sides use it. Then there’s no point in using it in the first place.

    wtf? if using a thing gives you advantage over not using a thing, then you use it, if both sides are using a thing then it’s just red queen race. lots of current war looks like it even if frontlines are static

    But markets, unlike, say, chemical weapons, are not directly visible on the battlefield. Each side would suspect the other of using them despite the ban and might try to secretly use them as well.

    and this changes what exactly? all it will cause is slight preference in targeting because there’s only so many drones to be given out, and drone operator has to do the everything else part of their job. dogshit reasoning




  • slightly more seriously: lots of lemmy users came from reddit, but mostly from older demographic (because of old reddit phaseout) and more FOSS-oriented, privacy-aware, tech-literate part (because of API shitshow/alternative apps blockage). there’s some barrier to entry (choice of instance) that would filter off the least technical users. there are some prominent programming oriented fedi servers (programming.dev, infosec.exchange). lemmy in general seems to be more lefty than reddit, less americacentric, and i guess that over half are linux users. i suspect that because of combination of technical skill and older age (compared to reddit) lots of lemmitors have well paying technical jobs (again compared to reddit) which allows/requires them to live in nicer parts of their countries (not specifically cali)