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.
(Semi-obligatory thanks to @dgerard for starting this.)
four thieves collective goes on 38C3 and i groan in anticipation of whatever stupid trick will they pull now https://fahrplan.events.ccc.de/congress/2024/fahrplan/talk/ASBXWW/ why they even are there
update: it's out and recorded https://streaming.media.ccc.de/38c3/relive/316 also update on intentionally bricked trains story from year ago https://streaming.media.ccc.de/38c3/relive/336
update 2: oh no. oh no no no no
I look forward to your reactions why this is all quite a bad idea (and not just a bit cringe).
so i figured out what their naloxone synthesis is, it's based on this paper https://sci-hub.se/10.1002/adsc.201300284 they say it's two step, it's not two step, it's 6 steps in two critical one-pot sequences. paper starts with oxymorphone and they start with oxycodone for some reason, that's one step extra. that transformation requires handling BBr3 which is nasty but clean or NaSEt which is also nasty but safer, but also requires column chromatography for purification. it still can fail in a way that gives products of activity opposite than intended. requires hard to get and rather more on expensive side reagents like vinylmagnesium bromide and burgess reagent, both require strictly anhydrous conditions to work. vinylmagnesium bromide and even solvent used with it (THF) will destroy that shitty PLA lid. final purification in paper requires column chromatography as well. not to mention elephant in the room, that if counterfeit oxy pills are used that contain fentanyl instead it gets you either nothing or fentanyl
what is in paper
what they have shown
this synthesis is fucking garbled and it's only one of many steps
same with cabotegravir
they're also using advanced intermediates that could be very hard to source, because this kind of stuff is made internally in company only, particularly that pyridone on left
and that's just naloxone. nothing particularly hard if you know what are you doing and have right starting materials. commercial synthesis is entirely different btw, and this is partially to make purifications easier and to use robust, high yielding chemistry using cheaper starting materials. they also want to make cabotegravir, mifepristone and fucking gene therapy, and diy hrt (they never cared about it before??) which was already a thing wayy before they got to it, it involved shipping steroids out of Ukraine iirc and it worked because no garage synthesis was involved at all. at least they admitted that making monoclonal antibodies is probably out of their reach, how merciful of them. and that's just first 15min
it looks like they're desperately pivoting for attention left and right, i see there nothing but grift
when you have to consider what this arduino jar is even capable of, just taking a look at that naloxone synthesis makes it absolutely fucking useless. it can't replace sep funnel, rotovap, chromatographic column; it can't provide inert atmosphere, required in steps 3 and 5 of original paper, it can't survive refluxing THF because lid will dissolve or melt and cave in, required in step 6 and whatever refluxing solvent is used in step giving oxymorphone from oxycodone, because they neglected to show it, and even if it did, there's no condenser on top. it really is juicero of backyard chemistry
update: yeah nah what the fuck laminar flow fumehood is wildly out of reach of normal people, making sterile injectables in a garage is not a safe option for 99.99% of people
update 2: analytical techniques included: homemade raman, melting point measurement, dancesafe drug test suite. and fucking taste test, going all the way to 1890s best practices i see. none of these are good at detecting impurities, it will only be good to detect if chinese vendor sent you wrong stuff and it's only if it was pure
update 3: WE'RE MAKING HRT! looks inside: we're buying APIs from India/China and compounding them in garage with zero real qc, also we'll solve HRT with garage gene therapy, promise, maybe, some years from now, donate in meantime
Thanks. The ending where he goes "how would I deal with company patent lawyers? Well flips them off" is a bit annoying as well. I heard some make diy E makers and distributers were jailed already. So setting up some assistance system for that would be nice (esp after you made it worse by making it easier for the courts to call them terrorists, sure the term has degraded but law wise this has consequences. I really hope he at least got some trans people involved before he started this (and i also really hope im wrong about the risks here, as trans people should get all the meds they want)).
he's already easily covered under personal/research nonprofit use so he doesn't have to care about any patents, it's even opposite, he can use all patents all he wants np as long as there's no profits associated with it. he takes donations tho and idk if it qualifies. not that copyright is the biggest problem here
i don't think that whatever he's doing will help transfolk cause too much, there already is some hormone supply and all he's doing is bringing unwanted attention. i hope i'm wrong on this one
I read through this with my wife who actually did a whole course of organic chemistry, pre-med, etc. Her reaction to your criticisms was largely "of course you would have to do that and that'd be a pain in the ass but it's definitely doable." And I feel like that's probably true but at the same time as a reasonably smart dude this is the first time I've heard the majority of these words.
It feels like they're reacting to the same tendency in tech culture that I've complained about before where specialized knowledge and domain expertise are treated like arcane revelations from beyond. It's not that your average person is incapable of understanding or going through the relevant processes; Cs ,as the saying goes, get degrees and I'm sure many of the labs actually doing this work at scale are staffed largely by those C students. But it's also worth acknowledging that there is a level of investment in time and resources required to actually do it and this kind of "you have nothing to lose but your pharmacological chains" rhetoric is dramatically underselling how difficult those processes are and how bad the consequences can be if you screw it up. Anyone who wants to try should first read The Iliad, the Oedipus cycle, and at least one other epic-sized meditation on hubris. And the once you've forged ahead read the relevant books on actually following the process for the love of God.
of course you can make it work but it's more expensive and harder than normal commercial synthesis. with such limited analytical methods you might not even be able to tell that something went wrong (melting points can be completely fucked up by traces of solvent, same with IR) naloxone is actually a nice example of how you can design synthesis in order to make your life easier, in terms of purification at least. one of commercial syntheses looks like this
anyway that's what i found in one chinese patent (CN104230945A). they start from oxycodone, which they make from thebaine, which they don't have to make because it's a natural product. there's a very useful purification technique, column chromatography, that works like this: you take a tube, fill it with silicagel, then pour hexane through it, then put your compound on top of that silicagel column. silicagel is polar, and the more polar compound is, the stronger it is bound to it. so now in order to get your pure compound you wash this column with increasingly polar solvents, and this way you can recover various compounds in order from least polar to most. this allows you to get pure compounds most of the time
now, small changes in or near polar groups mean that polarity changes little. in particular, we can ignore for five minutes all these hydroxyls and just focus on amine because it's the most polar part and any changes at other groups make polarity change in the same way anyway. step 2 is von braun degradation, and it removes methyl and turns amine into amide. this amide is very likely to have much lower polarity than starting product and so it can be easily separated on column. here specifically, it's no longer basic so unreacted acetyloxycodone can be just washed away with acid extraction, which is good for both low tech and large scale. step 3 is hydrolysis, which gives us amine back, which again gives more polar product which means again that separation is easy. if some acetyloxycodone was left there, it would give very similar compound, just with that N-methyl left and separating it would be pretty hard. this here is especially important as N-methyl and N-allyl compounds have opposite effects
that weird synthesis with burgess reagent and everything else also allows for separation of these unreacted starting materials, but this requires column chromatography in the middle. if you skip it, maybe it'll turn out alright or maybe you just fucked up for the last time. maybe mCPBA was old, or maybe burgess reagent or THF was wet, or any variety of random bullshit that someone inexperienced would not even register. and this is only one point that brings us to point 2: that jarduino is really juicero of backyard chemistry. to begin, you need dry solvents, and this is something you should do yourself if you want it to be done right. this means you need to reflux THF with drying agent of your choice, then distill it away to clean dry bottle, fill it with argon, ideally add molecular sieves and tape it shut. then you have to reflux something, this requires all glass flask because that 3d-printed head will melt under these conditions. at some point you also need sep funnel and rotovap and column, and so on and so on and it turns out that you already have all glassware to do it all the normal way and jarduino isn't even needed for anything. (also i don't understand their choice of peristaltic pumps, as they already put everything in syringes, this means that you can just use syringe pumps and use normal medical long needles for piping of sorts. it's very chemically resistant as long as plungers aren't rubber, which their demos had for some weird reason)
this is closer to the synthesis i thought they were using
~~if you swap oripavine for oxymorphone and cyclopropylmethyl bromide for allyl bromide, you should get naloxone, probably, in 2 steps.~~ this doesn't work keeping cyclopropylmethyl bromide and using oxymorphone gets you naltrexone which also works as antagonist and even slightly more potent one, it's from this paper https://cdnsciencepub.com/doi/10.1139/cjc-2014-0552
then there are all the sterility requirements, as they want to make injectables in garage. i'm not pharmacist or biologist, but i expect it would be a bit harder to make it reliably and repeatably than what they make it look like. i take that your wife is a medical professional so if she weighed in on that, that would be nice
also, part of their advice is to just eyeball powder as a part of identification. this is a bad idea because how stuff looks like and behaves can change depending on humidity, traces of solvents if any, and ambient temperature, especially for low melting solids, and crystal habit can vary from batch to batch anyway and it's not a reliable indicator of anything
Unfortunately actually working in bio/med didn't go well despite training for it aggressively and working her ass off given that she graduated at the perfect time to compete for entry-level positions with recently laid-off people with 5+ years of experience. Between that and chronic illness in the family will all the associated experience with the failings of our medical system I'm actually pretty sympathetic to the biohackers from a purely ideological perspective, but these people are just begging for a disaster.
Beyond reading through and enthusiastically agreeing with everything you had, she did say that if you're working on anything consumable or injectable using 3D printed parts at all is going to be a red flag. Your first two pieces of equipment should be an autoclave and a fume hood, at which point you're better off working with all glass for durability and not melting reasons. Making your work space actually sterile and sufficiently free of contaminants to do any of this jnt be first place is also going to be a pain, require a lot of tape and curtains and the like, and probably not work as well as you'd want.
Also even working in a proper university lab with a fume hood and climate controls you still get sufficiently different results that the mk1 eyeball is utterly insufficient for identification. You'll learn worse than nothing.
I keep having to remind a couple of my friends who got 3D printers for themselves as gifts that 3D printed parts aren’t ever food safe, much less whatever standard’s required to make safe injectables. specifically, bacteria likes to hide inside the layer lines on FDM parts, and resin parts are made of a material that shouldn’t be ingested or introduced into your bloodstream
on chemistry side, i guess you can wing it a bit and not strictly require fume hood in low population density area. not having rotovap, at best with appendages (chiller + chemical resistant vacuum pump, aspirator gives limited capability) makes all but simplest syntheses deeply unserious to impossible especially if you want to do some analysis later. especially if it's IR and melting point because solvents fuck up both
JFC
go back 200 years before the "gubmint" got involved in public health and tell me that average life expectancy was better than now
before the pandemic it was possible for people to believe that libertarianism was an answer to everything, turns out if it was a tiny minority would have hoarded all the PPE while the people they were gonna sell it to died of the plague. libertarians have not been able to square this circle since
I think there is value in giving people the tools and knowledge to make more involved decisions about their health, but using that sort of libertarian rhetoric in the covid era is at best really fucking irresponsible.
I have the feeling that they're not a British trans person talking about the NHS, or an American in a red state panicking about dying of sepsis because the baby they wanted so badly miscarried.
maybe it's more of a take acceptable for americans
Yeah, as somebody in the USA, I think that both you and @[email protected] are pearl-clutching over laboratory conditions while ignoring the other, more serious safety problems being addressed; the presentation was not exaggerating when they were talking about the lifesaving impact of gender-affirming therapy. Last thread, you sheepishly admitted that part of the synthesis is complicated by criminalization and over-regulation; this thread, I'd like a sheepish admission that about a third of the USA (by population) suffers from restrictions on their reproductive rights.
Like, yes, you shouldn't brew your own high-proof alcohol at home, because you can go blind from methanol poisoning. But also, there was a time in the USA when high-proof alcohol was over-regulated, and it incentivized a lot of people to homebrew.
i see this all more as a publicity stunt/attention grab than anything else. i wrote there about naloxone because laufer has put much more information about naloxone than about anything else in question there. he has put naloxone structure on his website all the way back in 2016 with "other molecules" description, suggesting that there's some work in progress. now he's talking about "releasing" procedure for naloxone synthesis ripped from a paper that came out in 2013, available on scihub for all to see. it took them so fucking long that since then: 1. availability of black market opioids shifted from genuine perc pills that you can divert from real pharmacy and that can be used to make naloxone, to possibly counterfeit ones containing fentanyl that you can't. were he releasing this all the way back in say 2018, this still could be marginally useful. 2. since then naloxone has been made available OTC making cooking it on your own obsolete. 3. there's also an option of using some other antagonists that can use codeine as starting material - i'd like to see this regulated - but these come with more side effects and absolutely zero work has been done in this direction either. whatever he's doing, it's not particularly fruitful other than getting talks for people who don't know any better
you're saying this as if it's american-only problem. diy hrt and diy plan-b were a thing way before laufer and will continue to be a thing until they're not needed, and these work by diverting legit pharmaceuticals. his miso card thing is possibly okayish if sealed but it works only because there's no synthesis involved, it's diverting veterinary drugs, which is fine because it's likely that these come from the same reactor anyway. if anything i guess he might be harmful in this one by bringing unwanted attention. if you take into attention that he floated an idea of making gene therapy on their own, with aim of introducing extra aromatase so that testosterone is transformed into estrogen almost completely, as an alternative to hrt, and possibly some other gene therapies, i cannot take him seriously. this gotta be a massive, overly long, deeply unserious attention grab. if it's grift, it's not a very good one, with $23k (current prices) in crypto donations since 2019 and $5/mo patreon
and btw there's no methanol in moonshine, at least not in harmful levels. there is methanol in denatured alcohol in countries where regulators don't give a fuck or where they believe that "morally deficient" people like addicts should suffer, like in US, in EU contaminants are nontoxic. methanol in counterfeit alcohol occurs only as intentional contamination and/or cost-cutting measure, or when whoever is cooking it does not know any better
The FDA is a response to people just making shit up and selling cough cures full of opium. "Raw milk" pushers are cut from the same cloth.
It also prevented the Thalidomide medication from causing much damage in the usa (compared to the rest of the world) https://en.m.wikipedia.org/wiki/Thalidomide_scandal and prob countless more, as it is a bit hard to cause problems if the problems are caught before it being brought to market. And I do worry that the "the fda is too cautious" pushers are actually motte baileying for the total removal of the fda.
they absolutely are, see also Scott Alexander stanning for these guys
NRx people was what I was thinking about. Every city a city state with bespoke medical experimentation going on. And if you don't like it, just leave and go to a different city state with different crazy medical experiments.
@Soyweiser Thalidomide was mostly a British problem (that led to the UK's CSM getting teeth). The FDA in the USA really got rolling after the Elixir Sulfanilamide poisonings in 1937: https://en.wikipedia.org/wiki/Elixir/_sulfanilamide
there were also a couple of cases since where DEG replaced glycerine in syrups, either by negligence by manufacturer of syrup, manufacturer of intermediate, or knowingly as a cost cutting measure, last one in 2022
Ah right, thanks! Weren't there also a lot of German victims?
there was austrian wine contamination incident in 1985
idk what went wrong there but village industry of altmed clinics seems to be an actual thing, and from what i understand it's apparently legal in some of red states
(from observation over some years) congress orga more than occasionally fucks up on paradox of tolerance by letting shit like this through
it's been a thing I've noticed and have wanted to actually discuss with some folks, but never really gotten to yet on account of life stuff
there were also the much, much less grey-area instances a couple of years back where they were far too open to a number of abusers (this was around the time the appelbaum shit hit wide daylight), so there is a possibility that the issue runs deeper (in a structural sense, at best; personal sense, at worst) too but I possess insufficient information to know one way or the other what exactly may constitute the problem here
I don't wanna pull national stereotypes here but aren't Germans really quite open about stuff like homeopathy? "be your own pharmacist" sounds like right up that alley
Yes, I can confirm this is true. Homeopathy is really accepted here and is even covered by most health insurances.
There is even a passage in the pharmaceutical law that specifically excludes homeopathic shit from having to prove its effectiveness (they only have to prove it’s not hurting anyone, and the rules for that are much laxer than for other medicine). It’s absolutely baffling.
There also is a lot of homeopathic meds in the Netherlands, dont know about the legal status, do know it didnt help much with my hayfever as a kid.
Theres a long rich history of German alt med. also (postwar) witch trials, if I can find the book I read on all this I’ll try to post.
Edit: think it was this one https://academic.oup.com/ahr/article-abstract/128/2/1015/7204469?login=false
whoah that looks interesting, how can I access it (semi-)legally?
Its on annas and amazon.
also on my fav book torrent tracker - even has an audiobook version!
I haven't really got enough information about that side of it, the details I have to go on are mostly about things particularly around the values CCC has tried to hold/build (and even there I am absolutely not intimately familiar, for reasons of distance and exposure and such)
never heard of them before. from skimming their wikipedia, it seems their grift is glossing over the details in the "science" part?
From what I heard: Skimming over science, best practices, risks of contamination, risk of producing horror chemicals, problems of sourcing materials, storing materials, storing the final product etc etc.
Here is a bsky thread from the last time they were in the publics eye (more here if you dont have an account) (the latter articles are clearly working on a diff definition of capitalism than I use so I chose not to be too annoyed with the weird digs about that).
This should be a very big red flag: "Mixæl Swan Laufer worked in mathematics and high energy physics until he decided to use his background in science to tackle problems of global health and human rights." (Ignoring all the other smaller red flags btw, I think I could point one out ever paragraph, if I had not heard about these people before, the final red pill reference would have made me think they were trolling).
interesting read, thanks. the red pill reference also had me rolling my eyes. i guess it's more virtue signalling than actually making a change.
It is a bit weird, it has very high EA vibes to me, started and did some good (epipen in 2017 vs EAs malaria nets), but end up to have some crazy plan for which the other things are more of a smokescreen for their real plans (an easy bake chemical oven make chems at home kit vs EAs stopping our lord and saviour the robotgod) using rethoric aimed at a specific subgroup (2000-2010 anarchist libertarian hackers vs nerdy altruists)
E: I really wonder if they were influenced by the dr sleepless series from the disgraced warren ellis, and the stuff around that.
i've complained about them previously https://awful.systems/comment/2754222