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Anarchist Drugs For All. Yeahboy.

I’ve had numerous requests for my opinion about this article, so here it comes: it’s largely bullshit.

It’s about “a volunteer network of anarchists and hackers developing DIY medical technologies”, and I can see why Vice.com is running the article, because that drugs/anarchists/hackers combo is absolute catnip to their demographic (or at least the editorial staff there figures it has to be). This network calls themselves Four Thieves Vinegar, and according to the article, they’ve been going around getting on the nerves of regulatory authorities, the pharma industry, and their allies for about ten years now. Well, all I can say is that they’re not doing a very high-profile job of it, because I’ve been doing research in the industry now for almost 30 years and writing this blog about it for over 16, and this is the first time I’m hearing about these guys. (Update: see this article from last year).

According to the article, they’re “living proof that effective medicines can be developed on a budget outside of institutional channels”. But that is exactly what they’re not. They have synthesized naloxone, Daraprim (pyrimethamine), Cabotegravir (GSK1265744, an HIV integrase inhibitor), mifepristone, and misoprostol (the last two used in abortions) with homemade apparatus, which is described in terms of Mason jars. And for the chemists in the audience – like me – here’s where the questions start. Apparently the only one that this anarcho-collective is offering at present is the pyrimethamine, which makes sense because chemically it’s by far the easiest on that list to synthesize. And as with any chemical synthesis, a key question is “What’s the starting material”?

That’s going to determine how much work you have to do. A nearly-retired undergraduate professor of mine back in the early 1980s (Bob Shideler) used to have you start out on paper with “lime and coke”, aka limestone and carbon. From that, he told us, you can make calcium carbide, which gives you acetylene, and Reppe chemistry and its successors showed you how to use that as a feedstock for all kinds of other stuff. You’d rather not do it that way. For example, naloxone has the morphinan backbone common to that class of natural products, and that framework is no joke to synthesize from scratch. Sensibly enough, the Vinegar boys make it from the much more, ahem, readily available oxycodone. You’ll need to demethylate the nitrogen, put in an N-allyl, and do an O-demethylation in one order or another, but these reactions should be no barrier to anarchists with Mason jars. The article quotes the group as saying that they go through the O-demethylated oxomorphone.

Fair enough. But what happens when you get to a molecule like Cabotegravir? 2,4-difluorobenzylamine is not available on the street, just to list one of the starting materials one would need. I’ve taken a look at the patent literature on the compound, and while the reactions aren’t difficult, it’s not a two-step synthesis, either. There are going to be reagents to be sources, purifications to be fun, and you’ll need to characterize the compound to make sure that you’ve made what you thought you made. Putting a compound like this in your body without at least an LC/MS and an NMR is a very foolish thing indeed, and I don’t see much indication that there’s a Four Thieves Vinegar instrumentation facility. To be sure, this issue is raised in the Vice article by a voice of sanity from MIT, who mentions the possibility of a Darwin award for the customers.

I understand that the folks doing this underground synthesis realize these problems exist, and are trying to come up with synthetic routes that are less likely to produce trouble. Well and good. But there’s another issue: the long-acting nature of Cabotegravir seems to be a property of a particular nanoparticle formulation, and I can tell you for sure that there is no Four Thieve Vinegar formulation facility that’s making API nanoparticles. No, what they’re doing, according to the article, is giving material to heroin dealers and persuading them to put some in their product, so that IV drug users can be protected from HIV. Interesting idea – but do the Vinegar guys know how stable the compound is under those conditions, and especially under the usual heroin-user-prep conditions? There’s no indication. Or how effective it is when injected in this way rather than in the (painstakingly arrived at) formulation that’s being used in the clinical trials? No. How could they? You have to do human trials to figure these things out, and that takes, like, capital, man, which is dirty and foul. Dosing people under uncontrolled conditions, though, that’s pure and admirable. Are we all straight on this?

Late in the piece, it’s mentioned that the anarcho-hackers would like to make Sovaldi next, and “If Four Thieves has its way, Hepatitis C will soon be a thing of the past for everyone, regardless of their income.” Peachy. That’s a combination therapy if you want to eradicate the virus, first of all, so you’re going to be making more than one drug. And there is no reason to think that there are enough easily available starting materials out there on the streets to make enough drugs to treat everyone with Hep C. It’s worth noting that if you bungle the dosing of antivirals or antibacterials by going too low in infected patients, you run a real risk of (a) not killing off the infectious agents and (b) producing resistant ones instead. So basement antivirals could easily end up making the hepatitis situation even worse. Oh, and there are so many patients out there that even a bunch of nonprofit anarchists will have to – ugh – raise serious money if they want to even contemplate an effort this size. This is a fantasy, a black-flag comic book.

The article goes on to talk about orphan diseases and biologics, and goes further and further off into the skies as it does so. There’s talk of sharing cells and cultures, fungal spores on book pages (so they can be shipped book-rate to save money, and no I’m not making that part up), and it’s all pretty ridiculous if you know the slightest thing about cell culture and propagation, natural product isolation, or indeed if you know much about anything relevant to the field whatsoever. Attacking this stuff would be fun but cruel, so I’ll move on.

There’s a lot of talk in the article about “liberating” medicine and the “free flow of information”. But you know what? You can already get the synthetic procedures for drugs right there in the patent literature if you want. They have to work, too, or any patent claiming those procedures is invalid. And there will be spectroscopic data in there, to prove that they made what they claimed they made, assuming that you’re in a position to follow up on that. Similarly, you can get dosing schedules and all sorts of other information, for free. So what information is being liberated, exactly?

Near the end, the head of the Vinegar folks talks about “science as a human right”. That has a fine sound to it, and it’s vague enough that it’s easy to sign on. But what does it mean? Do you have the right to an LC/MS machine, or an NMR spectrometer? That would mean that you also have rights, by the way, to things like liquid helium and trifluoroacetic acid/acetonitrile mixtures, but we’ll let that go past. What I’m getting at is that people like Four Thieves Vinegar are not developing drugs. They’re trying to find cheap, easily replicable ways to make and distribute drugs that other people have already spent the time and money to develop. If the capitalists of the world hadn’t ponied up the at-risk funding to find those drugs in the first place, there would be nothing for anarcho-hacker pharma collectives to do. Speaking for the Big Evil Pharma Industry, if I may, you Vinegar Thieves are living in our basement and subsisting on what we provide. So all the raised-fist liberation talk seems kind of eye-rolling. And that’s all the time I can stand to spend on this stuff.

 

106 comments on “Anarchist Drugs For All. Yeahboy.”

  1. Mad Chemist says:

    So they’re an anarchist organization? Isn’t that a contradiction? Does their organization have a constitution and bylaws? How about elections?

    1. Mikael says:

      Most Anarchist organizations over 50 members up to the largest (historically the international workingmen’s association had over 7 million members in only Europe and the US) have democratic structures, yes. My union is small, at 8000 members, but it also has a solid grass roots federalist membership democracy.

    2. PoliticsIsNotScience says:

      Anarchism isn’t against organisation, indeed most anarchist theorists emphasise the idea of cooperation over competition. I suppose you could think of it as horizontal organisation rather than vertical hierarchies.

      Although given their attitude towards chemistry I wouldn’t be entirely sure that these kids have a particularly sophisticated understanding of anarchism either 😉

  2. Wavefunction says:

    “Science as a human right”? I like Niels Bohr’s definition better: “The common goal of science is the gradual removal of all prejudices”. Will it help the Vinegar boys remove theirs?

  3. NewInPharma says:

    As a 20 something Chemistry major while I love the idea of anarchistic medicine and taking down Big Pharma the Four Thieves Vinegar sound like complete idiots. I currently am working an internship for a generic pharmaceutical company and even after three years of chemical education the amount of work I see going into knocking off medicine with a large amount of capital is dizzying. I can’t wait to see what happens to this Vice article when the group is linked back to the deaths of some people because to me this seems inevitable.

    1. Ian says:

      You shouldn’t love the idea of anarchistic medicine taking down big pharma. I think Derek outlined it pretty well in the article. Anarchistic medicine isn’t developing new drugs. What happens when their Hep C dosing is wrong and they create an immune strain of Hep C? Are they going to put in the hundreds of millions of dollars and man hours to develop a NEW drug that can take care of that new strain? And what, just to give it away for free?

      1. Courtney says:

        Nobody made any medical advancements before capitalism. Good point.

        1. microbiohno says:

          And capitalism is exactly the problem imo? Law and tight regulations are good, they can be incredibly helpful ensuring adequate care in the field of medicine. I don’t want anarchists to bypass safety regulations, those things exists for a reason. I just want the overwhelming drive for profit to stop funking with sick and/or dying people.

        2. Vader says:

          Having trouble determining if you’re being sarcastic or not. Adam Smith wrote in 1776, the same year George Washington’s Continental Army became the Army of the United States. This is the same man that became the first U.S. President, refusing to be elected a third time, refusing to be named as king (and thus causing George III, in a more lucid moment, to suggest Washington was the greatest man in the world) … and died when he was bled to death by a physician on the basis of medical theories going back over two thousand years.

          It may be too much to say that there were no medical advancements before capitalism, but it is probably not too much to say that there were few medical advancements before capitalism.

  4. Bagger Vance says:

    Let me just point out that the glorified leader of this enterprise, Michael Laufer, has graduate degree in Mathematics.

    One may suggest this is another data point on the Andy Grove Fallacy.

    1. tangent says:

      I am shocked, shocked that it is not Computer Science.

      (I am speaking as a computer scientist.)

  5. K says:

    “living proof that effective medicines can be developed on a budget outside of institutional channels”

    The word developed definitely should be synthesized. They aren’t developing any new medicines, they’re just synthesizing compounds that took many years to develop as therapies.

  6. Pittance says:

    I do not comment here often (not a chemist, but interested) but the fact that they are offering pyrimethamine is almost certainly because there is a route for that synthesis from commonly available precursors published on YouTube by the chemistry channel “NurdRage”. That was done for the challenge, not because it produces a safe endpoint.

    1. AZSkyeRx, PharmD says:

      Not to mention that daraprim for PCP require co-administration with dapsone and in all cases should be taken with leucovorin to avoid significant toxicity from interrupted folate synthesis. That information is even easier to access than the chemical synthesis steps but since these idiots have no medical training I’m not surprised they don’t know that.

  7. Peter S. Shenkin says:

    @MadChemist

    Anarchy and Organization are far from mutually incompatible. See the Wikipedia article on Anarcho-Syndicalism.

    Noam Chomsky and George Orwell both subscribe(d) to this philosophy; see Orwell’s “Homage to Catalonia”.

    There was a large global Anarcho-Syndicalist movement up through the 1920s. The closest to a major Anarcho-Syndicalist organization in the U.S. has been the IWW (International Workers of the World, the “Wobblies”), though some hesitate to apply that label to them.

    1. DH says:

      I *told* you! We’re an anarcho-syndicalist commune! We’re taking turns to act as a sort of executive-officer-for-the-week. But all the decisions *of* that officer have to be ratified at a special bi-weekly meeting. By a simple majority, in the case of purely internal affairs, by a two-thirds majority, in the case of more major issues…

      1. Tom says:

        Speaking for myself, I find it pretty tragic that in the year 2018 people see the idea of democracy as no more than the butt of a joke.

        1. UudonRock says:

          “Come and see the violence inherent in the system! Help! Help! I’m being repressed!”

  8. MTK says:

    Making the API is not making the drug, as everyone here probably realizes.

    Particle size, crystal form, excipients, etc are all important for proper drug behavior.

    But who cares as long as they’re sticking it to Big Pharma!

    1. Hap says:

      Sometimes you have to screw yourself over to screw someone else. That seems to be the philosophy behind a lot of things lately.

      1. Vader says:

        Yeah. “Burn it all down” is all the rage nowadays.

  9. a says:

    their points about the epipen and shrikelli regulation-hijacking (aptly covered in derek’s blog before) are valid

    but yeah, 90% BS.

  10. Chrispy says:

    This reminds me of the “Frozen Addicts” — MPTP contamination of batches of the opiate drug MPPP leads to almost instant and permanent Parkinsonism in those who inject it. This has happened a few times. On the plus side, it has provided a useful model of Parkinson’s in squirrel monkeys.

    Our health care system in this country is a mess, but the Vinegar boys aren’t helping.

    That said, I have known more than one chemist who has made compounds for their own consumption — with extensive characterization in a real lab. I even recall hearing of a biologic being made for pets — feline erythropoietin. That was made quite openly until the company’s lawyers heard and shut it down. That’s a pity, because anemia is common in cats, and now people are forced to use the human version, which is immunogenic in cats.

    1. Mark Thorson says:

      The MPTP incident was in Saratoga, CA. The guy who made it lived about a mile from where I lived at the time and where I live now. Robin Williams starred in a movie about the doctor who discovered the outbreak of Parkinson’s that resulted.

      1. Stephen says:

        er are you thinking of Awakenings which was about the discovery of L-Dopa treatment for Parkinson’s – nothing to do with MPTP

        1. Derek Lowe says:

          Sounds like Awakenings, but IIRC that was the result of an encephalaltis lethargica epidemic. That was a CNS disease of unknown origin that peaked in the early 1920s in many countries (not long after the huge influenza epidemic, which may well be no coincidence). From what I understand, the etiology of EL is still a major mystery, partly because nothing on that scale has ever happened since. But there certainly was damage to the dopaminergic regions of the brain, whatever the cause (infection by bacterial or viral agent, secondary autoimmune response to those or something else, perhaps primed by the influenza epidemic – who knows?)

          1. HTSguy says:

            It was the late Oliver Sacks who treated them with L-Dopa and who later wrote the book Awakenings.

    2. Prognathodon says:

      I initially read “anemia” as “amnesia”, and was wondering how you tell amnesia in cats from cats not caring to remember.

  11. tt says:

    Darwin Award….definitely. As a process chemist, this is laughable. Not just acquiring all the RMs, but thinking about QC and impurity control. cGMP exists for very good reasons…hopefully their “customers” don’t find this out the hard way.

  12. Laurent Wada says:

    Eh, don’t buy it if you don’t like it. I say good luck to them and their customers. They’ll need it.

    1. Steven K says:

      I’m typically of the mind “if you don’t like X, don’t buy/do X” instead of prohibiting X, but this has a good chance of creating treatment-resistant HCV strains that can go on to infect others who didn’t make the stupid decision to take these illegitimately produced drugs. But hey, I guess that would leave it up to a few colleagues of mine who recently published a paper on using machine learning to predict resistance susceptibility of new small molecules for antivirals, specifically in NNRTIs, to develop a next-generation HCV drug.

  13. a. nonymaus says:

    Lime and coke? Bah, back in my day, we had to start with a quark-gluon plasma…

  14. Bob Seevers says:

    I await their publication in the Journal of Irreproducible Results.

    1. Jeff says:

      I expect the results of this nonsense to be unusually reproducible: namely, a very reliable rate of personal harm scaling up to death.

  15. cynical1 says:

    I remember in the 80s where they had a bunch of non-chemist types trying to make the opiate MPPP and they wound up having batches with MPTP as an impurity. Had some pretty devastating effects on the junkies. It gave them irreversible Parkinson’s disease and MPTP is still used as a way to produce the disease in animal models. See, it turns out that stupid people can contribute to science in ways that they never imagined. This Four Thieves Vinegar group is on a bee line to a similar type of discovery. It is my humble opinion that stupid should hurt. I just hope it hurts them and not everyone else.

    Another aside, free access to naloxone from community sources is widely available as well as payment assistance programs. There are also community based resources for instruction on how to deliver the drug from an intranasal formulation for family and friends of opiate users. These resources are available throughout the US at some level. (I have personally been trained in one of those programs.) Why would you need these clowns to come up with a way to produce it from oxycontin? As someone who has run a drug treatment center, I’m going to tell you that opioid addicts who get access to oxycontin are not going to be converting it to naloxone just in case they overdose. And the friends and family of opiate addicts are not going to set up a home made lab in their basement to synthesize naloxone from illegally sourced oxycontin. The thought process here simply does not fit any reality I am aware of. Anarchists? Really? More like dumbasses.

    1. cynical1 says:

      Sorry, Chrispy above already made the same analogy to MPTP while I was writing the above…..

      1. Chrispy says:

        According to Wikipedia, MPTP was first discovered by a chemistry graduate student in 1976; he self-injected his batch of MPPP, which was contaminated with MPTP. A simple HPLC/MS would have revealed this impurity. Then again, I have been surprised at how relatively uncommon HPLC/MS setups are in academia, whereas in industry they’re all over the place.

        1. cynical1 says:

          Actually, Chrispy, not back in the early 80s. I was working back then in industry and we didn’t have access to a LC/MS in industry at that time. FAB was only invented in 1980. I was working at the biggest Pharma in the world in the 90s when we finally got an LC/MS……

    2. Istvan Ujvary says:

      Who on earth wants to make naloxone from oxycodone? Given that the opioid antagonist is readily available these days the “reverse” reaction path would seem more attactive (whether we like it or not).

    3. loupgarous says:

      The worst thing about the Four Thieves Vinegar narrative is that it blandly waves away the downsides of what they’re proposing to do. It doesn’t help that the VICE journalist abets them in that error, saying that nothing they are proposing to do violates Federal law, when (as Derek points out) the cheap, easy ways to make Narcan involve controlled drugs of abuse as feedstocks.

      What happens when these anarchemists decide to self-fund by working from (say) OTC loperamide to make street fentanyl? It’ll happen when some of them decide to be the arbiters of Social Good, servicing addicts out of libertarian zeal (how better to get cabotegravir into heroin than to make that, too? Fentanyl’s been sold as “China white” since the late 1980s).

      They’ll sagely reason that it’s better to make the opioids themselves, than to let the users die from all that carfentanil-cut product on the street, while they pre-medicate IV drug users against HIV.

    4. fajensen says:

      See, it turns out that stupid people can contribute to science in ways that they never imagined.

      Well, It bothers me. Technology works like an amplifier; it is a tool that amplifies the qualities of the users in a way. Which means that stupid people with powerful technology amplifying their stupidity is probably not going to be generally a good thing.

      There are worse – rather – more powerful technologies stupid people might dabble with.

      My lovely daughter has studied synthetic biology. She explains that gene splicing, it is pretty much like baking: There is a recipe, one orders some of the special ingredients, mixes them up with the target cells, waits for a while and your new heroin-making baking yeast is Good to go into the fermentation vessel.

      For a bunch of flakes to get splicing, it would take some basic equipment, 2 summer courses at DTU, about 800 EUR course fees and some basic lab-ware, probably 150 EUR from China.

      PS:
      “Four Thieves Vinegar” does sound a lot like those smart pot/acid- heads I used to hang out with during my misspent youth. There is lots of stoner- thinking and reasoning going on.

      Hopefully for the junkies then, like back in the day, it’s all “stoner tough talking”. Grand, Radical and unworkable ideas that sounds good while wasted and never actually gets implemented because execution would involve someone not being wasted for a while and where is the fun in that!?

      Give it 10 years and these people will be in some kind of leadership role, probably turning into highly reactionary and conservative people as a way of erasing their sinful past, so to speak.

  16. Rhenium says:

    It’s easy to make fun of these folks as most of the above commenters are, but they miss the point.

    This grows out of the Martin Shrkeli and his abuse of the system to corner Daraprim. We are aware that he is a bad actor among companies trying to good, but this is how most people view pharama companies generally.

    This is more a publicity stunt than an actually solution, but ignore it at your peril.

    1. Hap says:

      1) One prefers publicity stunts that don’t get (or aren’t likely to get) people killed, though. The compounding pharmacy deaths might also be an example as to why this might be a bad idea.

      2) If there were an easy solution (or even a moderately easy or tedious solution) to making drugs cheaper, someone would be doing it. We already should have known (from Trump, if no one else, because if there’s unmoored frustration, he’s there) that drug prices are a problem. Some of the reason the problem’s not getting solved is because there’s money in its existence, but not all. The publicity stunt seems to elide or actively turn away from the reasons that drugs cost so much, which doesn’t help people find a political solution that isn’t a trash fire.

      1. con-troll freak says:

        For the sake of argument:
        1) If people dye because of high drug prices it doesn’t make a flashy headline – it’s a baseline and long-term, so no one is outraged.
        2) If it could be done, somebody would already be doing it – is a flawed logic that leads only to maintaining of status-quo. All the drug prices issue is not about making drugs cheap-as-dirt it’s about not making them more expensive just because it’s legal to do so. It’s moral-vs-legal kind of argument. So the stunt doesn’t distract from the real issue, it’s exposing and exaggerates the issue. Because if it wouldn’t, see point 1).

        1. Hap says:

          Except drug companies want to lower their costs for finding and making drugs, too – they’d like to make more money doing it, but as lots of stuff here has shown, they can’t. The cost of manufacture doesn’t drive the cost of drugs. The patent-busting part is closer, but unless competitions work (which they haven’t yet), circumventing them means you don’t get drugs.

          Sometimes, problems are around for a long time not because people are really evil, but the problems are really hard.

  17. SP123 says:

    Our rule in synthesis class was you have to start from 50 cents/g or less in the Aldrich catalog.

    1. myma says:

      my course had that rule as well. Retrosynthesis back to the Aldrich catalog.
      (Cornell)

  18. Uncle Al says:

    Economics educates us that the cost/gram of synthesizing a gram is much less than the cost/gram of synthesizing a tonne given administrative. regulatory, infrastructure, marketing, record keeping, inventory storage…and false labor (ethics, diversity) costs.

    1. Chris Phoenix says:

      This doesn’t make sense to me.
      1) I simply couldn’t find the phrase “false labor” in connection with economics.
      2) Economics doesn’t teach us about politics. Many of the costs you mention are political.
      3) Economics actually teaches that if gram-scale synthesis really cost less per gram than ton-scale synthesis, people would simply do gram-scale synthesis and scale it up.

      So here’s my best attempt to translate what you wrote:
      “In medicine, commercial highly-regulated production, even in bulk, can cost a lot more per gram than unregulated lab-scale synthesis. By the way, I don’t like diversity so I’ll blame that for the cost. And I’ll claim this is economics because that makes me sound more credible.”

      1. Vader says:

        ” Economics doesn’t teach us about politics.”

        I invite you to read a good book on public choice economics.

  19. Chad Irby says:

    What they should be doing is finding the drugs that CAN be synthesized simply and safely in the home, and work from there.

    For example, using commonly-available household ingredients, you can make a very nifty drug with a lot of uses (including as a disinfectant), and the biggest challenge is making sure you don’t accidentally make methanol instead…

  20. J. Wm. Suggs says:

    They sold drugs in the 30’s and 40’s so I think one can do without LC/MS and NMR. The problems of starting materials and formulations are what I see as the real problems for this approach. Since the current pricing model of your money or your life is killing people (I know personally of people being priced out of proper insulin dosages for example) they probably will not kill as many people as some drug executives. I will sign my real name since I am being so negative here.

    1. Dominic Ryan says:

      This is a very interesting point. I wonder how robust the QC could be of a current drug if the only tools available were those from the 30s and 40s? That would be IR, UV/Vis (including fluorescence), rotation, mp, and mp of a range of derivatives at each step along the way and chromatography, again at multiple steps.
      To be sure, it is hard to be a 2D NMR for answering difficult questions, but once you have a route and a reference you would have derivatives and such. Now that’s cheating a bit since we’re only talking about synthesizing it not discovering it as was pointed out.

      1. cynical1 says:

        Actually, I just had my Valsartan recalled last week for being contaminated with N-nitrosodimethylamine which is a water soluble impurity. There’s a ton of people who take that drug as the generic. Evidently, it was just not the generic manufacturer that made my prescription. According to Wikipedia, it was quite a few other manufacturers as well. For what it is worth, I don’t know the QC assays they do on this drug but I’m not sure anything from the 30s or 40s would have picked up that impurity. I don’t even think that low levels of that impurity would be easy to detect unless they were specifically looking for it and knew about it, even today. Given the drug impurity is water soluble and valsartan is not, not sure how the hell this even wound up in there since it’s likely that the API is precipitated with water or through a pH adjustment in water and likely washed with water in the isolation.

        I also wonder how long and how much of that impurity has been in the Valsartan I’ve been taking for the past year. Currently, there is a class action lawsuit in Canada already. (I told my doctor to change the prescription to a different drug in the same class and told her which one.)

        One other point, my first position in the mid 80s was in process chemistry and we worked on a lot of old drugs at that company. And I have to tell you, those old drug routes before NMR and HPLC had a lot of crap in API. Granted, we all didn’t die from taking them but I think we are all happier with better QC results. Keep in mind the stories a few years back about the Indian generic manufacturer that was (knowingly) selling HIV drugs to Africa that were only 50-75% pure. For myself, I do not want to go back to the QC world of 1930 or 1940.

        1. will says:

          More likely than not all the affected companies were sourcing the api from the same manufacturer in Chindia, then formulating it without doing rigorous purity assay upon reciept.

  21. con-troll freak says:

    When pharma cuts corners by outsourcing materials from shady suppliers everyone shrugs and says, um, I suppose that’s how it works. Someone pockets a bonus for this brilliant idea and all are happy as long as FDA does not audit those sources. When bunch of youngsters propose virtually the same everyone is pointing fingers, hey we are in serious business here, don’t you mess with it!

    1. tt says:

      No. We have things called specifications and cGMP, the FDA, and failing that…ginormous lawsuits to keep us honest and patients safe.

  22. Isidore says:

    I blame television, specifically the series “Breaking Bad”. Now everyone thinks it’s easy and glamorous to make illegal substances in their trailer, and by doing this even have action figures of themselves made.
    https://www.walmart.com/ip/Breaking-Bad-Walter-White-as-Heisenberg-Action-Figure-Red-Shirt/47645111

    1. Chrispy says:

      OK, I have to admit that I kind of want one of those figurines…

  23. Ted says:

    Yes, the incorporation of fluorine will probably be the death of them. But, who knows, maybe you really can run a halex reaction in a Mason jar.

    Just to hasten the process, maybe someone should egg them on to cut ‘big pharma’ off early, and synthesize Gilead’s HIV capsid inhibitor…

    https://cen.acs.org/articles/95/i31/Conquering-HIVs-capsid.html

    It doesn’t say much about their intellectual prowess that they apparently haven’t discovered Dovebid…

    -t

  24. special sauce says:

    This thread seems to go full circle back to “The Anarchist Cookbook”, 1971. The AC was certainly more geared to high-yield redox reactions, although recipes for LSD and the like were also provided. However, its lack of finer details about the craft of bomb (or drug) making suggested it was to be used with extreme caution. Wikipedia cites the FBI as characterizing the AC as “one of the crudest, low-brow, paranoiac writing efforts ever attempted”. One wonders about the motivation for such a critique, if true. A research adviser once suggested the omission of key details was by design, perhaps by the FBI no less – what better way to cull an anarchist herd?

    https://en.wikipedia.org/wiki/The_Anarchist_Cookbook

    1. Ted says:

      A lab supply shop in Oregon used to alert the cops or DEA when people tried to buy certain reagents based on the “unconventional” names in the Anarchist’s Cookbook. This same place used (late 80s) to sell diethyl ether over the counter to people that reeked of it…

  25. RTW says:

    Most recently there has be a recall of Valsartan due to possible small contamination of some sourced API in its manufacture by more than one drug company. The potential trace contaminate is N-nitrosodimethylamine (NDMA). A pretty well studied cancer causing compound. Not all companies products are effected.

    See:
    https://www.express-scripts.com/medco/consumer/ehealth/ehsarticle.jsp?articleID=319953&packageTemplate=PA+article+XML&displayTemplate=ProdAlerts+Article+Template&leftNavParam=NewsAnon&GlobNav=1

    Also see:
    https://en.wikipedia.org/wiki/Valsartan
    The section on the Recall. Good reason to NOT allow drug reimportation!

    So if this can happen to legitimate Pharmaceutical API manufacturers it’s a safe bet it will happen a LOT more with the Anarchists. BTW more than once in my career I worked on drugs like Valsartan.

  26. Anon says:

    I can understand all the Pharma folks here balking at the dangerous lack of proper formulation and QC safety controls, since just one adverse event due to lack of purity could kill a person, or a billion dollar drug product, and even bring down a multi-billion dollar Pharma company.

    But what is the risk, really, from an individual patient perspective? Let’s say one, or even a few people did die, then news would quickly get around so that others would avoid the knock-off drug. But then as long as this had not happened, the downside risk for any one person taking the knock-off drug would be very low compared with the risk of not being able to afford the original drug, would it not?

    1. Ted says:

      You want a decreased price, and you expect diminshed performance. So, you’d be okay paying half price for a drug that was present half of the time (or at half the concentration), as long as it didn’t kill you outright? What about 10% of the price for 10% odds? 1% price for 1% return? It’s a form of the lottery, except sometimes you get a ‘scratch and die’ ticket.

      I think the ‘news would quickly get around’ hypothesis is less plausible then watching lemmings plummet over a cliff… so to speak!

      -t

      1. AZSkyeRx, PharmD says:

        Because if these people actually believed in the ethos of medicine, they would take do no harm to heart. Giving someone an impure, subtherapuetic dose of a drug is causing harm. Ignorance isn’t an adequate excuse. Patients are vulnerable, and while our current system exploits that for financial gain, these guys are exploiting that for their egos. The patients are just as harmed and all you do is lend more proof to those who are arguing against it in the first place. If your end result is, people die until everyone stops taking the drug, how has that bettered anything for anyone?

    2. CG says:

      We end up HIV super viruses that current treatments can do nothing against and we find ourselves right in the middle of another AIDS epidemic

  27. MoMo says:

    There’s 7 billion people on this planet.
    There are plenty of more animals they can experiment on.

  28. Synthon says:

    Years ago I used to run a lunchtime synthesis class for junior staff and decided to liven things up by downloading recipes for drugs from the internet. I think we compared the methods to the usual industrial route but I tried to get them to see how poor the methods were, involving mercury amalgam and other toxic reagents which were probably flushed down the drain or burned on an open fire with no regard to the environment. Hopefully FTV are better than that but I’d be interested to know what they do with toxic waste.

    1. Chris Phoenix says:

      Heh, just read Max Gergel’s books if you want to see some hair-raising stories of toxic waste disposal. Before the EPA, US chemical companies (not just his) used to just bury it in the backyard or dump it in the convenient marshland. Also, pre-OSHA, workers were exposed to all sorts of nasty stuff. Life was cheaper half a century ago. In _The Ageless Gergel_ he acknowledges that chemists tended to die young with used-up livers and kidneys, but he also gripes about modern regulatory agencies making it hard to do business.

      1. Bruce Hamilton says:

        Max Gergel died in July 2017, aged 96. It’s also fun to read online the EPA’s and other regulators views of the contamination and subsequent cleanup of the former Columbia Organic Chemical site.

  29. TFA boys says:

    Someone should teach the soy boys photoredox so they can readily assemble any target using visible light

  30. Grad school thoughts says:

    PI sux. Thanks all you need to know if you are starting your post-grad working for a Prof ( you know… a smart guy that we can all learn from ).

  31. Gradschoolthoughts says:

    I have to say…i love the smart alleck tone of the comments on this blog as of late, its much improved from the prior ” did you guys hear about this paper where they proved that the chrial center of benzene is also the ensymatic breakpoint of blablabla…..’. :dumb.

  32. Jim Mowreader says:

    Why do I get the feeling the Vinegar Thieves synthesized Daraprim by ordering a fifty-pound bag of pyrimethamine off Alibaba?

    1. myma says:

      I know, it would be far easier to “subvert the system” by buying the “not for human use” from China..

  33. milkshake says:

    A friend of mine had a clever little anarchist-drug business on side: His wife realized that cat and dog medications are grossly overpriced in US, so he obtained few APIs from China, analyzed them thoroughly to make sure the stuff was not poor quality, and hand-weighted them into softgel capsules, using analytical balances.

    Very tedious, and borderline illegal but not unethical because they did not pass them as counterfeit, and their friends-pet owners were glad to save quite a bit of money.

    1. CR says:

      Many of the drugs that our pets need are available at the local grocery store (especially antibiotics) for $4 or free. So there would be no need to “make” these vet drugs. We just call it in to the store – always funny to see the pharmacist call out there is a pickup for Meatball.

      1. milkshake says:

        these were not antibiotics but antihelmintics (praziquantel) and kidney medications – surprisingly large proportion of old cats suffers from kidney problems.

        1. Ted says:

          Yes, I remember weighing out many portions of Al(OH)3 for our cat when he was undergoing renal failure. It was ridiculous what the compounding pharmacy wanted for it. No way was I going to do that for someone elses cat, however…

          Prazi is widely used in koi/pond hobby for killing flukes, however it’s tough to find under $0.50/gram. An aquarium supply is a great place to get your hands on antibiotics. A friend of mine was doing syn bio in his garage, and found PetCo was the most convenient supplier to meet his plasmid control needs…

          -t

  34. peptoid says:

    Just another bunch of rich kids slumming it with a warehouse fantasy, i.e. Vice’s target audience. Lo-fi, lo-tech aspirationals who will one day put the whole thing aside and use the memories to add colour to their otherwise dreary, middle-class upbringing. If there were any ‘anarchists’ in their fold who posed a real threat, they would’ve been swiftly dealt with by now.

    Give them a few years and watch them ascend the ladders of middle management…

  35. Design Monkey says:

    Visited their website. For all the boasting and big words, actual content delivered was totally underwhelming.

    “Producing” so called “epipen” consists of printing fancy label and sticking it on commercially bought injection device, then using it the same way as it was supposed. Yeah right, that’s their rebellion, drug production revolution and what not. 😀

    Plans for AAA Ace Interplanetary Decontamination Service Configurator (or proposed mason jar universal synthesizer of life, the universe and everything) are blatantly lacking. Present are some bullshit design files for 3D printer to produce plasticky thingie, which supposedly can be sticked in mason jar. How it is going to revolutionize small scale organic synthesis, remains unknown.

    Not even a synthesis writeup for simple crap daraprim. The same amount of freed information (absolute zero) on more complex drugs.

    Conclusion: a lot of wind, no substance. Looks like what guy actually wants, is to rake in donations from idiots.

  36. BernYeeEyeSockets says:

    A few years ago a prominent biohacker named Gabriel Licina was putting chlorin e6, a compound extracted from plants and a porphyrin, into his eyes so he could see at night.

    His picture was all over the internet for a while and he looked like a space alien with inflamed eye sockets.
    Not what I call a role model but this is America and if you want to drip toxins into your eyes, that’s your call.

    Ow, My Eyes!

  37. LibrarianT says:

    If pirated, diy pharmaceuticals horrifies (or thrills) you try reading Autonomous by Annalee Newitz. The protagonist “reverse engineers” a new patented productivity drug and then releases it only to learn it is so addictive users start to die.
    Newitz also explores issues of intellectual property, artificial intelligence, and robot agency with a little bit of gender bending.

    https://www.goodreads.com/book/show/28209634-autonomous

  38. loupgarous says:

    The major issue with giving every addict subclinical doses of HIV drugs is you’re guaranteed (in those addicts who somewhere along the line contract HIV) to create strains of HIV resistant. And when, along the line, you think doses of Sovaldi out to treat more people, you’ll get fewer cures, but higher chance of resistant hepatitis C out in the population.

    I can’t think of a better reason for FDA and FBI to get on Four Thieves’ Vinegar’s case NOW. They aren’t just committing crimes and patent torts. They’re a public health issue in the making, and easier to shut them down now than later.

  39. loupgarous says:

    coffee-deficiency above.

    Giving every addict subclinical, non-curative doses of any HIV drug will soon create drug-resistant forms of HIV in the addict population. Similarly, doses of street Sovaldi thinned out to treat more Hepatitic C sufferers will create resistant hepatitis C virus in the general population.

    Can’t think of a better reason to go all Eliot Ness on Four Thieves’ Vinegar NOW.

    1. tangent says:

      Yeah, this is what really raised my eyebrows. Even a libertarian should understand the idea of negative externalities, and breeding viral resistance to some highly important drugs is a hell of a negative externality.

      (I will admit I don’t know how much we expect this to cause resistance in actual fact, but it seems at least the risk is there.)

    2. Design Monkey says:

      By and large, loupie, you are making a storm in a teapot. Look at Sovaldi molecule. They never ever will be able to produce any sizeble amount of it in their proposed mason jar reactors to distribute it anywhere. Their claims about giving out cabotegavir to heroin dealers are highly doubtful and likely are just wishful lies – again, they can not synthesize any sizeable amount of it with their mason jar thingies.

      Besides, their proposed modus operandi is to give out the “seeeecret” information how to synthesize drugs and plans of their mason jar reactor, and every sufferer is supposed to make those drugs by themselves. And that is just totally unworkable trainwreck. There won’t be any viral resistance arising from such self made products. At best there will be just a few dozens of self poisoned Darwin awardees.

      1. loupgarous says:

        I was giving our modern Tom Sawyers the benefit of the doubt, that they’d do what they said they could do. But you’re right, the more probable case is a lot of toxicity from side-reaction products, congeners and just plain fumbled syntheses, long before we get to worry “who’s monitoring these cases, and are the patients being dosed appropriately?”

        VICE News didn’t even touch, in their article, on “who’s going to destroy their license to practice medicine for prescribing homemade legend drugs?” They are endorsing a massive return to the quackery that required an FDA in the first place.

        I’m not even remotely tempted by their approach. The secret ingredient in the best treatment for my cancer is made in particle accelerators, and there’s no Mason jar substitute for those.

  40. kyosce says:

    These guys are so many levels of Glorious Anarchist stupid. I’ll just address the operational aspect. Many of us reading this blog are synthetic chemists in the pharmaceutical industry. In the unlikely we actually needed a small molecule medicine we couldn’t afford/insurance doesn’t cover/ineligible for patient assistance from supplier, how would we make it? (Assuming we don’t just buy the API from Chindia as suggested by others.) We would purchase the necessary glassware and reagents from a reputable supply house. Synthesize the API by patent procedures. Initial QC by TLC, then outsource NMR and LC-MS to a contract lab. Formulate according to patent or generically along the lines of a PK/PD study. Dose appropriately. Haz waste to contract disposal. All done in a well ventilated garage. Maybe not as Anarchist Cool and Sticking It to Big Brother as mason jars and scrounging the street for starting materials, but much more efficient and likely to succeed.

    1. Anonymous says:

      To kyosce about real chemists working at home: Maybe Four Theives have been selectively reading portions of Max Gergel’s “Excuse Me Sir, Would You Like to Buy a Kilo of Isopropyl Bromide?” and “Ageless Gergel.” Growing up in Columbia, SC, Kary Mullis (Nobel Prize for PCR in ’93) used to cook up chemicals for Gergel to sell through Columbia Organic Chemicals. There is a LOT of dangerous, toxic, lethal stuff going on in those books but they (mostly) lived to talk about it. I’m not sure the Four Thieves group of amateurs will do as well.

      From “Excuse Me”: “we formulated a delicious but deadly blend of sodium fluoride, pyrethrum and powdered sugar. We put it in coffee bags and called it “Roach’s Last Supper” and showed a copy of the Leonardo painting with roaches substituted for disciples.”

      “Dr. Bigelow called. … he asked whether I would be willing to make … methyl isocyanide. I … finally located a cursory reference to its preparation by Moissan in 1878. … I carefully mixed methyl iodide with silver cyanide. It formed a paste which immediately gave off an aroma so vile, so horrible, that I developed an instant headache and ran retching from the laboratory … “Dr. Bigelow, I asked, why is there such a hiatus between Moissan’s
      work with this methyl isocyanide and your requirement? Why is there such a
      paucity of literature references?” “It’s the toxicity, Gergel”, was his cheerful
      reply, “Didn’t you know that methyl isocyanide is one of the worst poisons
      known? It killed Moissan, and I didn’t want to kill John Cuculo as he is taking
      his Ph.D.” It was apparent (1) that rank has its privileges and (2) I was
      expendable.”

      From “Ageless Gergel”: “Certainly Frank [doing kitchen chemistry] did not use a hood on the day he ran his phosgenation. He, like most chemists, probably had an enlarged and over-functioning liver which routinely handled toxic substances, but the young man three houses away who died was not so fortunate. … His gases found their way through the village mains and via the kitchen sinks into the houses on his block. …The young man died while Frank, thoroughly alarmed, trundled the phosgene cylinders into the forest and buried them. This went badly for him at the inevitable trial.”

      1. Anonymous says:

        Sorry. Chris Phoenix mentioned Gergel in an earlier post but I didn’t catch it. I read Gergel when I was in grad school. I also like the “Ship Preacher!” story.

      2. loupgarous says:

        In another part of “The Ageless Gergel”, he talks about a chemist acquaintance who was made “an offer he can’t refuse” by the local drug-dealing mafiosos – “sell us quinine, or unpleasant things start happening to you, your wife… “, so for a while he was buying quinine from supply houses and reselling it at a mark-up to these wise guys.

        It’s possible Four Thieves Vinegar got their idea of putting cabotegravir into heroin from that passage. The local mob wanted the quinine to put in their heroin, to keep their customers from spreading a nasty strain of malaria around through dirty needles. Some ideas never die.

      3. loupgarous says:

        “The Ageless Gergel”, on page 218, is more pertinent to Four Thieves Vinegar (and their brain wave of putting cabotegravir in heroin as HIV prophylaxis:

        One of Gergel’s chemist friends in New Jersey was approached by some tough-looking guys who offered him a ridiculous amount of money for some quinine, no questions asked. His little chemistry firm didn’t make quinine, but he got some easily enough from a chemical supply house. Soon, he was reselling quinine regularly and making more money for doing it than the rest of his activities.

        Then he discovered why he was so favored. His customers were part of the local Mob, and they put some quinine into the heroin they sold, to keep their addict customers healthy (a bad strain of malaria was going from addict to addict via dirty needles).

        The chemist told his new customers he couldn’t get any more quinine for them, and they told him, very unemotionally, of the horrible things he and his wife would have happen to them if the quinine didn’t keep coming. He and his wife quietly shipped their belongings far away and left the area after the wise guys decided his lab would be the perfect place to both make heroin and mix it with quinine.

        1. loupgarous says:

          pages 115-117 of “The Ageless Gergel”, sorry

  41. bruce says:

    Reading the article, it sounds like they don’t do any purifications. Their approach to purity control is to simply come up with reaction sequences that generate no impurities, as if it’s trivial to do.

  42. Kaleberg says:

    Pharma does have a problem, and Four Thieves Vinegar is just a symptom. Most people are completely out of touch with where things come from. They are alienated from their own civilization, so they let their fantasies rule. This is basically the hundred mile per gallon carburetor or the car engine that runs on water, except for pharma where it can actually be more harmful.

    Right now, pharma is as transparent as Hollywood in terms of where it gets its money and where it goes. Blockbuster movies are technically money losers, and drug companies are constantly poor-mouthing while paying big dividends. It doesn’t help that pharma has burned a lot of its credibility with gratuitous price hikes e.g. for diabetes drugs & epipens and the astounding prices of certain drugs.

    1. loupgarous says:

      Four Thieves Vinegar hit the “two wrongs don’t make a right” target dead-on.

      There are things Big Pharma drops the ball on. Processing of clinical research data (the part of Big Pharma I know a little about) is ridden with inefficiencies owing to bureaucratic inertia, and contributes to the high cost of clinical trials. Expecting patients and their insurance companies in the US to bear the costs of new drug development for the rest of the world isn’t just, when many of the patients who benefit from lower costs elsewhere can afford to share those costs.

      Part of what makes drugs cost so much is the care required to make sure that they don’t hurt people more than absolutely necessary during medical treatment. It’s not a cheap process, and Four Thieves Vinegar haven’t explained their post-marketing pharmacovigilance, or their procedure for compensating people who are harmed or who lose loved ones by taking their basement-brewed concoctions. Probably because it doesn’t exist. But part of the anarchist rant against Big Pharma is crappy drug safety.

  43. OldChemist says:

    I wonder how long it will be before these guys end up with something like krokodil?

    1. loupgarous says:

      I can see a future in which, frustrated because pushers and big dealers won’t cooperate in putting enough cabotegravir in the junk they peddle to addicts, Four Thieves Vinegar and their distribution network decide to vertically integrate and make their own illicit opiates. They’ll compete with the guys already in that business by making comparatively pure fentanyl derivatives to mix with inositol or whatever as “heroin”, so the addicts get their HIV prophylaxis and their jollies in one shopping trip.

      Which is where Four Thieves Vinegar gets their Darwin Awards, most likely. Brewing drugs in Mason jars is one thing. Deadly street combat for the right to addle brains profitably is a whole other skill set.

      The more likely alternate scenario would be these guys going to work for the distributors of street drugs and helping them make (say) fentanyls here instead of importing them from China, just to make sure the cabotegravir goes out in high enough dosage to Do Good. The Road to Hell is paved with good intentions.

  44. Bioguy says:

    “There’s talk of sharing cells and cultures, fungal spores on book pages”

    This is how bio folks used to send each other plasmids (by accounts many still do). Spot a few μL onto a decoy letter, draw a circle around the area of interest, and pop it in the post. It’s a lot cheaper than a box full of dry ice.

  45. Luke Weston says:

    Just buy the raw API by the kilo from the big China/India API factories.

    But, they say, that doesn’t have careful quality control over the API! It’s not GMP! And it doesn’t respect IP law and the rights to that drug!

    Oh, wait a minute.

    1. loupgarous says:

      Yeah. Big Pharma charges too much for stuff (a fair comment sometimes), so the solution is Garage Pharma, where the costs of purity control, good manufacturing processes, research, and safety testing – those infamous “middlemen” – are cut out, leaving just a noble transaction between heroic anarchist chemists and their chumps and guinea pigs beneficiaries.

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