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.