[kragen]

What if the DIY medicines weren't of dubious quality? What if they were higher quality than the ones that cost US$750 a dose? What if everyone had an analysis machine that could analyze the medicines, DIY or not, to find out what was in them, and the DIY stuff turned out to be purer and more precisely dosed? That's what happened with Linux versus, say, Solaris and Microsoft Windows, and it's what's happening now with programmable insulin pumps.

Also, medical consequences have to get pretty costly before they're more costly than selling your home and emptying your retirement account and your kids' college funds.

[nwiswell]

> What if everyone had an analysis machine that could analyze the medicines, DIY or not, to find out what was in them

I can fairly confidently predict this will not happen like it did for software. Chemical analysis has been around a long time and remains difficult for experts to do accurately without context, let alone for a layman. Gas chromatography, for example, requires large and expensive machinery and some idea of what the substance is composed of in order to determine the concentration of analytes.

Reagent testing is cheap, simple, and straightforward, but it is generally only capable of detecting whether or not some class of substances are present above a particular concentration. You cannot use reagent testing to determine "how pure" a medicine is, let alone whether the impurities (which there will assuredly be) are potentially harmful.

As is currently the case for illicit drugs, I imagine there will be an ecosystem to verify that A) the active ingredient is actually present and B) some limited range of problem impurities are not present, but that is a much less stringent form of quality control than pharmaceutical companies perform.

[kragen]

Clearly making it happen will require a revolution in manufacturing, which may or may not already be underway, but making it happen for software required decades of continuous revolution in semiconductors and telecommunications.

Some kinds of analysis machinery, like GC, ICP, and DSC or DTA, are probably inherently fairly large; other kinds, like FT-IR, other kinds of spectrometry, TLC, HPLC, other kinds of liquid chromatography, XRF, XRD, and NMR, can be miniaturized and mass-produced. There hasn't been much pressure to do this because bio and chem labs don't care if their spectrophotometer costs US$0.12 or US$12000 or whether it weighs 100 mg or 100 kg; they need one to get their work done, they don't need it to be portable, and they aren't going to lose it because it stays in the lab. But that doesn't mean it can't be done. Even Victorian-era-style reagent testing can be made quantitative in some cases!

[nwiswell]

> Some kinds of analysis machinery, like GC, ICP, and DSC or DTA, are probably inherently fairly large; other kinds, like FT-IR, other kinds of spectrometry, TLC, HPLC, other kinds of liquid chromatography, XRF, XRD, and NMR, can be miniaturized and mass-produced

Many of the types of analysis listed here are elemental analysis only, which are useless for trying to identify pharmaceutical analytes or determine their concentration.

Out of all of these, microfluidic liquid chromatography is the least science fiction. There's plenty of literature about it but nobody really "has it working", and the reality is that it's not likely to ever have the same capability as benchtop HPLC.

[kragen]

> Many of the types of analysis listed here are elemental analysis only, which are useless for trying to identify pharmaceutical analytes or determine their concentration.

That's mostly true, but if a pill has significant amounts of lead, arsenic, and mercury in it, you know something went wrong, and you shouldn't take it. Even XRF might be enough to allow you to safely use lead-based or arsenic-based catalysts in your synthesis.

> Out of all of these, microfluidic liquid chromatography is the least science fiction. There's plenty of literature about it but nobody really "has it working", and the reality is that it's not likely to ever have the same capability as benchtop HPLC.

Thanks! Can you think of any other plausibly miniaturizable general-purpose analysis techniques? Those are just the ones I came up with off the top of my head. I think microfluidic liquid chromatography doesn't actually have to run faster than the bear, just faster than color-changing DanceSafe test kits.

As for science fiction, https://news.ycombinator.com/item?id=29816434 talks a bit about how today's science fiction is tomorrow's old news.

[taylorportman]

Probably the 'manufacturing revolution' will be modifying yeast, plants, etc. to produce the chemical compound of interest. Everyone needn't have expensive equipment - testing can be outsourced. Such an effort would need a GPL like agreement to keep people honest, but the technology exists.

[kragen]

Conceivably, but I was a lot more enthusiastic about this possibility 35 years ago before the humans had much experience with it. It turns out DNA is a really shitty programming language for humans. Like, worse than Malbolge.

[dekhn]

Miniaturized NMR? can you explain how that would work?

[philipkglass]

They use rare earth permanent magnets and don't offer the resolution of superconducting magnet NMR, but they are much smaller and cheaper (tens of thousands of dollars, new) than superconducting units or the even older resistive electromagnet NMR units. The first one I saw was from picoSpin, which has since been acquired by Thermo Fisher Scientific. I think that there are multiple vendors now. Here's a current picoSpin unit:

https://www.thermofisher.com/order/catalog/product/912A0913

[dekhn]

An 80MHz desktop NMR in 2022 is hilarious. This owuld be great to put in a research lab or to teach students, but it's not something that could be used in a high volume, high quality pharma testing situation.

(my phd in nmr is from 20 years ago... even then it was hard to justify the expense of nmr machines in structural biology...)

[kragen]

Benchtop NMR spectrometers already exist (for decades now), and some are already cryogen-free, permitting room-temperature measurements, eliminating the dewar and cryogens which account for a lot of the mass and volume of traditional NMR spectrometers. We now have room-temperature superconductors, which might work to eliminate the bulky, heavy permanent magnets in current benchtop devices, though the pressures required may turn out to be impractical. Beyond that I can handwave at improved electronics and SQUIDs, but I don't really know.

Do you think there are some fundamental obstacles to miniaturizing NMR, and if so, what?

[fabian2k]

Benchtops are at 60-90 MHz field strengths. That is not really enough to look at more complex molecules, the bigger routine NMR spectrometers are at 400-600 MHz (and there are even larger ones, but those are not used for small molecules that much). And even then those benchtops cost something close to 100k USD, that's quite far from affordable.

The "room temperature" superconductors are not used at room temperature in these cases, they're still cooled down. And so far the only spectrometer I know of where they are used is the still extremely new 1.2 GHz Bruker. And that one is almost certainly somewhere between 10 and 20 million USD. The new superconductors are low temperature superconductors, not room temperature. And even then they still work better at lower temperatures. At best you can remove the liquid helium from the system and use liquid nitrogen only, which is an advantage but still really far from room temperature.

[kragen]

Thank you for explaining!

Yes, I don't know if the current room-temperature superconductor material (which really is room temperature, 15°C) will ever be useful for this; it was only discovered in 02020, so it is very unlikely that anyone is using it in a product today, even if they find a way to apply the necessary pressure (267 GPa, thus requiring ultrahard anvils). You're probably thinking of something like YBCO, which is "high-temperature" in the sense you're describing, requiring only LN₂, not "room-temperature".

Costs change over time. There was a time when solar panels cost 100k USD, too. A lot of the costs you're describing are NRE; others are costs that can be reduced.

[dekhn]

benchtop NMR doesn't solve this problem, it's not powerful enough.

If you had improvements to NMR they would actually go first to other things than doing chemical analysis of anarchist drug batches. IE there are other industries that will buy all your machines if they existed.

The real question is why would you EVER use NMR for just about anything? It's really high cost and the total value of the data is lower than just about any other technique. It really only makes sense in research situations.

[kragen]

What are the companies, or at least the industries, that would buy all the machines?

Ultimately what everyday people will end up using is whatever is cheap and works well enough. Right now NMR isn't cheap, and neither is FT-IR or XRD, but these things change over time. Benchtop NMR is already good enough for distinguishing between significant classes of contaminants that could be in your purported insulin.

I'm typing this on a 50-gigaflops computer, which is faster than the Cray Y-MP Los Alamos had back in the 01990s, and people routinely buy teraflops video cards now, any one of which is faster than ASCI Option Red, if you remember that. I just drank a mass-produced soft drink out of a can made of aluminum, the metal Napoleon III preferred to gold to exhibit his wealth. Last year Chinese companies brought three covid vaccines to market within six months of the disease's discovery and started mass vaccinations, though most observers had predicted a minimum of 18 months. SpaceX is routinely landing reusable rockets on their tails now, and the world's energy infrastructure is rapidly shifting from fossil fuels to solar.

Things change. Today's science fiction is tomorrow's old news.

[notch656a]

I'm not arguing with what you're saying, but GC/MS can be bought for like $100 a sample and it's conceivable a system can be invented where private auditors audit the output of an unregulated pharmaceutical manufacturer in such a way that the QC assurances to the consumer are as good or better as in our current system, with much lower regulatory costs.

[nwiswell]

In the limit what you are describing is a generic drugmaker.

It's certainly possible to audit drug quality by sending it to labs, and people do that for darknet drugs all the time, but there are still problems:

1) There is no way to use ex-post analysis alone to achieve the kind of QA that pharmaceutical companies do; they have visibility into the entire manufacturing process and process control. Put another way, a sample of a drug cannot be used to verify that the process used to manufacture it is safe.

2) There is no assurance that anything you get in the future is made with the same process.

The only way I see this working, honestly, is for a rogue jurisdiction to offer safe harbor to "generic pirates". The rogue jurisdiction would offer legitimate regulatory oversight in exchange for tax revenue, and the drugs would be smuggled out of the jurisdiction for sale. To some extent this is already the case in grey markets where brand name drugs which are sold for less in other countries get arbitraged/smuggled back to high-cost markets.

[kragen]

Here's a possible approach.

Buy n = 1024 doses of your insulin or whatever, D(0, i) for i from 0 to n - 1 = 1023, homogenize each dose, and divide each one in half into half-doses called E(0, i) and F(0, i).

Mix pairs F(0, 2*i) and F(0, 2*i + 1) into 512 new doses D(1, i) for i from 0 to 511. Homogenize these new doses and divide each one in half into half-doses called E(1, i) and F(1, i).

Mix pairs F(1, 2*i) and F(1, 2*i + 1) into 256 new doses D(2, i) for i from 0 to 255.

And so on, until in step k = lg n = 10 step you mix the half-doses F(k - 1 = 9, 0) and F(9, 1) into a single dose D(k = 10, 0). Send this D(k, 0) off to the lab to be analyzed.

If the lab is equipped to detect dangerous impurities in your insulin at one-thousandth the danger level, which is reasonable for many contaminants, and the sample comes back clean, then you know that all 1024 doses were safe, though some of them may have the wrong dose. Mix the remaining 1023 doses well so that they all have the same dose and store them safely.

If not, you need to track down the contamination (or massive dilution), so in the next iteration, you send E(9, 0) and E(9, 1) to the lab for analysis. If one of them comes back safe, you know the 511 doses that were mixed into it were okay, and you can mix them well and store them safely, then repeat the process on the contaminated subtree.

Depending on your cost function (latency, shipping and handling costs, etc.) and your priors for correlation among the samples, it might be worthwhile to recurse more deeply on failure: instead of sending E(9, i) for i from 0 to 1 to the lab, you might instead send them E(6, i) for i from 0 to 15. If one out of 30 doses was randomly contaminated, for example, about 14 out of the 16 groups will be bad on average, while if it's one out of 100, then you'll have about 7 bad groups out of 16. At some point you need to give up on the recursion, too, or you'll end up testing almost all 1024 doses when they're all bad.

This of course doesn't solve the problem of future buys, just reduces it by the factor of n.

[notch656a]

I think we are seeing the same thing, a system designed to remove corruption/regulatory capture/lobbying as far as possible from the process. I'm seeing a "rogue" auditor that performs the same service, while you are seeing a rogue government. If the outcome is the same, I am fine with either. Your pointed weakness regarding auditing the manufacturing process could be incorporated into either.

[nwiswell]

> I think we are seeing the same thing, a system designed to remove corruption/regulatory capture/lobbying as far as possible from the process

Not really. It's more like a system to selectively remove intellectual property rights without destroying the financial incentive to develop drugs.

[notch656a]

Oh. So you don't want a system that removes corruption, regulatory capture, and lobbying as far as possible? I don't want to destroy the financial incentive either, I think it's great people that bring wanted goods to market profit from it.

IP is an interesting point, although I'm not convinced that generating the IP is more than a small fraction of the cost of a drug. An aggregate I saw from 2011-2018 puts Research at only 17% of revenue, and only some proportion of that is geared towards generating IP. That is to say, with all else removed you could generate an IP only company for 17% the cost of drug sales.

[LiquidSky]

>it's conceivable a system can be invented where private auditors audit the output of an unregulated pharmaceutical manufacturer in such a way that the QC assurances to the consumer are as good or better as in our current system, with much lower regulatory costs.

No, it's not. This is ideological libertarian nonsense. There's a reason pharma came to be regulated in the first place. All this will lead to are more injuries and death of consumers.

[notch656a]

>No, it's not. This is ideological libertarian nonsense.

If I could flag your post, I would. This is purely political nonsense and a god-like attempt to disprove something through fiat.

[rootusrootus]

Heck, even the FDA can't guarantee all generics are equivalent to the branded version (some anticonvulsants come to mind). Might be a while before this ability comes to the masses.

[R0b0t1]

A lot of machinery has been getting smaller. You can do GC/MS with a desktop device now.

[mrxd]

92% of contributors to the Linux kernel are paid by companies: https://www.suse.com/suse-defines/definition/linux-contribut...

Most major OSS projects are controlled by a few companies who pay developers to work on them. They're more like industry consortiums than DIY anarchist collectives.

[kragen]

Something can be both an industry consortium and a DIY anarchist collective, like Linux; the Linux Foundation isn't Linux. It turns out that industrial companies don't appreciate being subject to monopoly rents any more than private individuals do! The GPL is undeniably very anarchist, and it serves as a kind of constitution that keeps the companies that participate in GPL projects from controlling them. Consider, for example, Oracle and LibreOffice, MariaDB, and Jenkins, or GitHub (now Microsoft) and Git.

The solution isn't to destroy capitalism or exclude industrial companies from participation. We tried that a century ago. It went badly, because, as it turns out, capitalism is better at limiting the damage done by ambitious psychopaths than the alternative systems are; if Beria had been born in Ohio maybe he would have ended up running a soap company or a division of GE instead of mass-murdering dissidents.

Similarly, the GPL (and, to a lesser extent, non-copyleft open-source licensing) reduces the damage selfish companies can do to software projects and the people and companies that depend on them.

We need to figure out how to do the same thing to drug companies and the FDA, because they are just killing far too many people and causing far too much needless suffering today.

[beaconstudios]

It's misleading to mix up anarchism and marxism-leninism. While both are anti capitalist, ML is the one where you're just replacing one hierarchy (economic power) with another (party membership). Anarchism is fundamentally against coercive hierarchy.

[kragen]

Anarchism is indeed fundamentally against coercive hierarchy, yes, and I apologize for not being clearer about that. That said, Emma Goldman and many other anarchists were delighted to be deported to Soviet Russia until their famous disillusionment; historically speaking, the mainstream of anarchism considered state communism more friend than enemy, until they saw how it worked out in practice. And my own experiences with nominally anti-hierarchical organizations have not given me great faith.

[beaconstudios]

I think a lot of people had a lot of hope in the Soviet Union, especially when there were actual soviet councils involved. It didn't take long to devolve into a regular dictatorship. After all the state was supposed to be a vanguard for the implementation of socialism but power begets power and in the end it existed to serve itself.

I think that's the main reason that most sane leftists* are some flavour of anarchist these days.

* not including social democrats/other liberals in the "leftist" bracket.

[notch656a]

How can one be both anarchist and leftist? Doesn't re-allocating resources in an unprofitable way for the owner require some sort of involuntary transaction, or would you expect owners of capital will all relinquish them peacefully? It seems like capitalism is more compatible with anarchism as capitalism can be contained within voluntary transactions.

[notch656a]

Capitalism isn't incompatible with anarchism unless you're speaking with leftist.

[kragen]

Anarchism is leftist.

[notch656a]

I consider myself anarchist in the sense I do not believe in the legitimacy of government. I do not have any leftist view whatsoever, but I think people should retain ownership of their property except through consensual trade. Does that mean I'm not an anarchist, or does that mean I'm a leftist?

[kragen]

I suppose it depends on what definitions you're using of words like "government", "leftist view", "their property", and "anarchist"; clearly at least one of them differs from the mainstream definitions. I suspect it's "anarchist", since anarchism (as normally understood) opposes coercive hierarchy more broadly than just the usual definition of "government", including things sometimes described as "property", but I can't know for sure; you might be using a nonstandard definition of "government" instead, for example.

As I said before, though, you might benefit from reading at the introductory section of https://en.wikipedia.org/wiki/Anarchism.

[denton-scratch]

It means you're an extreme libertarian, but no anarchist.

[LiquidSky]

>What if everyone had an analysis machine that could analyze the medicines

Because, as a post below notes, this is a pure fantasy. At this point you're proposing actual magic.

>Linux versus, say, Solaris and Microsoft Windows

Your choice of operating system isn't going to severely harm or kill you. "Move fast and break things" is a problem when the "things" are people.

>medical consequences have to get pretty costly before they're more costly than selling your home and emptying your retirement account and your kids' college funds.

Welcome to the reality of healthcare in the US for the uninsured (and often times for the poorly-insured).

[notch656a]

Meh it's the classic black market vs white market debate, where here the white market is a huge oligopoly with insane markups to pay off lobbyists / regulator / advertisers / the rich people who own the pharma companies. Sometimes the black market is even more expensive but in DIY it often isn't.

If it were me I'd just make it all in one go, hopefully enough to be set for life, huge pile of it whatever drug I need to stay alive. Create a homogeneous mixture, GC/MS the mixture for purity and then package it for long term storage.

[LiquidSky]

>Meh it's the classic black market vs white market debate,

No, it's classic libertarian fantasy bullshit. Medicines aren't toys, and we know exactly what happens when they're unregulated.

[notch656a]

I wasn't aware that analytical instruments could measure your economic or political ideology.

[popcube]

some university will buy it first! actually this sounds like good, but this so difficult.

if someone glad to try some secret drug, maybe they can killed by error one...