13 ms·

Elixir Sulfanilamide

68 points by benbreen 4y ago

tobyhinloopen 4y ago
I was hoping for a new Elixir module or something
- Maultasche 4y ago
  I had a similar reaction: "What a strange name for an Elixir library!"
jefftk 4y ago
The FDA has a solid origin story: make sure drugs sold are safe. But the 1960s expansion into regulating efficacy has not been positive, and the organization today is not even clearly positive on balance. Today if the FDA approves a drug as safe, and effective for any single specific use, doctors are allowed to prescribe it "off label" for any other use. This generally works well, and contributes to pharmaceutical innovation. We should expand this to where doctors can prescribe anything the FDA has classified as safe. Restricting advertising and other carrots to drugs that have convinced that FDA of their efficacy (as we do today for off label uses) is probably still good, though.
- derbOac 4y ago
  In my personal opinion, medicines in the US are far too regulated. I agree with what you're saying about efficacy versus safety, but I'd even go further in my stance that safety is really overstated. There's a huge difference between something like the safety profile of elixir sulfanilamide and most of the drugs on the market today. Many of them could be distributed without a prescription over the counter, or distributed behind counter under the regulation of pharmacists, or distributed with a prescription by a wider range of providers. It's absurd to me that something like alcohol is something you can buy in the grocery, but something like acyclovir requires a prescription. I know my personal opinions about this are unusual, statistically speaking, but I think the pendulum has swung far too far in the other direction since the 1930s. It's frustrating to me that debates in the US are often framed in terms of two extremes, one resembling what we have, which is broken, and another where there's no safety oversight at all, as if those are the only options. I personally feel like the FDA should concern itself with regulating the characterization of basic safety profiles of substances, and with product purity and truth in labeling. Outside of that, it seems like you start getting into rent-seeking.
- adrianN 4y ago
  Why is it better to decentralize the burden of checking the science behind efficacy claims?
  - jefftk 4y ago
    It's primarily not centralizing checking the science I object to, but the setting a single threshold for all of society. People vary a lot in what level of efficacy evidence would make taking a given medication worth it for them, and in cases where safety evaluation has already gotten us to where the downside looks like "it doesn't do much, money wasted" I think making distribution of the substance illegal is much too restrictive.
- samatman 4y ago
  I don't think that advertising drugs to consumers should be legal. I'd go further, and restrict advertising to doctors to a specific format, something like the Nutrition Facts label we have for food. They'd be allowed the brand/trademark, but everything else is specified to be in effect a data sheet. The only thing allowing advertising to consumers will do is result in a lot of them insisting on, or agreeing to, drugs they don't actually need.
chromatin 4y ago
This is relevant in light of the US senate recently passing a measure that removes the requirement for animal testing of pharmaceutical products prior to commencement of phase 1 studies. Note that the congress.gov link is outdated: the bill unanimously passed in the senate on Sep 29. https://www.congress.gov/bill/117th-congress/senate-bill/2952/text?q=%7B%22search%22%3A%5B%22FDA+Modernization+Act%22%2C%22FDA%22%2C%22Modernization%22%2C%22Act%22%5D%7D&r=1&s=1 https://www.congress.gov/bill/117th-congress/senate-bill/295...
- gus_massa 4y ago
  Juts assuming that Big Pharma is greedy, isn't it cheaper to kill a few mice instead of a few humans in a phase 1 study? In which cases they can skip the animal tests?
- refurb 4y ago
  The bill doesn't prevent the use of animal studies, it just allows other studies to be used to prove pre-clinical safety. The requirement to prove a basic level of safety before doing human trials doesn't change. “(1) Cell-based assays. “(2) Organ chips and microphysiological systems. “(3) Computer models. “(4) Other non-animal or human biology-based test methods. “(5) Animal tests.”.
- lend000 4y ago
  This post on the eve of the animal testing requirement is honestly even less compelling than the argument "what about the bad guys" when politicians talk about outlawing encryption. The US FDA, as it exists today, is the single biggest hurdle to global medical progress (because other developed countries with socialized medicine are still getting about half their new drugs from the US). It costs a billion+ dollars (in FDA testing alone) and many years to push a single drug into the market. Even during an unprecedented pandemic where things are being rushed and all the world's pharmaceutical resources are poured into the drug development, it still took a solid year after vaccines were developed. 90 years ago, animal testing was often the best option. But in this specific example, the drug manufacturer didn't do any kind of testing at all, so it isn't much of a fair comparison. And as a sibling commenter mentioned, there are other effective tests that can be done before human trials, saving time and animals.
gnfargbl 4y ago
> The owner of the company, when pressed to admit some measure of culpability, infamously answered, "We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part." Could be a statement made by a drug company owner in the late 1930s, or an autocratic-government-friendly exploit broker in the early 2020s. Plus ça change.
- mannykannot 4y ago
  Richard Sackler in 2021: his family and Purdue Pharma are not to blame for US opioid crisis. https://www.cnn.com/2021/08/20/us/purdue-pharma-richard-sackler-testifies-opioid-bankruptcy/index.html https://www.cnn.com/2021/08/20/us/purdue-pharma-richard-sack...
  - anonym29 4y ago
    Any doctor who believed in addiction-proof opiates wasn't worth their salt to begin with. Opiates are opiates. Any consumer who took opiates and got addicted has exactly one person to blame - themselves for being uninformed. I love recreational drugs, and I've had back problems that required more than NSAID's alone, but I've never taken opiates, and I never will until I'm ready to die, because I know just how awesome they are. Blaming the manufacturer for opiate deaths is like blaming manufacturers for firearm deaths, rather than the shooters.
    - loceng 4y ago
      If you follow Gabor Mate and his understanding, you aren't prone to addiction if there isn't underlying trauma or suffering, possibly that you're unaware of and haven't processed yet. I've had many dozens of procedures where afterward I need an opiate prescription. I try to only take them for as long as necessary, usually no more than 2 days, because I know an extra 12-24 hours does start to get into mild withdrawal for me. The fearful scenario you're painting more sounds like when someone shoots up an opiate directly into their veins. More recently however I've had different procedures, surgeries, the prior being stem cell treatments - and I've needed to take opiates up to 4-5 days due to post surgery pain. But these surgeries reduced my pain so much that the mild withdrawal was the same or less than when I was used to just taking them for 2 days. What I actually wanted to is that as the pain in my body reduced (from whatever procedure I was getting done), then the withdrawal was easier, less present - arguably as there was returning into less pain in my body as the opiates wore off. I'm talking about physical pain above, but physical and emotional pain share the same pathways - and if someone isn't actually properly grounded, connected, to their body, and its sensory, they may not realize how much pain their body is actually signalling, and then I imagine opiates could quickly become a problem for someone. TL;DR: Opiates aren't actually that great unless you're in pain - though that's supposing you're taking the actual medicinal use level dose - and not taking 4-10x+ recommended; I can't speak to that.
TomMasz 4y ago
It's not clear they even tested to see if it worked at all, they just assumed it would based on the main ingredient and moved on.
- foobarian 4y ago
  Those times were pretty wild. Just bottle up random chemicals and cross fingers. Boy am I glad for the FDA.
- gus_massa 4y ago
  It's a good assumption. If one thing is an antibiotic and the other is not toxic, you can assume that the mix will be an antibiotic. Perhaps the solvent will cause the antibiotic to be absorbed slower or faster. Perhaps the solvent will cause the antibiotic to be eliminated slower or faster. So you may need to adjust the dose, or the time between takes. There are cases where the solvent will react with the antibiotic, and there are corner cases of weird interactions. Some can be predicted from general chemical rules, but some are unexpected. So instead of mixing random stuff and following advice of morons like me in the internet, it's better to ask a real medical doctor and a pharmacologist, and make some animal and clinical trial anyway.
  - onychomys 4y ago
    https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_interactions https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_intera...
assbuttbuttass 4y ago
This reminded me of another story I saw, where the same chemical diethylene glycol caused another mass poisoning https://youtu.be/qhN-o2ame-4 https://youtu.be/qhN-o2ame-4
- amelius 4y ago
  The story is very much related to this story. From Wikipedia: > In 1937, S.E. Massengill Co. (a Tennessee drug company), manufactured sulfanilamide dissolved with diethylene glycol, to create a liquid alternative of this drug. The company tested the new product, Elixir sulfanilamide, for viscosity, appearance and fragrance. At the time, the food and drug laws did not require toxicological analysis before releasing for sale. When 105 people died in 15 states during the months of September and October, the trail led back to the elixir, and the toxic potential of this chemical was revealed. https://en.wikipedia.org/wiki/Diethylene_glycol#Epidemiology https://en.wikipedia.org/wiki/Diethylene_glycol#Epidemiology
- pmarreck 4y ago
  “well, it’s cheap wine, what did you expect?” (As if I should be willing to accept a significant risk of death for a $13 bottle of wine!) If you aren't convinced that things haven't gotten better over the years, here's your proof.
CompelTechnic 4y ago
An honest analysis that seeks to understand the best level of regulation for testing of new drugs must consider both the people that will die due to inadequate testing and the people that will die from drugs never being developed (or being developed much later) due to overbearing testing requirements.
anvic 4y ago
What a manipulative article. All that is needed is a sob story about a dying child or something. Oh wait there it is.
- pmarreck 4y ago
  How is an example of a child death from it, "manipulative"? Are you not supposed to be moved by an example of a human death to a poison marketed as a drug?
  - anvic 4y ago
    I am supposed to be moved by it, which is precisely why it doesn't belong there.
    - pmarreck 4y ago
      I don’t see how eliminating all non-moving information is beneficial to truth dissemination. Some or most? Sure.
anonym29 4y ago
https://en.wikipedia.org/wiki/Perfluorooctanoic_acid https://en.wikipedia.org/wiki/Perfluorooctanoic_acid
kristofferR 4y ago
For people interested in this stuff, I recommend checking out Patrick Kelly on YouTube, his videos about medical history are amazing: https://www.youtube.com/c/PatrickKellyMedicalHistory https://www.youtube.com/c/PatrickKellyMedicalHistory This is the video containing the story about Sulfaninamide: https://www.youtube.com/watch?v=Vuhi1SR8Zuk https://www.youtube.com/watch?v=Vuhi1SR8Zuk
photochemsyn 4y ago
The whole story of the development of the sulfa drugs is pretty eye-opening, and is well-told in this popsci history book by Thomas Hager (2006), which also covers this toxic poisoning episode: https://en.wikipedia.org/wiki/The_Demon_Under_the_Microscope https://en.wikipedia.org/wiki/The_Demon_Under_the_Microscope One fascinating aspect of this is that Bayer originally tried to convince the world that their patented derivative of sulfonamide, Prontosil (note nitrogenous ring additive) was the one that worked. https://en.wikipedia.org/wiki/Prontosil https://en.wikipedia.org/wiki/Prontosil It turned out that the non-patentable sulfanilamide was the actual active species, which Bayer probably knew but kept secret because, well, patents and market share and so on: https://en.wikipedia.org/wiki/Sulfanilamide https://en.wikipedia.org/wiki/Sulfanilamide
- chasil 4y ago
  There is a chapter about this in "The Disappearing Spoon." It's this one: "Chapter 10. Take two elements, call me in the morning" https://en.wikipedia.org/wiki/The_Disappearing_Spoon https://en.wikipedia.org/wiki/The_Disappearing_Spoon

68 points by benbreen 4y ago

tobyhinloopen 4y ago

I was hoping for a new Elixir module or something

Maultasche 4y ago
I had a similar reaction: "What a strange name for an Elixir library!"

jefftk 4y ago

The FDA has a solid origin story: make sure drugs sold are safe. But the 1960s expansion into regulating efficacy has not been positive, and the organization today is not even clearly positive on balance. Today if the FDA approves a drug as safe, and effective for any single specific use, doctors are allowed to prescribe it "off label" for any other use. This generally works well, and contributes to pharmaceutical innovation. We should expand this to where doctors can prescribe anything the FDA has classified as safe. Restricting advertising and other carrots to drugs that have convinced that FDA of their efficacy (as we do today for off label uses) is probably still good, though.

derbOac 4y ago
In my personal opinion, medicines in the US are far too regulated. I agree with what you're saying about efficacy versus safety, but I'd even go further in my stance that safety is really overstated. There's a huge difference between something like the safety profile of elixir sulfanilamide and most of the drugs on the market today. Many of them could be distributed without a prescription over the counter, or distributed behind counter under the regulation of pharmacists, or distributed with a prescription by a wider range of providers. It's absurd to me that something like alcohol is something you can buy in the grocery, but something like acyclovir requires a prescription. I know my personal opinions about this are unusual, statistically speaking, but I think the pendulum has swung far too far in the other direction since the 1930s. It's frustrating to me that debates in the US are often framed in terms of two extremes, one resembling what we have, which is broken, and another where there's no safety oversight at all, as if those are the only options. I personally feel like the FDA should concern itself with regulating the characterization of basic safety profiles of substances, and with product purity and truth in labeling. Outside of that, it seems like you start getting into rent-seeking.
adrianN 4y ago
Why is it better to decentralize the burden of checking the science behind efficacy claims?
- jefftk 4y ago
  It's primarily not centralizing checking the science I object to, but the setting a single threshold for all of society. People vary a lot in what level of efficacy evidence would make taking a given medication worth it for them, and in cases where safety evaluation has already gotten us to where the downside looks like "it doesn't do much, money wasted" I think making distribution of the substance illegal is much too restrictive.
samatman 4y ago
I don't think that advertising drugs to consumers should be legal. I'd go further, and restrict advertising to doctors to a specific format, something like the Nutrition Facts label we have for food. They'd be allowed the brand/trademark, but everything else is specified to be in effect a data sheet. The only thing allowing advertising to consumers will do is result in a lot of them insisting on, or agreeing to, drugs they don't actually need.

chromatin 4y ago

This is relevant in light of the US senate recently passing a measure that removes the requirement for animal testing of pharmaceutical products prior to commencement of phase 1 studies. Note that the congress.gov link is outdated: the bill unanimously passed in the senate on Sep 29. https://www.congress.gov/bill/117th-congress/senate-bill/2952/text?q=%7B%22search%22%3A%5B%22FDA+Modernization+Act%22%2C%22FDA%22%2C%22Modernization%22%2C%22Act%22%5D%7D&r=1&s=1 https://www.congress.gov/bill/117th-congress/senate-bill/295...

gus_massa 4y ago
Juts assuming that Big Pharma is greedy, isn't it cheaper to kill a few mice instead of a few humans in a phase 1 study? In which cases they can skip the animal tests?
refurb 4y ago
The bill doesn't prevent the use of animal studies, it just allows other studies to be used to prove pre-clinical safety. The requirement to prove a basic level of safety before doing human trials doesn't change. “(1) Cell-based assays. “(2) Organ chips and microphysiological systems. “(3) Computer models. “(4) Other non-animal or human biology-based test methods. “(5) Animal tests.”.
lend000 4y ago
This post on the eve of the animal testing requirement is honestly even less compelling than the argument "what about the bad guys" when politicians talk about outlawing encryption. The US FDA, as it exists today, is the single biggest hurdle to global medical progress (because other developed countries with socialized medicine are still getting about half their new drugs from the US). It costs a billion+ dollars (in FDA testing alone) and many years to push a single drug into the market. Even during an unprecedented pandemic where things are being rushed and all the world's pharmaceutical resources are poured into the drug development, it still took a solid year after vaccines were developed. 90 years ago, animal testing was often the best option. But in this specific example, the drug manufacturer didn't do any kind of testing at all, so it isn't much of a fair comparison. And as a sibling commenter mentioned, there are other effective tests that can be done before human trials, saving time and animals.

gnfargbl 4y ago

> The owner of the company, when pressed to admit some measure of culpability, infamously answered, "We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part." Could be a statement made by a drug company owner in the late 1930s, or an autocratic-government-friendly exploit broker in the early 2020s. Plus ça change.

mannykannot 4y ago
Richard Sackler in 2021: his family and Purdue Pharma are not to blame for US opioid crisis. https://www.cnn.com/2021/08/20/us/purdue-pharma-richard-sackler-testifies-opioid-bankruptcy/index.html https://www.cnn.com/2021/08/20/us/purdue-pharma-richard-sack...
- anonym29 4y ago
  Any doctor who believed in addiction-proof opiates wasn't worth their salt to begin with. Opiates are opiates. Any consumer who took opiates and got addicted has exactly one person to blame - themselves for being uninformed. I love recreational drugs, and I've had back problems that required more than NSAID's alone, but I've never taken opiates, and I never will until I'm ready to die, because I know just how awesome they are. Blaming the manufacturer for opiate deaths is like blaming manufacturers for firearm deaths, rather than the shooters.
  - loceng 4y ago
    If you follow Gabor Mate and his understanding, you aren't prone to addiction if there isn't underlying trauma or suffering, possibly that you're unaware of and haven't processed yet. I've had many dozens of procedures where afterward I need an opiate prescription. I try to only take them for as long as necessary, usually no more than 2 days, because I know an extra 12-24 hours does start to get into mild withdrawal for me. The fearful scenario you're painting more sounds like when someone shoots up an opiate directly into their veins. More recently however I've had different procedures, surgeries, the prior being stem cell treatments - and I've needed to take opiates up to 4-5 days due to post surgery pain. But these surgeries reduced my pain so much that the mild withdrawal was the same or less than when I was used to just taking them for 2 days. What I actually wanted to is that as the pain in my body reduced (from whatever procedure I was getting done), then the withdrawal was easier, less present - arguably as there was returning into less pain in my body as the opiates wore off. I'm talking about physical pain above, but physical and emotional pain share the same pathways - and if someone isn't actually properly grounded, connected, to their body, and its sensory, they may not realize how much pain their body is actually signalling, and then I imagine opiates could quickly become a problem for someone. TL;DR: Opiates aren't actually that great unless you're in pain - though that's supposing you're taking the actual medicinal use level dose - and not taking 4-10x+ recommended; I can't speak to that.

TomMasz 4y ago

It's not clear they even tested to see if it worked at all, they just assumed it would based on the main ingredient and moved on.

foobarian 4y ago
Those times were pretty wild. Just bottle up random chemicals and cross fingers. Boy am I glad for the FDA.
gus_massa 4y ago
It's a good assumption. If one thing is an antibiotic and the other is not toxic, you can assume that the mix will be an antibiotic. Perhaps the solvent will cause the antibiotic to be absorbed slower or faster. Perhaps the solvent will cause the antibiotic to be eliminated slower or faster. So you may need to adjust the dose, or the time between takes. There are cases where the solvent will react with the antibiotic, and there are corner cases of weird interactions. Some can be predicted from general chemical rules, but some are unexpected. So instead of mixing random stuff and following advice of morons like me in the internet, it's better to ask a real medical doctor and a pharmacologist, and make some animal and clinical trial anyway.
- onychomys 4y ago
  https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_interactions https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_intera...

assbuttbuttass 4y ago

This reminded me of another story I saw, where the same chemical diethylene glycol caused another mass poisoning https://youtu.be/qhN-o2ame-4 https://youtu.be/qhN-o2ame-4

amelius 4y ago
The story is very much related to this story. From Wikipedia: > In 1937, S.E. Massengill Co. (a Tennessee drug company), manufactured sulfanilamide dissolved with diethylene glycol, to create a liquid alternative of this drug. The company tested the new product, Elixir sulfanilamide, for viscosity, appearance and fragrance. At the time, the food and drug laws did not require toxicological analysis before releasing for sale. When 105 people died in 15 states during the months of September and October, the trail led back to the elixir, and the toxic potential of this chemical was revealed. https://en.wikipedia.org/wiki/Diethylene_glycol#Epidemiology https://en.wikipedia.org/wiki/Diethylene_glycol#Epidemiology
pmarreck 4y ago
“well, it’s cheap wine, what did you expect?” (As if I should be willing to accept a significant risk of death for a $13 bottle of wine!) If you aren't convinced that things haven't gotten better over the years, here's your proof.

CompelTechnic 4y ago

An honest analysis that seeks to understand the best level of regulation for testing of new drugs must consider both the people that will die due to inadequate testing and the people that will die from drugs never being developed (or being developed much later) due to overbearing testing requirements.

anvic 4y ago

What a manipulative article. All that is needed is a sob story about a dying child or something. Oh wait there it is.

pmarreck 4y ago
How is an example of a child death from it, "manipulative"? Are you not supposed to be moved by an example of a human death to a poison marketed as a drug?
- anvic 4y ago
  I am supposed to be moved by it, which is precisely why it doesn't belong there.
  - pmarreck 4y ago
    I don’t see how eliminating all non-moving information is beneficial to truth dissemination. Some or most? Sure.

anonym29 4y ago

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

kristofferR 4y ago

For people interested in this stuff, I recommend checking out Patrick Kelly on YouTube, his videos about medical history are amazing: https://www.youtube.com/c/PatrickKellyMedicalHistory https://www.youtube.com/c/PatrickKellyMedicalHistory This is the video containing the story about Sulfaninamide: https://www.youtube.com/watch?v=Vuhi1SR8Zuk https://www.youtube.com/watch?v=Vuhi1SR8Zuk

photochemsyn 4y ago

The whole story of the development of the sulfa drugs is pretty eye-opening, and is well-told in this popsci history book by Thomas Hager (2006), which also covers this toxic poisoning episode: https://en.wikipedia.org/wiki/The_Demon_Under_the_Microscope https://en.wikipedia.org/wiki/The_Demon_Under_the_Microscope One fascinating aspect of this is that Bayer originally tried to convince the world that their patented derivative of sulfonamide, Prontosil (note nitrogenous ring additive) was the one that worked. https://en.wikipedia.org/wiki/Prontosil https://en.wikipedia.org/wiki/Prontosil It turned out that the non-patentable sulfanilamide was the actual active species, which Bayer probably knew but kept secret because, well, patents and market share and so on: https://en.wikipedia.org/wiki/Sulfanilamide https://en.wikipedia.org/wiki/Sulfanilamide

chasil 4y ago
There is a chapter about this in "The Disappearing Spoon." It's this one: "Chapter 10. Take two elements, call me in the morning" https://en.wikipedia.org/wiki/The_Disappearing_Spoon https://en.wikipedia.org/wiki/The_Disappearing_Spoon