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In the 1930s, a mistake that cost over a hundred lives helped usher in a new era of safer medicine.

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Sources:
http://annals.org/aim/article-abstract/708502/elixirs-diluents-passage-1938-federal-food-drug-cosmetic-act?volume=122&issue=6&page=456
https://www.the-scientist.com/?articles.view/articleNo/35714/title/The-Elixir-Tragedy--1937/
https://www.fda.gov/aboutfda/whatwedo/history/productregulation/sulfanilamidedisaster/
https://pubs.acs.org/cen/coverstory/83/8325/8325prontosil.html
https://pubchem.ncbi.nlm.nih.gov/compound/sulfanilamide#section=Top
http://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/sulfonamides
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109405/
https://www.nobelprize.org/nobel_prizes/medicine/laureates/1939/domagk-facts.html
https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html#us-penicillin-production
https://www.ncbi.nlm.nih.gov/pubmed/19586352
https://calpoison.org/news/diethylene-glycol-poisoning
https://pubchem.ncbi.nlm.nih.gov/compound/diethylene_glycol#section=Top
Images:
https://commons.wikimedia.org/wiki/File:Elixir_Sulfanilamide.jpg
https://commons.wikimedia.org/wiki/File:Sulfanilamida-3D.png
https://commons.wikimedia.org/wiki/File:Gerhard_Domagk_nobel.jpg
https://commons.wikimedia.org/wiki/File:Tube_of_Prontosil_tablets,_Germany,_1935-1950_Wellcome_L0057805.jpg
https://commons.wikimedia.org/wiki/File:Prontosil.svg
https://commons.wikimedia.org/wiki/File:Diethylene_glycol_3D_ball.png
https://commons.wikimedia.org/wiki/File:Haiti_medications_contaminated_with_DEG.png
https://commons.wikimedia.org/wiki/File:1933_-_American_Medicine_Company.jpg
https://commons.wikimedia.org/wiki/File:Japanese_World_War_II_first_aid_kit.jpg
The history of medicine is full of some huge triumphs, but also some pretty terrible mistakes.

Like how, in the 1930s, a company out to make a quick buck took a safe, effective drug and managed to make it a killer. But surrounding that tragedy are some pretty fascinating stories: how a dye became a wonder drug, how the US Food and Drug Administration became what it is today, and how one scientist walked home with a Nobel Prize.

The drug in question is called elixir sulfonamides, and it was briefly manufactured and sold by the S. E. Massengill Company of Tennessee in 1937.

But before this deadly elixir was concocted, sulfonamides had a good rep as an effective drug all on its own. Sulfonamides is an antibiotic, so it’s used to fight bacterial infections. It works by interfering with bacteria’s ability to make folic acid, which they need to reproduce.

It was derived from an earlier drug called Prontosil, which had a vivid red color and was actually developed by the dye industry. In 1932, chemist Gerhard Domagk found that this molecule wasn’t just pretty, it could cure bacterial infections in mice. And once Prontosil hit the market in 1935, it quickly grew popular and saved a lot of lives.

In fact, Prontosil and related compounds were some of the earliest widespread antibiotics. Penicillin had already been discovered, but wasn’t easily available yet. Now, further research showed that there were two parts to the Prontosil molecule.

One part was the dye, and the other was the antibiotic. The antibiotic half was sulfonamides, which researchers found could be used on its own, mostly in powder or pill form. While it had potential side effects, it was generally safe.

We actually still use sulfonamides to treat vaginal infections, though not very often because there are other antimicrobials out there nowadays. But the problem was that sulfonamides had already been synthesized by chemists, and the patent had expired. So anybody could make and sell variants of it.

Enter the Massengill company, who found that their customers liked their drugs in syrup form. They set out to make a liquid version of sulfonamides, and their researchers eventually found that the powder would dissolve in diethylene glycol. At the time, diethylene glycol was known as a solvent.

It has a sweet taste and smell, and once the lab added some caramel and raspberry flavoring, they figured they had a nice medicine and released it as an antibiotic elixir. Frankly, it sounds tastier than some cough syrups I’ve had. Except for one thing: diethylene glycol is super poisonous.

Back then, there were one or two scientific studies about its toxicity, but they weren’t widely known. These days it’s used as antifreeze, among other things, and we know it’s not a sweet treat. Inside your body, diethylene glycol takes time to do its dirty work.

At first, the symptoms resemble drunkenness. But after several hours, the poisoning gets worse. While scientists aren’t exactly sure how it kills, we do know it gets broken down by your liver into a nastier form.

From there, it shuts down the kidneys and can affect the nervous system too. The instructions that shipped with the deadly elixir sulfonamides said to keep giving it to patients until they got better. Which means that some people were poisoned by well-meaning loved ones who fed them antifreeze for days or weeks until they succumbed, usually from kidney failure.

In total, at least 105 people died. And if Massengill had just fed it to a handful of mice before shipping a bunch of it out, this tragedy might have been prevented. Before 1938, the United States FDA only had the power to prevent adulteration and mislabeling.

You couldn’t, for example, sell tablets of flour and say it was medicine. That was against the law. But you could sell something that was poison with zero safety testing beforehand — as long as it was what you said on the label.

The Massengill company’s elixir contained exactly what they said it did: sulfonamides and diethylene glycol, with some water and flavoring. But they did technically break the law. They called the stuff an elixir, but that word was only supposed to be used for products that contained ethyl alcohol.

Massengill’s syrup had none. The FDA seized on this technicality. They used it to track down the tainted medicine & slap Massengill with an unprecedented fine.

If not for the fine print, they would have been helpless, and many more people could have died. A new law was rushed through Congress in 1938, giving the FDA increased power over drug safety. That law is credited with preventing the infamous drug thalidomide, which was found to cause severe birth defects, from hitting US shelves many years later.

In the aftermath of this tragedy and new legislation, the chemist responsible for the antifreeze elixir committed suicide. The senator who sponsored the 1938 drug law died shortly after it passed, reportedly of exhaustion. Powder and pill forms of sulfonamides were still being made in labs and widely used as antibiotics by American soldiers in World War II.

As for Gerhard Domagk, developer of Prontosil, he won the 1939 Nobel prize in physiology or medicine for helping to usher in the antibiotic era. Because, really, prontosil, sulfonamides, and related compounds were used a lot at the time, and can be safe and effective antibiotics. Y’know, as long as you don’t take them with antifreeze.

Thanks for watching this episode of SciShow! If you want to learn more about health-related science and policy, you can check out videos with Dr. Aaron Carroll on our sister channel Healthcare Triage at youtube.com/healthcaretriage.