Thomas Hager wrote the biography of sulfa drugs in a novelette-like story, which is amazing! There are inspirations and tragic stories in the way of searching the cure for infections, the great maladies haunting human lives for centuries. I think this book should be a mandatory reading for anyone interested in medical and drug development, as this sulfa drugs were the first drug that confirmed the possibility of a ‘magic bullet’ (specific drug) for a disease (in this case, infection).
Sulfa-class drugs were the first antibiotic (even before the famous penicillin) widely used to treat various infections, from the infection of childbirth (which could kill more than 50% of mothers giving birth during its epidemic) to the war-related infections during WWII. Sulfa is also the drug that underlies the principle of pharmacology and toxicity tests before a drug can be launched to the market. And thanks to sulfa that the FDA gained its position as the ‘powerful’ drug regulatory agency nowadays. Alas, almost all of sulfa’s inventors suffered from tragic fate during WWII, despite the fact that they were the most meritorious people who ‘saved’ a lot of people during WWII.
And in this blog, I want to go into a more detail story about this sulfa drugs.
Human had looked for the remedy of infections for a very long time, yet the insight of this ‘magic’ remedy was achieved through a team of scientists in Bayer pharmaceutical industry, Germany. Gerhard Domagk was a former German soldier in WWI who turned out being a physician after he saw how war (and war-related infections) took a lot of his compatriots. He was obsessed to find the cure for the infections, and he found the right place and team in Bayer. Germany and Bayer were the leader of the chemical industry in the world during that time. Hence, there were a lot of talented chemists who could support Domagk to synthesize drug molecules. Among them are Josef Klarer and Fritz Mietzsch, while Domagk himself was responsible to test the efficacy of the synthesized molecules toward infected mouse and rabbits.
The Bayer team needed 8 years before they found a hint of antibiotic effect in sulfonamidochrysoïdine, an azo-sulfonamide molecule, with minimum side effect. Finally, in mid-1930s, the first antibiotic drug was released by Bayer with the patent name Prontosil. The news about the first cure of infections spread in Europe and the US. A lot of laboratories and pharmaceutical industries tried to crack the structure of Prontosil and marketed the drug in another name. Eventually, scientists in Pasteur Institute, France, found that the actual molecule acts as the antibiotic is only the sulfonamide, a rather simple molecule compared to sulfonamidochrysoïdine. This opened a bigger possibility for pharmaceutical industries to modify and marketed sulfonamide antibiotics in various forms. In the end of 1930s, there were dozens of sulfa-related drugs used in various parts of the world to cure infections.
The development of sulfonamide-related antibiotics involved a lot of cases. It was widely tested to mothers giving birth in London, who usually suffered from childbirth fever (infection after giving birth). It was also given to president FDR Jr, who got an infection from a blister in his foot during his teenage time. The largest ‘clinical trial’ of sulfonamide was during the war, where sulfonamide saved a lot of lives from was-related infections.
However, a bad case of sulfonamide was reported in the US. A sulfonamide elixir was found to poison hundreds of people in various part of the US. It was suspected that diacyl glycerol (which used as the elixir vehicle) was contaminated somewhere. During that time, the pre-market safety/toxicity tests were minimally conducted by a pharmaceutical company. There was no law or regulation that systematically regulate how a drug should be tested (pharmacology or toxicology) before being launched to the market. Even, the FDA has no power to regulate drugs at that time as they focused on inspecting food and chemicals. With the case of sulfa-drug, US congress and FDA finally made a rigorous regulation about drug testing before the drug reaches the market.
Eventually, Domagk was awarded the Nobel Prize in 1939 for his contribution in finding the first drug for antibacterial infection. However, due to political situation at that time, he could not receive the award at that year. The political situation and war also diminished the brilliant team of scientists in Bayer. Exceptionally, Domagk still tried his best to work during the war to find the cure for tuberculosis, which could not be treated with Prontosil. Finally, after the war, Domagk could stand in Nobel Laurates meeting in 1947 to receive his nobel prize.
The story of sulfonamide is the story of the modern drug that I think should be a staple read for every pharmacy and medical student.