1939 Nobel Prize in Physiology or Medicine — Gerhard Domagk
What You Will Learn
Understand how prontosil, the first chemotherapeutic agent for bacterial infections predating penicillin, was discovered, how its discoverer saved his daughter’s life with it, and why he was forced by the Nazis to refuse the Nobel Prize.
Antibiotics Existed Before Penicillin
We often remember the beginning of antibiotics as penicillin. Fleming’s accidental observation of mold (1928), Florey and Chain’s large-scale purification (1940), and its widespread use during World War II (1943–1945). This story is often presented as the archetype of antibiotics.
However, several years before penicillin was used clinically, there was another drug that dramatically treated bacterial infections. That was prontosil, and the sulfonamide class of drugs derived from it.
Within a few years of its first clinical success in 1935, prontosil became a standard drug in hospitals around the world. Septicemia, puerperal fever (postpartum infection), pneumonia, gonorrhea — the mortality rates of these diseases decreased dramatically. During the few years before penicillin became widely available, prontosil saved countless lives around the world.
The discoverer, a researcher from a German chemical company, was the 1939 Nobel laureate, and the story of him being arrested by the Gestapo for refusing to accept the Nobel Prize is a dramatic subplot of the award.
The Historical Context — The Outbreak of World War II
On September 1, 1939, Nazi Germany invaded Poland. On September 3, Britain and France declared war on Germany. This was the year World War II began.
Nazi Germany occupied Poland in just three weeks, and divided Poland with the Soviet Union (in accordance with the secret protocol of the Molotov-Ribbentrop Pact). The following spring, the Nazis occupied Norway, Denmark, Belgium, the Netherlands, and France in succession. This year marked the beginning of a trend in which most of Europe came under Nazi control.
The Nobel Committee announced the award to Domagk in October 1939. It was one month after the outbreak of the war. However, the Nazi regime, angry that the Nobel Peace Prize had been awarded in 1935 to Carl von Ossietzky, a journalist imprisoned for his anti-Nazi activities, had banned any German citizen from receiving a Nobel Prize.
Domagk was not allowed to travel to Stockholm to receive the award. Instead, he was arrested by the Gestapo and detained for a week. He was forced to send a letter to the Nobel Committee, refusing the award. He actually received the Nobel Prize eight years later, after the end of the war, in 1947.
At the same time, the Sino-Japanese War was in its third year in the Far East. The Soviet Union and Japan fought the Battle of Khalkhin Gol (May–September) in the border region of Manchuria, and the Soviet victory effectively thwarted Japan’s northward expansion in the Far East. This led to Japan’s shift in direction towards the south (the Pacific), which culminated in the attack on Pearl Harbor two years later.
When viewed in conjunction with Korean history, 1939 was the year that the imposition of name changes began (revision of the Joseon Civil Code in November). This was a measure to forcibly change the names and surnames of Koreans to Japanese. In Europe, people’s names were being forcibly removed from Nobel Prize documents, while in Korea, people’s names themselves were being forcibly changed. These were two different forms of forced manipulation of identity that occurred in parallel.
The Personal Story — A Chemical Company Researcher and His Daughter
Gerhard Domagk was born in 1895 in Lagow, Germany. He served in World War I in 1914 and was wounded. He spent the rest of the war as a field medic. What he witnessed during this period — young soldiers losing limbs or dying from bacterial infections — became the driving force behind his lifelong research.
After the war, he completed his medical studies and became the head of the experimental pathological laboratory at Bayer (which was then part of the IG Farben group). His mission was: to find chemicals that could treat bacterial infections.
At the time, this approach was considered radical. Since Paul Ehrlich discovered salvarsan, a treatment for syphilis, in 1910, the idea of killing bacteria with chemicals had only been pursued by a small number of researchers. Most believed that bacterial infections should only be treated with immune enhancement or serum therapy.
The Approach of Large-Scale Screening
Domagk’s strategy was large-scale screening. IG Farben was one of the largest chemical companies in the world and had a vast library of various dye compounds. He tested thousands of compounds one by one from this library.
The method for testing each compound was as follows:
- Infection experiment: Inject a lethal dose of streptococcus into mice
- Administration: Administer the test compound to the same mice
- Observation: Check after a few days whether the mice survived
Thousands of mice were used in this screening. Most of the compounds were ineffective, and the mice died. However, in one experiment in 1932, a surprising result was obtained.
The mice treated with "Prontosil Red", a red dye, all survived. The control group of mice all died.
Domagk reproduced this result several times in subsequent experiments and confirmed similar results in various models of bacterial infection. This was the first definitive demonstration that a chemical substance could treat bacterial infections in a living body.
His Daughter’s Life
The event that led Domagk to decide to carry out the first human use of this discovery was personal and urgent.
In 1935, his six-year-old daughter, Hilde, developed a streptococcal infection from a prick wound on her hand. Her entire arm swelled, and she developed septicemia. At the time, most cases of childhood septicemia ended in death, and the best treatment was amputation of the arm.
Domagk administered prontosil, which he had developed in his laboratory, to his daughter on an experimental basis. Within a few days, the infection improved dramatically, and she made a full recovery without losing her arm. She was one of the first human patients to be treated with this drug.
This personal success gave Domagk confidence, and he officially announced the clinical results of prontosil in 1935. Within a few years, this drug became a standard in hospitals around the world.
The lives of prominent figures, such as Franklin D. Roosevelt Jr., son of President Roosevelt (1936), and Winston Churchill (1943), were saved by this drug. These dramatic cases helped establish the drug’s reputation.
The French Team’s Purification — The Real Active Ingredient
The irony in the story of prontosil is that it soon became clear that the real active ingredient was not prontosil itself.
A French research team at the Pasteur Institute (the Trepóel couple and Nitze) investigated the metabolism of prontosil and found that prontosil was broken down into a simple compound called sulfanilamide in the body. This breakdown product was the actual antibacterial agent.
This led to two major consequences:
First, sulfanilamide was a substance that had already expired in 1908. This meant that the patent profits that IG Farben had hoped to obtain from prontosil were immediately lost.
Second, sulfanilamide could be produced in large quantities at a very low cost. This meant that the drug could be used on a large scale in poor countries. This had an immediate impact on the worldwide mortality rate from bacterial infections.
After this subsequent discovery, hundreds of sulfonamide derivatives were developed and are still used today (e.g., sulfamethoxazole/trimethoprim).
Why It Matters
Domagk’s Nobel Prize is still relevant today on three levels.
Clinical level: Sulfonamides dramatically reduced the mortality rate from bacterial infections in the few years before the widespread use of penicillin (1935–1945). Maternal mortality from puerperal fever (postpartum infection) decreased sharply in the few years after sulfonamides were introduced. If this drug had not been available, millions more lives would have been lost during that period.
Methodological level of drug discovery: The establishment of the methodology of screening a library of compounds on a large scale led to an explosive increase in drug discovery in the latter half of the 20th century. Most of the drugs we use today have been discovered through some form of screening.
Conceptual level of chemotherapy: The concept of “using chemical substances to kill microorganisms in the body without harming humans” was established with this discovery. This framework is the basis for most of today’s treatments for infectious diseases and cancer, including antibiotics, antiviral drugs, and antiparasitic drugs.
There is a lesson to be learned. “The answer to your problem may be in your own laboratory.” Domagk saved his daughter’s life with a drug he had developed in his laboratory. This personal success gave him the confidence to use it on a large scale clinically. Even today, we often have the tools to solve our own projects and problems within our own organizations, but we fail to see them. Domagk was able to recognize the value of what he had created.
As you read this sentence, sulfonamide-based drugs are likely being prescribed in hospitals around the world. The story of the recipient of this drug being forced to refuse his Nobel Prize is the dark side of this award.
Forced Refusal and Re-Award
The story of Domagk’s Nobel Prize ends with an eight-year delay.
After being forced to refuse the award in 1939, he was finally invited to Stockholm after the war in 1947 and received the award. However, according to the Nobel Foundation’s regulations, the prize money was returned to the Foundation, and he only received an honorary medal. The actual prize money was effectively lost as a result of the Nazi regime’s policy of refusing to award German citizens the Nobel Prize.
Nevertheless, Domagk devoted the rest of his life to research in bacteriology and chemotherapy, and made significant contributions to the study of tuberculosis treatment. He died in Düsseldorf in 1964.
Summary of the first antibacterial chemotherapy: Domagk demonstrated that prontosil could treat bacterial infections in living organisms by screening a large library of IG Farben compounds. This discovery saved countless lives in the years before the widespread use of penicillin, established a methodology for drug discovery (large-scale screening), and established the concept of chemotherapy. His actual award was delayed by eight years due to the Nazi regime’s forced refusal.
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