Gerhard Domagk

Gerhard Domagk: The First Cure for Blood Poisoning

In December 1935 a six-year-old girl in Wuppertal pricked her hand on a needle. The wound went septic, streptococci entered her blood, and her doctors proposed amputating the arm. Her father, a pathologist, had spent four years testing dyes on infected mice and had a red powder in his laboratory that had never been given to a child. "A serious worsening of the general condition and dizziness occurred," Gerhard Domagk wrote, "so that we were gravely worried about the child." He gave Hildegarde the powder. She kept the arm and recovered completely. The age of antibacterial drugs had begun on his own kitchen table.

A Vow Made Under Fire

Gerhard Johannes Paul Domagk was born in 1895 in Łagów, in Brandenburg. He was a medical student when the First World War began, and he served in it. He was shot in the head during the fighting in Poland and survived. What he saw afterwards, working with the wounded, set the direction of everything he did later: soldiers whose injuries had been survivable dying of the infections that followed, gas gangrene and sepsis running through field hospitals that had nothing to offer but amputation. He resolved to spend his life on bacterial infection.

He completed his medical degree in 1921 and worked in academic pathology before making the move that mattered. In 1927 he left the university for industry, joining the pharmaceutical division of IG Farben at Wuppertal-Elberfeld.

The Screening Programme

The German chemical industry's dye business had already given medicine one drug — Paul Ehrlich's Salvarsan — and the logic was well understood: dyes bind selectively to biological material, so somewhere in the vast catalogue of azo compounds there might be one that binds fatally to a bacterium and harmlessly to a human. Domagk's job was to find it. Working with the chemists Fritz Mietzsch and Josef Klarer, who synthesised the candidates, he tested them, hundreds of them, one after another.

His crucial methodological decision was to test in living animals rather than in culture. This was slower, costlier and less fashionable than the test tube, and it was the reason he won. In early 1931 the compound sulfamidochrysoidine — laboratory designation KL 730 — protected mice against otherwise lethal streptococcal infection. In the test tube it had done nothing at all. A researcher screening in vitro would have discarded it without a second look; the compound only becomes active once the body has metabolised it. Domagk saw the mice live, and believed the mice.

He published in 1935, with animal and human results. The drug was marketed as Prontosil.

What It Meant

It is difficult now to recover how total the change was. Streptococcal infections — puerperal fever in new mothers, erysipelas, septicaemia from a scratch, the meningitis and pneumonia that killed children — had no treatment. A doctor drained what could be drained, cut off what could be cut off, and waited. Prontosil, and the family of sulfonamides that followed it, gave physicians for the first time a pill that reliably killed bacteria inside a living patient. Streptococcal, staphylococcal and pneumococcal disease became treatable within a few years. It was the first commercially available antibacterial drug, and it preceded penicillin's arrival in general use by roughly a decade.

The Prize He Was Not Allowed to Take

In 1939 the Nobel Foundation awarded Domagk the prize in physiology or medicine "for the discovery of the antibacterial effects of prontosil." Hitler had decreed in 1937 that no German might accept a Nobel Prize, in retaliation for the 1935 Peace Prize given to the pacifist Carl von Ossietzky, then in a concentration camp. Domagk accepted anyway. The Gestapo arrested him in November 1939 and released him after he demonstrated the required political loyalty and formally declined the award. He was handed his medal and diploma in 1947, when the regime that had forbidden them was gone.

He did not stop working. The sulfonamide chemistry led him on to the thiosemicarbazones and into the search for drugs against tuberculosis, a line of research that fed into the development of isoniazid, still a first-line TB drug. He also discovered Zephirol, opening the field of quaternary ammonium disinfectants that remain in use in every hospital.

Why Gerhard Is Called a Genius

Domagk did not synthesise Prontosil; Mietzsch and Klarer did. He did not invent the strategy of screening dyes for antibacterial activity; Ehrlich had established it a generation earlier. What he contributed was a judgement about method, and it was the whole ballgame. Insisting on the infected mouse rather than the culture dish was an expensive, unglamorous choice that cut against the direction of contemporary practice, and it was the only choice that could have found this particular drug — a prodrug, inert until the body converts it. He then trusted an anomalous result instead of explaining it away, which is a rarer discipline than it sounds.

The honest counter-case has three parts. The immediate cause of his success was the industrial machine around him: thousands of compounds, two first-rate chemists, IG Farben's money. The credit for the discovery is genuinely shared, and the eventual recognition that the large dye molecule was not itself the active agent came from work outside his laboratory. And he was a company scientist in Nazi Germany, employed by a firm whose conduct in that period is indefensible; his own compromise before the Gestapo was minor and coerced, but he was not a man who resisted. What survives all of that is a single stubborn methodological conviction and a father who was willing to put an untested drug into his own daughter — the point at which a laboratory result becomes a moral act.

Legacy

Domagk died in 1964, having lived to see the drug class he opened become routine and then be partly displaced by the penicillins that followed it. The displacement is a measure of the achievement rather than an argument against it: sulfa drugs proved that chemotherapy of bacterial infection was possible, and every antibiotic since has been built on the assumption he was the first to justify. The proof of concept was a red dye, some mice, and a girl who kept her arm.

Achievements

• Nobel Prize in Physiology or Medicine — 1939
• Affiliated with University of Münster and University of Greifswald
• Educated at Kiel University
• Worked as biochemist, physician and university teacher