January 31, 2022
At the start of 2022 we live with medical miracles and nightmares. Millions worldwide have been vaccinated against the covid pandemic, which yet has killed more than 870,000 Americans, lately about 2,300 per day. Millions of vaccine refusers close their eyes to the death toll. Ignorance teaches hard lessons.
History offers hope. In October 1932 two German researchers, Josef Klarer, a chemist, and Gerhard Domagk, a physician, working for the big pharmaceutical firm Bayer, tested an experimental antibacterial drug. The process was routine, for four years they had followed it hundreds of times with no success.
The drug, called KI-695, combined a dye and a chain of sulfide molecules. They gave it to a select few of a test batch of mice infected with strep-causing bacteria. Domagk then went on vacation. When he returned he learned that the mice that did not get the drug all were dead. A lab assistant said those that received it “were jumping up and down very lively.” Then the assistant said, “You will be famous.”
Sulfa was the first antibiotic.
Domagk ordered further tests. Again the mice that received KI-695 survived, even with smaller doses. A new dye-sulfide drug, KI-730, proved still more effective. On Christmas Day 1932 Bayer applied for a German patent for the drug, named Strepozon.
Domagk continued the testing, adding rabbits as subjects. The drug cured strep with no side effects. Domagk and Klarer developed a variant without the dye. In 1933 a physician named Forster conducted the first human test when he gave Strepozon to a boy near death from a staph infection. Within days he was cured. Another physician gave the drug to a young girl dying of a severe strep infection. Her strep disappeared. Domagk used it to treat his own daughter’s strep. By 1934 the drug had been proven effective against strep in human patients.
Thomas Hager, in The Demon Under the Microscope, eloquently tells how medicine fought bacterial disease, initially with Klarer’s and Domagk’s sulfa drugs, and later with penicillin and other powerful antibiotics. He writes that in 1917 Domagk, first as a soldier and later as a medical assistant in a German frontline hospital in Poland, saw the horrible effects of gas gangrene caused by strep infections. Nearly all victims died. In British field hospitals in France, doctors were helpless when wounded soldiers developed gas gangrene from strep.
In early 1918 Domagk was sent to the Belgian front. “Disease was everywhere,” Hager writes. Domagk reported shocking scenes of hunger, young soldiers dying of strep, rotting corpses, public health systems destroyed, all causing an explosion of infectious disease that set off the worldwide influenza pandemic.
Before Strepozon and other sulfa offshoots, bacterial diseases like pneumonia, tuberculosis, diphtheria, cholera, and meningitis almost always killed their victims. People relied on sympathetic but usually helpless doctors and so-called patent medicines, many sold by unscrupulous companies and quacks. In the U.S., the Food and Drug Act of 1906 did not require new medications to be tested on animals or humans before being sold.
Strep was a ferocious, usually fatal disease. New mothers infected with strep in hospitals after giving birth died of “childbed fever.” In 1924, Calvin Coolidge Jr., son of the President, developed a blister on his heel playing tennis. Within a few days he was dead of a strep infection.
In December 1934 Bayer received its patent for Strepozon, renamed Prontosil. The company marketed the new medicine throughout Europe. In November 1936 Franklin D. Roosevelt Jr., FDR’s son, developed a sore throat and a fever and was rushed to the hospital. He coughed up blood, revealing a strep blood infection. The president’s physician gave him Prontosil. Within days he recovered. The news, Hager writes, ignited a worldwide demand for the drug.
Germany invaded Poland on Sept. 1, 1939. A month later Domagk learned he had been awarded the Nobel Prize for medicine. Hitler refused to allow him to accept it because Carl von Ossietsky, a German pacificist, had been awarded the 1935 Peace Prize. He died in a concentration camp. Under the Nazis medicine showed a dark underside, the ghastly concentration camp experiments. While Domagk searched for medicines, Bayer’s corporate parent, the chemical conglomerate IG Farben, produced the Zyklon B used in the gas chambers.
When the Japanese attacked Pearl Harbor, doctors at Tripler Hospital treated the soldiers and sailors wounded by explosions and burns with massive doses of sulfa drugs. Within ten days of the attack not a single patient had died of infection.
Domagk, while no Nazi, persuaded German Army medical officers to use sulfa to treat wounds. By 1943 German, British, and American troops carried packets of sulfa or could get it from a medic. That year the U.S. manufactured 4,300 tons of sulfa, enough to treat 100 million patients.
Domagk continued working until 1944, when all Bayer research stopped. By 1947 the company had recovered. Domagk resumed his work on a promising medicine, thiosemicarbazone, for use against TB. That same year he finally received his Nobel. By then, Hager notes, medicine had moved beyond sulfa drugs to penicillin, which did not have the side effects some patients experienced with sulfa, and then to powerful antibiotics like streptomycin, chloramphenicol, neomycin, and many others.
The antibiotic era, Hager writes, probably would have happened without sulfa, but would not have happened as quickly. Sulfa, he says, “cured the medical nihilism of the 1920s, dissipating the prevailing attitude that chemicals would never be able to cure most diseases. Sulfa proved that magic bullets were possible, encouraged their discovery, established the research methods needed to find them.”
Domagk died in 1964. Sulfa had given way to other drugs, and physicians found that bacteria were developing resistance to sulfa. Penicillin has been used to treat sulfa-resistant infections.
Still, Hager says, sulfa “kicked off a revolution in medicine.” Today we enjoy the benefits of the revolution: the age of antibiotics, and of the powerful vaccines, created by researchers guided by Domagk’s and Klarer’s mission, that protect against the covid virus in its multiple forms. Yet Hager’s note about medical nihilism resonates. It still is with us.