I recently finished reading The Demon Under The Microscope by Thomas Hager. As the author summarizes this book: “Once a bacterial disease took hold in the body, humans in 1931 were as much the prey of the invisible killers as they had been since the beginning of history. All that was about to change…Sulfa happened. It started in the mid-1930s, with a series of findings made in Germany and France, discoveries that were at the time hailed as “the miracle of miracles” in modern medicine, advances that secured humans their first effective way to stop bacterial infections once they started. The work then spread to Great Britain and the United States, where tests of the still-experimental drug on humans. including the son of the president of the United States, confirmed its power.”
Below are key excerpts from the book that I found to be particularly insightful:
Nothing like it had been seen before. IG Farben was on the day of its birth the largest corporation in Germany, the largest business in Europe, the largest and most powerful chemical company in the world. It was also the world s third-largest business of any sort measured by numbers of employees, bested in the mid-1920s only by U.S. Steel and General Motors. As Duisberg hoped, the IG Farben structure led to coordinated research and rationalized production; member firms began complementing one another’s efforts rather than duplicating them; resources were freed to invest in the next big products to generate the next big profits. At Bayer those products would include a number of new medicines.
Childbed fever was rampant in the wards attended by students. Something appeared to be passing the infection from the dead women to the students and physicians, then from them to women in the delivery room. Semmelweis thought it likely, given the pattern, that the student physicians were carrying something, some bits of infectious material, perhaps scraps of tissue from the autopsies, from the autopsy area to the wards. These were the days before Lister and before Pasteur had shown that bacteria could cause disease. Hand washing was minimal, if it was done at all. The students and medical staff wore no gloves. All the doctors, young and old, generally wore the same clothes for days. Semmelweis came to believe that the infectious material was likely carried on the hands. To test the idea, he instructed all of his students to start washing their hands thoroughly in chloride of lime after any autopsy and before touching any patient. Then he tracked the results. As he had hoped, deaths among women treated by his students fell dramatically. Semmelweis excitedly told everyone about his findings, and soon his hand-washing practices were adopted throughout the Vienna Lying-in Hospital. Within a few years, the death rate in Division 1 fell to match that in Division 2. The pregnant women of Vienna stopped begging to be given a midwife.
But, amn7inolv the second molecule, Kl-821—sulfanilamide linked not to an azo frame but instead to a relatively simple carbon-and-nitrogen string—worked, and worked extremely well. It stopped Strep infections in both mice and rabbits. When the first test results came in in mid-April, Domagk immediately ordered retests in strep-infected rabbits and got even better results.
The grand dream of an effective antibacterial chemical—history’s first—was about to be realized. Despite all the worries, skepticism, and disbelief, it appeared that Prontosil really cured human disease. A nontoxic internal disinfectant exquisitely targeted to bacteria, Ehrlich’s long-sought Zauherkugeln, had finally been found. Panacea, after thousands of years of failed attempts, had finally awakened.
By 1938, it was estimated that sulfa was saving the lives of ten thousand new mothers each year in Britain and the United States alone.
Science still seemed to offer reason for optimism. By the time Sir Henry accepted his Nobel medal in Stockholm, however. Hitler had marched troops into the demilitarized Rhineland, Japan and Italy had allied with Germany—and the French, just four years after the discovery of Prontosil, were about to make the new German miracle drug worthless.
Most important, however, was the discovery that the world’s most effective antibacterial medicine was also among the simplest ever found. Everyone had been searching through all these complicated dyes, tinkering around the edges, while the real power was in a colorless add-on. As Bovet later put it, the Germans’ complicated red car had a simple white engine.
Like all great discoveries, sulfa engendered a host of unexpected benefits. During the postwar period, Prontosil and its chemical oirspring gave birth not just to antibiotics but to other new approaches to disease. Domagk’s work, as noted, led to the semithiocarbazones for treating tuberculosis. That was just the beginning. When one doctor observed that patients taking sulfa urinated more often than others, subsequent research led to trying sulfa variants as a diuretic, a medicine used to increase urination and thus to alter the fluid balance in the body Eventually it led to the thiazide drugs, an important early family of diuretics used to treat hypertension. Understanding sulfas mode of action—its ability to act as an “antimetabolite” that substituted for a needed foodstuff, starving the target microorganism to death—led to research into other antimetabolites; the most important result was a family of new anticancer drugs. Another line of inquiry that started with sulfa led to antileprosy medications, another to a treatment for diabetes, another to a new line of antimalarials. In all these cases, the starting point was sulfa, but the end point was new kinds of medicine.
Every great drug discovery (and every modem technological advance) carries with it, like the blood of the Gorgon mentioned in the epigraph that begins this b0ok, two opposing qualities: one positive, healing, and helpful; one negative, often unintended, sometimes deadly The ancient Greeks understood that. We must remember it, too.
A highly recommended read in the area of medicine.