The Demon Under the Microscope by Thomas Hager

In my review of Molly Crosby's disappointing The American Plague that a good medical history weaves together scientific discovery, social history, and biography. Crosby's book fell flat because she focused too heavily on the social history at the expense of a decent exploration of the science.

In The Demon Under the Microscope, Thomas Hager does not make that mistake. His book explores not one particular illness, but the search for a drug that might treat the wide range of bacterial diseases that were taking hundreds of thousands of lives each year. This search, which would lead to the development of the world's first antibiotics, sulfa drugs, was spurred by the frustration of World War I doctors who saw thousands of soldiers die of wound infection:

[E]ven the most heroic and seemingly successful surgeries could go completely wrong a few days later. A soldier could wake one morning to find his carefully closed incisions, which had been fine the day before, now swollen, red, and painful. The edges, perhaps, had started to split open. Sometimes a foul-smelling, dark liquid oozed out. The skin around the wound began to take on a "curious half-jellified, half-mummified look," as one physician described it. These were cases of what military physicians feared most in their postoperative cases: Gasbrand, the Germans called it. Gas gangrene. The doctors knew what caused Gasbrand--an infection by bacteria--and they knew how it progressed... There was nothing much that could be done... Once gas gangrene was under way, the bacteria almost always won. Some patients fought it, railing and ranting for a day or two. Then they usually gave up, went silent and pale, temperature dropping, lips bluish. A day or two later, they quietly died of "green-black gangrene," one historian wrote," which emptied surgical wards into the graveyard."

One German doctor in particular, Gerhard Domagk, led the search and he is the main (but not only) protagonist of the story. Domagk's medical studies were interrupted by World War I, during which he would be wounded and serve as a medic on the Eastern Front, experiencing first-hand the destructive power of bacterial infection described above. After the war, he finished his medical degree, and after several stints in academic research positions, went to work for Bayer as the head of their new chemical drug research program. Hager gives a brief business history of the German chemical industry (including Bayer), which rose on the production of dyes; it was medicinal use of these dyes, pioneered by Paul Erlich, that Domagk was exploring at Bayer.

Indeed, the prominent role that Germany plays in the story leads to a variety of subplots. Crosby's book on yellow fever emphasized the backwards nature of medical education in 19th-century America, particularly as compared to that in Europe. This was part of a larger systemic difference in scientific academia, and the Germans were the innovators:

Until World War I broke the German monopoly on chemistry, no matter where you were in the world, you could not consider yourself a chemist (or much of a physicist, for that matter) until you first spent time in Germany studying with a master. Scientists from around the world flocked to Germany and came home to remake their own colleges. Johns Hopkins, founded in 1876, was the first German-model school in the United States, the first "research university." Hopkins introduced many German-style innovations into American education: undergraduate "majors" instead of a generic liberal arts degree; small seminars with their give-and-take with a professor in addition to lectures; an emphasis on original faculty research, especially in the sciences; "doctoral" degrees awarded to students once they had shown their own ability for independent and innovative inquiry. Soon virtually every major university in the United State was doing what Hopkins did, instituting polices that had been in place in Germany for a generation.

Not only was there a difference in the academic structure, there was also an interesting contrast regarding the perceived legitimacy of industrial scientific research vis a vis academica:

Doing science for a corporation was disdained by most academic scientists, who believed that only in a university setting or perhaps a government laboratory could a scientist follow the trial of pure knowledge, unsullied by commercial concerns. In Germany, however, the situation was different. German science had become the best in the world because German schools were among the best in the world, and German schools tended to have productive relationships with German industry.

If it sounds like there was a particularly close relationship between academia, industry, and the state, remember this was Imperial and then Nazi Germany. There are, no surprise, multiple Nazi connections to the story. Hager examines the folding of Bayer into the infamous German chemical conglomerate I.G. Farben, which would make substantial use of slave labor at Auschwitz during World War II, and produced the poison gas used by the Nazis to massacre Jews. He digs into the assassination of Reinhard Heydrich, who died from bacterial infection a week after a grenade explosion sent shrapnel deep into his body. According to Hager, allegations of insufficient use of sulfa as a treatment by Karl Gebhardt, Heinrich Himmler's personal physician, spurred medical experimentation on female prisoners at Ravensbruck. Gebhardt was executed after standing trial at Nuremberg. The Nazi regime even set its sights on Domagk, briefly imprisoning him for the audacity of replying politely to notification that he'd been awarded the 1939 Nobel Prize in Medicine.

While this exploration of political and social history of the era is fascinating, Hager's real success lay in the medical aspects of the story. Though multiple bacterial diseases are mentioned, it is those caused by streptoccus that are most prominently featured:

Strep was every doctor's nightmare. The organisms could be found everywhere, in dirt and dust, in the human nose, on the skin, and in the throat. Most strains of strep were harmless. But a few were deadly, and when they got into the wrong place--beneath the skin, through a wound, into the blood--they could cause at least fifteen different human diseases, each so different from each other that in the 1920s researchers had still not untangled them. The worst strains of strep could secrete three poisons, wipe out red blood cells, raise fevers, eat through tissue, fight their way through the body's natural defenses, and create a bewildering variety of different diseases as they went. A strep-infected scratch could lead to the burning rash of erysipelas, the old St. Anthony's Fire; a bit deeper it became cellulitis, a potentially fatal infection of the subcutaneous tissue; if it got into the bloodstream, it cause septicemia, a blood infection; in the spinal fluid, meningitis.

Not to mention it was responsible for scarlet fever, some forms of pneumonia, and one of the most potent forms of septicemia, childbed fever:

In the 1920s the paradigm for obstetrics--a field that primarily male physicians had finally taken over, during the previous three centuries, from primarily female midwives--was that of illness. "Pregnancy is a disease of nine months' duration," one physician had quipped; another advised, "It is best to consider every labor case as a severe operation." Their remarks underscored the pessimism of caregivers who lost many new mothers after childbirth. The process of birth included a natural wound, deep in the mother's body, where the placenta detached from the uterus... New mothers--especially those in maternity wards--risked a disease called cildbed fever, endemic in many hospitals, that killed tens of thousand of women every year... [S]tudies showed that childbed fever was caused by the same strains of Sreptococcus that had been found in soldiers... the primary cause of wound infections.

After thus reviewing the wide variety of diseases that prompted the search for some way to fight back, Hager returns to Domagk's laboratory at Bayer, where repeated manipulations of dyes led to the almost accidental addition of sulfur to the mix, with great results: the world's first antibiotic drug, Prontosil. Though it would take many months, and the intervention of French scientists seeking their own version of the drug, it was eventually discovered that the healing agent was not the dye but the sulfur, a cheap and abundant resource. This led to an explosion in sulfur-based drugs, and the American experience with these sulfur drugs revealed quite a bit about the state of pharmaceuticals at that time:

Almost any drug, as long as it was not a narcotic, could be sold without a prescription. There was no requirement that labels list all ingredients, proper dosages, or side effects... Patent medicines in the early part of the twentieth century were as firmly established a part of American culture as jazz or baseball. Americans were accustomed to medicating themselves, deciding on their own treatments, and buying their own drugs. It went against the grain to have some doctor or federal agency telling Americans how to cure themselves.

Manufacturers in this field jealously guarded secret recipes and sold their products directly to the public through massive advertising campaigns. They were masters of ballyhoo, filling every newspaper and papering every town with claims for the most amazing cures attributed to concoctions often brewed from the most worthless ingredients.

Efforts had been made early in President Roosevelt's presidency to update the old law, but they had failed in the face of lobbyists, manufacturers, and advertisers. One concoction would change everything and lead to a total transformation in American food and drug law, setting the model for the world. This drug, called Elixir Sulfanilamide, was not wholly worthless. It did, after all, contain sulfanilamide. Unfortunately, sulfanilamide was difficult to dissolve in water, so the chemist who created the elixir decided to mix it with diethylene glycol, which is just as poisonous as it sounds. More than 100 deaths later, Congress passed the 1938 Food, Drug and Cosmetic Act, which laid the foundation for modern food and drug regulation as we know it.

Hager has succeeded admirably in crafting a history that plumbs the scientific aspects of illness and medicine, ties these to the political, military, and social history of the early twentieth-century, and does justice to those who suffered, those who slaved, and those who succeeded in advancing the art and science of healing.