Whether called phthisis (Greek for “wasting away”), the white plague, or consumption, tuberculosis has been plaguing humanity all over the world for thousands of years. Texts describe the disease in India 3,300 years ago and in China a millennium later. In ancient Greece, Hippocrates called it “the most considerable of the diseases which then prevailed.” In 1680 the English writer John Bunyan ranked tuberculosis among other diseases as “the captain of all these men of death.”
In 19th-century Europe and the United States, tuberculosis epidemics were raging, killing an estimated one out of seven people. Those infected seemed to waste away, as if consumed. “Consumption” so traumatized society that its ravages were featured in some of the great works of art from the time, including Puccini’s opera La Bohème, Fyodor Dostoyevsky’s novel Crime and Punishment, and Edvard Munch’s painting “The Sick Child.”
The fight against tuberculosis reached a turning point on March 24, 1882, in a small meeting room of the Berlin Physiological Society. A 38-year-old doctor and microbiologist named Robert Koch methodically and in great detail used more than 200 microscopic preparations to identify the bacterium that causes tuberculosis: tubercle bacillus. It was the latest discovery in an astonishing career that would land Koch a Nobel Prize, honoring him as one of the most effective warriors in humanity’s long fight to curb infectious diseases.
Born in 1843 in Clausthal, a mining town in Lower Saxony (now part of Germany), Robert Koch was the third of 13 children. He was a lively child, bright and curious. At age five, he taught himself to read using newspapers left around the house.
Koch studied medicine at the University of Göttingen and earned his doctorate in 1866. He married in 1867 and became a father in 1868, all while working in several hospitals. In 1870 he volunteered as a surgeon in the German army during the Franco-Prussian War.
When the war ended, Koch took up the post of district physician in what is today Wolsztyn, Poland. His patients, many of them farmers, were dying from anthrax, an illness that devastated their livestock; over the course of four years, 528 people and 56,000 animals died in this district.
Despite the demands of a busy medical practice, Koch made a makeshift laboratory in his office and set out to solve the anthrax riddle.
Koch’s work would draw on recent advances made in the study of epidemiology. One of Koch’s teachers at Göttingen, Friedrich Gustav Jacob Henle, argued in 1840 that infectious diseases are caused by minute living organisms. In the early 1860s, French biologist Louis Pasteur proved that disease was transmitted by these tiny germs. Identifying and isolating the specific ones responsible for each disease, however, seemed a distant hope.
First, Koch visited anthrax-stricken farms to observe the cows and sheep. He witnessed how a healthy animal would die in a matter of days as its blood turned into a blackish paste. People in close contact with sick cows and sheep also fell ill, many dying of pneumonia.
Examining drops of black blood from dead cows under his microscope, Koch spotted structures shaped like thin grains of rice, which blood from healthy animals did not have. These germs were Bacillus anthracis, which had been first observed in the 1850s but not scientifically proven as the organism that caused anthrax.
To see if the bacteria were the cause of the illness, Koch devised his own testing methods. First he soaked a wood splinter with an infected animal’s blood; then he made a small incision at the base of a mouse’s tail and inserted the splinter into the body. The next morning, the rodents were dead. When Koch dissected their bodies, he found the same microscopic rodlike structures in their blood.
Koch not only found that the rods did play a key role in the disease’s progress; he also established that the bacteria-laden blood could only infect new victims for two days. Koch explored further and was able to observe how the anthrax bacilli pass through a life cycle when they are active and dormant. The rodshaped cells develop within themselves spores that can lie dormant in soil for years. When the right conditions are in place, they grow again into the deadly cells and infect creatures grazing there, which explains why some animals in certain fields became ill while others did not.
In 1876, after three years of painstaking work, Koch shared his findings with Ferdinand Julius Cohn, Germany’s leading botanist, and colleagues at the University of Breslau. In three days of presentations, he laid out the complete life cycle of the bacterium and proved it caused anthrax. One of the attendees enthused that Koch, despite his lack of academic training, “has done everything himself...I regard this as the greatest discovery in the field of pathology.” While other scientists had pioneered germ theory, Koch’s identification of a specific bacterium as the cause of a disease launched the field of medical bacteriology.
Finding the Culprit
In 1880 the German government opened a new bacteriological research institute in Berlin, and Koch was placed in charge. Now with a fully equipped laboratory and skilled research assistants, he could better control the conditions in his research into infectious diseases. For instance, in the ensuing months, his team perfected his plate technique for generating pure cultures of bacteria, a key advance since uncontaminated cultures could show that only the bacillus contained in them caused a disease.
This technique was crucial in perhaps the most important discovery of Koch’s career: identifying the cause of tuberculosis. He began by obtaining a culture of human tissue infected with tuberculosis. Then he injected samples of the tissue into 217 animals. Not only did they sicken, but their infected tissue teemed with the same bacillus taken from the human tissue. The tubercle bacillus had been identified.
When Koch presented his findings to the Berlin medical establishment in March 1882, they were stunned by not only Koch’s identification of the bacillus, but also his technical advancements: the use of pure testing cultures; the new methods of staining samples that made bacteria easier to see and identify; and the first photography of bacteria, which made it possible to share and confirm results.
Koch continued his work to identify bacterial origins of diseases. In 1883 he went to Egypt and then India to study outbreaks of cholera. It had been known that cholera spread through contaminated water, and Koch’s techniques were able to isolate and identify the bacterium. The bacteria Koch described as “a little bent, like a comma,” was later dubbed Vibrio cholerae.
As well as tracking down the origins of deadly epidemics, Koch believed he could find cures. In 1890 he announced he had found the cure for tuberculosis. He called the drug tuberculin, a substance derived from tubercle bacilli. The news gave rise to enormous hope around the world, but tuberculin turned out to be a major disappointment. More than ineffective, it even contributed to the death of some patients. To this day, no completely effective vaccine for tuberculosis has been found, but tuberculin has become a crucial part of testing for the disease.
Koch’s legacy, however, was secure. By identifying the cause of tuberculosis, he made it possible to diagnose it, to reduce its spread through improved hygiene, and to hasten the search for treatments. Koch’s groundbreaking work also resulted in valuable methodology that all scientists could employ.
These rules, known as Koch’s postulates, provide a checklist in identifying bacterial pathogens. First, the germ must be found in every case of the sickness. Next, a sample of the microorganism must be taken from an infected host and grown in a pure culture. Then, a healthy subject inoculated with this lab-grown bacterium must become ill with the same disease. Last, the bacteria must be obtainable from the experimentally infected subject.
In recognition of all his work, Koch was awarded the Nobel Prize for Physiology or Medicine in 1905. As Paul de Kruif notes in Microbe Hunters, Koch advanced medicine from “foolish hocus-pocus” to “an intelligent fight where science instead of superstition was the weapon.