The Legacy of Robert Koch

Never in the history of bacteriology did so much happen so quickly as in the last quarter of the 19th century. On the evening of March 24, 1882, an epoch-making lecture was delivered to a stunned audience at the University of Berlin's Physiological Institute. On the demonstration table lay more than 200 microscopic preparations, test tubes and plates with cultures, a microscope, and other accompaniments of a serious bacteriologist. The presenter of this monumental work was Robert Koch, who rose from humble beginnings as a country doctor to the pinnacle of scientific achievement. Three weeks later, Koch's work was published under the title “The Etiology of Tuberculosis” in the Berliner Klinische Wochenschrift. On April 22, 1882, an English summary of this momentous work appeared as a letter in the London Times, and news spread across the Atlantic to New York and soon to the entire world.

It is a formidable task for any historian to recount each of Koch's remarkable achievements. It can be said that history has seen but a few individuals whose extraordinary genius allowed them to leave such an immeasurable impact on human life. The list of Koch's scientific achievements is exhaustive, but he is most revered for his discovery of the causative organism of tuberculosis. During his career, Koch forever changed the face of medicine and firmly established the science of bacteriology. His work had far-reaching impact globally in the field of infectious disease and public health. His discovery of the tubercle bacillus was a starting point for a worldwide campaign against an age-old scourge of the human race.

Heinrich Hermann Robert Koch was born December 11, 1843, in Clausthal in Hanover (later a part of Germany). The son of a mining engineer, he was the third child in a family of 13, of whom 11 survived to adulthood. His uncle, Eduard Biewend, would leave a tremendous impact on the young Koch, encouraging an interest in nature, insect collection, and most of all, introducing him to the nascent field of photography. Koch's enduring interest in photography would become greatly enhanced with his bacteriologic research in later life.

Koch was a bright youngster and could read by age 5. He studied medicine at Göttingen University, graduating in 1866. As a student, he was influenced profoundly by Jacob Henle, who was a proponent of contagium animatum, a concept that disease could be caused by a living transferable entity. Koch's studies on the innervation of the uterus, carried out under the guidance of Wilhelm Krause, would win him a monetary award. Under physiologist Georg Meissner, Koch studied the metabolism of succinic acid. By 22 years of age, he had already published 2 substantial papers.

After graduation, Koch worked for a short time in Hamburg, followed by general practice in Langenhagen, Germany. He married Emmy Fratz in 1867, who later gave birth to a daughter, Gertrude. Later, Koch moved to Rakwitz (then part of Germany, now in Poland) and established a successful practice. When the Franco-Prussian war erupted in 1870, Koch served as a military surgeon. After being discharged in 1872, he started country practice as district physician in Wollstein, in Polish Prussia. This would mark a turning point in the life of the 29-year-old physician.

Koch also served as district health officer in Wollstein and established a busy practice. While things were going well in his clinical practice, the scientist in him was awakened in Wollstein. Part of the examining room at Koch's office was converted into a laboratory and part of the kitchen became a photographic dark room. Careful budgeting allowed him to purchase a good microscope. Koch read medical journals, visited research laboratories, and attended scientific meetings. In his primitive home laboratory, Koch embarked on his life's passion—the pursuit of microbes.

The first disease Koch would study was anthrax, a killer of livestock and occasionally of humans. In the first half of the 19th century, Aloys Pollender had observed rodlike organisms in the blood of cows that had died of anthrax. It was unknown at the time if the rodlike bodies were the cause or consequence of the disease. French scientist Casimir Davaine had shown that by inoculating blood that contained these bodies, the disease could be transmitted to healthy animals.

Koch set out to elucidate the life cycle of Bacillus anthracis. How he achieved this goal in a primitive laboratory without household electricity would stun any modern researcher. Koch invented the “hanging drop” preparation using ox-eye aqueous humor to grow the bacilli. In a remarkably short time, Koch worked out the life cycle of the anthrax bacillus and discovered the infectivity of the spores. Koch wrote to pioneer botanist and bacteriologist Ferdinand Cohn and was invited to Breslau to demonstrate his work on anthrax. Koch left a tremendous impression on Cohn and eminent pathologist Julius Cohnheim. Cohn and Cohnheim arranged an appointment for Koch at Breslau, but Koch returned to Wollstein in a short time.

While in Wollstein, Koch succeeded in obtaining the first photomicrographs of bacteria. Besides anthrax research, he focused on several other projects, including wound infections and micrococci in septicemic animals (later identified as streptococci and staphylococci).

In 1880, Koch accepted a position at the Imperial Health Office in Berlin, where he was provided with a good laboratory and 2 able assistants, Georg Gaffky and Friedrich Loeffler. Close proximity of the office to Berlin's Charité Hospital assured a steady supply of clinical material.

Koch's work in Berlin marked some of the most important milestones in bacteriology. Above all, Koch introduced the solid culture medium for cultivation of bacteria and the methodology of disinfection and sterilization. His solid culture plate technique would revolutionize bacteriologic research. After trying gelatin, Koch turned to agar for his plates. He perfected techniques to study bacteria microscopically, including methods of staining and photographing bacteria.

While Koch laid down the very foundations of bacteriology, it would be his work on tuberculosis that would make him a household name. By the time Koch initiated his work on tuberculosis in 1881, others had recognized its infectious nature. French physician Jean Antoine Villemin had shown that tuberculosis was transmissible to experimental animals. Koch examined numerous tubercular specimens under the microscope without much success until one day, with a modification of his staining technique, he was able to visualize the tubercle bacillus. Koch correctly surmised that the tubercle bacillus was surrounded by a “special wall of unusual properties.” In all tissues where tuberculosis had recently developed and was progressing rapidly, large numbers of bacilli could be visualized. Paul Ehrlich improved on Koch's staining procedure, using aniline instead of ammonia and fuchsin instead of methylene blue.

Koch more than anyone else was aware that the mere presence of an organism did not indicate that it was the cause of disease. Culture techniques that worked for anthrax and other bacteria did not work well on tuberculosis. After many attempts, Koch succeeded in creating tuberculosis cultures with a method using coagulated serum and obtained colonies. Final proof for the cultures came when they were tested for their virulence by inoculating guinea pigs, which succumbed to tuberculosis, and showed pathology similar to animals inoculated with human tuberculous material.

By March 1882, Koch had succeeded in determining the causative organism of tuberculosis. He showed that bacilli could be isolated in pure cultures and produce tuberculosis in animals that were inoculated. Koch's strict criteria of proof of etiology came to be defined as Koch's postulates.

In 1883, Koch headed the German cholera commission in Egypt and India, where he isolated the comma-shaped cholera bacillus. By 1885, Koch became Chair of the Institute of Hygiene at the University of Berlin. Subsequently, a new institute was opened for him in Berlin, which was later named the Robert Koch Institute.

In 1893, Koch and Emmy divorced and Koch married the much younger Hedwig Freiberg. His marriage to Freiberg created a scandal within the establishment of German professors.

Koch attracted an exceptional team of workers, such as August von Wasserman, Paul Ehrlich, Richard Pfeiffer, Emil von Behring, Shibasaburo Kitasato, Friedrich Loeffler, and Georg Gaffky, all of whom made their own mark in medicine. Koch was also noted for work in tropical medicine, especially trypanosomiasis, recurrent fever, typhoid fever, and the rinderpest outbreak in South Africa.

In 1890, Koch made a dramatic announcement at the Tenth International Medical Congress in Berlin, which caused a sensation in the medical world. He announced that he had a substance that hindered the growth of tubercle bacilli, cured tuberculosis in infected guinea pigs, and would probably be useful in the treatment of human tuberculosis. Koch later conceded that this substance, tuberculin, was a filtrate from a growth of tubercle bacilli on glycerol broth. While its therapeutic value was dubious, tuberculin's diagnostic value became evident.

No other discovery in infectious disease had more far-reaching implications than the etiology of tuberculosis, and Koch was awarded the Nobel Prize for this discovery in 1905. He entered bacteriology when it was in its infancy, but enriched it by his many contributions.

Koch died on May 27, 1910, of myocardial infarction.