Robert Koch: The Discovery of the Tubercle Bacillus and the Birth of Modern Microbiology (1905)

Nobel Information Card

• Award Year: 1905
• Field: Physiology or Medicine
• Award Rationale: For his research and discoveries in relation to tuberculosis.
• Born: 11 December 1843, Clausthal, Kingdom of Hanover
• Died: 27 May 1910, Baden-Baden, Germany
• Nationality: German
• Institution: Berlin University Institute of Hygiene

Life and Education

Robert Heinrich Hermann Koch was born on 11 December 1843 in Clausthal, Germany. His father, Hermann Koch, was a mining engineer; his mother, Mathilde Julie Henriette Biewend, was the daughter of a mining inspector. The third of thirteen children, Koch showed a strong curiosity about nature and science from an early age. He is said to have taught himself to read at the age of four.

After studying at his local school in Clausthal, Koch enrolled at the University of Göttingen in 1862. He had initially planned to study natural science but turned to medicine. At Göttingen he took classes with the anatomy professor Friedrich Gustav Jakob Henle. Henle was one of the pioneers of the hypothesis that infectious diseases are caused by living microorganisms, and his ideas deeply influenced the young Koch.

Koch received his medical doctorate in 1866 and worked briefly as a general practitioner in Hamburg and then in various small towns. He served as a volunteer military physician in the Franco-Prussian War of 1870–1871. After the war he began work as a district medical officer in the town of Wollstein (now Wolsztyn, Poland). It was in this small town, in modest conditions, that Koch's revolutionary microbiology work would begin.

Koch's wife Emmy had given him a microscope for his 28th birthday, and the gift would become one of the most productive instruments in the history of science. Koch turned part of his practice into a laboratory and there spent all the time he could spare from the patient care his profession required at the microscope.

Scientific Work

Koch's first great achievement was working out the life cycle of the anthrax bacillus. While working in Wollstein he began to investigate anthrax, then common in cattle in the area. In 1876 he elucidated the complete life cycle of Bacillus anthracis, including spore formation and the mechanism of disease production. The work was the first experimental proof that a specific microorganism causes a specific disease.

Koch's work on anthrax caught the attention of Ferdinand Cohn, professor of botany at the University of Breslau. Cohn invited Koch to the university and examined his work. Confirming the accuracy of Koch's findings, Cohn published the research in his own journal. This publication brought Koch recognition in the scientific world.

In 1878 Koch published a comprehensive monograph on the aetiology of wound infections. In it he experimentally demonstrated that different bacterial species cause different types of infection. He also made important innovations in techniques for staining, photographing and culturing bacteria. He perfected the method of culturing bacteria on solid media — a technique that made it possible to separate different bacterial species and to obtain pure cultures.

In 1880 Koch was appointed to the Imperial Health Office in Berlin and was able to continue his research under much better conditions. The bacteriological techniques he developed there became the foundation of the modern microbiology laboratory. Innovations such as agar-agar gelatine media, the Petri dish (developed by his assistant Richard Petri), the staining of bacteria with aniline dyes, and microphotography, spread from Koch's laboratory to the world.

The Discovery That Led to the Nobel Prize

Robert Koch's greatest achievement was the discovery of the tubercle bacillus, which he presented at the Berlin Physiological Society on 24 March 1882. That date is considered one of the most important days in the history of medicine and is now observed as World Tuberculosis Day.

Tuberculosis was the most destructive disease in 19th-century Europe, where it caused one in every seven deaths. Also known as the White Plague, it affected every social class and no definitive treatment was known. Various theories existed about its cause: hereditary predisposition, poor climatic conditions, malnutrition and infection were among them.

Koch followed a systematic approach in his quest to discover the tubercle bacillus. First he examined under the microscope the tissues of patients who had died of tuberculosis. Existing staining techniques were inadequate to show the bacillus, which would not take up standard dyes because of its lipid-rich cell wall. Koch developed a new staining technique using methylene blue and vesuvin (Bismarck brown), making the slender, rod-shaped bacilli visible in tuberculous tissue for the first time.

Koch did not stop at merely seeing the bacilli; he also succeeded in growing them in pure culture. He discovered that the tubercle bacillus grows extremely slowly — unlike other bacteria, it took weeks to form visible colonies. He successfully cultured the bacilli on a blood-serum-based solid medium and produced the disease experimentally by injecting the pure culture into guinea pigs. By re-isolating the bacilli from infected animals he closed the loop.

This work was the strongest application of the principles Koch would later formulate as Koch's postulates. Koch's postulates were: (1) The microorganism must be present in every diseased individual and absent from healthy individuals. (2) The microorganism must be isolated from a diseased host and grown in pure culture. (3) When the microorganism from the pure culture is introduced into a healthy host it must produce the same disease. (4) The same microorganism must be re-isolated from the experimentally infected host.

Koch's presentation on 24 March 1882 is regarded as one of the most influential scientific lectures in history. Paul Ehrlich, who was in the audience, described it as the most powerful scientific experience of his life. Koch's discovery proved beyond doubt that tuberculosis is a contagious disease and laid the scientific foundation for public-health measures against it.

In 1890 Koch announced a preparation he called tuberculin as a cure for tuberculosis. Tuberculin was a glycoprotein extract from the culture filtrate of the tubercle bacillus. The preparation, which Koch unveiled with great hopes, was a disappointment as a therapy and even caused some patients to deteriorate. The failure seriously damaged Koch's reputation. Tuberculin, however, later became an extremely valuable tool in the diagnosis of tuberculosis (the tuberculin skin test, or Mantoux test), and is still used today.

The Prize and After

In 1905 the Nobel Prize in Physiology or Medicine was awarded to Robert Koch for his research and discoveries in relation to tuberculosis. Koch received the prize in person at the ceremony held in Stockholm. In his Nobel lecture he emphasised that the fight against tuberculosis was not yet over and that research must continue.

After the Nobel Prize Koch concentrated on tropical diseases. He took part in many scientific expeditions to Africa and worked on malaria, sleeping sickness (Trypanosoma), rinderpest and East Coast fever. During these expeditions he demonstrated the effectiveness of quinine prophylaxis in the fight against malaria.

Koch's influence also continued through his students. Scientists trained in his laboratory included Emil von Behring, who developed the diphtheria and tetanus antisera; Paul Ehrlich, who introduced the concept of chemotherapy; Richard Pfeiffer, who worked on cholera and plague; and August von Wassermann, known for the Wassermann test.

Robert Koch died of a heart attack in Baden-Baden on 27 May 1910. The scientist, who passed away at the age of sixty-six, entered history as the founder of modern microbiology.

Legacy and Impact Today

Robert Koch's scientific legacy is one of the foundations of modern medicine. Koch's postulates have been used for more than a century as the basic framework for determining the cause of an infectious disease. Although some limitations of the postulates have become apparent in the era of modern molecular biology and virology, their conceptual framework still holds.

The bacteriological techniques Koch developed underpin the microbiology laboratory. Techniques such as the production of pure cultures on solid media, bacterial staining and microphotography are used in laboratories all over the world today.

More than 140 years after Koch's discovery, tuberculosis remains one of the deadliest infectious diseases worldwide. According to the World Health Organization, around 10 million new cases of tuberculosis occur each year and more than 1.5 million people die from it. The emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains keeps the importance of Koch's discovery topical.

The Robert Koch Institute in Berlin operates today as one of Germany's most important public-health bodies. It played a central role in Germany's response to the COVID-19 pandemic and continues to bear Koch's name.

Lesser-Known Facts

• Koch's microbiology career began with a microscope his wife gave him as a gift. In the modest conditions of the town of Wollstein, he turned a corner of his practice into a laboratory and changed the history of science.
• There was a fierce scientific rivalry between Koch and Louis Pasteur. The two scientists clashed sharply over anthrax vaccination and microbiological technique; the rivalry took on a national dimension and became a symbol of French–German scientific competition.
• The tuberculin scandal was the darkest period of Koch's career. The failure of the preparation he presented as a cure caused the deaths of some patients and gravely shook his scientific credibility.
• In 1893 Koch divorced his first wife and married his student Hedwig Freiberg. This was received as a scandal in the conservative society of the Victorian era.
• During Koch's cholera research expedition to Egypt in 1883, one of the team members died of the disease. Koch continued to work under these dangerous conditions and isolated the Vibrio cholerae bacillus.
• 24 March, the date on which Koch announced the discovery of the tubercle bacillus, has been declared World Tuberculosis Day by the World Health Organization.
• Five scientists trained in Koch's laboratory went on to win the Nobel Prize — an example of productivity unmatched in the history of science.