Robert Koch

Heinrich Hermann Robert Koch ( ; ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. He won the 1905 Nobel Prize in Physiology or Medicine "for his investigations and discoveries in relation to tuberculosis".

As the discoverer of the specific causative agents of deadly infectious diseases, including tuberculosis, cholera, and anthrax, he is regarded as one of the main founders of modern bacteriology. As such, he is popularly nicknamed the father of microbiology (with Louis Pasteur), and as the father of medical bacteriology. His discovery of the anthrax bacterium (Bacillus anthracis) in 1876 is considered the birth of modern bacteriology. Koch used his discoveries to establish that germs "could cause a specific disease" and directly provided proofs for the germ theory of diseases, therefore creating the scientific basis of public health, saving millions of lives. For his life's work, Koch is seen as one of the founders of modern medicine.

While working as a private physician, Koch developed many innovative techniques in microbiology. He was the first to use the oil immersion lens, condenser, and microphotography in microscopy. His invention of the bacterial culture method using agar and glass plates (later developed as the Petri dish by his assistant Julius Richard Petri) made him the first to grow bacteria in the laboratory. In appreciation of his work, he was appointed as the government advisor at the Imperial Health Office in 1880, promoted to a senior executive position (Geheimer Regierungsrat) in 1882, Director of Hygienic Institute and Chair (Professor of hygiene) of the Faculty of Medicine at Berlin University in 1885, and the Royal Prussian Institute for Infectious Diseases (later renamed Robert Koch Institute after his death) in 1891.

The methods Koch used in bacteriology led to the establishment of a medical concept known as Koch's postulates, four generalized medical principles to ascertain the relationship of pathogens with specific diseases. The concept is still in use in most situations and influences subsequent epidemiological principles such as the Bradford Hill criteria. A major controversy followed when Koch discovered tuberculin as a medication for tuberculosis which was proven to be ineffective, but developed for diagnosis of tuberculosis after his death. The day he announced the discovery of the tuberculosis bacterium, 24 March 1882, has been observed by the World Health Organization as "World Tuberculosis Day" every year since 1982.

Early life and education

Koch was born in Clausthal, Germany, on 11 December 1843, to Hermann Koch (1814–1877) and Mathilde Julie Henriette (née Biewend; 1818–1871). His father was a mining engineer. He was the third of thirteen siblings. He excelled academically from an early age. Before entering school in 1848, he had taught himself how to read and write.

At the age of 19, in 1862, Koch entered the University of Göttingen to study natural science. He took up mathematics, physics, and botany. He was appointed assistant in the university's Pathological Museum. After three semesters, he decided to change his area of study to medicine, as he aspired to be a physician. During his fifth semester at the medical school, Jacob Henle, an anatomist who had published a theory of contagion in 1840, asked him to participate in his research project on uterine nerve structure. This research won him a research prize from the university and enabled him to briefly study under Rudolf Virchow, who was at the time considered "Germany's most renowned physician".thumb|The Anthrax Disease Cycle. Anthrax particles live in a vegetative state until exposed to oxygen, where they form many infectious spores. They can live in the soil and be consumed by herbivores. Large herbivores, like cows, are most susceptible to anthrax disease, and humans are affected by animal waste, fecal matter, or corpses, from these herbivores. Anthrax infection is spread to humans when spores gain entry into the body, whether that is from inhalation, open wounds, or another method of entrance. Once inside, the spores are activated, allowing the bacteria to multiply and spread their toxins. Another spread of infection is through biting flies, like mosquitoes, that come in contact with the blood and feces of herbivores, preceded by contact with human flesh (information from Bergman et al., 2006).

Career

After graduating in 1866, Koch briefly worked as an assistant in the General Hospital of Hamburg. In October of that year, he moved to the Idiot's Hospital of Langenhagen (as it was known in English,), near Hanover, as a junior physician. In 1868, he moved to Neimegk and then to Rakwitz in 1869. After the Franco-Prussian War started in 1870, he enlisted in the German army as a volunteer surgeon in 1871 to support the war effort. Furthermore, he managed to isolate and grow selected pathogens in a pure laboratory culture. and invited Koch to demonstrate his new bacterium there in 1877. Koch was transferred to Breslau as district physician in 1879. A year later, he left for Berlin when he was appointed a government advisor at the Imperial Health Office, where he worked from 1880 to 1885. Following his discovery of the tuberculosis bacterium, he was promoted to Geheimer Regierungsrat, a senior executive position, in June 1882.

In 1885, Koch received two appointments as an administrator and professor at Berlin University. He became Director of Hygienic Institute and Chair (Professor of hygiene) of the Faculty of Medicine. In 1906, he moved to East Africa to research a cure for trypanosomiasis (sleeping sickness). He established the Bugula research camp, where up to 1000 people a day were treated with the experimental drug Atoxyl.

Scientific contributions

Anthrax

Robert Koch is widely known for his work with anthrax, discovering the causative agent of the fatal disease to be Bacillus anthracis. After officially becoming a district physician in Wollstein (today's Wolsztyn), Poland, in 1872, Koch began to study anthrax. Near Wollstein, anthrax was regularly taking the lives of humans and livestock without evidence explaining why. Eventually, in 1876, Koch discovered that anthrax was triggered by one singular pathogen. Koch's discovery of the dormant stage, the anthrax spores, allowed him to successfully unravel the mystery behind anthrax. By gaining a better understanding of this pathogen, he was able to shed light on the bacterium's resistance to environmental factors ("Robert Koch – Nobel Lecture" 2018). This groundbreaking achievement marked Koch as the pioneer scientist to discover that a microscopic organism was causing a disease to spread. His findings were especially impressive as they were done in a poorly equipped laboratory in Wollstein.

He published the discovery in a booklet as "Die Ätiologie der Milzbrand-Krankheit, Begründet auf die Entwicklungsgeschichte des Bacillus Anthracis" (The Etiology of Anthrax Disease, Based on the Developmental History of Bacillus Anthracis) in 1876 while working in Wollstein. His publication in 1877 on the structure of anthrax bacterium marked the first photography of a bacterium. His work with anthrax is notable in that he was the first to link a specific microorganism with a specific disease, rejecting the idea of spontaneous generation and supporting the germ theory of disease. Agar is a polysaccharide that remains solid at 37 °C, is not degraded by most bacteria, and results in a stable transparent medium.

Development of Petri dish

Koch's booklet published in 1881 titled "Zur Untersuchung von pathogenen Organismen" (Methods for the Study of Pathogenic Organisms) has been known as the "Bible of Bacteriology." In it he described a novel method of using glass slide with agar to grow bacteria. The method involved pouring a liquid agar onto the glass slide and then spreading a thin layer of gelatin over it. The gelatin made the culture medium solidify, in which bacterial samples could be spread uniformly. The whole bacterial culture was then put on a glass plate together with a small wet paper. Koch named this container as feuchte Kammer (moist chamber). The typical chamber was a circular glass dish 20 cm in diameter and 5 cm in height, and had a lid to prevent contamination. The glass plate and the transparent culture media made observation of the bacterial growth easy.

Koch publicly demonstrated his plating method at the Seventh International Medical Congress in London in August 1881. There, Louis Pasteur exclaimed, "C'est un grand progrès, Monsieur!" ("What a great progress, Sir!") The culture plate was given an eponymous name Petri dish. It is often asserted that Petri developed a new culture plate, but this was not so. He simply discarded the use of a glass plate and instead used the circular glass dish directly, not just as a moist chamber, but as the main culture container. This further reduced the chances of contamination. On the other hand, Paul Ehrlich later recollected that this moment was his "single greatest scientific experience." This absorbs the vaccine through the skin by means of multiple shallow punctures on the skin and many patients and doctors went to Berlin to get Koch's remedy. This is known as an extreme skin reaction that manifests itself at the BCG vaccination site within a few days after the vaccine is administered to an individual infected with tuberculosis. When a normal guinea pig was inoculated with pure tubercle bacillus, the wound would close rapidly and heal within several days. Afterwards, the site of the injection would open and form an ulcer until the animal died. However, if the same inoculated culture was injected into a guinea pig that was previously infected with tuberculosis, the site of the injection becomes dark and eventually heals normally and quickly (Moreland, 2024). The uncertainty in the chemical nature coined the term phenomenon in the name "Koch’s phenomenon."

Koch published his experiments in the 15 January 1891 issue of Deutsche Medizinische Wochenschrift, and The British Medical Journal immediately published the English version simultaneously. The English version was also reproduced in Nature, and The Lancet in the same month. The Lancet presented it as "glad tidings of great joy." and Koch subsequently adopted as "tuberkulin."

The first report on the clinical trial in 1891 was disappointing. By then, 1061 patients with tuberculosis of internal organs and 708 patients with tuberculosis of external tissues were given the treatment. An attempt to use tuberculin as a therapeutic drug is regarded as Koch's "greatest failure." Koch soon found that the intestinal mucosa of people who died of cholera always had bacterial infection, yet could not confirm whether the bacteria were the causative pathogens. As the outbreak in Egypt declined, he was transferred to Calcutta (now Kolkata), India, where there was a more severe outbreak. He soon found that the river Ganges was the source of cholera. He performed autopsies of almost 100 bodies, and found in each bacterial infection. He identified the same bacteria from water tanks, linking the source of the infection. His experiment using fresh blood samples indicated that the bacterium could kill red blood cells, and he hypothesized that some sort of poison was used by the bacterium to cause the disease. Koch reported his discovery to the German Secretary of State for the Interior on 2 February, and published it in the Deutsche Medizinische Wochenschrift (German Medical Weekly) the following month.

Although Koch was convinced that the bacterium was the cholera pathogen, he could not entirely establish critical evidence that the bacterium produced the symptoms in healthy subjects (following Koch's postulates). His experiment on animals using his pure bacteria culture did not cause the disease, and correctly explained that animals are immune to human pathogens. The bacterium was then known as "the comma bacillus", and scientifically as Bacillus comma. It was later realised that the bacterium was already described by an Italian physician Filippo Pacini in 1854, and was also observed by the Catalan physician Joaquim Balcells i Pascual around the same time. But they failed to identify the bacterium as the causative agent of cholera. Koch's colleague Richard Friedrich Johannes Pfeiffer correctly identified the comma bacillus as Pacini's vibrioni and renamed it as Vibrio cholera in 1896.

Acquired immunity

Koch observed the phenomenon of acquired immunity. On 26 December 1900, he arrived as part of an expedition to German New Guinea, which was then a protectorate of the German Reich. Koch serially examined the Papuan people, the indigenous inhabitants, and their blood samples and noticed they contained Plasmodium parasites, the cause of malaria, but their bouts of malaria were mild or could not even be noticed, i.e., were subclinical. On the contrary, German settlers and Chinese workers, who had been brought to New Guinea, fell sick immediately. The longer they had stayed in the country, however, the more they too seemed to develop a resistance against it.

Koch's postulates

During his time as government advisor, Koch published a report on how he discovered and experimentally showed the tuberculosis bacterium as the pathogen of tuberculosis. He described the importance of pure cultures in isolating disease-causing organisms and explained the necessary steps to obtain these cultures, methods which are summarized in Koch's four postulates. Koch's discovery of the causative agent of anthrax led to the formation of a generic set of postulates which can be used in the determination of the cause of most infectious diseases.

Although Koch worked out the principles, he did not formulate the postulates, which were introduced by his assistant Friedrich Loeffler. Loeffler, reporting his discovery of diphtheria bacillus in 1883, stated three postulates as follows:

:1. The organism must always be present in every case of the disease, but not in healthy individuals.

:2. The organism must be isolated from a diseased individual and grown in pure culture.

:3. The pure culture must cause the same disease when inoculated into a healthy, susceptible individual.

The fourth postulate was added by an American plant pathologist Erwin Frink Smith in 1905, and is stated as:

:4. The same pathogen must be isolated from the experimentally infected individuals.

Personal life

In July 1867, Koch married Emma (Emmy) Adolfine Josephine Fraatz, and the two had a daughter, Gertrude, in 1868.

Honours and legacy

thumb|upright|In 1938 the National Tuberculosis Association paid tribute to Koch and issued a U.S. [[Christmas Seal. Christmas seals were and continue to be sold as a way of raising funds to fight tuberculosis.]]

thumb|upright|Statue of Koch at Robert-Koch-Platz (Robert Koch square) in Berlin

alt=Koch's name as it appears on the LSHTM Frieze in Keppel Street|thumb|upright|Koch's name as it appears on the [[LSHTM frieze in Keppel Street, Bloomsbury, London|right]]

Koch was made a Knight Grand Cross in the Prussian Order of the Red Eagle on 19 November 1890, and was elected a Foreign Member of the Royal Society (ForMemRS) in 1897. In 1905, he was awarded the Nobel Prize in Physiology and Medicine "for his investigations and discoveries in relation to tuberculosis." In 1906, research on tuberculosis and tropical diseases won him the Order Pour le Merite and in 1908, the Robert Koch Medal, established to honour the greatest living physicians. Surgeon-General of Health Service, and Fellow of the Science Senate of Kaiser Wilhelm Society.

A large marble statue of Koch stands in a small park known as Robert Koch Platz, just north of the Charity Hospital, in the Mitte section of Berlin. His life was the subject of a 1939 German-produced motion picture that featured Oscar-winning actor Emil Jannings in the title role.

Koch and his relationship to Paul Ehrlich, who developed a mechanism to diagnose TB, were portrayed in the 1940 movie Dr. Ehrlich's Magic Bullet.

On 10 December 2017, Koch's birthday, he was celebrated in a Google Doodle.

Controversies

Louis Pasteur

At their first meeting at the Seventh International Medical Congress in London in August 1881, Koch and Pasteur were friendly towards each other. But the rest of their careers followed with scientific disputes. The conflict started when Koch interpreted his discovery of anthrax bacillus in 1876 as causality, that is, the germ caused the anthrax infections. Although his postulates were not yet formulated, he did not establish the bacterium as the cause of the disease: it was an inference. Pasteur therefore argued that Koch's discovery was not the full proof of causality, but Pasteur's anthrax vaccine developed in 1881 was. Koch published his conclusion in 1881 with a statement: "anthrax never occurs without viable anthrax bacilli or spores. In my opinion no more conclusive proof can be given that anthrax bacilli are the true and only cause of anthrax," and that vaccination such as claimed by Pasteur would be impossible. To prove his vaccine, Pasteur sent his assistant Louis Thuillier to Germany for demonstration and disproved Koch's idea. They had a heated public debate at the International Congress for Hygiene in Geneva in 1882, where Koch criticised Pasteur's methods as "unreliable," and claimed they "are false and [as such ] they inevitably lead to false conclusions." One week later, Koch publicised that the drug was a glycerine extract of a pure cultivation of the tuberculosis bacilli. This later assumption was taken as a fact in veterinary practice. Based on it, legislations were made in the US for the inspection of meat and milk. In 1898, an American veterinarian Theobald Smith published a detailed comparative study and found that the tuberculosis bacteria are different based on their structure, growth patterns, and pathogenicity. In addition, he also discovered that there were variations in each type. In his conclusion, he made two important points:

Human tuberculosis bacillus cannot infect cattle.
But cattle bacillus may infect humans since it is very pathogenic.

By that time, there was evidence that cattle tuberculosis was transmitted to humans through meat and milk. Upon these reports, Koch conceded that the two bacilli were different but still advocated that cattle tuberculosis was of no health concern. Speaking at the Third International Congress on Tuberculosis, held in London in July 1901, he said that cattle tuberculosis is not dangerous to humans and there is no need for medical attention. Chair of the congress, Joseph Lister reprimanded Koch and explained the medical evidence of cattle tuberculosis in humans.

1902 Nobel Prize

The Nobel Committee selected the 1902 Nobel Prize in Physiology or Medicine to be awarded for the discovery of the transmission of malaria. But it could not make the final decision on whom to give it to — the British surgeon Ronald Ross or the Italian biologist Giovanni Battista Grassi. Ross had discovered that the human malarial parasite was carried by certain mosquitoes in 1897, and the next year that bird malaria could be transmitted from infected to healthy birds by the bite of a mosquito. Grassi had discovered Plasmodium vivax and the bird malaria parasite, and towards the end of 1898 the transmission of Plasmodium falciparum between humans through mosquitoes Anopheles claviger. To the surprise of the Nobel Committee, the two nominees exchanged polemic arguments against each other publicly justifying the importance of their own works. Robert Koch was then appointed as a "neutral arbitrator" to make the final decision. To his disadvantage, Grassi had criticised Koch on his malaria research in 1898 during an investigation of the epidemic, Ross was selected for the award, as Koch "threw the full weight of his considerable authority in insisting that Grassi did not deserve the honour".

References

External links

Audio version of this page
, including the Nobel Lecture on 12 December 1905 The Current State of the Struggle against Tuberculosis
MPIWG-Berlin, Robert Koch Biography and bibliography in the Virtual Laboratory of the Max Planck Institute for the History of Science
Biography on the Science Museum web site
Musoptin.com, original microscope out of the laboratory Robert Koch used in Wollstein (1877)
Musoptin.com, microscope objectives: as they were used by Robert Koch for his first photos of microorganisms (1877–1878)