Heinrich Hermann Robert Koch ( , ; 11 December 1843 – 27 May 1910) was a German

physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...

and

microbiologist A microbiologist (from Ancient Greek, Greek ) is a scientist who studies microscopic life forms and processes. This includes study of the growth, interactions and characteristics of Microorganism, microscopic organisms such as bacteria, algae, f ...

. As the discoverer of the specific causative agents of deadly infectious diseases including

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...

(though the

bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

itself was discovered by

Filippo Pacini Filippo Pacini (25 May 1812 – 9 July 1883) was an Italian anatomist, posthumously famous for isolating the cholera bacterium ''Vibrio cholerae'' in 1854, well before Robert Koch's more widely accepted discoveries 30 years later. Pacini was born ...

in 1854), and

anthrax Anthrax is an infection caused by the bacterium ''Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The sk ...

, he is regarded as one of the main founders of modern

bacteriology Bacteriology is the branch and specialty of biology that studies the morphology, ecology, genetics and biochemistry of bacteria as well as many other aspects related to them. This subdivision of microbiology involves the identification, classificat ...

. As such he is popularly nicknamed the father of microbiology (with

Louis Pasteur Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named afte ...

), and as the father of medical bacteriology. His discovery of the anthrax bacterium (''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent ( obligate) pathogen within the genus ''Bacillus''. Its infection is a ...

'') in 1876 is considered as the birth of modern bacteriology. His discoveries directly provided proofs for the germ theory of diseases, and the scientific basis of

public health Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...

. 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 Microphotographs are photographs shrunk to microscopic scale.

in microscopy. His invention of the bacterial culture method using agar and glass plates (later developed as the

Petri dish A Petri dish (alternatively known as a Petri plate or cell-culture dish) is a shallow transparent lidded dish that biologists use to hold growth medium in which cells can be cultured,R. C. Dubey (2014): ''A Textbook Of Biotechnology For Class- ...

by his assistant

Julius Richard Petri Julius Richard Petri (31 May 185220 December 1921) was a German microbiologist who is generally credited with inventing the device known as the Petri dish, which is named after him, while working as assistant to bacteriologist Robert Koch. Li ...

) made him the first to grow bacteria in the laboratory. In appreciation of his work, he was appointed to 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 Humboldt-Universität zu Berlin (german: Humboldt-Universität zu Berlin, abbreviated HU Berlin) is a German public research university in the central borough of Mitte in Berlin. It was established by Frederick William III on the initiative o ...

in 1885, and the Royal Prussian Institute for Infectious Diseases (later renamed

Robert Koch Institute The Robert Koch Institute (RKI) is a German federal government agency and research institute responsible for disease control and prevention. It is located in Berlin and Wernigerode. As an upper federal agency, it is subordinate to the Federal ...

after his death) in 1891. The methods Koch used in bacteriology led to establishment of a medical concept known as

Koch's postulates Koch's postulates ( )"Koch"
''

Bradford Hill criteria The Bradford Hill criteria, otherwise known as Hill's criteria for causation, are a group of nine principles that can be useful in establishing epidemiologic evidence of a causal relationship between a presumed cause and an observed effect and have ...

. A major controversy followed when Koch discovered

tuberculin Tuberculin, also known as purified protein derivative, is a combination of proteins that are used in the diagnosis of tuberculosis. This use is referred to as the tuberculin skin test and is recommended only for those at high risk. Reliable admi ...

as a medication for tuberculosis which was proven to be ineffective, but developed for diagnosis of tuberculosis after his death. For his research on tuberculosis, he received the

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...

in 1905.Brock, Thomas. ''Robert Koch: A life in medicine and bacteriology.'' ASM Press: Washington DC, 1999. Print. The day he announced the discovery of the tuberculosis bacterium, 24 March, has been observed by the

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...

as "

World Tuberculosis Day World Tuberculosis Day, observed on 24 March each year, is designed to build public awareness about the global epidemic of tuberculosis (TB) and efforts to eliminate the disease. In 2018, 10 million people fell ill with TB, and 1.5 million die ...

" 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).Metchnikoff, Elie. ''The Founders of Modern Medicine: Pasteur, Koch, Lister.'' Classics of Medicine Library: Delanco, 2006. Print. 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. He completed secondary education in 1862, having excelled in science and math. At the age of 19, in 1862, Koch entered the

University of Göttingen The University of Göttingen, officially the Georg August University of Göttingen, (german: Georg-August-Universität Göttingen, known informally as Georgia Augusta) is a public research university in the city of Göttingen, Germany. Founded ...

to study natural science."Heinrich Hermann Robert Koch." ''World of Scientific Discovery.'' Gale, 2006. Biography in Context. Web. 14 April 2013. 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 Rudolf Ludwig Carl Virchow (; or ; 13 October 18215 September 1902) was a German physician, anthropologist, pathologist, prehistorian, biologist, writer, editor, and politician. He is known as "the father of modern pathology" and as the founder ...

, who was at the time considered as "Germany's most renowned physician." In his sixth semester, Koch began to research at the Physiological Institute, where he studied the secretion of

succinic acid Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

, which is a signaling molecule that is also involved in the metabolism of the mitochondria. This would eventually form the basis of his dissertation. In January 1866, he graduated from the medical school, earning honours of the highest distinction, ''

maxima cum laude Latin honors are a system of Latin phrases used in some colleges and universities to indicate the level of distinction with which an academic degree has been earned. The system is primarily used in the United States. It is also used in some Sou ...

''.

Career

After graduation in 1866, Koch briefly worked as an assistant in the General Hospital of Hamburg. In October that year he moved to Idiot's Hospital of Langenhagen, near Hanover, as a general physician. In 1868, he moved to Neimegk and then to Rakwitz in 1869. As the Franco-Prussian War started in 1870, he enlisted in the German army as a volunteer surgeon in 1871 to support the war effort. He was discharged a year later and was appointed as a district physician (''Kreisphysikus'') in Wollstein in

Prussia Prussia, , Old Prussian: ''Prūsa'' or ''Prūsija'' was a German state on the southeast coast of the Baltic Sea. It formed the German Empire under Prussian rule when it united the German states in 1871. It was ''de facto'' dissolved by an em ...

n Posen (now

Wolsztyn Wolsztyn (german: Wollstein) is a town in western Poland, on the western edge of Greater Poland Voivodeship. It is the seat of Wolsztyn County, and of the smaller administrative district of Gmina Wolsztyn. Geography The town is situated within ...

, Poland). As his family settled there, his wife gave him a microscope as a birthday gift. With the microscope, he set up a private laboratory and started his career in microbiology. Koch began conducting research on microorganisms in a laboratory connected to his patient examination room. His early research in this laboratory yielded one of his major contributions to the field of microbiology, as he developed the technique of growing bacteria.Madigan, Michael T., et al. ''Brock Biology of Microorganisms: Thirteenth edition.'' Benjamin Cummings: Boston, 2012. Print. Furthermore, he managed to isolate and grow selected pathogens in a pure laboratory culture. His discovery of the anthrax bacillus (later named ''

'') hugely impressed

Ferdinand Julius Cohn Ferdinand Julius Cohn (24 January 1828 – 25 June 1898) was a German biologist. He is one of the founders of modern bacteriology and microbiology. Ferdinand J. Cohn was born in the Jewish quarter of Breslau in the Prussian Province of Siles ...

, professor at the University of Breslau (now the

University of Wrocław , ''Schlesische Friedrich-Wilhelms-Universität zu Breslau'' (before 1945) , free_label = Specialty programs , free = , colors = Blue , website uni.wroc.pl The University of Wrocław ( pl, Uniwersytet Wrocławski, U ...

), who helped him publish the discovery in 1876. Cohn had established the Institute of Plant Physiology and invited Koch to demonstrate his new bacterium there in 1877. Koch was transferred to Breslau as district physician in 1879. A year after, he left for Berlin when he was appointed a government advisor at the Imperial Health Office, where he worked from 1880 to 1885.O’Connor, T.M. "Tuberculosis, Overview." ''International Encyclopedia of Public Health.'' 2008. Web. 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

. He became Director of Hygienic Institute and Chair (Professor of hygiene) of the Faculty of Medicine. In 1891, he relinquished his professorship and became a director of the Royal Prussian Institute for Infectious Diseases (now the

) which consisted of a clinical division and beds for the division of clinical research. For this he accepted harsh conditions. The Prussian Ministry of Health insisted after the 1890 scandal with

, which Koch had discovered and intended as a remedy for tuberculosis, that any of Koch's inventions would unconditionally belong to the government and he would not be compensated. Koch lost the right to apply for patent protection.Christoph Gradmann: Laboratory Disease, Robert Koch's Medical Bacteriology. The Johns Hopkins University Press, Baltimore 2009, , p. 111 ff. In 1906, he moved to East Africa to research a cure for

trypanosomiasis Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus ''Trypanosoma''. In humans this includes African trypanosomiasis and Chagas disease. A number of other diseas ...

(sleeping sickness). He established the Bugula research camp where up to 1000 people a day were treated with the experimental drug Atoxyl.

Scientific contributions

Techniques in bacteria study

Robert Koch made two important developments in microscopy; he was the first to use an oil immersion lens and a condenser that enabled smaller objects to be seen. In addition, he was also the first to effectively use photography (

microphotograph Microphotographs are photographs shrunk to microscopic scale.

y) for microscopic observation. He introduced the "bedrock methods" of bacterial staining using

methylene blue Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...

and Bismarck (Vesuvin) brown dye. In an attempt to grow bacteria, Koch began to use solid nutrients such as

potato The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae. Wild potato species can be found from the southern Unit ...

slices. Through these initial experiments, Koch observed individual colonies of identical, pure cells. He found that potato slices were not suitable media for all organisms, and later began to use nutrient solutions with

gelatin Gelatin or gelatine (from la, gelatus meaning "stiff" or "frozen") is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also ...

. However, he soon realized that gelatin, like potato slices, was not the optimal medium for bacterial growth, as it did not remain solid at 37 °C, the ideal temperature for growth of most human pathogens. And also many bacteria can hydrolyze gelatin making it a liquid. As suggested to him by his post-doctoral assistant

Walther Hesse Walther Hesse (27 December 1846 – 19 July 1911) is best known for his work in microbiology, specifically his work with his wife Fanny Hesse in developing agar as a medium for culturing microorganisms. Biography He was born in Bischofswerda, ...

, who got the idea from his wife

Fanny Hesse Fanny Hesse (born Angelina Fanny Eilshemius, June 22, 1850 – December 1, 1934) is best known for her work in microbiology alongside her husband, Walther Hesse. Following her initial suggestion of using agar as an alternative to gelatin, they ...

, in 1881, Koch started using agar to grow and isolate pure cultures. Agar is a

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wa ...

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 on to the glass slide and then spreading a thin layer of gelatin over. The gelatin made the culture medium solidify, in which bacterial samples could be spread uniformly. The whole bacterial culture was then put in 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 The International Medical Congress (french: Congrès International de Médecine) was a series of international scientific conferences on medicine that took place, periodically, from 1867 until 1913. The idea of such a congress came in 1865, dur ...

in London in August 1881. There,

exclaimed, ''"C'est un grand progrès, Monsieur''!" ("What a great progress, Sir!") It was using Koch's microscopy and agar-plate culture method that his students discovered new bacteria.

Friedrich Loeffler Friedrich August Johannes Loeffler (; 24 June 18529 April 1915) was a German bacteriologist at the University of Greifswald. Biography He obtained his M.D. degree from the University of Berlin in 1874. He worked with Robert Koch from 1879 to 1884 ...

discovered the bacteria of

glanders Glanders is a contagious zoonotic infectious disease that occurs primarily in horses, mules, and donkeys. It can be contracted by other animals, such as dogs, cats, pigs, goats, and humans. It is caused by infection with the bacterium ''Burkhol ...

(''

Burkholderia mallei ''Burkholderia mallei'' is a Gram-negative, bipolar, aerobic bacterium, a human and animal pathogen of genus ''Burkholderia'' causing glanders; the Latin name of this disease (''malleus'') gave its name to the species causing it. It is closely re ...

'') in 1882 and

diphtheria Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...

('' Corynebacterium diphtheriae'') in 1884; and Georg Theodor August Gaffky, the bacterium of

typhoid Typhoid fever, also known as typhoid, is a disease caused by '' Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several ...

(''

Salmonella enterica ''Salmonella enterica'' (formerly ''Salmonella choleraesuis'') is a rod-headed, flagellate, facultative anaerobic, Gram-negative bacterium and a species of the genus ''Salmonella''. A number of its serovars are serious human pathogens. Epidemi ...

'') in 1884. Koch's assistant

developed an improved method and published it in 1887 as "''Eine kleine Modification des Koch’schen Plattenverfahrens''" (A minor modification of the plating technique of Koch). The culture plate was given an eponymous name

. It is often asserted that Petri developed a new culture plate, but this was not so. He simply discarded the use of glass plate and instead used the circular glass dish directly, not just as moist chamber, but as the main culture container. This further reduced chances of contaminations. It would also have been appropriate if the name "Koch dish" had been given.

Anthrax

Robert Koch is widely known for his work with

, discovering the causative agent of the fatal disease to be ''

''. 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 at in Wöllstein. His publication in 1877 on the structure of anthrax bacterium marked the first photography of a bacterium. He discovered the formation of

spores In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...

in anthrax bacteria, which could remain dormant under specific conditions. However, under optimal conditions, the spores were activated and caused disease. To determine this causative agent, he dry-fixed bacterial cultures onto glass slides, used dyes to stain the cultures, and observed them through a microscope."Robert Koch." ''World of Microbiology and Immunology.'' Ed. Brenda Wilmoth Lerner and K. Lee Lerner. Detroit: Gale, 2006. Biography in Context. Web. 14 April 2013. 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 Spontaneous generation is a superseded scientific theory that held that living creatures could arise from nonliving matter and that such processes were commonplace and regular. It was hypothesized that certain forms, such as fleas, could arise fr ...

and supporting the

germ theory of disease The germ theory of disease is the currently accepted scientific theory for many diseases. It states that microorganisms known as pathogens or "germs" can lead to disease. These small organisms, too small to be seen without magnification, invade h ...

."Germ theory of disease." ''World of Microbiology and Immunology.'' Ed. Brenda Wilmoth Lerner and K. Lee Lerner. Detroit: Gale, 2007. Biography in Context. Web. 14 April 2013.

Tuberculosis

During his time as the government advisor with the Imperial Health Agency in Berlin in the 1880s, Koch became interested in

research. At the time, it was widely believed that tuberculosis was an inherited disease. However Koch was convinced that the disease was caused by a bacterium and was infectious. In 1882, he published his findings on tuberculosis, in which he reported the causative agent of the disease to be the slow-growing ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...

''. He published the discovery as "''Die Ätiologie der Tuberkulose''" (''The Etiology of Tuberculosis''), and presented before the German Physiological Society at Berlin on 24 March 1882. Koch said,

When the cover-glasses were exposed to this staining fluid ethylene_blue_mixed_with_potassium_hydroxide.html" ;"title="potassium_hydroxide.html" ;"title="ethylene blue mixed with potassium hydroxide">ethylene blue mixed with potassium hydroxide">potassium_hydroxide.html" ;"title="ethylene blue mixed with potassium hydroxide">ethylene blue mixed with potassium hydroxidefor 24 hours, very fine rod-like forms became apparent in the tubercular mass for the first time, having, as further observations showed, the power of multiplication and of spore formation and hence belonging to the same group of organisms as the anthrax bacillus... Microscopic examination then showed that only the previously blue-stained cell nuclei and detritus became brown, while the tubercle bacilli remained a beautiful blue.

There was no particular reaction to this announcement. Eminent scientists such as

remained skeptical. Virchow clung to his theory that all diseases are due to faulty cellular activities. On the other hand, Paul Ehrlich later recollected that this moment was his "single greatest scientific experience." Koch expanded the report and published under the same title as a booklet in 1884, in which he concluded that the discovery of tuberculosis bacterium fulfilled the three principles, eventually known as Koch's

postulates An axiom, postulate, or assumption is a statement that is taken to be true, to serve as a premise or starting point for further reasoning and arguments. The word comes from the Ancient Greek word (), meaning 'that which is thought worthy or f ...

, which were formulated by his assistant Friedrich Loeffler in 1883, saying:

All these factors together allow me to conclude that the bacilli present in the tuberculous lesions do not only accompany tuberculosis, but rather cause it. These bacilli are the true agents of tuberculosis.

Cholera

In August 1883, the German government sent a medical team led by Koch to

Alexandria, Egypt Alexandria ( or ; ar, ٱلْإِسْكَنْدَرِيَّةُ ; grc-gre, Αλεξάνδρεια, Alexándria) is the second largest city in Egypt, and the largest city on the Mediterranean coast. Founded in by Alexander the Great, Alexandria ...

, to investigate a cholera epidemic there. Koch soon found that the

intestinal mucosa The gastrointestinal wall of the gastrointestinal tract is made up of four layers of specialised tissue. From the inner cavity of the gut (the lumen) outwards, these are: # Mucosa # Submucosa # Muscular layer # Serosa or adventitia The muco ...

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 Kolkata (, or , ; also known as Calcutta , the official name until 2001) is the capital of the Indian state of West Bengal, on the eastern bank of the Hooghly River west of the border with Bangladesh. It is the primary business, comme ...

) India, where there was a more severe outbreak. He soon found that the river

Ganges The Ganges ( ) (in India: Ganga ( ); in Bangladesh: Padma ( )). "The Ganges Basin, known in India as the Ganga and in Bangladesh as the Padma, is an international river to which India, Bangladesh, Nepal and China are the riparian states." is ...

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. He isolated the bacterium in pure culture on 7 January 1884. He subsequently confirmed that the bacterium was a new species, and described as "a little bent, like a comma." 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. In 1959, Indian scientist

Sambhu Nath De Sambhunath De ; (1 February 1915 – 15 April 1985) was an Indian medical scientist and researcher, who discovered the cholera toxin, the ''animal model of cholera'', and successfully demonstrated the method of transmission of cholera pathogen ...

discovered this poison, the

cholera toxin Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex secreted by the bacterium ''Vibrio cholerae''. CTX is responsible for the massive, watery diarrhea characteristic of cholera i ...

. 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 a critical evidence the bacterium produced the symptoms in healthy subjects (following

Koch's postulates Koch's postulates ( )"Koch"
''

in 1854, and was also observed by the

Catalan Catalan may refer to: Catalonia From, or related to Catalonia: * Catalan language, a Romance language * Catalans, an ethnic group formed by the people from, or with origins in, Northern or southern Catalonia Places * 13178 Catalan, asteroid #1 ...

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 Richard Friedrich Johannes Pfeiffer FRS (27 March 1858 – 15 September 1945) was a German physician and bacteriologist. Pfeiffer was born to Otto Pfeiffer, a German pastor of the local Evangelical parish, and Natalia née Jüttner, in Treus ...

correctly identified the comma bacillus as Pacini's ''vibrioni'' and renamed it as '' Vibrio cholera'' in 1896.

Tuberculosis treatment and tuberculin

Koch gave much of his research attention on tuberculosis throughout his career. After medical expeditions to various parts of the world, he again focussed on tuberculosis from the mid-1880s. By that time the Imperial Health Office was carrying out a project for disinfection of sputum of tuberculosis patients. Koch experimented with

arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, but ...

and

creosote Creosote is a category of carbonaceous chemicals formed by the distillation of various tars and pyrolysis of plant-derived material, such as wood or fossil fuel. They are typically used as preservatives or antiseptics. Some creosote types were ...

as possible disinfectants. These chemicals and other available drugs did not work. His report in 1883 also mentioned a failed experiment on an attempt to make tuberculosis vaccine. By 1888, Koch turned his attention to

synthetic dyes A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution and ...

as antibacterial chemicals. He developed a method for examining antibacterial activity by mixing the gelatin-based culture media with a yellow dye, auramin. His notebook indicates that by February 1890, he tested hundreds of compounds. In one of such tests, he found that an extract from the tuberculosis bacterium culture dissolved in glycerine could cure tuberculosis in guinea pigs. Based on a series of experiments from April to July 1891, he could conclude that the extract did not kill the tuberculosis bacterium, but destroyed (by

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

) the infected tissues, thereby depriving bacterial growth. He made a vague announcement in August 1890 at the Tenth

in Berlin, saying,

In a communication which I made a few months ago to the International Medical Congress n London in 1881 I described a substance of which the result is to make laboratory animals insensitive to inoculation of tubercle bacilli, and in the case of already infected animals, to bring the tuberculous process to a halt. I can tell ��that much, that guinea pigs, which are highly susceptible to the disease uberculosis no longer react upon inoculation with tubercle virus acteriumwhen treated with that substance and that in guinea pigs, which are sick (with tuberculosis), the pathological process can be brought to a complete standstill.

By November 1890, Koch was able to show that the extract was effective in humans as well. Many patients and doctors went to Berlin to get Koch's remedy. But his experiments showed that tuberculosis infected guinea pigs developed severe symptoms when the substance was inoculated. The severity was more so in humans. This development of severe immune response, which is now known to be due to

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...

, is known as the "Koch phenomenon." The chemical nature was not known, and among several independent experiments done by the next year, only his son-in-law, Eduard Pfuhl, was able to reproduce similar results. It nevertheless became a medical sensation, and the unknown substance was referred to as "Koch's Lymph." Koch published his experiments in the 15 January 1891 issue of ''Deutsche Medizinische Wochenschrift'', and ''

The British Medical Journal ''The BMJ'' is a weekly peer-reviewed medical trade journal, published by the trade union the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world's oldest general medical journals. Origina ...

'' immediately published the English version simultaneously. The English version was also reproduced in ''

Nature Nature, in the broadest sense, is the physics, physical world or universe. "Nature" can refer to the phenomenon, phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. ...

'', and ''

The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...

'' in the same month. ''The Lancet'' presented it as "glad tidings of great joy." Koch simply referred to the medication as "brownish, transparent fluid." Josephs Pohl-Pincus had used the name tuberculin in 1844 for tuberculosis culture media, 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 of 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." With it his reputation greatly waned. But he devoted the rest of his life trying to make tuberculin as a usable medication. His discovery was not a total failure, the substance is today used for hypersensitivity test for tuberculosis patients.

Acquired immunity

Koch observed the phenomenon of acquired

immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity desc ...

. On 26 December 1900, he arrived as part of an expedition to

German New Guinea German New Guinea (german: Deutsch-Neu-Guinea) consisted of the northeastern part of the island of New Guinea and several nearby island groups and was the first part of the German colonial empire. The mainland part of the territory, called , ...

, which was then a protectorate of the German Reich. Koch serially examined the

Papuan people The indigenous peoples of West Papua in Indonesia and Papua New Guinea, commonly called Papuans, are Melanesians. There is genetic evidence for two major historical lineages in New Guinea and neighboring islands: a first wave from the Malay Arc ...

, the indigenous inhabitants, and their blood samples and noticed they contained ''

Plasmodium ''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a vert ...

'' parasites, the cause of

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

, 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 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.Amsterdamska, Olga. "Bacteriology, Historical." ''International Encyclopedia of Public Health.'' 2008. Web. Koch's discovery of the causative agent of anthrax led to the formation of a generic set of

which can be used in the determination of the cause of most infectious diseases. These postulates, which not only outlined a method for linking cause and effect of an infectious disease but also established the significance of laboratory culture of infectious agents, became the "gold standard" in 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 individuals. 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. Their marriage ended after 26 years in 1893, and later that same year, he married actress Hedwig Freiberg (1872–1945). On 9 April 1910, Koch suffered a heart attack and never made a complete recovery. On 27 May, three days after giving a lecture on his tuberculosis research at the

Prussian Academy of Sciences The Royal Prussian Academy of Sciences (german: Königlich-Preußische Akademie der Wissenschaften) was an academy established in Berlin, Germany on 11 July 1700, four years after the Prussian Academy of Arts, or "Arts Academy," to which "Berlin ...

, Koch died in

Baden-Baden Baden-Baden () is a spa town in the states of Germany, state of Baden-Württemberg, south-western Germany, at the north-western border of the Black Forest mountain range on the small river Oos (river), Oos, ten kilometres (six miles) east of the ...

at the age of 66. Following his death, the Institute named its establishment after him in his honour. He was irreligious.

Awards and honors

Robert Koch's name on the Frieze of LSHTM

Koch was made a Knight Grand Cross in the Prussian

Order of the Red Eagle The Order of the Red Eagle (german: Roter Adlerorden) was an order of chivalry of the Kingdom of Prussia. It was awarded to both military personnel and civilians, to recognize valor in combat, excellence in military leadership, long and faithful se ...

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 The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...

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 The Robert Koch Medal and Award are two prizes awarded annually by the German for excellence in the biomedical sciences. These awards grew out of early attempts by German physician Robert Koch to generate funding to support his research into the ...

, established to honour the greatest living physicians. Emperor Wilhelm I awarded him the Order of the Crown, 100,000 marks and appointment as Privy Imperial Councillor, Surgeon-General of Health Service, and Fellow of the Science Senate of Kaiser Wilhelm Society. Koch established the Royal Prussian Institute for Infectious Diseases in Berlin 1891. After his death it was renamed Robert Koch Institute in his honour. The World Health Organization observes "

" every 24 March since 1982 to commemorate the day Koch discovered tuberculosis bacterium. Koch's name is one of 23 from the fields of hygiene and tropical medicine featured on the frieze of the

London School of Hygiene & Tropical Medicine The London School of Hygiene and Tropical Medicine (LSHTM) is a public research university in Bloomsbury, central London, and a member institution of the University of London that specialises in public health and tropical medicine. The inst ...

building in

Keppel Street Keppel Street is a street in the London Borough of Camden that runs from the junction of Store Street and Gower Street in the west to Malet Street in the east. Before the construction of Senate House, it continued on to join Russell Square ...

, Bloomsbury. A large marble statue of Koch stands in a small park known as Robert Koch Platz, just north of the Charité, 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. On 10 December 2017, Google showed a Doodle in celebration of Koch's birthday. 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''.

Controversies

Louis Pasteur

At their first meeting at the Seventh

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." Koch later continued to attack Pasteur, saying, "Pasteur is not a physician, and one cannot expect him to make sound judgments about pathological processes and the symptoms of disease."

Tuberculin

When Koch discovered tuberculin in 1890 as a medication for tuberculosis, he kept the experiment secret and avoided disclosing the source. It was only after a year under public pressure that he publicly announced the experiment and the source. Clinical trials with tuberculin were disastrous and complete failures. Rudolf Virchow's autopsy report of 21 subjects treated with tuberculin to the Berlin Medical Society on 7 January 1891 revealed that instead of healing tuberculosis, the subjects died because of the treatment. One week later, Koch publicised that the drug was a glycerine extract of a pure cultivation of the tuberculosis bacilli. The German official report in the late 1891 declared that tuberculosis was not cured with tuberculin. From this moment onwards, Koch's prestige fell apart. The reason for his initial secrecy was due to an ambition for monetary benefits for the new drug, and with that establishment of his own research institute. Since 1885, he had tried to leave government service and create an independent state-run institute of his own. Following the disappointment, he was released from the University of Berlin and forced to work as Director of the Royal Prussian Institute for Infectious Diseases, a newly established institute, in 1891. He was prohibited from working on tuberculin and from claim for patent rights in any of his subsequent works.

Human and cattle tuberculosis

Koch initially believed that human (''Mycobacterium tuberculosis'') and cattle tuberculosis bacilli (now called ''Mycobacterium bovis'') were different pathogens when he made the discovery in 1882. Two years later, he revoked that position and asserted that the two bacilli were the same type. This later assumption was taken as a fact in veterinary practice. Based on it, legislations were made in US for 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. He said, "I therefore consider it unnecessary to take any measures against this form of TB. The fight against TB clearly has to concentrate on the human ''bacillus.''" Chair of the congress, Joseph Lister reprimanded Koch and explained the medical evidences of cattle tuberculosis in humans.

The 1902 Nobel Prize in Physiology or Medicine

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, while Ross had established a cordial relationship with Koch. Ross was selected for the award, as Koch "threw the full weight of his considerable authority in insisting that Grassi did not deserve the honor."

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

original microscope out of the laboratory Robert Koch used in Wollstein (1877)

microscope objectives: as they were used by Robert Koch for his first photos of microorganisms (1877–1878) * * * * {{DEFAULTSORT:Koch, Robert Robert Koch, 1843 births 1910 deaths People from Goslar (district) German bacteriologists German infectious disease physicians 19th-century German inventors German microbiologists German military personnel of the Franco-Prussian War German Nobel laureates German military doctors Humboldt University of Berlin faculty Members of the Prussian Academy of Sciences Members of the Royal Swedish Academy of Sciences Nobel laureates in Physiology or Medicine People from the Kingdom of Hanover Tuberculosis researchers Recipients of the Pour le Mérite (civil class) University of Göttingen alumni Foreign Members of the Royal Society Foreign associates of the National Academy of Sciences Prussian Army personnel Robert Koch Institute people Cholera Tuberculosis Physicians of the Charité Medical Microbiology and Immunology editors