Editing Robert Koch

{{Short description|German physician and bacteriologist (1843–1910)}}
{{other people}}
{{Use dmy dates|date=March 2021|cs1-dates=y}}

{{Infobox scientist
| name              = Robert Koch
| image             = RobertKoch cropped.jpg
| caption           = Koch {{circa|1900}}
| birth_name        = Heinrich Hermann Robert Koch
| birth_date        = {{birth date|df=yes|1843|12|11}}
| birth_place       = [[Clausthal]], [[Kingdom of Hanover]], [[German Confederation]]
| death_date        = {{death date and age|df=yes|1910|5|27|1843|12|11}}
| death_place       = [[Baden-Baden]], [[Grand Duchy of Baden]], [[German Empire]]
| nationality       = [[Germany|German]]
| field             = [[Microbiology]]
| work_institutions = Imperial Health Office, Berlin <br /> [[University of Berlin]]
| education         = [[University of Göttingen]]
| doctoral_advisor  = [[Georg Meissner]]
| academic_advisors = [[Friedrich Gustav Jakob Henle]]<br />[[Karl Ewald Hasse]]<br />[[Rudolf Virchow]]
| known_for         = [[Koch's postulates]]<br />[[Koch–Pasteur rivalry]]<br />[[Microbiological culture|Bacterial culture method]]<br />[[Germ theory of disease]]<br />[[Medical microbiology]]<br />[[Bacillus anthracis|Discovery of anthrax bacillus]]<br />[[Mycobacterium tuberculosis|Discovery of tuberculosis bacillus]] and [[tuberculin]]<br />[[Vibrio cholerae|Discovery of cholera bacillus]]
| prizes            = {{Plainlist|
* [[Fellow of the Royal Society|ForMemRS]] (1897)
* [[Nobel Prize in Medicine]] (1905)
* [[List of recipients of the Pour le Mérite for Sciences and Arts|Pour le Mérite]] (1906)}}
}}

'''Heinrich Hermann Robert Koch''' ({{IPAc-en|k|ɒ|x}} {{respell|KOKH}};<ref>[http://dictionary.reference.com/browse/koch "Koch"]. ''[[Random House Webster's Unabridged Dictionary]]''.</ref><ref name="AHD">{{Citation |title="Koch". The American Heritage Dictionary of the English Language |publisher=Houghton Mifflin Harcourt |url=https://ahdictionary.com/word/search.html?q=Koch}}</ref> {{IPA|de|ˈʁoːbɛʁt kɔx|lang|De-Robert Koch.ogg}}; 11 December 1843 – 27 May 1910) was a German [[physician]] and [[microbiologist]]. 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]]<ref>{{Cite journal|last=Fleming|first=Alexander|date=1952|title=Freelance of Science|journal=British Medical Journal|volume=2|issue=4778|pages=269|doi=10.1136/bmj.2.4778.269|pmc=2020971}}</ref>), and as the father of medical bacteriology.<ref>{{Cite journal|last1=Tan|first1=S. Y.|last2=Berman|first2=E.|date=2008|title=Robert Koch (1843-1910): father of microbiology and Nobel laureate|url=https://pubmed.ncbi.nlm.nih.gov/19037548|journal=Singapore Medical Journal|volume=49|issue=11|pages=854–855|pmid=19037548}}</ref><ref name=":9">{{Cite journal|last=Gradmann|first=Christoph|date=2006|title=Robert Koch and the white death: from tuberculosis to tuberculin|journal=Microbes and Infection|volume=8|issue=1|pages=294–301|doi=10.1016/j.micinf.2005.06.004|pmid=16126424|doi-access=free}}</ref> His discovery of the anthrax bacterium (''[[Bacillus anthracis]]'') in 1876 is considered as the birth of modern bacteriology.<ref name=":17">{{Cite journal|last=Lakhani|first=S. R.|date=1993|title=Early clinical pathologists: Robert Koch (1843-1910)|journal=Journal of Clinical Pathology|volume=46|issue=7|pages=596–598|doi=10.1136/jcp.46.7.596|pmc=501383|pmid=8157741}}</ref> Koch used his discoveries to establish that germs "could cause a specific disease"<ref>{{cite book | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK24649/#:~:text=In%20the%20final%20decades%20of,and%20suspected%20they%20caused%20anthrax | title=Science, Medicine, and Animals | chapter=A Theory of Germs | date=20 October 2023 | publisher=National Academies Press (US) }}</ref> and directly provided proofs for the [[germ theory of diseases]], therefore creating the scientific basis of [[public health]],<ref name=":16">{{Cite journal|last=Lakhtakia|first=Ritu|date=2014|title=The Legacy of Robert Koch: Surmise, search, substantiate|journal=Sultan Qaboos University Medical Journal|volume=14|issue=1|pages=e37–41|doi=10.12816/0003334|pmc=3916274|pmid=24516751}}</ref> saving millions of lives.<ref>{{cite web | url=https://history.info/on-this-day/1843-robert-koch-man-saved-millions-lives/ | title=1843: Robert Koch: The Man who Saved Millions of Lives &#124; History.info | date=10 December 2019 }}</ref> 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 (optics)|condenser]], and [[microphotography]] in microscopy. His invention of the [[Growth medium|bacterial culture method]] using [[Agar plate|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 to government advisor at the [[Federal Health Agency|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]].<ref>{{Cite journal|last=Margo|first=Curtis E.|date=11 April 2011|title=From Robert Koch to Bradford Hill: Chronic Infection and the Origins of Ocular Adnexal Cancers|url=https://jamanetwork.com/journals/jamaophthalmology/fullarticle/427189|journal=Archives of Ophthalmology|language=en|volume=129|issue=4|pages=498–500|doi=10.1001/archophthalmol.2011.53|pmid=21482875|issn=0003-9950}}</ref> 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. For his research on tuberculosis, he received the [[Nobel Prize in Physiology or Medicine]] in 1905.<ref name="Robert Koch A Life">Brock, Thomas. ''Robert Koch: A life in medicine and bacteriology.'' ASM Press: Washington DC, 1999. Print.</ref> 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 [[Klausthal|Clausthal, Germany]], on 11 December 1843, to Hermann Koch (1814–1877) and Mathilde Julie Henriette (née Biewend; 1818–1871).<ref name="The Founders">Metchnikoff, Elie. ''The Founders of Modern Medicine: Pasteur, Koch, Lister.'' Classics of Medicine Library: Delanco, 2006. Print.</ref> His father was a mining engineer. He was the third of thirteen siblings.<ref name=":0">{{Cite journal|last1=Blevins|first1=Steve M.|last2=Bronze|first2=Michael S.|date=2010|title=Robert Koch and the 'golden age' of bacteriology|journal=International Journal of Infectious Diseases|volume=14|issue=9|pages=e744–751|doi=10.1016/j.ijid.2009.12.003|pmid=20413340|doi-access=free}}</ref> He excelled academically from an early age. Before entering school in 1848, he had taught himself how to read and write.<ref name=":4" /> He completed secondary education in 1862, having excelled in science and math.<ref name=":13">{{Cite journal|last=Akkermans|first=Rebecca|date=2014|title=Robert Heinrich Herman Koch|url=https://pubmed.ncbi.nlm.nih.gov/24717622|journal=The Lancet|volume=2|issue=4|pages=264–265|doi=10.1016/S2213-2600(14)70018-9|pmid=24717622}}</ref>

At the age of 19, in 1862, Koch entered the [[University of Göttingen]] to study natural science.<ref name="Heinrich Hermann Robert Koch">"Heinrich Hermann Robert Koch." ''World of Scientific Discovery.'' Gale, 2006. Biography in Context. Web. 14 April 2013.</ref> He took up mathematics, physics and botany. He was appointed assistant in the university's Pathological Museum.<ref name=":1">{{Cite journal|last=Ernst|first=H. C.|date=1918|title=Robert Koch (1843-1910)|url=https://www.jstor.org/stable/25130022|journal=Proceedings of the American Academy of Arts and Sciences|volume=53|issue=10|pages=825–827|jstor=25130022}}</ref> 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 [[Germ theory of disease|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".<ref name=":0" /> In his sixth semester, Koch began to research at the Physiological Institute, where he studied the secretion of [[succinic acid]], which is a signalling molecule that is also involved in the [[Citric acid cycle|metabolism of the mitochondria]]. This would eventually form the basis of his dissertation.<ref name="Robert Koch A Life" /> In January 1866, he graduated from the medical school, earning honours of the highest distinction, ''[[Latin honors|maxima cum laude]]''.<ref name=":2">{{Cite journal|last=Sakula|first=A.|date=1982|title=Robert Koch: centenary of the discovery of the tubercle bacillus, 1882|journal=Thorax|volume=37|issue=4|pages=246–251|doi=10.1136/thx.37.4.246|pmc=459292|pmid=6180494}}</ref><ref name=":3">{{Cite journal|last=Sakula|first=A.|date=1983|title=Robert koch: centenary of the discovery of the tubercle bacillus, 1882|journal=The Canadian Veterinary Journal|volume=24|issue=4|pages=127–131|pmc=1790283|pmid=17422248}}</ref>

===Anthrax===
Robert Koch is widely known for his work with [[anthrax]], discovering the causative agent of the fatal disease to be ''[[Bacillus anthracis]]''.<ref name="Germ theory of disease">"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.</ref> After officially becoming a district physician in Wollstein (today's Wolsztyn), Poland, in 1872, Robert began to delve into the disease called Anthrax. Near Wollstein, anthrax disease was regularly taking the lives of humans and livestock without evidence explaining why. Eventually, in 1876, Koch was able to make an incredible discovery 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 the anthrax disease. By gaining a better understanding of this pathogen, he was able to shed light on the bacterium's remarkable 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 at in Wöllstein.<ref>{{Cite journal |last=Koch |first=Robert |date=2010 |others=Robert Koch-Institut |title=Die Ätiologie der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des Bacillus Anthracis |url=https://edoc.rki.de/handle/176904/5139 |journal=Cohns Beiträge zur Biologie der Pflanzen |language=de |volume=2 |issue=2 |pages=277 (1–22) |doi=10.25646/5064 |orig-year=1876}}</ref> His publication in 1877 on the structure of anthrax bacterium<ref>{{Cite journal |last=Koch |first=Robert |date=2010 |title=Verfahren zur Untersuchung, zum Konservieren und Photographieren der Bakterien |url=https://edoc.rki.de/handle/176904/5140 |journal=Beiträge zur Biologie der Pflanzen |language=de |volume=2 |pages=399–434 |doi=10.25646/5065 |via=Robert Koch-Institut |orig-year=1877}}</ref> marked the first photography of a bacterium.<ref name=":0" /> He discovered the formation of [[bacterial spore|spores]] in anthrax bacteria, which could remain dormant under specific conditions.<ref name="Heinrich Hermann Robert Koch" /> However, under optimal conditions, the spores were activated and caused disease.<ref name="Heinrich Hermann Robert Koch" /> 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.<ref name="Robert Koch">"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.</ref> 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]].<ref name="Germ theory of disease" /> 
[[File:Cycle of infection in anthrax.jpg|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 or corpses, by 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 graduation in 1866, Koch briefly worked as an assistant in the General Hospital of Hamburg. In October of that year, he moved to Idiot's Hospital of Langenhagen (as it was known in English,<ref name=":17" /><ref name=":1" /> later named KRH Psychiatrie Langenhagen<ref>{{Cite web |last=Kruse |first=G. |date=2021 |title=Geschichte der KRH Psychiatrie Langenhagen |trans-title=History of the KRH Psychiatry Langenhagen |url=https://psychiatrie-langenhagen.krh.de/ueber-uns/geschichte |access-date=2024-12-27 |website=psychiatrie-langenhagen.krh.de |language=de}}</ref>), near Hanover, as a junior 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.<ref name=":1" /> He was discharged a year later and was appointed as a district physician (''Kreisphysikus'') in Wollstein in [[Prussia]]n [[Province of Posen|Posen]] (now [[Wolsztyn]], 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.<ref name=":2" /><ref name=":3" />

Koch began conducting research on microorganisms in a laboratory connected to his patient's examination room.<ref name="Heinrich Hermann Robert Koch" /> 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.<ref name="Brock Biology of Microorganisms">Madigan, Michael T., et al. ''Brock Biology of Microorganisms: Thirteenth edition.'' Benjamin Cummings: Boston, 2012. Print.</ref> Furthermore, he managed to isolate and grow selected pathogens in a [[pure culture|pure laboratory culture]].<ref name="Brock Biology of Microorganisms" /> His discovery of the anthrax bacillus (later named ''[[Bacillus anthracis]]'') hugely impressed [[Ferdinand Julius Cohn]], professor at the University of Breslau (now the [[University of Wrocław]]), who helped him publish the discovery in 1876.<ref name=":1" /> Cohn had established the Institute of Plant Physiology<ref>{{Cite journal|last=Pick|first=E.|date=2001|title=Medical luminaries|journal=Nature|volume=411|issue=6840|pages=885|doi=10.1038/35082239|pmid=11418826|bibcode=2001Natur.411..885P|s2cid=30630349|doi-access=free}}</ref> and invited Koch to demonstrate his new bacterium there in 1877.<ref>{{Cite journal|last=Salomonsen|first=C. J.|date=1950|title=Reminiscences of the summer semester, 1877, at Breslau|url=https://pubmed.ncbi.nlm.nih.gov/15434544|journal=Bulletin of the History of Medicine|volume=24|issue=4|pages=333–351|jstor=44443542|pmid=15434544}}</ref> 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.<ref name="Tuberculosis, overview">O’Connor, T.M. "Tuberculosis, Overview." ''International Encyclopedia of Public Health.'' 2008. Web.</ref> Following his discovery of the tuberculosis bacterium, he was promoted to ''Geheimer Regierungsrat'', a senior executive position, in June 1882.<ref name=":11">{{Cite journal|last=Gradmann|first=C.|date=2001|title=Robert Koch and the pressures of scientific research: tuberculosis and tuberculin|journal=Medical History|volume=45|issue=1|pages=1–32|doi=10.1017/s0025727300000028|pmc=1044696|pmid=11235050}}</ref>

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.<ref name=":1" /> In 1891, he relinquished his professorship and became a director of the Royal Prussian Institute for Infectious Diseases (now the [[Robert Koch Institute]]) 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 [[tuberculin]], 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.<ref name=":14">Christoph Gradmann: Laboratory Disease, Robert Koch's Medical Bacteriology. The Johns Hopkins University Press, Baltimore 2009, {{ISBN|978-0-8018-9313-1}}, p. 111 ff.</ref> 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 [[Arsanilic acid|Atoxyl]].<ref>{{Cite web|last=Bonhomme|first=Edna|title=When Africa was a German laboratory|url=https://www.aljazeera.com/opinions/2020/10/6/when-africa-was-a-german-laboratory/|access-date=7 October 2020|website=www.aljazeera.com|language=en}}</ref>

==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 (optics)|condenser]] that enabled smaller objects to be seen.<ref name=":0" /> In addition, he was also the first to effectively use photography ([[microphotograph]]y) for microscopic observation. He introduced the "bedrock methods" of bacterial staining using [[methylene blue]] and [[Bismarck brown Y|Bismarck (Vesuvin) brown dye]].<ref name=":16" /> In an attempt to grow bacteria, Koch began to use solid nutrients such as [[potato]] slices.<ref name="Brock Biology of Microorganisms"/> Through these initial experiments, Koch observed individual colonies of identical, pure cells.<ref name="Brock Biology of Microorganisms"/> He found that potato slices were not suitable media for all organisms, and later began to use nutrient solutions with [[gelatin]].<ref name="Brock Biology of Microorganisms"/> 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&nbsp;°C, the ideal temperature for growth of most human pathogens.<ref name="Brock Biology of Microorganisms"/> Furthermore, many bacteria can hydrolyze gelatin, making it a liquid. As suggested to him by his post-doctoral assistant [[Walther Hesse]], who got the idea from his wife [[Fanny Hesse]], in 1881, Koch started using [[agar]] to grow and isolate pure cultures.<ref name=":7">{{Cite journal|last=Hufford|first=David C.|date=1988-03-01|title=A Minor Modification by R. J. Petri|url=https://academic.oup.com/labmed/article-lookup/doi/10.1093/labmed/19.3.169|journal=Laboratory Medicine|language=en|volume=19|issue=3|pages=169–170|doi=10.1093/labmed/19.3.169|issn=0007-5027}}</ref> Agar is a [[polysaccharide]] that remains solid at 37&nbsp;°C, is not degraded by most bacteria, and results in a stable transparent medium.<ref name="Brock Biology of Microorganisms"/><ref name=":5">{{cite book|author=Koch|first=Robert|title=Robert Koch |chapter=Die Ätiologie der Tuberkulose (1882) |series=Klassische Texte der Wissenschaft |date=24 March 1882|trans-title=The Etiology of Tuberculosis|chapter-url=http://edoc.rki.de/docviews/abstract.php?id=610|journal=Physiologische Gesellschaft zu Berlin/Berliner Klinische Wochenschrift|volume=19|pages=221–30|publisher=Springer |location=Berlin, Heidelberg |doi=10.1007/978-3-662-56454-7_4|isbn=978-3-662-56454-7|quote=From page 225: ''"{{lang|de|Die Tuberkelbacillen lassen sich auch noch auf anderen Nährsubstraten kultivieren, wenn letztere ähnliche Eigenschaften wie das erstarrte Blutserum besitzen. So wachsen sie beispielsweise auf einer mit Agar-Agar bereiteten, bei Blutwärme hart bleibenden Gallerte, welche einen Zusatz von Fleischinfus und Pepton erhalten hat.}}"'' (The tubercule bacilli can also be cultivated on other media, if the latter have properties similar to those of congealed [[blood serum]].  Thus they grow, for example, on a gelatinous mass prepared with [[agar-agar]], which remains solid at blood temperature, and which has received a supplement of meat [[broth]] and [[peptone]].)}}</ref>

==== Development of Petri dish ====
Koch's booklet published in 1881 titled "''Zur Untersuchung von Pathogenen Organismen''" (''Methods for the Study of Pathogenic Organisms'')<ref>{{Cite book|last=Koch|first=Robert|url=https://edoc.rki.de/handle/176904/5146|title=Zur Untersuchung von Pathogenen Organismen|publisher=Robert Koch-Institut|year=2010|location=Berlin|doi=10.25646/5071|orig-year=1881}}</ref> has been known as the "Bible of Bacteriology."<ref>{{Citation|last1=Booss|first1=John|date=2014|url=https://linkinghub.elsevier.com/retrieve/pii/B9780444534880000018|series=Handbook of Clinical Neurology|volume=123|pages=3–44|publisher=Elsevier|language=en|doi=10.1016/b978-0-444-53488-0.00001-8|isbn=978-0-444-53488-0|access-date=2021-04-15|last2=Tselis|first2=Alex C.|title=Neurovirology |chapter=A history of viral infections of the central nervous system |pmid=25015479}}</ref><ref>{{Cite journal|last=Hurt|first=Leslie|date=2003|title=Dr. Robert Koch:: a founding father of biology|url=https://linkinghub.elsevier.com/retrieve/pii/S1068607X02001671|journal=Primary Care Update for OB/GYNS|language=en|volume=10|issue=2|pages=73–74|doi=10.1016/S1068-607X(02)00167-1}}</ref> 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.<ref name=":8">{{Cite journal|last=Shama|first=Gilbert|date=2019|title=The "Petri" Dish: A Case of Simultaneous Invention in Bacteriology|url=https://pubmed.ncbi.nlm.nih.gov/31030894|journal=Endeavour|volume=43|issue=1–2|pages=11–16|doi=10.1016/j.endeavour.2019.04.001|pmid=31030894|s2cid=139105012}}</ref>

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!")<ref name=":2" /> It was using Koch's microscopy and agar-plate culture method that his students discovered new bacteria. [[Friedrich Loeffler]] discovered the bacteria of [[glanders]] (''[[Burkholderia mallei]]'') in 1882 and [[diphtheria]] (''[[Corynebacterium diphtheriae]]'') in 1884; and [[Georg Theodor August Gaffky]], the bacterium of [[typhoid]] (''[[Salmonella enterica]]'') in 1884.<ref name=":6" /> Koch's assistant [[Julius Richard Petri]] 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).<ref>{{Cite journal|last=Petri|first=Julius Richard|date=1887|title=Eine kleine Modification des Koch'schen Plattenverfahrens|url=https://archive.org/details/1887-petri-eine-kleine-modification-des-koch-schen-plattenverfahrens-2020-braus-|journal=Centralblatt für Bacteriologie und Parasitenkunde|volume=1|pages=279–280}}</ref> The culture plate was given an eponymous name [[Petri dish]].<ref>{{Cite journal|last=Mahajan|first=Monika|date=2021|title=Etymologia: Petri Dish|journal=Emerging Infectious Diseases|volume=27|issue=1|pages=261|doi=10.3201/eid2701.ET2701|pmc=7774570}}</ref> It is often asserted that Petri developed a new culture plate,<ref name=":0" /><ref>{{Cite journal|last=Zhang|first=Shuguang|date=2004|title=Beyond the Petri dish|url=https://pubmed.ncbi.nlm.nih.gov/14755282|journal=Nature Biotechnology|volume=22|issue=2|pages=151–152|doi=10.1038/nbt0204-151|pmid=14755282|s2cid=36391864}}</ref><ref>{{Cite journal|last1=Grzybowski|first1=Andrzej|last2=Pietrzak|first2=Krzysztof|date=2014|title=Robert Koch (1843-1910) and dermatology on his 171st birthday|url=https://pubmed.ncbi.nlm.nih.gov/24887990|journal=Clinics in Dermatology|volume=32|issue=3|pages=448–450|doi=10.1016/j.clindermatol.2013.10.005|pmid=24887990}}</ref> but this was not so. He simply discarded the use of 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 contaminations.<ref name=":7" /> It would also have been appropriate if the name "Koch dish" had been given.<ref name=":8" />

===Tuberculosis===
[[File:Aetiologie der Tuberkulose.jpg|thumb|Koch's drawing of tuberculosis bacilli in 1882 (from ''Die Ätiologie der Tuberkulose'')]]
During his time as the government advisor with the Imperial Health Agency in Berlin in the 1880s, Koch became interested in [[tuberculosis]] 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]]''.<ref name="Brock Biology of Microorganisms" /> He published the discovery as "''Die Ätiologie der Tuberkulose''" (''The Etiology of Tuberculosis''),<ref name=":5" /> and presented before the German Physiological Society at Berlin on 24 March 1882. Koch said,<blockquote>When the cover-glasses were exposed to this staining fluid [methylene blue mixed with [[potassium hydroxide]]] for 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.<ref name=":2" /><ref name=":3" /></blockquote>

There was no particular reaction to this announcement. Eminent scientists such as [[Rudolf Virchow]] remained sceptical. Virchow clung to his theory that all diseases are due to faulty cellular activities.<ref name=":12">{{Cite journal|last1=Kaufmann|first1=Stefan H. E.|last2=Schaible|first2=Ulrich E.|date=2005|title=100th anniversary of Robert Koch's Nobel Prize for the discovery of the tubercle bacillus|url=https://pubmed.ncbi.nlm.nih.gov/16112578|journal=Trends in Microbiology|volume=13|issue=10|pages=469–475|doi=10.1016/j.tim.2005.08.003|pmid=16112578}}</ref> On the other hand, [[Paul Ehrlich]] later recollected that this moment was his "single greatest scientific experience."<ref name=":9" /> Koch expanded the report and published it 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]], which were formulated by his assistant Friedrich Loeffler in 1883, saying:<blockquote>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.<ref name=":12" /></blockquote>

===Cholera===
[[File:Robert Koch (Deutsche Cholera-Expedition in Ägypten 1884).jpg|thumb|left|Photograph of Koch (third from the right) and other members of the German Cholera Commission in Egypt, 1884]]
[[File:Professors Koch and Pfeiffer working in a laboratory, invest Wellcome L0030175.jpg|thumb|Koch (on the microscope) and his colleague [[Richard Friedrich Johannes Pfeiffer]] (standing) investigating cholera outbreak in Bombay, India ]]
In August 1883, the German government sent a medical team led by Koch to [[Alexandria, Egypt]], to investigate a cholera epidemic there.<ref>{{Cite journal|last=Howard-Jones|first=N.|date=1984|title=Robert Koch and the cholera vibrio: a centenary|journal=British Medical Journal|volume=288|issue=6414|pages=379–381|doi=10.1136/bmj.288.6414.379|pmc=1444283|pmid=6419937}}</ref> 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.<ref name=":0" /> 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."<ref name=":32">{{Cite journal|last1=Lippi|first1=D.|last2=Gotuzzo|first2=E.|date=2014|title=The greatest steps towards the discovery of Vibrio cholerae|journal=Clinical Microbiology and Infection|volume=20|issue=3|pages=191–195|doi=10.1111/1469-0691.12390|pmid=24191858|doi-access=free}}</ref> 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.<ref name=":0" /> In 1959, Indian scientist [[Sambhu Nath De]] discovered this poison, the [[cholera toxin]].<ref>{{Cite journal|last1=Nair|first1=G. Balakrish|last2=Takeda|first2=Yoshifumi|date=2011|title=Dr Sambhu Nath De: unsung hero|journal=The Indian Journal of Medical Research|volume=133|issue=2 |pages=127|pmc=3089041|pmid=21415484}}</ref> 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.<ref>Koch, R. (20 March 1884) {{lang|de|2=[https://books.google.com/books?id=yY41AQAAMAAJ&pg=PA191 "Sechster Bericht der deutschen wissenschaftlichen Commission zur Erforschung der Cholera"]}} (Sixth report of the German scientific commission for research on cholera), ''{{lang|de|Deutsche medizinische Wochenscrift}}'' (German Medical Weekly), '''10''' (12):  191–192. On page 191, he mentions the characteristic comma shape of ''Vibrio cholerae'':  ''"{{lang|de|Im letzten Berichte konnte ich bereits gehorsamst mittheilen, dass an den Bacillen des Choleradarms besondere Eigenschaften aufgefunden wurden, durch welche sie mit aller Sicherheit von anderen Bakterien zu unterscheiden sind. Von diesen Merkmalen sind folgende die am meisten charakteristischen: Die Bacillen sind nicht ganz geradlinig, wie die übrigen Bacillen, sondern ein wenig gekrümmt, einem Komma ähnlich.}}"'' (In the last report, I could already respectfully report that unusual characteristics were discovered in the bacteria of enteric cholera, by which they are to be distinguished with complete certainty from other bacteria. Of these features, the following are the most characteristic: the bacteria are not quite straight, like the rest of the bacilli, but a little bent, similar to a comma.)</ref>

Although Koch was convinced that the bacterium was the cholera pathogen, he could not entirely establish critical evidence 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 pathogen. The bacterium was then known as "the comma bacillus", and scientifically as ''Bacillus comma''.<ref>{{Cite journal|last1=Winslow|first1=C. E.|last2=Broadhurst|first2=J.|last3=Buchanan|first3=R. E.|last4=Krumwiede|first4=C.|last5=Rogers|first5=L. A.|last6=Smith|first6=G. H.|date=1920|title=The Families and Genera of the Bacteria: Final Report of the Committee of the Society of American Bacteriologists on Characterization and Classification of Bacterial Types|journal=Journal of Bacteriology|volume=5|issue=3|pages=191–229|doi=10.1128/JB.5.3.191-229.1920|pmc=378870|pmid=16558872}}</ref> It was later realised that the bacterium was already described by an Italian physician [[Filippo Pacini]] in 1854,<ref>See:
* Fillipo Pacini (1854) {{lang|it|2=[https://books.google.com/books?id=xdtQAAAAcAAJ&pg=PA397 "Osservazioni microscopiche e deduzioni patologiche sul cholera asiatico"]}} (Microscopic observations and pathological deductions on Asiatic cholera), ''{{lang|it|Gazzetta Medica Italiana:  Toscana}}'', 2nd series, '''4'''(50):397–401; '''4'''(51):405–12.
* Reprinted (more legibly) as a [https://books.google.com/books?id=F9s_AAAAcAAJ&pg=PA1 pamphlet.]</ref> and was also observed by the [[Catalonia|Catalan]] physician Joaquim Balcells i Pascual around the same time.<ref name="Real Academia de la Historia 2018">{{cite web|year=2018|editor=Real Academia de la Historia|editor-link=Real Academia de la Historia|title=Joaquín Balcells y Pasqual|url=http://dbe.rah.es/biografias/18541/joaquin-balcells-y-pasqual|archive-url=https://web.archive.org/web/20190708211444/http://dbe.rah.es/biografias/18541/joaquin-balcells-y-pasqual|archive-date=8 July 2019|access-date=1 August 2020|language=es}}</ref><ref>{{cite web|year=2015|editor=Col·legi Oficial de Metges de Barcelona|editor-link=:ca:Col·legi Oficial de Metges de Barcelona|title=Joaquim Balcells i Pascual|url=http://www.galeriametges.cat/galeria-fitxa.php?icod=EGMM|archive-url=https://web.archive.org/web/20200801110910/http://www.galeriametges.cat/galeria-fitxa.php?icod=EGMM|archive-date=1 August 2020|access-date=1 August 2020|language=ca}}</ref> 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 cholerae|Vibrio cholera]]'' in 1896.<ref name=":42">{{Cite book|last=Hugh|first=Rudolph|url=https://books.google.com/books?id=NP7AY38J1hcC|title=Public Health Service Publication|date=1965|publisher=U.S. Department of Health, Education, and Welfare, Public Health Service, Environmental Health Service, National Air Pollution Control Administration|pages=1–4|language=en|chapter=Nomenclature and taxonomy of Vibrio cholerae Pacini 1854 and Vibrio eltor Pribam 1933}}</ref>

=== Tuberculosis treatment and tuberculin ===
Koch gave much of his research attention to 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]] and [[creosote]] as possible disinfectants. These chemicals and other available drugs did not work.<ref name=":0" /> His report in 1883 also mentioned a failed experiment in an attempt to make a tuberculosis vaccine.<ref name=":11" /> By 1888, Koch turned his attention to [[synthetic dyes]] as antibacterial chemicals. He developed a method for examining antibacterial activity by mixing the gelatin-based culture media with a yellow dye, [[Auramine O|auramin]]. His notebook indicates that by February 1890, he tested hundreds of compounds.<ref name=":9" /> 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]]) the infected tissues, thereby depriving bacterial growth. He made a vague announcement in August 1890 at the Tenth [[International Medical Congress]] in Berlin,<ref name=":12" /> saying,<blockquote>In a communication which I made a few months ago to the International Medical Congress [in 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.<ref name=":2" /><ref name=":3" />

I can tell […] that much, that guinea pigs, which are highly susceptible to the disease [tuberculosis], no longer react upon inoculation with tubercle virus [bacterium] when treated with that substance and that in guinea pigs, which are sick (with tuberculosis), the pathological process can be brought to a complete standstill.<ref name=":9" /></blockquote>By November 1890, Koch demonstrated the effectiveness of the extract in treating humans by administering the vaccine through the Bacillus Calmette-Guerin (BCG) technique.<ref name=":10">{{Cite journal|last=Sakula|first=Alex|date=1985|title=Robert Koch: The story of his discoveries in tuberculosis|url=http://link.springer.com/10.1007/BF02938285|journal=Irish Journal of Medical Science|language=en|volume=154|issue=S1|pages=3–9|doi=10.1007/BF02938285|pmid=3897123|s2cid=38056335}}</ref> 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.<ref name=":0" /> While this was effective in humans, his experiments also revealed that when the substance was inoculated into his tuberculosis-infected test guinea pigs, they presented with severe symptoms. This outcome, characterized by an exaggerated immune response, coined the term "Koch’s phenomenon."<ref>{{Cite journal|last=Hunter|first=Robert L.|date=2020|title=The Pathogenesis of Tuberculosis-The Koch Phenomenon Reinstated|journal=Pathogens|volume=9|issue=10|pages=e813|doi=10.3390/pathogens9100813|pmc=7601602|pmid=33020397|doi-access=free}}</ref> 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'',<ref>{{Cite journal|last=Koch|first=Robert|date=2010|orig-year=1891|title=Fortsetzung der Mitteilungen über ein Heilmittel gegen Tuberkulose|url=https://edoc.rki.de/handle/176904/5175|journal=Deutsche Medizinische Wochenschrift|language=de|volume=17|pages=101–102|doi=10.25646/5100|via=Robert Koch-Institut}}</ref><ref>{{Cite journal|last=Koch|first=Robert|date=1891|title=A Further Communication on a Remedy for Tuberculosis|journal=The Indian Medical Gazette|volume=26|issue=3|pages=85–87|pmc=5150357|pmid=29000631}}</ref> and ''[[The British Medical Journal]]'' immediately published the English version simultaneously.<ref>{{Cite journal|last=Koch|first=R.|date=1891|title=A Further Communication on a Remedy for Tuberculosis|journal=British Medical Journal|volume=1|issue=1568|pages=125–127|doi=10.1136/bmj.1.1568.125|pmc=2196966|pmid=20753227}}</ref> The English version was also reproduced in ''[[Nature (journal)|Nature]]'',<ref>{{Cite journal|date=1891|title=Dr. Koch's Remedy for Tuberculosis|journal=Nature|language=en|volume=43|issue=1108|pages=281–282|doi=10.1038/043281a0|bibcode=1891Natur..43..281.|s2cid=4050612|doi-access=free}}</ref> and ''[[The Lancet]]'' in the same month.<ref>{{Cite journal|last=Richmond|first=W.S.|date=1891|title=Professor Koch's Remedy for Tuberculosis|url=https://linkinghub.elsevier.com/retrieve/pii/S0140673602157059|journal=The Lancet|language=en|volume=137|issue=3514|pages=56–57|doi=10.1016/S0140-6736(02)15705-9}}</ref> ''The Lancet'' presented it as "glad tidings of great joy."<ref name=":10" /> Koch simply referred to the medication as "brownish, transparent fluid."<ref name=":4" /> Josephs Pohl-Pincus had used the name tuberculin in 1844 for tuberculosis culture media,<ref>{{Cite journal|last=Caspary|date=1884|title=Angioneurotische Dermatosen|url=https://doi.org/10.1007/BF02097828|journal=Vierteljahresschrift für Dermatologie und Syphilis|language=de|volume=16|issue=1|pages=141–155|doi=10.1007/BF02097828|s2cid=33099318|quote=Pohl-Pincus wrote: Wir werden deshalb alas Tuberculin darzustellen suchen [We shall therefore endeavor to describe it as tuberculin]}}</ref> and Koch subsequently adopted as "tuberkulin."<ref>{{Cite journal|last=Koch|first=R.|date=1891|title=Weitere Mittheilung über das Tuberkulin|url=http://www.thieme-connect.de/DOI/DOI?10.1055/s-0029-1206810|journal=Deutsche Medizinische Wochenschrift|language=de|volume=17|issue=43|pages=1189–1192|doi=10.1055/s-0029-1206810|s2cid=73993276 }}</ref>

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."<ref name=":12" /> With it his reputation greatly waned. But he devoted the rest of his life trying to make tuberculin as a usable medication.<ref name=":10" /> His discovery was not a total failure: the substance is now used to test for hypersensitivity in tuberculosis patients.<ref name=":0" />

=== Acquired immunity ===
Koch observed the phenomenon of acquired [[immunity (medical)|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 [[Indigenous people of New Guinea|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.<ref>{{lang|de|Hugo Kronecker: Hygienische Topographie}} In: A. Pfeiffer (Editor): {{lang|de|21. Jahresbericht über die Fortschritte und Leistungen auf dem Gebiete der Hygiene.}} 1903. Publisher: Friedrich Vieweg und Sohn, Braunschweig, 1905. p. 68</ref>

=== Koch's postulates ===
{{Main|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 postulates|Koch's four postulates]].<ref name="Bacteriology, historical">Amsterdamska, Olga. "Bacteriology, Historical." ''International Encyclopedia of Public Health.'' 2008. Web.</ref> Koch's discovery of the causative agent of anthrax led to the formation of a generic set of [[wikt:postulate|postulates]] which can be used in the determination of the cause of most infectious diseases.<ref name="Germ theory of disease" /> 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.<ref>{{Cite journal|last=Tabrah|first=Frank L.|date=2011|title=Koch's postulates, carnivorous cows, and tuberculosis today|journal=Hawaii Medical Journal|volume=70|issue=7|pages=144–148|pmc=3158372|pmid=21886302}}</ref>

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:<ref>{{cite journal |last1=Loeffler |first1=Friedrich |title=Untersuchungen über die Bedeutung der Mikroorganismen für die Entstehung der Diphtherie beim Menschen, bei der Taube und beim Kalbe |journal=Mittheilungen aus dem Kaiserlichen Gesundheitsamte (Reports from the Imperial Office of Public Health) |date=1884 |volume=2 |pages=421–499 |url=https://books.google.com/books?id=Y6lQAAAAYAAJ&pg=PA421 |trans-title=Investigations of the relevance of microorganisms to the development of diphtheria among humans, among doves, and among heifers |language=German}}  From 424:  ''"Wenn nun die Diphtherie eine durch Mikroorganismen bedingte Krankheit ist, so müssen sich auch bei ihr jene drei Postulate erfüllen lassen, deren Erfüllung für den stricten Beweis der parasitäten Natur einer jeden derartigen Krankheit unumgänglich nothwendig ist:''<br /> 
''1)  Es müssen constant in den local erkrankten Parteien Organismen in typischer Anordnung nachgewiesen werden.''<br />
''2)  Die Organismen, welchen nach ihrem Verhalten zu den erkrankten Theilen eine Bedeutung für das Zustandekommen dieser Veränderungen beizulegen wäre, müssen isolirt und rein gezüchtet werden.''<br />
''3)  Mit den Reinculturen muss die Krankheit experimentell wieder erzeugt werden können."''<br />
(Now if diphtheria is a disease that's caused by microorganisms, then it must also be able to fulfil those three postulates whose fulfilment is absolutely necessary for the strict proof of the parasitic nature of any such disease:<br />
1)  In the given diseased patients, there must always be shown [to be present] organisms in typical disposition.<br />
2)  The organisms to which one would attribute — according to their behaviour in the diseased parts — a relevance for the occurrence of these changes, must be isolated and cultured in pure form.<br />
3)  The disease must be able to be reproduced experimentally via pure cultures.)</ref>
: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.<ref name=":6">{{Cite journal|last=Weiss|first=Robin A.|date=2005|title=Robert Koch: the grandfather of cloning?|journal=Cell|volume=123|issue=4|pages=539–542|doi=10.1016/j.cell.2005.11.001|pmid=16286000|doi-access=free}}</ref><ref>{{Cite journal|last1=Byrd|first1=Allyson L.|last2=Segre|first2=Julia A.|date=2016|title=Adapting Koch's postulates|url=https://pubmed.ncbi.nlm.nih.gov/26816362|journal=Science|volume=351|issue=6270|pages=224–226|doi=10.1126/science.aad6753|pmid=26816362|bibcode=2016Sci...351..224B|s2cid=29595548}}</ref>

The fourth postulate was added by an American plant pathologist [[Erwin Frink Smith]] in 1905, and is stated as:<ref>{{cite book |last1=Smith |first1=Erwin F. |title=Bacteria in Relation to Plant Diseases |date=1905 |publisher=Carnegie Institution of Washington |location=Washington. D.C. |volume=1 |page=9 |url=https://www.biodiversitylibrary.org/item/60542#page/31/mode/1up}}</ref>

:4. The same pathogen must be isolated from the experimentally infected individuals.<ref>{{Cite journal|last=Hadley|first=Caroline|date=2006|title=The infection connection|journal=EMBO Reports|volume=7|issue=5|pages=470–473|doi=10.1038/sj.embor.7400699|pmc=1479565|pmid=16670677}}</ref>

== Selected publications ==

* Julius Schwalbe, Georg Gaffky, Eduard Pfuhl (eds.): Robert Koch. Gesammelte Werke. 3 vols. Leipzig 1912 (in German).
** [[iarchive:b21463608_0001|vol. 1]], at Internet Archive
** [[iarchive:b21353207_0001|vol. 2-1]]
** [[iarchive:b21353207_0002|vol. 2-2]]

==Personal life==
In July 1867, Koch married Emma (Emmy) Adolfine Josephine Fraatz, and the two had a daughter, Gertrude, in 1868.<ref name="Robert Koch A Life" /> Their marriage ended after 26 years in 1893, and later that same year, he married actress Hedwig Freiberg (1872–1945).<ref name="Robert Koch A Life" />

On 9 April 1910, Koch suffered a heart attack and never made a complete recovery.<ref name="Robert Koch" /> On 27 May, three days after giving a lecture on his tuberculosis research at the [[Prussian Academy of Sciences]], Koch died in [[Baden-Baden]] at the age of 66.<ref name="Heinrich Hermann Robert Koch" /> Following his death, the Institute named its establishment after him in his honour. He was irreligious.<ref>Thomas D. Brock (1988). Robert Koch: A Life in Medicine and Bacteriology. ASM Press. p. 296. {{ISBN|978-1-55581-143-3}}. "He loved seeing new things, but showed no interest in politics. Religion never entered his life."</ref>

== Awards and honours ==
{| style="margin:auto"
| [[File:Christmas Seal, Robert Koch, 1938 issue.jpg|thumb|upright=1.1|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.<ref>{{cite book |editor-last= Denune |editor-first=John Jr. |title=The Christmas Seal Catalog |volume= |author-link= |publisher=The Christmas Seal and Charity Stamp Society |location= |year=2014 |isbn= |url=https://www.seal-society.org/sites/default/files/pdf/news/166/The%20Christmas%20Seal%20Catalog-1.pdf |quote=The Christmas Seal Catalog is a simplified version of Green’s Catalog of TB Seals of the World, part 1, U.S. National Christmas Seals. |ref=catalog2014}}</ref>]]
| [[File:Statue of Robert Koch in Berlin.jpg|thumb|upright=1|Statue of Koch at Robert-Koch-Platz (Robert Koch square) in Berlin]]
| [[File:Robert Koch's name on the Frieze of LSHTM .jpg|alt=Koch's name as it appears on the LSHTM Frieze in Keppel Street|thumb|upright=1.2|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,<ref name="prus">{{citation|title=Königlich Preussische Ordensliste (supp.)|volume=1|chapter-url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015049878823&view=1up&seq=7&skin=2021|page=[https://babel.hathitrust.org/cgi/pt?id=mdp.39015049878823&view=1up&seq=13&skin=2021 7]|language=German|location=Berlin|year=1886|chapter=Rother Adler-orden|via=hathitrust.org}}</ref> and was elected a [[List of Fellows of the Royal Society elected in 1897|Foreign Member of the Royal Society (ForMemRS)]] in 1897.<ref name="frs">{{cite web|archive-url=https://web.archive.org/web/20150316060617/https://royalsociety.org/about-us/fellowship/fellows/|archive-date=16 March 2015|url=https://royalsociety.org/about-us/fellowship/fellows/|publisher=Royal Society|location=London|title=Fellows of the Royal Society}}</ref> In 1905, he was awarded the [[Nobel Prize]] in Physiology and Medicine "for his investigations and discoveries in relation to tuberculosis."<ref>{{Cite web|title=The Nobel Prize in Physiology or Medicine 1905|url=https://www.nobelprize.org/prizes/medicine/1905/summary/|access-date=2021-04-21|website=NobelPrize.org|language=en-US}}</ref> 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.<ref name="Robert Koch" /> Emperor Wilhelm I awarded him the Order of the Crown, 100,000 marks and appointment as Privy Imperial Councillor,<ref name=":16" /><ref name=":4">{{Cite journal|last=Ligon|first=B. Lee|date=2002|title=Robert Koch: Nobel laureate and controversial figure in tuberculin research|url=https://pubmed.ncbi.nlm.nih.gov/12491235|journal=Seminars in Pediatric Infectious Diseases|volume=13|issue=4|pages=289–299|doi=10.1053/spid.2002.127205|pmid=12491235}}</ref> Surgeon-General of Health Service, and Fellow of the Science Senate of Kaiser Wilhelm Society.<ref name=":1" />

Koch established the Royal Prussian Institute for Infectious Diseases in Berlin in 1891. After his death, it was renamed Robert Koch Institute in his honour.<ref name=":16" />

The World Health Organization has observed "[[World Tuberculosis Day]]" every 24 March since 1982 to commemorate the day Koch discovered the tuberculosis bacterium.<ref name=":4" />

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]] building in [[Keppel Street]], [[Bloomsbury]].<ref>{{Cite web|url=https://www.lshtm.ac.uk/aboutus/introducing/history/behind-frieze|title=Behind the frieze|website=LSHTM}}</ref>

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.<ref>{{Cite web|url=https://doodles.google/doodle/celebrating-robert-koch/|title=Celebrating Robert Koch|website=www.google.com}}</ref><ref>{{Cite web|url=https://www.youtube.com/watch?v=lEeBZceXjfg| archive-url=https://ghostarchive.org/varchive/youtube/20211111/lEeBZceXjfg| archive-date=2021-11-11 | url-status=live|title=Robert Koch Google Doodle| date=9 December 2017|via=www.youtube.com}}{{cbignore}}</ref>

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 ===
{{Further|Koch–Pasteur rivalry}}
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.<ref>{{Cite journal|last=Carter|first=K. C.|date=1988|title=The Koch-Pasteur dispute on establishing the cause of anthrax|url=https://pubmed.ncbi.nlm.nih.gov/3285924|journal=Bulletin of the History of Medicine|volume=62|issue=1|pages=42–57|jstor=44449292|pmid=3285924}}</ref> 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.<ref>{{Cite book|last=Koch|first=R.|url=https://edoc.rki.de/bitstream/handle/176904/5148/174-206.pdf?sequence=1&isAllowed=y|title=Mittheilungen aus dem Kaiserlichen Gesundheitsamte|publisher=Robert Koch-Institut|year=2010|location=Berlin|pages=174–206|chapter=Zur Ätiologie des Milzbrandes|trans-chapter=On the etiology of anthrax|orig-year=1881}}</ref> To prove his vaccine, Pasteur sent his assistant [[Louis Thuillier]] to Germany for demonstration and disproved Koch's idea.<ref>{{Cite journal|last1=Rietschel|first1=Ernst Th|last2=Cavaillon|first2=Jean-Marc|date=2002|title=Endotoxin and anti-endotoxin. The contribution of the schools of Koch and Pasteur: life, milestone-experiments and concepts of Richard Pfeiffer (Berlin) and Alexandre Besredka (Paris)|url=https://pubmed.ncbi.nlm.nih.gov/12028747|journal=Journal of Endotoxin Research|volume=8|issue=2|pages=71–82|doi=10.1179/096805102125000218|pmid=12028747}}</ref> 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."<ref name=":4" /> 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."<ref name=":0" />

=== 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.<ref name=":9" /> 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.<ref>{{Cite journal|last=Leibowitz|first=D.|date=1993|title=Scientific failure in an age of optimism: public reaction to Robert Koch's tuberculin cure|url=https://pubmed.ncbi.nlm.nih.gov/8429953|journal=New York State Journal of Medicine|volume=93|issue=1|pages=41–48|pmid=8429953}}</ref> One week later, Koch publicised that the drug was a glycerine extract of a pure cultivation of the tuberculosis bacilli.<ref name=":9" /> The German official report in late 1891 declared that tuberculosis was not cured with tuberculin.<ref name=":12" /> 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.<ref name=":13" /> Since 1885, he had tried to leave government service and create an independent state-run institute of his own.<ref name=":4" /> 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 claiming patent rights in any of his subsequent works.<ref name=":14" />

=== 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.<ref>{{Cite journal|last=Packer|first=R. A.|date=1987|title=Veterinarians challenge Dr. Robert Koch regarding bovine tuberculosis and public health: a chronology of events|url=https://pubmed.ncbi.nlm.nih.gov/11621492|journal=Veterinary Heritage|volume=10|issue=2|pages=7–11|pmid=11621492}}</ref> 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.<ref>{{Cite journal|last=Packer|first=R. A.|date=1990|title=Veterinarians challenge Dr. Robert Koch regarding bovine tuberculosis and public health|url=https://pubmed.ncbi.nlm.nih.gov/2406233|journal=Journal of the American Veterinary Medical Association|volume=196|issue=4|pages=574–575|doi=10.2460/javma.1990.196.04.574 |pmid=2406233}}</ref> 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.<ref>{{Cite journal|last=Smith|first=T.|date=1898|title=A comparative study of bovine tubercle bacilli and of human bacilli from sputum|journal=The Journal of Experimental Medicine|volume=3|issue=4–5|pages=451–511|doi=10.1084/jem.3.4-5.451|pmc=2117982|pmid=19866892}}</ref>

By that time, there was evidence that cattle tuberculosis was transmitted to humans through meat and milk.<ref>{{Cite journal|last=Bergey|first=D. H.|date=1897|title=Bovine Tuberculosis in its Relation to the Public Health|journal=Public Health Papers and Reports|volume=23|pages=310–320|pmc=2329987|pmid=19600776}}</ref><ref>{{Cite journal|date=1881|title=Reviews and Notices|journal=British Medical Journal|volume=2|issue=1072|pages=85–86|pmc=2263995}}</ref> 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.<ref name=":4" /> 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.''"<ref>{{Cite journal|last=Kaufmann|first=Stefan H. E.|date=2003|title=A short history of Robert Koch's fight against tuberculosis: those who do not remember the past are condemned to repeat it|url=https://pubmed.ncbi.nlm.nih.gov/12758195|journal=Tuberculosis (Edinburgh, Scotland)|volume=83|issue=1–3|pages=86–90|doi=10.1016/s1472-9792(02)00064-1|pmid=12758195}}</ref> Chair of the congress, [[Joseph Lister]] reprimanded Koch and explained the medical evidence of cattle tuberculosis in humans.<ref>{{Cite journal|last=Clark|first=Paul F.|date=1920|title=Joseph Lister, his Life and Work|url=https://www.jstor.org/stable/6707|journal=The Scientific Monthly|volume=11|issue=6|pages=518–539|bibcode=1920SciMo..11..518C}}</ref>

=== 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.<ref>{{cite journal|author=Cox FEG|year=2010|title=History of the discovery of the malaria parasites and their vectors|journal=Parasites & Vectors|volume=3|issue=1|pages=5|doi=10.1186/1756-3305-3-5|pmc=2825508|pmid=20205846 |doi-access=free }}</ref> 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]]''.<ref name=":15">{{cite journal|author=Capanna E|year=2012|title=Grassi versus Ross: who solved the riddle of malaria?|url=http://revistes.iec.cat/index.php/IM/article/viewFile/4c457c86cb18b.002/9548|journal=International Microbiology|volume=9|issue=1|pages=69–74|pmid=16636993}}</ref> 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.<ref>{{Cite journal|last1=Pai-Dhungat|first1=J. V.|last2=Parikh|first2=Falguni|date=2015|title=Battista Grassi (1854-1925) & Malaria Controversy|url=https://www.japi.org/oldwebsitecontent/march_2015/103_battista_grassi.pdf|journal=The Journal of the Association of Physicians of India|volume=63|issue=3|pages=108|pmid=26543977}}</ref> To his disadvantage, Grassi had criticised Koch on his malaria research in 1898 during an investigation of the epidemic,<ref name=":15" /> while Ross had established a cordial relationship with Koch.<ref>{{Cite journal|last=Ross|first=R.|date=1925|title=The mosquito-theory of malaria and the late Prof. G. B. Grassi|url=https://www.jstor.org/stable/43427633|journal=Science Progress in the Twentieth Century (1919-1933)|volume=20|issue=78|pages=311–320|jstor=43427633}}</ref> 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".<ref>{{cite book|author=Esch GW|url=https://books.google.com/books?id=88RH-7br9OAC|title=Parasites and Infectious Disease: Discovery by Serendipity and Otherwise|publisher=Cambridge University Press|year=2007|isbn=9781139464109|pages=137–138}}</ref>

== See also ==

* [[Robert Koch Institute]]

==References==
{{Reflist|30em}}

==Further reading==
* {{cite book |last=Brock |first=Thomas D. |author-link= Thomas D. Brock|title=Robert Koch: A Life in Medicine and Bacteriology |publisher=ASM Press |location=[[Washington, D.C.]] |year=1999 |isbn=978-1-55581-143-3 |oclc=39951653}}
* {{cite book|last=de Kruif|first=Paul|author-link=Paul de Kruif|date=1926|pages=105–144|title=Microbe Hunters|chapter=ch. IV Koch: The Death Fighter|series=Blue Ribbon Books|publisher=Harcourt Brace & Company Inc.|location=New York|chapter-url=https://archive.org/details/in.ernet.dli.2015.221187/page/n3/mode/2up|access-date=14 October 2020}}
* {{cite book |last=Morris |first=Robert D |title=The blue death: disease, disaster and the water we drink |url=https://archive.org/details/bluedeathdisease0000morr |url-access=registration |publisher=[[HarperCollins]] |location=New York |year=2007 |isbn=978-0-06-073089-5 |oclc=71266565}}
* {{cite book |last=Gradmann|first=Christoph |title=Laboratory Disease: Robert Koch's Medical Bacteriology |publisher=[[Johns Hopkins University Press]] |location=Baltimore |year=2009 |isbn=978-0-8018-9313-1}}
* Weindling, Paul. "Scientific elites and laboratory organization in fin de siècle Paris and Berlin: The Pasteur Institute and Robert Koch’s Institute for Infectious Diseases compared," in Andrew Cunningham and Perry Williams, eds. ''The Laboratory Revolution in Medicine'' (Cambridge University Press, 1992) pp: 170–88.
* Christoph, Hans Gerhard: Robert Koch " Trias deutschen Forschergeistes " Naturheilpraxis / Pflaum- Verlag / Munich 70.Jahrgang December 2017 pages 90–93

==External links==
{{Commons category|Robert Koch}}
* [https://soundcloud.com/charles-smyth488/robert-koch Audio version of this page]
* {{Nobelprize}}, including the Nobel Lecture on 12 December 1905 ''The Current State of the Struggle against Tuberculosis''
* [http://vlp.mpiwg-berlin.mpg.de/people/data?id=per99 MPIWG-Berlin], Robert Koch Biography and bibliography in the [[Virtual Laboratory]] of the [[Max Planck Institute for the History of Science]]
* [http://www.sciencemuseum.org.uk/broughttolife/people/robertkoch.aspx Biography on the Science Museum web site] {{Webarchive|url=https://web.archive.org/web/20160125125409/http://www.sciencemuseum.org.uk/broughttolife/people/robertkoch.aspx |date=2016-01-25  }}
* [http://www.musoptin.com/zeiss_3479.html Musoptin.com], original microscope out of the laboratory Robert Koch used in Wollstein (1877)
* [https://web.archive.org/web/20081218213235/http://www.musoptin.com/seibert_photoobjektive.html Musoptin.com], microscope objectives: as they were used by Robert Koch for his first photos of microorganisms (1877–1878)
* {{Gutenberg author | id=32531| name=Robert Koch}}
* {{Internet Archive author |sname=Robert Koch}}
* {{PM20}}
* {{Wikisource-inline|list=
** {{Cite Americana|wstitle=Koch, Robert|year=1920 |short=x |noicon=x}}
** {{Cite EB1911|wstitle=Koch, Robert |short=x |noicon=x}}
** {{Cite NIE|wstitle=Koch, Robert|year=1905 |short=x |noicon=x}}
}}
{{Nobel Prize in Physiology or Medicine Laureates 1901-1925}}
{{1905 Nobel Prize winners}}
{{History of infectious disease}}
{{Tuberculosis}}
{{Authority control}}

{{DEFAULTSORT:Koch, Robert}}
[[Category:Robert Koch| ]]
[[Category:1843 births]]
[[Category:1910 deaths]]
[[Category:People from Goslar (district)]]
[[Category:German bacteriologists]]
[[Category:German infectious disease physicians]]
[[Category:19th-century German inventors]]
[[Category:German microbiologists]]
[[Category:German military personnel of the Franco-Prussian War]]
[[Category:German Nobel laureates]]
[[Category:German military doctors]]
[[Category:Academic staff of the Humboldt University of Berlin]]
[[Category:Members of the Prussian Academy of Sciences]]
[[Category:Members of the Royal Swedish Academy of Sciences]]
[[Category:Nobel laureates in Physiology or Medicine]]
[[Category:People from the Kingdom of Hanover]]
[[Category:Tuberculosis researchers]]
[[Category:Recipients of the Pour le Mérite (civil class)]]
[[Category:University of Göttingen alumni]]
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[[Category:Prussian Army personnel]]
[[Category:Robert Koch Institute people]]
[[Category:Cholera]]
[[Category:Physicians of the Charité]]
[[Category:19th-century German biologists]]
[[Category:19th-century German physicians]]