Biography:Robert Koch

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Short description: German physician and bacteriologist (1843–1910)
For other people named Robert Koch, see Robert Koch (disambiguation).
Robert Koch
RobertKoch cropped.jpg
Born
Heinrich Hermann Robert Koch

(1843-12-11)11 December 1843
Clausthal, Kingdom of Hanover, German Confederation
Died27 May 1910(1910-05-27) (aged 66)
Baden-Baden, Grand Duchy of Baden, German Empire
NationalityGermany
EducationUniversity of Göttingen
Known forKoch's postulates
Koch–Pasteur rivalry
Bacterial culture method
Germ theory of disease
Medical microbiology
Discovery of anthrax bacillus
Discovery of tuberculosis bacillus and tuberculin
Discovery of cholera bacillus
Awards
  • ForMemRS (1897)
  • Nobel Prize in Medicine (1905)
  • Pour le Mérite (1906)
Scientific career
FieldsMicrobiology
InstitutionsImperial Health Office, Berlin
University of Berlin
Doctoral advisorGeorg Meissner
Other academic advisorsFriedrich Gustav Jakob Henle
Karl Ewald Hasse
Rudolf Virchow

Heinrich Hermann Robert Koch (English: /kɒx/ KOKH,[1][2] German: [ˈʁoːbɛʁt ˈkɔx] (About this soundlisten); 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[3]), and as the father of medical bacteriology.[4][5] His discovery of the anthrax bacterium (Bacillus anthracis) in 1876 is considered as the birth of modern bacteriology.[6] Koch used his discoveries to establish that germs "could cause a specific disease"[7] and directly provided proofs for that germ theory of diseases, therefore creating the scientific basis of public health,[8] saving millions of lives.[9] For his life's work Koch is seen as one of the founders of modern medicine.[10][11]

While working as a private physician, Koch developed many innovative techniques in microbiology. He was the first to use the oil immersion lens, condenser, and microphotography in microscopy. His invention of the bacterial culture method using agar and glass plates (later developed as the Petri dish by his assistant Julius Richard Petri) made him the first to grow bacteria in the laboratory. In appreciation of his work, he was appointed 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 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 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.[12] 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.[13] The day he announced the discovery of the tuberculosis bacterium, 24 March 1882, has been observed by the World Health Organization as "World Tuberculosis Day" every year since 1982.

Early life and education

Koch was born in Clausthal, Germany, on 11 December 1843, to Hermann Koch (1814–1877) and Mathilde Julie Henriette (née Biewend; 1818–1871).[14] His father was a mining engineer. He was the third of thirteen siblings.[15] He excelled academically from an early age. Before entering school in 1848, he had taught himself how to read and write.[16] He completed secondary education in 1862, having excelled in science and math.[17]

At the age of 19, in 1862, Koch entered the University of Göttingen to study natural science.[18] He took up mathematics, physics and botany. He was appointed assistant in the university's Pathological Museum.[19] After three semesters, he decided to change his area of study to medicine, as he aspired to be a physician. During his fifth semester at the medical school, Jacob Henle, an anatomist who had published a theory of contagion in 1840, asked him to participate in his research project on uterine nerve structure. This research won him a research prize from the university and enabled him to briefly study under Rudolf Virchow, who was at the time considered as "Germany's most renowned physician."[15] In his sixth semester, Koch began to research at the Physiological Institute, where he studied the secretion of succinic acid, which is a signaling molecule that is also involved in the metabolism of the mitochondria. This would eventually form the basis of his dissertation.[13] In January 1866, he graduated from the medical school, earning honours of the highest distinction, maxima cum laude.[20][21]

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.[19] He was discharged a year later and was appointed as a district physician (Kreisphysikus) in Wollstein in Prussian 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.[20][21]

Koch began conducting research on microorganisms in a laboratory connected to his patient examination room.[18] 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.[22] Furthermore, he managed to isolate and grow selected pathogens in a pure laboratory culture.[22] 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.[19] Cohn had established the Institute of Plant Physiology[23] and invited Koch to demonstrate his new bacterium there in 1877.[24] 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.[25] Following his discovery of the tuberculosis bacterium, he was promoted to Geheimer Regierungsrat, a senior executive position, in June 1882.[26]

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.[19] 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.[27] In 1906, he moved to East Africa to research a cure for trypanosomiasis (sleeping sickness). He established the Bugula research camp where up to 1000 people a day were treated with the experimental drug Atoxyl.[28]

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.[15] In addition, he was also the first to effectively use photography (microphotography) for microscopic observation. He introduced the "bedrock methods" of bacterial staining using methylene blue and Bismarck (Vesuvin) brown dye.[8] In an attempt to grow bacteria, Koch began to use solid nutrients such as potato slices.[22] Through these initial experiments, Koch observed individual colonies of identical, pure cells.[22] He found that potato slices were not suitable media for all organisms, and later began to use nutrient solutions with gelatin.[22] 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.[22] And also 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.[29] Agar is a polysaccharide that remains solid at 37 °C, is not degraded by most bacteria, and results in a stable transparent medium.[22][30]

Development of Petri dish

Koch's booklet published in 1881 titled "Zur Untersuchung von Pathogenen Organismen" (Methods for the Study of Pathogenic Organisms)[31] has been known as the "Bible of Bacteriology."[32][33] 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.[34]

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!")[20] 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.[35] 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).[36] The culture plate was given an eponymous name Petri dish.[37] It is often asserted that Petri developed a new culture plate,[15][38][39] 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.[29] It would also have been appropriate if the name "Koch dish" had been given.[34]

Anthrax

Robert Koch is widely known for his work with anthrax, discovering the causative agent of the fatal disease to be Bacillus anthracis.[40] 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.[41] His publication in 1877 on the structure of anthrax bacterium[42] marked the first photography of a bacterium.[15] He discovered the formation of spores in anthrax bacteria, which could remain dormant under specific conditions.[18] However, under optimal conditions, the spores were activated and caused disease.[18] 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.[43] 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.[40]

Tuberculosis

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.[22] He published the discovery as "Die Ätiologie der Tuberkulose" (The Etiology of Tuberculosis),[30] 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 [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.[20][21]

There was no particular reaction to this announcement. Eminent scientists such as Rudolf Virchow remained skeptical. Virchow clung to his theory that all diseases are due to faulty cellular activities.[44] On the other hand, Paul Ehrlich later recollected that this moment was his "single greatest scientific experience."[5] 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, 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.[44]

Cholera

Photograph of Koch (third from the right) and other members of the German Cholera Commission in Egypt, 1884
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.[45] 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.[15] 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."[46] 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.[15] In 1959, Indian scientist Sambhu Nath De discovered this poison, the cholera toxin.[47] 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.[48]

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). 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.[49] It was later realised that the bacterium was already described by an Italian physician Filippo Pacini in 1854,[50] and was also observed by the Catalan physician Joaquim Balcells i Pascual around the same time.[51][52] But they failed to identify the bacterium as the causative agent of cholera. Koch's colleague Richard Friedrich Johannes Pfeiffer correctly identified the comma bacillus as Pacini's vibrioni and renamed it as Vibrio cholera in 1896.[53]

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 and creosote as possible disinfectants. These chemicals and other available drugs did not work.[15] His report in 1883 also mentioned a failed experiment on an attempt to make tuberculosis vaccine.[26] 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, auramin. His notebook indicates that by February 1890, he tested hundreds of compounds.[5] 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,[44] saying,

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.[20][21] 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.[5]

By November 1890, Koch was able to show that the extract was effective in humans as well.[54] Many patients and doctors went to Berlin to get Koch's remedy.[15] But his experiments showed that tuberculosis infected guinea pigs developed severe symptoms when the substance was inoculated. The severity was more so in humans.[44] This development of severe immune response, which is now known to be due to hypersensitivity, is known as the "Koch phenomenon."[55] 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.[5] 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,[56][57] and The British Medical Journal immediately published the English version simultaneously.[58] The English version was also reproduced in Nature,[59] and The Lancet in the same month.[60] The Lancet presented it as "glad tidings of great joy."[54] Koch simply referred to the medication as "brownish, transparent fluid."[16] Josephs Pohl-Pincus had used the name tuberculin in 1844 for tuberculosis culture media,[61] and Koch subsequently adopted as "tuberkulin."[62]

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."[44] With it his reputation greatly waned. But he devoted the rest of his life trying to make tuberculin as a usable medication.[54] His discovery was not a total failure, the substance is today used for hypersensitivity test for tuberculosis patients.[15]

Acquired immunity

Koch observed the phenomenon of acquired immunity. On 26 December 1900, he arrived as part of an expedition to German New Guinea, which was then a protectorate of the German Reich. Koch serially examined the Papuan people, the indigenous inhabitants, and their blood samples and noticed they contained Plasmodium parasites, the cause of malaria, but their bouts of malaria were mild or could not even be noticed, i.e. were subclinical. On the contrary, German settlers and Chinese workers, who had been brought to New Guinea, fell sick immediately. The longer they had stayed in the country, however, the more they too seemed to develop a resistance against it.[63]

Koch's postulates

Main page: Medicine: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.[64] Koch's discovery of the causative agent of anthrax led to the formation of a generic set of postulates which can be used in the determination of the cause of most infectious diseases.[40] 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.[65]

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:[66]

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.[35][67]

The fourth postulate was added by an American plant pathologist Erwin Frink Smith in 1905, and is stated as:[68]

4. The same pathogen must be isolated from the experimentally infected individuals.[69]

Personal life

In July 1867, Koch married Emma (Emmy) Adolfine Josephine Fraatz, and the two had a daughter, Gertrude, in 1868.[13] Their marriage ended after 26 years in 1893, and later that same year, he married actress Hedwig Freiberg (1872–1945).[13]

On 9 April 1910, Koch suffered a heart attack and never made a complete recovery.[43] 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.[18] Following his death, the Institute named its establishment after him in his honour. He was irreligious.[70]

Awards and honors

Koch's name as it appears on the LSHTM Frieze in Keppel Street
Koch's name as it appears on the LSHTM frieze in Keppel Street, Bloomsbury, London
Statue of Koch at Robert-Koch-Platz (Robert Koch square) in Berlin

Koch was made a Knight Grand Cross in the Prussian Order of the Red Eagle on 19 November 1890,[71] and was elected a Foreign Member of the Royal Society (ForMemRS) in 1897.[72] In 1905, he was awarded the Nobel Prize in Physiology and Medicine "for his investigations and discoveries in relation to tuberculosis."[73] 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.[43] Emperor Wilhelm I awarded him the Order of the Crown, 100,000 marks and appointment as Privy Imperial Councillor,[8][16] Surgeon-General of Health Service, and Fellow of the Science Senate of Kaiser Wilhelm Society.[19]

Koch established the Royal Prussian Institute for Infectious Diseases in Berlin 1891. After his death it was renamed Robert Koch Institute in his honour.[8]

The World Health Organization observes "World Tuberculosis Day" every 24 March since 1982 to commemorate the day Koch discovered tuberculosis bacterium.[16]

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.[74]

A large marble statue of Koch stands in a small park known as Robert Koch Platz, just north of the Charity Hospital, in the Mitte section of Berlin. His life was the subject of a 1939 German produced motion picture that featured Oscar winning actor Emil Jannings in the title role. On 10 December 2017, Google showed a Doodle in celebration of Koch's birthday.[75][76]

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 information: Biology: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.[77] 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.[78] To prove his vaccine, Pasteur sent his assistant Louis Thuillier to Germany for demonstration and disproved Koch's idea.[79] 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."[16] 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."[15]

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.[5] 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.[80] One week later, Koch publicised that the drug was a glycerine extract of a pure cultivation of the tuberculosis bacilli.[5] The German official report in late 1891 declared that tuberculosis was not cured with tuberculin.[44] 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.[17] Since 1885, he had tried to leave government service and create an independent state-run institute of his own.[16] 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.[27]

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.[81] 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.[82] 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:

  1. Human tuberculosis bacillus cannot infect cattle.
  2. But cattle bacillus may infect humans since it is very pathogenic.[83]

By that time, there was evidence that cattle tuberculosis was transmitted to humans through meat and milk.[84][85] 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.[16] 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."[86] Chair of the congress, Joseph Lister reprimanded Koch and explained the medical evidences of cattle tuberculosis in humans.[87]

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.[88] 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.[89] 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.[90] To his disadvantage, Grassi had criticised Koch on his malaria research in 1898 during an investigation of the epidemic,[89] while Ross had established a cordial relationship with Koch.[91] 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."[92]

References

  1. ↑ "Koch". Random House Webster's Unabridged Dictionary.
  2. ↑ "Koch". The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt, https://ahdictionary.com/word/search.html?q=Koch 
  3. ↑ Fleming, Alexander (1952). "Freelance of Science". British Medical Journal 2 (4778): 269. doi:10.1136/bmj.2.4778.269. 
  4. ↑ Tan, S. Y.; Berman, E. (2008). "Robert Koch (1843-1910): father of microbiology and Nobel laureate". Singapore Medical Journal 49 (11): 854–855. PMID 19037548. https://pubmed.ncbi.nlm.nih.gov/19037548. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Gradmann, Christoph (2006). "Robert Koch and the white death: from tuberculosis to tuberculin". Microbes and Infection 8 (1): 294–301. doi:10.1016/j.micinf.2005.06.004. PMID 16126424. https://pubmed.ncbi.nlm.nih.gov/16126424. 
  6. ↑ Lakhani, S. R. (1993). "Early clinical pathologists: Robert Koch (1843-1910)". Journal of Clinical Pathology 46 (7): 596–598. doi:10.1136/jcp.46.7.596. PMID 8157741. 
  7. ↑ "A Theory of Germs". Science, Medicine, and Animals. National Academies Press (US). 20 October 2023. https://www.ncbi.nlm.nih.gov/books/NBK24649/#:~:text=In%20the%20final%20decades%20of,and%20suspected%20they%20caused%20anthrax. 
  8. ↑ 8.0 8.1 8.2 8.3 Lakhtakia, Ritu (2014). "The Legacy of Robert Koch: Surmise, search, substantiate". Sultan Qaboos University Medical Journal 14 (1): e37–41. doi:10.12816/0003334. PMID 24516751. 
  9. ↑ https://history.info/on-this-day/1843-robert-koch-man-saved-millions-lives/
  10. ↑ https://www.facebook.com/watch/?v=245261433654285
  11. ↑ "Louis Pasteur vs Robert Koch: The History of Germ Theory". https://www.youtube.com/watch?v=XCVnOb6VXmg. 
  12. ↑ Margo, Curtis E. (11 April 2011). "From Robert Koch to Bradford Hill: Chronic Infection and the Origins of Ocular Adnexal Cancers" (in en). Archives of Ophthalmology 129 (4): 498–500. doi:10.1001/archophthalmol.2011.53. ISSN 0003-9950. PMID 21482875. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/427189. 
  13. ↑ 13.0 13.1 13.2 13.3 Brock, Thomas. Robert Koch: A life in medicine and bacteriology. ASM Press: Washington DC, 1999. Print.
  14. ↑ Metchnikoff, Elie. The Founders of Modern Medicine: Pasteur, Koch, Lister. Classics of Medicine Library: Delanco, 2006. Print.
  15. ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 Blevins, Steve M.; Bronze, Michael S. (2010). "Robert Koch and the 'golden age' of bacteriology". International Journal of Infectious Diseases 14 (9): e744–751. doi:10.1016/j.ijid.2009.12.003. PMID 20413340. 
  16. ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 Ligon, B. Lee (2002). "Robert Koch: Nobel laureate and controversial figure in tuberculin research". Seminars in Pediatric Infectious Diseases 13 (4): 289–299. doi:10.1053/spid.2002.127205. PMID 12491235. https://pubmed.ncbi.nlm.nih.gov/12491235. 
  17. ↑ 17.0 17.1 Akkermans, Rebecca (2014). "Robert Heinrich Herman Koch". The Lancet 2 (4): 264–265. doi:10.1016/S2213-2600(14)70018-9. PMID 24717622. https://pubmed.ncbi.nlm.nih.gov/24717622. 
  18. ↑ 18.0 18.1 18.2 18.3 18.4 "Heinrich Hermann Robert Koch." World of Scientific Discovery. Gale, 2006. Biography in Context. Web. 14 April 2013.
  19. ↑ 19.0 19.1 19.2 19.3 19.4 Ernst, H. C. (1918). "Robert Koch (1843-1910)". Proceedings of the American Academy of Arts and Sciences 53 (10): 825–827. https://www.jstor.org/stable/25130022. 
  20. ↑ 20.0 20.1 20.2 20.3 20.4 Sakula, A. (1982). "Robert Koch: centenary of the discovery of the tubercle bacillus, 1882". Thorax 37 (4): 246–251. doi:10.1136/thx.37.4.246. PMID 6180494. 
  21. ↑ 21.0 21.1 21.2 21.3 Sakula, A. (1983). "Robert koch: centenary of the discovery of the tubercle bacillus, 1882". The Canadian Veterinary Journal 24 (4): 127–131. PMID 17422248. 
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 22.7 Madigan, Michael T., et al. Brock Biology of Microorganisms: Thirteenth edition. Benjamin Cummings: Boston, 2012. Print.
  23. ↑ Pick, E. (2001). "Medical luminaries". Nature 411 (6840): 885. doi:10.1038/35082239. PMID 11418826. Bibcode: 2001Natur.411..885P. 
  24. ↑ Salomonsen, C. J. (1950). "Reminiscences of the summer semester, 1877, at Breslau". Bulletin of the History of Medicine 24 (4): 333–351. PMID 15434544. https://pubmed.ncbi.nlm.nih.gov/15434544. 
  25. ↑ O’Connor, T.M. "Tuberculosis, Overview." International Encyclopedia of Public Health. 2008. Web.
  26. ↑ 26.0 26.1 Gradmann, C. (2001). "Robert Koch and the pressures of scientific research: tuberculosis and tuberculin". Medical History 45 (1): 1–32. doi:10.1017/s0025727300000028. PMID 11235050. 
  27. ↑ 27.0 27.1 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.
  28. ↑ Bonhomme, Edna. "When Africa was a German laboratory" (in en). https://www.aljazeera.com/opinions/2020/10/6/when-africa-was-a-german-laboratory/. 
  29. ↑ 29.0 29.1 Hufford, David C. (1988-03-01). "A Minor Modification by R. J. Petri" (in en). Laboratory Medicine 19 (3): 169–170. doi:10.1093/labmed/19.3.169. ISSN 0007-5027. https://academic.oup.com/labmed/article-lookup/doi/10.1093/labmed/19.3.169. 
  30. ↑ 30.0 30.1 Koch, Robert (24 March 1882). "Die Ätiologie der Tuberkulose (1882)". Robert Koch. Klassische Texte der Wissenschaft. 19. 221–30. doi:10.1007/978-3-662-56454-7_4. ISBN 978-3-662-56454-7. http://edoc.rki.de/docviews/abstract.php?id=610. "From page 225: "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.)" 
  31. ↑ Koch, Robert (2010). Zur Untersuchung von Pathogenen Organismen. Berlin: Robert Koch-Institut. doi:10.25646/5071. https://edoc.rki.de/handle/176904/5146. 
  32. ↑ Booss, John; Tselis, Alex C. (2014), "A history of viral infections of the central nervous system" (in en), Neurovirology, Handbook of Clinical Neurology, 123, Elsevier, pp. 3–44, doi:10.1016/b978-0-444-53488-0.00001-8, ISBN 978-0-444-53488-0, PMID 25015479, https://linkinghub.elsevier.com/retrieve/pii/B9780444534880000018, retrieved 2021-04-15 
  33. ↑ Hurt, Leslie (2003). "Dr. Robert Koch:: a founding father of biology" (in en). Primary Care Update for OB/GYNS 10 (2): 73–74. doi:10.1016/S1068-607X(02)00167-1. https://linkinghub.elsevier.com/retrieve/pii/S1068607X02001671. 
  34. ↑ 34.0 34.1 Shama, Gilbert (2019). "The "Petri" Dish: A Case of Simultaneous Invention in Bacteriology". Endeavour 43 (1–2): 11–16. doi:10.1016/j.endeavour.2019.04.001. PMID 31030894. https://pubmed.ncbi.nlm.nih.gov/31030894. 
  35. ↑ 35.0 35.1 Weiss, Robin A. (2005). "Robert Koch: the grandfather of cloning?". Cell 123 (4): 539–542. doi:10.1016/j.cell.2005.11.001. PMID 16286000. 
  36. ↑ Petri, Julius Richard (1887). "Eine kleine Modification des Koch'schen Plattenverfahrens". Centralblatt für Bacteriologie und Parasitenkunde 1: 279–280. https://archive.org/details/1887-petri-eine-kleine-modification-des-koch-schen-plattenverfahrens-2020-braus-. 
  37. ↑ Mahajan, Monika (2021). "Etymologia: Petri Dish". Emerging Infectious Diseases 27 (1): 261. doi:10.3201/eid2701.ET2701. 
  38. ↑ Zhang, Shuguang (2004). "Beyond the Petri dish". Nature Biotechnology 22 (2): 151–152. doi:10.1038/nbt0204-151. PMID 14755282. https://pubmed.ncbi.nlm.nih.gov/14755282. 
  39. ↑ Grzybowski, Andrzej; Pietrzak, Krzysztof (2014). "Robert Koch (1843-1910) and dermatology on his 171st birthday". Clinics in Dermatology 32 (3): 448–450. doi:10.1016/j.clindermatol.2013.10.005. PMID 24887990. https://pubmed.ncbi.nlm.nih.gov/24887990. 
  40. ↑ 40.0 40.1 40.2 "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.
  41. ↑ Koch, Robert (2010). Robert Koch-Institut. "Die Ätiologie der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des Bacillus Anthracis" (in de). Cohns Beiträge zur Biologie der Pflanzen 2 (2): 277 (1–22). doi:10.25646/5064. https://edoc.rki.de/handle/176904/5139. 
  42. ↑ Koch, Robert (2010). "Verfahren zur Untersuchung, zum Konservieren und Photographieren der Bakterien" (in de). Beiträge zur Biologie der Pflanzen 2: 399–434. doi:10.25646/5065. https://edoc.rki.de/handle/176904/5140. 
  43. ↑ 43.0 43.1 43.2 "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.
  44. ↑ 44.0 44.1 44.2 44.3 44.4 44.5 Kaufmann, Stefan H. E.; Schaible, Ulrich E. (2005). "100th anniversary of Robert Koch's Nobel Prize for the discovery of the tubercle bacillus". Trends in Microbiology 13 (10): 469–475. doi:10.1016/j.tim.2005.08.003. PMID 16112578. https://pubmed.ncbi.nlm.nih.gov/16112578. 
  45. ↑ Howard-Jones, N. (1984). "Robert Koch and the cholera vibrio: a centenary". British Medical Journal 288 (6414): 379–381. doi:10.1136/bmj.288.6414.379. PMID 6419937. 
  46. ↑ Lippi, D.; Gotuzzo, E. (2014). "The greatest steps towards the discovery of Vibrio cholerae". Clinical Microbiology and Infection 20 (3): 191–195. doi:10.1111/1469-0691.12390. PMID 24191858. 
  47. ↑ Nair, G. Balakrish; Takeda, Yoshifumi (2011). "Dr Sambhu Nath De: unsung hero". The Indian Journal of Medical Research 133 (2): 127. PMID 21415484. 
  48. ↑ Koch, R. (20 March 1884) "Sechster Bericht der deutschen wissenschaftlichen Commission zur Erforschung der Cholera" (Sixth report of the German scientific commission for research on cholera), Deutsche medizinische Wochenscrift (German Medical Weekly), 10 (12): 191–192. On page 191, he mentions the characteristic comma shape of Vibrio cholerae: "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.)
  49. ↑ Winslow, C. E.; Broadhurst, J.; Buchanan, R. E.; Krumwiede, C.; Rogers, L. A.; Smith, G. H. (1920). "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 of Bacteriology 5 (3): 191–229. doi:10.1128/JB.5.3.191-229.1920. PMID 16558872. 
  50. ↑ See:
  51. ↑ Real Academia de la Historia, ed (2018). "Joaquín Balcells y Pasqual" (in es). http://dbe.rah.es/biografias/18541/joaquin-balcells-y-pasqual. 
  52. ↑ Col·legi Oficial de Metges de Barcelona, ed (2015). "Joaquim Balcells i Pascual" (in ca). http://www.galeriametges.cat/galeria-fitxa.php?icod=EGMM. 
  53. ↑ Hugh, Rudolph (1965). "Nomenclature and taxonomy of Vibrio cholerae Pacini 1854 and Vibrio eltor Pribam 1933" (in en). Public Health Service Publication. U.S. Department of Health, Education, and Welfare, Public Health Service, Environmental Health Service, National Air Pollution Control Administration. pp. 1–4. https://books.google.com/books?id=NP7AY38J1hcC. 
  54. ↑ 54.0 54.1 54.2 Sakula, Alex (1985). "Robert Koch: The story of his discoveries in tuberculosis" (in en). Irish Journal of Medical Science 154 (S1): 3–9. doi:10.1007/BF02938285. PMID 3897123. http://link.springer.com/10.1007/BF02938285. 
  55. ↑ Hunter, Robert L. (2020). "The Pathogenesis of Tuberculosis-The Koch Phenomenon Reinstated". Pathogens 9 (10): e813. doi:10.3390/pathogens9100813. PMID 33020397. 
  56. ↑ Koch, Robert (2010). "Fortsetzung der Mitteilungen über ein Heilmittel gegen Tuberkulose" (in de). Deutsche Medizinische Wochenschrift 17: 101–102. doi:10.25646/5100. https://edoc.rki.de/handle/176904/5175. 
  57. ↑ Koch, Robert (1891). "A Further Communication on a Remedy for Tuberculosis". The Indian Medical Gazette 26 (3): 85–87. PMID 29000631. 
  58. ↑ Koch, R. (1891). "A Further Communication on a Remedy for Tuberculosis". British Medical Journal 1 (1568): 125–127. doi:10.1136/bmj.1.1568.125. PMID 20753227. 
  59. ↑ "Dr. Koch's Remedy for Tuberculosis" (in en). Nature 43 (1108): 281–282. 1891. doi:10.1038/043281a0. Bibcode: 1891Natur..43..281.. 
  60. ↑ Richmond, W.S. (1891). "Professor Koch's Remedy for Tuberculosis" (in en). The Lancet 137 (3514): 56–57. doi:10.1016/S0140-6736(02)15705-9. https://linkinghub.elsevier.com/retrieve/pii/S0140673602157059. 
  61. ↑ Caspary (1884). "Angioneurotische Dermatosen" (in de). Vierteljahresschrift für Dermatologie und Syphilis 16 (1): 141–155. doi:10.1007/BF02097828. https://doi.org/10.1007/BF02097828. "Pohl-Pincus wrote: Wir werden deshalb alas Tuberculin darzustellen suchen [We shall therefore endeavor to describe it as tuberculin]". 
  62. ↑ Koch, R. (1891). "Weitere Mittheilung über das Tuberkulin" (in de). Deutsche Medizinische Wochenschrift 17 (43): 1189–1192. doi:10.1055/s-0029-1206810. http://www.thieme-connect.de/DOI/DOI?10.1055/s-0029-1206810. 
  63. ↑ Hugo Kronecker: Hygienische Topographie In: A. Pfeiffer (Editor): 21. Jahresbericht über die Fortschritte und Leistungen auf dem Gebiete der Hygiene. 1903. Publisher: Friedrich Vieweg und Sohn, Braunschweig, 1905. p. 68
  64. ↑ Amsterdamska, Olga. "Bacteriology, Historical." International Encyclopedia of Public Health. 2008. Web.
  65. ↑ Tabrah, Frank L. (2011). "Koch's postulates, carnivorous cows, and tuberculosis today". Hawaii Medical Journal 70 (7): 144–148. PMID 21886302. 
  66. ↑ Loeffler, Friedrich (1884). "Untersuchungen über die Bedeutung der Mikroorganismen für die Entstehung der Diphtherie beim Menschen, bei der Taube und beim Kalbe" (in German). Mittheilungen aus dem Kaiserlichen Gesundheitsamte (Reports from the Imperial Office of Public Health) 2: 421–499. https://books.google.com/books?id=Y6lQAAAAYAAJ&pg=PA421.  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:
    1) Es müssen constant in den local erkrankten Parteien Organismen in typischer Anordnung nachgewiesen werden.
    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.
    3) Mit den Reinculturen muss die Krankheit experimentell wieder erzeugt werden können."
    (Now if diphtheria is a disease that's caused by microorganisms, then it must also be able to fulfill those three postulates whose fulfillment is absolutely necessary for the strict proof of the parasitic nature of any such disease:
    1) In the given diseased patients, there must always be shown [to be present] organisms in typical disposition.
    2) The organisms to which one would attribute — according to their behavior in the diseased parts — a relevance for the occurrence of these changes, must be isolated and cultured in pure form.
    3) The disease must be able to be reproduced experimentally via pure cultures.)
  67. ↑ Byrd, Allyson L.; Segre, Julia A. (2016). "Adapting Koch's postulates". Science 351 (6270): 224–226. doi:10.1126/science.aad6753. PMID 26816362. Bibcode: 2016Sci...351..224B. https://pubmed.ncbi.nlm.nih.gov/26816362. 
  68. ↑ Smith, Erwin F. (1905). Bacteria in Relation to Plant Diseases. 1. Washington. D.C.: Carnegie Institution of Washington. p. 9. https://www.biodiversitylibrary.org/item/60542#page/31/mode/1up. 
  69. ↑ Hadley, Caroline (2006). "The infection connection". EMBO Reports 7 (5): 470–473. doi:10.1038/sj.embor.7400699. PMID 16670677. 
  70. ↑ 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."
  71. ↑ "Rother Adler-orden" (in German), Königlich Preussische Ordensliste (supp.), 1, Berlin, 1886, p. 7, https://babel.hathitrust.org/cgi/pt?id=mdp.39015049878823&view=1up&seq=7&skin=2021 
  72. ↑ "Fellows of the Royal Society". London: Royal Society. https://royalsociety.org/about-us/fellowship/fellows/. 
  73. ↑ "The Nobel Prize in Physiology or Medicine 1905" (in en-US). https://www.nobelprize.org/prizes/medicine/1905/summary/. 
  74. ↑ "Behind the frieze". https://www.lshtm.ac.uk/aboutus/introducing/history/behind-frieze. 
  75. ↑ "Celebrating Robert Koch". https://www.google.com/doodles/celebrating-robert-koch. 
  76. ↑ "Robert Koch Google Doodle". https://www.youtube.com/watch?v=lEeBZceXjfg. 
  77. ↑ Carter, K. C. (1988). "The Koch-Pasteur dispute on establishing the cause of anthrax". Bulletin of the History of Medicine 62 (1): 42–57. PMID 3285924. https://pubmed.ncbi.nlm.nih.gov/3285924. 
  78. ↑ Koch, R. (2010). "Zur Ätiologie des Milzbrandes". Mittheilungen aus dem Kaiserlichen Gesundheitsamte. Berlin: Robert Koch-Institut. pp. 174–206. https://edoc.rki.de/bitstream/handle/176904/5148/174-206.pdf?sequence=1&isAllowed=y. 
  79. ↑ Rietschel, Ernst Th; Cavaillon, Jean-Marc (2002). "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)". Journal of Endotoxin Research 8 (2): 71–82. doi:10.1179/096805102125000218. PMID 12028747. https://pubmed.ncbi.nlm.nih.gov/12028747. 
  80. ↑ Leibowitz, D. (1993). "Scientific failure in an age of optimism: public reaction to Robert Koch's tuberculin cure". New York State Journal of Medicine 93 (1): 41–48. PMID 8429953. https://pubmed.ncbi.nlm.nih.gov/8429953. 
  81. ↑ Packer, R. A. (1987). "Veterinarians challenge Dr. Robert Koch regarding bovine tuberculosis and public health: a chronology of events". Veterinary Heritage 10 (2): 7–11. PMID 11621492. https://pubmed.ncbi.nlm.nih.gov/11621492. 
  82. ↑ Packer, R. A. (1990). "Veterinarians challenge Dr. Robert Koch regarding bovine tuberculosis and public health". Journal of the American Veterinary Medical Association 196 (4): 574–575. PMID 2406233. https://pubmed.ncbi.nlm.nih.gov/2406233. 
  83. ↑ Smith, T. (1898). "A comparative study of bovine tubercle bacilli and of human bacilli from sputum". The Journal of Experimental Medicine 3 (4–5): 451–511. doi:10.1084/jem.3.4-5.451. PMID 19866892. 
  84. ↑ Bergey, D. H. (1897). "Bovine Tuberculosis in its Relation to the Public Health". Public Health Papers and Reports 23: 310–320. PMID 19600776. 
  85. ↑ "Reviews and Notices". British Medical Journal 2 (1072): 85–86. 1881. 
  86. ↑ Kaufmann, Stefan H. E. (2003). "A short history of Robert Koch's fight against tuberculosis: those who do not remember the past are condemned to repeat it". Tuberculosis (Edinburgh, Scotland) 83 (1–3): 86–90. doi:10.1016/s1472-9792(02)00064-1. PMID 12758195. https://pubmed.ncbi.nlm.nih.gov/12758195. 
  87. ↑ Clark, Paul F. (1920). "Joseph Lister, his Life and Work". The Scientific Monthly 11 (6): 518–539. Bibcode: 1920SciMo..11..518C. https://www.jstor.org/stable/6707. 
  88. ↑ Cox FEG (2010). "History of the discovery of the malaria parasites and their vectors". Parasites & Vectors 3 (1): 5. doi:10.1186/1756-3305-3-5. PMID 20205846. 
  89. ↑ 89.0 89.1 Capanna E (2012). "Grassi versus Ross: who solved the riddle of malaria?". International Microbiology 9 (1): 69–74. PMID 16636993. http://revistes.iec.cat/index.php/IM/article/viewFile/4c457c86cb18b.002/9548. 
  90. ↑ Pai-Dhungat, J. V.; Parikh, Falguni (2015). "Battista Grassi (1854-1925) & Malaria Controversy". The Journal of the Association of Physicians of India 63 (3): 108. PMID 26543977. https://www.japi.org/oldwebsitecontent/march_2015/103_battista_grassi.pdf. 
  91. ↑ Ross, R. (1925). "The mosquito-theory of malaria and the late Prof. G. B. Grassi". Science Progress in the Twentieth Century (1919-1933) 20 (78): 311–320. https://www.jstor.org/stable/43427633. 
  92. ↑ Esch GW (2007). Parasites and Infectious Disease: Discovery by Serendipity and Otherwise. Cambridge University Press. pp. 137–138. ISBN 9781139464109. https://books.google.com/books?id=88RH-7br9OAC. 

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