Editing Robert Koch (section)

=== 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" />