The "golden era" of medical-hygiene studies of disease came to fruition as the biologically-based theories of pathogens gradually replaced chemically-based notions, such as continuing "spontaneous humoral generation," to explain contagion as well as related processes like putrefaction and fermentation. This shift was aided by parallel advances in instrumentation and techniques of microscopy and histology.

1810. Working with some 900 post-mortem results, Gaspard Laurent Bayle (1774-1816), a French pathologist and microscopist at the La Charité Hospital in Paris, identifies various types of lung phthisis and affirms the importance of the presence of small lung-tissue nodules "as being peculiar to consumption" (CF 226).

1810. Spotted Fever. Nathan Strong (1781-1837) publishes An inaugural dissertation on the disease termed Petechial, or Spotted Fever and presents his findings to the Connecticut Medical Society. His study concerns the elusive disease now known as cerebrospinal meningitis. See also Weichselbaum and Ricketts.

c.1828 Christian Gottfried Ehrenberg (1795-1876) introduces the new technical term bakteria (sing. bakterium) to replace the vaguer "germ" and "miasma."

c. 1829. Cholera epidemic reaches Europe, spreading to Russia and Hungary; to Germany by 1831; to Paris and London by 1832; and via shipping-lanes to New York and beyond. These and similar events beyond medical control were among the great fears of the time. Asiatic or genuine cholera will return to Europe in 1837 and 1849 with ready transfer to North America. It would be more than a half-century before a determined scientific-bacteriologic resolution is found. See Robert Koch, CF: 259.

c.1830. Turning to the study of microscopic organisms in water, soil, and dust, Ehrenberg describes many new types of unicells, Protista, diatoms and general infusoria.

1831. Cholera. J.R. Lichtenstadt publishes Die asiatische Cholera in Russland in den Jahren 1830 und 1831... (Berlin: Haude & Spener).

1832. G.E. Winslow publishes Essay on the Nature, Symptoms and Treatment of Asiatic Cholera (New York: Sleight & Robinson), a standard text on cholera from the pre-bacterial era.

1833. Johannes Peter Mueller (1801-1858), now considered the founder of modern physiology, is made Professor of Anatomy and Physiology at the Friedrich-Wilhelms-Universitaet (later Humboldt-Universitaet, Humboldt University) of Berlin. His students include three pioneers in bacteriology, Schwann, Remak, and Virchow.

1835. Ehrenberg coins the term bacillus for the short, spore-forming rod-like organisms.

1837. Typhus epidemic in Philadelphia.

1839. Theodor Schwann (1810-1882) demonstrates the cellular basis of the body.

c.1840. Johann Evangelista Purkinje (1787-1869), a pioneering Czech experimental physiologist and histologist, introduces term "protoplasma," derived from the Greek words "proto," meaning first, and "plasm," meaning mould or cast. He also left a legacy of new, eponymous micro-anatomical structures (Purkinje cells in the brain, Purkinje fibres in the heart), all supportive of the newly recognised cell/germ theory.

1840. Friedrich Gustav Jakob Henle offers his theory of contagion in Von den Miasmen und Kontagien. In this work he also articulates three of the four principles of disease causation that, with additional development by his pupil, Robert Koch, are eventually known as the Henle-Koch postulates of infectious diseases (also known as Koch's postulates).

1840. F. Cramer publishes Der Abdominal-Typhus (Kassel: J. Krieger).

1844. Mueller completes his landmark four-volume treatise on physiology, Handbuch der Physiologie der Menschen.

1844. Agostino Bassi (1773-1856), an Italian entomologist, applies to human beings his theories regarding the role played by pathogenic organisms in infectious diseases. Bassi's work would greatly influence and aid Louis Pasteur, who in 1865 would begin studies which saved the French silk industry by curing silkworm disease.

1844. Bubonic plague. G.F. Grohmann publishes Das Pest-Contagium in Egypten u. seine Quelle... (Vienna: Kaulfuss Prandel).

1846. Over the next three years, typhus decimates the population of Ireland during the Great Irish Famine and spreads to New York and elsewhere, resulting in quarantines in so-called "fever sheds." No medical help or understanding of typhus would be forthcoming until 1910. See Howard Taylor Ricketts.

1847. Cranston R. Low and T.C. Dodds publish the illustrated Atlas of Bacteriology (Edinburgh: E. & S. Livingstone).

1847. E.A. Parkes publishes Researches into the Pathology and Treatment of the Asiatic or Algide Cholera, 1847 (London: John Churchill), another standard text expressing pre-bacteriological views.

1846-53. Henle issues his Handbuch der rationellen Pathologie. With this two-volume work Henle offered concepts of contagion vivum and contagion animatum, both early expressions of the theory that microscopic organisms cause infections (that is, that they are the agents or vectors of infectious disease).

1847. Ignaz Semmelweis (1818-1865), a German-Hungarian physician-obstetrician working at the Vienna General Hospital, observes bedside visitor-practitioner cross-contamination with puerperal (child-bed) fever. His observation led him to introduce hand-washing and use of mild chloride-of-lime solution.

1849. Cholera breaks out in London, Paris, Liverpool, and is transmitted, via shipping lanes, to New York and Mississippi. In the poor, crowded district of Soho, London, physician John Snow (1813-58) begins landmark epidemiological studies that will continue until 1854. Disease outbreaks are traced to shared yards and communal water-taps and stand-pipes, indicating a contaminated water source.

1849. Anthrax, a scourge of cattle, is successfully shown to involve short rod-like bacilli in the blood, though without further evidence of causation (CF: 198, citing Pollender, Brauell). Cf. Koch.

1850. Auguste Haspel publishes Maladie de l'Algérie: des causes, de la symptomatôlogie, de la nature et du traitement des maladies endémo-épidémiques de la province d'Oran.

1851. The first Cholera Conference/International Sanitary Conference convenes in Paris. Subsequent conferences would be held in Paris (1859), Constantinople (1866), Vienna (1874), Washington, DC (1881; first participation of the U.S.), Rome (1885), Venice (1892), Dresden (1893), Paris (1894), Venice (1897), Paris (1903), and again in Paris (1911-12). The first two conferences focused primarily on quarantine regulations.

1853. James Paget (1814-1899), FRCS, London medical practitioner, delivers Lectures on Surgical Pathology to the Royal College of Surgeons of England. The volume is published the same year and reprinted in 1860. Paget supported the new directions indicated by Schwann, Henle and others.

1855. Robert Remak (1815-1865) becomes assistant to Johannes Mueller in Berlin and makes pioneering contributions to histological technique, so essential to adequate microscopy of tissues infiltrated with pathogenic bodies. Using blue copper sulphate in alcoholic vinegar to harden and stain dividing cell membranes, Remak discovers that cells are formed by division of pre-existing cells, contrary to the prevailing orthodoxy of Schwann and independently of Rudolf Virchow (Anderson, 1986). Such basic data were fundamental for the understanding of bacterial multiplication, survival, and behavior in the development of disease.

1857. Carl Zeiss (1816-1888), a German optical-instrument maker, produces his Stand I-compound model microscope.

1858. Rudolf Virchow (1821-1902) publishes Die Cellularpathologie in ihrer Begründung auf physiologische und pathologische Gewebelehre. (Berlin: August Hirschwald).

1858. Joseph von Gerlach (1820-1896) a professor of anatomy at Erlangen, introduces the use of carmine gelatin, the red color of which derives from crushed scale insects (e.g., cochineals), to histological staining. Earlier attempts at histological staining included use of weak saffron vegetable dye. W. H. Perkin contemporaneously produced "mauveine" dye (aniline-mauve, toluidine blue). Other durable coal-tar dyes would follow (basic/non-acidic dyes, gentian violet, methyl violet, methyl blue, fuchsin and Bismarck brown; with acid-fuchsin and eosin). See Loeffler, Weigert, Pfeiffer, Ziehl, Gram, Ehrlich, and others to 1899.

1858. Louis Pasteur (1822-1895) publishes Mémoire sur la fermentation appelée lactique, regarded as the foundation stone of cell theory, microbiology, and bacteriology.

1859. Virchow attends the Second Cholera Conference in Paris (also called the Second International Sanitary Conference). His remarks at this meeting prove so influential they are quoted verbatim by Fraenkel in CF twenty years later (274).

1860. Elisha Harris publishes The Utility and Application of Heat as a Disinfectant (Boston: Rand & Avery).

1861. Typhoid fever repeatedly flares up during the American Civil War to 1865. Also known as "camp fever," typhoid fever killed more soldiers than did combat in all wars until 1915. See Almroth Wright.

1862. With physiologist Claude Bernard (1813-1878), Pasteur experiments with heat control of microbial processes in milk and wine. He generalises his ideas to human diseases similarly caused by invisible microbes (yeasts, fungi, bacteria), influencing Lister. Pasteur decisively contradicts current ideas of spontaneous chemical generation of living organisms and advances the germ theory of unicellular microbes as agents of disease.

1863. A. S. Packard (1839-1905) and G.F. Leuckart (1822-1898) publish Die menschlichen Parasiten (Leipzig & Heidelberg), an influential study of parasites affecting humans, in two volumes between 1863 and 1876. Meanwhile Robert Koch undertakes his second year of study of the natural sciences at the University of Goettingen.

1863. The spread of anthrax is demonstrated experimentally via blood inoculations between infected and symptom-free animals. Cf. Koch.

1865. In Paris, the French medical bacteriologist Jean Antoine Villemin (1827-92), having discovered bovine tuberculosis around 1854, demonstrates by inoculation into healthy animals the contagious nature of material from the pathological nodules. His results are later improved upon by Cohnheim and by Koch.

1867. Lister publishes "On the Antiseptic Principle in the Practice of Surgery," on the use carbolic acid (phenol), in the Lancet. Influenced by the "germ theory" of Louis Pasteur, Lister subsequently develops a thoroughgoing aseptic-environment approach.

1867. Charles Murchison (1830-1879) publishes Die typhoiden Krankheiten...Die Epidemie des recurrirenden Typhus in St. Petersburg 1864-1865... (Braunschweig: Vieweg).

1871. Weigert publishes "Ueber Bakterien in der Pockenhaut" (Berlin: Hirschwald) on smallpox (Pockenhaut).

1872. Ferdinand Julius Cohn (1818-1898) publishes Untersuchungen ueber Bacterien (Breslau: J. Kern). With this work, he becomes the first to accord a separate status to bacteria, viewing them as part of the vegetable kingdom and re-shaping the early classification by Ehrenberg.

1873. Murchison (1830-1879) traces a typhoid outbreak in West London to a polluted source of milk.

1873. Gerhard Henrik Hansen (1841-1912) discovers Mycobacterium leprae as the cause of leprosy. The microbe is stained and its existence confirmed by Neisser in 1879 using samples provided by Hansen.

1873. On 7 April, Lister transmits "A contribution to the germ theory of putrefaction and other Fermentative Changes, and to the Natural History of Torulae and Bacteria" to the Royal Society of Edinburgh. The paper is published two years later in the Transactions of the Royal Society of Edinburgh. Lister's missive was against the more humoral theory that Sir John Scott Burden-Sanderson (1828-1905) described in his 1871 report, "On the origin and distribution of microenzymes in water."

1874. Christian A. Th. Billroth (1829-1894) detects chains of spherical organisms in surgical wound infections and coins the genus name "Streptococcus." See Rosenbach.

1875. Histological staining becomes a major technique. "Rapid progress was now made; everybody began to stain; the isolated and the double staining were introduced, and...the art of staining has already reached a high state of perfection. The names of Weigert, Koch and Ehrlich are closely connected with these advances." (CF: 38 & 39-48.)

1876. Robert Heinrich Hermann Koch (1843-1910) shows both that the specific agent Bacillus anthracis is always present in the diseased animal and that the bacillus spores also produce anthrax. These two observations become part of "Koch's Postulates" for all contagion of bacterial origin.

1876. Attracted by Pasteur’s germ theory, John Tyndall studies fractional sterilization by heat and heat-resistant spores. His early observation, famously repeated by Alexander Fleming in the 1920s, that moulds such as Penicillium sp. inhibit the growth of bacteria was a half-century ahead of its time.

1877. Edgar M. Crookshank (1858-1928), pupil of Lister, publishes Manual of Bacteriology (London: H.K. Lewis & Co.). A third edition follows in 1890; a fourth, in 1896.

1878. Koch, Gaffky, and others visit Egypt to observe a cholera outbreak.

1878. Pasteur publishes Germ Theory and its Applications to Medicine and on the Antiseptic Principle of the Practice of Surgery, a summary collection of three classic papers of his own and Lister's iconic contributions.

1878. The French botanist Antoine Magnin (1848-1926) publishes Les bactéries. An English translation by Sternberg follows in 1880; it becomes the first textbook of bacteriology in the U.S.

1879. Gonorrhoea. Albert Ludwig S. Neisser (1855-1916) identifies the microbe later named after him, Neisseria gonorrhoeae.

1880. Koch moves to Berlin and the Imperial Department of Health, later becoming Professor of Hygiene, University of Berlin, and Director of the Institute for Infectious Diseases. His co-workers and/or students during this period include Gaffky, and Hueppe, Loeffler. Fraenkel, Petri, Pfeiffer, and Wassermann.

1880. Typhoid. While assisting Koch in Berlin, Carl Josef Eberth (1835-1926) becomes the first to describe a suspect rod-like bacillus (Eberthella typhi) in a case of typhoid. Gaffky, who is also working in Koch's laboratory, confirms this finding. The organism, known at first as the "Gaffky-Eberth bacillus," is later renamed Salmonella enterica serovar Typhi in commemoration of Dr. D.E. Salmon (see Theobald Smith).

1880. Julius F. Cohnheim (1839-1884), who studied "pus" and migration of protective white blood corpuscles (cf. Metchnikoff), invents the freezing technique of preparing histological thin-sections for tissues or bacteria.

1881. Agar-agar, a tough gelatinous component of seaweed, replaces the earlier potato slice and animal gelatin for bacterial cultures. The Berlin laboratory of Koch is responsible, thanks to his assistant Walther Hesse (1846-1911), and the improvement quickly becomes widespread. Cf. Petri.

1881. Jean J.H. Toussaint (1847-90), Professor of Veterinary Pathology, University Toulouse, independently of Pasteur, produces an early anthrax vaccine (CF 126 passim).

1881. Pneumococcus is independently isolated by Pasteur in Paris and by Sternberg in the U.S.

1881. Koch publishes Zur Untersuchung von pathogenen Organismen (Berlin: Gerschel), on the study of pathogenic organisms.

1881. Ehrlich's eponymous reagent, a solution (stain) made from aniline dyes (introduced histologically by Weigert, his cousin) is widely used as the basis of a urine test for typhoid.

1882. Annus mirabilis for bacteriology. Tuberculosis: the disease was then responsible for almost a seventh of all deaths (CF 225). On 24 March, before the Physiological Society of Berlin, Koch announces that he has "found the cause of tuberculosis, which was due to a peculiar bacillus of a special shape" (op. cit., 226). Crucial to the lasting impression created by the news were the investigator's methodological rigour and certainty. Koch's important report, published as "Der Aetiologie der Tuberculose" in the Berliner klinische Wochenschrift (vol. 19, pp. 221-230), featured the new agar-agar culture medium. For this and related advances Koch would be awarded the Nobel Prize for Medicine in 1905.

1882. Phagocytosis. Elie (Ilya) Metchnikoff (1845-1916) formulates his principal theory of "phagocytosis" whereby macrophages (white blood cells) surround and engulf microbes, inflammation, or both.

1882. Franz Ziehl (1857-1926), a professor bacteriology at Lubeck, develops the carbol-fuchsin stain for visualizing the tubercle bacillus. In 1883, working Friedrich Neelsen (1854-1898), a professor of pathology at Rostock, Ziehl perfected the Ziehl-Neelsen acid-fast stain, which is still in use today. The original Ziehl stain was prepared from 1g of fuchsin and 5g of carbolic acid/phenol in a 10% v/v solution of alcohol in distilled water.

1882. Carl Friedlaender (1847-1887), a German pathologist and bacteriologist, isolates the pneumonia bacterium from the lungs of persons dying from the illness and controversially asserts a causative link. "Friedlaender's bacillus" is recommended by others, and new stains are employed between c.1883-87, including that of Gram.

1882. A supporter of Koch's postulates, Alexander Ogston (1844-1929) distinguishes the string-like Streptococci sp. from the clustered Staphylococcus sp., asserts them both as causative of disease, and notes golden-yellow growth in a culture of Staph. aureus. Whilst many of Ogston's contemporaries remain sceptical of his results, Lister encourages him.

1883. Inaugural publication of the Zeitschrift für Wissenschaftliche Mikroskopie und für Mikroskopische Technik, edited by Wilhelm Julius Behrens (Braunschweig: Harald Bruhn).

1883. Diphtheria. Edwin Klebs and Friedrich Loeffler independently discover the causative agent of diphtheria, then called "Klebs-Loeffler bacterium." The discovery is followed by a host of confirmatory studies, including those by Escherich, Roux and Yersin. The discovery leads to the antitoxin treatment of 1890 (see Behring).

1883. Max Joseph Pettenkofer (1818-1901), a chemist and hygienist, becomes editor of the Archiv für Hygiene, a position he will hold until 1894.

1883. A new outbreak of Asiatic cholera in India prompts the German Imperial Government to organise a medical mission to resolve the problem of causation. Koch is chosen to lead. Before long he is able to announce proven causative links between the newly isolated spiral organism or Spirillum - the Comma bacillus or Vibrio cholera asiaticae - with its constant presence and symptoms in live victims, and its constant presence in intestines of the deceased. Supportive studies were soon forthcoming from others associated with Koch, e.g., Loeffler, Hueppe, and Kitasato (CF 259-61). Koch was already theorising on the intestinal involvement of proteinaceous "toxalbumins" or active poisons produced by the cholera microbe (op. cit.: 275).

1884. While working with Carl Friedlaender in Berlin, the Danish bacteriologist Hans Christian Gram develops the Gram stain, composed of iodine and potassium iodide-arsenite treated with gentian violet. The Gram stain soon proves particularly useful for studying medically pertinent organisms, as it identifies them as either Gram-positive or Gram-negative.

1884. On Malta during an outbreak of undulating fever among the troops, Major-General Sir David Bruce succeeds in isolating the causative agent, a small, Gram-negative, rod-shaped coccobacillus, later named Brucella sp.

1884. Scarlet fever, "scarlatina." Friedrich Julius Rosenbach (1842-1923) isolates and names Streptococcus pyogenes, the infectious agent in "scarlet throat." Loeffler demonstrates that the streps are always present in the scarlatina patient's throat.

1884. Tetanus. Arthur Nicolaier (1862-1942), physician and assistant to bacteriologist and pioneer hygienist Carl Flugge (1847-1923) at Goettingen, isolates an anaerobic, Gram-positive, club-shaped bacillus that Flugge names Clostridium tetani.

1885. Rabies. Louis Pasteur and Émile Roux make their celebrated first application of a vaccine for "canine madness." They explain that the vaccine works by "cautious inoculation of micro-organisms in various degrees of attenuation" (CF 140). The work stems, however, from the mistaken hypothesis that the disease is bacterial in origin. Until 1896 and the pioneering bacteriophage work of Hankin, the terms virus, microbe, and bacterium were largely interchangeable and scarcely differentiated.

1885. Ludwig Brieger (1849-1919), a German physician and organic chemist specialising in the chemical group of ptomaines and bacterial food poisoning such as botulism, isolates cadaverine and putrescine (tetramethylenediamine).

1885. The physicians G. Sims Woodhead and A. W. Hare publish Pathological Mycology. An Enquiry into the Etiology of Infectious Diseases. Reviews attached by the publisher included the Lancet, which called it "essentially a laboratory hand-book"; the Medical Press, which noted disparagingly that "Bacillus culture is the humour of the age"; and the Birmingham Medical Review, which hedged all bets with the caveat "whatever may be the ultimate position of micro-organisms in pathology."

1885. E.E. Klein (1844-1925), a Croatian-born physician and researcher, isolates several types of bacteria, including the microbe Streptococcus pyogenes as the causal agent of scarlet fever. Klein tutored Ronald Ross (1857-1932), who microscopically detected the non-bacterial parasite of malaria in the intestine of the mosquito and was awarded the Nobel Prize for Medicine 1902.

1886. E.M. Crookshank publishes An Introduction to Practical Bacteriology. Based Upon the Methods of Koch (New York: J.H. Vaill).

1886. After two years in Naples during a cholera epidemic, the German-Austrian pediatrician and bacteriologist Theodor Escherich (1857-1911) publishes Die Darmbakterien des Sauglings (The Intestinal Bacteria of Infants). A specialist in faecal enterobacteria, he pioneered familiarity with the coliforms now named after him, Escherichia coli (E.coli).

1886. Theobald Smith (1859-1934) isolates the gram-negative bacillus responsible for enteric typhoid.

1886. William Halstead (1852-1922), a Professor of Surgery at Johns Hopkins University, establishes the first school of scientific surgery in the United States.

1887. Loeffler founds the journal Zentralblatt für Bakteriologie und Parasitik and publishes Geschichte zur Bakteriologie, Vol. I. The latter work was recommended by Bulloch (1938).

1887. Surgical masks come into wide use after bacteria-laden "Flugge droplets" are demonstrated as leaving the mouth even during quiet speech.

1887. Meningitis. Anton Weichselbaum (1845-1920) isolates the bacterium Diplococcus intracellularis meningitides from the cerebrospinal fluid of patients diagnosed as with bacterial meningitis. (The causative agent would be renamed Neisseria meningitides in 1901 by Albrecht & Ghon.)

c.1887. The Petri dish. Julius Richard Petri (1852-1921) invents the celebrated Petri dish, a lidded glass container specifically designed for the use of agar-agar in the culture, identification and study of micro-organisms. He describes his innovation in "Eine kleine Modification des Koch'schen Plattenverfahrens" (A small modification of Koch's plate-method), published in Centralblatt für Bakteriologie und Parasitenkunde 1 (1887): 279.

1887. Metchnikoff observes blood leukocytes approaching and surrounding certain bacteria, a process later known as "leukocyte killing," valuable in antiserum and acquired immunity studies. See Almoth Wright.

1887. The Pasteur Institute is founded in Paris. Collaborators of Pasteur include Émile Roux, who from 1889 would teach the world's first microbiology course at the Institute. Other early colleagues there included Émile Duclaux Charles Chamberland, Jacques-Joseph Grancher, and Elie Metchnikoff See also Alexandre Yersin.

c. 1889. Proof of the human aetiology of tetanus is given by Japanese bacteriologist Kitasato.

1889. Carl Fraenkel and Richard Pfeiffer publish Mikrophotographischer Atlas der Bakterienkunde (Berlin: August Hirschwald). Cf. Ricketts.

1889. Nicholas Senn (1844-1908) brings out Surgical Bacteriology (Philadelphia: Lea Brothers). A second edition follows in 1891. Senn was Professor of Surgery and Surgical Pathology at Rush Medical College in Chicago. Cf. George Sternberg.

1889. The Society of American Bacteriologists is founded.

1889-90. Sergei Nikolai Winogradsky (1856-1953), a soil bacteriologist, discovers the nitrogen-fixing bacteria Nitrosamonas sp., Nitrococcus sp., and Nitrobacter sp., which underlie the nitrate-nitrite and amino acid-protein cycles of plants.

c.1890. Émile Roux (1853-1933) works on an antitoxin to the diphtheria germ, parallel to the initiatives of Behring and Kitasato.

1890. Halstead at Johns Hopkins University Medical School introduces sterile operative procedures with the use of rubber gloves.

1890. Henry E. Roscoe and Joseph Lunt publish "Contributions to the Chemical Bacteriology of Sewage" in Proceedings of the Royal Society of London, Vol. 49.

1890. Behring discovers tetanus and diphtheria antitoxins, for which he is awarded the first Nobel Prize for Physiology and Medicine in 1901, though there is some controversy over his poor treatment of collaborator Ehrlich. See also Roux and Kitasato.

1890. Kitasato Shibasaburo (1852-1931) collaborates with Behring on working towards antitoxins for tetanus and diphtheria before returning, in 1891, to Japan, where he founds an institute for the study of infectious diseases.

1890. Albert Calmette (1863-1933), French physician and bacteriologist, returns to Paris from French West Africa after research on malaria, sleeping sickness, and other tropical maladies. See Guérin.

1890s. Richard F. Pfeiffer (1858-1945), a German physician and bacteriologist who worked for a number of years with Koch, introduces a typhoid vaccine. Cf. Almroth Wright.

1891. Koch becomes Director of the Institute for Infectious Diseases, Berlin. His colleagues there would include Paul Ehrlich and August von Wassermann.

1891. Koch invites Paul Ehrlich (1854-1915) to work at the Berlin Institute where, in 1896, he is given his own, specialised section for serum research.

1891. R. W. Philip publishes Koch's New Treatment of Tuberculosis (Edinburgh: Young J. Pentland). The book sells for 1 shilling or approximately 25 cents. Philip, an MD, worked at the Royal Infirmary Edinburgh & Victoria Dispensary for Consumption and Diseases of the Chest.

1891. The Seventh International Congress of Hygiene & Demography is held in London from August 10-17. The second volume of their Transactions, devoted to bacteriology, appears that year.

1891. Walter Migula (1863-1938), a Polish-German botanist and bacteriologist, discovers the gram-negative, flagellated-motile rod-like bacillus Pseudomonas sp, later renamed Pseudomonas pyocyaneas (aeruginosa), a dangerous hospital pathogen.

1891. Percy F. Frankland & Marshall Ward, "First Report to the Water Research Committee on the Present State of Knowledge Concerning the Bacteriology of Water..." Proceedings of the Royal Society of London, Vol. 51, p. 97.

1891. The third edition of An Encyclopedia of the Practice of Medicine Based on Bacteriology by J. Buchanan is published by R.R. Russell of New York.

1892. Pettenkofer tests on himself a dose of the dangerous Vibrio cholera provided by Koch.

1892. Bacillus influenza isolated by Pfeiffer. Originally known as "Pfeiffer's bacillus," and later as Haemophilus influenza, it was believed to be the cause of flu epidemics. The situation was shown to be otherwise following the influenza pandemic of 1918-19.

1892. Anton Weichselbaum publishes Grundrisse der pathologischen Histologie. An English translation, Elements of Pathological Histology (London: Longmans, Green & Co.), follows in 1895.

1892. Neisser continues his controversial studies of dermatology, sexually transmitted diseases, and the contemporary Prostituiertenproblem: "Pathologie des Ekzems" (eczema, from Greek = "ekzema"). Archiv für Dermatologie und Syphilis, Supplement: 116-161.

1892. The U.S. Army physician George M. Sternberg (1838-1915) takes charge of the quarantine station for receiving immigrants on the New York City dockside. He becomes U.S. Surgeon General the following year, in which he also publishes his major work, Textbook of Bacteriology (New York: William Wood). Cf. Walter Reed.

1892. Alexander C. Abbott (1860-1935) brings out The Principles of Bacteriology: A Practical Manual for Students and Physicians (Philadelphia: Lea Brothers). Abbott was a bacteriologist at the University of Pennsylvania where he was Professor of Hygiene and Director of the Laboratory of Hygiene.

1893. August Koehler (1866-1948), a German zoologist and microscopist, develops advanced "Koehler" illumination for standard microscopes of the day, publishing his work in Zeitschrift für wissenschaftliche Mikroskopie 10.4 (1893): 433-40. An English summary appears in the Journal of the Royal Microscopical Society in 1894.

1893. The first volume of the Journal of Pathology and Bacteriology is published. Both Virchow and Metchnikoff contribute to early issues.

1893. Samuel Leopold Schenk (1840-1902), a German bacteriologist working in Vienna, publishes Grundrisse der Bakteriologie für Aertze und Studierende (Vienna: Urban & Schwarzenberg). That same year, W. R. Dawson's English translation is published as Elements of Bacteriology for Practitioners and Students (London: Longmans, Green).

1893. Percy Frankland publishes "Bacteriology in its Relations to Chemical Science" in the Report of the British Association for the Advancement of Science.

1893. Georgy Gabrichevsky (n.d.), Russian bacteriologist, publishes Rukovodstvok klinicheskoj bacteriologii (St. Petersburg: Ricker), an illustrated manual of bacteriology for laboratory and clinical use. It is followed by a German translation by K. Gappina of the Dorpat Veterinary Institute.

1894. Hans Buchner (1850-1902), a German bacteriologist, succeeds Pettenkofer as Professor of Hygiene at Munich.

1894. Calmette researches a serum antitoxin for the plague bacillus of Alexandre Yersin (1863-1943), a Swiss-French physician and bacteriologist who worked with Pasteur and Roux in Paris.

1894. Yersin demonstrates the presence in rats of the the plague bacillus that Kitasato had isolated, thereby revealing how the disease is transmitted.

1894. Frederick G. Novy publishes Directions for Laboratory Work in Bacteriology (Ann Arbor: George Wahr).

c. 1895. Jules Jean Bordet (1870-1961) discovers the serum protein "alexine," now called "complement" and used in certain "complement-fixation" tests for bacteria such as syphilis (see Wassermann).

1895. Harold C. Ernst publishes "Bacteriology" in volume 4 of the Annual of the Universal Medical Sciences (Philadelphia: F. A. Davis).

1895. Volume 9 of the Annales de l'Institut Pasteur is published with contributions by Yersin, Metchnikoff, Calmette and Bordet. Yersin's paper was the second part of his "La peste bubonique" (with Calmette & Borrel).

1895. Dairy Bacteriology: A Short Manual, edited by E.V. Freudenreich and translated from the German, appears (London: Methuen).

1895. A report on "The New Treatment of Diphtheria" appears in Century Illustrated Magazine (Vol. XLIX, no. 3) in January. The report describes the new anti-toxin serum treatment. See Roux and Behring.

1896. Ferdinand Adolf Hueppe (1852-1938) publishes Naturwissenschaftliche Einführung in die Bakteriologie (Wiesbaden: C.W. Kreidel Verlag). An English translation by E.O. Jordan follows in 1899, titled Principles of Bacteriology.

1896. Yellow Fever. Walter Reed (1851-1902) demonstrates that yellow fever is not spread by drinking water from a local river, thus opening the way for a correct aetiology.

1896. Bacteriophage. Ernest Hanbury Hankin (1865-1939), who studied with Koch and with Pasteur, discovers the "bacteriophage," a small, non-bacterial organism.

1896. Max von Gruber (1853-1927) discovers, with his British pupil Herbert Durham (1866-1945), "specific serum agglutinins" reactive with bacteria for immunological-diagnostic purposes. This discovery is published in "Ueber active und passive Immunität gegen Cholera und Typhus, sowie ueber die bacteriologische Diagnose...", Wiener klinische Wochenschrift, 9: nos. 11 & 12. Gruber's earlier work was on the distinctions between the Vibrio of Asiatic cholera and other forms such as "Finkler-Prior" and "Koch's Vibrio" (the "Kommabacillen"). (Fraenkel gives a fuller discussion in CF, 259-284.)

1896. Georges-Fernand Widal (1862-1929), a French physician, researcher, and professor in the Department of Pathological Anatomy at the University of Paris, invents the Widal Test, a serum-specific antibody procedure used to diagnose enteric-undulating fever/typhoid fever (Salmonella typhi).

1897. Bacteriology is now an established field with many valuable applications based on empirical and reproducible methodologies. Notable work is done in the dairy industry, the meat industry, relevant segments of the veterinary industry, the wine and beer brewing industries, the oyster and shellfish industries, the medical-pathology and epidemiological professions, the nursing profession, soil and agriculture. Evidence of this consolidation may be found in appearance of two standard works: Essentials of Bacteriology. Being a Concise and Systematic Introduction to the Study of Micro-Organisms for the Use of Students and Practitioners (Philadelphia: W.B. Saunders) which went through six editions by 1908; and Applied Bacteriology, published as part of the "Saunders' Question Compends" Series, with a second edition in 1898.

1897. William Bulloch (1868-1941), a British bacteriologist later notable for his history of the science (Bulloch 1938), is appointed Lecturer in Bacteriology at the London Hospital, a position which in 1917 would become the Goldsmith's Professor of Bacteriology of the University of London.

1897. Robert Muir and James Ritchie publish Manual of Bacteriology (Edinburgh: Young J. Pentland). Their book goes through six editions by 1913, indicating the continual growth of the science over two decades.

1898. Charles Slater and Edmund Spitta. An Atlas of Bacteriology. Plates and photomicrographs by staff members, St. George's Hospital Medical School, London (London: Scientific Press).

c.1898. Dysentery. Shiga Kiyoshi (1871-1957), a Japanese physician and bacteriologist who, during a severe epidemic of dysentery in 1897-98, discovers the effective bacterium, subsequently named in his honor Shigella dysenteriae. The "shiga toxin" is produced by the microbe, a non spore-forming, non-motile rod-shaped gram-negative bacillus. Transmission is by contaminated water supplies and via dirty hands and unwashed produce.

1898. In the U.S., Sternberg and Major Walter Reed create the first Typhoid Fever Board, one of the type later known as "Walter Reed Boards." In the same year, Sternberg is made an honorary member of the Epidemiology Society of London.

Hueppe publishes Principles of Bacteriology, (Chicago: Open Court and London: Kegan, Paul, Trench & Trubner).

1899. William H. Park (1863-1939), a U.S. bacteriologist specializing in diphtheria who served as Director of laboratory at the Board of Health Division of Pathology, Bacteriology and Disinfection, New York City between 1893-1936, brings out a standard text, Bacteriology in Medicine and Surgery: A Practical Manual (Boston: Lea Brothers & Co.). It is followed by a British edition published in London by Henry Kimpton in 1900.

Late 1890s. Almroth Edward Wright (1861-1947) works on typhoid vaccine and the measurement of protective "opsonins" in the blood, citing the avoidable loss of life in the Second Boer War (1899-1901) to convince the government.

1900. Wright introduces a typhoid inoculation for the British troops in South Africa in the Second Boer War.

1900. Félix d'Hérelle (1873-1949) begins bacteriological work in Guatemala and Mexico.

1900. In Cuba Walter Reed demonstrates that the mosquito "Aedes aegypti” functions as transmission vector for yellow fever.

1901. Indicators of this growing field of study include the publication of H.W. Conn, Agricultural Bacteriology (Philadelphia: Blakiston's Son & Co.) and Frederick D. Chester, A Manual of Determinative Bacteriology (London: Macmillan).

1901. The Rockefeller Institute of Medical Research opens in New York. Simon Flexner (1863-1946) is appointed the Institute's first Medical Director. His bacteriological colleagues there included Theobald Smith and Noguchi Hideyo (1876-1928).

1901. With Rudolf Otto Neumann (1868-1952), Karl Bernhard Lehmann (1858-1940) publishes Atlas und Grundriss der Bakteriologie. An English translation by George H. Weaver, of Rush Medical College in Chicago, appears later the same year.

1902. The first volume of Pathogen Mikro-organismen by August von Wassermann (1866-1925) and W. Kolle (1868-1935) appears. Subsequent installments of this massive six-volume work appear to 1909.

1902. Carl Julius Salomonsen (1847-1924) establishes a Serum Institute in Copenhagen.

1903. Protozoan-caused disease. William Boog Leishman (1865-1926) confirms the causative microbe of kala-azar, also known as leishmaniasis, as Leishmania donovani, a trypanosome. He does this work with Charles Donovan (1863-1951), Calcutta-born of Irish parents, Professor of Physiology, Madras Medical College and Indian Government General Hospital. See Carlos Chagas and Ronald Ross (1857-1932) on other non-bacterial parasites.

1903. George M. Sternberg brings out Infection and Immunity with Special Reference to the Prevention of Infectious Diseases (New York & London: G. Putnam's Sons).

1903. Charles Nicolle (1866-1936) becomes director of the Pasteur Institute in Tunis where where he investigates body-lice as the transmission agent of epidemic typhus, work for which he will receive the Nobel Prize in 1928.

1904. Gaffky succeeds Koch as Director of the Berlin Institute for Infectious Diseases, a position Gaffky will hold until 1913.

1904. The Practical Medicine Series of Year Books (Chicago: The Year Book Publishers) includes bacteriology, pathology, and the latest advances.

1904. Frank Clowes and A.C. Houston bring out The Experimental Bacteriological Treatment of London London County Council, 1892-1903 (London: L.C.C.).

1905. Émile Roux becomes the new director of the Pasteur Institute in Paris, a position he will hold until 1918.

1905. M. Klopstock and A. Kowarsky publish Praktikum der klinischen chemisch-mikroskopischen und bakteriologischen Untersuchungsmethoden. It subsequently appears in English translation as A Manual of Clinical Chemistry, Microscopy and Bacteriology, (London: Rebman Ltd.).

1905. Syphilis. Fritz Schaudinn (1871-1906), with the assistance of dermatologist Erich Hoffmann (1868-1959), discovers the microbe responsible for syphilis. Spirochaeta pallida, now known as Treponema pallidum, is a very fine organism that may take a Gram stain and be G-negative, and requires dark field illumination with the light microscope. Special stains were later developed, as were serological tests. See Wassermann.

1905. The International Tuberculosis Conference provides the forum for Behring to announce a new vaccine substance, obtained from "the virus of tuberculosis," for bovine rather than human use. His publications on serum therapy dated from at least the early 1890s (see "Die Blutserumtherapie" of 1892 and "Die Geschichte der Diphtherie" of 1893), though he was also involved in a conflict with Ehrlich over denial of recognition and remuneration to the latter for their joint collaboration on the new diphtheria anti-serum.

1906. Jean-Marie Camille Guérin (1872-1961). French veterinarian and bacteriologist who joined Calmette at the Institute Pasteur-Lille in 1897. The two became celebrated for their anti-TB serum based on Guérin's demonstration that bovine Mycobacterium bovis exerts an immunological-protective effect in experimental rabbits. The result was their BCG (Bacillus-Calmette-Guérin) vaccine against tuberculosis, which has been improved continually over the following two decades and, indeed, to the present day.

1906. Whooping cough (pertussis). Bordet, working with Octave Gengou (1875-1957), isolates the causative agent of whooping cough, "Haemophilus pertussis," later renamed and reclassified Bordetella pertussis.

1906. Syphilis. August Paul von Wassermann (1866-1925), German bacteriologist and hygienist who worked with Koch in the 1890s, becomes Director of Experimental Therapy at the Koch Institute in Berlin and develops the famous "Wassermann Test" for syphilis, employing a blood-antibody reaction based on Bordet's work on alexine (complement) fixation. See also the earlier work of Schaudinn.

1906. Carl Fraenkel pursues research on typhus and Blutpraparaten (blood-preparations).

1907. Bordet becomes Professor of Bacteriology, University Libre de Bruxelles.

1907. Charles Alphonse Laveran (1845-1922) receives the Nobel Prize for Medicine or Physiology for his discovery of the Plasmodium responsible for malaria and the Trypanosome responsible for African sleeping sickness.

1907. Indicators of the growing influence of bacteriology include the publication of Edward B. Voorhees and Jacob G. Lipman's A Review of Investigations in Soil Bacteriology (Washington D.C.: U.S. Dept. of Agriculture) and the appearance of the 4th revised edition of Muir & Ritchie's Manual of Bacteriology, published originally in 1897. A sixth edition appears in 1913. For more on Robert Muir, see Mackie.

1907. S. Maria Elliott (1854-1942) publishes Household Bacteriology. The Library of Home Economics, Vol. II (Chicago: American School of Home Economics). The volume, which treats topics of dust, flies, yeasts and moulds, sanitation and food hygiene, becomes a standard text for Simmons College in Boston, where Elliott is a professor of home economics.

1908. Guérin and Calmette begin a thirteen-year process of attenuation of the microbe that causes tuberculosis, undertaking a series of some 239 isolations and re-cultures in order to produce a viable vaccine in 1921.

1908-09. Bacteriology continues to gain ground as a field of study; indicators include the publication of Samuel Cate Prescott and Charles Winslow, Elements of Water Bacteriology; E.R. Stitt, Practical Bacteriology, Blood Work and Animal Parasitology (Philadelphia: Blakiston's Son & Co.), which included bacteriological keys and clinical notes; and Edwin O. Jordan, A Text-Book of General Bacteriology (Philadelphia: W.B. Saunders & Co.), with a second edition in 1910; S. Jeremiah, Normal Histology and Microscopical Anatomy (New York: D. Appleton & Co.); and A. Dieudonne and C.F. Bolduan, eds. Bacterial Food Poisoning. A Concise Exposition of the Etiology, Bacteriology, Pathology, Symptomatology, Prophylaxis and Treatment of So-Called Ptomaine Poisoning. (New York: Treat & Co.). See also Brieger.

1908. Laveran, while working at the Pasteur Institute in Paris, uses his Nobel Prize money to establish a laboratory of tropical medicine there and hires Roux and Metchnikoff. Laveran founds the Société de Pathologie Exotique in the same year.

1908. Alexander Fleming (1881-1955) is honored by St. Mary's Hospital Medical School in Paddington, London with a Gold Medal in Bacteriology. During this early period he works at St. Mary's as assistant to Almroth Wright and as Lecturer to the hospital. His epochal re-discovery of the anti-microbial value of penicillin is still some twenty years in the future.

1909. Chagas disease. Carlos Chagas (1879-1934) discovers a new tropical disease afflicting railroad workers near the Amazonian city of Belem (now Belem, Estado de Para). Chagas showed the insect vector, the flagellate protozoan in its intestines, and the transmission to test animals. He named the parasite "Trypanosoma cruzi" in honor of his friend Oswaldo Cruz (1872-1917). The new disease is known as "Chagas disease."

1909. Salvarsan. Paul Ehrlich, working in Berlin, initiates the modern phase of chemotherapy with his discovery after many empirical trials of the arsphenamine-arsenical compound "Salvarsan."

1909. E.J. McWeeney. Observations on the Micro-Organisms of the Gaertner Group ("Meat-poisoning bacilli").... Report of the British Association for the Advancement of Science 79th Meeting. Winnipeg.

1910. Rocky Mountain Spotted Fever. Howard Taylor Ricketts (1871-1910), an American pathologist, demonstrates transmission of spotted fever by insect vector (the tick).

1910. Emily Stoney publishes Bacteriological and Surgical Technic for Nurses (Philadelphia: W.B. Saunders & Co.). The work goes through four editions by 1916.

1911-12. William Boog Leishman becomes President of the Royal Society of Tropical Medicine & Hygiene.

1912. Albert Schneider, Pharmaceutical Bacteriology with Special Reference to Disinfection and Sterilization (Philadelphia: Blakiston's Son & Co.).

1912. Clemesha William Wesley, The Bacteriology of Surface Waters in the Tropics (Calcutta: Thacker, Spink & Co. London: E. and F.N. Spon Ltd.).

1912. Almroth Wright publishes Technique of the Teat and Capillary Action, and its Application in Medicine and Bacteriology (London: Constable & Co.).

1913. Neisser publishes Monograph on Syphilis and Salvarsan (Berlin: Springer Verlag). Neisser's new therapy was based on the novel chemotherapy of Ehrlich 1909; Erlich and Neisser had known each other since their schooldays.

1914-1918. The Great European War. Many of the younger bacteriologists who trained during the Victorian period served in aid stations and field hospitals close to the fighting. See Fleming, Mackie, Dakin, among others. During these years, Almroth Wright organises a research laboratory at British Hospital No. 13 in Boulogne, France, to produce vaccines for Allied troops fighting in trenches.

1914. Lester A. Round publishes Contributions to the Bacteriology of the Oyster: Results of Experiments and Observations made and Authorized by the Commission of Shell Fisheries of the State of Rhode Island (Providence: E.L. Freeman).

1914. J. MacNeal Ward and H.E. Williams publish Pathogenic Micro-Organisms: A Text-book of Microbiology for Physicians and Students of Medicine (Philadelphia: Blakiston's Son & Co.).

1914. Thomas Jones Mackie (1888-1955), a Scottish bacteriologist associated with the University of Glasgow and the Glasgow Western Infirmary, joins the Army Medical Corps. After serving in the Middle East, he is placed in command of the Central Bacteriological Laboratory in Alexandria, Egypt.

1915. Charles-Edward Amory Winslow (1877-1957), an American bacteriologist-hygienist, founds the Yale Dept. of Public Health as part of the Yale Medical School.

1916. Founding of the Journal of Bacteriology, with Editor-in-Chief Winslow. It was the organ of the American Society of Bacteriologists, founded in 1899, with Winslow as the then-youngest founder-member.

1916. Carrel-Dakin wound-treatment solution. Henry Drysdale Dakin (1880-1952) and Alexis Carrel (1874-1944) devises a low-tech means of preventing and treating gas gangrene by killing the bacilli that cause it. Their wound treatment solution, which consisted of 0.5% sodium hypochlorite bleach with 4% boric acid in water, was used in surgery and splashed around liberally as a disinfectant.

1917. Virus and bacterium. Félix d'Hérelle re-discovers the "bacteriophage" of Hankin, which could pass through the finest porcelain filters, in September 1917 while working on the production of vaccines for the Allied armies. Much smaller than the bacteria they preyed upon, these true virus particles heralded a new era in microbiological science. D'Hérelle worked to produce a "phage therapy" for diphtheria, dysentery and cholera, with some success post-war across Europe.

Brief Bibliography and Short-Title Used

CF - Carl Fraenkel. 1887. Grundriss der Bakterienkunde. English trans. by J.H. Linsley MD, Professor of Pathology and Bacteriology, Medical Dept. of the University of Vermont. Text-Book of Bacteriology, pp. 376 from 3rd German edn. Edinburgh: Young J. Pentland.

Anderson, T. "Robert Remak and the multi-nucleated cell: eliminating a barrier to the acceptance of cell-division." Bulletin of the History of Medicine 60.4 (1986): 523-43.

Bulloch, William. The History of Bacteriology. University of London Heath Clark Lectures for 1936. Oxford: Oxford University Press, 1938.

de Kruif, Paul. Microbe Hunters. New York: Harcourt Brace & Co., 1926.

Flaumenhaft, E. "Evolution of America's pioneer bacteriologist: George M. Sternberg's formative years." Military Medicine 158.7 (1993): 448-57.

Geison, Gerald. The Private Science of Louis Pasteur. Princeton: Princeton University Press, 1995.

Loeffler, Friedrich. Vorlesungen uber die Geschichtliche Entwickelung der Lehre von den Bacterien. 1887. Noted by Bulloch (1938). No English translation is available of this early history of bacteriology.

Herter, Christian A. The Influence of Pasteur on Medical Science: An Address to the Medical School of Johns Hopkins University. New York: Dodd, Mead & Co, 1904.

McGrew, Roderick. Encyclopaedia of Medical History. New York: McGraw-Hill, 1985. pp. 25-30.

Nicolle, J. Louis Pasteur. A Master of Scientific Enquiry. London: Hutchinson, 1971.

Riecke, Carl Friedrich. Die Reform der Lehre von den Contagionen, Epidemien und Epizootien. Quedlinburg: Verlag von H.C. Huch, 1854.

Vogelsang, Thomas. International Journal of Leprosy, 1963 & 1964.

Weiss, Emilio and S. Bernard. "The life and career of Howard Taylor Ricketts." Reviews of Infectious Diseases 13 (1991): 1241-2. University of Chicago, 27 December 1990.

Wrench, G.T. Lord Lister. His Life and Work. New York City: Frederick Stokes, 1910.

Created 25 January 2017

Last modified 24 February 2023