Dark field method of diagnosis for presence of T. pallidum.

Levaditi’s method of staining T. pallidum.

The “Wassermann reaction”, a specific diagnostic blood test for syphilis, and a modification of the complement-fixation reaction of Bordet and Gengou. With A. Neisser and C. Bruck.

After many experiments on the action of synthetic drugs upon spirochetal diseases, Ehrlich and Hata in 1909 discovered Arsphenamine (Salvarsan, "the arsenic that saves", also known as “606”), an effective treatment for syphilis and trypanosomiasis. Arsphenamine was the first modern chemotherapeutic agent.

Manufactured by the German chemical company Hoechst, Salvarsan quickly became the most widely prescribed drug in the world. It was the first blockbuster drug, and remained the most effective drug for syphilis until penicillin became available in the 1940s. Digital facsimile of the German edition from the Internet Archive at this link. English translation, New York, 1912.

Ehrlich's discovery became the subject of the 1940 biographical film entitled Dr. Ehrlich's Magic Bullet. The film was released by Warner Bros., with some controversy over the subject of syphilis in a major studio release. 

Pure culture of T. pallidum first obtained. Digital facsimile from digitalcommon.oshu.edu at this link.

Introduction of neoarsphenamine (neosalvarsan).

Lange’s colloidal gold test for the diagnosis of cerebrospinal syphilis. See also Berl. klin. Wschr., 1912, 49, 897-901.

Meinicke diagnostic reaction.

Sachs–Georgi diagnostic reaction.

Weichardt’s reagent.

Warthin and Starry’s method.

Introduction of sodium-potassium bismuth tartrate in the treatment of syphilis.

Kahn test.

Kolmer test.

Clinical introduction of bismarsen, synthesized by G. W. Raiziss in 1924.

Eagle flocculation test.

Introduction of mapharsen.

Clinical use of mapharsen. With R. L. McIntosh, L. M. Wieder, H. R. Foerster, and G. A. Cooper.

Cardiolipin antigen for serological diagnosis of syphilis. For isolation and purification see J. biol. Chem., 1942, 143, 247-56.

Mahoney and colleagues introduced penicillin in treatment of syphilis. This was the report of the first four cases of patients with early stages of the disease. Digital facsimile of the version published in the the American Journal of Public Health from PubMedCentral at this link.

See John Parascandola, "John Mahoney and the introduction of penicillin to treat syphilis," Pharmacy in history, 43 (2001) 3-13.

V. D. Research Laboratory test (Harris test). With A. A. Rosenberg and L. M. Riedel.

Nelson’s treponemal immobilization test.

See also H. Reiter, Brit. J. vener. Dis., 1960, 36, 18-20.

Fluorescent treponemal antibody test. With V. H. Falcone and A. Harris.

Absorbed fluorescent treponemal antibody (FTA-ABS) test. With W. E. Deacon and P. E. Meyer.  The text is available from the NLM PubMedCentral at this link.

Treponemal hemagglutination (TPHA) test.

Gives texts of German tracts on syphilis published between 1495 and 1510.

French translation, 1847; English translation as The plague of lust, being a history of venereal disease in classical antiquity, and including: Detailed investigations into the cult of Venus, and phallic worship, brothels, the nousos thelēia (Femine disease) of the Scythians, Paederastia, and sexual perversions amongst the ancients, as contributions towards the exact interpretation of their writings. Translated from the Sixth (unabridged) German edition by An Oxford M.A. 2 vols. (Paris: Charles Carrington, 1901). Digital facsimile of the 1839 edition from the Hathi Trust at this link; of the 1901 English translation at this link.

Bloch was a chief modern supporter of the theory of the Columbian origin of syphilis.

Sudhoff believed in the pre-Columbian existence of syphilis.

Forms Heft 5 of K. Sudhoff & G. Sticker: Zur historischen Biologie der Krankheitserreger.

Gives, in an appendix, a list of writers on syphilis from 1495 to 1829.  Digital facsimile from wellcomecollection.org at this link.

Forms tome I of Traité de la syphilis, ed. by E. Jeanselme and E. Shulmann.

A very thorough history of the discovery of the Wasserman reaction, and its acceptance by the scientific community. English translation: Genesis and development of a scientific fact, Chicago, Univ. of Chicago Press, 1979.

Aretaeus left many fine descriptions of disease; in fact Garrison ranks him second only to Hippocrates in this respect. In the printed editions of this bibliography, before the present online version, the Adams edition was cited no less than 12 times for individual diseases, plus its first citation in "Collected Works" (No. 22.) This number of citations is, of course, greater than any other specific work by any other author, though the number of citations may be a reflection of idiosyncracies of the compilers rather than a proportionate measure of the significance of Aretaeus in the history of medicine. The citations are as follows:

3162. On angina, or quinsey. In his Extant works, ed. F. Adams, 249-52, 404-07.

3163. On pleurisy. In his Extant works, ed. F. Adams, 255-58, 410-16.

2433. On elephas, or elephantiasis. In his Extant works, ed. by F. Adams, 366-73, 494-98. Classic description of “elephantiasis Aretaei”, nodous leprosy.

5046. On ulcerations about the tonsils. In hiis Extant works, ed. F. Adams, 253-55. Aretaeus’s description of ulcerations about the tonsils, which he called “ulcera Syrica”, clearly referred to diphtheria, of which it was the first unmistakable description. For his treatment of the disease, see pp. 409-10 of the same work.

5089. On dysentery. In his Extant works, ed. F. Adams. 353-57. Prior to Lösch’s discovery of E. histolytica, all forms of dysentery were differentiated only on clinical grounds.

4915. Extant works. Ed. F. Adams. Aretaeus wrote important accounts of melancholy (298-300, 473-78) and madness (301-04).

5146. On tetanus. In his Extant works, ed. F. Adams,  246-49, 400-04. Aretaeus left a full account of tetanus.

4484,  On arthritis and sciatica. In his Extant works, ed. by F. Adams,  362-65, 492-93,

3612. On jaundice, or icterus. In his Extant works, ed F. Adams, 324-28.

4510. On paralysis. In his Extant works, ed. F. Adams.

4808. On epilepsy, in his Extant works, ed F. Adams,  243, 296, 399, 468. Aretaeus was well acquainted with hemi-epilepsy from local injury in the opposite half of the brain; partly from this knowledge he formulated the “decussation in the form of the letter X” of the motor path. He first described epilepsy resulting from a depressed fracture of the skull. In his excellent description he made the first mention of the aura.

3925. On diabetes.In his Extant works, ed. F. Adams. 338-40, 485-86. The first accurate account of diabetes, to which Aretaeus gave its present name; he insisted on the part which thirst plays in the symptomatology. 

According to the Wikipedia article on Headache, Aretaeus also provied the first recorded classification system for headaches: "He made a distinction between three different types of headache: i) cephalalgia, by which he indicates a shortlasting, mild headache; ii) cephalea, referring to a chronic type of headache; and iii) heterocrania, a paroxysmal headache on one side of the head." 

Digital facsimile of Adams's Greek and Latin edition from the Internet Archive at this link.

First modern description of leprosy (“Danielssen-Boeck disease’’). Danielssen, physician to the leprosy hospital at Bergen, was the founder of scientific leprology. The extremely rare Atlas  consists of 24 plates and two pages of text. French translation, Paris, J. B. Baillière, 1848; the atlas was also reproduced in French, Rio de Janeiro, in 1946.

Chaulmoogra oil was first introduced into Western medicine by Mouat, having been used for many centuries previously by the Chinese

Hansen discovered the leprosy bacillus on 28 February 1873. He had been stimulated by the previous work of Danielssen and Boeck, and his own demonstration of the leprosy bacillus is one of the earliest observations of pathogenic bacteria. For an English translation of the paper see Brit. for. med. -chir. Rev., 1875, 55, 459-89.

Neisser obtained leprosy tissue from Hansen and, using aniline dyes for staining Myco. leprae, was able to demonstrate it more convincingly than Hansen.

Murine leprosy described.

Hydnocarpus wightiana or Chaulmoogra is a tree in the Achariaceae family. The oil from seeds of Hydnocarpus wightiana or Chaulmoogra, a tree in the Achariaceae family, was widely used in Indian medicine and Chinese traditional medicine for the treatment of leprosy and other skin diseases. Digital facsimile from the Internet Archive at this link.

Rost cultivated the leprosy bacillus, and he prepared leprolin, formerly used in treating leprosy.

Unna was among the first to maintain that the lymphatics were involved in leprosy and that it was curable.

Mitsuda (lepromin) reaction. English translation by the author in Int. J. Leprosy, 1953, 21, 347-58.

The scraped-incision slit-skin method for bacterial examination in leprosy.

G. A. H. Buttle, T. Dewing, G. E. Foster, W. H. Gray, S. Smith, and D. Stephenson discovered the potency of dapsone (DDS).

Promin (sodium glucosulphone) introduced in the treatment of leprosy. With R. C. Pogge, F. A. Johansen, J. F. Dinan, B. M. Prejean, and C. G. Eccles.

Muir found diasone (a sulphone) valuable in the treatment of leprosy.

Clinical use of solapsone (sulphetrone).

Introduction of diphenylthiourea (thiambutosine) therapy.

Ditophal (Etisul) in leprosy.

Transmission of leprosy to animals. See also J. exp. Med., 1960, 112, 445.

With J. M. H. Pearson and M. F. R. Waters.

Supplements 1-5, 1952-62.

Tyson gave one of the first descriptions of the anatomy of Ascaris lumbricoides.

Redi was among the first of the parasitologists. He demonstrated the reproductive organs of Ascaris lumbricoides and also ascaris eggs. The results of his experiments appear in the above work, which also records his study and description of 108 different species.

The first medical parasitology text– an exhaustive study of the parasites of man, the diseases associated with them and their treatment. Andry’s views were often ahead of his time. Unlike most of his contemporaries, he did not believe in the spontaneous generation of parasites but clearly stated that their seeds entered the body from outside sources and that some foods were particularly liable to contain them. English translation, London, 1701.

A system of helminthology. Rudolphi gave the name “echinococcus” to the common vesicular hydatid, describing three species. Digital facsimile from Biodiversity Heritage Library at this link .

Kuchenmeister conducted research on tapeworms, trichinosis, and other parasites and wrote about it several works. In 1852, his theory that bladder-worms are juvenile tapeworms gained the attention of the medical profession. Digital facsimile from the Hathi Trust at this link.

Cobbold was the most distinguished helminthologist of his time. He named Filaria bancrofti, Bilharzia haematobia, and several other parasites. He was a friend of Manson, several of whose papers he communicated to the Linnean Society and the Quekett Microscopical Club.

Includes the first complete and accurate account of the life history and morphology of Taenia echinococcus. Leuckart proved the relationship between hydatid cysts and minute tape-worms in dogs. English translation, Edinburgh, 1886. Digital facsimile of the German edition from Google Books at this link; facsimile of the English translation at this link.

A collection of several papers written by Manson.

Digital facsimile from the Internet Archive at this link.

In vol. 46 of Smithsonian Miscellaneous Collections. Leidy was called the greatest descriptive naturalist in mid-19th century America.

Wenyon was one of the world’s foremost authorities on medical protozoology.

Includes (De febribus, cap. X, XIV) first description of epidemic typhoid. English translation in his Practice of physick, 1684, Treatise II, 83-98, 1111-18.

Contains the earliest suggestion that fermentation is an intestinal or internal motion of particles; the analogy between putrefaction and fermentation is also noted.

Records discovery of bacteria in the mouth, with the first illustrations of the basic types – what were much later called cocci (round or oval), bacilli (rod-shaped) and spiriillum (spiral) forms. Although Leeuwenhoek had observed bacteria earlier, calling them animalcules, this paper is usually considered the first memoir on what were later called bacteria. At this early date the concept of microbiome did not yet exist; however, this paper also marks the beginning of our understanding of how parts of the human body are normally populated by bacteria. Digital facsimile from the Royal Society at this link.

Gleichen was probably the first to attempt to stain bacteria; he used carmine and indigo.

Müller was the first to attempt a systematic classification of infusoria. He published several papers on the subject, the best being the above posthumous work. Muller described 8 species of the genus Vibrio (included in Infusoria).

Fabbroni was the first to promote modern ideas on the nature of fermentation. He showed that air was not considered necessary for fermentation to take place; he was first to regard the ferment as an albumenoid substance. Pasteur considered Fabbroni’s work the beginning of modern ideas on the subject. Fabbroni’s theory of the fermentation of wine was influential throughout the 19th century. Several of the terms used by him are in use today.

The first workable process for canning foods. In 1795 Appert began developing the process under Napoleon’s auspices as a way to maintain food on military expeditions. For strategic reasons he was not allowed to publish the secret method until 1810. Appert’s method was strictly empirical. Pasteur eventually discovered a scientific explanation for the process and refined its operation. See Nos. 2479 & 2480. Digital facsimile of Appert's work from BnF Gallica at this link. Appert's work was translated into English as The art of preserving all kinds of animal and vegetable substances for several years (London, 1811).

Botulism first described. Kerner published an expanded study as Neue Beobachtungen über die in Würtemberg so häufig vorfallenden tödtlichen Vergiftung durch den Genuss geräuchter Würstem, Tübingen, 1820. He published his most extensive report as Das Fettgift oder Die Fettsäure und ihre Wirkungen auf den thierischen Organismus, ein Beitrag zur Untersuchung des in Würsten giftig wirkenden Stoffes (1822). This monograph "reviewed 155 cases of poisoned patients and precisely described the autonomic dysfunctions: “The tear fluid disappears, the gullet becomes a dead and motionless tube; in all mucous cavities of the human machine the secretion of the normal mucus stands still, from the largest, the stomach, to the tear duct and the excretory ducts of the lingual glands. No saliva is secreted. No drop of wetness is felt in the mouth…”. (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)78793-6/fulltext).

In this monumental work in folio format Ehrenberg extended Otto Friedrich Müller’s bacteriological classification. Like Müller, he made no distinction between protozoa and bacteria, classing them both as infusoria. His classification included Bacterium, which he described and named in 1828, and published in 1830, Vibrio, Spirillum and Spirochaeta. The fine hand-colored plates in this book were drawn by Ehrenberg himself. Includes (p. 80) first description of B. subtilis.

Ehrenberg's book was translated into French with the atlas in reduced  8vo format and condensed to 8 uncolored plates, as Traité pratique du microscope, et de son emploi dans l'étude des corps organisés par le docteur L. Mandl; suivi de Recherches sur l'organisation des animaux infusoires par D.-C.-G. Ehrenberg. Accompagné de quatorze planches. (Paris: J.-B. Baillière, 1839). Digital facsimile of the 1839 translation from Biodiversity Heritage Library at this link.

Further modification of and improvements in the classification of bacteria.

First description of Sarcina ventriculi, discovered by Goodsir.

First demonstration of the connection between a specific fermentation and the activity of a specific living micro-organism. This paper is often considered the beginning of bacteriology as a modern science. The above work is a very much abridged “Extrait par l’auteur” of the complete text of Pasteur’s full paper which underwent roughly simultaneous publication in Mémoires de la Société des Sciences, de l’Agriculture et des Arts de Lille, 2e sér., 1858, 5, 13-26, and in Ann. de Chim. et de Phys., 3e sér., 1858, 52, 408-18.

This and the preceding entry mark Pasteur’s commencement of the study of fermentation. This paper described Pasteur’s method of cultivating micro-organisms in a medium free of organic nitrogen to produce fermentations. The method was absolutely fundamental to his work, but not developed for his initial paper on lactic fermentation. He found that the conversion of sugar to lactic acid in fermentation is due to small corpuscles, isolated or grouped.

In these easily reproducible experiments, prefaced by an important historical introduction, Pasteur demonstrated beyond dispute that fermentation is caused by the action of minute living organisms, and that if these are excluded or killed fermentation does not occur. The heating process which Pasteur recommended for sterilization was the earliest form of “pasteurization”. The above paper marks the downfall of the theory of spontaneous generation. Pasteur’s researches on fermentation led him to the discovery of the bacteria and yeasts and hence to the germ theory of disease; from this all modern bacteriology and immunology have developed.

The discovery of strict anaerobiosis, important for general biology since it shows that oxygen gas is not a requisite for life.

Pasteur confirmed the fact, established by Schwann (No. 674) that putrefaction was a biological process.

Pasteur was the first to differentiate between aerobic and anaerobic organisms. (See also Nos. 2476-77.)

Although Pasteur’s method of preserving wine by partial heat sterilization (“pasteurization”) turned out to be a revival of Appert’s invention (No. 2467.1), Pasteur did rescue the method from oblivion and established on the basis of rigorous scientific experiments what had been only a poorly tested and entirely empirical technique.

Pasteur proved that a microorganism was essential to acetification and developed a patented method which greatly increased the efficiency of production.

This work saved the French silk industry, which had been crippled by the disease pébrine. After three years of research on the problem, Pasteur was able to show that the disease known as pébrine was caused by a parasite, and that the disease known as flacherie, which authorities had thought to be a manifestation of pébrine, was in reality a bacterial disease with its own character and etiology. He developed a screening method, still used today, that employs systematic microscopic examination to separate infected silkworm eggs from healthy ones.

Weigert was the first to stain bacteria. He introduced many of the best staining methods in use today. Weigert discovered bacteria in hemorrhagic smallpox. In the same paper is described how carmine will color cocci.

Cohn’s morphological classification of bacteria. He founded the Beiträge.

Isolation of Bacterium lactis, the specific micro-organism responsible for the lactic acid fermentation of milk.

Pasteur resumed his studies on fermentation in 1876, and in this book took into account the developments in this field since his previous publications on the subject. He described a new and perfected method of preparing pure yeast and acknowledged that a limited quantity of oxygen was important for brewing. Digital facsimile from the Internet Archive at this link. English translation as Studies on fermentation. The diseases of beer, their causes and the means of preventing them.... A translation, made with the author's sanction (London, 1879). Digital facsimile of the English translation from the Biodiversity Heritage Library at this link.

In this paper Weigert showed that methyl violet will reveal cocci in tissues.

Ehrlich’s first paper on the staining of specific granulation in white blood corpuscles by means of aniline dyes. His work immensely affected subsequent technical methods of staining.

Koch greatly improved staining methods; he laid the foundations of the technical procedures employed in bacteriology today. In the above paper he described his method of slide preparation, making films of bacteria on cover-slips and fixing them gently by heat, his methods of staining, and preserving the specimens. He also gave details of his method of photographing bacteria, and reproduced the first photomicrographs of bacteria. In some of his reproductions of photomicrographs the cilia are clearly perceptible.

Lister was the first to obtain a pure culture of a bacterium (Bact. lactis).  Lister first presented the results of this research in an address to the Royal Society on December 18, 1877. Because of its historic significance the text of the lecture was almost immediately published in Lancet,II, 918-921 in the issue of December 22, 1877. His full report in the Transactions of the Pathological Society of London appeared significantly later, in 1878. In the lecture Lister actually demonstrated before his audience how to obtain a "pure culture" of an organism.
(Thanks to Juan Weiss for this reference and its interpretation.)

"Joseph Lister's goal was to show that a pure culture of Bacterium lactis, normally present in milk, uniquely caused the lactic acid fermentation of milk. To demonstrate this fact he devised a procedure to obtain a pure clonal population of B. lactis, a result that had not previously been achieved for any microorganism. Lister equated the process of fermentation with infectious disease and used this bacterium as a model organism, demonstrating its role in fermentation; from this result he made the inductive inference that infectious diseases of humans are the result of the growth of specific, microscopic, living organisms in the human host.... By demonstrating that a microscopic living entity smaller than a yeast cell could cause fermentation, he was able to argue ‘that other organisms may exist … smaller than the B. lactis’, and not readily visible in diseased human tissues, could be the cause of infectious disease in humans.³ This paper was a landmark for two reasons. It was the first example of the use of a bacterium as a model organism and also for the invention of a procedure, now characterized as the limiting dilution method, for isolating a specific bacterium in a pure form, providing a first case of bacterial cloning.^{4 (Santer, "Joseph Lister: first use of a bacterium as a 'model organism' to illustrate the cause of infectious disease of humans," Notes and Records of the Royal Society, 64, 2009) .}

Discovery of Vibrion septique (Cl. septicum), the first pathogenic anerobe to be found. Pasteur and Joubert were probably the first to realize the practical implications of antibiosis. They noted the antagonism between Bacillus anthracis and other bacteria in cultures.

See No. 2495.

Translated into English by George M. Sternberg as The bacteria (Boston, 1880). Sternberg illustrated the American edition with 5 heliotype reproductions of his own photomicrographs.

In this study of furunculosis (“boils”) and osteomyelitis Pasteur left the first recognizable descriptions of staphylococcus and streptococcus. The term streptococcus had been coined by Billroth in 1874; however, Pasteur did not use it here. Ogston (see No.2494) named staphylococcus in 1881.

Introduction of methylene blue in bacteriological staining.

Ogston showed that micrococci are constantly present in acute and chronic abscesses. He discovered Staphylococcus aureus. Ogston named staphylococcus in his paper, "Micrococcus poisoning," J. Anat. Physiol., 1882, 16, 526-6; & 1883, 17, 24-58.

Tyndall interested himself in atmospheric germs and dust. His experiments on sterilization by heat led him to the discovery in 1877 of fractional sterilization (Tyndallization). His work on the subject is included in the above book, in which he also described the bactericidal effects of moulds. The researches of Tyndall, even more than those of Pasteur, dealt the final blow to the doctrine of spontaneous generation; they were fundamental for the progress of bacteriology. See No. 1932.

Koch’s description of his methods of growing bacterial cultures in gelatine solutions, making films of bacteria on cover slips and fixing them by gentle heat, and staining slides differentially by aniline. These methods are the bases on which bacteriology largely rests.

Discovery of Strep pyogenes, infectious agent of scarlet fever and other streptococcal illnesses. Fehleisen cultured it from perierysipelas lesions on humans. English translation, 1886.

Isolation of Pseudomonas aeruginosa (Ps. pyocyanea).

Isolation of Pasteurella pseudotuberculosis.

Chamberland filter, an unglazed porcelain bar with pores smaller than bacteria, enabled the earliest distinction between viruses and bacteria and led in 1898 to the re-introduction of the Latin word "virus" with the infectious agent now named tobacco mosaic virus.

Gram’s method of staining bacteria (Gram stain). While not all bacteria may be definitively classified in this way, it is almost always the first step in the preliminary identification of a bacterial organism.