Ludwig Sigesmund Albert Neisser and insights into etiology and pathophysiology of gonorrhea at Creds time

Ludwig Sigesmund Albert Neisser (1855-1916) was a German physician and bacteriologist [25-32]. He was a school classmate of Paul Ehrlich (1854-1915) in Breslau - former Germany - and studied medicine mainly in Breslau thereafter. Consecutively, he started specializing in dermatology, although he primarily intended to specialize in internal medicine but could not get an appointment as assistant in Breslau. Apart from working on echinococcosis (PhD thesis), leprosy and syphilis, he was the person who discovered the "Micrococcus" as the causative pathogen of gonorrhea.

As a basis for this discovery, the botanist Ferdinand Cohn (1828-1898) taught Neisser Robert Koch's (1843-1910) smear test for the microscopic examination of bacteria. Julius Friedrich Conheim (1839-1884) and Carl Weigert (1845-1904) taught him bacterial staining techniques, including the methylene blue staining technique. Further, Neisser had access to an excellent innovative Zeiss microscope that was equipped with Ernst Abbe's (1840-1905) innovative condenser system and an oil-immersion object lens system. This equipment allowed him detailed microscopic examinations, which were not the usual "state of the art" in 1879, the year when Neisser discovered the "Micrococcus" microscopically.

Finally, in 1879 Neisser published a paper "Über eine der Gonorrhoe eigenthümliche Micrococcenform" ("A form of Micrococcus typical for gonorrhea") [33]. In this paper he was the first person to describe that a very typical form of a somewhat peach-like (semmelartig) "Micrococcus/Diplococcus" ("Micrococcus" [33, 34], "Micrococcenhaufen" [33], "Semmelform" [33, 34], "Diplococcus" [34]) was always found as sole bacteria in a large quantity in genital smears of patients suffering from symptomatic gonorrhea. He mostly observed this "Micrococcus" topologically associated with inflammatory cells and/or epithelia. Further, he stated that the best diagnostic results were obtained using the methylene blue staining technique, and that the microscopic picture was extremely typical for the disease and for him to be certain of the association. Beside a few doubts and the recommendation for a scientific proof, based on something like the later-discussed, communicated and published Koch-Henle postulates (1875-1885; ideas arising and postulated by Robert Koch in the late 1870s, "Wollsteiner Zeit") [35], Neisser was at that time rather convinced that the "Micrococcus" was the causative agent of gonorrhea. This statement was the milestone of Neisser's discovery of the "Micrococcus" as causative pathogen of gonorrhea. He further stated that he found this "Micrococcus" in eye smears of gonorrheal eye infections in adults and children. He already started with cultivation approaches in 1879, which were at that time not successful, probably due to the fact that Neisser's poor health condition restricted the time he could spend on his scientific activities beside his clinical duties.

In 1882 he published a second paper "Die Micrococcen der Gonorrhoe" ("Micrococci and gonorrhea") [34]. This paper was a very comprehensive, but from the author's view, somewhat unconventionally structured review paper in which Neisser - in the beginning - points out in a disappointed manner that it took over a year after his first publication for other scientists to pick up the topic of the "Micrococcus" and gonorrhea, and publish new insights on this issue. In this paper Neisser (a) extensively repeated his observations as stated in [33], and additionally (b) gave a drawn picture of the "Micrococcus" and its different division stages, (c) pointed out that other colleagues had also verified his observations (e.g., Aufrecht, Bokai, Brieger, Ehrlich, Gaffky, Haab, Hirschberger, Leber, Sattler, and Weiss), (d) reported that he successfully treated a case of gonorrheal eye infection with silver nitrate solution, (e) reported that he - beside other colleagues - had been successful in cultivating the "Micrococcus" in 1881/1882, (f) gave information on Bokai's successful inoculation experiments with cultured "Micrococcus" material in volunteer male students achieving an acute and typical genital gonorrhea, (g) gave information that the "Micrococcus" was apathogenic on inoculating the conjunctiva of dogs and rabbits, and (h) gave information on current treatment options and the pathophysiology of gonorrhea, highlighting genital and ocular gonorrheal infections. Indeed, the name of Carl Crede was never mentioned.

As Bokai's insights appeared not to have convinced Neisser, he repeatedly stated in this paper [34] that the strict proof for the "Micrococcus" as causative agent of gonorrhea still had to be produced. This seems an exaggerated skeptic statement considering this broad data basis and the aspect that Neisser repeatedly stated in this paper that the "Micrococcus" could always, and only, be found in case of symptomatic gonorrhea. In contrast, the Koch-Henle postulates became overemphasized within the scientific community at that time, which also put Neisser under an extreme pressure concerning the validity of his insight that the "Micrococcus" was the causative agent of gonorrhea, due to the categorical force of demonstrating that a pathogen unambiguously fulfilled these postulates.

Finally, it was Neisser's friend and school classmate Paul Ehrlich who named Neisser's "Micrococcus" the "Gonococcus". Therefore, a lot of Neisser's students named Neisser the "Father of Gonococcus" [30].

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