History
Introduction
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Although the association between Campylobacter (Helicobacter) pylori and ulcers was discovered by Robin Warren in 1979, and the organism was cultured by Barry Marshall in 1982, resulting in their seminal publications in Lancet in 1983, the historical origins of its discovery are rooted in the latter half of the nineteenth century. It was during this period that the eminent German bacteriologist Robert Koch proved scientifically that bacteria were the cause of certain diseases. Almost simultaneously, the Frenchman Louis Pasteur, having been galvanized by Koch’s contributions, was in the process of developing vaccines against the microbes causing cholera and rabies. In Sicily, in a small homemade laboratory in Messina, an émigré Russian, Elie Metchnikoff, had discovered phagocytosis, thus initiating an entirely new vista of biologic investigation: host defense mechanisms.
Early bacteriology
Although Leeuwenhoek was probably the first to see both gastrointestinal and oral bacteria, it was O. F. Muller (1730-1784) of Copenhagen who provided the first definitive observations and descriptions of microorganisms; he also coined
the terms bacillus and spirillum. Ferdinand Cohn (1828-1898) from Breslau, the botanist now regarded as one of the founders of bacteriology, classified microorganisms into several groups—bacterial (short, cylindric cells), bacilli (longer cells), spirilla (wavy or spiral forms), and coccoid (spheric)—and noted the fixity of bacterial species. Thus, even under varying conditions, he was never able to obtain cocci from bacilli and vice versa. In 1870, Cohn established his own journal, Beitrage zur Biologie der Pflanzen, and in this communication hosted most of the original, classic bacteriology papers, authored by both himself and his young protégé, Robert Koch. The classic postulates of the latter would subsequently form the logical basis for the investigation and identification of the disease-causing potential of bacteria. In 1872, Cohn published his mature exposition on bacteriology entitled Untersuchungen über Bakteria, wherein he further expanded the classification of bacteria into genera and species. He suggested an expanded classification into four groups: sphaerobacteria (cocci), microbacteria, desmobacteria (bacillus and vibrio), and spirobacteria (spirillum and spirochete). This work was well received and became so popular that it was reprinted in 1875 and again in 1876.
the terms bacillus and spirillum. Ferdinand Cohn (1828-1898) from Breslau, the botanist now regarded as one of the founders of bacteriology, classified microorganisms into several groups—bacterial (short, cylindric cells), bacilli (longer cells), spirilla (wavy or spiral forms), and coccoid (spheric)—and noted the fixity of bacterial species. Thus, even under varying conditions, he was never able to obtain cocci from bacilli and vice versa. In 1870, Cohn established his own journal, Beitrage zur Biologie der Pflanzen, and in this communication hosted most of the original, classic bacteriology papers, authored by both himself and his young protégé, Robert Koch. The classic postulates of the latter would subsequently form the logical basis for the investigation and identification of the disease-causing potential of bacteria. In 1872, Cohn published his mature exposition on bacteriology entitled Untersuchungen über Bakteria, wherein he further expanded the classification of bacteria into genera and species. He suggested an expanded classification into four groups: sphaerobacteria (cocci), microbacteria, desmobacteria (bacillus and vibrio), and spirobacteria (spirillum and spirochete). This work was well received and became so popular that it was reprinted in 1875 and again in 1876.
 From left to right: Leeuwenhoek, Cohn, Koch. A. Leeuwenhoek (1632-1723), the enthusiastic pioneer of the biologic microcosmos, was the first to see gastrointestinal bacteria (mouth, colon) but due to his lack of medical training ascribed no pathologic importance to this new world. Once microscopes had sufficiently evolved, order was brought to the vague Linnaean genus of “Chaos” by F. Cohn’s (1828-1898) morphologic classification of bacteria. Cohn’s protégé, R. Koch (1843-1910), one of the founders of modern bacteriology, was also first to develop the correct theory of species-specific infectious diseases. |
Observations on Gastric Infection | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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In 1878, the term microbe was introduced by C. E. Sedillot (1804-1883), a French surgeon who was responsible for undertaking the first gastrostomy and may have unwittingly happened on the organism. He proposed this term, derived from the Greek for “small life,” with the caveat that such “small lives” must have the special ability to cause fermentation, putrefaction, or a disease process. This was a proposal much favored by T. Schwann (1810-1882), who had himself not only discovered pepsin in 1834 but also had written extensively on the role of fermentation, as well as the single-cell theory of disease.
Early data on gastric bacteriology
Careful analysis of gastric contents revealed that under fasting conditions, the normal stomach contained mucus, a few bacilli, and some yeast cells, whereas in stagnant gastric contents, obtained from patients with gastric disease, bacilli, micrococci, yeast, and fungus could readily be seen. Such early observations supported speculations regarding a putative causative role of these “foreign bodies” in gastric pathology. It was unclear, however, to these early, eager gastric bacteriologists whether a specific organism was the cause of a gastric disease entity or whether it was simply an abnormal accumulation of organisms in the stomach itself that culminated in gastric disturbances.
One of these first gastric bacteriologists was G. Bottcher, a German who, along with his French collaborator M. Letulle (1853-1929), could demonstrate bacterial colonies in the ulcer floor and in its mucosal margins. His convictions in regard to the disease-causing potential of ingested organisms were so ardent
that by 1875, he had attributed the causation of ulcers to the bacteria that they could demonstrate. However, this was not a popular point of view, and in spite of an 1881 report by the pathologist C. Klebs of a bacillus-like organism evident both free in the lumen of gastric glands and between the cells of the glands and the tunica propria, with corresponding “interglandular small round cell infiltration,” the “bacterial hypothesis” fell into disuse. Bottcher was, however, probably the first to formally report the presence of spiral organisms in the gastrointestinal tract of animals, although spiral organisms were already well known and had been described as early as 1838 by Ehrenburg. The pathogenic properties of these particular organisms had similarly been recognized by Obermeier of Berlin, who, in 1872, could demonstrate their presence in the blood of patients with relapsing fever. An examination of the report of Klebs indicates that he had noted the presence of an inflammatory infiltration, although he made no specific comments with regard to its significance. However, could this have been the first notation, if not of H. pylori infectious gastritis, then at least of lymphoid tissue in the gastric mucosa?
that by 1875, he had attributed the causation of ulcers to the bacteria that they could demonstrate. However, this was not a popular point of view, and in spite of an 1881 report by the pathologist C. Klebs of a bacillus-like organism evident both free in the lumen of gastric glands and between the cells of the glands and the tunica propria, with corresponding “interglandular small round cell infiltration,” the “bacterial hypothesis” fell into disuse. Bottcher was, however, probably the first to formally report the presence of spiral organisms in the gastrointestinal tract of animals, although spiral organisms were already well known and had been described as early as 1838 by Ehrenburg. The pathogenic properties of these particular organisms had similarly been recognized by Obermeier of Berlin, who, in 1872, could demonstrate their presence in the blood of patients with relapsing fever. An examination of the report of Klebs indicates that he had noted the presence of an inflammatory infiltration, although he made no specific comments with regard to its significance. However, could this have been the first notation, if not of H. pylori infectious gastritis, then at least of lymphoid tissue in the gastric mucosa?
 In 1889, W. Jaworski discovered and postulated a pathogenic role for the spiral organisms (Vibrio rugula) that he found in gastric contents. |
In 1889, Walery Jaworski, professor of Medicine at the Jagiellonian University, Cracow, Poland, was the first to describe in detail spiral organisms in the sediment of washings obtained from humans. Among other things, he noted a bacterium with a characteristic spiral appearance, which he named Vibrio rugula. He suggested that it might play a possible pathogenic role in gastric disease. Jaworski supposed that these “snail” or “spiral” cells were only to be found in rare cases. However, Ismar Boas (Berlin), already a luminary for his gastrointestinal contributions and for the discovery of the “Oppler-Boas” lactobacillus, found these cells quite constantly in all “fasting” gastric contents containing hydrochloric acid. Further detailed analysis by Boas’ assistant, P. Cohnheim, indicated that such “cells” could be induced by the reaction of bronchial or pharyngeal mucus and hydrochloric acid. This led to the suggestion that Jaworski had consistently observed acid-altered myelin and that similar secondary structures, threads, and small masses could also be induced by these simple chemical reactions. Cohnheim and Boas, therefore, inferred from their experiments that Jaworski’s “cells” were most probably the product of gastric mucus and acid chyme.
The observations of Bottcher and Letulle had suggested a causative bacterial agent in ulcer disease, and by 1888, Letulle was actively searching for this postulated entity. A few years earlier, in 1881, the Scottish surgeon and bacteriologist, Alexander Ogston (1844-1929), had identified Staphylococcus pyrogenes aureus both in acute and chronic abscesses. Noting the similarity of this bacterium to their postulated entity, Letulle, in the time-honored tradition of his day, undertook a classic experiment. He used two modes of administration in guinea pigs: intramuscular injection of Ogston’s pure, cultured Staphylococcus or oral intake of the agent. Not surprisingly, this resulted in the formation of acute gastric lesions perfectly
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