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A Century of Helicobacter pylori

Paradigms Lost – Paradigms Regained

Kidd M. · Modlin I.M.

Author affiliations

Gastric Surgical Pathobiology Research Group, Yale University School of Medicine, New Haven, Conn., and West Haven Veteran’s Administration Medical Center, West Haven, Conn., USA

Corresponding Author

Irvin M. Modlin, MD, PhD

Yale University School of Medicine

PO Box 208062

New Haven, CT 06520-8062 (USA)

Tel. +1 (203) 937 4785, Fax +1 (203) 937 4783

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Digestion 1998;59:1–15

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The investigation of gastric bacteria properly began in the latter half of the nineteenth century when microscope resolution had sufficiently advanced. Whilst a bacterial etiology was demonstrated for dysentery, tuberculosis and syphilitic ulcers, problems in the isolation and culture of pure strains circumvented a role for bacteria in gastric pathology. Furthermore, dogma and the intellectual chorus were in harmony advocating that gastric acid was critical in ulcer disease. The consideration of a role for a pathogen or pepsin was regarded as whimsical in the context of mucosal ulceration. Indeed, the effects of acid inhibitory agents were held as gospel truth whilst the use of antibiotics or metallic ions were deemd to be quackery or at least ill judged. Nonetheless, spiral-shaped bacteria had been identified in both mucosa and gastric contents of patients as early as 1889. Elegant studies had documented the infectivity of these organisms, and suggested but not proven a causative role in gastric disease. The prescient identification by Doenges of organisms associated with gastritis in both man and monkey, was buried by the observations of Palmer, and an opportunity for early progress lost. It required two decades and Antipodean pathological perspicacity to elucidate the warren of previous archaic gastric bacterial misinformation. The subsequent marshalling of clinical and pathological data established the fatal flaw in the mucosa to be bacteria and not only acid on the mucus shore. It is now widely apparent that Helicobacter is ubiquitous, pathological and, a century after its initial discovery, still remains a paradox of as yet incompletely determined biological consequence. It is of note that an organic helical configuration has twice in this century provided biological information of unique import.


  1. de Kruif P: Microbe Hunters. New York, Harcourt Brace, 1996.
  2. Gray T: Elegy; in Warren RP, Erskine A (eds): Six Centuries of Great Poetry. New York, Dell, 1992.
  3. Modlin I: From Prout to the Proton Pump: A history of the Science of Gastric Acid Secretion and the Surgery of Peptic Ulcer. SG&O 1990;170:81–96.
  4. Avicenna. Liber canonis. Mediolani, P. de Lavagna, 1473.
  5. Donati M: De medica historia mirabili. Mantuae, Fr. Osanam, 1586.
  6. Moutier F, Cornet A: Les Gastrites. Paris, Masson, 1955.
  7. Morgagni GB: De sedibus et Causis Morborum per anatomen indigatis libri quinque. Venetiis, Typographia Remondiniana, 1765.
  8. Baillie M: The Morbid Anatomy of Some Aspects of the Human Body. London, Johnson & Nicol, 1793, p 87.
  9. Broussais FTV: Histoire des phlegmasies ou inflammations chroniques, fondée sur de nouvelles observations de clinique et d’anatomie pathologique. Paris, Gabon, 1822.
  10. Nepveu PF: Sur le cancer de l’estomac, considéré comme l’une des terminaisons de la gastrite chronique, Paris, 1821.
  11. Cruveilhier J: Considérations générales sur les ulcérations folliculaires de l’estomac; in: Atlas d’Anatomie Pathologique, Paris, Baillière, 1842.
  12. Davenport HW: A History of Gastric Secretion and Digestion. New York, Oxford University Press, 1992, p 266.
  13. Fenwick S: On the Atrophy of the Stomach and Nervous Affections of the Digestive Organs. London, Churchill, 1880.
  14. Garrison FH: Introduction to the History of Medicine. Philadelphia, Saunders, 1929.
  15. Muller OF: Animacula infusoria fluviatilia et marina, quae detexit, systematice descript et ad vivum delineari. Huaniae, N. Molleri, 1786.
  16. Cohn FJ: Untersuchungen über Bacterien. Beitr Biol Pflanzen 1872;1(Heft 1):127–224.
  17. Cohn FJ: Untersuchungen über Bacterien. Beitr Biol Pflanzen 1872;1(Heft 3):141–207.
  18. Sedillot CE: De l’influence de M. Pasteur sur les progrès de la chirurgie. Co R Acad Sci (Paris) 1878;86:634–640.
  19. Schwann T: Mikroskopische Untersuchungen über die Übereinstimmung in der Struktur und dem Wachsthum der Thiere und Pflanzen. Berlin, 1839.
  20. Bottcher G: Dorpater Med Z 1875;184.
  21. Klebs C: Über Infectiöse Magenaffectionen. Allgemein Wien Med Z 1881;29/30.
  22. Ehrenberg CG: Die Infusionsthierchen als vollkommene Organismen. Leipzig, Voss, 1838.
  23. Jaworski W: Podrecznik Chorob zoladka. Wydawnictwa Dziel Lekarskich Polskich 1889;32.
  24. Boas I: Diseases of the Stomach. Philadelphia, Davis, 1907.
  25. Ogston A: Report upon microorganisms in surgical diseases. Br Med J 1881;i:369–375.
  26. Letulle M: Origine infectieuse de certains ulcères simples de l’estomac ou du duodénum. Soc Méd Hôp Paris 1888;5:360.
  27. Wurtz R, Leudet R: Recherches sur l’action pathogène du bacille lactique. Arch Méd Exp Anat Pathol 1891;3:485.
  28. Enriquez H, Hallion R: Ulcère gastrique expérimental par toxine diphtéritique. Co Re Soc Biol 1893;45:1025.
  29. Bezançon F, Griffon V: Ulcérations gastriques au cours de la septicémie pneumococcique chez le cobaye. Bull Soc Anat Paris 1899;74:409.
  30. Bizzozero G: Sulla ghiandole tubupari del tubo gastro-enterico. Appendice: Sulla presenza di batteri nelle ghiandole rettali e nelle ghiandole gastriche del cane. Centralbl Bakt 1893;1:623.
  31. Salomon H: Über das Spirillum des Säugetiermagens und sein Verhalten zu den Belegzellen. Zentralbl Bakteriol 1896;19:433–442.
  32. Kasai K, Kobayashi R: The stomach spirochete occurring in mammals. J Parasitol 1919;6:1–11.
  33. Shiga K: Über den Dysenteriebacillus (Bacillus dysenteriae). Zentralbl Bakteriol 1898;23:599–600.
  34. Hemmeter JC: Diseases of the Stomach. Philadelphia, Blakiston’s, 1902, pp 438–444.
  35. Riegel F: Diseases of the stomach, in Stockton CG (ed): Nothnagel’s Encyclopedia of Practical Medicine. Philadelphia, Saunders, 1905.
  36. Moynihan B: Duodenal ulcer. Practitioner 1907;76:249.
  37. Schwarz K: Über penetrierende Magen- und Jejunal-Geschwüre. Beitr Klin Chir 1910;67:96–128.
  38. Krienitz W: Über das Auftreten von Spriochaeten verschiedener Form im Mageninhalt bei Carcinoma ventriculi. Dtsch Med Wochenschr 1906;32:872.
  39. Luger A, Neuberger H: Über Spirochätenbefunde im Magensaft und deren diagnostische Bedeutung für das Carcinoma ventriculi. Z Klin Med 1921;92:54.
  40. Turck FB: Ulcer of the stomach: Pathogenesis and pathology: Experiments in producing artificial gastric ulcer and genuine induced peptic ulcer. JAMA 1906;46:1753.
  41. Turck FB: Experimental studies on round ulcers of the stomach and duodenum. J Med Res 1908;17:365.
  42. Gibelli C: Contributo critico sperimentale all’eziologica dell’ulcera gastrica in rapporto coi traumi. Arch Int Chir 1910;4:127.
  43. Rosenow EC: The production of ulcer of the stomach by injection of streptococci. JAMA 1913;61:1947.
  44. Rosenow EC: The causation of gastric and duodenal ulcer by streptococci. J Infect Dis 1916;19:333.
  45. Rosenow EC: The specificity of the streptococcus of gastroduodenal ulcer and certain factors determining its localization. J Infect Dis 1923;33:248.
  46. Hardt LLJ: Contributions to the physiology of the stomach. XXXIII. The secretion of gastric juice in cases of gastric and duodenal ulcers. Am J Physiol 1916;40:314.
  47. McGown OS: Perforation of a gastric ulcer in a guinea pig following subcutaneous injection of urine containing streptococci. Urol Cutan Rev 1920;24:393.
  48. Waisbren S, Modlin IM, Lester R: Dragstedt and his role in the evolution of therapeutic vagotomy in the United States. Am J Surg 1994;167:344–359.
  49. Dragstedt LR: Contributions to the physiology of the stomach XXXVIII Gastric juice in duodenal and gastric ulcers. JAMA 1917;LXVIII:330–333.
  50. Modlin IM, Kidd M, Marks IN, Tang LH: The pivotal role of John S Edkins in the discovery of gastrin. World J Surgery 1997;21:226–234.
  51. Edkins JS: Spirella regaudi in the cat. Parasitology 1923;15:296–307.
  52. Lim RKS: A parasitic spiral organism in the stomach of the cat. Parasitology 1920;12:108.
  53. Hoffman A: Experimental gastric and duodenal inflammation and ulcer, produced with a specific organism fulfilling Koch’s postulates. Am J Med Sci 1925;170:212.
  54. Saunders EW: The serologic and etiologic specificity of the alpha-streptococcus of gastric ulcer. Arch Intern Med 1930;45:347.
  55. Doenges JL: Spirochaetes in gastric glands of Macacus rhesus and humans without definite history of related disease. Proc Soc Exp Biol Med 1938;38:536–538.
  56. Freedberg AS, Barron LE: The presence of spirochetes in human gastric mucosa. Am J Dig Dis 1940;7:443–445.
  57. Sazerac R, Levaditit C: Traitement de la syphilis par le bismuth. C R Acad Sci Paris 1921;173:338–340.
  58. Chiari H: Über Magensyphilis. Int Beitr Wiss Med 1891;2:295–321.
  59. Noguchi H: A method for the pure cultivation of pathogenic Treponema pallidum (Spirochaeta pallida). J Exp Med 1911;14:99–108.
  60. Palmer ED: Investigation of the gastric mucosa spirochetes of the human. Gastroenterology 1954;27:218–220.
  61. Luck JM: Gastric urease. Biochem J 1924;18:1227–1231.
  62. Luck JM, Seth TN: The physiology of gastric urease. Biochem J 1925;19:357.
  63. Conway EJ: The Biochemistry of Gastric Acid Secretion. Springfield, Thomas, 1952.
  64. Fitzgerald O, Murphy P: Role of gastric urease. Nature 1948;162:896–897.
  65. Kornberg HL; Davies RE: Gastric urease. Physiol Rev 1955;35:169–177.
  66. Dintzis RZA: A study of urea breakdown in the animal body; PhD thesis, Cambridge, Radcliffe College, 1953.
  67. Fitzgerald O, Murphy P: Studies on the physiological chemistry and clinical significance of urease and urea with special reference to the stomach. Irish J Med Sci 1950:97–159.
  68. Burke JO, Page SG: The effects of orally administered urea on healthy subjects and their gastric secretory response to histamine. Gastroenterology 1954;26:503–505.
  69. Fitzgerald O, Murphy P: The use of urea in peptic ulcer therapy. Part III. Irish J Med Sci 1950:119–159.
  70. Lieber CS, Lefevre A: Effect of oxytetracycline on acidity, ammonia and urea in gastric juice in normal and uremic subjects. C R Soc Biol Paris 1957;151:1038–1042.
  71. Lieber CS: Gastritis and Helicobacter pylori; Forty years of antibiotic therapy. Digestion 1997;58:203–210.
  72. Lieber CS, Lefevre A: Ammonia and intermediary metabolism in hepatic coma. Value of the determination of blood ammonia in the diagnosis and management of cirrhosis. Acta Clin Belg 1958;13:328–357.
  73. Lieber CS, Davidson CS: Complications resulting from renal failure in patients with liver disease. Arch Intern Med 1960;106:749–752.
  74. Dasani BM, Sigal SH, Lieber CS: The role of Helicobacter pylori in the pathogenesis and treatment of chronic hepatic encephalopathy. Hepatology 1995;22:161.
  75. Wyllie JH, Limbosch JM, Nyhus LM: Inhibition of gastric acid secretion by bacterial lipopolysaccharide. Nature 1967;215:879.
  76. Baume PE, Nicholls A, Baxter CH: Inhibition of gastric acid secretion by a purified bacterial lipopolysaccharide. Nature 1967;215:59–60.
    External Resources
  77. Sarner A, Babyatsky MW: Peptic ulcer disease: Paradigm’s lost. Mt Sinai J Med 1996;63:387–398.
  78. Steer HW: Ultrastructure of cell migration through the gastric epithelium and its relationship to bacteria. J Clin Pathol 1975;28:639–646.
  79. Ramsey EJ, Carey KV, Peterson WL, Jackson JJ, Murphy FK, Read NW, Taylor KB, Trier JS, Fordtran JS: Epidemic gastritis with hypochlorhydria. Gastroenterology 1979;76:1449–1457.
    External Resources
  80. Graham DY, Alpert LC, Smith JL, Yoshimura HH: Iatrogenic Campylobacter pylori infection is a cause of epidemic achlorhydria. Am J Gastroenterol 1988;83:974–980.
  81. Steer HW, Colin-Jones DG: Mucosal changes in gastric ulceration and their response to carbenoxolone sodium. Gut 1975;16:590–597.
  82. Warren JR: Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983;i:1273.
  83. Marshall B: Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983;i:1273–1275.
  84. Marshall BJ, Armstrong JA, McGechie DB, Glancy RJ: Attempt to fulfill Koch’s postulates for pyloric campylobacter. Med J Aust 1985;142:436–439.
  85. Morris A, Nicholson G: Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am J Gastroenterol 1987;82:192–199.

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Published online: January 08, 1998
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