Heuristic Reevaluation of the Bacterial Hypothesis of Peptic Ulcer Disease in the 1950s

Abstract

Throughout the first half of the twentieth century the research on peptic ulcer disease (PUD) focused on two rivaling hypothesis: the “acidity” and the “bacterial” one. According to the received view, the latter was dismissed during the 1950s only to be revived with Warren’s and Marshall’s discovery of Helicobacter pylori in the 1980s. In this paper we investigate why the bacterial hypothesis was largely abandoned in the 1950s, and whether there were good epistemic reasons for its dismissal. Of special interest for our research question is Palmer’s 1954 large-scale study, which challenged the bacterial hypothesis with serious counter-evidence, and which by many scholars is considered as the shifting point in the research on PUD. However, we show that: (1) The perceived refutatory impact of Palmer’s study was disproportionate to its methodological rigor. This undermines its perceived status as a crucial experiment against the bacterial hypothesis. (2) In view of this and other considerations we argue that the bacterial hypothesis was worthy of pursuit in the 1950s.

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Notes

  1. 1.

    This hypothesis was embedded in a broader research program on bacterial diseases, sometimes also referred to as the germ theory paradigm or Pasteur-Koch paradigm, which governed epidemiology from the second half of the nineteenth century until the mid twentieth century [see e.g. (Carter 2003)].

  2. 2.

    Staining of bacteria allows for them to be much better observed under the microscope. The method was introduced during the advancements in microscopy in the second half of the nineteenth century (Kornhauser 1930).

  3. 3.

    Urease is an enzyme that catalyzes the hydrolysis of urea into carbon dioxide and ammonia, and it can originate from bacteria, which are thus described as urea-splitting organisms.

  4. 4.

    Culturing of bacteria is considered one of the necessary steps in proving their causal role in a certain disease, according to Koch’s postulates. We discuss these postulates in Sect. 4.2.

  5. 5.

    (Pindak et al. 1965) do not discuss PUD, but they mention Palmer’s results as a shifting point in the investigation of spirochetes in human stomachs.

  6. 6.

    By examining the literature it is quite obvious that the two hypotheses had been developed as two distinct research programs. Even in the 1920s, when the bacterial hypothesis still had many proponents, authors analyzing the influence of acidity rarely took bacterial infection as a possible etiological factor. This was possibly due to the fact that scientists could experimentally produce peptic ulcers in animals, in numerous ways, without a direct recourse to bacteria. However, the possibility of bacterial infection was not completely ignored as it was from the 1950s on. For instance, (Mann and Williamson 1923) speak of a variety of methods of producing ulcers in animals, all of which require the presence of acid in the stomach. Rosenow’s method of producing ulcers by the administration of bacteria is mentioned as one of them, with a remark that a possible etiological role of bacteria in PUD is an issue that should be further looked into (p. 420). It is interesting to notice that the authors do not mention any other results or papers discussing spirochetes as possible causal factors of PUD.

  7. 7.

    Note that Zetzel’s article dates from 1953, a year before Palmer’s results were published. Nevertheless, it does not even mention bacterial infection (or any research on it) as a possible etiological factor. We will come back to this point in Sect. 6.

  8. 8.

    (Schlicke 1963) lists a number of complications that may follow this surgical treatment, while (Wastell 1967) lists some derangement of digestion and absorption that may result from it. Over the years attempts were made at reducing the operative mortality rate [(Edwards et al. 1963) report the operative mortality rate of 2.7 %].

  9. 9.

    Additionally it should be noted that silver staining was routine in the detection of spirochetes in the research on syphilis [see e.g. (Sahyoun 1939)].

  10. 10.

    Barron’s comment is preceded by Gorham’s one, which we mentioned in Sect. 2.2.

  11. 11.

    It should also be mentioned that F&B’s conclusion is more skeptical than that presented by Warren and Marshall. They merely conclude that “there was no evidence in our specimens indicating that these organisms have any pathogenic significance” (Freedberg and Barron 1940, p. 444) which does not imply that their role has been established as non-pathogenic, but that this question is still open, as Gorham points out in the discussion following this article (see Sect. 2.2).

  12. 12.

    It is interesting to mention that the first home-made produced fiber optic endoscope (produced by Hirschowitz, Peters, and Curtiss) “was used to perform the first successful beroptic endoscopy in February 1957 on the wife of a dental student with a duodenal ulcer” (Lau et al. 1997, p. 445, italics added).

  13. 13.

    This point holds especially in view of the methodological constraints posed by the Koch postulates, see point 4 below and Footnote 4.

  14. 14.

    It is worth mentioning that (Bartle and Harkins 1925) point out that different types of bacteria posses different levels of resistance to the acid environment (p. 388).

  15. 15.

    For a list see (Zetzel 1953).

  16. 16.

    Koch established requirements for a bacterial cause of tuberculosis, which were then codified by his colleague Loeffler as general conditions for demonstrating the parasitic nature of a disease (Thagard 2000, p. 59).

  17. 17.

    It is worth mentioning though that satisfying all four criteria proved not to be possible even in the 1990s (Marshall 1995). But as (Thagard 2000) points out, fulfilling Koch’s postulates is not the only way to establish the causal role of a pathological agent:

    By far, the most impressive evidence that H. pylori causes peptic ulcers is the demonstration that eradication of H. pylori strongly contributes to the elimination of ulcers and the prevention of their recurrence (Thagard 2000, p. 62).

    As we have already mentioned, investigating the effect of antibiotics on PUD was a possible research avenue already in the 1950s, or at least at the end of the 1950s, in view Lieber’s and Lefèvre’s results (see Sect. 2.3). This is not to say that scientists would have accepted the bacterial hypothesis were antibiotic treatment proven successful, but it certainly would have made it an attractive research program, worthy of further investigation.

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Correspondence to Dunja Šešelja.

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The research of this paper was supported by the Special Research Fund (BOF) Ghent University and the Research Foundation—Flanders (FWO).

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Šešelja, D., Straßer, C. Heuristic Reevaluation of the Bacterial Hypothesis of Peptic Ulcer Disease in the 1950s. Acta Biotheor 62, 429–454 (2014). https://doi.org/10.1007/s10441-014-9219-7

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Keywords

  • PUD
  • Peptic ulcer disease
  • Bacterial hypothesis
  • Crucial experiment
  • Pursuit worthiness
  • Heuristic appraisal