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Historical introduction
Digestion and the role of the stomach in maintaining health have interested man since early times (reviewed in ref. 1 ). The ancient Greeks noted the bitter-sour nature of the gastric contents and, in the 16th century, both Paracelsus 2 and van Helmont 3 believed acid to be present in the stomach and necessary for digestion. Subsequent observations by Reaumur 4 and Spallanzani 5 suggested the 'solvent' effects of gastric juice on animal tissue, but it was not until 1823 that William Prout published his work on the nature of gastric acid secretion. 6 The first observations of William Beaumont on his gastric fistula patient, Alexis St Martin, were published only 3 years later in 1826. 7 His meticulous observations over almost a decade described gastric digestion in a human during normal life experiences including the effects of stress.
In the early 20th century, control of gastric secretion was explored by ablation of the coeliac axis and vagotomy as therapeutic interventions and this emphasised the complex nature of the control of gastric secretion. This led to a rapid increase in interest and the work of Dale and Laidlaw on histamine, 8 which led to the critical discovery by Popielski of histamine's effect on gastric secretion, 9 Bayliss and Starling's discovery of secretin 10 and Edkins' treatise on gastrin. 11 These discoveries ushered in a new era in our understanding of gastric disease leading to the dramatic advances in the pharmacological management of peptic ulcer disease with the discovery of the H 2 -receptor antagonists by Sir James Black in 1972. 12 The emphasis on acid-related disease preoccupied research in the middle and latter half of the 20th century until the groundbreaking discovery of Helicobacter pylori in 1983 by Marshall and Warren. 13 This was counterintuitive to then current thinking, where the stomach was considered microbiologically sterile, despite the many observations of numerous bacterial populations in gastric juice among others by Jaworski 14 and the Nobel Prize-winning (1908) contribution of Metchnikoff for his work with Lactobacillus and gut immunity. 15 Some clinicians at that time already advocated aspiration of gastric juice in search of flagellated bacilli in patients with suspected gastric ulcer disease, followed by prescription of high doses of bismuth salts. 16
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