By the sixteenth century, there still existed considerable controversy as to the events that occurred in the lumen of the stomach. A number of reactionary and thoughtful individuals, including Paracelsus, Van Helmont, and Spallanzani, had written effectively about their individual concepts of gastric function. Their ideas ranged from chemical principles of an undefined nature, to archei (spirits), to the presence of acid, as proposed by Spallanzani. Many investigators in numerous countries considered the fundamental problem of digestion at many different levels. Of particular interest was the philosophic approach used by individuals who, although learned, had no formal training in science. Most interesting among these was the gourmand Brillat-Savarin.

The question of acid in the stomach had been a vexatious one for many years. Opinions had ranged from there being no acid in the stomach at all to its originating from the pancreas. Physicians of the fifteenth and sixteenth centuries felt that any acid present in the stomach was the result of putrefaction or fermentation and did not in any way reflect an active secretory process of the
body or the stomach itself. It was, however, the general opinion of physiologists up to the time of Spallanzani that a free, or at least unsaturated, acid usually existed in the stomach and was necessary for digestion. Indeed, the studies of Edward Stevens in Edinburgh and Lazzaro Spallanzani in Pavia had concluded that the antiseptic powers of gastric juices invalidated the possibility of fermentation as a means of gastric digestion.

A second controversial issue surrounded what the exact nature of the acid might be. Johann Tholde had first described the acid known as hydrochloric acid, although it had also been called muriatic acid for many years. The detection of this substance in the stomach was first reported by William Prout in 1823. At a meeting of the Royal Society in London on December 11, 1823, in a lucid and elegant discourse, he provided incontrovertible evidence that gastric juice of many different animals (hares, dogs, horses, cats) contained hydrochloric (muriatic) acid. In addition, Prout demonstrated that the same acid was present in dyspeptic patients, and that the amount of this acid appeared to be related to the degree of dyspepsia. Thus, the subject of the exact nature of the acid in gastric juice appeared to be resolved. Unfortunately, however, this was not to be the case, because physiologists as eminent as Claude Bernard were of the opinion that lactic acid (a product of fermentation) was present in gastric contents. Indeed, as late as 1885, Ewald and Boas reported that all acid present in the stomach at the beginning of a meal was lactic. It was their theory that hydrochloric acid gradually replaced the lactic acid during eating, with the result that, by the end of a meal, only hydrochloric acid was evident.

The French Académie des Sciences was interested in the exact nature of acid in the stomach and established an essay contest for which it offered a prize of 3,000 Francs for the answer to this question. A panel of distinguished judges was selected to evaluate the essays. One year later, the prize was awarded jointly to Leuret and Lassaigne of Paris and Tiedemann and Gmelin of Heidelberg. Leuret and Lassaigne declared that the acid in gastric juice was lactic, whereas Tiedemann and Gmelin confirmed Prout’s earlier observations that it was hydrochloric acid. When asked to share the prize, the Germans declined and withdrew, having been offended by the contradiction provided by the judges. At this time, Berzelius was regarded as the ranking authority on chemistry in Europe. As a result, his comments on the literature were anxiously scanned by authors in an attempt to gauge the level of acceptance of their thoughts. Thus, Wöhler, in a letter of May 17, 1828, told Berzelius how pleased Tiedemann and Leopold Gmelin were to have noted in the Årsberättelser 7, 297 the deprecatory comments of Berzelius about the “unbedeutende Arbeit” of Leuret and Lassaigne.

The work of Leuret and Lassaigne was not inconsequential. Their experimental studies on dogs demonstrated for the first time that acid introduced into the duodenum elicited the secretion of pancreatic juice and bile.

Seventy years later, in 1894, a student of Pavlov, Ivan Leukich Dolinsky, rediscovered this effect and noted that acid in the duodenum of the dog stimulated pancreatic secretion. It was on the basis of the earlier French observations that William Bayliss and his brother-in-law, Ernest Starling, on the afternoon of January 16, 1901, tested Dolinsky’s thesis and proved the existence of chemical messengers (hormones) that regulated secretion.

Claude Bernard (1813-1878) was born of a modest family in the town of Saint Julien on the Rhône; he attended a Jesuit college at Villefranche and then became a pharmacist’s assistant in Lyon. Bernard is best known for his book on experimental physiology, in which he outlined a number of the major concepts that he felt were critical to the pursuit of physiologic science. In particular, his delineation of the “milieu intérieur” has remained one of the critical physiologic observations ever made.

Apart from his numerous contributions, which included the identification of the glycogenic function of the liver and the delineation of the vasomotor mechanism, Bernard was noted for his contributions to the study of digestion. Before his work, it had been held that gastric digestion itself encompassed all digestive physiology. Bernard, however, demonstrated that “gastric digestion is only a preparatory act” and in particular delineated the enzymatic role of the pancreas. He demonstrated that pancreatic juice emulsified fat, converted starch into sugar, and was a solvent for proteins undigested by the stomach. Bernard was a creative investigator and had adopted Nicholas Blondlot’s canine model of the gastric fistula for the study of gastric secretion. In 1840, Blondlot of Nancy, a surgeon, had used Bernard’s innovative experimental model to determine that there was no acid or chloride in the stomach and concluded that the active principle was 1% calcium phosphate. Blondlot had been inspired to devise his canine model after reading of Beaumont’s studies of Alexis St. Martin. His innovative work in this area was later taken up by Pavlov, who constructed a series of vagally innervated and denervated pouches to evaluate the effects of neural regulation on gastric secretion. This was the so-called Pavlov pouch, which formed the basis of many of the subsequent experimental models used by the great physiologist and his pupils.

Investigations on the vagus nerve began 2,000 years ago. Marinus, in the first century AD, studied the anatomy of the vagi and was the first to assign to the cranial nerves a numeric sequence. Although none of the original work by Marinus
survives today, Galen cited his studies in the second-century anatomy text On the Usefulness of the Parts of the Body.

Galen, who was born in Pergamon Mysia, which is now part of Turkey, in 130 AD, expanded on the work of Marinus by speculating on the possible function of the nerves to the stomach:

The anatomy of the vagus undoubtedly contributed to the name applied to it. The term vagus, or per vagum, means “wandering part.” A more anatomically correct name was given to the nerve in the early nineteenth century, when the term pneumogastric appeared in the French and Italian literature. It then became a frequent term in the English and American literature. In Germany, however, the nerve was always referred to as the vagus. Thus, by the end of the nineteenth century, when German scientific research attained prominence, the term pneumogastric fell from common usage in the surgical community.

Once its anatomy became better defined, studies into vagal function were initiated. In 1814, Brodie published some of the first known experiments on vagal physiology and gastric function. In the report of his findings to the Royal Society of London, he noted that his work was inspired by Edward Home’s report of “some facts which render it probable that the various animal secretions are dependent on the influence of the nervous system.” Home, in fact, studied secretion in the electric eel:

Thus, the observation by Home of the electric eel inspired Brodie to be the first to perform the surgical procedure that is now accepted as a vagotomy. The pioneering work of Brodie, however, was not on humans but on a total of four dogs. His first experiment was a bilateral cervical vagotomy.

He noted that this operation prevented arsenicstimulated gastric secretion but was complicated by the development of severe respiratory compromise. To remedy the subsequent respiratory embarrassment, he modified his procedure to that of a subdiaphragmatic vagotomy. With the latter operation, the animals no longer experienced the “laborious breathing” and circulatory arrest observed during cervical vagotomy.

The earlier findings of “no watery or mucous fluid in the stomach or small intestines” seen with the cervical vagotomy were confirmed in the animals that underwent abdominal vagotomy. Brodie concluded “that the suppression of secretion in all of them was to be attributed solely to the division of the nerves: and all of the facts which have been stated sufficiently demonstrate, that the secretions of the stomach are very much under the control of the nervous system.” This observation was a watershed in the history of gastrointestinal physiology, as the concept of nervous control of gastrointestinal secretion had not been previously demonstrated.