The earliest experimental work on the hunger mechanism was directed to the nerves of the stomach, namely, the vagi and the splanchnics. Sedillot, Bernard, Bidder and Schmidt, Budge, Brunner and Hensen, Longet, Schiff, Ewald, Sherrington, Ducceschi, and others observed that animals will continue to exhibit desire for food and to eat after section of the vagi, the splanchnic, and even the taste nerves. Some of these men concluded that hunger does not rise from stimulation of sensory nerves in the stomach, on the assumption that an animal will eat from hunger only. Ludwig, Cannon, and others have questioned the validity of this assumption. It is certain that man at any rate may eat from appetite alone in the absence of hunger, as in the case of eating sweets or dessert at the conclusion of a dinner. Man may even eat from habit or a sense of duty, in the absence both of hunger and appetite, but it is not likely that this applies in a like measure to animals below man. Assuming, for the present, that appetite is in part a memory process, and hence a central nervous system phenomenon essentially, it is clear that section of the vagi would not affect it; hence the fact that an animal eats after section of the vagi tells us nothing as to presence or absence of hunger. Luciani states that fasting dogs refuse to eat for some time after double vagotomy. Valenti cocainized the vagi and the gastric mucosa in fasting dogs and reports that the animals refused food for some hours. These results of Valenti on dogs are called in question by L. R. Mtiller on the basis of analogous experiments on man. Muller states that cocaine by mouth has little or no influence on the gastric hunger pangs, but it abolishes the feeling of weakness whether the drug is taken by mouth or injected subcutaneously. He concludes that this is a central action of the cocaine after absorption into the blood.

The advance of modern surgery has made possible the nearly complete removal of the stomach in man and experimental animals. It is reported that such persons continue to experience hunger after the operation, but it is not clear that patients and observers differentiated between hunger and appetite. A dog minus the greater part of the stomach will eat, but we have already pointed out that this is no absolute criterion of hunger. It should be noted here that complete excision of the stomach is impossible, or at least has not yet been accomplished. There always remains a considerable portion of the stomach around the cardia where the union with the duodenum is made, and in healthy individuals at any rate this gastric remnant gradually.hypertrophies and dilates to form a considerable stomach pouch, sufficient in all likelihood to give rise to hunger pangs, especially as these are primarily originated in the cardiac end of the stomach. The recent observations of Perthes are of importance in this connection. In cases of resection of the stomach for gastric ulcers, Perthes states, when the location of the ulcer is such that the operation removes most of the greater curvature of the stomach body, after recovery X-ray observations show the pylorus permanently open, the diminutive stomach exhibits hypermotility, and the food passes out of the stomach practically at once and without any gastric digestion. All these patients complained of bulimia or excessive hunger pangs. In some cases the hunger pangs were strong enough to wake the persons up from sleep. In order to be comfortable they had to eat every two hours. This excessive hunger did not develop in patients with stomach so resected that the main body or reservoir of the stomach was left intact.

The observations of Busch, in 1862, on a woman with a duodenal fistula, have been extensively quoted in subsequent discussions on the hunger mechanism. The patient was a woman thirty-one years old. She was greatly emaciated owing to loss of chyme from the fistula, weighing only 68 lbs. when she came under Dr. Busch's care. She had inordinate hunger (bulimia) and felt the hunger even when her stomach was practically filled with food. But taking food into the stomach relieved that part of the hunger which may be described as a painful or gnawing sensation in the stomach. Hunger was also relieved in part by the introduction of chyme into the duodenum. The woman was so emaciated that the stomach and intestinal movements could be seen in detail through the abdominal wall, and Busch observed periods of active peristalsis alternating with periods of rest in the case of the empty intestines. He could not make out any regularity in the recurrence of these activity periods. Busch concludes: The sensation of hunger is made up of two elements. The first is a condition of the central nervous system, in consequence of actual tissue starvation; the second is due to stimulation of nerves in the alimentary trace.

In extreme starvation the central element persists even when the alimentary tract is filled with food.

Nicolai, in 1892, made some observations on normal persons, and on persons with various gastero-intestinal disorders. He found that the mere act of swallowing or passing the stomach tube abolishes hunger temporarily. Passing water, salt solution, or indigestible material through the tube into the stomach also allays hunger for varying pferiods. These observations are now readily explained by the inhibitory reflexes from the mouth and the gastric mucosa to the gastric musculature. Nicolai concludes that "the sensation of hunger involves sensory impulses not only from the stomach, but also from the esophagus, and the pharynx," and that appetite and hunger are fundamentally different sensations, either of which may be experienced without the other.

Schlessinger, in 1893, fed normal patients and persons exclusively per rectum for periods varying from 1 to 20 days. He reports that rectal feeding does not abolish completely' the sensation of hunger, even when this feeding leads to an increased body weight. At the most there is a decrease in the hunger sensation for a short time after each rectal feeding. On the basis of more recent work, this is probably due to inhibitory reflexes from the rectum and large intestine to the gastric musculature. Schlessinger reports further that local anesthesia of the gastric mucosa (pieces of ice, chloroform, cocaine in the stomach) causes only a slight or temporary abolition of hunger. But if the persons had been previously fed per rectum, local anesthesia of the gastric mucosa led to complete disappearance of hunger. He therefore concludes that hunger has a double origin: (1) peripheral or gastric, and (2) central stimulation of a hunger center by starvation blood.