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THE CONTROL OF HUNGER IN 
 HEALTH AND DISEASE 
 
THE UNIVERSITY OF CHICAGO PRESS 
 CHICAGO, ILLINOIS 
 
 THE BAKER & TAYLOR COMPANY 
 
 NEW TOEK 
 
 THE CAMBRIDGE UNIVERSITY PRESS 
 
 LONDON AND EDINBURGH 
 
 THE MARUZEN-KABUSHIKI-KAISHA 
 
 TOKYO, OBAKA, ETOTO, FUKUOKA, BBNDAI 
 
 THE MISSION BOOK COMPANY 
 
 BEANSHAI 
 
THE 
 
 CONTROL OF HUNGER 
 
 IN HEALTH 
 
 AND DISEASE 
 
 By 
 
 ANTON JULIUS CARLSON 
 
 THE UNIVERSITY OF CHICAGO PRESS 
 CHICAGO, ILLINOIS 
 W 
 
'COPXKIGHTISI® BV 
 
 The University or Chicago 
 
 All Rights Reserved 
 
 Published September 1916 
 Second Impression October 1919 
 
 Composed and Printed By 
 
 The UnS^sityol Chicago Press 
 
 CWcaeo, Illinois. II.S.A. 
 
PREFACE 
 
 The following pages contain a summary of the work on the 
 stomach, with special reference to hunger and appetite, carried out 
 in the Hull Physiological Laboratory of the University of Chicago 
 during the last four years. We have aimed to present this digest 
 in the hght of the entire biological and clinical literature on the 
 subject, hoping that it may encourage more intensive work on 
 hunger and appetite control, particularly in the fields of clinical 
 medicine and comparative physiology, as the work of the past on 
 this problem is not commensurate with its biological, medical, and 
 economic importance. 
 
 ;- The v,omplete analysis of hunger may not )deld us control over 
 the himger mechanism, but it is at least the most promising line of 
 attack. The scientist will concede its value to biology, and the 
 physician readily appreciates its significance for rational thera- 
 peutics; but the layman may question the practical utility of 
 hunger control to society as a whole, in view of the fact that it has 
 played no r61e in past evolution. This is granted. But the 
 elimination of many biological correctives by the artificialities 
 of modern civilization calls for rational ^dance oFall phases of 
 human behavior, including the desire for food. In these times of 
 plenty, overfeeding, with its physiological penalties and economic 
 waste, is on the whole more prevalent than undernutrition, because 
 of the barbaric indulgence in the pleasures of the table in the 
 absence of the physical stress of more primitive social condition. 
 And when hunger becomes pathologicallj^ exaggerated the j)h^i J 
 cian of today knows no remedy; when it fails in disease, he dis- 
 penses the "bitter herb" of tradition — and hopes for the best. 
 Hence) when the reader has followed us through these we hope 
 not too technical pages, we believe that he will agree that there is 
 yet much work to be done on the problem of hunger control — work 
 worth doing, co-operative work of the clinic and the biological 
 
 laboratory. 
 
 A. J. Carlson 
 University oj Chicago 
 September, 1916 
 
TABLE OF CONTENTS 
 
 CHAPTER PAGE 
 
 I. The Biological Significance of Hunger .... i 
 
 II. Historical i6 
 
 III. The Stomach in Hunger 30 
 
 ly. The Stomach in Hunger (Continued) 56 
 
 V. Some Accessory Phenomena in Hunger 84 
 
 VI. The Relation of Hunger to Appetite 96 
 
 VII. The Sensibility of the Gastric Mucosa . . . . ioi 
 
 VIII. Hunger and Age 119 
 
 IX. Hunger in Prolonged Starvation 125 
 
 X. The Nervous Control of the Hunger Mechanism . . 149 
 
 XI. The* Nervous Control of the Hunger Mechanism' (Con- 
 tinued) 161 
 
 XII. The Nervous Control of the Hunger Mechanism (Con- 
 tinued) . . ■ 199 
 
 XIII. The Chemical Control of the Hunger Mechanism . 217 
 
 XIV. Secretion of Appetite Gastric Juice in Man . . . 232 
 XV. The Chemistry of Human Appetite Gastric Juice . 248 
 
 XVT. Hunger and Appetite in Disease 261 
 
 XVII. Hunger and Appetite in Disease (Continued) . . . 289 
 
 Bibliography 303 
 
 Index .............. 317 
 
CHAPTER I 
 THE BIOLOGICAL SIGNIFICANCE OF HUNGER 
 
 I. HUNGER IN THE UNICELLULAR ANIMALS 
 
 The complex of sensation that in man and the higher animals 
 urges and compels to ingestion of food is called hunger and appetite. 
 From the standpoint of the persistence of living organisms the 
 ingestion of food is as important as" reproduction. Consequently 
 the himger sensation is as fxmdamental as the urge or appetite of 
 sex. In fact, if we define hunger biologically as the conditions 
 (rather than the sensation colnplex) that lead to taking food, hun- 
 ger is even more fundamental or primitive than the sexual urge 
 (libido), since feeding is a necessity in all forms of life, while sexual 
 reproduction is not. 
 
 Whatever be the underlying mechanisms in the genesis of the 
 hxmger urge, in the higher animals this urge is obviously a sensa- 
 tion involving a more or less complex nervous organization. Hun- 
 ger as a sensation or conscious process is therefore probably confined 
 to animals having a nervous system and an alimentary canal. But' 
 all living organisms feed. What, then, are the ftictors that lead to 
 the ingestion of food in unicellular animals and in the simpler 
 metazoa having no specialized nervous system? And are there 
 any essential connections between these primordial factors that 
 cause the ameba to pursue and engulf another moving protozoan, 
 and the mechanism of the hunger urge compelling a starving wolf 
 to chase, capture, and devour a rabbit ? 
 
 All the imicellular animals live, at least during their periods of 
 activity, in water, in animal and plant fluids, or within the living 
 cells of other animals. In the case of the simpler organisms that 
 are parasitic the conditions of feeding are essentially those of the 
 tissue cells of the higher animals. That is to say, the food materials 
 are in solution in the medium surrounding the cell or the animal. 
 According to Putter, this also applies to all lower forms of hfe 
 
2 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 inhabiting the waters of the earth. It is not known to what extent 
 the organic material in solution in the sea water actually sustains 
 the lower animal life, but it is in all probability a very small, if not 
 entirely a negligible factor (Biedermann, Lipschiitz, Kerb, Mor- 
 gulis). We do know that all metazoa feed on other unicellular 
 animals and plants, whole or in fragments. That is, they take 
 into their bodies as food other solid bodies. As regards the actual 
 processes of ingestion of soUds by the protozoa, we have practically 
 identical conditions in the case of the special phagocytic cells in 
 the higher animals, although the latter is probably not a feeding 
 process primarily. 
 
 What determines the amount and the avidity of food ingestion 
 in the unicellular animals? During the active stage the feeding 
 appears to be on the whole as continuous as contact with food 
 particles permits.. Nutrient and non^nutrient particles are taken 
 up somewhat indiscrimiaately, although there are many exceptions 
 to this rule. In some cases minute motile organisms may by the 
 force of their own motility penetrate into a imicellular animal only 
 to be digested by the latter, but the taking up of solid particles by 
 protozoa is mainly due to active ameboid movements. Augmenta- 
 tion of ameboid movements, increased rate of contraction of 
 pseudopodia acting as feeders, increased ciliary motion both in 
 free swimming and in sessile forms might be taken as external 
 expressions of states of hlmger as these would enhance the securing 
 of food.. 
 
 Are such expressions of hunger state actually present ? Jen- 
 nings, in his studies of the feeding processes of ameba, is silent on 
 this point, except for a few incidental observations that an ameba 
 may remain at rest for a few minutes after having taken up a 
 morsel of food, but since the ameba is on the go again before this 
 food is actually digested, the brief rest period cannot.be interpreted 
 as a state of satiety. Verwom thinks that all the phenomena of 
 feeding in the protozoa, including a certain capacity of selection of 
 food, involve automatic motility (chemo- and steireotropism) only, 
 but we are not informed whether the rate of this motihty varies 
 with the degree of htmger. In vorticella Hodge and Aikens found 
 
BIOLOGICAL SIGNIFICANCE OF HUNGER 3 
 
 that the cilia worked unifomily and continuously night and day, 
 in drawing in and assorting food particles: "all efforts to surfeit 
 the tiny animals with food produced no appreciable effect in satis- 
 fying their apparent hxmger." In the presence of an abundance of 
 food the body cilia of Paramecium beat less actively, thus bringing 
 the animal to rest, while the oral cilia continue in activity, drawing 
 the food*particles into the mouth (Jennings). Wallengren, on the 
 other hand, found no change in ciliary movements and vacuole 
 contractions, or in the excitabihty of the paramecium during hun- 
 ger except that ciliary and vacuole activity is decreased when the 
 organism is near death from starvation. 
 
 Schaeffer has described in stentor certain differences in behavior 
 between the states of hunger and satiety. When stentor is gofged 
 with food it remains somewhat contracted, the activity of the 
 membranellae are greatly decreased, the animal is less excitable to 
 external stimuli, and it discriminates more perfectly between food 
 particles and indigestible particles in the water current. The 
 degree of satiety appears to depend on other factors beside the 
 amoimt of food in the body. It seems clear, then, that a state of 
 depletion or himger in the stentor leads to increased excitabihty, 
 increased motihty, and increased avidity of food ingestion. It is 
 not unlikely that future investigations will reveal similar differences 
 in most of the protozoa. Parker found that meat or meat extract 
 reverses the stroke of the labial cilia in sea anemones, so that the 
 water current carries the food particles into the esophagus. This 
 appears to be an instance of a considerable degree of specialization. 
 Will meat extract in the sea water induce this reversal after the 
 anemone is gorged with meat or othpr forms of food ? 
 
 As regards food substances in solution, we may assume that 
 the rate and quantity of ingestion depend on the diffusion rate of 
 the substance and the permeability of cell surfaces. Dilution of 
 food material within the cell may increase surface permeability, 
 and vice versa. We know so little of the correlation of the inter- 
 nal processes in Hving cells and unicellular animals that we cannot 
 predict what effect scarcity of nutrient material within the cell 
 has on ameboid and ciliary movements, except that when the 
 
4 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 depletion approaches exhaustion these movements probably suffer 
 depression. In some animals partial or complete starvation ap- 
 pears to accelerate metamorphosis and redifferentiation, but the 
 factors involved in these processes are obviously more complex 
 than that of simple and direct cell stimulation. 
 
 In the ingestion of organic particles or cells by the special 
 phagocytes in the higher animals, certain new factors enter into 
 play. In the first place, phagocytosis in the metazoa is not pri- 
 marily a feeding process; but concerned with destruction of cellular 
 d6bris and cells foreign to the organism. So far as we know, the 
 metazoan phagocytes feed on the organic substances in solution 
 in the body fluids, just like the cells of other tissues. Secondly, 
 the rate and quantity of ingestion of the foreign cells depend in 
 part, not on the condition of the phagocyte, but on certain sub- 
 stances (opsonins) in the body fluids that act on the foreign cells. 
 This factor is not known to be involved in the feeding phagocytosis 
 of the protozoa. Thirdly, even apart from the opsonin factor, cer- 
 tain of the phagocytic cells of the metazoa appear capable of being 
 "trained" to increased activity. The mechanics of this capacity 
 is a matter of conjecture. These differences in the biological 
 meaning of phagocytosis in the metazoa, and the feeding phagocy- 
 tosis in the protozoa do not imply that the essential mechanics of 
 the phagocytic processes in the two groups are different. 
 
 There are indications, then, that relative depletion of ingested 
 food material, at least in some of the protozoa, results in increased 
 motility (ameboid, ciliary) and increased avidity for food or rate 
 of food intake. These phenomena probably indicate a condition of 
 increased cell excitability. That is to say, a state of hunger in the 
 protozoa is a state of increased excitability. The question how a 
 state of cell hunger causes primarily a state of increased cell excita- 
 bility caimot be entered into here. To those who prefer anthropo- 
 morphic concepts the pursuit, capture, and selection of food by 
 the protozoa become expressions of conscious states analogous to 
 those in higher animals under like conditions. But, for the present, 
 at any rate, simpler explanations are not only adequate, but more 
 useful. The principles of diffusion and selective permeability or 
 
BIOLOGICAL SIGNIFICANCE OF HUNGER 5 
 
 absorption suffice to account for ingestion of food in solution. 
 The selection of solid food, so far as this principle is in evidence, is 
 probably a matter of inherited mechanism for differential response 
 to chemical and mechanical stimuli. The ameboid and ciliary 
 motility involved in the hunger state introduces more complex 
 factors. Rhumbler endeavored to analyze the former into purely 
 physical surface tension phenomena. Jennings has shown, at least 
 for the ameba, that the surface-tension theory is untenable. But 
 while we are thus forced back on unknown factors in the organiza- 
 tion of the cell, there is no reason for believing that when once 
 analyzed these cell processes are not, individually, quite as definitely 
 physical and chemical phenomena as surface tension. Hamburger 
 has recently shown that lack of oxygen acts as a primary stimulus 
 to phagocytosis. But this is in all probability not the mechanism 
 that induces increased cell motility in state of cell hunger, as there 
 is no evidence that a decrease in the food material in the cell is 
 accompanied by oxygen want. 
 
 II. HUNGER IN PLANTS 
 
 This general biological conception of hunger is probably as 
 applicable to the lowest, or imiceUular plants, as to the unicellular 
 animals. But we have been imable to find any data bearing directly 
 on this question. We have extensive studies on the chemotactic 
 and general tropic behavior of the lower plants (Pfeffer, Kniep, 
 Kusano, Shibata, etc.). Kniep ascribes senses of taste and smell 
 to bacteria, and shows that the response of bacteria to certain 
 chenaical stimuh depends on the reaction of the culture medium, 
 but he does not seem to have raised the question whether the 
 quantity and quality of the food in the culture medium is also a 
 factor in this response. Nor is the question of the effect of starva- 
 tion on the behavior of bacteria raised in the recent extensive 
 studies on the metabohsm of bacteria by Kendall and his pupils. 
 
 The swarm cells of the spore-producing plants appear to feed 
 by phagocjrtosis, just like the unicellular animals, and it is likely 
 that this feeding phagocytosis in plants is influenced by hunger 
 in the same way as in the lower animals. Lister describes the 
 
6 CONTROL OF HUNGER IN HEAL'TH AND DISEASE 
 
 ingestion of microspores and bacteria by the swarm cells of 
 mycitozoa, and records the following feeding behavior: 
 
 In one instance, after taking in two stout bacilli, and inclosing them in 
 separate vacuoles, the swarm cell remained quiescent for a length of time. 
 I watched the gradual process of digestion of the baciUi. After remaining 
 (quiescent) under observation for nearly an hour and a half the swarm cell 
 swam off with vigorous lashing movement of the cilium. 
 
 With the exception of some of the bacteria, the swarm cells of 
 the sporoph3d:es, the group of "parasitic" plants and, to a certain 
 extent, the so-called "carnivorous" plants, the vegetable organisrris 
 feed primarily on the inorganic material in the soil and on the 
 carbon dioxide of the air, and in these feeding processes motility 
 of the plant, apart from growth, plays a minor part. The plant 
 cannot move itself, nor can it move its food, even to the extent that 
 both are possible in sessile animals. We may speak with perfect 
 justification of starvation in plants, but in the case of the higher 
 plants there is no evidence that starvation increases excitability 
 and motility, that is, 'induces a biological state of hunger, nor would 
 such changes aid the higher plants iri securing food. 
 
 III. HUNGER IN THE HIGHER ANIMALS 
 
 As experienced by man, the hunger urge is a more or less uncom- 
 fortable feeling of tension or pressure and pain referred to the 
 region of the stomach. In normal persons the htmger must become 
 exceptionally strong to be markedly painful. Ordinarily the feeling 
 is one of somewhat imcomfortable tension, accompanied by a 
 feeling of "emptiness" in the epigastric region. 
 
 Another characteristic element in the hunger feeling as known 
 in man is its periodicity or intermittency, even when the stomach 
 continues empty and the physical d,ctivity of the individual proceeds 
 without interruption. The significance of this attribute has been 
 especially emphasized by Bardier, Sternberg, Polimanti, Caimon 
 and Washburn. It probably appHes to the hunger sensation ia 
 most mammals and birds. In the lower animals, so far investigated, 
 this periodicity is of a different type, or is possibly lacking. Some 
 persons appear to experience a certain feeling or sensation in the 
 
BIOLOGICAL SIGNIFICANCE OF HUNGER ^ 
 
 esophagus, the throat, and the muscles of mastication synchronously 
 with the gastric hunger. The writer has never experienced these 
 esophagus and throat elements. From all accounts, they differ 
 from the gastric sensation in not being uncomfortable or painful. 
 In the species of birds having a region of the esophagus dilated 
 into a crop, the hunger sensation probably has its origin in the crop 
 rather than in the muscular stomach or gizzard. 
 
 The epigastric sensation of varying degrees of pain is, however, 
 the one indispensable element in hunger. But frequently certain 
 accessory phenomena are present. The most common of these is a 
 feeling of general lassitude or weakness. Headache, nausea, nervous 
 irritability, vaso-motor instability, and even fainting may appear as 
 part of the hunger complex. Strictly speaking, a certain degree 
 'of nervous hyperexcitability is a necessary effect of hunger of e^en 
 moderate intensity, and should therefore not be called, an accessory 
 phenomenon. But in normal persons with stable nervous organi- 
 sation, strong hunger may be present without any. feeling of weak- 
 ness, headache, or obvious manifestations of nervousness. In some 
 individuals, on the other hand, the feeling of weakness, headache, 
 and general restlessness may be so marked as to crowd out of 
 consciousness the central factor of hunger, the gastric hunger pangs. 
 
 In man the genesis of the hunger sensation requires a stomach 
 empty or nearly empty of food. Adult persons eating three to five 
 large meals per day probably seldom experience hunger unless 
 engaged in severe physical labor or exposed to intense cold. In 
 such individuals the nervous impulses from the stomach that give 
 lise to the hunger pangs do not become sufficiently intense to affect 
 consciousness. ' 
 
 We shall show later that the genesis of the hunger pangs is due 
 to certain contractions and tonus states in the stomach, the afferent 
 nervous impulses thus initiated affecting certain parts of the brain. 
 Himger as known in man thus requires a nervous system, a mus- 
 cular digestive tract, and an afferent or sensory pathway connecting 
 the two. These anatomical conditions are common to all verte- 
 brates, and to the various invertebrate groups down to and including 
 the coelenterates. 
 
8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The influence of the hunger state on the behavior is essentially 
 the same in all these animals.,jA fundamental characteristic is 
 increased nervous excitability and restlessness. ^pThe restlessness 
 is probably not primarily due to the consciousness of the himger 
 feeling, since it is in evidence in animals deprived of their cerebrum 
 (dogs, birds). The strong hunger urge evidently inhibits fear, as 
 the starving animal becomes more bold and ferocious. It is gen- 
 erally held that the state of hunger in man tends to produce a 
 cantankerous or unsocial disposition! t)n^the other hand, pro- 
 longed fasting by the religious devotee is supposed to make him 
 more worthy or fit to commune with the gods. 
 
 In the normal man, and probably in the carnivorous animals, an 
 empty or a nearly empty stomach is a requisite for the appearance 
 of the hunger feeling. This is evidently not the case in the ruminat- 
 ing animals and in the herbivora in general, for in these animals 
 the stomach is never empty — ^not even after days of starvation. 
 Birds, also, feed more or less continuously, even though the crop 
 or the stomach is quite filled with food. Either these animals do 
 feel himger on a partially filled stomach, or else they eat, not because 
 of feeling the himger urge, but because of appetite. 
 
 On the other hand, hunger may be apparently absent in some 
 animals, even though the stomach is completely empty of food 
 for weeks or months. It is generally accepted as a fact that the 
 Rhine and the Pacific species of salmon do not feed after entering 
 the rivers to spawn, although the fish is doing great muscular work 
 in going hundreds of miles against river currents, in ascending faHs, 
 and in fighting rivals. Voit thought that under these conditions 
 the fish cannot be feeling hunger. When in captivity, certain 
 animals may refuse food even to the point of starving to death in 
 the presence of plenty. jThe call of the empty stomach, if suffi- 
 ciently strong, wakes up the sleeping child, the sleeping man, or 
 the sleeping dogjbut the empty stomach does not appear to disturb 
 the hibernating animal. " The caterpillar," says the great physiolo- 
 gist Haller, "does nothing but eat and defecate." After the cater- 
 pillar has turned into a butterfly he may never feed again, 
 particularly if his span of Ufe is a short one, despite great physical 
 
BIOLOGICAL SIGNIFICANCE OF HUNGER 9 
 
 exertion in flight and reproduction. It does not appear that this 
 diminution or absence of feeding in many insects after the final 
 metamorphosis is associated with atrophy or absence of the ali- 
 mentary tract. These special conditions obviously involve changes 
 in the brain processes, in the stomach, or in the nervous connections 
 between the brain and the stomach, which must be cleared up by 
 new lines of work; but they do not overthrow the foregoing view 
 of the r61e of the hunger urge in feeding, or the r61e of the empty 
 stomach in the genesis of this urge. 
 
 Except in the peculiar and special cases referred to above there 
 is evidence that the intensity or persistence of the himger urge 
 rims parallel with the degree of activity and the rate of metabolism 
 in the normal individual. jHunger is thus more marked in the 
 young and growing than in the aged and inactive individual. 
 There are indications in mammals that hunger may be experienced 
 even before birth. In warm-blooded animals hunger is augmented 
 by external cold, and depressed by external heat. The reverse 
 is probably true in the cold-blooded aninlals, but this point has 
 not been experimentally determined. These relations do not 
 obtain in various conditions of disease. 
 
 IV. HUNGER, APPETITE, AND THE INGESTION OF FOOD 
 
 Why does this feeling of uncomfortable tension or hunger pang 
 in the stomach induce us to take food ? The obvious reply is that we 
 know that eating will abohsh the pangs. That is, it is a matter of 
 individual experience. This answer does not seem adequate in the 
 case of the newborn animal. Even if the animal experienced the 
 sensation of hunger before birth, he caimot have experienced what 
 effect the ingestion of food has on this sensation. What induces 
 the newborn animal to take his first meal ? Is it a matter of inherited 
 reflexes or "instinct" ? Gemelli and others refer to hunger as an 
 "instinct." The animal emerges from >the egg or uterus provided 
 with all the essential reflexes, the working order of most of these 
 probably already tried out before entering upon the new mode of 
 living. The feeding reflexes are there; so are the defensive ones 
 in the way of rejection of impalatable or really injurious substances 
 
lo CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 once in the mouth. We have seen that the hunger state of the 
 stomach augments the reflex excitability. This leads to greater 
 degree of moving about on the part of the newborn animal capable 
 of locomotion, and to greater activity of the feeding reflexes in all. 
 This the writer has observed in decerebrated pigeons kept in good 
 condition for months after the operation. When the crop becomes 
 empty this bird not only becomes restless and keeps walking about 
 incessantly, but picks at the floor, the walls of the cage, or the 
 empty air. If it happens to pick at food before it, there is no indi- 
 cation of "recognition" of it as food. Nor does it open its beak in 
 going through the motion of picking. The significant fact in this 
 connection is the inducing of the picking reflex by the hunger state. 
 
 In the newborn everything within reach goes into the mouth 
 to be rejected or swallowed according to its chemical character or 
 physical consistency. It would, then, seem that the newborn connects 
 up the gastric hunger urge with the processes of feeding as a matter of 
 individual experience by the method of trial and error. In man there 
 is conscious direction on the part of the mother. Conscious direc- 
 tion as well as the factor of imitation probably plays a r61e in newly 
 hatched chickens "learning" to feed. In the young birds that 
 secure their food by thrusting their beak and head down the throat 
 of the mother, maternal direction is also probably the initial factor. 
 The hunger sensation induces the movements of sucking in the 
 newborn mammal, while in the newly hatched and immature bird 
 it causes the beak to be set wide open. Such minor differences 
 are obviously a matter of inherited reflexes, and we need n'ot fall 
 back on "instincts" to account for them. 
 
 On the foregoing hypothesis the connection between the primary 
 sensation of hunger and the processes. of feeding is a matter of 
 individual experience by the method of "trial and error." The 
 fundamental factors are the augmentation of all reflexes by the 
 gastric himger state, the removal of the hunger pangs, and the 
 production of the opposite sensation of satiety by sucking, masti- 
 cation, and ingestion of food. The theory demands the presence 
 of memory, otherwise each feeding act or feeding period becomes a 
 matter of trial and error. 
 
BIOLOGICAL SIGNIFICANCE OF HUNGER ii 
 
 We may ask whether this gap between the pure sensation of 
 hunger' and the ingestion of food in the newborn is not in reaUty 
 bridged by the factor of appetite. There is as yet great uncertainty 
 and confusion in regard to the elements of appetite, and the relation 
 of appetite to hunger. Many physiologists appear to accept the 
 view that appetite and hunger involve identical mechanisms and 
 differ only in degree of intensity. That is, a mild state of hunger 
 is called appetite, and a strong appetite is called hunger. There 
 are others who maintain that hunger and appetite are different, 
 both in the quahty of the sensation and in the mechanisms involved 
 in the genesis of the sensation. The latter view appears to make the 
 nearest approach to actual conditions. 
 
 Appetite, as we know it, cannot be separated from our memory 
 of past experience with food, that is, the taste, smell, and appear- 
 ance of food. In fact, it appears to be essentially pleasant memory 
 processes of these past experiences, and the "urge" in appetite 
 may be only a special case of the general desire for pleasure. If 
 this is the case, there can be no urge for food in the absence of past 
 experience with food on the part of the individual, and as this is 
 lacking in the newborn, the appetite urge must also be wanting. 
 Hence it is not the factor that guides the newborn individual for 
 the first time to aboUsh the pangs of hunger by ingestion of food. 
 However, it is conceivable that appetite contains an elemental urge 
 for food as an inherited mechanism and thus not dependent on 
 individual experience, and that when the individual has such 
 experience with food, memory processes of this experience fuse 
 with or overshadow the inheritance factor, so that the two cannot 
 be dissociated in consciousness. This inherited appetite urge, if it 
 exists at aU, is probably essentially a positive chemotropism (smell, 
 taste), although birds hatched sufficiently mature to seek their 
 own food probably select or seek the food by vision rather than 
 by smell. 
 
 This positive chemotropism for food may in the newborn of 
 the higher animals involve an element of pleasure. It is clear that 
 such an inherited positive chemotropism augmenting the motihty 
 and guiding the movements, plus the inherited reflexes of taking 
 
12 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 everything within reach into the mouth, will lead to food ingestion 
 in the newborn, even in the absence of hunger. But if the latter is 
 present the food ingestion completes the experience of removal of 
 the impleasant hungef pangs by feeding. Loeb and others have 
 referred to a positive chemotropism as a factor in the finding and 
 selection of food, especially in the lower animals, but we do not know 
 whether in the species thus controlled a state of hunger means an 
 increased excitability and augmented motor response to the specific 
 chemical stimuli. 
 
 It would thus seem that the first ingestion of food on the part 
 of the newborn or newly hatched animal that feeds unaided by the 
 parents can be accounted for by either of the theories outlined 
 above. Given the hunger pangs with its effects in the way of 
 increased motility and reflex excitability and the inherited reflexes 
 of putting everything within reach into the mouth, plus the reflexes 
 causing rejection of injurious or "disagreeable" material, the in- 
 gestion of food becomes only a question of it being within reach, 
 and the experience of removing the uncomfortable pangs of hunger 
 by feeding is quickly established. On the other hand, given an 
 inherited appetite urge or positive chemotropism, so that certain 
 olfactory and gustatory stimuli initiate and direct the reflexes 
 and possibly produce a sensation of pleasure, ingestion of food is 
 equally ineAdtable. 
 
 The first experience of feeding once gained, the individual will 
 feed again because of appetite, that is, the pleasure in the tasting 
 and smelling of food, and the pleasure in the sensation of satiety, 
 or because of hunger and the experience that feeding removes the 
 hunger pains. 
 
 In the discussion so far we have used the term "food" mostly 
 in the restricted sense of organic food substances. In a wider 
 sense the term "food" includes all materials necessary for the 
 continuance of the life of the animal. The sensations induced by 
 the lack of water (thirst) and by impairment of the external pro- 
 cesses of respiration (dyspnea) have nothing in common with the 
 sensation of hunger (due to lack of pabulum in the stomach), 
 either in their genesis or in their character, except that all three 
 
BIOLOGICAL SIGNIFICANCE OF HUNGER 13 
 
 sensation complexes are more or less uncomfortable or painful. 
 But we may speak of the sensation of thirst for water as analogous 
 to the sensation of himger for food. There is, however, no appetite 
 for water analogous to the appetite for food. This is probably due 
 to the absence of taste qualities in pure water, and hence to absence 
 of memory representations of taste. In the case of beer or other 
 artificially flavored drinks that may be taken to satisfy thirst, 
 taste quaUties are present, and persons may develop an appetite 
 for these drinks in connection with as well as in the absence of actual 
 thirst, just as we may have appetite for certain foods with or without 
 actual hunger sensation. 
 
 v. "salt hunger" 
 
 The condition referred to by physiologists as "salt hunger" is 
 not ordinarily experienced by man, except as a preference for some 
 degree of salt flavor in the diet. But this cannot be the factor that 
 makes some herbivorous animals travel great distances to "salt 
 licks," because the salt is not actually mixed with their food. It 
 is well known that depletion of the sodium chloride content of the 
 blood and the tissues below a certain limit leads to serious disturb- 
 ances in organ activity, but we do not know their specific effect on 
 consciousness. Possibly it is a feeling of general discomfort and 
 weakness, rather than any specific quality of sensation referred to 
 any one part of the body, although marked reduction of the NaCl 
 in the blood leads to absence of the hydrochloric acid in the gastric 
 juice and, in consequence, digestive disorders. 
 
 The experiments of Forster on dogs and pigeons, and those of 
 Lunin on mice showed that animals succumb sooner on a salt-free 
 •diet than if they are given no food at aU. The symptoms developed 
 by these animals are: weakness and cachexia, nervous hyper- 
 ■excitabiHty, tremors, and gastero-intestinal disorders (indigestion, 
 vomiting, refusal of food). It is still an open question whether any 
 animal, man included, actually needs sodium chloride in addition 
 to the salts present in all natural foodstuffs. Smith, the veterinary 
 physiologist, maintains that "both camivora and herbivora obtain 
 in their natural diet a sufl&ciency of salts, although there is a 
 
14 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 general impression that the wild herbivora long for sodium. It is 
 quite certain that under conditions of domestication horses can be 
 kept in perfect health without receiving any sodium chloride other 
 than that contained in the food, and the amount of this in vegetable 
 substances is very small." Nevertheless, it is a fact that herbivorous 
 animals, wild as well as domesticated, ingest sodium chloride when 
 available, while this is not done by the out-and-out carnivorous 
 species. History seems to show that it is the agricultural races or 
 tribes that have developed the need or at least the greatest desire 
 for salt. According to Bunge, among the races living exclusively 
 or mainly on animal food, salt is either unknown, unused, or actually 
 disliked, while some of the agricultural tribes in Central Africa 
 cherish salt as ardently as our children desire sweets. It is even 
 beheved by some anthropologists that this need or desire for salt 
 or animal-food is a -factotiii-cannibaHsm. 
 
 Mimgo Park, the traveler, describes his own feelings on long- 
 continued salt want as follows : "I found the scarcity of salt actually 
 painful. The continued subsistence on nothingburvegetablefoDd: 
 produced finally a desire for salt so painful that it can hardly be 
 described." We are not familiar with any prolonged experiments 
 with salt-free diets on man. But persons on ordinary diets who have 
 gone for a long time without sodium chloride complain in general of 
 lack of appetite (owing to the unpalatability of the food), and of 
 some vague or general bodily distress — a condition similar to that 
 induced by monotonous and incomplete diets, 
 
 But even if we assmme that the herbivora do experience a "salt 
 hunger" in the sense of general bodily discomfort and weakness, 
 of special distress referred to the digestive tract, how do the animals 
 know that eating salt will reKeve these sensations, and how do 
 they know where to find the salt ? In all probability it is a matter 
 of individual experiences and memory. We may assume that a 
 certain amount of salt flavor is pleasant to these animals as a matter 
 of inherited reflexes or because of its slight stimulating action. 
 Hence they will eat or lick the salt wherever found, irrespective 
 of actual need. Now, if actual salt need is expressed in a feeling 
 of general bodily distress, and salt being available, the animal wiU 
 
BIOLOGICAL SIGNIFICANCE OF HUNGER 15 
 
 sooner or later encounter the experience that eating salt eases the 
 distress. As long as the calf feeds on the milk, of its mother, no 
 additional salts are required in its diet. But, of course, the calf 
 follows the mother to the "salt licks," and through imitation or 
 curiosity learns the taste of salt as well as the location of the " Ucks," 
 both before and after he actually experiences salt hunger. Thus 
 by aid of the parents or the herd, the individual experience is 
 established. 
 
CHAPTER II 
 
 HISTORICAL 
 
 I. THEORIES OF HUNGER AND APPETITE 
 
 The theories so far advanced to explain the genesis of hunger 
 and appetite fall into three main groups, namely, those involving 
 the stimulation of sensory nerves mainly in the digestive tract — a 
 peripheral origin; those involving a direct stimulation of a hypo- 
 thetical "hunger center" in the brain by the blood, or by some 
 changes in the metabohsm in the center itself — a central origin; 
 and lastly those involving a combination of both central and general 
 peripheral factors of hunger — a general sensation. 
 
 Theories of peripheral origin of hunger. — The theories of a purely 
 peripheral origin of hunger may in turn be grouped under two 
 heads,' viz., (i) The stimulation of a strictly local group of sensory 
 nerves (mainly in the stomach), and (2) the stimulation of all 
 afferent nerves by some change in the tissues or in the blood. We 
 shall first outline the theories that account for the hunger sensation 
 by the stimulation of sensory nerves in the digestive tract. There 
 are, to the author's knowledge, at least six such theories, namely: 
 (i) Hunger is due to mechanical stimulation of sensory nerves in 
 the gastric mucosa by mechanical rubbing or pressure from con- 
 traction of the stomach. (2) Hxmger is due to chemical stimulation 
 of sensory nerves in the gastric mucosa . (the acid of the gastric 
 juice, etc.) . (3) Hunger is due to the stimulation of sensory nerves 
 in the gastric mucosa by a state of turgescence of the gastric glands. 
 (4) Hunger is due to the stimulation of sensory nerves in the gastric 
 mucosa by some change in the blood due to starvation. (5) Hunger 
 is due to stimulation of sensory nerves in the stomach by the atony 
 and absence of contractions of the empty stomach. (6) Hunger is 
 due to the stimulation of sensory nerves in the wall of the stomach 
 (muscularis or submucosa) especially in the fundus and cardiac 
 regions, by contraction of the empty or partly empty stomach. 
 
 1.6 
 
HISTORICAL 17 
 
 Sternberg's literary essays on hunger and appetite contain 
 numerous references to the conceptions of hunger and appetite 
 held by the ancient and mediaeval poets and philosophers; but 
 there appears to be little or nothing specific concerning the hunger 
 and appetite mechanisms in the writings of either Hippocrates or 
 Galen, although the popular view that prolonged starvation or 
 hunger is extremely painful dates back at least to the time of Homer. 
 Hippocrates does remark in one of his famous Aphorisms, that 
 "strong wine cures hunger," but the modus of this cure did not 
 appear to interest him. The theory that the sensation of hunger 
 is due to mechanical stimulation of sensory nerves in the gastric 
 mucosa goes back at least one hundred and fifty years to the great 
 physiologist Haller. On the subject of the immediate cause of 
 hunger, Haller wrote: 
 
 Hunger is initiated and intensified by bodily vigor, as in the athlete Mile, 
 in lions, and in aU animals possessing great strength by a peculiar strength of 
 the stomach and by physical labor of all kinds, especially at low temperature, 
 since hunger is intensified in cold climates. 
 
 Hunger is increased by the presence of intestinal worms, as they consume 
 part of the nutrient juice. It is also augmented by the patency of the pylorus, 
 a condition normally present in voracious animals, and resulting in an almost 
 continuously empty stomach. The sensation of hunger is sometimes even ex- 
 cited by certain acids, such as cream of tartar, lemon juice, and similar sub- 
 stances while regurgitation by putrefying intestinal contents into the stomach 
 depresses and prevents hunger. The numerous kinds of fruits especially enjoyed 
 by the people of the Orient are generally acid. 
 
 A greater degree of excitability of the (gastric) nerves also induces greater 
 hunger. 
 
 Finally there are imperfectly understood conditions characterized by an 
 inordinate augmentation of hunger, excessive eating, and ingestion of imusual 
 or indigestible substances. 
 
 Among animals, those having the shortest span of life, such as the 
 insects, are the most voracious feeders. The caterpillar eats and defecates 
 continuously. 
 
 Thus, we see, on the basis of the phenomena of hunger in the entire animal 
 kingdom, the immediate cause of the sensation of hunger is the grinding or 
 rubbing (tritus) of the delicate and vilous folds of the gastric mucosa against 
 each other, through a motion or contraction inherent in the stomach, aided 
 by the diaphragm and the abdominal muscles. These I consider as facts 
 
i8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 already demonstrated. A famous man' has suggested that the gastric nerves 
 thus irritated are restored by the congestion of blood in the mucus folds, as 
 occurs in all cases of irritation. 
 
 We can show, moreover, that the empty stomach is contracted so that 
 no lumen exists. In a hungry man the stomach is contracted (pinched). 
 
 From our knowledge of the intolerable sensation produced by rubbing 
 the exposed nerves in a region where the skin has been lacerated or broken, 
 we are permitted to estimate how acute must be the sensation caused by this 
 friction or stimulation of exposed nerves on the gastric mucosa, as in prolonged 
 hunger. 1 would not care to face such a sinister exitus. 
 
 These considerations make it clear why a long-continued fast causes only 
 mild hunger in animals like the snake, in whose stomach there is scarcely any 
 grinding action, as it is not stifSciently muscular; besides the strength of the 
 abdominal muscles and the diaphragm is almost nil. They also explain why 
 chickens die sooner from starvation than do dogs, cats, and carnivorous animals 
 in general. Indeed, the grinding action of the stomach in the galUnaceous 
 birds is stronger than in the quadrupeds. In some insects with feeble peristalsis 
 of the alimentary tract there is no hunger in winter, but in the summer the 
 hunger is greater the greater the heat. 
 
 So far Haller. It is probable that Haller confiise^ hunget with 
 appetite when he speaks of acids or bitter fruits augmenting hun- 
 ger, although if the sensory nerves of the hunger sense are distrib- 
 uted in the gastric mucosa, the possibihty of these nerves being 
 stimulated by certain chemicals in the stomach cavity cannot be 
 excluded. The central facts in Haller's conception are the tonicity 
 and contractions of the empty, stomach stimulating the hunger 
 nerves in the mucosa by pressure and rubbing. 
 
 Erasmus Darwin thought that the hunger pain is due to the 
 atonicity and absence of contractions in the empty stomach. The 
 view that the empty stomach of normal individuals is atonic and 
 quiescent has persisted in physiological and medical literature to 
 this day, despite both early and recent evidence to the contrary. 
 
 Johannes Miiller, one of the fathers of modern biology, staites 
 that hunger is a kind of negative sensation — or simply due to the 
 absence of the positive sensation generated in the stomach during 
 digestion. If this is the case, an individual should always feel 
 hunger after excision of the stomach or after section of both vagi 
 
 ' The physiologist Senac. 
 
HISTORICAL 19 
 
 nerves. Miiller notes, however, that the stomach of animals after 
 prolonged fasting or after death from starvation appears very much 
 contracted. 
 
 Weber considered it probable that "sudden and strong contrac- 
 tion of the empty stomach, completely obliterating the gastric 
 cavity, gives rise to a part of the sensation we call hunger." As 
 analogies to the hunger pangs he refers to the labor pains (uterine 
 contraction), the pangs from the large intestine in tenesmus, and 
 from the small intestine in cases of colic. Weber does not explain 
 how the gastric contractions stimulate the hunger nerves. This 
 general view that the hunger is caused by contractions of the empty 
 stomach has been accepted by a nvmiber of physiologists and clini- 
 cians (Vierordt, Hertz, Rnapp, and Sternberg), and finally demon- 
 strated by Cannon and Washburn, and Carlson. Voit, Albu, 
 Stiller, Nicolai, and others assume a gastric genesis of hunger 
 without going into the question of how the stimulation is brought 
 about. Sternberg has designated hunger as "Pruritus stomachi," 
 or a tickh'ng sensation, similar to that evoked from mechanical 
 stimulation of certain cutaneous areas. He also suggests that 
 appetite is in some way correlated with the peristalsis of the esoph- 
 agus and stomach and that absence of appetite or nausea is 
 similarly associated with antiperistalsis. Sternberg's papers on 
 the subject of hunger and appetite contain no original observations, 
 and one meets with a number of contradictions and far-fetched 
 analogies that prove nothing. Thus Sternberg says that "the 
 empty stomach is anatomically an atonic folded tube." Now, an 
 atonic stomach cannot give rise to hunger by contraction or peri- 
 stalsis, for the simple reason that these are not present, except when 
 there is a certain degree of tonus. 
 
 The turgescence theory of hunger as formulated by Beaumont is 
 untenable, for the reason that there is no actual accumulation of 
 gastric juice in the crypts of the glands in the empty stomach to 
 stimulate the gastric nerves by distension. Moreover, there may 
 be a continuous secretion of gastric juice during a hunger period. 
 Yet the theory is accepted, at least in part, by some recent workers 
 (Luciani, Valenti). 
 
20 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The theory that the sensation of hunger is a mere negative 
 phenomenon, or the absence of the positive sensation accompanying 
 the filled stomach, has not received much attention. If we consult 
 our own experience, the hunger urge appears to be a sensation as 
 positive as pain. We also know that the mere emptiness of the 
 stomach does not initiate the sensation. 
 
 The view that hunger is due to the chemical stimulation of 
 nerves in the gastric mucosa appears also to lead back at lea^t to 
 Haller. x Soemmering ascribes the hxmger pains of fasting to the 
 action of gastric juice on the mucosa nerves. Bostock accepts the 
 theory and credits it to "the chemical physiologists" (the itra- 
 chemical school?). Cannon thinks it is based mainly on clinical 
 evidence in cases of so-called gastric hyperacidity and h37persecre- 
 tion. Pavlov appears to accept it, when he cites his own experience 
 of hunger being initiated by a small quantity of wine passed into 
 the stomach. It is well established, however, that we may feel 
 hunger when the stomach is completely empty of gastric Juice and 
 other substances that may be capable of stimulating the nerves 
 in the mucosa. Some mucus is always present in the stomach, but 
 there is no evidence that this can act as chemical stimulus. It is 
 also known that in cases of complete absence of hydrochloric acid 
 in the gastric juice (achylia gastrica) hunger may be present. 
 
 Theories of the central origin of hunger. — Magendie thought that 
 hunger is strictly of central origin, not even directly due to depletion 
 of the blood or the tissues, since both the gastric sensation and the 
 general feeling of weakness may pass away without the individual 
 partaking of food. He denied tonic or periodic contractions of the 
 empty stomach, at least during the first 3 to 5 days of fasting, and 
 quotes only to reject mechanical stimulation of the stomach walls,, 
 traction on the liver by the diaphragm, fatigue (atony) of the 
 gastric musculature, bile and gastric juices in the stomach as causes- 
 of hunger; but he does not deny that sensory impulses for the organs 
 in general may be contributing factors. Tidemann, Schiff, Ewald, 
 Wundt, Milne Edwards, and others adhere in the main to this 
 theory but assume that the hunger center is stimulated by a starva- 
 tion state of the blood. Many authors have pointed out the' 
 
HISTORICAL 21 
 
 analogous condition in the case of the respiratory center being 
 stimulated by the venous condition of the blood. 
 
 The main objection urged against this theory is its failure to 
 explain, (i) the reference of the hunger sensation to the stomach; 
 (2) the fact that hunger may be temporarily abolished by the 
 eating of indigestible materials, and (3) the periodicity of the 
 "hunger sensation. 
 
 The main arguments urged by exponents of the central theories 
 against the gastric origin of hunger are: (i) Man and animals will 
 eat after excision of the stomach, or after section of the sensory 
 nerves to the stomach. (2) Hunger may be present, even when the 
 stomach is partly filled with food. (3) Hunger may be appeased 
 by feeding per rectum as well as by intravenous injections of food- 
 stuffs. 
 
 Hunger a general sensation. — ^As formulated by Bardier, this 
 theory assumes that the hunger center in the brain is stimulated 
 <iirectly by some change in the blood, arid indirectly by afferent 
 nervous impulses from all organs of the body, the stimulation of 
 these afferent nerves being also due to some change in the blood 
 induced by the state of hunger. With certain minor modifications 
 and additions, this view is accepted by Longet, Beaunis, Roux, 
 M. Foster, J. L. Miiller, Schlessinger, and others. According to 
 Roux the gastric moiety of the peripheral part of the hunger sense 
 constitutes appetite, that is, appetite is due to the stimulation of 
 sensory nerves in the stomach by the starvation changes in the 
 blood. Miiller, writing in 1915, cannot very well deny the gastric 
 hunger contractions, but-he assumes that these contractions are 
 caused through motor impulses in the vagi nerves by stimulation of 
 the himger center in the brain by the blood, although this possibility 
 was disproved in 1913 by Carlson. That the stimulation, central 
 and peripheral, is brought about by some changes of the blood 
 in starvation, is the main element in the theory. The analogy of 
 this mechanism to that of the genesis of thirst from the osmotic 
 concentration of the blood has been frequently pointed out in 
 support of the theory. DuBois-Reymond (quoted from Nicolai) 
 postulated a vagus hunger (gastric origin) and a tissue hunger (the 
 
22 CONTROL OF HUNGER IN HEAI.TH AND DISEASE 
 
 feeling of weakness) . Turro advances a " trophic reflex mechanism " 
 of hunger. Lack of nutrient material stimulates nerve-endings in 
 all organs. The impulses pass to a h}^othetical trophic center in 
 the basal ganglia of the brain, and these lower centers, in turn, 
 affect consciousness. He intimates that this "trophic hunger' 
 mechanism " is so perfectly adjusted by inheritance that the animal 
 on seeing food knows instinctively, as it were, just how much 
 salt, water, fat, starch, and protein to ingest. 
 
 The objections raised by various authors agaiust this theory 
 are: (i) Himger may set in before intestinal absorption is com- 
 pleted, and therefore before there can be any starvation change 
 in the blood. (2) There are not very marked chemical changes in 
 the blood even in prolonged starvation. (3) Hunger is abolished 
 temporarily by the eating of indigestible matter, and by taking 
 food hunger ceases before any of the food is digested and absorbed. 
 (4) Hunger is usually more or less periodic with sudden onsets and 
 endings, while changes in the composition of the blood from starva- 
 tion are more hkely to be gradual and continuous. (5) In very 
 prolonged starvation hunger does not, at least in man, increase in 
 intensity with the supposed depletion of the blood, and in fevers 
 himger may be absent despite prolonged starvation with increased 
 metabolism. 
 
 That the sensation of hunger is not an evidence of the immediate 
 need of food because of starvation changes in the blood was pointed 
 out by Voit in the following way. The people of Ireland, used to 
 voluminous rations of potatoes, complain of starvation and hunger 
 when given even greater food values, but in smaller bulk. The 
 same is true of the bread-eating peasants of Bavaria when put on 
 a diet of meat. 
 
 II. HISTORICAL STEPS IN THE EXPERIMENTAL INVESTIGATION 
 OF THE HUNGER MECHANISM 
 
 The earhest 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 
 
HISTORICAL 23 
 
 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 essen- 
 tially, it is clear that section of the vagi would not a£fect 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. Miiller 
 on the basis of analdgous 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 absorp- 
 tion into the blood. 
 
 The advance of modem 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 himger 
 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 riemains a consider- 
 able portion of the stomach aroimd the cardia where the imion 
 with the duodenum is made, and in healthy individuals at any rate 
 
24 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 this gastric remnant gradually hypertrophies and dilates to form a 
 considerable stomach pouch, sufficient in all hkelihood 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 ex- 
 hibits hypermotihty, 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 ahmentary tract. 
 
HISTORICAL 25 
 
 In extreme starvation the central element persists even when the 
 alimentary tract is fiUed 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 periods. 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 exclu- 
 sively per rectum for periods varying from i 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 shght 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 : (i) peripheral or gastric, and (2) central stimulation 
 of a hunger center, by starvation blood. 
 
 Boring, a psychologist, has recently reported a subjective 
 analysis of the character of the hunger sensation, based on the 
 experiences of a great number of persons. He concludes that hun- 
 g;er is a complex of pressure and pain. 
 
 Upon a background of dull pressure, which is sometimes recognized defi- 
 nitely as kenisthesis or the equivalent muscular pressure, there is set a dull 
 ache or gnawing pain which characterizes the hunger. Both pain and pressure 
 
26 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 are referred to the region of the stomach. The pain is noted as fluctuating, as 
 rhythmical, as unstable. Three of the observers described in addition a com- 
 plex kinesthesis in the throat, and oral sensations arising from the free flow of 
 saliva, a complex which meant for them a desire for food or appetite. Here 
 we have the true sensory basis for appetite. 
 
 According to Boring hunger is a twofold experience. It is pres- 
 sure in its weak form, pain and pressure when intense. This recog- 
 nition of a pressure or kinesthetic element in the hunger pains is 
 important, and has been made by previous observers. 
 
 As the reader will recall, the great physiologist, Haller, stated 
 that the "stomach of a starving man is contracted," and the 
 sensation of hunger is due to the rubbing of the folded mucosa by 
 this contraction. But during the one himdred and fifty years since 
 Haller's Elementa appeared the contracted condition of the stomach 
 in starvation has been questioned, denied, or forgotten. Schifl 
 A!(frote (in 1867): "The movements of the empty stomach are 
 rare, and much less energetic "than during digestion," and as 
 late as the year 19 10 Valenti stated that contractions in the empty 
 stomach are rare and feeble. The authors who followed Haller 
 and Weber in accepting the gastric contraction theory of hunger 
 did so essentially without experimental evidence. We take it that 
 all men have observed or experienced rumbling noises (borborygmi) 
 in the abdomen during the period when they feel strong hunger. 
 The noises are due to movements of gas by contraction of some 
 part of the alimentary tract below the esophagus. When the 
 noises are accompanied by the expulsion of gas or air from the 
 stomach into the esophagus the contractions are evidently in 
 the stomach itself, since this occurs in the absence of contractions 
 of the abdominal muscles and the diaphragm. However, in certain 
 "nervous" persons the borborygmi may be very pronotmced with- 
 out being associated with hunger, and it is obvious that these 
 noises may be produced in the large as well as the small intestines. 
 Hertz thinks that these noises arise exclusively from contrac- 
 tions of the small intestines. Nevertheless, the fact that the 
 borborygmi are so frequently associated with himger does not 
 appear to have been fully appreciated in connection with the 
 
HISTORICAL 27 
 
 genesis of the hunger sensation, until Hertz and .Cannon recently 
 called attention to it. 
 
 The view that the empty stomach is atonic and quiescent is 
 the more readily accepted, as contractions would seem to have no 
 useful purpose, except when there is food in the stomach. Now 
 and then later observers (Bettmann, Wolff, His) did record that 
 the stomachs of starving men and other animals are tonically 
 contracted, but the first important study and conclusive demon- 
 stration of the motor phenomena of the stomach in starvation we 
 owe to Boldyreff in 1905, although this investigator did not coimect 
 the gastric contractions with the genesis of the hunger sensation. 
 Working on dogs with inflated balloons in the stomach, Boldyreff 
 found that the stomach of starving dogs exhibits alternate periods 
 of strong contractions and absolute quiescence, at least during the 
 first 3 to 4 days of starvation. The contraction periods last 20 to 
 30 minutes, the quiescent periods for i| to 2§ hours. The period of 
 activity is made up of 10 to 20 contractions separated by intervals 
 of I to I J minutes, beginning with feeble contractions and gradually 
 reaching their maximum strength at the end of the period. During 
 these periods of gastric motor activity there were also contractions 
 in the intestines. Boldyreff states that the contractions of the 
 empty stomach are stronger than the gastric peristalsis during 
 digestion. There were no contractions in the empty stomach dur- 
 ing the periods when the gland secreted gastric juice copiously. 
 Hertz (1911) gave a different interpretation to these contractions; 
 namely, that they give rise to the hunger sensation. ^ 
 
 These are fundamental and important facts. Boldyreff did not 
 think that these gastric contractions gave rise to the sensation of 
 hunger, mainly because they diminished in strength with the length 
 of starvation. He suggests the possibihty that the state of hungeii 
 in the brain initiates the gastric and intestinal contractions via the^ 
 motor nerve fibers in the vagi. It seems hardly necessary to point 
 out that the genetic relations of the contractions of the empty 
 stomach to the hunger sensations cannot be established with cer- 
 tainty on experimental animals below man, because of the difficulty 
 in determining the kind of sensation experienced by the animal. 
 
28 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 In 1 910 Hudek and Stigler reported that the stomach empties 
 faster when the food is eaten with hunger than when eaten without 
 hunger. Cannon cites this fact as evidence that the stomach is in 
 greater tonus in the hunger state. It is obvious, however, that an 
 equally important factor is the greater rate of digestion owing to 
 the appetite gastric juice. The difference in the time of emptying 
 of the stomach observed by Hudek and Stigler may be due to this 
 factor alone. 
 
 In 191 1 Cannon and Washburn by experiments on man (Wash- 
 bum) proved that the periods of contractions in the empty stomach 
 aresjTichronous with the periods of hunger sensation, and that each 
 separate contraction is synchronous with a hunger pang. In their 
 experiments a small balloon was swallowed into the stomach and 
 the stomach contractions were recorded graphically parallel with a 
 signal showing when the subject felt the hunger. These observers 
 also obtained evidence of contractions in the lower third of the 
 esophagus, sjmchronous with the gastric contractions, and con- 
 clude that the esophagus plays a part in the genesis of hunger. 
 While noting that the hunger sensation tends to lag behind the 
 gastric contraction both at its beginning and its cessation, their 
 experiments, nevertheless, do not prove that the gastric and 
 esophagus contractions cause the sensation of hunger by stimu- 
 lation of sensory nerves, but they assume this to be the mechanism. 
 Nor do they indicate, on this assumption, whether the nerves stimu- 
 lated are those in the gastric mucosa, or in the muscular wall of 
 the stomach. This demonstration of the synchrony of the gastric 
 jcontractions and the subjective feeling of hunger is an important 
 step, but it does not inform us which is the cause and which the 
 effect. In other words, adherents of central or hunger-center 
 theory may still maintain that the gastric contractions are initiated 
 by motor discharges via the vagi nerves under the influence of a 
 periodic activity in the hunger center in the brain. 
 
 A year later (19 12) Carlson and his pupils, using essentially 
 the methods of Morat, Boldyreff, Cannon, and Washburn, demon- 
 strated on man and experimental animals that a certain type of 
 contractions in the empty or nearly empty stomach gives rise to 
 
the gastric mucosa, but in the submucosa or muscularis. These 
 hunger contractions of the empty stomach are primarily initiated 
 in the stomach itself and are thus independent of motor impulses 
 from the brain or the spinal cord. The perigheral_oiLgastn£origin 
 of the essential element in the sensation of hunger was thus finally 
 esfabKshedr 
 
CHAPTER III 
 THE STOMACH IN HUNGER 
 
 I. METHODS OF INVESTIGATION 
 
 Several methods are available for studying the tonus and con- 
 tractions of the empty stomach both in man and experimental 
 animals, namely: (i) direct inspection by means of a permanent 
 opening (gastric fistula) into the stomach through the abdominal 
 wall; (2) the introduction of a rubber balloon into the stomach, 
 either through the esophagus or through the gastric fistula, and 
 recording the variations in pressure on the distended balloon due 
 to contractions in the stomach; (3) the introduction into the 
 stomach of a balloon coated with bismuth paste on the inside. 
 This permits graphic recording of the stomach movements syn- 
 chronously with X-ray photography or inspection by aid of the 
 fluoroscope, and, in man, recording the subjective sensations. 
 
 In our work all three methods have been employed. During 
 the last four years the author has been fortunate in having in his 
 service a "second Alexis St. Martin," a man with complete closure 
 of the esophagus and a permanent gastric fistula of twenty years' 
 standing. The gastric fistula is large enough to permit direct 
 inspection of the interior of the stomach, and the introduction of 
 balloons, rubber tubes, and small electric lights for various investi- 
 gations. This man, Fred Vlcek, a native of Trebone, Bohemia, is 
 now thirty-one years old. For the last twenty years, or since 1897, 
 he has fed himself through a permanent gastric fistula owing to 
 complete closure of the esophagus, as a result of accidentally drink- 
 ing a strong solution of caustic soda. 
 
 Previous to the swallowing of the caustic the boy had always 
 been healthy. Since the completion of the gastric fistula in 1897, 
 he has enjoyed good health except that he suffered an attack of 
 pneumonia in 1908. Mr. V. came to America in 1910. He is in 
 good physical condition, height 5 ft. 8 in.; weight, 62 kg. With 
 
 30 
 
THE STOMACH IN HUNGER 
 
 31 
 
 the exception of the closed esophagus and the gastrostomy, the man 
 is in every respect in normal health, and of good average physical 
 development. The size, form, and position of the stomach is that 
 of the "orthotonic" type. The opening into the stomach is on the 
 lesser curvature about 4 cm. on the fundus side of the "transverse 
 band." The fistula is large enough to admit a rubber tube three- 
 fourths of an inch in 
 diameter, and a rubber 
 tube of this size is 
 always kept in the fis- 
 tula. It is usually 
 pushed in to a depth 
 of 3 to 4 inches. The 
 outer end (about 
 3 inches) is kept corked 
 and bent under the 
 bandage between 
 meals. The tube is 
 changed once a month. 
 Although the tube fits 
 rather snugly in the 
 opening, there is at 
 times some leakage of 
 gastric juice around it, 
 and in consequence 
 some corrosion of the 
 skin for a considerable 
 area around the tube. 
 The stomach mucosa joining the skin or scar tissue has the same 
 appearance and seems to show the same sensitiveness as the rest 
 of the stomach mucosa. X-ray photographs and direct inspection 
 by the fluoroscope show that the esophagus is completely closed 
 at the level of the sternum. 
 
 A normal person readily learns to swallow a small rubber balloon 
 with a small flexible rubber-tube attachment, and to keep these in 
 place for hours without the least discomfort or annoyance. There 
 
 Fig. I. — Mr. F. V. Twenty years after perma- 
 nent closure of the esophagus and estabhshment of 
 the gastric fistula. 
 
32 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 is some salivation to begin with, but this soon ceases. Adults as 
 well as infants with this apparatus in the stomach and mouth find 
 no difficulty in going to sleep during an observation period. It is 
 easier to swallow this apparatus than an ordinary stomach tube, 
 
 Fig. 2. — Photograph showing permanent gastric fistula of Mr. F. V., with rubber 
 tube in situ. 
 
 as the latter is too thick and inflexible. The method has been used 
 on newborn infants with success. It is being used in the author's 
 laboratory by graduate and medical students. The method is 
 so readily mastered as to make it generally available in physio- 
 logical, psychological, and clinical work. The main points involved 
 
THE STOMACH IN HUNGER 33 
 
 are: (i) the selection of balloon and rubber tubing of proper size 
 and flexibility; (2) the balloon and tube must be swallowed, not 
 pushed down into the stomach; (3) the avoidance of discomfort 
 or aversion by proper training. 
 
 The stomach contractions are recorded from the balloon in the 
 stomach connected by a rubber tube with a water, bromoform, or 
 chloroform manometer. The balloons used by us on man varied 
 in capacity from 75 to 150 c.c. In our observations on infants 
 balloons of smaller size were, of course, employed. And in the 
 work of the stomach (rumen) of goats, balloons of greater strength 
 and capacity are preferable. When bromoform manometers were 
 used a manometer tube 1.5 cm. in diameter was found serviceable. 
 The air pressure in the balloon with the stomach at relative rest 
 was usually adjusted at 3 to 6 cm. of bromoform. After trying 
 out balloons of varying capacities and thickness, we concluded 
 that a condum of the thinnest rubber available in the market was 
 the most serviceable, as this balloon when collapsed is easily swal- 
 lowed. The advantage of such a delicate balloon is in recording 
 the weaker tonus changes or contractions, and the pulse beat in the 
 stomach. The only disadvantage is the occasional breaking of the 
 balloon by an exceptionally sudden and vigorous stomach contrac- 
 tion, especially when a bromoform manometer is used for recording. 
 
 For the convenience of the reader who may not be familiar with 
 the ordinary technique of graphic registration, a diagram illus- 
 trating the balloon method as used on man is shown in Fig. 4 in 
 the hope that it may aid in interpreting the various stomach 
 tracings reproduced in this and subsequent chapters. 
 
 II. MOVEMENTS OF THE EMPTY STOMACH IN MAN 
 
 > The movements of the empty stomach in mammals were exten- 
 sively studied by Boldyreff in dogs by means of the gastric fistula. 
 Rubber balloons were introduced into the stomach and connected 
 by air or water transmission to the recording manometer. Accord- 
 ing to Boldyreff the empty stomach of the dog exhibits alternating 
 periods of complete quiescence during the first three or four days 
 of fasting. The periods of activity vary in length from twenty to 
 
34 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 thirty minutes, and the intervening periods of rest last from i| to 2| 
 hours. Both the fundus and the pyloric region of the stomach are 
 involved in the activity of the contraction period, the fundus giving 
 lo to 20 very vigorous contractions. Boldyreff states definitely — 
 and the published tracings seem to support the statement — that 
 
 Fig. 3. — Photograph showing arrangements for simultaneous recording of the 
 gastric hunger contractions and the vasomotor and cardiac changes (arm plethys- 
 mograph) of Mr. F. V. 
 
 between the period of strong rhythmical contractions the stomach 
 is in complete rest. The period of activity begins with weak 
 contractions, and these increase gradually in strength until the 
 period ends abruptly with the strongest contractions. Inasmuch 
 as the tracings pubhshed by Boldyreff do not show the stomach 
 
THE STOMACH IN HUNGER 
 
 35 
 
 respiratory pressure or the stomach pulse pressure, it #ould seem 
 that the methods of registration were not delicate enough to detect 
 feeble rhythms of contractions that might have been present during 
 the periods of relative rest. 
 
 Cannon and Washburn studied the movements of the empty 
 stomach in man by introducing a balloon through the esophagus 
 into the stomach. The observations were made 6 to 20 hours after 
 meals. They found that the periodic activity of the empty human 
 
 Fig. 4. — ^Diagram showing method of recording gastric hunger contractions of 
 the empty stomach of normal persons. B, rubber balloon in stomach. D, kymograph. 
 F, cork float with recording flag. M, manompter. L, manometer fluid (bromoform, 
 chloroform, or water). R, rubber tube connecting balloon with manometer. S, stom- 
 ach. T, side tube for inflation of stomach balloon. 
 
 stomach is very similar to that in the dog, but the average dura- 
 tion of the periods is not given. The fundus contractions were 
 about 30 seconds in duration, and the pause between the contrac- 
 tions lasted about 60 seconds. The pubUshed tracings show a 
 gradual tonus contraction of the fundus during the pause. The 
 observations of Cannon and Washburn were mainly directed 
 toward estabhshing the relation between the contraction periods 
 of the stomach and the sensation of hunger. They seem to agree 
 with Boldyreff in the absolute quiescence of the stomach between 
 the periods of strong rhythmical contractions. "Before the hunger 
 
36' CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 was experienced by W. the recording apparatus revealed no sign 
 of gastric activity." There is some indication of a feeble rhythm 
 during the rest period in one of their published tracings. 
 
 When the pressure in the balloon in the empty stomach of a 
 normal person is properly adjusted and the manometer-recording 
 devices made as delicate as- possible, the tracings obtained form 
 a composite of the following pressure variations in the gastric 
 cavity: 
 
 1. Periods of powerful rhythmical contractions, alternating with 
 periods of relative quiescence. As the duration of each individual 
 contraction in these periods is approximately 30 seconds, we may 
 call these contractions the "3o-sec6nds rhythm." The entire con- 
 traction period we will designate, provisionally, as the "hunger 
 period," and the individual contractions in the period the "hunger 
 contractions." 
 
 2. A tonus rhythm (tonus contraction of fundus) of wonderful 
 uiiiformity in rate, but fluctuating in amplitude, the rate varjong 
 from 18 to 22 seconds with an average of 20 seconds. The tonus 
 rhythm increases in amplitude without change in rate during the 
 periods of the powerful rhythmical contractions of the fimdus, and 
 are weakest immediately after these periods. But they are alwa3rs 
 present in the empty stomach of man, provided the subject is in 
 good health. For the sake of brevity we may designate these 
 contractions provisionally as "20-seconds rhythm." The method 
 used by Caimon and Washburn was evidently not delicate enough 
 to detect this tonus rhythm, and hence they concluded, erroneously, 
 that the empty stomach of man is completely quiescent between 
 the periods of the strong hxmger contractions. 
 
 3. A pulse pressure rhythm, always present. 
 
 4. A respiratory pressure rhythm, always present. 
 
 The periods of relatively powerful rhythmical contractions 
 (30-seconds rhythm) are practically identical with the periods of 
 "himger contraction" of Caimon and Washburn. The individual 
 contractions of these periods usually begin as a feeble tonus rhythm; 
 they gradually increase in amplitude pari passu with shortening of 
 the intervening pauses, and may or may not end in tetanus or 
 
THE STOMACH IN HUNGER 37 
 
 prolonged tonus contractions, followed by a relatively abrupt 
 relaxation and quiescence. 
 
 When the contractions are relatively feeble, the periods of 
 activity are always short, the variation being from 6 to 20 minutes, 
 with an average duration of 12 minutes. The number of strong 
 contractions in these periods varies from 10 to 25, with an average 
 of about 14 contractions. The duration of each individual con- 
 traction is approximately 20 to 25 seconds. The stronger con- 
 tractions are usually in the middle of the periods, the initial and 
 final contractions being the weakest. In no case have we seen 
 such a period end in tetanus. 
 
 The periods of more powerful contractions exhibit some char- 
 acteristic features. The periods are always initiated by weak 
 contractions with long intervening pauses. These pauses may be 
 of several minutes' duration. Then, the individual contractions 
 gradually increase in amphtude, and the intervening pauses become 
 shorter, until the climax is reached in a niraiber of very powerful 
 and rapid contractions approaching incomplete tetanus. The 
 tetanus when present usually lasts from 2 to 5 minutes. The cessa- 
 tion of these periods of activity is always abrupt. In Mr. V. there 
 were at times two or three periods of nearly complete tetanus at 
 the end of the period. On five different days these final tetanus 
 periods lasted for from 10 to 15 minutes. This is, however, excep- 
 tional. When the period does end in tetanus, the tetanus usually 
 lasts only 2 to 3 minutes. 
 
 This ending of the contraction period in an incomplete tetanus 
 appears to be characteristic of young and vigorous individuals. 
 In older people the period usually ends in a single vigorous con- 
 traction without tetanus, except under certain conditions. The 
 ending in tetanus appears to be an evidence of relatively great 
 tonicity of the stomach. In ojie perfectly normal man (Mr. O.) 
 on whom himdreds of observations were made, the entire period 
 (15 to 20 minutes) was virtually a nearly complete gastric tetany. 
 
 The duration of each contraction varies from 20 to 30 seconds. 
 The contraction time is shortest at the final stage of greatest 
 activity. When the contrary appears to be the case, the tracings 
 
38 
 
 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 show that the prolonged curve is a fusion of two or more contrac- 
 tions. The interval between .the contractions varies from 2 to 5 
 minutes at the beginning of a period to nothing at the end. The 
 duration of the period varies from ^ to i^ hours. The usual run is 
 30 to 45 minutes, the longer periods being exceptional, when there is 
 no experimental interference with the stomach. The number of 
 individual contractions in a period varies from 20 to 70. The period 
 
 Fig. 5. — The three upper tracings are typical records of the gastric hunger 
 contractions of normal adult persons toward the end of a hunger period. The tracings 
 are recorded and are to be read from left to right, and in each case the gastric hunger 
 contractions cease spontaneously near the right end of the tracings. The more rapid 
 excursions are due to the movements of respiration. The bottom tracing shows typical 
 gastric hunger contractions of a normal dog. 
 
 of relative motor quiescence of the empty stomach between the con- 
 traction periods varies from | to 2^ hours in normal adult persons. 
 A few characteristic records of these strong periods of motor activity 
 of the empty stomach in normal persons are shown in Fig. 5. 
 
 There remains to be noted a rather atypical form of activity 
 of the empty stomach occasionally observed. This consists in 
 
THE STOMACH IN HUNGER 39 
 
 contractions, feeble or powerful, that do not fall into distinct groups 
 or periods. These contractions are usually irregular both in strength 
 and in rate. The average rate is slow, the interval between the 
 contractions varying from 5 to 10 minutes. Similar solitary con- 
 tractions may also appear in the interval between two typical 
 periods of rhythm. These contractions may come two or three 
 in sequence, t3^ical of the beginning of an activity period, but 
 instead of a gradually increasing activity the stomach relapses 
 into relative quiescence for another 10 to 30 minutes. 
 
 The reader may question the accuracy of denoting these con- 
 tractions as motor activities of the empty stomach. In all of these 
 cases the stomach was certainly empty of food. But may not the 
 distended balloon act as food, so far as the food acts mechanically 
 in the way of producing stomach movements? This is, indeed, 
 claimed to be the case by Mangold for the muscle stomach of the 
 buzzard. It is not difficult to prove that certain forms of mechanical 
 stimulation, such as the sudden distension of a rubber balloon in 
 the gastric cavity, may cause brief contractions in the stomach, 
 but it can be shown just as conclusively that the stomach rhythms 
 described above are not caused by the presence of the foreign objects 
 in the stomach. 
 
 1. The presence of the distended balloon in the stomach 
 between the contraction periods does not induce these con- 
 tractions. 
 
 2. In Mr. V. the gastric contractions can be observed directly 
 through the large fistula without any balloon in the stomach. 
 
 3. The contraction periods come on just as frequently without 
 any balloon in the stomach and produce the same effect on con- 
 sciousness (himger). 
 
 4. In pigeons the periodic strong contractions of the empty 
 crop can be seen directly through the skin and a balloon in the crop 
 does not alter their frequency or intensity. 
 
 The stomach piilse. — ^When the empty stomach is moderately 
 contracted, direct inspection by the aid of a small electric bulb 
 in the gastric cavity shows distinct oscillations of the rugae S3ai- 
 chronous with the arterial pulse. The oscillations of the rugae 
 
40 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 cause similar oscillations of the gastric juice (mixed with mucin), 
 which is always present in the otherwise empty stomach. When 
 the strong contractions (30-seconds rhythm) appear, the pulse 
 oscillations of the rugae seem to disappear, either because of the 
 greater rigidity of the stomach folds, or else owing to the difficulty 
 of distinguishing the pulse oscillations when the rugae are closely 
 packed and shde rapidly over and past one another, as they do 
 when the fundus contracts. The picture revealed by the gastric 
 cavity when the empty stomach is in a period of rhythmic con- 
 tractions is interesting, but rather bewildering, and we have 
 ceased to wonder how Beaumont could have so completely failed 
 to grasp the character of the stomach movements in digestion, 
 as he relied mainly on such direct inspection of the stomach of 
 Alexis St. Martin. 
 
 III. TONUS AND CONTRACTIONS OF THE EMPTY STOMACH 
 IN THE NEWBORN INFANT 
 
 T he gastric hunger mechanism is probably inheri ted. At any 
 rate, the frequency and duration of the periods of gastric hunger 
 contractions are related to the feeding habits of the individuals 
 or the species only so far as the feeding time and food quantity are 
 factors in the time required for emptying of the stomach, and hence 
 for the appearance of the hunger contractions. On the other 
 hand, the hunger mechanism determines to a certain extent the 
 feeding habit. Animals and children probably eat as soon as the 
 stomach is nelarly empty, if food is at hand, and the greater 
 frequency of the gastric hunger periods in the young is probably 
 related to the more continuous feeding on the part of the young 
 animal. 
 
 We have made observvations on a number of newborn, infants, 
 with results showing that the empty stomach at birth and in the 
 prematurely born exhibits the typical periods of tonus and hunger 
 contractions of the adult, the only difference between infant and 
 adult being the greater frequency of these periods in the young. 
 In some of the infants the observations were made before their 
 first nursing. It is thus clear that in the normal individual the 
 
THE STOMACH IN HUNGER 
 
 41 
 
 gastric hunger mechanism is completed, physiologically, and 
 probably active some time before birth. 
 
 The recording of the gastric hunger contrac- 
 tions of the newborn human infant offers no great 
 difficulties, if one uses delicate rubber balloons of 
 15 c.c. capacity, attached to a flexible rubber 
 catheter of 2 mm. diameter. Most of the infants 
 swallowed this apparatus without difficulty and 
 went to sleep in our arms during the observation 
 periods. The results were always most satisfac- 
 tory with the infants asleep, as that eliminated 
 all nervous inhibitory factors, and the disturbances 
 from body movements and from irregularities in 
 respiration. Practically nothing can be done with 
 the balloon method if the infant is at all restless. 
 All of our observations were made on healthy and 
 vigorous infants. 
 
 In human infants, periods of gastric tonus 
 and hunger contractions are in evidence shortly 
 after birth and before any food has entered the 
 stomach. These gastric hunger periods exhibit all 
 the pecuKarities of the gastric hunger contractions 
 of the adult, except that the periods of motor 
 quiescence of the stomach between the hunger 
 periods are on the whole much shorter (10 to 15 
 minutes). When the gastric hunger contractions 
 become very vigorous the sleeping infant may 
 show some restlessness, and may even wake 
 up and cry. If the infant is awake the very 
 vigorous hunger contractions frequently induce 
 crying and restlessness. A tracing showing a 
 typical hunger period in a 9-hour-old infant 
 before first nursing is reproduced in Fig. 6. The 
 reader's attention is called to the fact that in 
 infants the gastric hunger periods usually end in 
 incomplete tetanus, an index of youth and vigorous stomach 
 
 IS 
 
 t-x=:jji U) 
 
 a 
 
 t3 
 
42 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 IV. MOVEMENTS OF THE EMPTY STOMACH IN DOGS 
 
 The contractions of the empty stomach in dogs were recorded 
 by means of a bromoform manometer coimected with a delicate 
 rubber balloon in the stomach. In the dogs the balloon was intro- 
 duced into the stomach either through a gastric fistula or through 
 the esophagus. We were surprised to note the ease with which a 
 small rubber balloon and rubber-tube attachment can be passed 
 through the esophagus into the stomach in dogs. If gentle dogs 
 are selected for the work and the dogs are handled gently, they 
 make little or no resistance after the first two or three experiments. 
 We have never observed vomiting or gagging in dogs as a result of 
 the introduction or the presence of the stomach tube in the 
 esophagus. On the contrary, the dog with the rubber tube and 
 balloon in the stomach and esophagus will lie quietly for hours in 
 the lap of an attendant, while the tonus and movements of the 
 empty stomach are being registered on the k3ntnograph. Frequently 
 the dog will go to sleep during the experiments. This is especially 
 the case if the dog is covered up with a coat or a comforter. The 
 tube in the esophagus does not cause distress or inhibition of the 
 stomach movements. After some training the dogs do not even 
 chew or bite on therubber tube in the mouth. 
 
 Some of the observations were made on dogs with a fistula 
 in the fimdus of the stomach. In our first dog we made use of the 
 classical silver cannula. In all the other dogs we discarded the 
 metal cannula and adopted the surgical methods followed in 
 human gastric fistula cases. The incision (3 to 4 cm. in length) is 
 made 3 cm. below the last rib and 5 to 6 cm. to the left of the linea 
 alba. The oblique and transverse muscles are carefuUy separated 
 without cutting them. The desired region of the gastric fundus 
 is pulled out through this opening. The peritoneum is sutured 
 to the fundus pouch. The abdominal muscles are similarly sutured 
 to the pouch. In making these sutures care is taken not to pene- 
 trate deeper than the muscle layers of the pouch. The apex of the 
 fundus pouch is then slit open, and the edges sutured to the edges 
 of the skin. A closed rubber tube i cm. in diameter is passed 
 through the opening into the stomach and kept in place for 4 days. 
 
THE STOMACH IN HUNGER 43 
 
 Then the tube and dressing are removed. It is found that the 
 abdominal muscles compress this narrow pouch to such an extent 
 that there is virtually no leakage from the stomach, much less 
 leakage, in fact, than even in the most successful fistula using 
 the metal cannula. There is no trouble in closing up of the 
 fistula as long as the animal is being used two or three times a 
 week. The dog takes care of the sHght leakage, so there is no 
 corrosion of the skin. We have dogs now in the laboratory with 
 such fistula of 18 months' standing, and the dogs are in the best 
 of condition. In fact, it is obvious that this fistula leaves the stom- 
 ach much more normal than does the silver cannula method. We 
 have obtained normal himger contractions of the empty stomach 
 36 to 48 hours after making the fistula. Nothing like normal 
 himger contractions is seen in the stomach for 6 to 10 days after 
 making the fistula by means of the metal tube. The old silver 
 tube method should be abandoned in all experimental work on 
 the stomach. 
 
 In the beginning of this work the animals were kept suspended 
 in comfortable hanmiocks during the observations on the gastric 
 hunger movements. It soon became apparent, however, that any 
 kind of mechanical restraint on a young, vigorous, and very hun- 
 gry dog causes restlessness and evident distress, especially when 
 continued for hours. Training will overcome this in part, but not 
 completely. Distress and restlessness will obviously interfere 
 with the stomach movements. We, therefore, tried the expedient 
 of having an attendant keep the dog snugly in his lap during the 
 observation period. This proved very satisfactory, except for the 
 \attendant. It is irksome, to say the least, to sit still for 2 to 8 
 hours at a stretch. We can appreciate the reason for the dog's 
 restlessness when restrained mechanically in a hanmiock or on a 
 couch for that length of time. When the attendant knows how 
 to handle dogs, even a very hungry dog wiU lie in his lap quietly 
 for hours, and wiU usually cuddle up and go to sleep. After a 
 few experiments most dogs seek the research room by preference, 
 and jump into the attendant's lap voluntarily. Some of our dogs 
 became so well trained that they would lie quietly on a pillow for 
 
44 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 2 to 3 hours at a time without any restraint whatever. It is obvious 
 that mental stress and restlessness interfere with the stomach 
 contractions, not only in the way of direct inhibition, but also 
 by the varying tonus and irregular contractions of the abdominal 
 muscles. The animals used in these experiments were mostly 
 young and vigorous females. 
 
 The contractions of the empty stomach, as registered by means 
 of a delicate balloon in the fundus, fall into three types according 
 to the degree of tonus of the stomach. 
 
 Type I: When the stomach shows feeble tonus, the hunger 
 contractions show an average duration of about 30 seconds, and 
 the intervals between the contractions vary from J to 3 or 4 min- 
 utes. This type of contractions usually falls into groups, separated 
 by intervals of relative quiescence. The duration of the groups 
 varies from ^ to 3 hours, and the number of contractions in each 
 group varies correspondingly. It is very rare that a contraction 
 group of tjTpe I ends in a tetanus sp frequently observed in man. 
 The group usually begins with feeble contractions but of longer 
 than average duration and relatively far apart, and the contractions 
 become gradually stronger and the intervals shorter. The end of 
 the group is usually characterized by contractions of gradually 
 decreasing strength. 
 
 Type II: When the stomach is in relatively strong tonus the 
 hunger contractions follow one another in rapid succession, that 
 is, without any intervening pause. The duration of the contractions 
 varies between 20 and 30 seconds. These contractions are fre- 
 quently interrupted by periods of incomplete tetanus lasting from 
 I to 5 minutes. These periods of tetanus are practially identical 
 with those previously described in man. The contractions of this 
 type do not fall into distinct groups. They may vary to some 
 extent in amplitude and rate, but otherwise be continuous for an 
 observation period lasting from 2 to 6 hours. If the animal be- 
 comes restless during the observation period the hunger contrac- 
 tions become irregular and may cease altogether, but this is probably 
 due to splanchnic inhibition, and cannot be regarded as a spon- 
 taneous cessation of the hunger contractions. 
 
THE STOMACH IN HUNGER 45 
 
 This type of hunger contractions seems to be present only in 
 young and vigorous individuals in excellent physical condition. 
 Similar contractions were observed in man, but less frequently 
 than in our young and vigorous dogs. From observations on man, 
 it is certain that the hunger sensation is practically continuous 
 during these contractions. 
 
 Type III: The hunger contractions designated as type III 
 constitute virtually an incomplete tetanus of the stomach. This 
 tetanus is characterized by periods of strong and relatively persistent 
 tonus on which are superimposed a series of rapid contractions. 
 The duration of these rapid contractions averages 12 to 15 seconds. 
 These contractions are evidently analogous to the 20-seconds 
 rhythm in man. These tetanus periods vary in length from i to 10 
 minutes. In prolonged starvation they may last much longer. In 
 moderate hunger they are interspersed between groups of the 
 type II rhythm. ( 
 
 This description of the gastric hunger contractions in dogs is 
 based on observations on more than fifty individuals. The shortest 
 observation period on each animal was two weeks, the longest five 
 months with records taken, on the whole, every third day. The 
 data should therefore be typical. The three types of contractions 
 may be observed in the same dog on different days, or type I may 
 obtain for a few days, and then be superseded by type II, etc. As 
 a general rule type I predominated in some of the dogs and types, 
 II and III in others. Some of the tracings also disclose what may 
 be termed transition stages. Thus, near the end of a contraction 
 period of type I the rapidity of the contraction may approach that 
 of type II, and occasionally the individual contractions of type II 
 will for short periods slow up to such an extent that they parallel 
 type I. This is to be expected, since the types of the hunger con- 
 tractions seem to vary with the degree of gastric tonus, and this 
 tonus may vary considerably during a single observation period. 
 It is also to be noted that the hunger contractions may occasionally 
 be feeble, irregular, or practically absent for at least 2 to 4 hours 
 at a time in dogs that are seemingly in good condition. ' And this is 
 usually "the case if the dogs are in poor condition from any cause. 
 
46 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The credit of discovery of the rhythmical contractions of the 
 empty stomach in dogs belongs to Boldyreff, but his account of the 
 rhythm is incomplete and partly misleading. According to Boldy- 
 reff the contractions always come in groups of 20 to 30 minutes' 
 duration, and during the i^ to 2I hours' intervals between these 
 groups in which the stomach is completely quiescent. The con- 
 tractions observed by Boldyreflf were evidently short and feeble 
 periods of the type I contractions, but the duration of the interval 
 between the contractions given by Boldyreflf is on the whole much 
 greater than that shown in my series. Boldyreflf evidently never 
 obtained the rhythm of t3ipes II and III in his animals. The 
 diflference in the results of Boldyreflf and our own are probably due 
 to (i) the condition of the animals, (2) the method of handling the 
 animals, and (3) the method of registering the stomach contrac- 
 tions. Boldyreflf used the classical silver cannula for the gastric 
 fistula. This depresses the stomach. All the dogs had in addition 
 to the gastric fistula (fundus) also duodenal, pyloric, pancreatic, or 
 hepatic fistulae. His dogs were therefore subjected to much 
 greater disturbance of digestion and metabolism than is the case 
 of a simple fistula of the fimdus as prepared by me. As the dogs 
 were not in the best of condition, it is not surprising that they 
 showed only the feeble rhythm of type I. But it seems likely that 
 forcing the dogs by mechanical means to lie or stand in one position 
 for 6 to 12 hours at a time is also partly responsible for the brevity 
 of the contraction periods and the length of the intervening periods 
 of quiescence. It is my experience that dogs thus treated become 
 restless, and restlessness always is accompanied by gastric inhibi- 
 tion, probably through the splanchnics. When the dog is allowed 
 to make himself comfortable in the lap of an attendant he Hes 
 quietly and usually without any restraint. This condition is cer- 
 tainly more nearly normal. 
 
 The tracings published by Boldyreff do not show the respiratory 
 intragastric pressures, nor do they indicate the slightest variations- 
 of the gastric tonus during the observation periods. His method 
 of registration was therefore not dehcate enough to detect small 
 variations in the intragastric pressure. It would seem, however. 
 
THE STOMACH IN HUNGER 47 
 
 that his method ought to have recorded the type II contractions, 
 if they had been present in his dogs. 
 
 V. MOVEMENTS OF THE RABBIT'S STOMACH DURING HUNGER 
 
 Rogers, working in the author's laboratory, made gastric 
 fistulas in rabbits by opening the abdominal cavity about i inch 
 to the left of the mid-ventral line and as close to the costal border 
 as possible and suturing the muscularis of the fimdic portion of 
 the stomach to the peritoneum and oblique muscles and then the 
 gastric mucosa to the skin. These fistulas were made rather small, 
 so that there would be little leakage of gastric juice or loss of food. 
 At times a small rubber tube was inserted into the stomach and 
 left there for longer or shorter times to prevent closing of the fistula. 
 Within 36 hours after the operation the animals are usually feeding. 
 These rabbits, if properly taken care of, are in as good condition as 
 normal animals. 
 
 Graphic records were made using the rubber balloon method 
 with a manometer pressure of 2 to 4 cm. of chloroform. Medium- 
 sized adult rabbits were used in this set of experiments. In no 
 case did any animal survive a period of continuous starvation of 
 more than 7 days. In animals that died of starvation there were 
 always considerable amounts of residue in the stomach. In the 
 moist condition in which this was removed from the stomach it 
 weighed from 8 to 13 gm. Normally the moist contents of the 
 adult rabbit's stomach weigh 90 gm. or more. Soon after being 
 deprived of its usual food the rabbit provides a substitute by 
 eating its own excreta. Putting the animal in a wire-bottom 
 cage does not prevent this. The only practicable way to pre- 
 vent it is to inclose the animal in a cage so fitted with a lid, 
 that the rabbit's head is held outside, its body inside the cage. 
 No doubt such a position proves very irksome to the rabbit, 
 but after becoming accustomed to the position the activities of 
 the stomach were not inhibited. In an animal so fixed, the 
 stomach, as noted by Swirski, empties itself in about 24 hours. 
 Nevertheless, during normal conditions of life the rabbit's stomach 
 is never empty. 
 
48 
 
 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 Since nomially the stomach is never empty, it is to be expected 
 that gastric digestion peristalsis will always persist. But as the: 
 period of starvation is prolonged, the stomach contractions are 
 altered. Instead of being the gentle peristalsis of normal digestion, 
 they become relatively powerful contraction waves which rapidly 
 follow one another, with a tendency for each peristaltic wave to 
 pass into a short period of tetany. There is no indication of rest 
 or periodicity to these stronger contractions until a short time 
 
 Fig. 7. — Contractions of the rabbit's stomach, a, normal digestive peristalsis; 
 b, after 24 hours' starvation; c, after 75 hoiirs' starvation; d, after 92 hours' starva- 
 tion; e, after no hours' starvation. The animal died a few hours after this tracing (c) 
 was taken (Rogers). 
 
 before death from starvation. Auer has pointed out that during 
 normal peristalsis in the rabbit, the stomach is incessantly active.. 
 During hunger the strength of these contractions is accentuated. 
 Following this period of increased activity during starvation, 
 there comes a period of depression. This is coincident with marked 
 general weakness of the animal or even coma. The dechne in the 
 vigor of the stomach activities comes on gradually. The contrac- 
 tions become weaker, of shorter duration, and alternating with 
 short periods of rest. In the last stage of starvation there may 
 
THE STOMACH IN HUNGER 49 
 
 occur prolonged contractions or periods of tetany lasting from 2 
 to 3 minutes (Fig. 7). 
 
 Gastric tonus variations were frequently seen during hunger, 
 but not commonly during normal digestion peristalsis. May not 
 the increasing muscle tone of the stomach, as starvation is pro- 
 longed, play a part in causing the sensation of hunger ? Certainly 
 a state of greater contraction of the stomach on the substances 
 remaining within it, as starvation is prolonged, is the first apparent 
 change. Rabbits will show signs of hunger, such as restlessness, 
 gnawing of dry wood, and eating cotton, before the character of 
 the movements as recorded by this method shows any striking 
 change from the normal digestion peristalsis. The increased 
 activity of the stomach that later appears is no doubt also 
 accompanied by psychic changes. The appearance of gastric 
 tetany, if the animal is still able to move about, is marked by 
 restlessness. 
 
 In order to determine whether or not the stomach of the rabbit 
 when it contains no food is quiescent, the animal was so caged as 
 to be excluded from its feces. The only difference observed be- 
 tween an animal so caged and one free to move about was that the 
 increased vigor of the stomach contractions comes on sooner in 
 the former. In about 12 hours after feeding the contractions 
 become very much stronger than normal digestion peristalsis, and 
 this activity both of contractions and tonus variations persists 
 after the stomach has emptied itself of food. 
 
 VI. GASTRIC HUNGER CONTRACTIONS OF THE GUINEA-PIG 
 
 Sixteen animals weighing from 450 to 900 gm. were studied by 
 Dr. Helena King over periods varying from 13 to 66 days. The 
 guinea-pig is so foreshortened that the gastrostomy operation was 
 beset with some difficulties — the fundic portion of the stomach is 
 pushed up imder the diaphragm in such a manner that it must be 
 pulled downward and stitched to the abdominal wall to make a 
 fistula, or an opening must be in the pyloric region. Both methods 
 proved satisfactory, and the possible objection to the lower opening 
 that the balloon did not lie in the fundus was obviated by the use 
 
50 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 of a small balloon or of a finger cot from 3 to 5 c.c. in capacity, 
 pushed well up into the stomach. Several animals killed with the 
 balloon in place left no doubt of the ease with which it was properly 
 inserted. Very small fistulas were made so that when the wounds 
 healed they often measured less than i cm. across. Since the 
 animals began eating within 12 hours, the food in the distended 
 stomach prevented the openings from closing. 
 
 The guinea-pig, like other herbivorous animals, feeds at fre- 
 quent intervals — ^probably every hour — and vmder normal conditions 
 the stomach is never found empty. Even within 2 hours after 
 exclusion from food it begins eating its own excreta, a fact noted by 
 other observers, and after 12 hours will eat paper, pasteboard, or 
 anything of that nature within reach. The easiest and most effec- 
 tive method found for excluding it from its own feces was to place 
 the body of the animal in a bag, sufficiently small to prevent much 
 freedom of movement, and then to draw the bag closely about 
 the neck. 
 
 In the guinea-pig contractions of the stomach were observed in 
 5 hours after taking the food away. Frequently continuous records 
 were made from the time the food was removed until the onset of 
 such vigorous movements. The mild peristaltic waves of digestion 
 become more and more intense imtil contractions such as might be 
 classified as type I appear — that is, periods of tonus lasting 2 or 3 
 minutes with 4 or 5 superimposed contractions. This t3^e may 
 continue for 4 hours, but they gradually merge into the more vigor- 
 ous type II and possible t)T)e III. The contractions follow one 
 another in rapid succession — one in 18 seconds on the average — • 
 such a period terminating in complete quiescence of the stomach. 
 At times a period of violent coughing precedes the inhibition. 
 Contractions of types I and II have been recorded continuously 
 for 6 hours with but two periods of rest lasting 8 and 6 minutes 
 respectively. 
 
 That discomfort is experienced by the guinea-pig when food is 
 withheld for even 4 or 5 hours is evidenced by restlessness, the 
 eating of the animal's own excreta, chewing movements, and some- 
 times crying, when the contractions are unusually vigorous. The 
 
THE STOMACH IN HUNGER 51 
 
 animal evidently experiences hunger while the stomach still con- 
 tains an abundance of food. 
 
 VII. CONTRACTIONS OF THE PARTLY EMPTY STOMACH (rUMEn) 
 OF THE RUMINATING ANIMALS 
 
 Like the stomach of the herbivora in general, the various divi- 
 sions of the stomach in the ruminants are probably never completely 
 empty of food. Digestion in these animals is therefore a more or 
 less continuous process, and if they eat because feeling hunger, 
 they must be capable of experiencing hunger with the stomach 
 partly filled with food, and while the blood is still receiving a 
 constant stream of digested pabulum from the small intestines. 
 
 By a balloon method and with a fistula in the rumen. Dr. Schalk 
 and the writer studied the contractions of this stomach pouch in 
 the goat. We started the work on the rumen, as this corresponds 
 to the cardiac or fundus part of the stomach of other mammals, 
 and is, therefore, probably the region most directly concerned with 
 the causation of hunger. 
 
 The body of the rumen of the goat exhibits strong periodic 
 contractions, independent of those concerned with the regurgitation 
 of the food bolus into the mouth, i.e., the act of rumination. The 
 contractions vary in intensity, but appear to be practically con- 
 tinuous; that is, there appears to be no period of real quiescence. 
 When the goat is starved for several days or the greater part of the 
 food in the rumen is removed through the fistula, these contractions 
 become stronger without much change in rate. So far, observa- 
 tions have been made only on the rumen of one goat, but the motor 
 conditions found are essentially similar to those already described 
 in the rabbit and the guinea-pig. The digestion contractions of 
 the filled rumen pass gradually into the stronger contractions of 
 the empty or partly empty rumen. We may provisionally call the 
 latter "hunger contractions," assuming that it is the partly empty 
 rumen that gives the impetus to feed. So far as we know the only 
 difference between the completely filled and the partly empty 
 rumen is this difference in tonus and strength of contraction. 
 There is no gastric juice secreted in the rumen, hence there is no 
 
52 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 acidity except that due to the action of bacteria, and there is no 
 regurgitation of the acid content of the true stomach (abomasum|i| 
 into the rumen. Unless we assume with J. Miiller that the sensa- 
 tion of hunger is purely negative, or due to the absence of satiety, 
 the hunger in the ruminant must in some maimer be associated 
 with these powerful contractions of the partly empty rumen. 
 
 Vin. CONTRACTIONS OF THE EMPTY CROP IN BIRDS 
 
 In normal pigeons, with appetites satisfied, the crop is very 
 much distended, and only occasional contractions of the crop can 
 be detected by means of the balloon in the cavity (Rogers). These 
 contractions caimot be detected by inspection of the skin covering 
 the crop. An hour or two after feeding stronger contractions in 
 groups of 3 to 4 appear at 15- or 20-minute intervals. The motor 
 activity of the crop is gradually increased until, 8 to 12 hours after 
 feeding, groups of 8 to 20 strong contractions appear at intervals 
 of 10 to 30 minutes. Later the crop of young birds passes into a 
 state of continuous rhythmical contractions. When the food con- 
 tent of the crop is reduced to about one-third of the crop's capacity, 
 the contractions are visible through the skin. At this time they 
 involve only the lower part of the crop. When the crop is com- 
 pletely empty the contractions occur in periods of 10 to 60 minutei 
 apart, with 8 to 20 contractions in each group. The contractions 
 of the empty .crop begin at the upper end, and pass over the entire 
 crop as a peristaltic wave. Each contraction requires 12 to 15 
 seconds to pass over the crop. The balloon in the crop does not 
 initiate contractions unless the pressure is excessive. A small fistula 
 in the crop has no effect on the contractions. 
 
 It is thus evident that the empty or nearly empty crop of 
 gallinaceous birds exhibi ts periods of powerful contractions involving 
 the entire organ, while in the filled crop the periodic contraction^ 
 are confined to the lower end of the organ mainly (Fig. 8, c), 
 
 Rogers' studies on the crop in the pigeon have not yet been 
 extended to muscular stomach or gizzard. Accoirding to Rossi 
 the stomach of chickens shows greater motor activity when empty 
 than during digestion, but Mangold states 'that the empty muscle 
 
THE STOMACH IN HUNGER 
 
 53 
 
 iM \m 
 
 
 Fig. 8. — fi, tracings of the gastric hunger contractions of the empty stomach of 
 the bullfrog, 12th day of starvation (Patterson); b, tracing of the gastric hunger 
 contractions of the turtle, zist day of starvation (Patterson); c, tracing showing the 
 periodic hunger contractions of the crop of birds (pigeon) , 2d day of starvation (Rogers) . 
 
54 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 stomach of the buzzard is quiescent. Stiibel, on the other hand, 
 reports that the empty muscle stomach of pigeons and chickens 
 and ducks shows a rhythmical action current, which obviously 
 implies a corresponding activity or rhythm. 
 
 In the species of birds with the food reservoir in the esophagus 
 (crop), the contractions of this region of the esophagus are probably 
 the most important element in the genesis of the hunger sensation, 
 because the crop is emptied sooner than the gizzard. 
 
 IX. CONTRACTIONS OF THE EMPTY STOMACH OF AMPHIBIA 
 AND EEPTILIA 
 
 Observations (Patterson) were made on the bullfrog (Rana 
 caterbiana) and the common snapping turtle (chelydra serpen- 
 tina) by the balloon and the balloon X-ray method. In the turtles 
 the balloon was introduced through an ordinary gastrostomy open- 
 ing. In the frogs a stomatotomy was made by a small incision 
 between the ramus of the inferior maxillary and the anterior 
 coronary of the hyoid bone through the skin, the mylo-hyoid 
 muscle, and the mucous membrane of the throat. 
 
 There are slight, if any, tonus variations in the empty stomach 
 of frogs and turtles. In healthy frogs the stomach exhibits continu- 
 ous rhythmical contractions. These contractions are remarkably 
 strong, sustaining a column 15 to 22 cm. high. The contraction 
 phase is abrupt; the relaxation is slower; in fact, it proceeds 
 until the next contraction. The X-ray studies in the intact 
 animal as well as observations on the isolated stomach showed 
 that each contraction is a perista,ltic wave starting at or near the 
 cardia and sweeping over the entire stomach, just as is the case 
 with the gastric hunger contraction in the mammals. The striking 
 difference between the bullfrog and the mammal is the absence of 
 periodicity or grouping of the frog's gastric contractions (Fig. 8, a). 
 
 The amplitude of these contractions in the frog is increased 
 during prolonged starvation, but there is no obvious increase in 
 tonus. The contractions cease at temperatures above 38° C. and 
 below 13° C. lb is significant that the cessation of the hunger 
 contractions of the empty stomach at low temperature (i3°C.) is 
 
THE STOMACH IN HUNGER 55 
 
 not in tonus, but in atony of the stomach. It would thus seem 
 the gastric hunger mechanism is paralyzed in the hibernating frog. 
 The hunger contractions of the empty stomach of the turtle 
 are very similar to those of the bullfrog. The rate of the contrac- 
 tion is somewhat less, and there are periods of relative quiescence 
 of the empty stomach similar to that in mammals and birds. In 
 prolonged starvation the contractions become stronger and show 
 a tendency to pass into short periods of incomplete tetanus 
 (Fig. 8, b). 
 
CHAPTER IV 
 THE STOMACH IN HUNGER {Continued) 
 
 I. RELATION BETWEEN DIGESTION CONTRACTIONS OF THE FILLED, 
 AND HUNGER CONTRACTIONS OF THE " EMPTY" STOMACH 
 
 As we have seen in the case of the rabbit and the guinea-pig 
 and the goat, the digestion contractions of the filled gradually pass 
 into the hunger contractions of the empty or nearly empty stomach. 
 In the frog and the turtle the digestive peristalsis of the filled stomach 
 is practically identical with the hunger peristalsis of the empty 
 stomach. What are the conditions in man and the higher carnivor- 
 ous mammals ? Is it likely that the situation is different in animals 
 with a stomach always more or less filled with food and in animals 
 with a stomach usually empty before they experience hunger ? 
 
 To answer this question Rogers and Hardt, working in the 
 author's laboratory, used the two standard methods of investigating 
 the movements of the stomach: the rubber balloon and the X-ray 
 methods. The balloon was swallowed shortly after a meal, and 
 continuous graphic records of the intragastric pressure variations 
 were made until after the onset of a typical hunger period. Soon 
 after eating an average meal the subject of the experiment swal- 
 lowed the balloon and put himself into a comfortable position, 
 either sittii^ in a chair or lying on a cot. The results were similar, 
 irrespective of the position; the best results were obtained while 
 the subject was asleep. 
 
 In order actually to see the hunger movements, we coated a 
 balloon with a bismuth paste and observed its niovements in the 
 stomach with the X-ray. These balloons were prepared by painting 
 the outer wall of one with a paste made of bismuth subnitrate and 
 vaseline. This balloon was then inclosed in another of the same 
 size; hence the two balloons were separated by a thin wall of bis- 
 muth paste. One is thus able to make graphic tracings with simul- 
 taneous direct fluoroscope observation. 
 
 S6 
 
THE STOMACH IN HUNGER 
 
 57 
 
 Our records show, that the fundus is quiescent immediately 
 after a large meal has been eaten. The pressure upon the balloon 
 is maintained at a steady level. If a light meal is taken, the tonus 
 variations may be demonstrated immediately after eating. At 
 first they are so slight as to seem insignificant, but they increase 
 in vigor and are usually visible 30 minutes after the meal. In one 
 experiment an unusually large meal was eaten and the .tonus 
 waves were distinctly in evidence 20 minutes later. They increase 
 in intensity and may, but do not always, become more rapid. 
 Each wave is of i to 3 minutes' duration. When the stomach is 
 
 w0mf^^0^MAf^ 
 
 Fig. 9. — Tracing showing the tonus rhythm of the stomach (man) 3 hours after 
 <iinner (beefsteak, spaghetti, bread, butter, apples and cream, milk). 
 
 nearly empty (as determined by the stomach tube or induced 
 vomiting) they become conspicuous, and at this stage of the 
 digestion there usually appear, superposed upon them, stronger 
 contractions which increase in vigor and are felt by the subject as 
 hunger pains. Although it is by no means always the case, it is 
 significant that the first contractions felt as a hunger pang in man 
 may occur when the stomach still contains traces of food. 
 
 We have seen that the onset of a hunger period is marked by 
 the appearance of a slow tonus rhythm which gradually increases 
 in vigor and culminates in the hunger contractions. This tonus 
 rhythm is present, not only as an immediate precursor of the hunger 
 period, but also throughout the course of normal gastric digestion. 
 
58 
 
 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 Other workers have employed the rubber balloon in recording 
 the digestion movements in the stomach, but none of the pubhshed 
 tracings, so far as we are aware, indicate the presence during 
 normal digestion of the slow continuous rhythm here described. 
 Moritz reported contractions of the fundic end of the stomach 
 occurring 2^ to 3I times per minute. According to Dietlan the 
 
 Fig. 10, A . — X-ray photograph of the appearance of the bismuth-coated balloon 
 in the stomach (man) when the empty stomach is quiescent. 
 
 time required for the peristaltic contractions of the pyloric end 
 of the stomach is 20 to 24 seconds. The tracings of Moritz prob- 
 ably record the intragastric pressure variations due to the pyloric 
 peristalsis. Sick, using the balloon method, describes tonus varia- 
 tions of the fundic end of the stomach which give rise to the peris- 
 taltic waves. These occur at the rate of 2 to 4 per minute in the 
 
THE STOMACH IN HUNGER 
 
 59 
 
 full or empty stomach. The tracings of Sick show three kinds 
 of pressure variations: respiratory, cardiac, and "Magen tonus 
 schwangungen," the latter averaging 20 seconds each in duration. 
 The duration of these "stomach tonus variations" coincides with 
 the time intervals required for the pyloric peristalsis. 
 
 Is the hunger contraction simply an augmented peristaltic con- 
 traction or a contraction of the fundus as a whole ? To answer 
 
 Fig. 10, B. — X-ray photograph of the bismuth-coated balloon in the stomach 
 (manj at the height of a gastric hunger contraction (gastric hunger pang) (Rogers 
 and Hardt). 
 
 this question the stomach movements of the dog and in man were 
 studied by the "balloon-X-ray" method. We were able to make 
 direct observations of the movements of the balloon in the stomach 
 and at the same time to note the character of the graphic record. 
 The upper part of the balloon was held in the cardiac end of the 
 stomach. A young and vigorous dog was employed for the experi- 
 ments. The dog was starved for intervals of 36 to 48 hours, and 
 
6o CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 in order not to have the hunger contractions completely inhibited 
 by the excitement attendant upon the X-ray examination, frequent 
 repetitions were made until "the dog became accustomed to the 
 necessary manipulations. The vigor of the stomach contractions 
 thus made visible to the naked eye is surprising. The weaker 
 type of hunger contractions begin as a constriction in the cardiac 
 end of the stomach and pass down toward the pyloric end as a 
 rapid peristaltic wave. In the very vigorous contractions the 
 wave spreads over the stomach so rapidly that it is difficult to 
 decide whether there is a contraction of the fundus as a whole or a 
 very rapid peristalsis. This contraction may well be compared 
 to the peristaltic rush of the intestine as described by Meltzer and 
 Auer. 
 
 The balloon-X-ray observation of the hunger contractions was 
 made on Mr. R. when in a reclining position. When a hunger 
 pang was felt, and the recording manometer showed the typical 
 rise in the intragastric pressure, a series of constrictions were seen 
 passing rapidly over the balloon. Beginning at the cardiac end, 
 they swept rapidly toward the pyloric end, increasing in strength 
 as they proceeded. It was readily seen that the hunger contrac- 
 tions are powerful peristaltic contractions, which, arising at or near 
 the cardiac sphincter, swept downward over the entire stomach. 
 During a typical hunger period the stomach exhibits movements 
 which resemble very closely the movements which have been 
 described by some clinicians in patients after a bismuth meal as 
 hyperperistalsis, but described by Cole as normal "peristalsis of a 
 stomach that contains small quantities of food. Observations on 
 the dog were made after 36 hours of deprivation of food, on man 
 after 15 hours. Prolonged starvation in the case of the dog was 
 necessary to overcome the inhibitory influence of the excitement 
 attendant upon the X-ray examination. Whether or not the stom- 
 ach of man after a long period of starvation would show a condition 
 approaching that described for the dog, we are not in a position 
 to state. 
 
 The current teaching with reference to the part played by the 
 fimdus during digestion is that it is a reservoir, exerting a tonic 
 
THE STOMACH IN HUNGER 
 
 6i 
 
 grasp upon its contents. The kinematographic figures of the 
 stomach pubHshed by Kastle, Ridder, and Rosenthal show that 
 the fundus is not quiescent during digestion. Cole has shown that 
 when food is in contact with the cardiac end of the stomach in 
 man, contractions begin in the fundus and frequently are as deep 
 
 Fig. II. — Hunger contractions of the dog's stomach 30 hours after a meal. 
 
 A, outline of bismuth-coated balloon in stomach between the gastric contractions; 
 
 B, outline of balloon at the height of a hunger contraction (Rogers and Hardt). 
 
 in this region as in the pylorus. According to Forsell, with the 
 subject in the standing position, the fundus shows no peristalsis. 
 In the reclining position there occur typical peristalses of the 
 fornix. At the conclusion of gastric digestion there occur circular 
 contractions of the wall. 
 
62 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 It is thus evident that the digestion contractions of the filled 
 stomach pass gradually over into the hunger contractions of the 
 empty stomach. This explains how the hunger sensation may be 
 aroused by the stomaph contractions before the stomach is actually 
 empty. It is merely a question of intensity of the fundus contrac- 
 tions. But it is still true that the digestion contractions are pri- 
 marily concerned with the pyloric end of the stomach, while the 
 himger contractions of the empty stomach are initiated at the 
 cardia and involve the entire stomach. 
 
 II. ORIGIN OF THE HUNGER SENSATION 
 
 We have now discussed in some detail the tonus and the con- 
 tractions in the empty or partly empty stomach, esophagus, and 
 intestine of man and of a number of other species of vertebrates. 
 Do these contractions initiate the sensation of hunger, does the 
 central state or sensation of hunger initiate the contractions, or is 
 there no genetic relation between the two series ? We have seen 
 that these questions have been answered in various ways by physi- 
 ologists, psychologists, and clinicians, but without conclusive prpofs. 
 
 We owe the actual demonstration of the synchrony of the 
 himger sensations with the strong contractions of the empty 
 stomach to Cannon and Washburn. These observers recorded by 
 means of an electric signal the subjective sense of hunger simul- 
 taneously with the intragastric pressure, and found that the 
 stomach contractions and hunger sensations ran parallel. The fact 
 that the beginning of the stomach contractions is in evidence 
 before the hunger sensation is felt and that the sensation lasts 
 longer than the active phase of the contraction is adduced by 
 them in support of the view that contractions in some way stimu- 
 late afferent nerves in the stomach, and that these impulses give 
 rise to the hunger pangs. 
 
 The beautiful demonstration of Cannon and Washburn leaves 
 undecided the question where the contraction stimuU act in the 
 stomach, and the cause of the peculiar periodicity of these con- 
 tractions. But there can be no further question of the parallel 
 between the stomach contractions and the hunger sensation, even 
 
THE STOMACH IN HUNGER 63 
 
 though the evidence that the former are the cause of the latter is 
 incomplete. We do not appreciate the force of Cannon's argument 
 that no other condition than the contractions as the cause can 
 account for the periodicity or intermittency of the hunger sensa- 
 tions. Assuming that the stomach contractions constitute the 
 primary stimuli in the genesis of hunger, does that really solve the 
 problem of periodicity ? It would seem that the problem is only 
 shifted a httle; for these stomach contractions must depend on 
 corresponding periodic rhythmical activities in the gastric muscles 
 (idio-muscular contractions, "nodal tissue" rhythm) or in central 
 or peripheral motor nervous mechanisms. That such rhythm 
 should give rise to the hunger sensations indirectly through con-^ 
 tractions in the digestive tract is just as difficult to explain as a 
 similar central nervous rhythm giving rise to or constituting the 
 hunger sensation directly. 
 
 In our experiments the subject was either standing, sitting, or 
 lying down. His position was such that he could not see the 
 kymograph or any of the recording apparatus. The signal key or 
 keys for recording the hunger sensation were placed in his hand, 
 and he was instructed to press the key as soon as he felt hunger 
 and to keep on pressing it till the hunger was no longer felt. There 
 was no difficulty in keeping a person's attention fixed on this for 
 shorter periods of i or 2 hours and under conditions of hunger 
 of moderate intensity. But in the case of Mr. V., when the obser- 
 vations were continued without interruption for 5 to 6 hours and, 
 therefore, during several periods of strong hunger, he would 
 usually become restless, and unable to give undivided attention 
 to the introspection. 
 
 Most of the observations were made within a period of from 
 4 to 10 hours after meals, and only a few as long as 24 to 120 
 hours after a meal, for the reason that the hunger pains in many 
 persons become gradually severe to the point of discomfort, and 
 the man becomes restless and tired. 
 
 As a check on the intragastric respiratory pressure, records of 
 the respiratory movements (chest pneumograph) were usually 
 taken simultaneously with that of the stomach movements. 
 
64 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The general results of our work on more than fifty men are in 
 complete accord with those of Cannon and Washburn. When the 
 empty stomach shows strong contraction, the subject invariably 
 signals that he feels hunger, and, on being questioned, he invariably 
 rephes that he feels the hunger in his stomach. There is, on the 
 whole, a fairly close correspondence between the duration of 
 stomach contractions and duration of the subjective sensations of 
 hunger. On days when the stomach does not exhibit these strong 
 contractions, the person does not feel hungry. These "hunger 
 contractions" of the empty stomach are primarily those of the 
 strong periodic rhythm already described. 
 
 Relation between the strength of the stomach contractions and the 
 intensity of the hunger sensation. — ^Data on this point were obtained 
 in the following manner: Three signal magnets were arranged to 
 record on the drum perpendicularly to the recording point of the 
 bromoform manometer, and the corresponding keys were placed 
 in the subject's hand. He was then instructed to press key No. i 
 when he felt, without question, even the faintest hunger; No. 2 
 when he felt hunger of moderate strength; and No. 3 when he 
 felt the strongest hunger. 
 
 The subject presses key No. i (weak hunger) at the beginning 
 of a contraction period when the individual contractions are rela- 
 tively feeble. Then, as the contraction increases in strength, there 
 comes a period of vacillation between key No. i and key No. 2 
 (moderate hunger). As the contractions grow stUl stronger, key 
 No. 2 is used for a while without any change. Then follows a 
 period of alternation between key No. 2 and key No. 3, and in 
 the final stage of maximum activity of the contraction period the 
 signal is made with key No. 3 exclusively. In other words, there is 
 a fairly close correspondence between the strength of the stomach 
 contractions and the degree of hunger sensations experienced 
 simultaneously. 
 
 This account applies particularly to the first hunger period 
 appearing after a meal and for the milder hunger periods in general. 
 On more prolonged fast, that is, after ha,ving experienced several 
 hunger periods in succession, the subject may not signal with key 
 
THE STOMACH IN HUNGER 65 
 
 No. I at all, and sometimes not even with key No. 2, but starts in 
 with key No. 3 (strongest hunger) at the very begirming of a period, 
 despite the fact that the strength of the stomach contractions is 
 not greater (or might be even less) than those designated as very 
 mild or moderate hunger some hours or days earlier. This seems 
 to indicate an increased exdtabihty of the afferent nerves in the 
 stomach, or an increased excitability of some parts of the brain. 
 
 The close parallel between the degree of the stomach contrac- 
 tions and the intensity of the hunger sensations is further shown 
 by the fact that the beginning of a strong contraction is frequently 
 signaled by key No. 2 (moderate hunger), and then a shift made to 
 key No. 3 (strong hunger) nearer the apex of the contraction. 
 Evidently, it is possible to distinguish a gradually increasing 
 intensity of the hunger sensation during and parallel with the 
 individual himger contractions in the stomach. But this distinc- 
 tion is never made in very strong hunger and corresponding 
 contractions. 
 
 Fusion of the hunger sensations into hunger tetanus parallel with 
 strong and rapid contractions or tetanus of the stomach contractions. — • 
 The essential features and conditions of. the incomplete tetanus of 
 the stomach contraction at the end of the period of very vigorous 
 contractions are already familiar to the reader. These tetanus 
 periods of the stomach are invariably accompanied by a similar 
 fusion or tetanus of the hunger sensation. The fusion of the hun- 
 ger sensation appears to be more complete than the fusion of the 
 stomach contractions. When the rate of the strong stomach con- 
 tractions approaches 2 per minute, the fusion of the hunger sensa- 
 , tions is practically complete, that is, a person is then unable 
 to distinguish any rhythmical variations in the hunger intensity. 
 These phases of the stomach contractions are always signaled with 
 key No. 3 (strongest hunger). The greater fusion of the hunger 
 sensations than is shown by the synchronous stomach contractions 
 is probably due to the tonus element, as a strong and persistent 
 state of tonus gives rise to a continuous hunger sensation. The 
 fact that the strong individual sensations lag or persist longer than 
 the corresponding stomach contractions may also be a factor. 
 
66 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The abrupt cessation of the gastric tetanus at the end of a 
 strong contraction period is accompanied by an equally abrupt 
 and complete cessation of the hunger sensations. 
 
 Individual contractions of the "20-seconds rhythm" may give 
 rise to a mild hunger pang, in which case they are usually stronger 
 than those not definitely recognized in consciousness. But occa- 
 sionally there may be no marked difference in the amplitude of 
 the contractions. Each consecutive contraction of the " 20-seconds 
 rhythm" is never signaled as a hunger contraction imless the con- 
 tractions are very strong, in which case they can hardly be 
 distinguished from the moderate contraction of the periodic or 
 "30-seconds rhythm." 
 
 Assimiing that the " 20-seconds rhythm " is an antrum rhythm, 
 and that the stomach contractions cause the hunger sensations, 
 it follows that strong contractions of the pyloric region should 
 cause hunger. Now, such strong contractioifs of this region of the 
 stomach occur during vomiting, yet vomiting is, to our knowledge, 
 never accompanied by hunger sensations, although epigastric pain 
 and distress may be felt. Of course it is possible that the change 
 in the physiological condition in the central and the gastric nervous 
 mechanisms usually present in vomiting may accoimt for the 
 absence of hunger. The recognition of only an occasional contrac- 
 tion of the "20-seconds rhythm" as a hunger contraction when all 
 the contractions are of nearly uniform intensity is probably due to 
 variations in attention. 
 
 The significance of the time relations between the stomach contrac- 
 tions and the hunger sensations. — ^It was pointed out by Cannon and 
 Washburn that the time relations between the stomach contractions 
 and the hunger sensations might serve to determine the nature of 
 their causal relationship. It is doubtful, however, whether the 
 data secured by the methods so far employed are of much signifi- 
 cance as regards this point. Unless the balloon in the stomach 
 completely fills the stomach cavity and the pressure in the balloon 
 is very slight, it is clear that the manometer does not register the 
 very beginnings of the contractions. And on the subjective side 
 we have the fluctuation of attention as a source of error. 
 
THE STOMACH IN HUNGER 67 
 
 The recognition of the stomach contraction as a hunger pang 
 depends not only on the strength of the contraction, but also on 
 the rapidity of development of the contraction phase; that is, two 
 contractions may indicate equal degrees of shortening of the stom- 
 ach musculature, but if the contraction phase of one covers a 
 minute or more, while that of the other half a minute or less, the 
 latter contraction only is accompanied by a definite hunger sensa- 
 tion. The stomach may thus exhibit slow tonus midulations of 
 considerable magnitude without any attendant hunger feehng. 
 This relation of the rate of the contraction of the hunger sensation 
 is in accord with one of the general "laws of stimulation," and 
 would seem to strengthen the view that the sensation is the result 
 of the contraction. 
 
 In no instance out of the numerous tests made on man was the 
 hunger felt before the beginning of the stomach contractions. 
 But when the balloon and the manometer are adjusted as deUcately 
 as possible, the hunger signal and stomach contractions appear 
 nearly simultaneously. But inasmuch as the manometer probably 
 does not register the very beginning of the contractions, it is evident 
 that some seconds of the contraction phase always precede the 
 hunger feeling. 
 
 When the stomach contraction is of moderate strength and 
 hunger sensation of correspondingly moderate intensity, the hun- 
 ger sensation usually ceases at the height of the contraction, but 
 when the contractions are very strong the hunger sensation persists . 
 also during the relaxation phase. In other words, the sensation 
 lags, both at the beginning and at the end of the contraction. 
 
 A certain degree of constant or tonic contraction in the empty 
 stomach appears to give rise to a continuous hunger sensation. — ^Thite 
 sensation is a somewhat incomplete feeling of tension or pressure 
 in the epigastric region, but usually less intense and less definitely 
 localized than the pangs of hunger caused by the strong rhythmical 
 contractions. This constant epigastric tension may thus be present 
 during an entire hunger period lasting for 15 to 60 minutes or more, 
 but augmented to distinct hunger pangs with each strong contrac- 
 tion. The degree of tonus or constant contraction of the stomach 
 
68 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 during a hunger period differs with the individual man, and this 
 tonus is not in evidence in some of the lower animals. But it is 
 likely that close introspection will reveal uniformly both the longer 
 hunger rhythms (15 minutes to i| hours) and the more rapid 
 rhythm (30 seconds) of the hunger pangs. 
 
 The stomach contractions give rise to the hunger sensations. — ^The 
 consideration of the cause of the gastric hunger contractions will be 
 taken up later, but the simpler question of the action of the con- 
 tractions may be briefly dealt with now. Assuming, for the present, 
 that the stomach contractions give rise to the hunger sensations 
 through the action of afferent nerves from the stomach, in what 
 way does the contraction act as a stimulus to these nerves ? Does 
 the hunger sensation arise (i) from the stimulation of nerves in 
 the mucosa; (2) from the stimulation of nerves in the muscular 
 coats and in the connective tissue; or (3) is it due to an inter- 
 central discharge from the Auerbach's plexus to the brain, asso- 
 ciated with the motor discharge from the same plexus to the 
 stomach musculature ? 
 
 As regards the first possibility, the following experiments have 
 been made, with negative results. It would seem that the only 
 way in which contraction of the stomach musculature can stimulate 
 nerve-endings in the mucosa is by mechanical pressure. This may 
 be imitated in the following way on Mr. V. During the period of 
 relative quiescence of the stomach between two periods of strong 
 hunger, when the afferent nerves concerned are in such condition 
 that their stimulation will give rise to hunger, mechanical pressure 
 on the mucosa by distension of the balloon or rubbing the mucosa 
 by the closed end of a test tube never causes sensations of hunger 
 unless these procedures lead to contractions. Mr. V. always 
 stated that he felt these pressures, but the sensations were not like 
 hunger. The objection might be raised against these experiments 
 that the pressure is not sufficiently strong, and, in the case of the 
 test tube, does not touch a sufficiently large area of the mucosa. 
 We admit that a more intense mechanical stimulation of the mucosa 
 could be produced by Pavlov's method on dogs of blowing sand 
 into the stomach by bellows. But we have not felt justified in 
 
THE STOMACH IN HUNGER 69 
 
 using similar procedures oi» Mr. V. The methods used do not, 
 of course, produce the strongest possible mechanical stimulation 
 of the mucosa, but these stimulations were sufficient to affect 
 consciousness. They were perceived, but not as hunger sensations. 
 It seems, therefore, highly probable that the afferent nerves in 
 the mucosa are not primarily concerned in the genesis of the 
 hunger sense. They are, however, concerned in the inhibition of 
 hunger. 
 
 The hunger sensation seems to be produced by the contractions 
 only. When the empty stomach is normal, strong contractions, how- 
 ever caused, produced a sensation of hunger. Thus, if the balloon 
 in the stomach is rather suddenly distended, this may produce 
 one, two, or three strong contractions of the previously quiescent 
 stomach, and these- are recognized as hunger contractions identical 
 with those of the "spontaneous" hunger periods. It seems to 
 us that this experiment constitutes a demonstration of the periph- 
 eral genesis of hunger, as the subjective state clearly is induced 
 by the peripheral change. A tracing illustrating this phenomena 
 is reproduced in Fig. 12. 
 
 But how do the contractions stimulate the afferent nerves in 
 the muscle layers ? Contraction in skeletal muscle stimulates 
 afferent nerve fibers in the muscle. But it seems to us that the 
 pain experienced from contractures or " cramps " in skeletal muscles 
 and in the intestines in the case of coKc or tenesmus is somewhat 
 different from the hunger pangs, even though pain is inherent in 
 hunger. The difference may be only an apparent one, due to the 
 fact that the latter pains arouse the memories of previous agreeable 
 experiences with food. Because of the folding of the mucosa and 
 the submucosa into rugae and the changes in the arrangement 
 of the cells in the muscle layers in the stomach during contractions, 
 there must be a great variation in tension on the nerve-fibers in 
 the contracted and in the relaxed condition of the stomach walls. 
 This variation in tension, rather than actual pressure, may con- 
 stitute the stimulus, so far as the stimulus is a mechanical one. 
 Hunger, therefore, contains elements of kinesthetic sensation as 
 well as pain, the latter predominating in strong hunger. 
 
70 
 
 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 We have been strongly impressed by Mr. V.'s ability to recog- 
 nize feeble stomach contractions as hunger states. Very strong 
 stomach contractions can be recognized as separate hunger pangs 
 by most people, but there are great individual variations in the 
 ability to recognize each individual contraction, unless the con- 
 tractions are very strong. 
 
 ^*''V'''**v-j^ 
 
 Fig. 12. — Two-thirds the original size. .4, stomach contractions; B, respiratory 
 movements; a, b, signals for moderate and strong hunger respectively. The pressure 
 in the balloon is slight. There is no evidence of strong stomach contractions, and Mr. V. 
 feels no hunger. At x the pressure in the balloon is suddenly increased. This disten- 
 sion of the balloon initiates a few strong stomach contractions, which in turn cause 
 the hunger states. A demonstration of the gastric genesis of himger. 
 
 Two explanations of Mr. V.'s unusual ability in recognizing the 
 stomach activities have occurred to the writer. Since early boyhood 
 the stomach has been to Mr. V. the object of special care and atten- 
 tion. In consequence of such special attention to the stomach the 
 afferent nervous impulses from the stomach may attain a clearer 
 definition in consciousness analogous to the remarkable development 
 
THE STOMACH IN HUNGER 71 
 
 of analysis in the tactile or pressure senses in the absence of vision. 
 That this type of education or training does take place, the author 
 is satisfied from his own experience during the four years that he 
 has studied the hunger mechanism on himself. At the point of 
 the gastrostomy Mr. V.'s stomach adheres to the parietal peri- 
 toneum. There may be adhesions of greater extent in consequence 
 of the operation. The hunger sensation of Mr. V. may therefore 
 include a greater degree of pain than is the case in normal men, 
 as the contracting stomach may pull on the parietal peritoneum, 
 which, according to many observers, is very sensitive to painful 
 stimuU. The weaker stomach contractions may thus be recog- 
 nized as hunger because more painful than under normal conditions. 
 Confirmatory evidence (or the opposite) ought to be obtainable 
 without much difl&culty, as cases of gastrostomy are fairly common. 
 Clinicians having such cases in hand would do a service to physi- 
 ology if they could determine whether gastrostomy invariably 
 augments the hunger sensations or makes the hunger pangs more 
 painful. 
 
 We have shown that in all animals so far studied the empty or 
 partly, empty stomach exhibits the tonus and contractions which 
 in man give rise to the hunger sensation. There are some differ- 
 ences in these contractions in different species, but these are 
 probablyof nainor importance. Manknows that asensation of strong 
 hunger is felt synchronously with the strong contraction. We have 
 a right to conclude that the lower animals experience the same 
 sensation simultaneously with the corresponding contraction. We 
 have, then, in the tonus and contractions of the empty stomach an 
 objective criterion for the presence or absence of hunger in experi- 
 mental animals in normal health. 
 
 HI. THE ESOPHAGUS AND THE CARDIA IN HUNGER 
 I. METHODS OF INVESTIGATION 
 
 There is some evidence in the literature of contractions of the 
 esophagus synchronous with the periods of gastric hunger con- 
 tractions. Some people refer the hunger sensation or hunger pangs, 
 
72 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 not only to the stomach, but also to the chest and throat. This 
 appears to be true, not only of ignorant people, such as those 
 interrogated by Schiff, but also of persons of special training in 
 introspection. Cannon and Washburn have described periodic 
 contractions of the lower end of the esophagus in man, and these 
 contractions seemed to give rise to hunger pangs just as in the 
 case of the contractions of the empty stomach. They suggest 
 that the esophagus contractions are synchronous with the gastric 
 hunger contractions, but they did not prove the hypothesis by 
 recording the stomach and esophagus contractions simultaneously. 
 
 We studied the motor conchtions of the esophagus in hunger on 
 three men who experienced no difficulty in swallowing simul- 
 taneously the gastric and the esophageal balloons with their flexible 
 rubber tube attachments. In part of the work we used the best 
 quality of rubber condums also for the esophagus balloon, not in 
 their entire length, as in the case of the stomach, but cut down to 
 a length of 3 to 4 cm. We soon encountered difficulties in the work 
 with the esophagus, difficulties apparently not noticed by Cannon 
 and Washburn. Thinking that part of these difficulties might be 
 due to the diameter of the esophagus balloon, we resorted to the 
 rubber finger cot employed by these observers. But even the 
 best rubber finger cots are not as satisfactory as the condum 
 balloon. 
 
 The position of the balloon in the esophagus was usually deter- 
 mined by the distance from the incisor teeth to the lower end of 
 the balloon. If the balloon is clear above the cardia the movements 
 of inspiration decrease the positive pressure in the distended bal- 
 loon in proportion to increase in the negative pressure in the 
 thoracic cavity. But if the balloon is located in the region of the 
 cardia itself, it depends on the relative preponderance of diaphragm 
 and chest movements whether the act of inspiration leads to increase 
 or decrease in the balloon pressure. The esophagus balloon can be 
 well in the cardia and still show negative pressure in inspiration 
 if the inspiration is predominantly costal.. On the other hand, if 
 the lower end of the balloon is just within or at the cardiac orifice, 
 a diaphragmatic inspiration increases the pressure in the balloon. 
 
THE STOMACH IN HUNGER 73 
 
 although not to the same extent as when the balloon is in the 
 fundus of the stomach. 
 
 In the case of A. J. C. and J. H. L. it was found that when 
 the distance from the lower end of the esophagus balloon to the 
 incisor teeth was 15I to 16 inches the balloon was as far down as 
 it could be located without being directly affected with the con- 
 tractions of the cardia and the stomach. Allowing the balloon to 
 slip down J to I inch farther brought it to the cardia and the 
 cardiac end of the stomach. In the case of A. B. L. the distance 
 from the incisor teeth to the lower end of the balloon could not 
 exceed 14^ to 15 inches, if pure esophagus effects were to be 
 obtained. When the esophagus balloon is located 14 to 16 inches 
 from the incisor teeth, it is obviously well below the level of the 
 heart, and therefore in the region of myenteric plexus and non- 
 striated musculature of the esophagus. 
 
 The esophageal and stomach tubes were usually Joined together 
 firmly, so that the lower end of the esophagus balloon' was i§ 
 inches above the upper end of the stomach balloon. The pressure 
 in the esophagus balloon varied between i and 4 cm. of chloroform. 
 
 2. RESULTS IN MAN 
 
 Local contractions and peristalsis. — When the esophagus balloon 
 is distended with a pressure of 2 to 4 cm. chloroform the esophagus 
 usually exhibits rapid continuous contractions. These contrac- 
 tions are at times quite regular both in rate and amplitude. The 
 total time of each contraction is less than 2 seconds. 
 
 In addition to these contractions the esophagus mdy show 
 contractions of a tonic character. The duration of these contrac- 
 tions varies from a few seconds to several minutes. If these tonus 
 contractions are only moderately strong, the rapid contractions, 
 just .mentioned, continue and are superimposed on the former. 
 In some cases the tonus contractions are quite regular in rate and 
 intensity, but this is exceptional. 
 
 Both t3Tpes of contractions appear to be local. They are not 
 related to esophageal peristalsis, although a peristalsis (caused by 
 swallowing) may induce them in a quiescent esophagus. They are 
 
74 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 not related to gastric contractions, for they occur when the empty 
 stomach is quiescent. They may also occur during gastric hunger 
 contractions, but in this case there is no synchrony between the 
 gastric and the esophageal contractions. They are local contrac- 
 tions of the esophageal tube and not peristaltic, because they do 
 not move the distended balloon. But occasional peristaltic con- 
 tractions of local origin appear during these contractions. This 
 is shown by the pull on the tube if this is fixed to the teeth, or by 
 the downward movement of the tube if it is not fixed. In this way 
 the esophagus balloon is worked through the cardia unless the 
 tube is secured to the teeth. This peristalsis is obviously identical 
 with the "secondary esophageal peristalsis" of Meltzer. 
 
 These esophageal contractions do not give rise to hunger and are 
 in no way associated with this sensation. The rapid contractions 
 do not affect consciousness, but more prolonged tonic contractions 
 are felt if they are strong or moderately strong. They are felt, not 
 as hunger pangs, but as a fulness in the chest or throat, as of some- 
 thing having stuck in the throat. This sensation is so character- 
 istic and distinct that there is no possibility of confusing it with 
 hunger pangs of gastric origin. 
 
 These contractions arei caused by the local mechanical stimu- 
 lation of the distended balloon. The contractions are more marked 
 the greater the pressure in the balloon, but at times they appear 
 even with a balloon pressure of less than i cm. chloroform. They 
 are most marked immediately after the introduction and distension 
 of the balloon, but they may persist during an entire observation 
 period of 4 to 5 hours if the balloon pressure is above i to 2 cm. 
 chloroform. We did not observe any decrease in these local con- 
 tractions during the progress of the experiments, as one might have 
 expected in case there was any appreciable "education" of the 
 esophagus to the pressure of the balloon. Evidently the esophagus 
 mechanisms are so adjusted that local mechanical stimulation 
 causes local contractions interspersed with occasional peristalsis 
 until the stimulus is removed, that is, the material forced into the 
 stomach. The local contractions as well as the secondary peristalsis 
 may be reflexes via the medulla, as indicated by Meltzer's observa- 
 
THE STOMACH IN HUNGER 75 
 
 tions. But the absence of the contractions after section of the vagi 
 does not prove it, at least for the part of the esophagus provided 
 with non-striated musculature and myenteric plexus. It is known 
 that this part of the esophagus responds to local stimulation with 
 local contractions and peristalsis after recovery from the temporary 
 hypotonicity following section of both vagi. 
 
 These local contractions of the esophagus were -evidently not 
 encountered by Cannon and Washburn, although the only differ- 
 ence between our technique and theirs is the additional balloon in 
 the stomach (and, in consequence, two rubber tubes in the esopha- 
 gus). Is the local excitability of the esophagus increased by the 
 presence of a distended balloon in the stomach, a rubber tube in 
 the cardia, and a second rubber tube in the esophagus and mouth ? 
 AH the men used in our experiments showed these contractions. 
 Can it be the esophagus of Mr. Washburn is exceptional ? Or did 
 Cannon and Washburn have the esophagus balloon actually located 
 in the cardia, so that their tracings record the behavior of the 
 cardia rather than that of the esophagus proper ? 
 
 Boldyrefl pointed out that the balloon method cannot be used 
 for recording the periodic contractions of the empty intestines, for 
 the reason that the distended balloon causes local contractions 
 through mechanical stimulation. Fortunately this is not true for 
 the gastric fvmdus, but it is true for the esophagus, at least to an 
 extent to impair greatly the efl&cacy of balloon method. For when 
 the esophagus baUoon is distended sufficiently to register the 
 slightest tonus variations and contractions of the esophagus, the 
 local contractions are most prominent and disturbing. 
 
 Contractions synchronous with the gastric hunger contractions. — 
 The weaker gastric hunger contractions at the beginning of a 
 himger period are usually not accompanied by any esophageal 
 contractions. But synchronous with the strong hunger contrac- 
 tions' that mark the culmination of a gastric hunger period there 
 is some persistent increase in the tonus of the esophagus and brief 
 contractions simultaneously with the individual stomach contrac- 
 tions. This increased tonus and rhythmic contractions of the 
 esophagus parallel with the hunger activity of the stomach are in 
 
76 
 
 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 evidence even when the esophagus exhibits the rapid local contrac- 
 tions described above. The esophagus contractions appear to lag 
 behind the gastric contractions and are as a rule of briefer duration. 
 The frequent culmination of the gastric hunger contractions in a 
 period of incomplete tetanus of var)ang durations seems to have no 
 parallel in the esophagus in the way of strong and prolonged 
 contractions. ' 
 
 Fig. 13. — Simultaneous records from the stomach (lower curve) and the lower 
 fourth of the esophagus (upper curve) of A. J. C. during the culmination of a period of 
 vigorous gastric hunger contractions. Lower end of esophageal balloon = 16 cm. from 
 incisor teeth, that is, at the cardia. Pressure in baUoon = 3 cm. chloroform. Showing 
 weak esophageal contractions synchronous with the gastric hunger contractions. 
 One-half original size. 
 
 These esophageal contractions parallel with the gastric hunger 
 contractions are apparently not identical with the esophageal con- 
 tractions reported by Caimon and Washburn. These observers 
 noted that the esophageal contractions were more prolonged than 
 the gastric contractions of the same man during other hunger 
 
THE STOMACH IN HUNGER 77 
 
 periods. The contractions noted by us are usually briefer than the 
 parallel stomach contractions. Washburn was able to associate 
 the esophageal contractions with the sensation of hunger pangs. 
 None of us are able to do that. In the first place the esophageal 
 contractions that occur spontaneously during quiescence of the 
 empty stomach contractions that may be identical in rate and 
 strength with those parallel with the gastric hunger contractions 
 are either not felt at all, or else felt as a disagreeable fulness in 
 the throat, something stuck in the esophagus, and not as the uncom- 
 fortable emptiness that characterizes the genuine pangs of hunger. 
 To be sure, when the gastric hunger contractions are sufficiently 
 intense to be definitely accompanied by esophageal contractions 
 aU of us feel the pangs of hunger strongly, but these are of gastric 
 origin and are referred to the stomach and not to the esophagus 
 or throat. 
 
 Contractions of the cardia. — ^That there is an increase of the 
 tonic contraction of the cardia during the gastric hunger contrac- 
 tions is rendered probable by the fact that the air and other gases 
 always present in the stomach are not forced into the esophagus 
 during these contractions even when they are very strong. Cannon 
 and Washburn state that this fact argues for contractions of the 
 esophagus parallel with the contractions of the empty stomach. 
 Did they not overlook the fact that the cardia is capable of doing 
 this even in the absence of esophageal contractions ? There is no 
 escape of air from the stomach during the periods of incomplete 
 gastric tetanus at the end of a hunger period, although these con- 
 tractions are practically never accompanied by any esophageal 
 contractions. In the dog esophageal contractions are known to be 
 permanently abolished by section of both vagi, yet this does not 
 lead to belching of air even during the greatest increase in intra- 
 gastric pressure that the contractions of the empty stomach are 
 capable of producing. 
 
 It is therefore evident, not only that the cardia itself is 
 able to prevent the escape of air into the esophagus during 
 increased intragastric pressure, but also that the cardia in 
 all probability contracts more powerfully during the gastric 
 
78 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 hunger contractions, thus increasing its efl&dency as a guard. 
 Direct graphic evidence of the latter is, however, difl&cult to 
 secure. 
 
 When the empty stomach is quiescent the cardia offers only 
 slight resistance to the withdrawal of a distended balloon of the 
 size of a rubber finger cot from the stomach into the esophagus. 
 A larger baUoon, such as the condum used for the stomach, en- 
 counters somewhat greater resistance at the cardia, as well as in 
 the esophagus itself. If one attempts to withdraw the balloon 
 from the stomach at the height of a gastric hunger contraction, 
 the resistance offered by the cardia is distinctly increased. This 
 can mean only one thing, viz., an increase in the contraction of 
 the cardia. If the contraction of the cardia did not increase, the 
 withdrawal of the baUoon would be actually facilitated by the pres- 
 sure exerted by the stomach contractions. For example, increasiag 
 the intragastric pressure by forcible contraction of the abdominal 
 muscles may force the stomach balloon into the esophagus in case 
 the stomach is quiescent. 
 
 It is difi&cult to keep an inflated balloon actually in the cardia 
 for any considerable time, especially during the strongest gastric 
 hunger contractions. Strong esophageal peristaltic movements 
 keep pushing it toward the stomach, and at times the gastric con- 
 tractions actually push it back into the esophagus. At the best 
 the balloon will stay in the cardia during two or three successive 
 gastric contractions of the weaker type, that is, at the beginning 
 of the hunger period. The type of balloon used for these tests was 
 the rubber finger cot 3 cm. in length. A balloon of greater length 
 could, of course, be lodged in the cardia with greater ease, but a 
 baUoon of greater length than 3 cm. would be influenced not only 
 by the cardia, but also by the cardiac ends of the stomach and the 
 esophagus. In fact this probably occurs, but to a less extent, even 
 when a short balloon is used, as the physiological cardia is probably 
 less than i cm. in width. Anatomically the cardia is not sharply 
 differentiated in man. We judged the position of the balloon in 
 the cardia by the distance of the balloon from the incisor teeth and 
 by the influence of the respiratory movements, moderate inspira- 
 
THE STOMACH IN HUNGER 79 
 
 tion, mainly costal, causing lowered tension, and moderate dia- 
 phragmatic inspiration causing increased tension. When the 
 balloon is in this position the cardia exhibits the 20-seconds 
 rhythm previously reported for the fundus of the empty stomach. 
 This rhythm of the cardia is in evidence even when the empty 
 stomach is quiescent. When the empty stomach shows hunger 
 contractions the cardia shows parallel contractions or periods of 
 increased tonus. The contractions of the fundus and of the cardia 
 are strictly sjmchronous, but those of the cardia appear to be more 
 persistent or tetanic. The tracings secured by us from the balloon 
 in the cardia resemble those published by Cannon and Washburn 
 as esophageal contractions more than do the actual esophageal 
 contractions obtained by us. 
 
 Contractions of the upper end of the esophagus. — In a few experi- 
 ments the esophageal balloon was placed in the esophagus 7 to 10 
 inches from the incisor teeth, that is, in the lower part of the neck 
 and upper part of the chest. The spontaneous local contractions 
 are in evidence also in this part of the esophagus. There is usually 
 a slight increase of tonus when very strong gastric hunger contrac- 
 tions are present, but nothing like the strength of contractions 
 during the peristalsis of deglutition or those caused by the local 
 mechanical stimulation. The tonus increase of the upper half of 
 the esophagus parallel with the gastric contractions is insignificant 
 compared with the corresponding contractions of the lower third of 
 the esophagus. This is probably correlated with the gradual dis- 
 appearance of non-striated musculature and myenteric plexus in 
 the oral half of the esophagus in man. 
 
 3. RESULTS ON DOGS 
 
 All of our dogs used in this work were provided with a gastric 
 fistula for the introduction of the stomach balloon. The esophagus 
 was left intact and the esophageal balloon introduced through the 
 mouth. The dog is of special interest in this connection, because 
 the dog's esophagus is composed of striated musculature throughout 
 its whole length. The myenteric plexus is probably lacking. It 
 is needless to say that all the dogs were subjected to preliminary 
 
8o CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 training in the way of getting used to the balloons in stomach and 
 esophagus. As a matter of fact all the dogs were accustomed to 
 these procedures, having been used for other lines of work on the 
 hunger mechanism, so that they would lie quietly and comfortably 
 in the lap of an attendant during the tests. It is absolutely essen- 
 tial that the dogs be quiet, if possible sleeping, during these tests, 
 for restlessness increases the disturbance of the esophagus even 
 more than of the stomach. 
 
 Local spontaneous contractions. — The presence of the inflated 
 balloon in any region of the esophagus caused rapid local contrac- 
 tions, more rapid than those of the human esophagus, alternating 
 with an occasional peristalsis, also of local origin, and occasionally 
 more prolonged tetanic contractions. These tetanic contractions 
 usually last for only half a minute to a minute. In one case it 
 lasted IS minutes. Tetanic spasms lasting up to 5 minutes are 
 not uncommon. These contractions have no relation to, the hun- 
 ger contractions of the empty stomach, as they may appear during 
 a hunger period as well as during gastric quiescence. They depend 
 on the local stimulation of the balloon in the esophagus and are, 
 therefore, more marked the greater the tension in the balloon. 
 They are also more marked when the dogs are excited, evidently 
 owing to increased reflex excitability of the medullary centers and 
 some increase in the tonus of the esophagus. The disturbance is 
 greatest when the balloon is first introduced, but it may keep up 
 for hours even when the pressure in the balloon is only 2 to 3 cm. 
 of bromoform or chloroform. A single swallowing act may induce 
 these local contractions, lasting for many minutes, in a quiescent 
 esophagus. The same thing has been observed in man. It is 
 probably due to increased reflex excitability of the medulla and to 
 increased tonus of the esophagus, as the latter is equivalent to in- 
 creased tension in the balloon, and therefore increased strength 
 of the local mechanical stimulation. 
 
 When: the esophagus contracts in tetanus on the balloon, addi- 
 tional disturbing factors appear. Evidently this kind of contrac- 
 tion causes the same sensation in man and dog, that is, the feeling 
 of something stuck in the throat, for when these contractions 
 
THE STOMACH IN HUNGER 8i 
 
 are present the dogs become restless and sometimes swallow 
 repeatedly. 
 
 Condition of the esophagus during gastric hunger contractions. — 
 The gastric hunger contractions are not accompanied by contrac- 
 tions or changes of tonus in any part of the esophagus. If the 
 gastric hunger contractions are very intense, so that they cause the 
 dog to moan or swallow, contractions may appear in the quiescent 
 esophagus, but this is obviously due to the general disturbance of 
 the animal. There is no synchrony between the gastric and the 
 esophageal contractions. If the dog lies quietly or is sleeping, a 
 strong gastric hunger period may run its course without the least 
 evidence of esophageal contractions. 
 
 Inhibition of the gastric hunger contractions during the tetanic 
 contractions of the esophagus. — ^TEd strong and prolonged local 
 contractions of the esophagus cause inhibition of the gastric tonus 
 and the gastric hunger contractions, while the rapid esophageal con- 
 tractions seem to have no effect on the stomach. This is evidently 
 a special instance of the "law of the intestine," that is, inhibition 
 caudal or aboral to a region in the state of contraction. Other 
 factors may also be concerned in this inhibition of the stomach. 
 The tetany of the esophagus causes some distress, and this may 
 lead to inhibitory action via the splanchnic nerves. The gastric 
 inhibition ordinarily lasts as long as the tetanus in the esophagus. 
 
 Contractions of the esophagus in response to seeing and smelling 
 food. — Seeing and smelling meat on the part of a hungry dog almost 
 invariably led to contractions of the otherwise quiescent esophagus. 
 Ordinarily the contractions are of the local rapid tj^ie, and the 
 disturbance of the esophagus lasts only for lo to 30 seconds. But 
 occasionally the sight or smell of food may send the esophagus 
 into complete tetanus lasting for several minutes. Both tj^es of 
 esophageal contractions are accompanied by inhibition of the^ 
 stomach. A single act of swallowing, as we have seen, may produce 
 the same disturbance in the part of the esophagus where the bal- 
 loon is located, and the dog frequently swallows or at least elevates 
 the larynx at the sight of the food. But these contractions on the 
 sight of food also appear when the dog does not swallow. The 
 
82 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 phenomenon is probably to be explained as follows : The sight or 
 smell of food on the part of the hungry dog causes temporary 
 increase in neuro-muscular tonus, including the tonus of the esoph- 
 agus. The increase in esophagus tonus causes greater pressure on 
 the balloon, and in consequence stronger mechanical stimulation 
 of the afferent nerves in the esophagus, and hence the rapid or 
 tetanic contractions. It is therefore probable that the actual con- 
 tractions of the esophagus on seeing food are artifacts, so to speak, 
 due to the presence of the balloon. 
 
 4. THE. INTESTINES IN HUNGER 
 
 Periods of active contraction of the small intestines in hunger 
 were observed in the duodenal fistula case of Busch. BoldyrefE 
 found that the intestines (presumably both the large and small 
 intestine) exhibit rhythmic contractions during the periods of gas- 
 tric hunger contractions. His evidence consisted of the sounds 
 produced by the moving gas in the intestines and the appearance 
 of the free end of the fistula of the small intestine, during the 
 periods of strong rhythmical contractions of the empty stomach. 
 More accurate methods of registration should be devised. We 
 have observed in dogs with duodenal fistula evidences of contrac- 
 tions in the duodenum during hunger contractions of the stomach 
 (expulsion of bubbles of gas, fluid, debris, etc.) . There can be no 
 doubt that Boldyrefl's observation is correct. In two dogs we 
 introduced balloons both into the stomach and into the large 
 intestine (descending and transverse colon) . The large intestine 
 showed some contractions, but these were not correlated with the 
 periods of gastric hunger contractions, although the interesting 
 ~theory recently developed by Alvarez seems to imply that increased 
 tonus and contractions of the stomach must lead to increased 
 motor activity in the entire gut below the stomach. 
 
 Rumbhng intestinal sounds may be heard when the stomach 
 is quiescent. These are probably due to local stimulation resulting 
 from distension by the gases, hence mostly confined to the large 
 intestine. Rtimbhng intestinal sounds are usually heard during 
 gastric hunger periods, and it seems to us, one can at times actually 
 
THE STOMACH IN HUNGER 83 
 
 feel the intestinal movements. If this is the case, the intestinal 
 hunger movements must be much more vigorous than the digestive 
 movements. The character of the intestinal hunger contractions 
 is not known. Do they consist in peristalsis, in segmentation, or in 
 pendulum movements ? Or is it a type of contraction not seen 
 during digestion: rhythmic contractions and relaxations through- 
 out the whole intestine and s3Tichronous with the systole and 
 diastole of the hunger beats of the stomach and the lower end 
 of the esophagus ? This would imply a type of co-ordination of 
 the neuromuscular mechanism of the entire digestive tract not 
 revealed by the movements of digestion. In the movements of 
 digestion the esophagus, the cardia, the fundus, antrum pylori, 
 the pyloric sphincter, and the intestines act as relatively inde- 
 pendent mechanisms and appear to be governed by laws of 
 their own in harmony with the r61e played by these regions 
 in digestion. 
 
 While we admit the possibility that the contracting esophagus 
 and intestines may contribute to the sensation of hunger, the proof 
 for this is stiU wanting, and in any event the stomach is the main I 
 factor. The hunger pangs run absolutely parallel with the periods 
 of gastric hunger contractions, only lagging some seconds both at 
 the beginning and the end of each contraction. A strong contrac- 
 tion artificially induced in the empty stomach is recognized as a 
 hunger pang; a similar contraction induced in the esophagus when 
 the stomach is empty is recognized as something quite different 
 from hunger. And this will in all probability prove to be true 
 also of the intestines. No one can fail to recognize the difference 
 between the sensations initiated by strong contractions in the 
 small and large intestines and the rectum (intestinal cramp, tenes- 
 mus, defecation) and the gastric hunger pangs. 
 
CHAPTER V 
 SOME ACCESSORY PHENOMENA OF HUNGER 
 
 Many apparently normal persons experience in hunger, besides 
 ithe gnawing pressure-pain sensation in the stomach, a feeling of 
 Weakness, "emptiness," headache, and sometimes even nausea. A 
 certain degree of increased excitability of the central nervous sys- 
 tem, as shown by restlessness, irritability, diminished concentra- 
 tion and attention, and some sahvation are always present and 
 must be looked upon as a necessary efed of hunger rather than 
 accessory elements. 
 
 We call these states or symptoms accessory hunger phenomena, 
 because they are not always present in hunger, and because their 
 relative preponderance depends on the length of starvation and on 
 some individual peculiarity in the person. It must be admitted, 
 however, that in some individuals these accessory hunger phe- 
 nomena appear to overshadow, if not entirely to suppress, the 
 pressure-pain sensations from the stomach. This is probably due 
 to a relatively unstable condition of certain central nervous mech- 
 anisms rather than to actual absence of the hunger tonus and 
 hunger contractions of the empty stomach, although there are 
 unquestionably great individual variations in the latter, even in 
 comparatively healthy persons. The question can be settled by 
 direct test on persons who claim to feel weakness but no gastric 
 hunger pangs in starvation. 
 
 We think most observers will agree that in the normal person 
 the hunger experienced 4 to 10 hours after a meal is primarily the 
 gastric gnawing pangs, with practically no feehng of weakness, 
 and no marked or obvious hyperexcitability of the brain and spinal 
 cord. This is the Justification for calling the gastric sensation the 
 primary and essential factor in the hunger complex. Let us now 
 consider the cause of the accessory hunger phenomena, and their 
 relation to the gastric hunger pangs. 
 
 84 
 
SOME ACCESSORY PHENOMENA OF HUNGER 85 
 
 I. GASTRIC TONUS ANT* HUNGER CONTRACTIONS INCREASE 
 REFLEX EXCITABILITY OF CENTRAL NERVOUS SYSTEM 
 
 This is readily made out by recording the amplitude of the 
 knee jerk (or any other motor reflex) parallel with the graphic 
 recording of the gastric contractions. Such records show without 
 exception a marked increase in the reflex excitability of the spinal 
 cord simultaneously with the strong hunger contractions of the 
 empty stomach. The reflex excitability usually falls to normal 
 level during the pauses between the single contraction, and after 
 the strong hunger period it appears to be somewhat lower than 
 normal. The hunger contractions of the empty stomach frequently 
 increase the reflex response of the cord to such an extent that a 
 standard minimal stimulus causes a maximal response. The degree 
 of augmentation of the reflex is, on the whole, proportional to the 
 amplitude of the stomach contractions, and this can be shown 
 frequently during the shortening phase of a single contraction. 
 There are many exceptions to this last statement, to be sure. But 
 this is to be expected in view of the fact that under conditions as 
 nearly uniform as possible two successive stimuli of equal charac-' 
 ter and intensity rarely give two successive responses of equal 
 magnitude. 
 
 Some attention was paid to the question whether this augmen- 
 tation of the reflex excitabihty of the central nervous .system 
 synchronous with the hunger contractions of the stomach is in 
 evidence before the contractions have given rise to the conscious 
 hunger pangs. This much is certain, that the augmentation is 
 greatest at the height of the stomach contraction when the hunger 
 pang is the most intense. The present data do not warrant any 
 statement on the question whether or not the beginning of (he 
 augmentation precedes the conscious hunger pang to the same 
 extent that the stomach contraction precedes the hunger pang, 
 because little importance can be attached to slight variations in 
 the amplitude of the reflex response, except when the general 
 average is made significant by the great number of the individual 
 experiments. The stomach contraction is the primary factor or 
 stimulus, whether or not conscious cerebral processes constitute a 
 
86 
 
 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 necessary link in the chain of events that results in augmentation 
 of the reflexes. 
 
 Lombard concluded from experiments on himself that hunger 
 depresses the knee jerk. No account is given of the degree of 
 hunger experienqed by him before lunch and dinner. Possibly he 
 
 J L 
 
 _L 
 
 i ttiinftttftttiiuttittttitttt r- 
 
 -i titmnitMitttitttfjttttttuittiiifmuiitttttitttiiitititiit 
 
 Fig. 14. — ^I. A, record of the knee reflex; B, hunger contractions of the empty 
 stomach; showing augmentation of the knee reflex during the hunger contractions. 
 Time, five seconds. About one-half original size. 
 
 II. A, contractions of the empty stomach; B, plethysmograph record of volume 
 of the left arm; showing a vasomotor rhythm parallel with the strong hunger con- 
 tractions of the empty stomach. About one-third original size. 
 
 experienced only appetite and the feeble and "indefinite" hunger 
 that may be present in the absence of the strong stomach con- 
 tractions. In such conditions there is no augmentation of the knee 
 jerk in our subject. It should also be noted that in some cases 
 Lombard found his knee reflex greater before the meal (hunger ?) 
 than after the meal. 
 
SOME ACCESSORY PHENOMENA OF HUNGER 87 
 
 It may be questioned whether a comparison of the ampUtude 
 of the knee reflex before and after a meal is an adequate criterion 
 of the effect of hunger states on the reflex excitability of the spinal 
 cord. It seems to us that this is a comparison between hunger (or 
 appetite) and satiety, and not between hunger and the absence of 
 hunger. The partaking of food when hungry involves many changes 
 of a positive character besides the aboUtion of hunger. Hence it 
 is clear that there is no contradiction between our results and 
 Lombard's results on himself. The two series cannot be compared, 
 because the conditions of the subjects were not comparable. We 
 have made no tests on Mr. V. before or after a meal, similar to^ 
 those of Lombard. But when the comparison is made between the 
 state of hunger (as differentiated from appetite) and the absence 
 of hunger, the evidence is conclusive that hunger leads to or is 
 associated with an increased excitability of the cerebro-spinal axis. 
 This condition probably accounts for the irritability, restlessness, 
 and inability to maintain a fixed attention — always noted in con- 
 nection with strong hunger, and in some persons, even in case of 
 moderate hunger. The afferent nervous impulses from the stomach 
 in hunger interfere with other reflex and central processes by^ 
 monopoly of attention as well as by changes in the reflex centers/ 
 According to Weygandt starving persons dream more than usual 
 in their sleep. 
 
 Stimulation of the gastric mucosa produces a similar increase in 
 reflex responses. Thus hot or cold water, introduced into a stomach 
 by a tube, so that there is no stimulation of the nerves in the mouth 
 or the esophagus invariably augments the knee jerk in man. 
 
 Since the gastric hunger contractions actually induce the 
 increased excitability of the central nervous system reflexly, it 
 follows that this is a necessary phenomenon in hunger. The 
 precise degree of this central effect will depend on the intensity 
 of the hunger contractions, the irritability of the afferent gastric 
 nerves, and the stabihty of the central organization. The increased 
 reflex excitability and restlessness are, at least in part, subconscious 
 phenomena, since it is in evidence even in animals deprived of 
 their cerebrum (Goltz, Rogers). 
 
88 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 II. INPLXIENCE OF GASTRIC HUNGER CONTRACTIONS ON THE 
 HEART AND ON THE VASOMOTOR MECHANISM 
 
 1. The heart 6eoi.— During the period of strong stomach con- 
 tractions the rate of the heart beat is increased. At the cessation 
 of the contraction period the heart rate becomes slower again. 
 The return to the normal rate is gradual. If the motor activities 
 of the empty stomach are very vigorous, so that the pauses between 
 the contraction periods are relatively short, the pulse rate may not 
 return quite to the normal during these pauses. The average 
 increase in the rate of the heart beat during the hunger contractions 
 of the stomach is eight to ten beats per minute. But strong indi- 
 vidual contractions or tetanus periods may show an increase of 
 thirty beats per minute. 
 
 When the details of the contraction periods are further analyzed, 
 it is found that the greatest acceleration of the heart beat is on the 
 whole synchronous with the individual strong contractions, and 
 that the pauses between the contractions usually show less accel- 
 eration. It is not known whether this effect on the heart is a 
 reflex from the stomach, or due to a direct lowering of the 
 vagus tonus. 
 
 2. Vasomotor changes synchronous with the contractions of the 
 empty stomach, — It is weU known that the vasomotor center is 
 acted upon not only by practically all afferent impulses, but also 
 by the conscious centrifugal impulses ftom the cerebrum. None of 
 these disturbing factors can be controlled completely. The most 
 we can do is to endeavor to make the external conditions and the 
 cerebral processes as uniform as possible. This was attempted in 
 two ways during these experiments. The subject was permitted 
 to read stories; he was required to add figures, or his eyes were 
 covered and he was instructed to think of liothing in particular. 
 Aside from the varying cerebral states, auditory stimuli are the 
 greatest disturbing factors. 
 
 The periods of strong contractions of the empty stomach are 
 synchronous with great variations in the vasomotor tone, and in 
 most cases the vasomotor variations exhibit a rhythm similar to 
 
SOME ACCESSORY PHENOMENA OF HUNGER 89 
 
 that of the stomach. There is an increase in volume of the arm 
 (vasodilation) pari passu with an increasing tonus of the stomach 
 and with the beginning of the individual contractions, but the arm 
 begins to shrink (vasoconstriction) before the stomach contraction 
 has reached its maximum. Or the volume of the arm shows a 
 definite increase parallel with the strong contractions, and a cor- 
 responding diminution in the arm volume during the stomach 
 pauses. These two types of vasomotor rhythms were the ones 
 usually obtained during periods of moderate hunger contractions. 
 If the experiments were continued for long periods (4 to 6 hours) , 
 so that the hunger contractions and hunger tetanus became very- 
 strong, the vasomotor variations were in evidence, but the rhythms 
 were rarely synchronous with the stomach rhythms. In such 
 instances the subject gave unmistakable signs of restlessness. 
 Under these conditions the vasomotor rhythm' may be slightly 
 faster or slightly slower than the stomach rhythm, or the two 
 rhythms may be practically identical, but the contraction phase 
 of the stomach activity may be synchronous with a decrease in the 
 volimie of the arm (vasoconstriction). 
 
 Before the appearance of the first period of hunger contractions 
 after a meal, and during the pause or relative quiescence of the 
 stomach between the periods of moderate hunger contractions, 
 another type of vasomotor rhythm appears in the plethysmographic 
 records. Considerable attention was given to this rhythm, because 
 the rate of it suggested some correlation with the "20-seconds 
 rhythm " of the empty stomach. These slight variations in the arm 
 volume are frequently irregular, so that its rate cannot be made 
 out with certainty, but when the fluctuations are fairly regular 
 the rate corresponds closely to the "20-seconds rhythm" of the 
 empty stomach. The contraction and relaxation phases of the two 
 rhythms do not seem to correspond, but that is of little significance 
 in view of probable difference in the latent time of the respective 
 neuro-muscular apparatus as well as of the recording devices. 
 This type of vasomotor rhythm is most marked when the "20- 
 seconds rhythm" of the stomach is the strongest, that is, at the 
 begiiming of a period of strong hunger contractions. 
 
go CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 In view of the fact that the vasomotor center is acted on by 
 so many factors, central and peripheral, the parallelism between 
 the vasomotor tone and the motor activity of the empty stomach 
 during the hunger period is too regular to be accidental. When 
 the synchrony fails, this is probably due to central or peripheral 
 factors that cannot be controlled or recorded. The question, then,, 
 remains how this synchrony is brought about, and what is the 
 biological significance of it. (i) The co-ojfdination may be due to 
 associations between the vasomotor center and the center for gas- 
 tric tonus in the medulla. (2) It may be due to a d/rect action on 
 the vasomotor center by afferent impulses from the stomach 
 initiated by the stomach contractions. (3) Or, it may be due to the 
 influence on the vasomotor center of the conscious processes of 
 hunger, which are caused by the stomach contractions. Brodie 
 and Russel, and Miller have studied the effect on the blood pres- 
 sure of stimulation of the central end of the gastric branches of 
 the vagi in animals under general anesthesia. The changes in the 
 blood pressure are variable and complicated by respiratory changes 
 and vomiting movements. In dogs and cats the primary effects 
 may be either an increase or a decrease in the arterial pressure, while 
 in rabbits the stimulation seems to cause a rise in the blood pres- 
 sure only. It will probably be difficult to secure experimentally 
 the selective stimulation of the afferent gastric nerve fibers that 
 are stimulated by the contraction of the empty stomach. There 
 may be some coimection between the vasomotor rhythms described 
 above and the well-known Traube-Hering blood-pressure variations, 
 as the latter are frequently induced by experimental interferences 
 with the vagi. 
 
 III. SALIVATION 
 
 When a suitable cannula is put in the Stenson's duct in man 
 so that the rate of flow of the sahva can be measured accurately, 
 and with a balloon in the stomach to register the gastric hunger 
 contractions, one can demonstrate that there is a rhythm of the 
 salivary flow parallel to the gastric hunger-contraction rhythm. 
 Each strong hunger contraction is accompanied by a brief gush of 
 
SOME ACCESSORY PHENOMENA OF HUNGER 91 
 
 saliva from the duct. The amount of salivation varies with the 
 individual person, and it varies somewhat from day to day in the 
 same individual. The feebler contractions have no evident effect 
 on the saliva flow. This saliva flow is independent of the memory, 
 sight, or smell of palatable food during the hunger, but itas certain 
 that these stimuli and the central processes induced by them will 
 augment the salivation. 
 
 The increased flow of saliva that occurs simultaneously with 
 the strong hunger contractions is probably a reflex effect from 
 stimulation of sensory nerves in the stomach by the contractions. 
 It is well known that strong stimulation of gastric nerves induces 
 salivation and vomiting. Such stimulation is usually held to act 
 on the nerves in the mucosa, while the stomach contractions 
 stimulate the nerves in the muscularis mainly. It is probable 
 that strong stimulation of the sensory nerves in the sub-mucosa 
 and in the muscular layers also causes reflex salivation. 
 
 Some increased salivation is therefore a necessary effect of 
 strong hunger, irrespective of the presence of appetite, or the 
 memory, sight, or smell of good food. But the more copious 
 "watering of the mouth" that accompanies the thought or sight 
 of appetizing food is not of gastric origin. 
 
 rV. EFFECTS ON THE VASOMOTOR CENTER OF STIMULATION OF 
 THE GASTRIC MUCOSA 
 
 When cold or hot water is introduced into the stomach through 
 the tubes in quantities of 50 to 100 c.c. at a time, there is nearly 
 always a shrinking of the arm, that is, vasoconstriction. Water 
 at body temperature does not seem to affect the tonus of the vaso- 
 motor center. Water at 10° C. causes less vasoconstriction than 
 water at 55° C. 
 
 In order to ascertain whether this reflex is due to the influence 
 on the vasomotor center by conscious processes, similar experi- 
 ments were performed while the subject was asleep. It is not an 
 easy matter to go to sleep with a plethysmograph on one arm and 
 two rubber tubes in one's throat and esophagus. But, after marked 
 physical fatigue it is possible. The same rhythmic variation in the 
 
92 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 vasomotor tone is observed as before, but perfectly relaxed. There 
 is a gradual increase in the size of the arm as the tonus of the 
 stomach increases. This increase or vasodilation is greatest when 
 the stomach contractions are highest and the size of the arm de- 
 creases as the stomach relaxes. From this it seems evident that 
 this activity of the vasomotor center is not due to conscious 
 processes. 
 
 Moderately hot or moderately cold water in the stomach does 
 not seem to affect the activity of the vasomotor center during 
 sleep. Very cold water either does not have any very marked effect, 
 or else the stimulation is sufficient to awaken the subject. Warm 
 water did not cause a marked vasoconstriction unless the subject 
 woke up as a result of the injection. The marked vasoconstriction 
 observed when the stomach mucosa is stimulated with very cold or 
 very warm water, therefore, seems to be due mainly to the effect 
 of conscious processes on the vasomotor center. 
 
 v. FEELINGS OF WEAKNESS, "EMPTINESS," HEADACHE, AND 
 NAUSEA IN HUNGER 
 
 I. The weakness accompanying hunger is evidently of complex 
 origin, or partly due to sensory impulses from the digestive tract, 
 and partly toi relative exhaustion in the tissues. Voit thought 
 that the feeling of weakness is a general sensation in some way 
 caused by lack of nutrient materials in the blood. That in moderate 
 hunger only the first or reflex factor is involved is evident from the 
 fact that this weakness is abolished by taking food into the stomach, 
 before there is any digestion and absorption of the food material 
 into the blood. After several days of starvation, the feeling of 
 weakness does not all disappear immediately following a meal. 
 Hence we must here be dealing also with the factor of replenishing 
 the tissues. How does the hunger state of the stomach and intes- 
 tines induce the feeling of weakness ? We have seen that this 
 hunger state means strong tonus and contractions of the empty 
 stomach and intestines. It probably also involves a greater degree 
 of tonus of the abdominal muscles in the maintenance of , the intra- 
 abdominal pressure. It is not clear, however, why tonus and 
 
SOME ACCESSORY PHENOMENA OF HUNGER 93 
 
 contractions in the empty, stomach should in some people pro- 
 duce the feeling of weakness. 
 
 We are not convinced that the vasomotor disturbances caused 
 by the hunger contractions are great enough to produce the feeling 
 of weakness. There are probably other reflex factors at present 
 unknown. At the same time, the degree of weakness caused by 
 identical peripheral factors evidently depends on the stability 
 of the central nervous organization, for in disease (hysteria, 
 neurasthenia, etc.) a degree of hunger which, in a normal person, 
 would not induce the feeling of weakness may cause extreme 
 prostration. 
 
 2. The feeling of "emptiness." — Strong sensation of hunger is 
 usually accompanied by a peculiar feeling of "emptiness" in the 
 entire abdominal region. This feeling is continuous, not inter- 
 mittent like the pangs of hunger. The "emptiness" feeling does 
 not disappear entirely during the relative quiescences of the empty 
 stomach between the hunger periods. 
 
 This feeling is probably more complex in its origin than the 
 hunger pangs. It is well known that a very complete evacuation 
 of the large intestines, as by enemas or purgatives, induces a feeling 
 of emptiness. The feeling may be partly abohshed by moderate 
 but steady pressure on the abdominal wall. It is probable that 
 the increased tonus of the abdominal muscles, in consequence of 
 the empty state of stomach and intestines, contributes to the feel- 
 ing in some way. It is well known that the intra-abdominal pres- 
 sure remains nearly constant under varjdng degrees of fulness and 
 emptiness of the digestive tract. 
 
 Since in starvation there is persistent hypertonus of the 
 abdominal muscles, we question whether any part of the feeling 
 of emptiness originates in the stomach itself. It is not so difficult 
 to understand how a hypertonic and rhythmically contracting 
 empty stomach may give rise to sensatipns of tension, pressure, 
 and gnawing pain. But how can it cause the sensation of empti- 
 ness, unless this feeling is merely the negative of the sensation of 
 fulness ? On the other hand, if the tonus of the abdominal muscles 
 does not suffice to maintain the normal intra-abdominal pressure 
 
94 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 when stomach and intestines are relatively empty and strongly 
 contracted in hunger, the tension on all the visceral organs would 
 be diminished, and this in turn would alter the pressure relation 
 to the peritoneum and the mesentery. If this is a factor in the 
 origin of the feeling of abdominal "emptiness" in hunger, the 
 sensation should be diminished in man by lying down, in compari- 
 son with that felt when standing. The writer cannot test this 
 hypothesis on himself, as the feeling of "emptiness" is not a 
 prominent part of his hunger complex. 
 
 3. Headache and nausea. — The author experiences slight head- 
 ache and a suggestion of nausea only after 4 or 5 days' starvation, 
 but there is no doubt that a few apparently normal people experi- 
 ence both, or more particularly the headache, during the moderate 
 hunger that comes on 4 to 6 hours after eating. Some of Boring's 
 subjects had difficulty in distinguishing between hunger and nausea 
 in their own consciousness. In such cases there can be no starva- 
 tion change in the blood and tissues. And the fact that headache 
 as well as nausea is greatly relieved at once by taking food into 
 the stomach seems to show that they are essentially of gastric or 
 reflex origin. It is well known that both headache and nausea 
 can be produced by disturbances in circulation, and that nausea 
 can be caused by stimulation of nerves in the stomach mucosa 
 (normal stimulation of hj^erexcitable nerves, or excessive irrita- 
 tion of the normal nerves) . Possibly the strong hunger contractions 
 of the empty stomach cause sufficient stimulation of the gastric 
 nerves to induce both headache and nausea in certain individuals. 
 This can be determined experimentally on such persons. Unfor- 
 tunately, the author does not himself experience these accessory 
 hunger phenomena, nor has he been able to secure as subject a 
 person with these hunger symptoms sufficiently marked to make 
 it worth while investigating. In prolonged starvation there is 
 a contributory factor, namely, a greater degree of increased 
 excitability both of the gastric nerves and of the central nervous 
 system. 
 
 So far as established facts permit conclusions or point the way, 
 the accessory hunger phenomena, excepting the exhaustion fatigue 
 
SOME ACCESSORY PHENOMENA OF HUNGER .95 
 
 of prolonged starvation, are caused reflexly by the hunger tonus 
 and the hunger contractions of the empty stomach. The degree 
 with which they are manifested in hunger depends on the intensity 
 of the hunger contractions, the excitability of the sensory nerves 
 of the stomach, and on the relative stability of the central nervous 
 organization of the individual person. 
 
CHAPTER VI 
 THE RELATION OF HUNGER TO APPETITE 
 
 Physiologists, psychologists, and clinidans who have devoted 
 no special attention to the nature of hunger and appetite appear 
 to accept the common view of the laity that the two sensations are 
 the same in quahty, and differ only in intensity. Thus mild himger 
 is called appetite, while strong appetite is called hunger. If the 
 two sensation complexes are in a linear series and thus involve 
 identical mechanisms, either the term appetite or the term hunger 
 is superfluous, and it would be more correct and less confusing to 
 speak of mild and strong appetite or mild a^d strong hunger. We 
 do not apply different terms to the sensation of sweetness or of 
 red according to the intensity of the sweet sensation or the satura- 
 tion of the red color. A sensation remaining identical in quality 
 but differing in intensity should have only one name, and the 
 intensity variation should be denoted by the usual adjectives. 
 
 Most authors who have given some special attention to hunger 
 and appetite take the position that the two sensations are funda- 
 mentally different, that is, that they differ in quality. This view 
 is supported by Albu, Boas, Boring, Cannon, Carlson, Krehl, 
 Nicolai, Roux, Sternberg, Stiller, and many others. Stiller thinks 
 that appetite is the sensation of hunger plus the memories of taste 
 and smell of foods; hence one may experience hunger without 
 appetite, but not appetite without hunger. But others maintain 
 that one may also experience appetite without the sensation of 
 I hunger, as in the case of eating palatable desserts at the end of a 
 jfuU and satisfying meal. 
 
 Practically all writers who have recognized the qualitative 
 difference between hunger and appetite state that hunger is pri- 
 marily an impleasant and painful sensation and more or less inter- 
 mittent, while appetite is essentially pleasant in character and 
 without definite periodicity. Hunger, again, is referred to the 
 
 96 
 
THE RELATION OF HUNGER TO APPETITE 97 
 
 stomach, while the appetite complex is referred to the mouth 
 and throat. 
 
 We have seen that hunger is an uncomfortable pain sensation 
 caused by stomach contractions. Is appetite also a sensation, or 
 is it essentially a memory process ? If appetite is or contains imme- 
 diate sensory elements, what mechanisms in the mouth and throat 
 initiate the sensory impulses ? In one of his earlier papers Stem- 
 berg suggested that appetite is in some way associated with the 
 tonus of the muscles of mastication and deglutition; and that 
 absence of appetite, that is, nausea, is due to atony of these muscles. 
 Later Sternberg suggested that appetite is caused by peristalsis of 
 the esophagus and stomach, wMle lack of appetite is due to anti- 
 peristalsis in these organs. This appears to us a very superficial 
 suggestion. It is logical, to be sure, but it is contrary to fact. In 
 the very full stomach there is active peristalsis, but that does 
 not necessarily cause appetite. And there is no peristalsis in 
 the esophagus except that induced by swallowing. If esophageal 
 and gastric peristalsis are the stimuli that initiate appetite, 
 this sensation should show a rhythmicity similar to that of 
 hunger. 
 
 Sternberg, and after him Vorkastner, and others are guilty of 
 a singular misrepresentation of Pavlov's conception of appetite. 
 These German writers charge Pavlov with saying that "Appetit 
 ist saft" — appetite is gastric juice. We caimot find any such 
 statement in Pavlov's work, and the view is obviously inconsistent 
 with the whole trend of his research on the work of the digestive 
 glands. Pavlov has shown that appetite is a necessary condition 
 for the secretion of appetite gastric Juice, but appetite by itself 
 does not induce the secretion, nor does the gastric juice by itself 
 induce appetite, although it may contribute to it by gentle stimu- 
 lation of the gastric mucosa. 
 
 According to Camion, "appetite is related to previous sensa- 
 tions of the taste and smell of food. These sensory associations 
 determine the appetite for any edible substance, and either this 
 memory or present stimulation can arouse the desire." In brief, 
 appetite is caused either by the immediate taste and smell of 
 
98 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 palatable food, or induced by the memory processes of such taste 
 and smell sensations. 
 
 Some of Boring's subjects described " a kinesthesis in the throat 
 and oral sensation arising from the free flow of saliva, a complex 
 which to them meant desire for food. Here we have a true sensory 
 basis of appetite. Tlie ideation of food is no doubt a usual con- 
 comitant, and presumably it often constitutes a desire for food 
 that lacks sensory components entirely." Boring thus includes in 
 appetite the sensations aroused by increased salivation, and pos- 
 sibly from increased tonus in the muscles of mastication and deglu- 
 tition, but not the taste and smell sensations, to which Cannon 
 gives such a prominent position. It may be noted, however, that 
 salivation or increased tonus either singly or combined do not by 
 themselves induce the sensation of appetite. 
 
 The delineation of the appetite complex and its relation to 
 hunger is a question of analysis of one's own sensation under such 
 experimental control as can be applied. Now, it is obvious that 
 neither the sight, the taste, nor the smell of good food, the memory 
 of these sensations, or salivation and throat kinesthesis can by 
 themselves invariably induce appetite. We all know that the 
 taste or smell of the best of food in the case of severe gastritis 
 induces, not appetite, but nausea. Salivation induced by a drop 
 of vinegar in the mouth does not cause appetite. And in nervous 
 anorexia all of the immediate stimuli and the memory processes 
 mentioned by -Cannon and Boring may be present or called forth 
 .without producing a desire for food. It is thus clear that a certain 
 sensation complex from the viscera and an approximately normal 
 state of central correlations constitute a necessary background fqr 
 the development of appetite. Given this background, the central 
 and essential element in appetite is the memory processes of past 
 experience (sight, smell, taste) with palatable foods. These memo- 
 ries are reinforced by present stimulation of these nerves by the 
 food, since everyone knows that appetite, unless intense at the 
 outset, is increased by the very act of eating. 
 
 It will be shown that part of this augmentation is due to chemical 
 stimulation of the nerves in the gastric mucosa. The mouth and 
 
t 
 
 V THE RELATION OF HUNGER TO APPETITE 99 
 
 throat kinesthesis and the sensation due to salivation are, in the 
 author's judgment, accessory elements in appetite analogous to 
 the sensations of weakness and emptiness in hunger. 
 
 But how can we account for the desire for food that seems to 
 be inherent in the appetite elements ? We have suggested elsewhere 
 that this urge may be an inherited (partly subconscious) factor 
 (positive chemotropism), fusing with the memory processes of taste 
 and smell of foods as soon as these become a part of the individual's 
 :xperience. It seems that this urge is present in appetite even when 
 4;here is no call for food on the part of the empty stomach; hence it 
 is not a vague hunger. Pleasant sensations of different kinds, such 
 as are induced by works of art, music, or the beauties of nature do 
 not seem to contain or arouse analogous desires. In the author's 
 experience the fragrance of the rose in the garden is as pleasing 
 as the fragrance of the roast in the kitchen, but the desire to enjoy 
 the former cannot be compared with the urge to ingest the latter. 
 
 It seems to us that the old view that hunger and appetite are 
 different intensities on the same sensation curve is no longer tenable 
 even as a theory. The conception came about through lack or 
 difficulty of analysis of all factors involved, and the tendency to 
 fuse or confuse in consciousness heterogeneous sensations that are 
 usually aroused simultaneously, as is the case with the taste and 
 smell of food. In the normal individual hunger and appetite are 
 usually experienced simultaneously. If only vague or mild hunger 
 is present, the appetite elements occupy the high seat in conscious- 
 iness; when hunger becomes markedly painful, attention is focused 
 Ion this element. If we start to masticate palatable food or by 
 means of a stomach tube put a hquid or liquid food directly into the 
 stomach at the height of a period of gastric hunger contractions, 
 the latter are inhibited at once and the unpleasant hunger sensa- 
 tion disappears at the same time, while the pleasant appetite 
 complex is initiated or intensified. In this way we institute a 
 successive contrast between hunger and appetite, so that they can 
 be compared with greater accuracy. 
 
 In everyday life of adult persons having access to a liberal food 
 supply thelnemory' elements of appetite are probably a greater 
 
lOO CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 factor in the ingestion knd digestion of food than hunger^as short 
 intervals between large meals do not permit the development ^f 
 s trong h unger unless the individual is engaged in hard physical 
 work. U ndei,-these circumstances. appgtite_and habit_supplant 
 hunger as nature^s_dietary guide. Everyone knows that if the 
 food^is made suflSciently palatable we may consume large jg^iantitigs 
 of it without ^ing hungry oi- actually needing the food, es peciall y 
 if one has formed the habit of giving marked„attention to th e 
 pleasures oFthFtable. 
 
CHAPTER VII 
 THE SENSIBILITY OF THE GASTRIC MUCOSA 
 
 The active controversy concerning the sensibility of the visceral 
 organs that has been going on since the time of Haller is essentially 
 a question to what extent afferent nervous impulses from the viscera 
 influence conscious processes. Haller thought the visceral organs 
 were insensitive, especially to pain. Afferent or sensory nerve- , 
 fibers are distributed to all the internal organs. But the stimula- 
 tion of these nerves may produce local reflexes only^ or central 
 reflexes of subconscious character (tonus, vascular, respiratory, 
 etc.). Lennander, a surgeon, observing numerous patients in 
 abdominal operations, under local anesthesia for the abdominal 
 wall, reached the conclusion that, excepting the parietal peritoneimi, 
 the entire viscera (stomach included) is insensitive, especially to 
 pain. If Lennander's view is correct the hunger pains cannot be 
 of gastric origin. We presume Leimander would ascribe them to 
 mechanical tension or pressure on the parietal peritoneum from 
 the strong contractions of the empty stomach. Lennander's assist- 
 ant, Nystrom, and MacKenzie, Becher, and Mitchell have accepted 
 and attempted still further to substantiate and defend this radical 
 theory. But other workers have shown that it is imtenable. Kast 
 and Meltzer obtained distinct evidence of pain on injury or strong 
 stimulation of the viscera, and showed, moreover, that local anes- 
 thetics (subcutaneous injection of cocaine) tend to depress visceral 
 sensibility. Kast and Meltzer, and Ritter suggest that this accounts 
 for Lennander's erroneous conclusion, as local anesthesia was used 
 in practically all his patients. New experimental facts as well as 
 critical considerations demonstratiag certain sensibilities of all the 
 visceral organs have also been published by Neumann, Hertz, 
 Head, Rivers and Sherran, Boring, and others. But in the present 
 work we are concerned with the sensibiHty of the alimentary canal, 
 and especially that of the stomach. 
 
I02 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 I. ABSENCE OF PAIN SENSATION FROM THE NORMAL 
 GASTRIC MUCOSA 
 
 The sensation of pain cannot be produced from the normal 
 gastric mucosa except by stimuli that evidently cause some destruc- 
 tion of cells and nerve-endings, such as strong acids, oil of mustard, 
 absolute alcohol, excessive heat, etc. The normal mucosa can be 
 pressed or squeezed with forceps until crushed, pins may be pushed 
 into the mucosa anjrwhere, or the mucosa may be incised with a 
 scalpel, without causing pain in a normal person. The gastric 
 pain caused by strong and destructive chemicals acting on the 
 normal mucosa may be due to over-stimulation of nerve-fibers 
 other than those of "protopathic" pain. In the case of a hyper- 
 excitable stomach mucosa, as in certain types of gastritis, sub- 
 stances normal to the stomach cavity (water, gastric juice) may 
 cause pain. Strong tonus and contraction of the stomach are 
 painful, and it is not certain that the kinesthetic pain from gastric 
 contraction is excluded in all cases of pain from destructive chemical 
 stimulation of the normal mucosa, or normal stimulation of the 
 hypersensitive mucosa, since the motor conditions of the stomach 
 in these states have not been studied sufficiently. Hertz supports 
 the view that all so-called gastric pains, even those induced by 
 destructive' chemical stimulation of the mucosa, are due to exces- 
 sive contractions of the pylorus and the pyloric end of the stomach. 
 There can be little doubt that strong acids on reaching the duode- 
 nimi will cause temporary spasms or tetany of the upper part of 
 the duodeniun, and probably of the pylorus. The precise genesis 
 of these pains must still be considered an open question. In our 
 own experience these pains are too persistent to be due to peristalsis. 
 If they are of purely muscular origin, the stomach and duodenal 
 contractions giving rise to them must be prolonged tonus or tetany 
 contractions. It is probable that the pain is essentially muscular, 
 but the injured mucosa may also be a factor. 
 
 Excessive distension of the stomach by food, water, gas, or 
 inflated balloons causes pain referred to the stomach, but there is 
 no evidence that this pain is due to stimulation of the mucosa 
 nerves. 
 
THE SENSIBILITY OF THE GASTRIC MUCOSA 103 
 
 We are thus forced to the conclusion that the only physiological 
 pains from the stomach are the pangs of hunger, and these do not 
 arise from the mucosa nerves. All pains possibly originating in the 
 mucosa are indices of pathological processes, that is, either destruc- 
 tive stimuli acting on the normal nerve, or normal stimuli action 
 on hyperexcitable nerves. These gastric pains will be considered 
 in greater detail in the chapter on hunger and appetite in disease 
 (chap. xvi). 
 
 n. THE ABSENCE OF TRUE TACTILE SENSIBILITY 
 
 Everyday experience tells us the stomach mucosa is not sensitive 
 to touch. Pavlov states: "It can hardly be doubted that under 
 normal conditions the surface of the stomach has a certain degree 
 of tactile sensibility." The term tactile sensibiUty is evidently used 
 here in the sense of a general response to mechanical stimulation 
 rather than as implying a true tactile sensibility. When solid food 
 is swallowed, no tactile sensation is felt after the food has passed 
 the pharynx, unless the mass is so large that it causes unusual 
 distension of the esophagus. In that case it may be felt all the 
 way down the esophagus, but this is due to the distension of the 
 wall of the esophagus and is not a tactile sensation from contact 
 with the mucosa. 
 
 Hertz tested on himself the tactile sensibility of the mucosa of 
 the esophagus by means of an esophagoscope with a slit down the 
 side, so that a metal bulb in a long holder could be moved along 
 the mucous membrane of the esophagus and the pharynx. The 
 pharyngeal mucosa was foxmd to be sensitive to touch; the esoph- 
 ageal was insensitive. 
 
 The author has tested the tactile sensibility of his own gastric 
 mucosa, swallowing a good-sized rubber tube, through which was 
 passed a test-tube brush attached to a strong piano wire. Pulling 
 the test-tube brush about in the cavity of the stomach produced 
 no sensation. 
 
 Numerous tests were made on the gastric mucosa of Mr. V., 
 our gastric fistula case. Gently touching or striking the mucosa 
 with blunt objects produced no sensation. If the mucosa is rubbed 
 
104 CONTROL OF HTOTGER IN HEALTH AND DISEASE 
 
 or pressed very vigorously with a blunt object Mr. V. says he "can 
 feel it"; he cannot describe the sensation thus produced except 
 in a negative way. It is not like touch, nor is it pain or himger. 
 Whatever the character of the sensation may be, we are satisfied 
 that it is a real change in the stream of consciousness, for he recog- 
 nizes these stimuli when he has no other means of knowing that 
 the gastric mucosa is being handled. The sensation may not orig- 
 inate in the mucosa, but in the muscularis (tonus relaxation through 
 reflex inhibition) or possibly in the visceral peritonetun, as the 
 pressure must be considerable to produce it. We are satisfied that 
 the stimulation of the normal gastric mucosa of Mr. V. does not 
 produce tactile sensation. The same conclusion has been reached 
 by previous workers using himian gastric fistula cases. 
 
 in. GASTRIC TEMPERATURE SENSATIONS 
 
 In 1846 Weber suggested that the sensation of cold or warmth in 
 the epigastrium, after drinking ice-cold or very warm water, 
 originates in the skin of the abdomen over the stomach and not in 
 the stomach mucosa. According to Weber sufiicient conduction 
 takes place through the waUs of the stomach and abdomen to 
 stimulate the temperature nerves of the skin. Becher swallowed 
 a single rubber tube and through it injected water of different 
 temperatures into the stomach. He did not experience any heat 
 or cold sensation before the heat or cold had passed through the 
 walls of the tube and stimulated the mucosa of the esophagus. 
 Mueller concluded that ice water produced no sensation in the 
 stomach. Zimmerman irrigated his stomach with hot or cold 
 water through a thick rubber tube. He claims that hot or cold 
 sensations were felt only when the lower end of the tube was 30 
 to 25 cm. distant — whence not far from the lower end of the esopha- 
 gus. He therefore concludes that the sensation is projected from 
 the esophageal mucosa. MacKenzie believes that the temperature 
 sensations induced by hot and cold water entering the stomach is 
 due to reflex vasomotor changes in the skin of the abdomen. 
 Nystrom reports that touching the gastric mucosa of a man having 
 gastric fistula with a hot piece of metal or piece of ice, does not 
 
THE SENSIBILITY OF THE GASTRIC MUCOSA 105 
 
 call forth any definite temperature sensations. According to 
 Hertz the hot or cold sensations felt in the epigastrium, upon swal- 
 lowing hot or cold water, come from the lower end of the esophagus. 
 The water accumulates here before the cardiac orifice opens, and 
 that part of the esophagus is thus stimulated more than the parts 
 above. He defends his conclusion by this observation : by auscul- 
 tation over the epigastriima after swallowing a mouthful of very 
 hot or cold water, one will find that immediately after the second 
 deglutition sound, which occurs after the last trace of food has 
 entered the stomach, the hot or cold sensation disappears. He 
 also states that upon injecting hot or cold water through a double 
 rubber tube, no temperature sensation was noticed before 3 or 4 
 'ounces had passed into the stomach. An ill-defined temperature 
 sensation was then experienced, but he concludes that this was 
 due to the conduction of heat or cold to the esophageal wall. 
 Hence, according to Hertz, the stomach mucosa is not endowed 
 with heat or cold nerve-endings. Quincke introduced hot and cold 
 water into the stomach of a boy with a gastric fistula and reports 
 that the patient experienced vague heat or col^ sensations. Neu- 
 mann and Roux, injecting hot and cold water into the stomach 
 through a double rubber tube, experienced hot and cold sensations 
 in the stomach, the cold sensations being the more pronounced. 
 Head, Rivers, and Sherren injected water at different temperatures 
 into the colon of a patient, upon whom a colostomy had been 
 performed, and foimd that water at 20° to 40° C. produced no 
 sensation at all, but water at 50° C. and very cold water did give 
 rise to temperature sensations, but that these sensations were by 
 no means as pronounced and as easily localized as those produced 
 by applying water at the same temperatures to the skin. Head 
 concludes that the viscera is endowed with "protopathic" tem- 
 perature sensibility only. 
 
 Boring reports that water at 40° C. produces a sensation of 
 warmth, and water at. 30° C. a sensation of cold referred to the 
 stomach. In his first paper Boring inclined to the view that these 
 sensations originate not in the stomach but in the abdominal wall; 
 in the second paper he concludes that they arise either in the stomach 
 
io6 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 itself or in tissues closer to the stomach than the abdominal wall 
 and the esophagus. 
 
 It is thus evident that by far the majority of those who have 
 investigated this problem have experienced a vague hot or cold 
 sensation, in the region of the epigastrium, upon stimulating the 
 stomach mucosa with hot or cold water. Those who do not beUeve 
 that the sensations arise in the stomach mucosa explain its origin 
 in one of the following ways: (i) It is due to conduction to the skin 
 of the abdomen. (2) It is due to reflex vascular changes of the 
 skin of the abdomen. (3) It is projected from the esophagus. (4) 
 It arises in the lower part of the esophagus. 
 
 Our own experiments on Mr. V. and on ourselves go to show 
 that the above-mentioned theories are untenable. That is to say, 
 we find that the gastric mucosa is endowed with protopathic tempera- 
 ture sensibility. 
 
 The first series of experiments was on Mr. V. He was blind- 
 folded and was not told the nature of the experiments. The water, 
 40 to 60 c.c, was injected through a small rubber tube which was 
 passed through the large permanent tube of the fistula. With 
 water at 50° C. he said that he felt a hot sensation in the stomach, 
 after a latent period of about ^ seconds. When the same amount 
 of water at 10° C. was injected, a cold sensation was felt after a 
 slightly shorter latent period. A metal rod 5 mm. in diameter, 
 heated to about 50° C, was passed down through the fistula 
 catheter until the end -touched the mucosa of the dorsal wall of 
 the stomach. A longer latent period elapsed here before any 
 sensation of heat was noticed. "When, however, a small piece of 
 ice, held by a pair of forceps, was brought into contact with the 
 stomach mucosa, the latent period was not much longer than when 
 cold water had been injected. A cold sensation was distinctly felt. 
 These experiments were repeated over and over again, and Mr. V. 
 was invariably able to recognize whether the mucosa was being 
 stimulated with hot or cold media, provided the media was 45 to 
 55° C. and the cold at least 13° C. 
 
 The temperature sensations initiated by touching the gastric 
 mucosa directly with hot or cold solids cannot come from the 
 
THE SENSIBILITY OF THE GASTRIC MUCOSA 107 
 
 stimulation of the esophageal mucosa. The latent period is too 
 short to allow temperature conductions to the skin of the abdomen. 
 But since it is possible that the cardia and the lower end of the 
 esophagus of Mr. V. are patent, water injected through the fistula 
 may reach the lower end of the esophagus. This possibility was 
 guarded against in a second series of experiments, where we injected 
 the hot and cold water into a very delicate rubber balloon previously 
 introduced into the stomach. The hot and cold water was correctly 
 recognized as hot or cold, just as in the test with the water touching 
 the mucosa directly, the only difference being a somewhat longer 
 latent period. It is clear from the above that the gastric mucosa 
 of Mr. V. is endowed with protopathic temperature sense. 
 
 A third series of experiments was carried out on the author and 
 on one assistant (Mr. B.). Three rubber tubes of suitable size were 
 placed one inside the other so as to have three walls of rubber and 
 two air spaces between the liquid in the inside tube and the eso- 
 phageal mucosa, for the purpose of retarding heat conduction. The 
 inside tube had a diameter of 3 mm. The subject was blindfolded 
 and 50 c.c. of water at 50° C. were injected into the stomach. A 
 sensation of heat was noted about 10 to 15 seconds after the injec- 
 tion, and about 60 seconds before enough conduction had taken 
 place to cause the tube to feel warm in the mouth and throat. 
 When the same amount of water at 10° C. was injected, a definite 
 cold sensation was felt from 5 to 10 seconds after the injection had 
 comftienced and about 60 seconds before the tube began to feel 
 cold to the fingers or to the throat. 
 
 Both of us experienced hot and cold sensations and never made 
 the mistake of confusing the heat sensation with the cold sensation. 
 Confirming Neumann and others, we found the cold sensation to 
 be more distinct and better localized than the heat sensation. 
 
 This certainly does not seem to indicate that the stomach 
 mucosa is devoid of temperature sensations, nor that this sensa- 
 tion is projected from the esophagus, as has been suggested by a 
 number of investigators. However, there is a possibihty that some 
 of the water might reach the wall of the lower end of the esophagus 
 by being forced up along the tube. In view of the small amoimt 
 
io8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 of water necessary to evoke the hot and cold sensations and in 
 view of the short latent period mentioned above, this seems very 
 unlikely. 
 
 To make sure that the sensation did not arise as a result of the 
 stimulation of the esophagus, as well as to prove that the sensation 
 is not due to conduction to the skin of the abdomen, or to reflex 
 vascular changes in the skin of the abdomen, a fourth series of 
 experiments was performed. For these experiments a rubber tube 
 I cm. in diameter was used. Inside this large tube we placed two 
 smaller tubes, side by side; one of these was s mm. in diameter 
 and the other was 3 mm. The smaller of these two tubes was not 
 pulled clear through the outside tube, but only so far that its 
 lower end was about an inch above the lower end of the outside 
 tube. The 5 mm. tube was pulled through the outside tube so 
 that it extended about 10 cm. below the lower end of it. A small 
 glass tube 5 mm. long was now forced up into this longer tube as 
 far as to the lower end of the outside tube. The lower end of the 
 outside tube was then tied securely about the longest tube at this 
 point. This apparatus was now swallowed far enough down, so 
 that the lower end of the outside tube reached just through the 
 cardiac orifice. The longest tube, the end of which of course was 
 open, therefore extended far down into the stomach. The smallest, 
 whose lower end was within an inch of where the outside tube 
 was tied, that is, within 2 to 3 cm. of the cardia, was now con- 
 nected with a pressure bottle. It had previously been found'that 
 hot water, in passing through a glass tubing and connections of 
 the pressure bottle, lost approximately 8° C, and that water placed 
 in the bottle at 10° C. was raised to 12° C. in passing through. 
 Water at 58° C. was now placed in the pressure bottle and per- 
 mitted to flow down through the smallest inside tube. It naturally 
 was forced up again between and around the two inside tubes. 
 By so doing the heat was conducted through the wall of the outside 
 tube and stimulated the heat nerve-endings in the esophagus, so 
 that a definite heat sensation was felt along its whole course, as 
 well as in the mouth and pharynx. The striking feature about 
 this, however, was that, although the walls of the lower end of the 
 
THE SENSIBILITY OF THE GASTRIC MUCOSA 109 
 
 outside tube naturally became hot before those of the upper, the 
 heat sensation was first felt in the mouth and throat and then 
 gradually traveled down the whole length of the esophagus. At 
 all times, however, the heat sensation was more intense in the 
 throat and in the upper part of the esophagus tfcan in its lower 
 end. While the walls of the esophagus/were thus being stimulated, 
 50 c.c. of water at 50° to 55° C. was injected into the stomach 
 through the longest inside tube which opened into the stomach, and 
 after a latent period of about 10 seconds, a spreading heat sensa- 
 tion was felt lower down than that resulting from the stimulation 
 of the esophagus. The sensation also seemed better localized than 
 that from the. esophagus, so that it was not very difl&cult to keep 
 the two sensations apart in consciousness. The reason for the 
 better localization might, of course, be due to the fact that more 
 nerve-endings were stimulated in the stomach mucosa, as the 
 Water came into direct contact with it, than in the case of the 
 esophagus, where probably the rubber tube did not come into 
 contact with the mucosa at all points. 
 
 When water at 10° C. was placed in the pressure bottle — the 
 outside tube stimulating the esophagus thus being filled by water 
 at 12° C. and 50 c.c. of water at 12° C. was injected into the stomach, 
 a distinct, spreading, cold sensation was felt lower than that result- 
 ing from the stimulation of the esophagus. There was no difiiculty 
 in recognizing two separate and distinct cold sensations, one coming 
 from the esophagus and the other from the stomach. 
 
 While the esophagus was being stimulated by water at 12° C. 
 in this tube system, a water bottle which was filled with water at 
 12° C. was placed on the skin of the abdomen. The two cold 
 sensations resulting could easily be kept apart in consciousness. 
 Next, 50 c.c. of water at the same temperature were injected into 
 the stomach, and a third, distinct, spreading, cold sensation was 
 felt in the stomach. This experiment was repeated several times 
 with hot and cold water, as indicated above, and with the same 
 results. 
 
 If the temperature sensation felt on introducing hot or cold 
 liquids into the stomach is due to heat conduction through to the 
 
no CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 skin of the abdomen, or to reflex vascular changes in the skin of 
 the abdomen, or is projected from the esophagus, how is it possible 
 that one can distinguish in consciousness the sensations coming 
 from the esophagus, the stomach, and the skin, at the same time^ 
 when each is bdng stimulated by water at the same temperature,, 
 as shown above? 
 
 To make sure that the sensation was not due to conduction 
 through the abdominal wall to the skin of the abdomen, the bulb 
 of a thermometer was pressed close to the skin over the stomach 
 and covered with absorbent cotton. After it had become stable, 
 200 c.c. of water at 10° C. were injected into the stomach and the 
 mercury in the thermometer watched for a period of 5 minutes. 
 This was repeated several times. In each case, after a latent period 
 of 5 minuties, the mercury had fallen only a small fraction of a 
 degree. It is therefore evident that the cold sensation which one 
 feels after a latent period of from 5 to 10 seconds, after the injection 
 of 20 c.c. of cold water into the stomach, is not due to conduction 
 through the abdominal wall and stimulation of the nerve-endings 
 in the skin. 
 
 Boring has shown that 500 c.c. of water at 0° C. in the stomach 
 loA^rers the skin temperature only 0.05° C. It is therefore out of 
 the question that 25 c.c. of water in the stomach at 25° to 30° C. 
 stimulate the temperature end organs in the skin. Moreover, the 
 adequate temperature stimulus in the stomach cavity is less than 
 5° above and 10° below the body temperature. 
 
 We agree with Hertz that when one swallows a mouthful of 
 ice water, the most intense cold sensation seems to come from the 
 lower end of the esophagus, and that this is undoubtedly due to 
 the fact that the water accumulates there and is detained for a 
 shorter or longer period before the cardiac orifice opens so that it 
 can flow into the stomach. He further states that the cold sensa- 
 tion disappears after the water has entered the stomach. This 
 we cannot corroborate. We invariably feel a vague, spreading, 
 'Cold sensation after the water has entered the stomach, which 
 disappears after a few seconds. Even if it were the case that no 
 cold sensation could be felt after the water had passed into the 
 
THE SENSIBILITY OF THE GASTRJC MUCOSA iii 
 
 stomach, this could not prove that the stomach mucosa is devoid 
 of heat and cold nerve-endings. In the first place, a mouthful of 
 cold water in passing down into the stomach is warmed sufficiently 
 to raise its temperature several degrees. On this account the nerve- 
 endings in the mucosa of the stomach are not stimulated as intensely 
 as are those in the esophagus. The empty stomach contains lo to 
 50 c.c. of fluid at 38° C. which rapidly mixes with and thus raises 
 the temperature of the swallowed water. It is also well known 
 that stronger impulses, reaching the central nervous system from 
 one part, tend to suppress in consciousness weaker impulses of 
 the same nature, reaching it from some other part, so that it is 
 difficult to separate thet two sensations in consciousness. 
 
 From our experiments we conclude: (i) The stomach mucosa is 
 endowed with heat and cold nerve-endings. (2) These fibers are, as 
 Head suggests, of the protopathic type; that is, they are not stimu- 
 lated by slight temperature changes, or if they are, the impulses do 
 not affect consciousness. (3) They are more abundant, or more 
 readily stimulated in the throat and esophagus than in the stomach. 
 
 rV. THE SENSATION OF FULNESS AND SATIETY ' 
 
 All who have studied the origin of the sensations of fulness and 
 satiety seem to agree that they do not originate in the mucosa of 
 the stomach, and our own results agree with this view. The 
 literature is extensively reviewed by Hertz. 
 
 Hertz and his co-workers inflated the stomach of two healthy 
 men with air through a tube connected with a manometer. They 
 found that a "sensation of fulness or tightness' in the upper partj 
 of the abdomen, associated with a desire to eructate, was felt as 
 soon as the intragastric pressure reached respectively 12 and 14 mm. 
 of mercury in the two cases. The pressure fell after 20 seconds by 
 approximately 2 mm., owing apparently to relaxation of the tone 
 of the stomach, and simultaneously the sensation of fulness dis- 
 appeared. Now, on slowly injecting more air, the pressure gradu- 
 ally rose to its original height and the sensation reappeared; it 
 again disappeared ■ after 20 seconds, the pressure sunultaneously 
 falling 2 mm., after which it remained constant. Exactly the same 
 
112 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 rise in pressure and the same sensation of fulness, followed by a fall 
 of pressure and a disappearance of the sensation, were produced 
 four times in succession by injecting air, none being allowed to 
 escape in the interval. These observations proved that the tension 
 exerted from within on the circular muscle fibers of the stomach is 
 the cause of the sensation of fulness." 
 
 That this is the main source of its origin seems quite clear. 
 There is a possibility that the stretching of the abdominal muscles 
 as well as the pressure on other structures in the abdominal cavity 
 contribute to the sensation of fulness. As a proof that this element 
 has little if any significance in giving rise to the sensation, Hertz 
 related experiments on persons with atonic stomachs. When 6 gm. 
 each of sodium bicarbonate and tartaric acid are swallowed sepa- 
 rately, 1,700 c.c, of carbon dioxide are given off under atmos- 
 pheric pressure at body temperature. This invariably causes an 
 xmpleasant and sometimes painful sensation of fulness in normal 
 individuals, while in persons with atonic stomachs it does not 
 cause any sensation of fulness. Hertz, therefore, concludes that 
 "the sensation of fulness in the stomach is due to tension on its 
 muscular coat, and depends very little and only in extreme cases 
 on the stretching of the abdominal wall." 
 
 To these observations of Hertz we can add our negative findings 
 in regard to the gastric mucosa as a contributing factor. Chemical 
 or mechanical stimulation of the mucosa (whether the stomach is 
 in strong or in feeble tonus) never produces a sensation similar 
 to that of fulness. At the same time, it must be noted that mere 
 tension on the muscular coats, that is, intragastric pressure, will not 
 under all conditions give rise to the sensation. The degree of intra- 
 gastric pressure required to cause a feeling of fulness, according 
 to Hertz, is frequently exceeded at the height of a period of hunger 
 contractions of the empty stomach, when a distended balloon is 
 in the stomach, yet the sensation referred to the epigastrium in 
 these conditions is that of emptiness, not fulness. It is therefore 
 clear that a certain amount of tonus reaction of the stomach must 
 be present before tension or pressure on the walls of the stomach 
 produce the sensation of fulness. 
 
THE SENSIBILITY OF THE GASTRIC MUCOSA 113 
 
 The sensation of satiety felt after an abundant and palatable 
 meal involves several factors, none of which appear to depend 
 primarily on the nerves in the gastric mucosa. One must have 
 some degree of hunger and appetite before eating, the food must 
 be palatable, and enough food must be consumed to produce 
 moderate distension of the stomach. If either of these factors is 
 lacking, complete satiety is not felt after the meal. One may feel 
 great himger and consimie unpalatable food till the sensation of 
 fulness develops, but satiety does not follow. If the hunger factor 
 is present and the food is to the king's taste, but of insufl&cient 
 bulk, although more than ample for the needs of nutrition, satiety 
 is also lacking. Hence the sensation complex of satiety involves 
 the element of contrast between the imcomfortable tension of] 
 himger and the sensation of fulness, together with the lingeringj 
 memories of the taste and smell of the food. Normal motor, secre- 
 tory, and sensory fimctions in the stomach are thus a prerequisite; 
 rather than a direct factor in the genesis of satiety. 
 
 V. NAUSEA ,0F GASTRIC ORIGIN 
 
 The sensation complex of nausea and vomiting can be initiated 
 by stimulation of nerves in the gastric mucosa; but many of the 
 sensory elements in nausea involve mechanism outside the stomach. 
 When nausea is induced by the odor, sight, or taste of disgusting 
 substances, or by the memory of such substances we may call it 
 strictly physiological processes. But most cases of nausea are 
 due to pathological processes or disease. Some of these patho- 
 logical conditions are pressure, partial anemia, or action of specific 
 toxic substance on the medulla; intense and prolonged pains of peri- 
 pheral origin, toxemias, hyperexcitability, or excessive stimulation 
 of the visceral nerves. 
 
 The sensation of nausea is very complex. A certain feel- 
 ing of bodily weakness and a characteristic pain and distress 
 ("sinking feeling") in the stomach are always present. With 
 these one may also experience headache, dizziness, chills (from 
 cutaneous vasoconstriction and perspiration), formication, etc. 
 The violent contractions of the pyloric end of the stomach pre- 
 
114 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 ceding and accompanying the act of vomiting may even be felt 
 as painful. 
 
 When nausea is produced by excessive or destructive stimulation 
 of the normal gastric mucosa, or by what may be called normal 
 stimulation (water, food, gastric juice, etc.) of a hyperexcitable 
 mucosa, what sensory elements in nausea are due to this stimula- 
 tion directly? Since strong contractions of the stomach cause a 
 pressure-pain sensation, and excessive stimulation of the mucosa 
 may also cause pain, it is evident that the tension, pressure, and 
 pain referred to the epigastric region in nausea are of peripheral 
 or gastric origin. The peculiar "sinking feeling" or the feeling 
 of "helplessness" is probably in the main also a direct effect of 
 the gastric states. At any rate that feeling is not experienced 
 except in nausea sufl&ciently intense to approach vomiting. The 
 weakness, dizziness, and headache are probably in the main indi- 
 rect effects, that is, due to disturbances in the circulation. 
 
 Michael Foster considered "nausea allied to himger." Boring 
 states that some of his subjects (normal men) confused mild nausea 
 with the sensation of hunger. Thus 5 per cent of hydrochloric 
 acid put directly into the stomach by a tube produced gastric pain 
 identical with hunger, except that it was more continuous. One 
 of Boring's men who was subject to spells of indigestion reports 
 "when I feel nauseated [from indigestion] I generally stop eating. 
 I begin with my meals again as soon as I feel hungry, but I cannot 
 always tell whether I am hungry or still nauseated." 
 
 We believe this fusion or confusion of nausea with himger is 
 either pathological or else due to superficial analysis. It is true 
 that the gastric factors in both hunger and nausea are imcomfort- 
 able tension and pain; that hunger as well as nausea causes sali- 
 vation ; that in some people hunger as well as nausea includes bodily 
 weakness, headache, etc., but the distinct "sickness" character of 
 the gastric distress in nausea is not even present in any stage of 
 htmger in normal persons. Hunger involves the kinesthetic nerves 
 of the stomach, while nausea is caused by stimulation of nerves in 
 the gastric mucosa. The central effects of himger and nausea 
 in normal persons are also different. Hunger is compatible with 
 
THE SENSIBILITY OF THE GASTRIC MUCOSA 115 
 
 and intensifies appetite and desire for food, while nausea and appe- 
 tite are mutually exclusive. But since hunger is, and nausea may 
 be, caused by stimulation of gastric nerves, it is likely that in 
 persons with hypersensitive vagi, or with unstable central nervous 
 organization, strong hunger may contain elements of nausea, or 
 actually pass into nausea. 
 
 Normal persons may experience hunger pangs and something 
 like mild nausea or "sick stomach" at the same time, without 
 confusing the two sensations, provided there is a certain degree 
 of hyperexcitability of the nerves in the gastric mucosa. This 
 was noted by the author on the fifth day of starvation. On that 
 day the sensation of hunger was tinged with a "burning" sensation 
 also referred to the stomach. This sensation was probably caused 
 by pressure or acid stimulation of hyperexcitable nerve-endings 
 in the gastric mucosa. It is known that prolonged starvation 
 leads to such hyperexcitability, and in this case there was addi- 
 tional indications of it in the nausea caused by smoking. 
 
 VI. THE GASTRIC ELEMENT OF APPETITE 
 
 Substances like strong alcohol or acid (5 to 20 per cent HCl) , 
 mustard, pepper, etc., introduced by tube directly into the stomach 
 in sufl&cient quantities, cause varying degrees of pain, accompanied 
 at first with a peculiar feeling of warmth in the stomach. In 
 concentrations sufiicient to cause pain, all chemicals evidently 
 injure the mucosa and its nerve-endings, as shown by the develop- 
 ment of gastritis. Boring states that the pain induced by 2 to 10 
 per cent HCl in the stomach is identical with the pangs of hunger, 
 and surmises that the acid in the stomach causes gastric hunger 
 contractions. This surmise is contrary to all experimental facts, at 
 least on normal men and dogs. 
 
 When these and other chemical substances are put into the 
 stomach too dilute to cause ache, pain, or discomfort, their contact 
 with the normal gastric mucosa still affects consciousness, but in 
 a maimer the very opposite to that of pain. The sensation pro- 
 duced by this gentle chemical stimulation of the mucosa has a 
 character of its own that resembles if it is not identical with appe- 
 
ii6 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 tite. We cannot understand how Hertz and Schmidt could have 
 reached the conclusion, on the basis of experiments on man, that 
 the normal mucosa is insensitive to chemical stimuli, including 2 
 per cent mineral acids (HCl). 
 
 Pavlov concludes that "the tactile sensation of the stomach 
 at the moment of entry of food is capable of awakening or increasing 
 appetite." In the experiments cited by Pavlov in support of this 
 conclusion the stimulation of the nerve-endings in the mouth and 
 in the esophagus was not excluded. 
 
 The author, working on himself, soon recognized that moderate 
 chemical stimulation of the nerve-endings in the gastric mucosa 
 modified the flow of consciousijess, although this modification did 
 not consist in the sensation of himger. This can readily be experi- 
 enced by anyone who is sufl&ciently interested to try, by introducing 
 moderately cold water, beer, wine, weak acids (0.5 tp 2.0 per cent 
 HCl), weak alcohol, or carbonated drinks through a tube into the 
 stomach so as to avoid stimulation of nerve-endings in the mouth 
 and esophagus. The sensation produced by these substances in 
 the stomach is rather transitory, but may persist for several min- 
 utes. With the exception of cold water, which is also felt as cold, 
 these various substances give rise to a characteristic sensation 
 which fuses with, or cannot be distinguished from appetite. It 
 is like the sensation of increased appetite experienced by most 
 people at the beginning of a meal, after eating a few morsels of 
 palatable food. The sensation is pleasant, and turns the attention 
 toward food and eating. 
 
 We are accustomed to think that the substances named above 
 affect consciousness solely through stimulation of nerve-endings 
 in the mouth. This view is no longer tenable. By introducing 
 these substances through the stomach tube at the height of a 
 gastric hunger contraction, one actually experiences a successive 
 contrast of the sensations of hunger and appetite, as these substances 
 temporarily inhibit the hunger contractions in stimulating the gas- 
 tric mucosa. From the first it was clear that, when beer or cold or 
 hot wat§r was first introduced into the stomach during a vigorous 
 himger contraction, the sensation resulting was the exact opposite 
 
THE SENSIBILITY OF THE GASTRIC MUCOSA 117 
 
 of that caused by the hunger contraction. In place of an unpleasant 
 tense sensation, associated with restlessness, the sensation caused 
 by these different stimuli is one of relief. A pleasant, tingling sensa- 
 tion is felt in the stomach. One feels perfectly at ease, but the 
 thoughts tend to revert to the dinner table. At first, we were not 
 able to say just what this sensation was like, although it was a 
 familiar one. After paying close attention to the sensation experi- 
 enced at meals just after a few mouthfuls of good food or drink 
 have been swallowed, we became convinced that the two sensations 
 are very much, alike, if not identical. 
 
 How do we know that the sensation temporarily produced by 
 the above-named substances in the stomach is directly due to 
 stimulation of nerve-endings in the gastric mucosa? Since the 
 introduction of these substances in the stomach inhibits the gastric 
 tonus and the gastric hunger contractions, may nbt the sensation 
 be one of negative character, so to speak, that is, diminution or 
 absence of hunger? We are in position to answer this question 
 definitely in the negative. In the first place, the sudden and 
 spontaneous relaxation of the stomach at the end of a period of 
 gastric hunger contractions is accompanied by a characteristic 
 sense of rehef and disappearance of a certain tension or unpleasant 
 mental stress, but this sensation complex has not the positive 
 character that directs attention to food and eating. It is essentially 
 rehef from pain. Secondly, -putting these substances into a stomach 
 which is quiescent and very greatly relaxed, nevertheless, inaugu- 
 rates this temporary appetite or appetite-like sensation. Hence 
 we conclude that it is directly induced by stimulation of certain 
 nerve-endings in the gastric mucosa itself. Of course, if the nerve- 
 endings in the gastric mucosa are thus stimulated at the time the 
 muscularis is in strong tonus and himger contractions, the appetite- 
 like sensation is fused with that of rehef from the pangs of hunger. 
 
 It is significant that normal human gastric juice having full 
 acid strength (0.45 to 0.50 per cent free HCl) is capable of inducing 
 this sensation from the stomach. This has been verified repeatedly 
 by introducing 50 c.c. of appetite gastric juice into Mr. V. through 
 the stomach tube. Gastric juice of weaker acidity (0.20 per cent) 
 
ii8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 does not have this effect. As this full-strength gastric juice is 
 rapidly secreted in the stomach at the beghming of eating, it is 
 probably a factor in the augmentation of appetite by the very act 
 of eating. It may be pointed out that the foregoing facts permit 
 us to see a suggestion of truth in Beaimiont's theory that turges- 
 cence of the gastric glands is the cause of hvmger. In the first 
 place, Beaumont, in common with most physiologists, did not 
 clearly distinguish between hunger and appetite, but used the two 
 terms interchangeably. If we, then, substitute appetite for hunger, 
 we see that with the stomach normal, the appetite sensation may 
 be actually initiated or augmented by gastric juice, not through 
 mechanical pressure of the juice in the ducts, but by acid stimu- 
 lation of nerve-endings in the gastric mucosa. 
 
 It need scarcely be pointed out that when foods or liquids are 
 taken into the mouth and swallowed in the normal way their 
 main influence on appetite is by way of nerve-endings in the 
 mouth. In fact, this influence is so predominant that only by 
 excluding it are we able clearly to distinguish the gastric factor. 
 The memory factor in appetite is therefore pre-eminently gustatory 
 and olfactory. 
 
CHAPTER VIII 
 HUNGER AND AGE 
 
 I. HUNGER IN INPANTS 
 
 That the yoiing and growing individual experiences greater 
 hunger than the adult or aged individual is common knowledge. 
 This is an obvious biological correlation. In addition to the forma- 
 tion of new tissues, the young mammal is usually more active than 
 the adult, and its body surface is larger in proportion to body 
 weight, and hence (if warm-blooded) he loses proportionately more 
 heat. All these factors call for greater amounts of food. There 
 are a number of conditions that may operate to produce this greater 
 hunger in the young, (i) There may be a greater rate of secretion 
 of gastric juice, so that the digestion in the stomach requires less 
 time. This would give a more continuously empty stomach. (2) 
 There may be relative hypermotility of the filled as well as of the 
 empty stomach because of the actual youth of the stomach tissues, 
 because of greater motor innervation from the brain (vagus tonus), 
 or as the result of greater concentration of specific chemical stimuli 
 in the blood correlated with the higher rate of metabolism. (3) 
 There may be greater sensitiveness to afferent impulses on the 
 part of the brain concerned in the hxmger sensation. Either factor 
 alone, or all combined, would result in greater frequency and 
 intensity of himger and appetite. 
 
 The first question to be determined is whether the stomach of 
 the young exhibits greater hujiger contraction than the stomach 
 of adult and aged individuals of the same species. On the basis 
 of work done on man and dogs this question can now be answered 
 in the affirmative, at least for these two species. 
 
 The empty stomach of the newborn infant shows the periods 
 of gastric himger contractions before the infant has had any experi- 
 ence with food. The hunger periods are more frequent in the 
 infant than in the adult; that is to say, the duration of motor 
 
 119 
 
I20 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 quiescence of the empty stomach between the hunger periods is 
 shorter. In the newborn and very young infant the quiescence of 
 the empty stomacEnasts from lo to 60 minutes; in the adult 
 usually from I to 3 hours^ 
 
 This greater frequency of hunger in the child is also shown by 
 the more rapid development of the hunger period after a previous 
 meal. In'an adult (after a full meal) gastric hunger contractions 
 do not develop for from 4 to 6 hours. If the individual is lying in 
 bed, \he time is even longer. In the normal breast-fed infant the 
 average time of app earance^a hunger period^ after a full meal is 
 o nly 2| hours. 
 
 Pediatricians differ as to the incidence of hunger in infants, 
 because up to the last few years there has been no certain objective 
 criterion for the existence of hunger. This has led to varying views 
 and practices in regard to the frequency with which infants should 
 be nursed, some favoring an interval of 2 hours, some one of 2J to 
 3 hours, and some a 4-hour interval between nursing. Since the 
 contractions peculiar to the cardiac and fundal ends of the empty 
 stomach are, in normal individuals at least, an objective index of 
 hunger, the balloon method enables us to determine the time of 
 onset of hunger ia infants after previous feeding, and the answer 
 to this question may aid in fixing the time that should elapse between 
 the nursings of normal infants. 
 
 Our observations were made on thirty normal breast-fed infants, 
 from 24 hours to 4 weeks old. In every case the infant nursed 
 until it was satisfied. Introduction of the balloon into the stomach 
 directly after nursing leads to vomiting of the balloon and some of 
 the food, The balloon is readily retained from 45 minutes to i 
 hour after feeding; Forty-five observations were made on the 
 thirty infants. Thej^verage^time between nursing and the appear- 
 ance of the period of hunger contractions^a^sT hours "ajid" 40 
 minu tes, wit h a nuxmmn of 3 hours jand and a mini- 
 
 mum of 2 hours and 20 minutes. 
 
 Our tracings show that when the stomach is full of food the 
 inflated balloon in the fundus reveals practically no contractions. 
 As the stomach gradually empties, feeble tonus contractions appear. 
 
HUNGER AND AGE I2i 
 
 and increase in rate and intensity until they end in a period of 
 typical hunger contractions from 2| to 3 hours after the previous 
 nursing. This change of the tonus contractions of the fundic end 
 of the stomach partly filled with food into the hunger contractions 
 of the empty stomach has already been described. Our results 
 with the balloon method confirm the X-ray observations of Pisek 
 and Le Wald, Czemy, Leo, and others, who contended that the 
 emptying time of a child's stomach is ij to 3 hours. The tim e 
 required for emptying the stomach dlepends, of course, on the 
 quajitity"aii"d~quality of" the food as well as on the rate of the 
 gastric~secretion and the vigor of the gastric digestion peristalsis. 
 
 In this connection it may be of interest to note that the mam- 
 malian infant, except when under the strict control of a pediatrician 
 feeds, on the whole, as soon as the himger sensation is strong 
 enough to be uncomfortable, provided food is at hand; and he 
 thrives on this procedure; while the infant whose routine is ordered 
 by the pediatrician nurses every 2, 3, or 4 hours, irrespective of 
 the onset or intensity of the periods of hunger. Of course, a certain 
 period of rest for the gastric glarids may be beneficial, 
 
 The infant's stomach shows feeble tonus contractions of the 
 fimdal end i hour after nursing. As the stomach discharges its 
 contents these tonus imdulations gradually increase in frequency 
 and intensity until by the end of from 2^ to 3 hours these become 
 transformed into vigorous hunger contractions. The time of onset 
 of hunger contractions after previous feeding vanes for each infant. 
 In our present series the minimimi is 2 hours and the maximum 3 
 hours. In the normal individual the presence of vigorous hunger 
 contractions is probably a biologic evidence that the stomach is 
 in proper condition to receive food. If this is the case, the stomach 
 of a normal infant is ready to receive food from 2 to 3 hours after 
 the previous nursing. 
 
 U. HUNGER IN YOUNG DOGS 
 
 The experiments on dogs were made on pups delivered by 
 Caesarian section 8 to 14 days before term, on pups 5 weeks to 5 
 months of age, on young adults, and on old adults. In all cases 
 
122 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 care was taken to choose only dogs in good condition and perfect 
 health, as far as could. be judged by actions and external appear- 
 ances. Except in the case of the prematurely born pups, the 
 observations were made 24 hours after feeding, in order to assure a 
 completely empty stomach. The animals were given at least one - 
 day or more of rest after each experiment, so as to be in a perfectly 
 normal condition when used again. During the taking' of the 
 records they were held in the lap, apparently without any appre- 
 ciable discomfort, for they nearly always slept through a large part 
 of the experiment. Ten different series of records of the hunger 
 movements of the empty stomach were obtained from each dog 
 on ten separate days, the continuous experimental periods ranging 
 from 2^ to 4I hours, respectively. 
 
 The results summarized in the accompanying table were com- 
 puted from the tracings, and the figures in each case represent 
 as nearly as possible the true time of activity and rest of the 
 empty stomach, everything in the records of a doubtful charac- 
 ter, or of an abnbrmal nature caused by disturbing influences, 
 being eliminated. 
 
 GASTRIC HUNGER CONTRACTIONS IN DOGS OF DIFFERENT AGES 
 
 Dogs 
 
 Old adult 
 
 Adult 
 
 Young adult 
 
 Pup (age S to 6 months) .... 
 Young pup (age s to 6 weeks) 
 Prematurely bom pups. . . . 
 
 Length of 
 Contraction Period 
 
 30 min. to 2 hours 
 if to 3 hours 
 2I to 31 hours 
 3 to 4 hours 
 41 to sf hours 
 Continuous 
 
 Length of 
 Quiescent Period 
 
 li to 3f hours 
 if to 2 hours 
 I to ri hours 
 S to 10 min. 
 2.5 to 3.4 min. 
 None 
 
 As regards variation of stomach movements between dogs of 
 different ages, the chief and practically the only constant difference 
 was found in the length of the periods of contraction and the 
 periods of quiescence. In all cases the periods of quiescence are 
 the longest in old dogs, varying from i|- to 4I hours, and rapidly 
 decreasing in length proportionately to age to 2^ to 3yV minutes in 
 pups a few days to five or six weeks old. Conver sely the period sof. 
 
HUNGER AND AGE 123 
 
 contraction are the longest in the young dogs — for instance, in 
 the very young p^ the recorded periods run from 4J to 5I 
 hours^^ahd' they fapi31y"^ecrease in length proportionately to 
 age^^oirthe old dogs from 30 m inutes to 2 Jiours — thus showing 
 thaf th e stomach's activity is in dire ct proportion t o the age of 
 the animal (Patterson). ~ 
 
 The rapidity of the s trong hunger c ontractio ns during the 
 active perio ds appears on the whole to be greater in young animals 
 thairm^oldl The tonus of the stomach and also the strength of 
 the conffactions in yoimg animals may be slightly higher, but they 
 are subject to great variations. The decrease in the activity of 
 the stomach as the animal approaches senility 7i£._probably an 
 explanatiOTi^_in_partjLt Jeastj^ of the more chronic gastric disturb- 
 ances in the aged. 
 
 "I'o smnmarize: in healthy dogs the hunger contractions of the 
 empty stomach decrease with age. This decrease appears to some ( 
 extent in the tonus and in the rapidity of the himger contractions, 
 but is particularly marked in the duration of the periods of hunger 
 activity and the intervening periods of quiescence of the stomach. 
 On the whole, the decrease in the gastric hunger activity is pro- 
 portional to the advance in age. In very yoimg dogs the hunger 
 contractions of the empty stomach are practically continuous. 
 
 Two factors are probably involved in this age variation in the | 
 gastric himger contractions, namely, (i) t he actual age (reduced 
 metabolism) of the mo tor tissue in the s tomach its en7"and (2) ai 
 lowering of metabolism in the entire body, which may imply a 
 smaller quantity of chemical stimuli to the gastric hunger mech- 
 anism in the circulation. Patterson attempted to determine the\ 
 relative importance of these two factors by studying the influence of 
 prolonged starvation on the gastric hunger contractions in very 
 yoimg and in very old dogs. If the rate of general body metabolism, 
 that is, starvation metabolism, is the main factor, we should expect 
 that in prolonged starvation the gastric himger contractions of old 
 dogs would approach the vigor of the normal himger contractions 
 of young dogs. This is not the case. It is true that starvation 
 causes some increase in the vigor of the stomach tonus and con- 
 
124 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 tractions in the old dogs. Starvation metabolism of the body in 
 general is therefore a factor. But the actual age of the stomach 
 tissues is the most important element. How actual age of the 
 gastric motor mechanism reduces the vigor and duration of the 
 himger contractions cannot be answered until we know what 
 constitutes the physiological aging of the tissues. 
 
CHAPTER IX 
 HUNGER IN PROLONGED STARVATION 
 
 I. EXPERIMENTS ON MEN 
 
 In the popular mind prolonged starvation is associated with 
 
 great pain and distress, despite reliable reports to the contrary 
 
 from many persons who have undertaken voluntary starvation. 
 
 ( Such persons state, almost without exception, that after the first 
 
 three or four days of starvation, the sensation of hunger is no longer 
 
 \ felt, or at least is not excessively painful or uncomfortable. 
 
 This brings up some important physiological and biological 
 questions. If hunger ceases entirely, or at least loses its painful 
 urge after a few days of starvation, what makes the starving 
 animal fight for food as long as his strength enables him to move ? 
 In man this struggle for food may be due to the desire to hve or 
 the fear of death, but can we assume this degree of conscious fore- 
 sight in the lower animals? Is the reported absence* of hunger 
 sensation in man after the first few days of starvation due to 
 failure of the gastric hunger mechanism, or to changes in the brain 
 that prevent the htinger impulses from reaching consciousness ? 
 One might naturally expect a decrease in the intensity of the hun- 
 ger sensation when starvation reaches a point where the brain and 
 stomach are greatly enfeebled by loss of hving substance or by 
 too high an acidity of the blood, but this state is. not reached in a 
 healthy man by three or four days' deprivation of food. If the 
 hunger mechanism is controlled even in part by the starvation 
 changes in the tissues (stomach, brain) and in the blood, we should 
 expect the himger sensation to increase in strength up to the point 
 of tissue marked depletion, unless the starvation itself sets up other 
 inhibitory processes. 
 
 These questions can be answered only by direct experiments, 
 and these were accordingly undertaken both on man and on the 
 lower animals. The work on man was carried out on the author 
 and one assistant (Mr. L.), in such a way that the gastric hunger 
 
 I2S 
 
126 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 contractions and the subjective hxrnger sensation were recorded, 
 day and night, during the entire starvation period. In animals 
 below man we can, of course, record the gastric hunger contractions 
 only, as we have as yet no means of determining the intensity or 
 quality of the sensations caused by these contractions. 
 
 During the five days' starvation period the two men continued 
 their usual work during the day, and records 6f the stomach tonus 
 and hunger contractions were taken at varying intervals. During 
 the night continuous records were taken beginning 8 : oo to 9 : oo 
 P.M. and ending at 5 : 00 to 6 : 00 a.m. Neither the writer nor Mr. L. 
 foimd much difficulty in sleeping for 6 to 8 hours every night with 
 balloon and tube in the stomach. The room was kept dark, except 
 for a feeble light focused on the drvun, so as to enable the assistant 
 to take care of the recording. And the assistant took special care 
 to keep everything as quiet as possible. One assistant took care 
 of the recording from 8 : 00 a.m. to 2 : 00 p.m., and a second assistant 
 from 2 : 00 p.m. to 6 : 00 a.m. The time from 6 : 00 to 8 : 00 a.m. and 
 from 6 : 00 to 8 : 00 p.m. was usually spent in walking in the parks — 
 in any event, outside the laboratory. 
 
 I. THE OBJECTIVE PHENOMENA. THE HUNGER CONTRACTIONS 
 
 Before beginning the starvation period-, observations on the 
 gastric hunger contractions of the writer were made every second 
 or third day for three weeks. These observations were usually 
 made in the morning after dispensing with breakfast, or else during 
 the middle of the day, thus dispensing with lunch. No observa- 
 tions were made during night or sleep. These records are quite 
 imiform in character, and represent the degree of hunger contrac- 
 tions exhibited by the writer's stomach 6 to 15 hours after a meal. 
 We now wish to direct the reader's attention to the following 
 summary of the observations' during the starvation period, from 
 June 29 to July 4, 1914. 
 
 A. J. C, 
 Jiine 29. No breakfast. Fifst hunger period began gradually at 8:45 a.m., 
 
 lasting for about 45 minutes; 16 strong contractions in 30 minutes. 
 
 A second period ended at 11:30, lasting about 30 minutes. There 
 
 were 22 strong contractions in 30 minutes. 
 
HUNGER IN PROLONGED STARVATION 127 
 
 Last meal. Two slices of toast and a glass of milk at 12 :30 P.M. Body weight 
 
 74 kg.; no observations during the night. 
 June 30. A.M. II : 50 to 12 : 20, fairly strong contractions. 
 12 : 20 to I : so, quiescence. 
 P.M. 1:50 to 2:30, 18 fairly strong contractions. 
 2:30 to 4:30, quiescence. 
 
 Interruption 
 9:15 to 10:00, 22 strong contractions. 
 10:00 to II : 10, fairly quiescent. 
 II : 10 to II : so, continuous feeble contractions. 
 ii:So to 12:30, 36 strong contractions. 
 July I. A.M. 12:30 to 12:40, quiescence. 
 
 12 : 40 to 1 : 20, continuous feeble contractions. 
 1 : 20 to 2 : 25, 45 strong contractions. 
 2 : 25 to 2 : so, continuous feeble contractions. 
 2:50 to 3:30, 27 strong contractions. 
 3:30 to 4:00, quiescence. 
 4:00 to 4: 30, continuous feeble contractions. 
 4:30 to 5:20, 26 strong contractions. 
 
 Interruption 
 8:4s to 9:ss, 43 strong contractions. 
 10: 20 to 12 : 20, contractions all the time, but feeble. 
 P.M. 12:20 to 1:00, 19 strong contractions. 
 Interruption 
 3 :4s to 4:00, 20 fairly strong contractions. 
 
 Interruption 
 8:3s to 9:25,37 strong contractions. 
 9:25 to 1 1 : 20, continuous, fairly strong contractions. 
 1 1 : 20 to 12 : 25, 47 very strong contractions. 
 July 2. A.M. 12 : 25 to 12 : so, fairly quiescent. 
 
 12:50 to 2:3s, continuous, fairly strong contractions (60). 
 2 : 3 S to 3:30, fairly quiescent. 
 
 3: 30 to 4:50,70 strong contractions, ending in tetanus 
 (4 min.). 
 Interruption 
 6:30 to 7:40, quiescence. 
 7 : 40 to 8 : 40, $s strong contractions. 
 
 Interruption 
 10:25 to 11:15, 29 strong contractions. 
 Interruption 
 P.M. 1 : 00 to 3 :oo, continuous, fairly strong contractions, stronger 
 toward the end. 
 Interruption 
 
128 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 Julys. P.M. 8:4s to 9:00, 22 strong contractions. 
 
 9 : 00 to 9 : so, continuous feeble contractions. 
 9:50 to 10:30, 27 strong contractions. 
 10:30 to 11:30, continuous, fairly strong contractions. 
 11:30 to 12:30, 34 strong contractions. 
 July 3. A.M. 12:30 to 2:25, continuous, fairly strong contractions. 
 
 2:25 to 3:40, 60 strong contractions, ending in incomplete 
 
 tetanus (s min.). 
 3:40 to 4:05, continuous feeble contractions. 
 4:05 to 5:00, 42 strong contractions. 
 
 Interruption 
 8:30 to 9:2s, 30 strong (not maximum) contractions. 
 II : 25 to I :'oo, continuous, fairly strong contractions. 
 1:00 to 1:40, 30 strong contractions. 
 
 Interruption 
 4 : 45 to 5:15, continuous feeble contractions. , 
 9:00 to 9:45, 38 strong contractions. 
 9:4s to II : 20, continuous feeble contractions. 
 II : 20 to 12 : 10, 39 strong contractions. 
 July 4. A.M. 12:10 to 1 : 10, continuous feeble contractions. 
 1 : 10 to 2 :3s, 60 strong contractions. 
 2 : 3 S to 3 : 40, fairly quiescent . 
 3 : 40 to 5 : 40, 50 strong contractions. 
 
 End of experiment: Body weight, 69.8 kg. Loss of body weight, 4.2 kg. 
 
 * 
 
 Confining our attention for the present to the objective phe- 
 nomena, i.e., the gastric tonus and the hunger contractions, we 
 find the following facts to be apparent: 
 
 I. There is no decrease in the gastric tonus and the hunger 
 contractions, but, on the contrary, an increase, especially in the 
 tonus, and in the frequency of the hunger periods. An increase in 
 the intensity of the hunger contractions is also evidenced in the 
 appearance of the incomplete hunger tetanus on the fourth and 
 fifth days of starvation. 
 
 2; There was a continuous but probably scanty secretion of 
 gastric juice during the entire hunger period, as the balloon on 
 being withdrawn from the stomach > always tasted acid and gave 
 the acid reactions. 
 
 The five days' hunger period of Mr. J. H. L. began on July 14 
 and was concluded on July 19. During July 10 to- 14 daily 
 
HUNGER IN PROLONGED STARVATION 129 
 
 observ&.tions were made of the gastric hunger contractions, in order 
 to establish the normal frequency and general character of these 
 contractions in Mr. L. The periods 0|f hunger contractions of 
 Mr. L. under normal conditions of eating differ from those of the 
 writer by usually ending in the incomplete tetanus previously 
 described in Mr. V. This is probably due to the fact that Mr. L. 
 is sixteen years yoxmger than the writer. 
 
 Summary or the Observations on Mr. J. H. L. 
 Control Period 
 
 Jiily 10. No breakfast or lunch; 1:30 to 4:25 p.m., period of observation; 
 2:00 to 2:40 P.M., gradually increasing contractions ending in 11 strong 
 contractions and strong tetanus (3^ mm.). Feeble rapid contractions 
 began to reappear at 3 : 15 and gradually increased in amplitude. 
 
 July II. No breakfast; 9:00 a.m. to 12:00 p.m., continuous fairly strong 
 contractions. Period of 15 strong contractions; 10:30 to 11 :oo a.m. and 
 11:00 A.M. to 12:00 M., continuous fairly strong contractions (22 con- 
 tractions). 
 
 July 12. No breakfast; 9:35 to 10:10 a.m., 22 contractions of gradually 
 increasing strength in 30 minutes, ending in 3-minute incomplete tetanus. 
 
 July 13. No lunch; 12:00 to 12:30 p.m., continuous, fairly strong contrac- 
 tions. A small group (10) of strong contractions 12:30 to 12:4s P.M. A 
 period of strong contractions (22 gradually increasing ending in 3-minute 
 tetanus) 1:50 to 2:30 p.m. 
 
 July 14. 10:00 A.M. to 1:00 p.m. No breakfast; 10:00 to 10:50 a.m., 31 
 gradually increasing strong contractions ending in tetanus (2 min.); 
 11:30 A.M. to 12:00 M., 14 fairly strong contractions, no tetanus; 12:3010 
 1 :oo P.M., 21 gradually increasing strong contractions ending in a 3-minute 
 
 tetanus. 
 
 Fasting Period 
 
 Last meal, July 14, 2 : 00 p.m. Body weight, 62.8 kg. 
 July 15. p.m. 7:4s to 8:25, 19 fairly strong contractions. 
 8 : 25 to S:ss, quiescence. 
 8:35 to 9:00, 28 fairly strong contractions. 
 9 : 00 to 9:15, quiescence. 
 
 9: 15 to 9:4s, period of 21 fairly strong contractions. 
 9:4s to 9:55, quiescence. 
 
 9:55 to 10:25, period of 21 fairly strong contractions. 
 10:25 to n:oo, period of 18 fairly strong contractions. 
 11:05 to 11:40, period of 17 fairly strong contractions. 
 Interruption 
 
II 
 
 Fig. is 
 
Fig. 15. — I. Recordsof the contractions of the empty stomach of A.J. C. Bromo- 
 f orm manometer. A , final ten minutes of a typical period of hunger contractions ten 
 hours after a meal; B, final after ten minutes of a typical hunger period after 
 five days' starvation. Note in tracing B the prolonged period of incomplete tetanus 
 at the culmination of the hunger period, and the reappearance of a feeble 20-seconds 
 rhythm immediately following the cessation of the period of strong hunger con- 
 tractions. Showing the increase in the tonus and the hunger contractions of the 
 empty stomach during prolonged starvation. Four-ninths original size. 
 
 11. Typical record (10 minutes) of the hunger contractions of the stomach of 
 dogs. A , after 8 days' starvation; B, after ten days' starvation; showing a persistence 
 of the gastric hunger contractions during prolonged starvation. C, tracing showing 
 end of a gastric tunger period of a dog after 6 days' starvation. The vagi and splanch- 
 nic nerves sectioned before the starvation period. About one-half original size. 
 
132 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 July i6. A.M. 9: 20 to 10: 25, period of gradually increasing very strong con- 
 tractions (33), ending in tetanus (2 min.). 
 Interruption 
 P.M. 1:00 to 1:40, period of gradually increasing strong contrac- 
 tions (25), ending in tetanus (3 min.). 
 Interruption 
 3 : SS to S : 00, quiescence. 
 5:00 to 5:50, period of fairly strong contractions (17). No 
 
 tetanus. 
 8:3s to 9:3s, period of very strong contractions (37), ending 
 
 in 3 -minute tetanus. 
 9:35 to 10:20, quiescence. 
 
 10: 20 to II : 20, continuous, fairly strong contractions. 
 11:20 to 11:30, fairly quiescent. 
 
 11:30 to 12:00, period of fairly strong contractions (11). No 
 tetanus. 
 July 17. A.M. 12:00 to 12:40, continuous feeble contractions. 
 1 2 : 40 to 1:30, quiescence. 
 1 : 30 to 2 : 00, continuous feeble contractions. 
 2 : 00 to 3 : 00, quiescence. 
 3:00 to i'-^o, continuous feeble to fairly strong contractions. 
 
 Interruption 
 9 : 30 to 10:10, period of very strong, gradually increasmg con- 
 tractions (36), ending in tetanus of 2j 
 minutes. 
 Interruption 
 P.M. 12:15 to 3 : 30, practically continuous, feeble to moderately 
 strong, and strong contractions. 
 Interruption 
 8:40 to 10:00, continuous feeble to moderately strong con- 
 tractions. 
 10:00 to 10:40, period of very strong, gradually increasing 
 contractions (20), ending in tetanus (2 min.). 
 10 : 40 to II : 00, quiescence. 
 
 11:00 to 11:50, period of moderately strong coptractions (23). 
 No tetanus. 
 July 18. A.M. 11:50 to 2 :30f mainly quiescent (occasional feeble contrac- 
 tions). 
 2:30 to 3:30, period of very strong, gradually increasing 
 
 contractions (34). No tetanus. 
 3: 30 to 4:00, fairly quiescent (occasional feeble contrac- 
 tions). 
 
HUNGER IN PROLONGED STARVATION 133 
 
 July 18. A.M. 4:00 to 5:00, period of strong, gradually increasing contrac- 
 tions (24), ending in tetanus (25 min.). 
 5:00 to S-4S) continuous feeble contractions. 
 
 Interruption 
 9:20 to 10:10, period of fairly strong contractions (35). No 
 
 tetanus. 
 10: 10 to II : 15, fairly quiescent. 
 
 11:15 to 12:00, period of strong contractions (22). No 
 tetanus. 
 Interruption 
 P.M. 2 : 30 to 3 : so, continuous, very feeble contractions. 
 3 : 50 to 4:05, period of 10 fairly strong contractions. 
 4:05 to 4:15, quiescence. 
 4: 15 to 4:40, period of 13 strong contractions. 
 4 : 40 to 4 : so, quiescence. 
 
 4:50 to 5:30, period of very strong contractions (22), ending 
 in tetalnus. 
 Interruption 
 8:35 to 9:20, 32 strong contractions, practically continuous. 
 
 Strong tonlis. 
 9:20 to 10:00, continuous feeble contractions. 
 10:00 to 10: so, IS strong contractions (long drawn out). One 
 
 tetanus period. 
 10: so to 11:30, period of strong contractions (22), ending in 
 
 very strong tetanus (3 min.). 
 11:30 to 12:40, fairly quiescent, but a few fairly strong con- 
 tractions. 
 July ig. A.M. 12:40 to 1:2s, period of very strong contractions (37). No 
 
 tetanus. 
 1 : 2 s to 1 : 4S, quiescence. 
 1:4s to 2:1s, period of fairly strong contractions (11). No 
 
 tetanus. 
 2:15 to 2:30, quiescence. 
 2:30 to 3:10, period of very strong contractions (22), ending 
 
 in a 3-minute tetanus. 
 3 : 10 to 4:00, continuous very feeble contractions. 
 4: 15/ to 6:00, continuous strong contractions (36), ending in 
 tetanus (3 min.). (Long and irregular 
 pauses evidently due to psychic inhibition, 
 as Mr. L. was very restless.) 
 End of experiment: Body weight, S9 kg- Loss of body weight, 3.8 kg. 
 
 It is clear that the results on Mr. L. practically duplicate those* 
 on the writer, (i) There is no decrease, but, on the contrary, an 
 
134 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 increase in the gastric tonus and in the hunger contractions. (2) 
 The stomach showed an, acid reaction all the time during the 
 hunger period, evidently due to a continuous but scanty secretion 
 of gastric juice. 
 
 2. THE SUBJECTIVE PHENOMENA 
 
 1. General condition. — Mr. L., as well as the writer, continued 
 in good health and in fairly good spirit throughout the starvation 
 period. On the fourth and fifth" days both men felt somewhat 
 weak. Some mental depression was also experienced, especially 
 on the fifth day, by Mr. L., who complained of feeling dizzy on 
 getting on his feet aftfer lying down. An hour's lecturing seemed 
 quite an effort on the fourth starvation day, and on the fifth day 
 both men felt distinctly better when lying down than when sitting 
 or standing. Both slept fairly well during the four nights of the 
 starvation period, despite the persistent hunger contractions and 
 the imusual surroundings of the research laboratory as a sleeping- 
 room. The secretion of urine was diminished, although water was 
 taken whenever desired. In some cases a glass of water was taken 
 to diminish the hunger pangs. The writer did not enjoy a cigar 
 after the second day; in fact, smoking tended to produce nausea. 
 This is an indication of increased excitability of the nerves of the 
 gastero-intestinal canal. 
 
 2. The sensations of hunger and appetite. — During the period of 
 control observations both subjects trained themselves in judging 
 the relative intensity of the individual himger pangs, and in this 
 both of them attained, a fair degree of efl&ciency. They can invari- 
 ably tell the onset of a hunger period before the contractions have 
 reached a sufficient intensity to be recognized as individual hunger 
 pangs. This initiation of the himger period consists in a gradually 
 increasing tonus and feeble and more or less rhythmical contrac- 
 tions, and this is felt as a continuous mild hunger or a moderately 
 steady and somewhat uncomfortable tension in the epigastric 
 region. This sensation is not dependent on or influenced by the 
 distended balloon in the stomach cavity. In this way one can 
 usually manage to record practically every hunger period during 
 the day, simply by starting observations as soon as one feels the 
 
HUNGER IN PROLONGED STARVATION 13S 
 
 very onset of the hunger period. The periods of strongest hunger con- 
 tractions, or the hunger tetanus, are also felt as continuous and 
 intense hunger. And there is a characteristic relief from the 
 diminished tension within a minute or so after the period of hunger 
 contractions is at an end. 
 
 During the first two or three days the hunger sensations seemed 
 both to Mr. L. and the writer somewhat more severe than any 
 hunger experienced during the control period, in fact, more severe 
 than seemed warranted from the degree of intensity of the gastric 
 contractions. To be sure, the himger contractions of the stomach 
 were usually somewhat stronger than, and in every case at least 
 as strong as, during the control period, but the hunger sensations 
 seemed even stronger proportionately. During the fourth and 
 the fifth hunger days, on the other hand, the hunger sensation 
 seemed somewhat weaker than one could have predicted from 
 Ithe intensity of the hunger contractions. In fact, the sensation 
 did not even seem to be as keen as that produced by a period of 
 strong himger contractions 6 to 10 hours after the previous meal. 
 The reader will recall that the gastric himger contractions on the 
 last two days were of normal or greater than normal intensity. 
 
 The sensation of hunger was almost continuous after the first 
 day of starvation. That is to say, the hunger sensation referred 
 to the epigastrium did not wholly disappear during the intervals 
 between the vigorous gastric contractions. This feeble but con- 
 tinuous hunger sensation is evidently caused by the increased 
 gastric tonus and more or less continuous but feeble rhythmical 
 contractions that represent the periods of quiescence of the empty 
 stomach during prolonged starvation. On the fifth day of starva- 
 tion the continuous hunger sensation seemed to be tinged with a 
 peculiar "burning" sensation, also referred to the stomach, the 
 .fusion resembling somewhat the feeling of "sick stomach" with 
 lits attendant central depression. This "burning" sensation was 
 probably caused by acid stimulation of hyperexcitable nerve-endings 
 in the gastric mucosa. 
 
 The appetite during the starvation period ran practically par- 
 allel with the sensation of hunger. It was distinctly increased 
 
136 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 during the first two or three days, and diminished on the fourth 
 and fifth days. In fact, the depression of appetite on these two 
 days seemed distinctly greater than the depression of the hunger 
 sensation. Instead of an eagerness for food, there was ahnost an 
 indifference toward food, despite the persistent hunger call of the 
 empty stomach. This was particularly true of Mr. L. He stated 
 several times on the fourth and fifth days that the sight of food 
 led, not to a feeling of eagerness for eating, but to a feeling par- 
 taking of the nature of revulsion or nausea. This was not experi- 
 enced by the writer. Food looked good to him throughout the 
 starvation period, but he found it much easier to dismiss thoughts 
 of food and eating from his mind toward the end than at the 
 beginning of the period. 
 
 The reasons for this seeming discrepancy in the parallel between 
 the intensity of gastric hunger contractions and the intensity of 
 the subjective himger sensation during the five days' hunger period 
 can only be conjectured, at present. We are inclined to believe 
 with Stohr that the weakening of the hunger and the appetite 
 sensations toward the end of the period is due to a depression 
 lof the central nervous system. This central depression, how- 
 ever caused, was clearly in evidence both in Mr. L. and the 
 writer. Afferent impulses from the viscera, differing from the 
 normal quantitatively, probably also play a part in the . situa- 
 tion. 
 
 jMore prolonged starvation in man appears to lead at times 
 to a heightened or abnormal cerebral activity, as shown by the 
 ieeling of exaltation, visual and auditory hallucinations, etc. These 
 phenomena are probably determined quite as much by the type of 
 emotional processes of the individual as by the effects of starvation, 
 since they are reported more frequently by religious ascetics, than 
 by 'Worldly minded men starving for purposes of science or health. 
 The hallucinations may be due to depression of certain cerebral 
 centers, and hence similar to dreaming rather than to actual 
 increase in cerebral excitability. In any case, these phenomena 
 are probably due to starvation changes in the blood and the brain 
 tissues, rather than to the gastric hunger mechanism.r— 
 
HUNGER IN PROLONGED STARVATION 137 
 
 3. After-effects of the starving period. — Both in Mr. L. and the 
 writer practically all of the mental depression and some of the feeling 
 of weakness disappeared during the partaking of the first meal after 
 the fasting period. This central depression is therefore essentially 
 a reflex condition depending probably on afferent impulses from 
 the digestive tract, rather than a result of lack of nutrient material 
 in the blood. But complete recovery from the bodily weakness 
 did not take place until the second or third day after breaking 
 the fast. 
 
 From the second day on both men felt unusually well, distinctly 
 better, in fact, than before the hunger period, although both men 
 are normally in good health and vigor and not hampered by exces- 
 sive fat. The writer felt as if he had had a month's vacation in 
 the mountains. The mind was unusually clear and a larger amount 
 of mental and physical work was accomplished without fatigue. 
 In the writer's own case, the five days' starvation period increased 
 the vigor of the gastric hunger contractions to th^t of a young 
 man of twenty or twenty-five, and the empty stomach retained 
 this increased vigor for at least three weeks after the hunger period, 
 when observations were discontiaued owing to absence from the 
 University. This improvement or rejuvenation of the stomach 
 is not a matter of subjective feeling of opinion, but a matter of 
 objective record on the tracings. Neither Mr. L. nor the writer 
 can be considered as ordinarily eating to excess, although the daily 
 intake of protein and calories is greater than the minimum require- 
 ment advocated by Chittenden. The cause of the improvement 
 was not loss of excessive adipose tissue. 
 
 Mr. L. states that the augmentation of hunger and appetite 
 persisted for at least two or three weeks after the end of the starva- 
 tion period. 
 
 We are familiar with but not particularly impressed by the 
 arguments of enthusiasts who advocate starvation as a panacea 
 for various human ills. But this personal experience leads us to 
 feuspect that there is more value in some of these measures than is 
 qrdinarily considered. Civilized man has traveled far from the 
 conditions of life among wild animals and primitive man, with 
 
138 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 whom periods of starvation are not uncommon. Occasional 
 periods of starvation, say once or twice a year, in the case of 
 healthy adult persons may not only add to the joy of living but 
 also to the length of life. There is some evidence resulting from 
 experiments with animals that periods of starvation may accelerate 
 growth and improve the general body metabolism (Deland, 
 McColliim, Howe, Morgulis). 
 
 4. Discomforts of starvation. — During the entire starvation 
 period the himger sensation was strong enough to cause some 
 discomfort, but not to a degree that could be called marked pain or 
 suffering. This discomfort was at no time sufficient to interfere 
 seriously with work. And since practically all observers agree 
 that the hunger discomfort is greatest during the first few days 
 of starvation, it seems probable that our five days of starvation 
 gave us a taste of the maximtmi discomfort that would be experi- 
 enced in more protracted fasts. Accounts of acute sufferings from 
 mere starvation (water being at all times available) must therefore 
 be wholly imaginary, or the result of fear and panic. Voluntary 
 starvation is in no'sense a heroic act, and citation of hunger experi- 
 ments on animals in the interest of science as instances of cruelty 
 to animals is without foundation. 
 
 II. RESULTS ON NORMAL DOGS 
 
 No attempt was made to take continuous records of the motor 
 activity of the empty stomach in the starving dogs. Observations 
 were made for periods of 2 to 6 hours each day, beginning the 
 second or third day of starvation. The result on the five normal 
 dogs can be seen at a glance from the following summary: 
 
 Dog I. — ^Young Vigorous Female 
 Starvation Day: 
 
 2d day. 10:25 A.M. to 12:00 M., continuous vigorous contractions; 
 
 type II and III. 
 3d day. 2:00 to 4:00 P.M., continuous vigorous contractions, type II 
 
 mainly. 
 4thday. 10:25 a.m. to 12:35, p.m., continuous contractions, type II 
 
 mainly. 
 
HUNGER IN PROLONGED STARVATION 139 
 
 Sth day. 1 130 to 3 : 30 p.m., continuous contractions, t)fpe II mainly. 
 6th day. 10:55 a.m. to 1:00 p.m., continuous contractions, type III 
 
 mainly. 
 7th day. 9 : 00 a.m. to i 2 : 00 m., continuous contractions, type III mainly. 
 Sth day. 9:35 to 11:35 a.m., continuous contractions, type II mainly. 
 9th day. 10:35 a.m. to 12:35 ^■^- continuous contractions, t3T)e III 
 
 mainly, 
 loth day. 9:35 a.m. to 3 :35 p.m., very vigorous contractions, types II and 
 
 III only. Tonus on the average, 12 cm. bromoform. 
 End of experiment 
 
 Dog II. — -Young Vigorous Female 
 
 3d day. 10:00 A.M. to 3 : 00 p.m., strong tonus and continuous contrac- 
 tions of type III. 
 
 4th day. 10:12 A.M., strong tonus and continuous contractions of type 
 III. 
 
 5th day. 1:00 to 3:00 P.M., strong tonus and continuous contractions. 
 
 6th day. 9:00 a.m. to 12:00 m., strong and continuous contractions. 
 Tonus about 10 cm. bromoform. 
 End of experiment 
 
 Dog III.— Old Female 
 
 2d day. 10:00 A.M. to 12:00 m., feeble contractions, type I. 
 
 3d day. 9 : 00 to 1 1 : 00 A.m., a few irregular contractions, type I ; stom- 
 ach hypotonic. 
 
 4thday. i:oot03:oop.M., afewirregularcontractions, typel; stomach 
 hypotonic. 
 
 5th day. 8:00 to 11:00 A.M., practically no contractions; stomach 
 hypotonic. 
 
 6th day. 1:00 to 4:00 p.m., practically no contractions; stomach 
 h3rpotonic. 
 
 End of experiment 
 
 Dog IV. — ^Young Vigorous Female 
 
 3d day. 9:30 to 11:30 A.M., strong tonus, continuous contractions, 
 types II and III. 
 
 4th day. 1 : 00 to 3 : 00 p.m., fairly strong tonus, types I and II contrac- 
 tions. 
 
 5th day. 8 : 00 to 1 1 : 00 a.m., strong tonus, types II and III contractions. 
 
 7ihday. 9:40 a.m. to 12:00 M., fairly strong tonus, type III contrac- 
 tions. 
 
 Sth day. 1 : 00 to 3 : 00 p.m., very strong tonus, type III contractions. 
 
I40 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 9th day. 8:00 to 10:00 A.M., feeble tonus, feeble contractions, type II. 
 loth day. 8:00 to 11 :oo a.m., fairly strong tonus; fairly strong tj^e II 
 contractions. 
 
 End of experiment 
 
 Dog. v.— Six-Months-Old Female 
 
 2d day. Fast 30 hours; t3^e II contractions; tonus 3 to 4 cm. Chloro- 
 form. 
 
 3d day. Type II contractions; tonus 3 to 4 J cm. 
 
 4th day. Tj?pe II contractions; tonus 3 to 4! cm. 
 
 5th day. Typt II contractions; tonus 3 to 45 cm. 
 
 6th day. Types II and III contractions; tonus 3 to 4I cm. 
 
 7th day. Types II and III contractions; tonus 3 to 4 J cm. 
 
 8th day. Tjrpes II and III contractions; tonus 3 to 5} cm. 
 
 9th day. Types II and III contractions; tonus 3 to 6\ cm. 
 
 loth day. Type III contractions; tonus 3 to 7 cm. 
 
 nth day. Type III contractions; tonus 3 to 6j cm. 
 
 1 2th day. Tjrpe III contractions; tonus 3 to 65 cm. 
 
 13th day. Type III contractions; tonus 3 to 6jcm. 
 
 14th day. Type II and prolonged type III contractions; tonus 3 to 7 cm. 
 
 iSth day. Type III contractions; tonus 3 to 65 cm. 
 
 i6thday. Six hours before death from starvation; type II and prolonged 
 type III contractions; tonus 3 to 91 cm. 
 
 Dogs I, II, and IV exhibited either normal or greater than 
 normal hunger contractions of the empty stomach during the 
 entire starvation period. The increased tonus of the stomach was 
 particularly marked. In consequence of this increased tonus the 
 types of hunger contractions were usually those previously de- 
 scribed as II and III, that is, practically incomplete tetanus. 
 Judging from observations on man, the dogs probably felt con- 
 tinuous and intense hunger during these contractions. 
 
 The only old dog in this series. No. Ill, had shown rather feeble 
 and irregular gastric hunger contractions before the starvation 
 period. The reason for this was not apparent. The dog was in 
 good condition and would eat greedily, even when the empty 
 stomach was practically quiescent and distinctly hypotonic. This 
 dog showed virtually no gastric hunger contractions after the third 
 day of starvation, and the stomach appeared distinctly hypotonic. 
 The dog was eager for food, however. 
 
HUNGER IN PROLONGED STARVATION 
 
 141 
 
 The stomach of the dogs showed acid reaction throughout the 
 hunger period, just as was the case with the stomachs of the 
 starving men. 
 
 It will thus be seen that Ihe empty stomach of men and dogs 
 exhibits ordinarily either normal or greater than normal hunger 
 contractions during starvatioi; periods of from 5 to 15 days. 
 
 The cause of this increased hunger activity of the stbmach 
 may be: (i) an increase in the tonus innervation via the vagi; 
 (2) changes in the blood in consequence of starvation; (3) starva- 
 tion metabolism of the motor tissues of the stomach itself. 
 
 
 
 
 
 
 
 
 
 
 1 JL lUi^h-iM 
 
 i 
 
 \ 
 
 
 
 
 
 ' 
 
 \ 
 
 
 
 ' 1 
 
 1 / 
 
 I / 
 
 1 1 
 
 \ 1 
 
 7 
 
 
 
 J 
 
 J 
 
 
 
 \i 
 
 U 
 
 i 
 
 
 1 
 
 y 
 
 n 
 
 11 
 
 U 
 
 y 
 
 M 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Fig. 16. — ^Diagrammatic representation of the amplitude of a gastric hunger 
 contraction on the base of the rising tonus as constructed from the daily tracings 
 during starvation of a young dog. Each of the above squares represents i sq. cm. 
 The erect pyramids indicate the amplitudes of the hunger contractions in centimeters 
 arranged on the rising tonus as a base line. Spaces left to right indicate number of 
 days of starvation; spaces from botto'm to top daily increase in the gastric tonus in 
 centimeters. Note the rapid increase in gastric tonus and decline in amplitude of 
 contractions on the 15th day as produced by the prolonged type III himger contractions 
 (Patterson). 
 
 III. EXPERIMENTS ON DOGS WITH THE STOMACH ISOLATED 
 FROM THE CENTRAL NERVOUS SYSTEM 
 
 In order to decide between these three possibilities starvation 
 tests were made on two dogs with complete isolation of the stomach 
 from the central nervous, system by section of the vagi and the 
 splanchnic nerves and on one dog with the vagi nerves severed, 
 
142 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 the splanchnic nerve being left intact. The following is a brief 
 summary of the results: 
 
 Dog VI. — ^Young Female. Section of the Vagi and Splanchnic Nerves 
 Two Weeks before Starvation Period 
 Starvation Day: 
 
 4th day. io:oo a.m. to i:oo p.m., one group, type I contractions (15), 
 
 fairly strong. 
 5th day. 2:00 to 5:00 P.M., tjrpe I contractions, fairly strong but with 
 
 long intervening pauses. 
 6th day. 10:00 a.m to 12:00 m., 30 strong (type I) contractions ending 
 
 in tetanus (Fig. s^l). 
 7th day. 1:00 to 4:30 P.M., continuous contractions of t3T)e III; tonus 
 about 10 cm. btomoform. 
 
 End of experiment 
 
 Dog VII. — ^Adult Fairly Vigorous Female. Vagi and Splanchnic Nerves Cut 
 
 Sth day. 9:00 to 11:00 a.m., 9 very vigorous contractions and tetanus 
 
 periods. 
 6th day. 1:00 to 3:00 p.m., fairly strong contractions of type I; long 
 
 pauses between contraction^. 
 7th day. 1:00 to 5:00 P.M., stomach hypotonic; no contractions. 
 End of experiment 
 
 Dog VIII. — ^Young, Fairly Vigorous Female. Vagi Nerves Sectioned 
 
 3d day. 9:00 to 11:00 A.M., fairly strong tj^pe I contractions. 
 
 5th day. 1:00 to 5:00 P.M., strong (type I) contractions, long pauses 
 between contractions. 
 
 6th day. 9:00 to 11 : 00 a.m., stomach hs^jotonic, practically no contrac- 
 tions. 
 
 7th day. 1:00 to 4:00 P.M., fairly strong type I contractions, prolonged 
 and partly tetanic; long pauses between contractions. 
 End of experiment 
 
 The gastric hunger contractions of Dog IV were absent on the 
 seventh day of starvation, but Dogs V and VII showed either 
 normal or greater than normal hunger contractions throughout 
 the starvation period. Since the increase in the hunger contrac- 
 tions appeared to be just as marked in the dogs with the stomach 
 isolated from the central nervous, system as in normal dogs, it 
 follows that the cause of this increase is not an augmentation of 
 the vagus tonus. 
 
HUTSTGER IN PROLONGED STARVATION 
 
 143 
 
 These starvation periods were not of sufi&cient length to cause 
 very marked asthenia either in the men or in the dogs (except 
 Dog V). They do show that the hunger tonus and contractions 
 persist with normal or greater than normal vigor during shorter 
 starvation periods. Cases of gastric hypotonus and decreased gas- 
 tric motility cannot therefore be due to starvation as such, but to 
 some special and exceptional factors. The depression may be due 
 (i) to a primary asthenia of the stomach; (2) to central inhibition 
 via the splanchnic nerves (pains, depressions, etc.); (3) to acid 
 inhibition from the stomach mucosa owing to copious secretion of 
 gastric juice. This question requires further investigation. 
 
 IV. EXPERIMENTS ON DOGS WITH PANCREATIC DIABETES 
 
 It is well known that men and other animals afHicted with 
 diabetes lose weight rapidly, despite greater appetite and increased 
 food consumption. In the last stage of diabetes in dogs the animal 
 shows greater emaciation than a normal dog at death from lack of 
 food. Dr. Luckhardt studied the gastric tonus and himger con- 
 tractions in two diabetic dogs, and found them persisting and even 
 augmented to within a few hours of death, when the animal is too 
 emaciated and feeble to stand, or to masticate and swallow food. 
 It is true that death from diabetes involves factors that are not 
 present in the normal animal dying from starvation, but dogs 
 dying from pancreatic deficiency have all the appearances of an 
 animal in the most extreme state of emaciation. Nevertheless, 
 there is no gastric atony, and the animal gives evidence of hunger 
 and appetite in his avidity for food to within a few hours of death. 
 
 v. EXPERIMENTS ON RABBITS 
 
 Rabbits succxmib ^o starvation much more rapidly than does 
 man or the dog. Rogers found no indication of depression or rest 
 in the continuous gastric hunger contractions of the starving rabbit 
 until within a few hours of death. Then they became weaker, of 
 shorter duration, and may alternate with periods of quiescence. 
 Shortly before death from starvation the rabbit's stomach may 
 go into periods of strong tetanus, or spasms lasting even for two 
 
144 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 to three minutes. Similar periods of gastric tetanus were observed 
 by Patterson in starving dogs shortly before death. In a normal 
 animal these tetanic contractions of the stomach would give rise 
 to intense hunger pangs, but we CEinnot know what sensation, if 
 any, they produce in the animal in extreme starvation since we 
 have no data concerning this condition in man. In fact, we do 
 
 not even know the motor condition 
 of man's stomach near death from 
 starvation. 
 
 VI. DISCUSSION OF RESULTS 
 
 So far as we are aware, this is 
 the first time that actual records 
 have been taken of the gastric 
 hunger contractions in man during 
 Fig. i7.-Superimposed life-size prolonged starvation; and also the 
 tracings of the stomachs of two adult first time that the physiologists 
 rabbits; the larger represents the themselves have done the Starving, 
 stomach of a rabbit killed after eat- -r. ^ , j_ t j_i 
 
 ing; the smaller the stomach of a ^"^ we have many accounts of the 
 rabbit which died of starvation, but subjective feeling of hunger and 
 had been permitted to eat its own appetite in man during long fasts, 
 eces ( ogers). - ^ comparison of these accounts 
 
 with our own results is rendered difficult by the confusion between 
 the sensations of hunger and of appetite that unfortxmately obtains 
 in physiological and medical hterature. Leaving out the cases com- 
 plicated by water starvation, there appears to be a general agreement 
 that the sensations of hunger and appetite increase during the first 
 few (2 or 3) days, of starvation, and then decrease even to complete 
 abolition. Succi reverted to drugs to deaden the hunger pangs 
 only during the first two days of his 30-day fast. Viterbi, who 
 starved himself to death voluntarily and kept a daily record of his 
 feelings, noted complete absence of hunger after the fifth day. 
 Cetti and Breihaupt did not experience any discomfort from hun- 
 ger after the first few days, but it is not clear that hunger and 
 appetite were altogether lacking. The young man starving for 5 
 days under the observation of Johansson, Landergren, Sonden and 
 
HUNGER IN PROLONGED STARVATION 145 
 
 Tigerstedt complained of weakness, dizziness, and cold, but did 
 not feel particularly hungry at the end of the fast. Carrington 
 cites many cases of men and women in prolonged starvation where 
 hunger sensation subsided or disappeared after the third day. All 
 these persons cited by the last author were, however, suffering 
 from this, that, or the other ailment, and some of them were lying 
 in bed during the entire starvation period. These remarks apply 
 also to various popular accounts of cases of prolonged fasting to 
 cure digestive or nervous disorders. All cases of compulsory starva- 
 tion (persons shipwrecked, explorers and hunters lost, or cut off 
 from supplies, etc.) are usually complicated by lack of water, by 
 the effects of exposure, and by fear, panic, etc., so that the state 
 of the actual hunger sensation cannot be determined. 
 
 In the case of the 31-day fast recently reported by Benedict, 
 the subject, a man forty years old, having had previous training 
 in long fasts, insisted that he felt no hunger at any time during 
 the long starvation. Langfeld thinks that this might have been 
 due to strong auto-suggestion, the subject being a vegetarian and a 
 firm beUever in fasting as a cure-all. If Benedict's man told the 
 truth, there must have been some abnormality in his hunger 
 mechanism, or else he was able to shunt the visceral hunger impulses 
 out of consciousness by hypnosis. Polimanti states that hunger 
 can be induced by suggestion or hypnosis. We doubt the truth of 
 this statement, at least as regards the real gastric hunger; but if it 
 is true it is probable that hypnosis may also inhibit the hunger. 
 
 All these accounts are based on the statements of persons who 
 were in no sense trained observers. In view of that fact, it is 
 probable that the consensus of opinion that hunger disappears 
 after the third day of starvation means no more than that after 
 the third day the hunger sensatioii is not so persistent or painful 
 as to dominate consciousness. 
 
 There was, certainly, some decrease in the hunger and especially 
 in the appetite sensation of the writer, and of Mr. L., on the fourth 
 and fifth days. But it was a decrease, not an absence of hunger 
 sensation. It has already been pointed out that the decrease in 
 intensity of the hunger sensation was not due to a decrease in, 
 
146 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 the intensity of the gastric hunger contractions, but to depression 
 of the central nervous system, or some disturbance in the complex of 
 impulses from proprioceptors. We do not deny the possibility that 
 the sensation of hunger may actually disappear in some persons 
 after two or three days of fasting, but this is not due to starvation 
 as such, but to special conditions, such as prinxary asthenia of 
 the stomach, great cerebral depression, inhibition via the splanch- 
 nic nerves through pain or other factors causing hyperactivity of 
 the sympathetic system, or to copious and continuous secretion of 
 gastric juice causing acid inhibition. In view of our results on 
 experimental animals it seems probable that during periods of 
 prolonged starvation the sensation of hunger will prove most 
 persistent in young and vigorous persons. 
 
 Boldyreff states that the periodic contractions of the empty 
 stomach in dogs become feeble and irregular during prolonged 
 fasting and cease entirely after a fast of 3 to 4 days. After that time 
 there is a copious and continuous secretion of gastric juice. If this 
 spontanjeous secretion of gastric juice is sufficiently rapid, there 
 will, of course, be an acid inhibition of the hunger contractions. 
 
 Only one of our dogs (No. Ill) corroborates the results of 
 Boldyreff. Dog III showed practically no hunger contractions 
 after the third day. The reader will recall that this was the oldest 
 dbg in the series, and that he had shown relatively weak and 
 irregular hunger contractions during the control period before 
 starvation. This fact probably indicates an asthenic condition 
 of the stomach, in addition to the certain factor of age. 
 
 Boldyreff's dogs had duodenal, biliary, and pancreatic fistulae, 
 in addition to the fistula of the stomach. As these animals were 
 thus subjected to greater disturbance of digestion and metabolism 
 than were the dogs used in our starvation tests, it seems probable 
 that the dogs used by Boldyreff were subnormal in respect to 
 some asthenia of the digestive tract. This may be a factor in the 
 early disappearance of gastric hunger contractions during the pro- 
 longed starvation. Multiplication of fistulae also increases the 
 chances for reflex inhibition of the stomach from adhesions, pain, 
 etc. While the difference in Boldyreff's results and our own may 
 
HUNGER IN PROLONGED STARVATION 147 
 
 be due mainly to the difference in the condition of the dogs at the 
 beginning of the hiinger tests, it may also be noted that Boldyrefl's 
 method of registering the gastric contractions was not delicate 
 enough to show the weaker contractions and the variations in 
 tonus. The strong continuous tonus and rapid contractions (type 
 III) which we have designated the "hunger tetanus" would prob- 
 ably not have been recorded on Boldyreff's tracings. It was 
 precisely this hunger tetanus which was mostly in evidence in our 
 normal starving dogs. 
 
 Boldyreff found that during the first three days of starvation 
 there are periods of apparently spontaneous secretion of gastric 
 juice, and that during this secretion the gastric contractions ceased. 
 After the third day the gastric secretion became continuous. We 
 did not subject our dogs to the additional inconvenience of accurate 
 determination of the rate of gastric secretion, but incidental obser- 
 vations in other lines of work on cats with the stomach pouch of 
 Pavlov have convinced us that there may be considerable fluctua- 
 tion in the rate of the secretion of the empty stomach. The 
 secretion of gastric juice must be relatively rapid, however, in 
 order to maintain complete inhibition of the tonus and contractions 
 of the healthy and vigorous stomach through acid stimulation of 
 local and long reflexes. The stomach of the writer, of Mr. L., and 
 of all the dogs was acid throughout the starvation period, which 
 indicates a more or less continuous secretion of gastric juice, even 
 during the first three days of starvation. But the quantity or 
 strength of hydrochloric acid in the stomach at any one time was 
 not sufficient to produce the acid inhibition either in man, dog, 
 or rabbit. 
 
 That starvation in man will ultimately lead to marked weak- 
 ening (and eventually absence) of the sensation of hunger owing to 
 the depression of the central nervous system and asthenia of the 
 gastric motor mechanism is self-evident, but in young and vigorous 
 animals this depression is abse^it imtil the skeletal neuromuscular 
 asthenia is very marked. That prolonged starvation in the case 
 of healthy individuals should completely abolish the sensation of 
 hunger and appetite while the organism is still in fair state of 
 
probably due to pathological complications. Starvation increases 
 the desire for food (that is, hunger and appetite) in wild animals, 
 at least up to the point where the asthenia reaches a degree that 
 renders locomotion impossible. This is shown by the increased 
 boldness and disregard of danger on the part of the starving animal 
 (herbivorous as well as carnivorous) in his search for food. 
 
CHAPTER X 
 
 THE NERVOUS CONTROL OF THE HUNGER MECHANISM 
 
 The question of the nervous control of the gastric hunger 
 mechanism embraces several important physiological problems, 
 none of which are as yet completely solved. 
 
 1. On the motor side we have the possibility of actual initiation 
 of the gastric hunger contractions through the motor fibers in the 
 vagi nerves by impulses from cerebral as well as lower centers 
 acting on the motor nuclei of the vagi in the medulla. Even if 
 contractions are not actually caused in this manner, it can be shown 
 that they are in part dependent on a "tonus" influence exerted 
 on the stomach by the vagi nerves. Hence the control of the 
 vagus tonus becomes a question of paramount importance in the 
 physiology and pathology of hunger. 
 
 2. On the afferent or sensory side we must determine the central 
 paths of the afferent gastric nerves in order to elucidate the genesis 
 of the conscious hunger sensation as well as the conscious and 
 subconscious reflexes evoked by these afferent impulses. This 
 raises the question of the sensory hunger center in the cerebrum. 
 
 3. We have also to deal with the very important reflex control 
 of the gastric hunger mechanism as well as of the nervous foci in 
 the medulla, mid-brain, and cerebrum concerned in the conduction 
 of sensory and motor hunger impulses. ' 
 
 4. And, lastly, we must consider the automatic or reflex ele- 
 ments in the gastric hunger mechanism itself, independent of all 
 central nervous system control. An understanding of these several 
 factors is of particular importance for the interpretation and the con- 
 trol of the changes in hunger and appetite that we meet in disease. 
 
 I. INFLUENCE OF THE CEREBRUM 
 
 I. Ejffed of removal of the cerebrum. — Removal of the cerebral 
 hemispheres in the guinea-pig leads to somewhat increased gastric 
 tonus and himger contractions (Dr. King). In the pigeon this 
 
 149 
 
ISO CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 operation does not change the hunger contractions of the empty- 
 crop, except that visual and auditory stimuli do not lead to inhibi- 
 tion of these movements in the decerebrated bird (Rogers). In 
 frogs removal of the cerebriun has no effect on the himger con- 
 tractions of the stomach (Patterson). Goltz's decerebrated dog 
 showed hunger. We may therefore conclude that in so far as the 
 stomach hunger contractions are dependent upon tonus and motor 
 nervous impulses via the vagi nerves, these impulses do not 
 originate in the cerebral hemispheres. 
 
 2. The gastric hunger mechanism during sleep. — In man (infants 
 as well as adults) the gastric himger contractions are at least as 
 frequent and intense during sleep at night as during the waking 
 state. In our five days' starvation experiment continuous records 
 of the stomach contractions were taken during sleep at night. 
 These records show that the stomach was in strong tonus and 
 hunger contractions practically half of the time of sleeping. The 
 hunger periods were less frequent during the day when the subject 
 was about his work- 
 Numerous experiments on dogs show that the himger contrac- 
 tions and the gastric tonus are more vigorous and regular when 
 the animal is sleeping than when he is awake and taking notice 
 of things about him. The only apparent exception to this condition 
 so far observed in any species is the rumen of the goat. A few 
 observations on one goat seemed to show that the hunger con- 
 tractions of the rumen or first stomach pouch decrease in intensity 
 when the animal is lying down sleeping. We shall not be satisfied 
 that this is so until the same result is obtained on, a number of 
 rimiinants. Possibly the gastric motor part of the vagi nervous 
 apparatus in the ruminating animals is under a more direct control 
 from the cerebrum than is the case in other species. 
 
 During sleep there is decreased activity of the central nervous 
 system in general; decreased tonus of the skeletal muscles; de- 
 creased tonus of the musculature of the blood vessels, at least in 
 certain parts of the vascular system; decreased tonus of the 
 urinary bladder, etc. ; in short, a lowered activity of all the neuro- 
 muscular mechanisms so far investigated. One might have ex- 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 151 
 
 pected that so far as the tonus of the empty stomach depends on a 
 central influence by way of the vagi the gastric tonus and hunger 
 contractions would be diminished during sleep. But instead of 
 being depressed in sleep the hxmger contractions continue with 
 the same vigor as during the waking state, and in many instances 
 with increased vigor. The increase in the gastric hunger con- 
 tractions during sleep may be due to the elimination of all inhibi- 
 tory impulses via the splanchnic nerves. But the absence of 
 depression certainly indicates that the vagogastric tonus mech- 
 anism, at least in man and dog, occupies a unique position in the 
 organism — a degree of independence of afferent impulses (extero- 
 ceptors) and central processes not known in the case of any other 
 neuromuscular apparatus. 
 
 n. EFFECT OF CEREBRAL STATES (EMOTIONAL STATES, 
 INTELLECTUAL PROCESSES) 
 
 In the dog the cerebral processes of joy, fear, anger, eagerness 
 (for food), attention, etc., cause temporary inhibition of the gastric 
 hunger contractions. This inhibition takes place by way of the 
 splanchnic nerves, not by a depression of the vagus tonus. This, 
 again, points to an unusual independence of the vagogastric tonus 
 apparatus. The sight or smell of food on the part of the starving 
 dog does not initiate or augment the gastric hunger contractions.' 
 Dr. Luckhardt has recently shown that when the sleeping dog 
 dreams the gastric hunger contractions are inhibited in the same 
 way that cerebral and emotional processes tend to inhibition of 
 the contraction when the animal is awake. 
 
 In man intellectual processes (attention, reading, figuring, 
 arguing) have no distinct influence on the course of the hunger 
 period. Actual anxiety causes temporary inhibition (probably 
 through the splanchnics). We have not been in a position to make 
 observations on the effect of actual anger, fear, and joy, but there 
 is no reason to believe that these processes act differently in man 
 from that in the dog. In man we have paid particular attention 
 to the effects of seeing and smelling palatable food, as it seemed a 
 priori reasonable that the impulses generated by these stimuli 
 
152 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 might make more intimate connection with the vagogastric tonus 
 apparatus. Cannon assiunes a "pyschic gastric tonus" analogous 
 to the "psychic secretion" of gastric juice. Gliicksmann states 
 that the borborygmi are increased in rate and intensity on seeing 
 and smelling palatable food. He ascribes this to increased gastric 
 contraction. Extensive experiments on Mr. V. and on the author 
 seem to show that this is not the case. These stimuli neither initiate 
 nor augment the gastric tonus and hunger contractions; so far as 
 they influence them at all, it is in the direction of inhibition. One 
 of the tests on the author might be given. Before beginning the 
 five days' starvation period, our colleague. Dr. Luckhardt, was 
 asked to bring in, unknown to the author, a tray of choice food in 
 the midst of a himger period. The arrangements being made the 
 matter was dismissed from the author's thoughts. At one o'clock 
 on the morning of the fourth starvation day the subject was asleep 
 and the record showed him to be in the midst of a period of vigorous 
 and regular hunger contractions. _ He was awakened to behold 
 Dr. Luckhardt and the assistant enjoying a feast of porterhouse 
 steak with onions, fried potatoes, and a tomato salad. The tray 
 of edibles was placed not more than 4 inches from the subject's 
 face, and the dehcious odor of the food filled his nostrils. He felt 
 the hunger pangs as imusually intense, and there was considerable 
 salivation. However, the gastric hunger contractions were not 
 increased either in rate or intensity. In a few minutes, on the 
 contrary, the himger contractions became weaker and the intervals 
 between them greater, and the period terminated by this gradual 
 depression much sooner than it probably would have done in the 
 absence of the dinner scene. This was undoubtedly due to local 
 acid inhibition from copious secretion of appetite gastric juice. 
 
 When the hungry individual sees or smells good food the gastric 
 hunger pangs are more intense, although there is no change or even 
 when there is some decrease in the strength of the gastric hunger 
 contractions. This is therefore a phenomenon of central rein- 
 forcement. 
 
 Our data on normal men and dogs seem incapable of any other 
 interpretation than that the vagogastric tonus apparatus, so far 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 153 
 
 as it concerns the empty stomach, occupies a unique and physiologi- 
 cally isolated position in the way of nervous control, while the 
 inhibitory apparatus via the splanchnic nerves is readily influenced 
 by central and reflex processes. We feel, however, that these 
 observations must be extended to other groups of vertebrates as well 
 as to such pathological cases in man in which there are indications 
 of abnormalities of the vagogastric tonus before final explanations 
 are attempted or speculation indulged in as to the usefulness of this 
 physiological isolation. 
 
 This evidence for the physiological isolation of the hunger 
 mechanism in the way of positive cerebral or central control is of 
 interest in connection with the view that the cravings of hunger 
 and appetite are subjective and largely a matter of habit, and that 
 the periodicity or intensity of these cravings may be altered almost 
 at the will of the individual. Chittenden states this view as follows : 
 
 The so-called cravings of appetite are largely artificial and mainly the 
 lesidt of habit. Anyone with a little persistence can change his or her habits 
 of life, change the whole order of cravings, thereby indicating that the latter 
 are essentially artificial and have no necessary connection with the welfare or 
 needs of the body. The man who for some reason deems it advisable to adopt 
 two meals a day in place of three or four at first experiences a certain amomit 
 of discomfort, but eventually the new habit becomes a part of the daily routine, 
 and the man's life moves forward as before, with perfect comfort and without a 
 suggestion of craving or a pang of hunger. 
 
 Our studies of the hunger mechanism seem to show that the 
 foregoing view is essentially wrong. In the normal individual 
 the gastric hunger periods begin as soon as the stomach is empty 
 and continue (in the absence of inhibitory processes) as long as 
 the stomach is empty, irrespective of the time of day or night, and 
 without reference to the time the individual is accustomed to eat. 
 In individuals accustomed to the usual three meals in daytime and 
 to sleep during the night the gastric hunger periods are more 
 frequent and usually more vigorous during the night (in sleep) 
 than during the day, provided, of course, the stomach is empty. 
 In the normal individual the empty stomach exhibits periodic 
 hunger activity, and there is no evidence to show that this primary 
 automatism of the empty stomach is in the least influenced by 
 
154 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 eating one or by eating five meals a day. The basis for the view 
 that the time of appearance of the "cravings of hunger" can be 
 changed at will is probably to be sought in the fact that the milder 
 hunger contractions do not enter consciousness as pangs of hunger if 
 the individual's attention is directed into other channels. They are 
 felt as hunger pangs if the individual's attention is directed toward 
 food and eating. The attentfon is thus directed, consciously or 
 subconsciously, about the time the individual is accustomed to eat. 
 The periodicity of this subjective attention to the milder hunger 
 cravings can probably be altered by training. But this appKes 
 only to relatively mild pangs of hunger. The more severe " cravings 
 of hunger" caused by the gastric hunger tetanus rise above the 
 limen of consciousness, except in deep sleep or under conditions 
 of cerebral process involving intense interest. When an individual 
 who is accustomed to eat three tim'es a day turns to a regimen of 
 one meal a day, the quantity of food ingested in that one meal is 
 much greater than that at any one of the three meals a day regi- 
 men. The emptying of the stomach and the appearance of the 
 pangs of hunger are correspondingly delayed. The view that 
 prompt appearance and the persistence of the gastric hunger 
 activity in the empty stomach have no relation to the actual need 
 of the individual for food cannot be seriously maintained for the 
 normal animal. 
 
 III. INTLUENCE OF THE LOWER BRAIN CENTERS (mID-BRAIN 
 medulla) on THE GASTRIC HTJNGER CONTRACTIONS 
 
 The most direct and at the same time the least objectionable 
 method of attack on this problem is the section of the extrinsic 
 nerves to the stomach, although this operation abolishes not only 
 all direct influences from the brain of a motor or inhibitory type, 
 but also the central reflexes (motor or inhibitory) that may be 
 called into action through the sensory nerves in the stomach. The 
 splanchnic nerves were sectioned through a median incision. 
 The vagi nerves were sectioned 2 to 3 cm. above the diaphragm, 
 thus leaving the fibers to the esophagus, the heart, and the lungs 
 intact. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 155 
 
 I. Complete section of the splanchnic nerves. — Observations were 
 made on five dogs with complete sections of the splanchnic nerves 
 on both sides. The longest period of observation after the splanch- 
 nic section was two months. Observations were in some cases 
 begun two hours after the operation. When the records of these 
 five dogs are viewed as a whole, it is clear the complete section 
 of the splanchnic nerves in dogs increases the gastric tonus and aug- 
 ments the gastric hunger contractions. The hunger contractions 
 become more rapid and continuous, that is, there is less evidence 
 of the periodic groups with intervening periods of relative quies- 
 cence. It is not uncommon to observe contractions at the rate of 
 about two per minute during an entire observation period of 2 to 4 
 hours. The section of the splanchnic nerves does not abolish the 
 periodicity completely, however. It seems to be a question of 
 relative degree of gastric tonus. If for any reason the tonus of 
 the empty stomach is relatively low on any day, the hunger con- 
 tractions are less frequent, and there is greater evidence of periods 
 of relative quiescence. We desire to emphasize the fact that this 
 conclusion is based on the observations as a whole. Even the dogs 
 with the splanchnic nerves sectioned showed on some days no 
 greater tonus of the empty stomach and no greater rate and per- 
 sistence of the gastric hunger contractions than does the dog with 
 these nerves intact. And occasionally a dog with the splanchnic 
 nerves intact exhibits as great a degree of gastric tonus and rate 
 and persistence of the gastric hunger contractions as the maximum 
 observed in dogs with the splanchnic nerves cut. This is to be 
 expected, as by section of these nerves one eliminates only one 
 (and in the normal animal probably one of the least important) of 
 the factors in the motor activity of the empty stomach. The 
 conditions that affect the stomach through the blood and through 
 the vagi are still subject to practically the same variations as in the 
 animal with the splanchnic nerves intact. 
 
 After complete section of the splanchnic nerves the psychic or| 
 reflex inhibition of the gastric hunger contractions is greatly dimin-1 
 ished. The stimuli that cause anger, fear, pain, joy, or pleasure 
 no longer lead to complete cessation of the hunger contractions. 
 
IS6 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The maximum effect is a slight and transitory weakening of the 
 contractions. It is therefore evident that the inhibitory fibers in 
 
 . the splanchnic nerves (and possibly also the secretory fibers of the 
 adrenals) constitute the main efferent path in this type of inhibition. 
 The sHght degree of inhibition usually in evidence after section 
 of the splanchnic nerves must be due to some central inhibition of 
 the vagus tonus or to action of the few inhibitory fibers in the vagi. 
 Particular attention was given to the effect of seeing and 
 smelling food on the hunger contractions in these dogs with section 
 of the splanchnic nerves, in order to determine whether these 
 stimuli augment the tonus of the vagi and thus increase the hunger 
 contractions. The results were negative. Even with the greater 
 part of the extrinsic inhibitory fibers to the stomach eliminated, the 
 sight, smell, and taste of food not only fail to inhibit or augment 
 the gastric hunger contractions, but, so far as these stimuli affect 
 the stomach at all, it is in the direction of inhibition of the hunger 
 movements. The apparent increase in the intensity of the himger 
 pangs in man on seeing or smelling palatable food must therefore 
 be essentially a central phenomenon of "facilitation" or Bahnung. 
 2. The section of the vagi.- — ^Section of both vagi in the chest was 
 made in three dogs, and after this operation observations on the 
 gastric hunger contractions were continued for from two weeks to 
 three months. Observations were made in some cases two hours 
 after the vagi section. 
 
 Section of the vagi leaves the empty stomach on the whole per- 
 manently hypotonic; that is, at least for a period of up to three 
 months after the operation. The tonus of the empty stomach in 
 these dogs varies somewhat from day to day, and occasionally the 
 tonus may approach that' of a dog with the vagi intaict, but on 
 
 /'the whole the tonus is permanently much lower than normal. 
 This is evident, not only from the observations by means of the 
 balloon in the gastric cavity, but also on direct inspection and by 
 palpation (introducing the finger through the fistula). 
 
 The hunger contractions of the empty stomach are changed 
 
 .-mainly in rate and regularity. The duration of each individual 
 contraction is about normal, or on the whole less than normal. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 157 
 
 The long-drawn-out contractions or tetanus are rarely seen. But 
 the intervals between the contractions vary on the whole from 
 2 to 5 minutes or even up to 8 minutes. The strength, or rather 
 the amplitude, of the individual contractions may appear greater 
 than normal, evidently because the contractions start rather sud- 
 denly and without any marked prehminary increase in tonus, and 
 the maximal contractions are evidently so complete that all the air 
 is forced out of the balloon. These contractions may continue of 
 fairly tmiform amplitude and rate for 2 to 3 hours, that is, during 
 a whole observation period. The contractions vary in strength 
 and rate from day to day, and on some days they may be completely 
 absent during the entire observation period (2 to 4 hours). 
 
 The periodicity of the hunger rhythm is, on the whole, obscured, 
 except on the days when the gastric tonus approached that in 
 normal dogs. On such days the contractions appear at shorter 
 intervals, and tend to fall into groups similar to those in normal 
 dogs. Periods of gastric hunger contractions of normal rate and 
 intensity have been observed as early as 12 hours after complete 
 section of the vagi in the chest. The period of most powerful 
 himger contractions so far observed in any dog was recorded in one 
 dog 24 hours after the vagi section. The dog had during the four 
 weeks preceding the vagi section showed almost invariably the 
 type II rhythm. It was therefore a dog with unusually intense 
 gastric motor activity. The complete section of the vagi causes 
 on the whole less depression in dogs that exhibit great hunger 
 contractions while the vagi are intact. The variations in the rate 
 and intensity of the gastric hunger contractions in different dogs 
 are therefore primarily due to individual variations in the condition 
 of the stomach rather than to variations in the central innervation 
 or the central inhibition. 
 
 In the dogs with the vagi sectioned, but the splanchnic nerves 
 intact, the "psychic" or reflex inhibition of the gastric hunger 
 contractions is still in evidence, but the inhibition appears not to 
 be so marked as when the vagi are intact. Accurate comparisons 
 are, however, difl&cult to make because of the lowered tonus and 
 the usual long intervals between the hunger contractions after 
 
IS8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 section of the vagi. We expected an augmentation of the inhibition 
 through the splanchnics after the vagi section. Instead of finding 
 this to be the case, there actually appeared a gradual diminution 
 in the influence of the splanchnic nerves on the empty stomach in 
 the dog observed for 3 months after section of the vagi. It was 
 not due to the regeneration of the vagi fibers, and consequent 
 restoration of the vagus tonus. If further work should establish 
 this as a fact, we should have a significant instance of physiological 
 readjustment — either an actual diminution in the inhibitory im- 
 pulses through the splanchnics in consequence of a dynamic 
 readjustment in the central nervous system, or else an increased 
 resistance ("tolerance") to the splanchnic impulses on the part of 
 gastric motor mechanism. It is also evident from this experiment 
 that if adrenalin is a factor in the inhibition of the gastric contrac- 
 tions via the splanchnic nerves, section of the visceral branches of 
 the vagi^leads to a decreased output of this substance from the 
 adrenal gland under the influence of the splanchnic nerves. 
 
 3. Section of both splanchnic and both vagi nerves. — Complete 
 sections of the splanchnic and vagi nerves were made on four dogs 
 and observations made on the gastric hunger contractions for 30 to 
 60 days after the operation. The sections of the splanchnic nerves 
 were made 7 days after the section of the vagi. After this complete 
 isolation of the dog's stomach from the central nervous system, 
 there is practically a permanent hypotonus of the stomach except 
 under conditions of prolonged starvation. The gastric hunger 
 contractions are much the same as when the vagi alone are severed. 
 The contraction^ are usually of great amplitude, but the intervals 
 between the contractions are frequently longer than in normal dogs. 
 The grouping of the contractions in periods is usually in evidence. 
 These contractions of the isolated and empty stomach were present 
 10 to 20 hours after the vagi section, and there was some improve- 
 ment in the rhythm or an approach toward the normal tonus and 
 contraction rate during the 30 to 60 days of observation. On the 
 whole, the hunger contractions of the isolated stomach conform 
 to type I. The type II is rare except during prolonged starvation. 
 Short periods (2 to 3 minutes) of incomplete tetanus are frequently 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 159 
 
 seen, especially during prolonged starvation, and during the first 
 half of the hunger period. It is therefore clear that all the essential 
 characteristics of the hunger contractions of the empty stomach 
 are determined by the local gastric mechanisms rather than by the 
 character of the central iimervation or the central inhibition. 
 
 Cannon has reported observations on the effects of vagi and 
 splanchnic section on the gastric movements of digestion in cats. 
 Section of the splanchnic nerves did not affect the movements of 
 digestion; section of the vagi caused slowing and weakening of 
 the peristalsis of digestion, but the normal rate of peristalsis was 
 practically restored in a few days. Combined vagi and splanchnic 
 section left the digestive movements of the stomach practically 
 normal, even shortly after the operation. It seems that section of 
 the vagi or complete section of the vagi and the splanchnic nerves 
 in dogs causes on the whole a greater change in the movements of 
 the empty stomach than does the same lesion in cats in case of the 
 movements of the filled stomach. This probably means that the 
 tonus of the vagi plays a greater r61e in the movements of the 
 empty than in the niovements of the filled stomach. For it is not 
 likely that there is such marked difference in the relative importance 
 of the vagi nerves in cats and dogs. 
 
 The changes in the character of the gastric hunger contractions 
 after isolation of the stomach from the central nervous system 
 seem primarily due to the persistent hypotonus. This is indicated 
 by the fact that on days when the stomach of a normal dog shows 
 relatively slight tonus the himger contractions approach the type 
 shown by the isolated stomach, and on days when the isolated 
 stomach exhibits tonus approaching that in normal dogs the hunger 
 contractions tend to assume the normal type. Occasionally records 
 are obtained from the empty and isolated stomach that practically 
 demonstrate the above point. During a period of relatively slow 
 hunger rhythm the tonus for some unknown reason may increase 
 markedly for periods of varying length, and during these periods 
 the hunger contractions are identical in rate and character with 
 those of the intact stomach in normal (strong) tonus. In one of 
 the dogs with the vagi and splanchnic nerves sectioned six days 
 
i6o CONTROL OF/ HUNGER IN HEALTH AND DISEASE 
 
 of fasting led to the appearance of periods of very great gastric 
 tonus, and during these periods (virtually periods of incomplete 
 tetanus) the gastric contractions assumed the form of type III. 
 
 However, the details of the changes in the himger rhythm 
 after isolation of the stomach from the central nervous system 
 seem of minor importance in this connection. The essential point 
 is that since the empty stomach, completely isolated from the 
 central nervous system, does exhibit the typical himger contrac- 
 tions, the primary role of the gastric nerves is that of modifying 
 or regulating essentially automatic mechanisms in the stomach waU. 
 In other words, the extrinsic nerves to the stomach play a r61e 
 similar to that of the nerves to the heart in the regulation of the 
 heart rhythm. Further analysis of the hunger mechanism miist 
 be directed primarily to the intrinsic neuromuscular apparatus of 
 the stomach, and secondarily to the factors that control the vagus 
 tonus. 
 
CHAPTER XI 
 
 THE NERVOUS CONTROL OF THE HUNGER MECHANISM 
 
 (Continued) 
 
 I. INHIBITION FROM THE MOUTH IN MAN AND OTHER ANIMALS 
 
 Our gastric fistula man, Mr. V., offers an exceptional oppor- 
 tunity for studying the relations of certain conscious states, par- 
 ticularly those associated with foods and with eating, on the 
 activities of the empty stomach. The esophagus is completely 
 closed at the level of the upper end of the sternum, so that nothing 
 can enter the stomach from the mouth. The swallowing mechan- 
 isms are normal, and the man can swallow and hold in the eso- 
 phageal pouch about 25 c.c. of material. The gustatory (and 
 olfactory) sense is normal. The senses of thirst and hunger are 
 normal. He masticates his food in the usual way, and the chewing 
 processes are accompanied by the normal conscious states. The 
 masticated food is placed in a syringe and introduced into the 
 stomach through the fistula, which does not involve any pain or 
 discomfort, and the man is adjusted to this condition, as this has 
 been his method of feeding for the last twenty years. Because of 
 the ample size of the gastric fistula the man may sit down at the 
 dinner table, see, smell, taste, and chew his food in the usual man- 
 ner up to the point of introducing the food through the fistula, 
 while tracings are being taken of a tonus and the movements of 
 the stomach, and records made of the secretion of the gastric juice. 
 
 We know, particularly through the researches of Pavlov on 
 dogs, and from many observations on man, that when appetite is 
 present the sight, smell, taste (especially taste) of palatable foods 
 causes a reflex secretion of gastric juice, the so-called "psychic 
 secretion." The efferent nerve-fibers for this reflex reach the 
 stomach through the, vagi. The more recent work of Cannon and 
 others has demonstrated that the tonus of the stomach musculature 
 is also primarily dependent on efferent nervous impulses through 
 
 161 
 
i62 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 the vagi. A certain degree of tonus is normally a prerequisite for 
 peristalsis or contractions in the empty stomach. The suggestion 
 is therefore obvious that the same stimuli which lead to psychic 
 secretion of gastric juice may at the same time cause an augmenta- 
 tion of the tonus and the contractions of the stomach musculature. 
 Caimon postulated such a "psychic tonus," but no evidence for 
 its existence has been recorded. 
 
 It is a universal experience of normal persons that the sight or 
 smell (or even the memory) of palatable foods seems to induce 
 hunger and appetite, or intensify these sensations if they are already 
 present. The simplest explanation of this fact would be that the 
 smell or taste of palatable foods initiates or augments the stomach 
 contractions, thus increasing the hunger sensation by increasing the 
 intensity of the gastric stimulation. The facts, at least in man and 
 dogs, are the very opposite of those demanded by this hypothesis. 
 
 There are two sources of error in experiments of this character. 
 In the first place, the periods of contraction of the empty stomach 
 vary in intensity and duration, and the intervening periods of 
 relative quiescence vary in length. The periods of quiescence may 
 be interrupted by occasional contractions. This being the case, 
 the initiation of stomach contractions simultaneously with tasting 
 palatable food during quiescence of the stomach, for example, may 
 be a mere coincidence. An augmentation of the contractions 
 seemingly due to tasting food during a contraction period may 
 simply be the usual increase in strength of the stomach contraction 
 during such period. In the same way, if tasting food toward the 
 end of a contraction period should be followed by cessation of 
 the stomach contractions, this apparent inhibition may be a coin- 
 cidence, the cessation of the contractions being "spontaneous" 
 and not casually connected with the tasting of food. These diffi- 
 culties were realized before the work was undertaken, as it was 
 preceded by an extended survey of the "spontaneous" stomach 
 movements when not interfered with experiinentally. Because of 
 the variabiKty of the "spontaneous" stomach activity, the indi- 
 vidual test must be repeated a great nimaber of times, and httle 
 or no significance can be ascribed to exceptional results. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 163 
 
 A source of error, more serious because not so readily controlled, 
 lies in certain subjective states of an inhibitory character. Pavlov 
 found that while the sight and smell of palatable foods ordinarily 
 caused "psychic" secretion of gastric juice in dogs when hungry, 
 if the dogs knew from past experience that they were not to be 
 permitted to eat the food, the same stimuli caused no secretion. 
 We may have analogous conditions in regard to the stomach tonus 
 and movements. It is possible that, no matter how great the 
 hunger or appetite in man, the knowledge that the seeing, smelling, 
 or tasting food was part of an experiment might initiate cerebral 
 processes of an inhibitory character. This source of error has been 
 controlled in -two ways: (i) in Mr. V.'s case the mastication or 
 tasting food was made part of his ordinary routine in preparing 
 the food to be put into the stomach, and the man knew that as 
 soon as the food was prepared it would be introduced into the 
 stomach in the usual way; (2) records were made of the presence 
 or absence of the psychic secretion of gastric juice. If the tasting 
 and chewing of food start a copious flow of gastric juice, we can 
 infer that the tasting and chewing do not give rise to cerebral 
 processes of an inhibitory character. 
 
 I. Inhibition of the hunger contractions of the empty stomach by 
 stimulation of the gustatory end organs in the mouth. — The substances 
 used for stimulation were sugar (solid and in solution), quinine in 
 weak solution, sodium chloride (solid and in solution), weak solu- 
 tions of acetic and hydrochloric acids. Tests were made at all 
 stages of activity of the empty stomach. The results were uniform 
 and practically identical for the four kinds of stimuli employed. 
 If the substances were used in suflicient concentrations to affect 
 the stomach activity, the effects were inhibition of the tonus and 
 contractions. These inhibitory effects follow promptly on placing 
 the substances in the mouth, and disappear, on the whole, very 
 soon after removing the substances from the mouth and rinsing 
 the mouth with warm water. Quinine and the acid produced the 
 longest inhibitory after-effects, probably because of the difficulty 
 in completely removing these substances by rinsing the mouth 
 with water. 
 
i64 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 This gustatory inHbition is, oi^ the whole, proportional to the 
 strength of the stimuli (i.e., the concentration of the substance) 
 and varies inversely with the degree of the stomach activity. Thus 
 a weak solution of acetic acid that produced distinct inhibition 
 during the first stage of a period of hunger contraction when the 
 individual contractions are relatively weak may have little or no 
 effect when placed in the mouth during the tetanus stage of the 
 contractions. 
 
 If the gustatory stimuli are weak and allowed to act in the 
 mouth for 5 to 15 minutes, the stomach "escapes" from the inhibi- 
 tion gradually. This is practically true of sweet (sugar). Moder- 
 ate strength of acids and quinine may hold the stomach in nearly 
 complete inhibition up to 15 minutes. The stimulating substances 
 are, of course, gradually diluted by the secretion of saliva. 
 
 Are these gustatory inhibitions primary and relatively simple 
 reflexes independent of the states of consciousness, or are they of 
 the type of conditional reflexes, and therefore due to cerebral states 
 of unpleasant affective tone ? This question must be answered by 
 experiments on lower animals with less development of the cere- 
 briun and especially on decerebrated mammals and on so-caUed 
 "acephalic" infants. 
 
 2. Inhibition of the tonus and the contractions of the empty stomach 
 by chewing indifferent substances. — -We have been unable to obtain 
 any definite evidence of inhibition of the stomach movements by 
 the movements of mastication when the mouth is empty. But 
 chewing what may be called indifferent substances, such as parafl&n, 
 gimi, or straw, produces distinct inhibition. Most of the experi- 
 ments were made by chewing parafl&n. Most people can chew 
 paraflSn without any sensation of a disagreeable or unpleasant tone, 
 or of a pleasant tone, either, for that matter. Mr. V. said he "did 
 not care for the parafl&n," naturally. But he has no dislike for it. 
 The chewing of indifferent substances produces, on the whole, less 
 inhibition than do gustatory stimuli. The stomach "escapes" 
 from the inhibition in a few minutes, even though the chewing is 
 continued with uniform vigor. The chewing usually fails to pro- 
 duce any effects in the tetanus stage of the stomach activity. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 165 
 
 Inasmuch as the masticatory movements do not cause inhibition 
 if the mouth is empty, we may conclude that inhibition produced 
 by chewing indifferent substances is initiated by mechanical 
 stimulation of afferent nerve-endings in the mouth. 
 
 3. Inhibition of the tonus and the hunger contractions of the empty 
 stomach by chewing palatable foods when hunger and appetite are 
 present. — ^Tests were made with all food substances 'palatable to 
 Mr. V. and during all stages of gastric tonus and contractions, 
 which imply all degrees of hunger and appetite. But most of the 
 experiments were made with meats in the form of stews, fricassees, 
 or pot roasts, fried eggs, and crackers or bread soaked in milk, 
 soups, or meat gravy. The results are uniform without exception. 
 Chewing or tasting palatable foods inhibits the tonus and the move- 
 ments of the empty stomach. The inhibition is in evidence within 
 a few seconds after placing the food in the mouth, and may or may 
 not continue for some time after removing the food from the mouth 
 and rinsing the mouth with warm water. The inhibition is least 
 in evidence during the hunger tetanus. In fact, we are uncertain 
 whether the chewing of palatable foods is able materially to affect 
 the stomach in hunger tetanus. It is dif&cult to determine whether 
 cessation of the hunger tetanus that follows — ^usually not very 
 promptly — the placing of palatable food in the mouth is a " spon- 
 taneous" cessation, or due to inhibition from the mouth. The 
 records show, however, that so far as the stimuli in the mouth 
 affect the processes of the hunger tetanus, the influence is in the 
 direction of inhibition. 
 
 The inhibition of the motor activity of the stomach by chewing 
 palatable foods does not appear to have any after-effects in the 
 nature of increased tonus or contractions. Some of the tracings 
 do suggest a motor after-effect,' but we are inclined to interpret 
 them in a different way. These effects are obtained only when the 
 tests are made during the relative quiescence of the stomach or at 
 the beginning of a contraction period ("30-seconds rhythm"). 
 Moreover, these results were not always secured even during these 
 periods. It would therefore seem that these apparent augmentary 
 after-effects represent the "spontaneous" initiation of a contraction 
 
I 
 
 1 66 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 period, or the gradual increase in the magnitude of the contrac- 
 tions characteristic of the periods of the 30-seconds rhythm. 
 
 4. Factors involved in the inhibition of the contractions of the 
 empty stomach by palatable foods in the mouth. — Boldyreff has reported 
 that the contractions of the empty stomach in the dog cease during 
 the periods of "spontaneous" secretion of gastric juice. We know- 
 that tasting or chewing palatable foods leads to reflex or "psychic" 
 secretion of gastric juice in mammals (includiag man). May not 
 the inhibition described above be an indirect one, due to the 
 secretion of gastric juice, rather than a reflex inhibition of more 
 direct character ? This question has been investigated and settled. 
 A rapid secretion of gastric juice is associated with cessation, 
 partial or complete, of the stomach contractions in Mr. V. We 
 shall show later that this is due, not to the processes of secretion, 
 as such, but to acid stimulation of nerve-endings in the mucosa. 
 When the chewing or tasting of palatable foods leads to copious 
 secretion of gastric juice, this gastric juice is one factor in the 
 accompanying inhibition of the stomach movements. 
 
 We know, from Pavlov's work on dogs, that the latent period 
 of the "psychic " secretion is about 5 minutes. The latent period of 
 the "psychic" secretion in man is shorter (2 to 3 minutes). The 
 inhibition of the stomach tonus and movements follows within a 
 few seconds after placing the food in the mouth. Hence it is not 
 an acid inhibition from the stomach. The same thing can be shown 
 when the tasting or chewing of the food produces only a scanty 
 secretion of gastric juice. The inhibition appears in the normal 
 way, and the concentrations reappear on removing the food from 
 the mouth despite the slow secretion of gastric juice. 
 
 It seems that a certain quantity of gastric juice must accumulate 
 in the stomach or the free hydrochloric acid in the stomach must 
 reach a certain concentration before the acid inhibition takes place. 
 Thus, if the period of chewing or tasting the palatable food is short 
 (4 to 6 minutes), the stomach contractions may reappear at the 
 end of the stimulation in the mouth, and shortly afterward again 
 be inhibited by the acid gastric juice. This inhibition continues 
 during the phase of rapid "psychic" secretion. When the psychic 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 167 
 
 secretion is more copious, the reflex inhibition from the mouth 
 merges into the acid inhibition from the stomach. 
 
 5. Inhibition of the tonus and the hunger contractions of the empty 
 stomach by swallowing movements. — It has been shown by Cannon 
 and Lieb for the dog that the movements of swallowing lead to a 
 temporary inhibition of the tonus of the stomach. This inhibition 
 is designated the "receptive relaxation" of the stomach. This 
 inhibition is readily demonstrated in man. When Mr. V. makes 
 repeated swallowing movements with only enough saliva in the 
 mouth to initiate the swallowing reflex, a prompt but transitory 
 inhibition of gastric tonus and contractions is produced. The 
 reader will recall that the swallowed saliva does not reach the 
 stomach, but collects in the esophagus pouch. Complete inhibi- 
 tion of the stomach contractions was never secured through the 
 swallowing act, and when the stomach is in the condition of hunger 
 tetanus, or in very strong and rapid contractions bordering on 
 tetanus, the mere swallowing movements seem to have no effect 
 on the stomach. The inhibition of the stomach tonus due to the 
 act of swallowing is most readily demonstrated at the beginning 
 of a period of hunger contractions. 
 
 6. Relation of the reflex inhibition of the tonus and the movements 
 of the empty stomach from the mouth to the sensation of hunger. — The 
 stimulation of the gustatory end organs in the mouth, the chewing 
 of indifferent substances, and the tasting and chewing of palatable 
 foods would abolish the sensations of hunger to the same degree 
 that these measures inhibit the stomach contractions. The inhibi- 
 tion of the stomach activity and the cessation of the hunger pains 
 run parallel. This conclusion is based on experiments on a number 
 of men besides Mr. V. 
 
 In the dog, food or other substances in the mouth cause inhibition 
 of the hunger contractions of the stomach. But since these manipu- 
 lations disturb the animal and induce salivation, and in many cases 
 swallowing movements, the precise mechanism of the inhibition 
 must remain in doubt until it can be investigated on dogs from which 
 the cerebrum has been removed, since most of the dog's cerebral 
 processes (pleasant or unpleasant) induce the same inhibition. 
 
i68 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 In the rabbit, the sight, smell, or taste of food, or the chewing 
 (without swallowing) of such foods as cherries, carrots, apples, 
 carrot leaves moistened with sugar, acid, or quinine do not inhibit 
 the stomach contractions (Rogers). The same is also true for the 
 guinea-pig (Dr. King) . In the case of the single goat so far studied, 
 the chewing of ordinary food (hay, oats, carrots) appeared to 
 increase rather than decrease the hunger contractions of the rumen. 
 
 In the pigeons, Rogers ehcountered the same difficulties that we 
 met in the dogs. Any disturbance of the normal pigeon inhibits 
 the hunger contractions of the empty crop. And since it is not 
 possible to put food or other substances in the mouth of these birds 
 without more or less disturbance by the handling, we cannot be 
 sure that the resulting inhibition proceeds from stimulation of 
 nerves in the mouth. In the decerebrated bird, visual and auditory 
 stimuli do not inhibit the crop, but handling the bird, as in feeding 
 or placing anything in the mouth, causes inhibition. If the dis- 
 turbing factors other than the mouth stimulation could be elim- 
 inated, it is likely that the mouth stimulation alone would cause 
 little or no inhibition unless accompanied by swallowing. 
 
 In the frog, stimulation of the nerve-endings in the mouth by 
 food substances, acids, or alkalies cause little or no inhibition of 
 the empty stomach. This is true whether the frog is normal or 
 decerebrated (Patterson). 
 
 It is thus evident that the marked reflex inhibition of the gastric 
 hunger contractions from mechanical and chemical stimuli acting 
 in the mouth of man is much less in evidence, although not entirely 
 absent in the lower mammals, birds, and frogs. This leads us to 
 suspect that in man and the higher animals, where this reflex is 
 preponderant, it involves conscious cerebral processes. The ques- 
 tion could possibly be settled by experiments on infants (normal 
 and acephaUc) and on persons in very deep sleep. 
 
 II. THE INFLUENCE OF STIMULATION OF THE GASTRIC MUCOSA 
 ON THE HUNGER CONTRACTIONS OF MAN 
 
 The character of the periodic and continuous motor activity 
 of the empty stomach in man and other animals has been described. 
 It has also been shown that the contractions of the empty stomach 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 169 
 
 give rise to the sensation of hunger or the "hunger pangs" by 
 stimulation of afferent nerve-endings in the gastric mucosa. We 
 have also seen that in man the hunger contractions of the stomach 
 are inhibited, reflexly, by all stimuli acting on end organs of taste 
 and general sensations in the mouth cavity, so that in case of 
 chewing palatable foods when in hunger we have the so-called 
 psychic secretion of gastric juice preceded and paralleled by a psy- 
 chic inhibition of gastric motility and tonus. It has also been 
 shown that the hunger contractions persist in their essential char- 
 acter after section of the nerves connecting the stomach with the 
 central nervous system. If we are to attempt to determine more 
 specifically the cause of the hunger contractions our attention 
 must be directed to the stomach itself. The contractions of the 
 empty stomach may be due to any one of these four conditions. 
 
 I. CONDITION OR STIMULATION OF THE GASTRIC MUCOSA 
 
 The absence of food means absence of mechanical stimuli and 
 cessation or diminution of the secretion of gastric juice, and hence 
 a diminished acidity. Carbon dioxide may be secreted into the 
 empty stomach and may act as the primary stimulus. Carbon 
 dioxide and other gases may enter the stomach from the intestines 
 and act as stimuli. Succus entericus, pancreatic juice, and bile 
 may enter the stomach and act as the primary stimulus through 
 alkalinity or by means of specific substances, such as the bile acids. 
 The reader will recall that a number of workers maintain that bile 
 facilitates the intestinal movements. 
 
 2. CONDITION OF THE BLOOD, SUCH AS THE RELATIVE CONCENTRATION 
 OF NUTRIENT SUBSTANCES, TISSUE METABOLITES, AND HORMONES 
 
 It is possible that the neuromuscular apparatus of the stomach 
 is specially sensitized to slight variations in these substances. While 
 we recognize the condition of the blood as a possible factor, it does 
 not seem a probable one; in the first place, because the composition 
 of the blood is on the whole more constant than the composition of 
 the tissues, and because in young and vigorous individuals the 
 hunger contractions of the stomach begin as soon as the stomach 
 is empty and while digestion and absorption are still in progress 
 
I70 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 in the intestines, so that there can be no lack of nutrient substances 
 in the blood. In view of the relative constancy of the composition of 
 the blood as shown by all past work on the blood serum and blood 
 plasma, the existence of a periodic fluctuation in the concentration 
 of any one substance in the blood parallel with the periodicity of the 
 hunger contractions seems improbable. 
 
 3. MOTOR NERVOUS IMPULSES THROUGH THE VAGI 
 
 It is well known that the tonus of the stomach depends, in part, 
 
 on impulses from the vagi, and that the stimulation of the peripheral 
 
 end of the vagi induces strong contractions in the stomach, whether 
 
 \ empty or filled with food. It is also known that the stomach is 
 
 , capable of carrying out the movements of digestion to a fair degree of 
 
 ( \ efficiency after section of both the vagi and the splanchnic nerves. 
 
 \In other words, the neuromuscular apparatus of the stomach seems 
 
 to be primarily automatic as regards the genesis of the movements 
 
 of the digestion. 
 
 The experiment of sectioning the vagi does not prove this point, 
 however. The experiment does prove the plasticity of the gastric 
 motor mechanism. One would expect that the extrinsic gastric 
 nerves bear the same relation to the movements of the filled and of 
 the empty stomach. This phase of the problem cannot be studied 
 in man. If it should develop that the periodic hunger contractions 
 of the empty stomach are caused by periodic discharges through 
 the vagi, the ultimate question of the cause of hunger would again 
 become a problem of physiology of the central nervous system. 
 
 4. PRIMARY AUTOMATICITY OF THE LOCAL NEUROMUSCULAR 
 MECHANISM OF THE STOMACH 
 
 This can be established only by exclusion of the three other 
 possibilities outlined above. A primarily automatic mechanism 
 might still be influenced by the blood, by the extrinsic nerves, and 
 by local reflexes from the gastric mucosa. The periodicity of the 
 automatic activity might be due, not to a parallel periodicity in 
 any essential stimulus, but to some pecuUarity in the metabolism 
 of the stomach developed as a special adaptation, similar to peri- 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 171 
 
 odicity in other organs. The absence of the hunger contractions 
 during digestion, or possibly the modification of the hunger con- 
 tractions into the movements of digestion, must, in this case, be 
 due to specific inhibitory or regulatory impulses from the gastric 
 mucosa. 
 
 Mr. V. is admirably adapted for determining the relation of 
 stimulation of the gastric mucosa to the hunger movements, as the 
 fistula is large enough to permit the balloon and connecting tube, 
 and a tube for the introduction of liquids and gases, to be placed 
 in the stomach simultaneously. The liquids and gases can be 
 introduced with or without the man's knowledge. Furthermore, 
 the contents of the stomach (fluid and gas) can be withdrawn for 
 analysis at any stage of the hunger movements and without any 
 material disturbance. But the results first obtained on Mr. V. 
 have been abundantly confirmed on other individuals. This can 
 be done by simply introducing a small tube into the stomach in 
 addition to the balloon with tube connection, so that substances 
 can be put into the stomach without touching the mouth or 
 esophagus. 
 
 I. The action of water. — Water, at body temperature, or nearly 
 ice cold, inhibits the tonus and the hunger contractions of the 
 stomach. The inhibition following the introduction of a glass of 
 water (100 to 200 c.c.) directly into the stomach lasts on the whole 
 only 3 to 5 minutes, and is never followed by any augmentation of 
 the tonus or the hunger contractions. The cold water causes 
 greater inhibition than the water at body temperature. If the 
 water is introduced into the stomach during very intense hunger 
 contractions ("hunger tetanus"), there may be no perceptible 
 inhibition. In other words, the degree of inhibition by water in 
 the stomach is inversely proportional to the intensity of the hunger 
 contractions present at the time the water is introduced. Water, 
 warm or cold, introduced directly into the stomach during the 
 period of relative relaxation and quiescence does not increase tonus 
 or initiate a contraction period. 
 
 The statement that cold water causes on the whole greater 
 inhibition than water at body temperature requires the following 
 
172 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 1 
 
 Fig. i8. — Records of gastric hunger contractions of Mr. V. A, a.txa. teaspoonful 
 of sugar was put in the mouth; at X' the sugar was rinsed out with warrtf water; 
 showing inhibition of the stomach contractions by stimulation of end organs for the 
 sense of sweetness. One-half original size. B, at X a, teaspoonful of table salt was 
 put in the mouth; at X' the salt was rinsed out with warm water; showiiig inhibition 
 of the stomach contractions. One-half original size. C, at X 15 c.c. weak acetic acid 
 was put in the mouth; at X' the mouth was rinsed with warm water; showing inhibi- 
 tion of the stomach contractions. One-third original size. D, X-X', vigorous chewing 
 of paraflBn; showing inhibition of the hunger contractions of the stomach by chewing 
 i ndifferent substances. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 173 
 
 qualification. The record of the stomach movements was taJcen 
 by means of an air-inflated balloon in the stomach cavity. Now, 
 when cold water is introduced the water surrounds the balloon, at 
 least partly, and cools the air in the balloon. This itself will lower 
 the tension somewhat, until the temperature is restored to that of 
 the body by the warming of the water or by the passing of the 
 water into the intestine. We do not think that this is a serious 
 
 wv/ 
 
 \\0if^i^^*»m4fMim 
 
 Wj^ WvvJ,*J«hJ*^^ 
 
 -^WMMTWaui, 
 
 MlWJ « ..<i « -tM 
 
 Fig. 19. — A, record of the contractions of the empty stomach of Mr. V. At X 
 100 c.c. cold water introduced directly into the stomach; showing the temporary 
 inhibition. About two-thirds original size. B, records from the empty stomach of 
 A. J. C. At X introduction of 15 c.c. brandy in 25 c.c. warm water directly into the 
 stomach; showing the alcohol inhibition of the hunger contractions. C, record of the 
 contractions of the empty stomach of Mr. V. At X 25 c.c. of himian gastric juice 
 (V.'s own gastric juice, psychic secretion, secured 2 hours previously) introduced 
 into the stomach; showing the acid inhibition. About one-half original size. D, 
 record from the empty stomach of dog with gastric fistula. At X 25 c.c. of 0.5 per 
 cent HCl (warm) introduced directly into stomach; showing the prolonged acid 
 inhibition, with gradual recovery^ Total time of the part of the tracing reproduced, 
 30 minutes. About one-half original size. 
 
174 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 source of error for this reason. A few experiments were made with 
 water at 50° C. This causes greater inhibition than when the water 
 is at 38° C. Water at 50° C. will, of course, increase the air tension 
 in the balloon, yet the inhibition of the stomach tonus and move- 
 ments is sufficiently marked to mask the effect of slight warming 
 of the air. 
 
 How does water in the stomach produce this temporary inhibi- 
 tion ? It goes without saying that in these experiments the water 
 was not introduced fiast enough to cause contractions by distension 
 of the stomach wall, although this occurred unavoidably in a few 
 instances. The only possible ways that water at body.temperature 
 can stimulate the nerve-endings in the mucosa seem to be (i) by 
 mechanical pressure, (2) by osmosis, or (3) by changing the chemical 
 equilibrium of the content of the stomach. Cessation of the inhibi- 
 tion probably marks the passing of the water out of the stomach into 
 the intestine or the addition of sufficient salts to prevent stimu- 
 lation by h5^otonicity. The greater inhibitory action by cold 
 water and by water above the body temperature is evidently to 
 stimulation of the protopathic temperature nerve-endings in addi- 
 tion to those acted on by pressure and osmosis. 
 
 It is clear that the action of water on the stomach mucosa is 
 in the direction of inhibition of the hunger contraction. How can 
 this be reconciled with the view that a glass of cold water induces 
 or augments hunger ? It is to be remembered that in these experi- 
 ments the water had no chance to act on the nerve-endings in the 
 mouth and the esophagus. The alleged action of cold drinks on 
 hunger and appetite is probably the reflex effects (cold) from the 
 mouth and esophagus. In the writer's own case a glass of ice water 
 causes increased muscular tonus, sometimes even to the point of 
 shivering and formication. This increased kinesthetic sense prob- 
 ably acts in the way of Bahnung for the hunger sensation, if it is 
 not actually a part of the himger complex. Cannon and Wash- 
 burne suggest that the effect of a cold drink on the hunger sensation 
 is due to "the power of cold to induce contraction in smooth 
 muscle." Although their meaning is not clear to us, they probably 
 have in mind the contraction of the stomach musculature. This 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 175 
 
 could not come about by the cold acting on the stomach muscula- 
 ture directly. The reflex ef3fects of cold water from the mouth and 
 esophagus are very complicated as regards the stomach, while cold 
 water acting on the gastric mucosa directly causes inhibition, and 
 cooling the frog's stomach causes depression and atony in proportion 
 to the degree of cooling. 
 
 2. The action of acids. — ^AU acids, or liquids containing acids, 
 including normal human gastric juice, cause inhibition of the 
 movements and the tonus of the empty stomach when introduced 
 directly into the stomach cavity. No acid has been tested in 
 stronger concentration than 0.5 per cent. The duration of the 
 inhibition is on the whole directly proportional to the concentration 
 and the total quantity of acid introduced; 200 c.c. of 0.5 per cent 
 of HCl will usually inhibit for a period of 25 to 30 minutes only. 
 
 This inhibition by acids can be made evident during all stages 
 of activity of the empty stomach. If the acid is introduced during 
 relative quiescence of the stomach, the appearance of the next 
 period of hunger contractions is delayed; if introduced during the 
 active contractions, these are abolished or depressed. 
 
 The duration of the acid inhibition is probably determined by 
 three factors, namely, (i) passing of the acid into the duodenum, 
 (2) fixation and neutralization of the acid of the mucous gastric 
 secretion, (3) neutralization by bile and intestinal juice which at 
 times pass into the stomach through the dilated pylorus. 
 
 While it is a striking fact that gastric juice of full normal 
 acidity (0.48 to 0.53 per cent) and other acid solutions inhibit the 
 hunger contractions, it does not follow that a neutral or alkaline 
 reaction in the gastric cavity is a prerequisite for these contractions. 
 During the strong contractions the stomach secretes a juice rich in 
 mucin and combined HCl, but usually containing some free HCl. 
 After the introduction of acids the contractions reappear before 
 all the acid has passed out of the stomach or has been completely 
 neutralized. And in case Mr. V. chews palatable food during a 
 strong himger period, the hunger contractions reappear before 
 there is complete cessation of the psychic secretion of gastric juice. 
 In other words, the hunger contractions are not inhibited by weak 
 
176 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 concentrations of acids in the stomach. A neutral or alkaline 
 reaction of the mucosa is not necessary for these contractions. If 
 the food is sufficiently palatable and the mastication is continued 
 long enough, the inhibition produced reflexly from the mouth fuses 
 with the acid inhibition from tJie stomach. If the food is not 
 especially palatable or the mastication period brief, the contrac- 
 tions may resume on cessation of the chewing and then again be 
 inhibited for a time during the period of most rapid secretion of 
 the appetite gastric juice. 
 
 The degree of inhibition produced by normal gastric juice is the 
 same as that caused by an equal quantity of hydrochloric acid of a 
 concentration equal to. the free acidity of the gastric juice. It 
 would thus seem that the hydrochloric acid in the gastric juice 
 constitutes the stimulus that leads to the inhibition. 
 
 This acid inhibition of the hunger contractions is of peculiar 
 interest in connection with the neuromuscular mechanisms of these 
 hunger movements and the gastric movements in normal digestion. 
 In man the movements of the stomach in digestion are not inhibited 
 by acids in the stomach, that is, at least not by acids in concen- 
 trations equal to that of the gastric juice. The fact that the inten- 
 sity of movements of the antrum increases as the gastric digestion 
 advances may even indicate that a certain degree of free acidity 
 facilitates the movements of digestion. At first it occurred to us 
 that since acid in the stomath inhibits the hvmger contractions, but 
 not the digestion contractions, the mechanisms involved in these 
 two types of gastric activity are different, at least as regards the 
 character of the afferent impulses from the gastric mucosa. But 
 on further reflection it became apparent that this is not necessarily 
 the case, for the digestive movements involve primarily the 
 pyloric end, while the hunger movements (as studied by our method) 
 involve the fundus of the stomach. It is possible that acid stimu- 
 lation of the nerve-endings in the gastric mucosa leads, reflexly, to a 
 temporary inhibition of the fundus and to peristalsis of the pyloric 
 region of the stomach. 
 
 3. The action of alkalies. — ^The tests were made with sodium 
 carbonate in concentrations varying from 0.2 to i.o per cent, and 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM I'j'j 
 
 in varying quantities. In concentrations of 0.2 per cent or less the 
 sodium carbonate solution appears to have the same influence on 
 the hunger contractions as equal quantities of -water, that is, a 
 shght temporary inhibition. This inhibition is evidently due, not 
 to the alkalinity, but to the bulk of the solution. In concentrations 
 of 0.2 per cent to i .0 per cent the degree of inhibition produced is on 
 the whole directly proportional to the concentration and the quan- 
 tity of the solution put into the stomach; 200 c.c. of i per cent sodium 
 carbonate causes about the same degree of inhibition as 200 c.c. 
 J per cent hydrochloric acid. It is thus clear that alkalinity has 
 the same effect as acidity, only to a less degree, both acids and 
 alkahes causing inhibition without any after-effect of the nature of 
 augmentation. 
 
 The fact that 0.2 per cent sodium carbonate has no more effect 
 on the hunger movements than equal quantities of water seems to 
 show that a shght alkalinity of the gastric mucosa is compatible 
 with the hunger contractions of the empty stomach. It makes it 
 also evident that the entrance of bile or intestinal juice into the 
 stomach will have little or no effect on these movements, while any 
 concentration that influences these movements produces inhibition. 
 
 4. The action of local anesthetics. — Solutions of some local 
 anesthetics were tested with the view of determining whether the 
 sensory nerves in the gastric mucosa play only an inhibitory role 
 in the processes of gastric hunger contractions. Phenol, chloreton, 
 orthoform, quinine-urea-hydrochloride, and adrenalin chloride were 
 used in quantities and concentrations compatible with absolute 
 safety to Mr. V. It was not considered advisable to use cocaine. 
 The solutions of the drugs were introduced in quantities of 100 to 
 200 c.c. 
 
 In the concentrations employed no specific action of any of the 
 above substances could be determined. For example, 100 c.c. of 
 phenol (dilution i to 10,000) has the same effect as 100 c.c. of water, 
 that is, a shght temporary inhibition. The same applies to the 
 other drugs. No appreciable anesthesia of the gastric mucosa was 
 produced by any of the drugs. It seems probable that the solutions 
 of these drugs pass out of the stomach just as rapidly as equal 
 
178 CONTROL' OF HUNGER IN HEALTH AND DISEASE 
 
 quantities of water, and hence do not remain long enough in the 
 stomach to produce local anesthesia. Because of the danger 
 attending the use of local anesthetics in strong concentrations in 
 the stomach, this work was not carried further on man. It seemed, 
 however, that adrenalin chloride introduced into the stomach in 
 considerable quantities could not be particularly injurious. But 
 even in large quantities (100 c.c. of a dilution of 1-10,000) the 
 adrenalin acting in the gastric cavity has no other effect on the 
 hunger movements than equal quantities of water. 
 
 5. The action of alcoholic beverages. — Tests were made with sour 
 and sweet wines, beer, brandy, and pure alcohol (dUuted). The 
 taking of alcoholic beverages with meals is a habit with many 
 people. It is claimed by many people that a glass of wine, beer, or 
 some mixture of alcohol taken before meals increases the appetite 
 (and possibly the hunger). The writer is neither a total abstainer 
 nor a habitual user of alcoholic beverages. But it is his experience 
 that a glass of beer taken at mealtime seems to awaken or increase 
 appetite. This effect is rather immediate and therefore not due 
 solely to the absorption of the alcohol. Pavlov has recorded an 
 instance from his own experierice where a drink of wine seemed to 
 initiate the sensation of hunger the very minute the wine reached 
 the stomach. Frotn inquiries as extensive as opportunities have 
 permitted we are inclined to believe that this apparent augmen- 
 tation of hunger or appetite by alcoholic beverages is rather a 
 common experience. In view of this fact, we expected to find that 
 these alcoholic beverages increased the tonus and the contractions 
 of the empty stomach, since it is the tonus and the contractions of 
 the empty stomach that give rise to the hunger sensation. To our 
 surprise the results proved to be the very opposite. Wine, beer, 
 brandy, and pure alcohol (diluted) introduced directly into the 
 stomach inhibit the hunger contractions and the tonus of the 
 empty stomach instead of increasing them. This is true, whether 
 these fluids are cold or at body temperature. If these alcoholic 
 beverages are greatly diluted with water, a degree of dilution can 
 be reached which has the same action on the empty stomach as 
 equal quantities of water, although the specific beverage is readily 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 179 
 
 detected when the mixture is placed in the mouth. In no instance 
 have we been able to make out any undoubted augmentation of 
 the stomach tonus and hunger contractions after the inhibition 
 period. In other words, alcohohc beverages when introduced 
 directly into the empty stomach in quantities and concentrations 
 that directly affect the tonus and the contractions of the stomach 
 cause inhibition, and inhibition only. 
 
 The pure alcohol was liever used in stronger concentrations 
 than 10 per cent. The brandy was usually diluted one-half with 
 water, while the beer and wines were put in the stomach undiluted. 
 
 We have seen that acids in the stomach cause inhibition of the 
 hunger contractions. Pure alcohol also causes inhibition. It is 
 therefore evident that the alcohol and acids are primarily respon- 
 sible for the inhibition following the introduction of alcoholic 
 beverages into the empty stomach. For the sake of brevity we 
 may designate it as " the alcohol inhibition." 
 
 The duration of the alcohol inhibition varies directly with the 
 quantity and concentration of the beverage introduced into the 
 stomach. Thus 50 to 100 c.c of 10 per cent alcohol may inhibit 
 the hunger contractions for i to 2 hours; or if introduced during a 
 period of relative quiescence it delays correspondingly the onset of 
 the next hunger period. Inhibition for 30 to 60 minutes is caused 
 by 200 c.c. of beer. The sour wines on the whole cause greater 
 inhibition than the sweet wines, probably through their acids. 
 
 It must be stated that these alcoholic beverages were put into 
 the stomach of Mr. V. and the other subjects, including the author, 
 with their consent and without any protest, resentment, fear, or 
 disgust on their part, which might account for the stomach inhibi- 
 tion. Mr. V. takes wine and beer occasionally. At times he bought 
 his own choice of wine and beer and introduced into the stomach 
 the desired quantities. The effect on the hunger contractions was 
 always the same. We are therefore dealing with a characteristic 
 alcohol and acid inhibition, and" not with a masked "psychic" 
 inhibition. 
 
 How are these results to be harmonized with the seeming stimu- 
 lation of the appetite by alcoholic beverages taken by the mouth ? 
 
i8o CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 In the first place, the local inhibitory action of alcohohc beverages 
 in the gastric cavity is so marked and so invariable that we feel 
 ^confident that this is always the gastric effect of these beverages' 
 in man, whether taken normally by the mouth or introduced into 
 the empty stomach without coming in contact with the mouth or 
 esophagus. Alcoholic beverages can therefore not initiate or increase 
 hunger, since hunger is caused by the stomach contractions, and 
 these are inhibited by the alcohol. Since most of the alcoholic 
 beverages stimulate the end organs of taste and smell as well as 
 those of general sensibility in the mouth cavity and in the esoph- 
 agus, it is possible that this stimulation in some way augments or 
 initiates appetite for food. If this is the case, we have the singular 
 condition of alcoholic beverages augmenting appetite and inhibiting 
 hunger at the same time. There can be little doubt that cerebral 
 states, as modified by training and habit, are also factors in this 
 apparent action of alcoholic beverages on appetite. It is certain 
 that the individual's first taste of alcohol, beei?, or sour wines does 
 not focus his attention on food and eating. 
 
 If alcoholic beverages in the stomach caused as marked inhibi- 
 tion of the stomach movenients in digestion as they do in the 
 stomach movements in hunger, even moderate drinking with meals 
 would lead to acute indigestion. As this is not the case, it is evident 
 that alcoholic beverages affect the mechanism of these two types 
 of movements differently. 
 
 6. The action of carbon dioxide and air. — The action of carbon 
 dioxide in the cavity of the empty stomach was studied in two 
 ways: (i) by introduction of water charged with CO2, (2) by intro- 
 duction of CO2 gas. An excess of carbon dioxide in the blood of the 
 abdominal vessels is supposed to augment the tonus of the digestive 
 tract, although some recent work of Hooker throws doubt on this 
 interpretation of the stimulating action on intestinal peristalsis by 
 partial asphyxia. An excess of CO2 is sometimes found in the 
 gaseous contents of the empty or partly filled stomach. It is known, 
 furthermore, that carbon dioxide in sufficient concentration acts as 
 a powerful stimulus to the nerve-endings in such membranes as 
 those of the mouth and nose and of the cornea and conjunctiva. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM i8i 
 
 Carbon dioxide in the cavity of the empty stomach was at first 
 considered a possible stimulus to the gastric hunger contractions, 
 but this hypothesis proved entirely erroneous. So far as the carbon 
 dioxide in the cavity of the stomach affects the himger movements, 
 the influence is in, the direction of inhibition. 
 
 Water saturated with CO2 under pressure has practically no 
 more effect than similar quantities of pure water. It produces the 
 same degree of temporary inhibition without any after-effect of 
 augmentation. As such carbonated water stimulates the nerve- 
 endings in the mouth in the characteristic way, it follows that the 
 nerve-endings in the stomach are less affected by CO3 than are 
 the nerve-endings in- the mouth. 
 
 When the CO2 is forced into the stomach in the form of gas and 
 under pressure, the results are complicated by the mechanical 
 action of the gas in forcibly distending the walls of the stomach 
 and raising the intragastric pressure, and hence increasing the 
 pressure on the balloon in the fundus. A sudden and forcible 
 distension of the empty stomach, no matter how produced, leads 
 to a few strong contractions. This factor can be fairly well con- 
 trolled by introducing the gas slowly. When this precaution is 
 taken, the empty stomach can be considerably distended with CO2 
 gas, without any marked effect, either on the tonus or on the hunger 
 contractions. But the chemical effect of CO2, so far as it is demon- 
 strable at all, is in the direction of inhibition. 
 
 It will undoubtedly occur to the reader that this slight inhibitiop 
 by the CO2 may be an instance of "psychic" inhibition from the 
 distress of an overdistended stomach. This possibility has been 
 guarded against. In the first place, the stomach was not distended 
 to the point of painfulness by the carbon dioxide. Furthermore, 
 the stomach cavity was irrigated, so to speak, with the gas without 
 raising the intragastric pressure perceptibly, by introducing the 
 inlet tube to the cardiac end and allowing the gas to escape by 
 way of the mouth, or, in the case of Mr. V., by the open fistula. 
 Under these conditions the same slight inhibitory effects were 
 recorded without signs of primary or secondary augmentation. It 
 is thus clear that so far as carbon dioxide in the gastric cavity 
 
1 82 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 affects the gastric tonus and hunger contractions at all the action 
 is in the direction of inhibition. This is probably due to the acid 
 stimulation of the nerve-endings in the mucosa. 
 
 The introduction of air into the empty stomach has no effect 
 whatever on the tonus and the hunger contractions, provided the 
 stomach is not overdistended by the air, or the air introduced 
 rapidly and under such pressure as to cause sudden and forcible 
 distension of the stom.ach walls. This leads to a few contractions. 
 But the same thing is produced by sudden inflation of the balloon 
 in the fundus. It is therefore purely mechanical. Oxygen in 
 greater concentrations than that of the air has not been tried. 
 But it is evident that the 20 per cent oxygen ol the air acts neither 
 favorably nor unfavorably on the hunger movements. 
 
 The fact that nothing but inhibition is produced by substance 
 acting on the gastric mucosa suggests that this may be in every 
 case a "psychic" inhibition masking any weak action that may be 
 of a positive or augmentation type. The very consciousness that 
 these substances were introduced into the stomach for experi- 
 mental purposes might be the primary element in this possible 
 psychic inhibition. That cerebral states may inhibit the gastric 
 hunger movements is certain from results both on man and on 
 dogs. In one instance, when preparing to introduce 200 c.c. of 0.5 
 per cent acidic acid into the stomach in the midst of the period of 
 powerful hunger contractions, Mr. V. somehow thought that we 
 ill tended to introduce that much concentrated acid (or vinegar). 
 As we were going about with the preparations it was noticed that 
 the stomach contractions suddenly became very feeble. Mr. V. 
 looked worried. We inquired if he did not feel right, and he asked 
 if we intended to put all that vinegar into the stomach. "It will 
 surely hurt me," he said. To assure him, the author drank half 
 of the acid himself, and then asked him to take a mouthful of it. 
 Then he laughed and said, "Oh, I thought it was pure vinegar." 
 In two minutes after the mental stress and anxiety was over the 
 hxmger contractions returned to their normal rate and ampUtude. 
 
 The following facts speak against the possibihty of the results 
 being due to psychic inhibition: (i) There was no evidence that 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 183 
 
 Mr. V. or any of the subjects were in any way afraid, displeased, 
 disgusted, or impatient with the experiments. (2) The direct 
 proportion between the quantity and the concentration of the 
 substance introduced into the stomach and the degree of inhibition 
 produced is contrary to the hypothesis of a psychic inhibition. The 
 displeasure or disgust ought to have been practically the same on 
 introduction of o.i per cent and of 0.5 per cent HCl, of i per cent 
 and 10 per cent alcohol, as in most cases the subjects did not know 
 the strength of the material used. (3) In many cases the subject 
 was purposely deceived as to the nature of the material, using 
 water for acids and vice versa. The stomach reaction was invari- 
 ably in accordance with the substance actually introduced. 
 
 We feel satisfied, even on the basis of the tests on man, that 
 psychic inhibition plays no rdle in these results. But to meet the 
 possibility once and for all, we have repeated and confirmed all* of 
 the above tests on dogs. The parallel on the two series on man 
 and dog is complete. May not psychic inhibition play a role in the 
 tests on dogs ? It does not, and for the following reasons : (i) The 
 dogs could not have known either the difference between the sub- 
 stances introduced into the stomach or the different concentrations 
 of the same substance. (2) Tests were made during sleep and with- 
 out the animal waking up. The results were the same. (3) Psychic 
 inhibition of the gastric hunger movements in dogs is invariably of 
 much shorter duration than the inhibition caused by acids, alkalies, 
 and alcoholic beverages. 
 
 It is therefore clear that these results on man are fundamental 
 facts in the physiology of the stomach and not primarily dependent 
 on afferent impulses that enter consciousness. ^ 
 
 5. rNTLUENCE OF THE INHIBITIONS FROM THE GASTRIC MUCOSA ON THE 
 FUNDAMENTAL RHYTHM OF THE GASTRIC HUNGER CONTRACTIONS 
 
 During the progress of this work it soon became apparent that 
 these temporary inhibitions described above do not cut short a 
 hunger period, but simply delay its culmination. The contractions 
 that appear as the inhibition ceases are the continuation of the 
 period temporarily checked by the inhibition. They are not the 
 
1 84 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 beginning of a new period. When the tetanus stage of the hunger 
 period is reached a stimulation of the gastric mucosa sufficiently- 
 strong to cause prompt cessation of the contractions seems actually 
 to terminate the period, for when the contractions reappear they 
 are not the incomplete tetanus or strong and rapid contractions 
 of the culmination of the period, but the feeble and slow movements 
 characteristic of the beginning of a period. By careful adjustment 
 of the quantity and strength of the material introduced into the 
 stomach during the first part of the hunger period and by renewing 
 the inhibition on reappearance of the rhythm, it is possible to 
 lengthen a 30- to 40-minute period into a 90- to 120-minute period. 
 In other words, the motor mechanisms of the hunger contractions 
 may be compared to the spring of a watch. When the spring is 
 wound up it will run the' watch for a certain number of hours, and 
 it makes no difference whether or not these hours are consecutive. 
 
 It seems to us that this fact has an important bearing on the 
 question of the primary stimulus to the hunger movements. It 
 seems to point to a primary automatism, peripheral or central, or 
 both, relatively independent of the condition of the blood as well 
 as of the afferent nervous impulses. The fact speaks particularly 
 strongly against the hypothesis that the primary stimulus is to be 
 sought in the condition of the blood. For example, if the primary 
 stimulu~S is in some condition of the blood, this condition must be 
 present and to a gradually increasing degree from 1 2 : 30 to i : 00 p.m. 
 to parallel a hunger period beginning at 12:30 p.m. and ending at 
 1 : 00 P.M. And this condition of the blood must be absent from i : 00 
 P.M. to 1 : 45 P.M., as the stomach is relatively quiescent during that 
 time. The hypothesis seems to be rendered untenable by the 
 manipulations which do^not, at least in some cases, involve any 
 change in this hypothetical condition of the blood. The culmina- 
 tion of the hunger period may be delayed till i :3o or i :4s p.m., so 
 that the strongest hunger contractions fall in the time when the 
 blood does not stimulate the gastric mechanism in a way to cause 
 hunger movements. 
 
 But what is the significance of this inhibition in the normal 
 work of the stomach ? The inhibition of the hunger contractions 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 185 
 
 by mechanical and chemical stimulation of the gastric mucosa in 
 the normal person prevents the appearance of these contractions 
 during the period of gastric digestion. This negative control of the 
 hunger movements from the stomach cavity is obviously a useful 
 co-ordination. The primary or actual stimulus to the hunger con- 
 tractions is therefore to be sought in the vagus tonus, in some 
 condition of the blood, or in a primary automatism of the gastric 
 neuromuscular mechanism. We have some evidence that the 
 latter is the essential factor and that extrinsic nerves and the 
 condition of the blood only modify the primary automatism. If 
 this is the case the hunger contractions ought to appear as soon as 
 the stomach is empty of food or other substances capable of stimu- 
 lating the nerve-endings in the mucosa. We should also expect 
 these contractions to be more or less continuous as long as the 
 stomach is empty, at least in young and vigorous individuals, and 
 when the condition of the individual as a whole does not lead to 
 increased activity of the extrinsic inhibitory nerves (splanchnics). 
 On this hypothesis the gradual tonus contraction of the gastric 
 fimdus pari passu with the progress of the gastric digestion repre- 
 sents the algebraic sum of the inherent automatism and the 
 inhibitory effects from the gastric cavity. A gradual fatigue of 
 the inhibitory mechanisms is probably also a factor, as we have 
 abundant evidence (in man and dog) of such "escape" of the 
 stomach from inhibitory nervous processes. 
 
 We should probably look for the closest parallelism between 
 the gastric hunger contractions and the absence of stimulation 
 of the gastric mucosa in infants and young children, that is, before 
 cerebral (and possibly gastric) habits relative to feeding have been 
 estabhshed. We have made a close study of a healthy (bottle-fed) 
 infant touching this point. It is well known that, other things 
 being equal, the more food put into the stomach the longer is the 
 time required for the completion of gastric digestion. If this 
 infant (five months old) is given only 4 ounces of food he calls for 
 more after about 2 hours. If he is given 7 to 8 ounces of the same 
 food the call for more food is delayed for 3 to 4 hours. If he is 
 given 5 ounces of the food at 6:00 p.m. he nearly always wakes up 
 
1 86 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 and calls for more at 12:00 or 1:00 o'clock, while if he is given 
 as much food as he will take {^^ to 8 J ounces) at 6:00 p.m. he 
 rarely wakes up and calls for food until 3 : 00 or 5 : 00 o'clock the 
 following morning. There is evidently a close parallel between 
 the time of the emptying of the stomach and the appearance of the 
 hunger contractions. The more frequent calls for food during 
 the day are obviously due to the fact that the gastric hunger con- 
 tractions must reach a certain degree of intensity before they cause 
 the soundly sleeping infant to wake up. This is certainly true in 
 the case of dogs. A dog may sleep on peacefully and quietly during 
 gastric hunger contractions of moderate intensity. When these 
 contractions become very intense the dog moves or moans in his 
 sleep and sometimes wakes up. 
 
 While we have m^de no observations on the action of acids, 
 alkalies, and alcoholic beverages on the gastric movements of 
 digestion in man, it is well known that these substances do not 
 inhibit these movements to the extent that they inhibit the hunger 
 contractions. The movements of digestion are primarily concerned 
 with the pyloric region, while the hunger contractions involve the 
 cardiac and fundus region. Evidently these two regions of the 
 stomach react differently to local chemical stimulation of the gastric 
 mucosa. 
 
 In view of the fact that acids as well as normal gastric juice 
 inhibit the gastric hunger contractions, one might expect that 
 persons having gastric hypersecretion should experience little or 
 no true hunger sensations or pangs of gastric origin. At the same 
 time we must consider, in cases of prolonged hypersecretion, the 
 possibihty of a readjustment of such a character that the acid 
 stimulation of the mucosa causes less inhibition than is the case in 
 the normal stomach. 
 
 III. INHIBITORY REFLEXES FROM THE GASTRIC MUCOSA IN DOGS 
 AND OTHER ANIMALS 
 
 The work on man led to the conclusion that any substance 
 capable of stimulating the nerve-endings in the gastric mucosa 
 causes inhibition of the tonus and hunger contractions, and inhibi- 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 187 
 
 tion only, as there is no evidence of any increase in the gastric tonus 
 or hunger contractions following the primary inhibition. The 
 experiments on dogs were undertaken primarily to determine the 
 character of this reflex, that is, whether central, or local, or both. 
 The liquids were introduced into the stomach through the fistula 
 by means of a soft rubber tube, so that swallowing acts and the 
 stimulation of nerve-endings in the mouth, the pharynx, and the 
 esophagus were completely eliminated. 
 
 I. Action of water, acids, alkalies; and alcoholic beverages.— The 
 observations were made on six dogs with all the extrinsic gastric 
 nerves intact; on six dogs with the splanchnic nerves cut; and on 
 four dogs with complete section of both of the vagi and the splanch- 
 nic nerves. The results on the normal dogs are practically identical 
 with those on man. Gastric juice (human, canine), weak acids and 
 a^ahes, brandy, wines, and beer introduced directly into the 
 empty stomach during hunger contractions produce immediate 
 inhibition of the gastric tonus and contractions. Thus the same 
 quantity of gastric juice or wine seems to cause more prolonged 
 inhibition in dogs showing the type I than in the dogs showing 
 type III hunger rhythms. The duration of these inhibitions can 
 best be studied in the dogs showing types II and III of himger 
 contractions, as these two forms are practically continuous, so 
 that the errors from spontaneous periods of relative quiescence 
 are eliminated. In normal dogs showing contractions of types II 
 and III, 25 c.c. gastric juice or 0.5 per cent HCl usually causes 
 complete inhibition for 20 to 30 minutes. The return of the hunger 
 contractions is always gradual. In hke manner, 25 c.c. of beer will 
 inhibit for 15 to 25 minutes. In one case 50 c.c. of beer caused 
 complete inhibition for one hour. 
 
 If these substances are introduced into the stomach of dogs 
 during a period of relative quiescence and tonus relaxation the only 
 effect appears to be a still greater tonus relaxation and prolongation 
 of the quiescent period. In some cases one or two hunger con- 
 tractions follow immediately on introducing the material into 
 the stomach. We are inclined to attribute these contractions 
 to the mechanical distension of the stomach wall rather than to 
 
1 88 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 stimulation of nerve-endings in the mucosa. This phenomenon was 
 never observed when the stomach was in strong tonus and hunger 
 contractions. 
 
 2. Action of carbon dioxide. — The influence on the hunger con- 
 tractions of CO2 in the stomach cavity is the same in dog and man. 
 The experiments on dogs were made with water saturated with CO2 
 and with CO2 gas. When the gas was employed, at times enough of 
 it was passed into the stomach via the fistula to cause escape of 
 the gas through the esophagus. The water saturated with CO2 has 
 practically the same action as ordinary water, liiat is, a slight 
 temporary inhibition without any after-effect (rf the nature of 
 increased tonus or contractions. This is true whether the car- 
 bonated water is introduced during active hunger contractions or 
 during relative quiescence. The CO2 gas usually initiates some 
 contractions if introduced into the stomach during a period of 
 quiescence. This is evidently due to mechanical distension of the 
 stomach walls and not to chemical stimulation of nerve-endings 
 in the mucosa. If the empty stomach is in vigorous tonus and 
 hunger contractions the CO2 gas causes a slight temporary inhibi- 
 tion without any stimulating after-effect. This temporary in- 
 hibition is in all probability due to a weak acid stimulation in the 
 nerve-endings in the mucosa. 
 
 3. Effects of complete section of the splanchnic nerves. — ^The 
 inhibition of the gastric tonus and hunger contractions by acids, 
 alkalies, alcohol, etc., in the stomach cavity persists after section 
 of the splanchnic nerves, but it is on the whole less complete and 
 of shorter duration than in dogs with all the extrinsic gastric nerves 
 intact. This applies to all substances used in this series of experi- 
 ments. When, as in the present series, the test with each substance 
 is repeated at least ten times on each animal, some variation in the 
 intensity and duration of the inhibition appears. That is to be 
 expected, because the degree of inhibition depends on several 
 variable factors, such as the excitability of the nerve-endings in 
 the mucosa, the excitability of the Auerbach plexus and of the 
 central nervous system, the tonus of the stomach, etc. It is there- 
 fore true that the most pronounced inhibition observed after section 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 189 
 
 of the splanchnic nerves may be as marked as the feeblest inhibition 
 obtained in the normal dogs. But when all the results in the two 
 series of dogs are compared there is no question but that section of 
 both splanchnic nerves diminishes the inhibition following chemical 
 stimulation of the gastric mucosa by acids, alkalies, alcohol, etc. ' 
 
 Several explanations of this fact suggest themselves, (i) Since 
 section of the splanchnic nerves in dogs increases on the whole the 
 tonus and, the hunger contractions of the empty stomach, the 
 diminished inhibition may be due to this greater vigor of the 
 stomach rather than cutting the efferent path of a long reflex. 
 We do not think that this is the main or important factor, because 
 the typical marked inhibition is obtained in normal dogs, even 
 when the stomach shows as vigorous tonus and hunger contractions 
 as the maximum shown by dogs with the splanchnic nerves severed. 
 Moreover, the inhibition is still incomplete in splanchnetomized 
 dogs that show relatively feeble hunger contractions. (2) The 
 substances stimulate afferent vagi nerve-endings in th€ mucosia, 
 and the afferent vagi impulses via conscious or subconscious cen- 
 ters finally stimulate the efferent inhibitory neurones in the splanch- 
 nic system. It is well known that the vagi carry afferent fibers 
 from the stomach mucosa and that the splanchnic nerves carry 
 inhibitory fibers to the stomach. The present experiments give 
 the first intimation that the afferent vagus and the efferent splanch- 
 nic systems'are so intimately associated in gastric motor reflexes. 
 It is possible that the reflex also involves the adrenal glands, so 
 that the inhibition mentioned above is to be accounted for, in 
 part, by the depressor action of an increased output of epinephrin. 
 4. Effect of section of the vagi nerves and of the vagi and the 
 splanchnic nerves. — When all the records are compared it appears 
 that section of the vagi nerves alone or section of both the splanchnic 
 and the vagi nerves diminishes the inhibitory reflex from the gastric 
 cavity on the whole more than does the section of the splanchnic 
 nerves alone. A fact of greater importance, however, is the per- 
 sistence of the reflex after complete isolation of the stomach from 
 the central nervous system. The inhibition is therefore a primary 
 , local reflex. The decrease of the inhibition after the vagi section 
 
igo CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 may involve two mechanisms. It is well known that the vagi con- 
 tain some efferent inhibitory fibers to the stomach motor mechan- 
 ism, and these may be, together with the splanchnic inhibitory 
 fibers, involved in the long inhibitory reflex. But since the gastric 
 
 II 
 
 i^jil>^/V\yv''»''''«*^'^ 
 
 ''\w%AoAiuiiN(W#v^ 
 
 •«W' w^^***' U*^^ 
 
 i,,,,,.,^^,^^^ 
 
 Fig. 20. — I. Tracings from empty stomachs of dogs. A, normal dog; B, dog 
 with both splanchnic nerves cut; X, introduction of 25 c.c. 0.5 per cent HCl into 
 the stomach; showing less complete inhibition of the hunger contractions by acid 
 in the stomach after section of the splanchnic nerves. One-third original size. 
 
 II. Tracings from the empty stomach of dogs. A, normal dog; B, dog with 
 section of the vagi and splanchnic nerves; X, introduction of 1 2 c.c. of brandy + 1 2 c.c. 
 of water into the stomach; showing less complete inhibition by alcohol in the case of 
 the stomach isolated from the central nervous system. One-half original size. 
 
 tonus fibers in the vagi and the gastric inhibitory fibers in the 
 splanchnic nerves are practically antagonistic, it is highly probable 
 that afferent influences leading reflexly to the stimulation of the 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 191 
 
 inhibitory neurones lead at the same time to the inhibition of the 
 tonus or motor neurones. 
 
 The reader may object that we are now discussing interferences 
 that do not necessarily follow from the facts so far at hand. The 
 facts, in brief, are these. The inhibition of the tonus and the con- 
 traction of the empty stomach by stimulation of the gastric mucosa 
 persist after isolating the stomach from the central nervous system, 
 but the inhibition is diminished in intensity and duration after 
 section of the splanchnic nerves, and somewhat more so after 
 section of the vagi nerves. It has been shown that section of the 
 vagi leaves the stomach on the whole permanently hypotonic, 
 except during prolonged starvation, although there seems to be a 
 gradual improvement in the efficiency of the local tonus mechanism. 
 Is it not possible that the lessened inhibition after the vagi lesion 
 is due to the depression of the excitability of the local afferent 
 nerve-endings in the mucosa or depression of the local reflex center 
 similar to the tonus depression ? Our experiments do not exclude 
 this possibility, but the results on the dogs with only the splanchnic 
 jierves severed show conclusively that it is not the sole factor; for 
 in these dogs there is no gastric hypotonus, and yet the inhibition 
 from the gastric mucosa is diminished. 
 
 Another possibility has occurred to us. When the same quantity 
 (25 to 50 c.c.) of acids, alkalies, or alcoholic beverages is introduced 
 into the stomach in tonus and into a stomach in hypotonus, it 
 seems likely that the solution will come in contact with more of the 
 mucous membrane in the tonic than in the atonic stomach. This 
 might result in less inhibition in the case of atonic stomach from the 
 mere fact of stimulation of less of the afferent nervous mechanism. 
 We have tested this possibiUty by introducing a greater quantity 
 of the respective solutions in the hypotonic stomach. But if 25 c.c. 
 of acid or beer fail to produce complete inhibition, 50 c.c. of the 
 same liquid usually also fail. This is to be noted, however, that 
 the depression of inhibition following splanchnic and vagi section is 
 most marked for a week or two after these nerve lesions are made, 
 and there is a distinct tendency in the efficiency of the local reflex 
 pari passu with the improvement of the local tonus mechanism. 
 
1^2 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 This is probably an instance of readjustment of local reflex 
 mechanisms to a fair degree of efficiency in the absence of central 
 tonus and accessory central long reflexes. 
 
 The experiments on man and on normal dogs led to the con- 
 clusion that contractions of the empty stomach cannot be induced 
 by the stimulation of the gastric mucosa — that such stimulation 
 causes inhibition only. It was noted that one or two contractions 
 occasionally follow immediately on the introduction of these liquids 
 into the stomach, but it seemed probable that these contractions 
 were due to the mechanical distension of the stomach walls rather 
 than to the chemical or mechanical stimulation of the nerve-endings 
 in the mucosa. These initial contractions following the introduc- 
 tion of acids, alkalies, or alcoholic beverages into the stomach 
 occur more frequently in the hypotonic stomach isolated from the 
 central nervous system. This is true even when special care is 
 taken to introduce the substance slowly so as not to cause sudden 
 distension of the stomach walls. I am not yet satisfied that this 
 primary motor response is actually due to stimulation of nerve- 
 endings in the mucosa. If it is, there must be in the mucosa a few 
 afferent nerve-endings of the excitatory type; but the afferent 
 inhibitory nerve-endings are so much more mmierous that the 
 influence of the former group is completely submerged by the 
 latter, except occasionally, when the stomach is hypotonic, or else 
 local afferent nerve-endings in the mucosa are all of one type; 
 but the type of reflex produced by this stimulation may depend 
 in part on the tonus condition of the reflex centers (Auerbach 
 plexus). 
 
 The local and long reflex mechanisms governing the tonus and 
 the hunger contractions of the empty stomach demanded by the 
 foregoing work on dogs are diagrammatically represented in Fig. 21. 
 It may be noted that this diagram is not intended to represent all 
 the afferent gastric nerve components, such' as those acting in 
 various ways on consciousness, on the vasomotor centers, etc. 
 The adrenal glands are indicated simply as a possible factor, 
 because conclusive data have not yet been obtained on that point. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 193 
 
 Rogers found that water, weak alcohol (10 per cent), weak 
 acids (0.2 to 0.4 per cent HCl), sugar solutions, fruit juices, etc., 
 introduced directly into the stomach in rabbits cause temporary- 
 inhibition of the hunger contrac- 
 tions, but have no apparent effect 
 on the digestion peristalsis when 
 introduced in the filled stomach. 
 In the guinea-pig Dr. King failed 
 to obtain definite inhibition of 
 the hunger contractions by chemi- 
 cal stimulation of the mucosa. 
 In these experiments it is possible 
 that the stomach was not com- 
 pletely empty, hence the resist- 
 ance to locaLchemical stimulation, 
 as Rogers and Hardt found that 
 even in man the tonus rhythm 
 of the fimdus that is present 
 during the digestion peristalsis is 
 much more resistant to inhibition 
 from chemical stimulation of the 
 mucosa than is the very same 
 tonus contraction in the empty 
 stomach of the same individual. 
 
 Water and weak acids, etc., 
 introduced directly into the empty 
 crop of pigeons cause inhibition of 
 the hunger contractions. In the 
 bullfrog water, -weak acids, weak 
 alkalies, etc., inhibit temporarily 
 both the hunger contractions and 
 the digestion peristalsis. In the 
 frog the inhibition from the gastric 
 
 mucosa is much more marked than that produced by chemical 
 stimulation of the nerve-endings in the mouth (Patterson). 
 
 Fig. 21. — Diagram to represent the 
 local and the long reflex mechanisms 
 Involved in the inhibition of the gastric 
 .tonus and the hunger contractions from 
 stimulation of the gastric mucosa. A , 
 adrenal gland; B, gastric mucosa; C, 
 stomach musculature; D, Auerbach's 
 plexus; E, local afferent neurones from 
 the gastric mucosa to Auerbach's plexus 
 (these neurones are predominantly in- 
 hibitory) ; H, tonus or motor neurones 
 to the stomach via the vagi; L, afferent 
 neurones in the vagi from the gastric 
 mucosa; P, neurones in the splanchnic 
 nerves; -[- = stimulation; — = inhibition. 
 
194 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The inhibitory reflexes from the gastric mucosa to the gastric 
 musculature are thus preesnt in all animals so far studied. The 
 mechanism is probably present in all animals with a well-developed 
 stomach. But the efficiency of the reflexes varies in different spe- 
 cies, and in the same species or individuals they vary with the 
 condition of the stomach (filled or empty). 
 
 V 'i 
 
 V '. \JiikJUiiMM^ 
 
 Fig. 22. — a, lo c.c. of 0.25 per cent hydrochloric acid put into the rabbit's stom- 
 ach during normal digestion peristalsis; b, 10 c.c. of 0.25 per cent hydrochloric acid 
 put into the stomach of a hungry rabbit; c, 10 c.c. of water put into the stomach of a 
 hungry rabbit; d, 10 c.c. of 10 per cent alcohol put into the stomach of a hungry rab- 
 bit. Note the inhibitory effect of these solutions on the hunger movements (Rogers). 
 
 IV. INHIBITORY REFLEXES FROM THE INTESTINAL MUCOSA 
 TO THE EMPTY STOMACH 
 
 We have seen that the tonus and contractions of the empty 
 stomach are temporarily inhibited by stimulation of nerves in the 
 mouth, in the esophagus, and in the gastric mucosa itself. Can 
 the tonus and hunger contractions of the empty stomach be 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 195 
 
 influenced reflexly by stimulation of the intestinal mucosa ? The 
 answer to this question might explaia the diminution or abolition 
 of hunger by the introduction of chyme into the intestine. If such 
 reflex relations exist, it is obvious that the intestinal mucosa must 
 be an important factor in the control of the gastric tonus and hunger 
 mechanism. 
 
 Boldyreff reports that acids in the intestine inhibit the periodic 
 activity of the empty stomach. The inhibition was not obtained 
 by water or alkaline solutions. In fact, Boldyreff appears to imply 
 that the periodic contractions of the empty stomach may be 
 initiated by the introduction of a solution of 0.3 per cent NaaCOj 
 into the intestine. He therefore concludes that the reflex inhibition 
 is due to an acid stimulation of nerves in the intestinal mucosa. 
 If chemical stimulation of the intestinal mucosa induces increased 
 intestinal tonus and contractions, we should expect the increased 
 motility of the intestines to cause some inhibition both of the 
 digestion peristalsis and the hunger contractions of the stomach 
 according to the interesting theory of gastero-intestinal co-ordination 
 recently advanced by Alvarez. 
 
 In our work we used 24 young female dogs. Intestinal fistulas 
 were made by Abbe's lateral anastomosis in the first loop of the 
 small intestine below the pancreas, the cephalad end being sutured 
 into the abdominal wall and left open to the exterior. The gastric 
 fistula was made after recovery from the first operation. 
 
 In another group of dogs a Tiery fistula was made, but no gas- 
 tric fistula, the recording apparatus being introduced into the 
 stomach through the esophagus. 
 
 In the third group the gastric fistula was made near the pyloric 
 end of the stomach. Through this fistula a small stomach tube was 
 passed through the pylorus into the small intestine for varying 
 distances. This tube was kept in the gut throughout the experi- 
 ment for the introduction of the liquids into the intestine. The 
 recording balloon was passed into the stomach either through the 
 gastric fistula or through the esophagus. 
 
 In the last group of dogs the vagi and splanchnic nerves were 
 cut and after recovery from the operation, gastric fistula was 
 
B 
 
 196 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 established in the antrum pylori. In all tests on this group the 
 fluids were introduced into the intestine by means of a tube 
 passed through the pylorus, and the stomach balloon was passed 
 down through the esophagus. 
 
 The following solutions were introduced into the intestine in 
 10 c.c. quantities, in most cases at body temperature: normal 
 gastric juice (dog and man); 10 per cent Witte's peptone in 0.2 
 
 Fig. 23. — Tracings of the empty stomach of dogs. A, a, mechanical stimulation 
 of intestinal mucosa (gently moving a rubber tube in the lumen) ; J, lo c.c. water intro- 
 duced into the intestine; c, 10 c.c. of 0.3 per cent Na^COj introduced into the intes- 
 tines; B,a,jo c.c. of 10 per cent peptone in 0.2 per cent HCl introduced into intestine; 
 b, 10 c.c. fresh milk introduced into the intestine; showing temporary inhibition of 
 tonus and hunger contractions of the empty stomach by mechanical and chemical 
 stimulation of the intestinal mucosa. 
 
 per cent HCl; pepsin in 0.2 per cent HCl; hydrochloric acid 
 (a. I per cent to 0.5 per cent); saturated H2CO3 solution; neutral 
 olive oil; fresh milk; water; mechanical stimulation of the intes- 
 tinal mucosa (glass rod or rubber tube). 
 
 When the vagi and splanchnic nerves are intact all mechanical 
 and chemical stimulations of the intestinal mucosa cause inhibition 
 of the gastric tonus and hunger contractions. The effect of a 
 purely mechanical stimulation (rubbing the mucosa with a glass 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 197 
 
 rod or rubber tube) is the most transitory. • In general pure gastric 
 juice and the 0.5 per cent HCl cause the longest inhibition. The, 
 acid peptone solution followed these closely. The weaker acids! 
 produced inhibition of less duration. Saturated carbonic acid 
 solution did not give quite so distinct an inhibition as the other 
 acids. Inhibition with pure gastric juice and the acid peptone 
 
 ^r' vVW ''\mJ'^I'J''*'^^'^'^''''^'' 
 
 B 
 
 \m0^'l^!^^0^&^^^ 
 
 Fig. 24. — Tracing showing tonus and hunger contractions of the empty stomach 
 of dogs. A, 10 CO. of gastric juice introduced into small intestine at a; B, 10 c.c. 
 o-s per cent HCl introduced into small intestine at a; C, 10 c.c. i per cent Na^COj 
 introduced into smaU intestine at a; showing reflex inhibition of the tonus and the 
 hunger contractions of the empty stomach by chemical stimulation of intestinal 
 mucosa. 
 
 mixture varied in duration from 3 to 20 minutes, depending appar- 
 ^ently largely on the condition of the animal at the time. The 
 sodium carbonate solution caused inhibition of less duration than 
 acid mixtures, but of longer duration than the water or the neutral 
 
198 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 mixtures in general. However, the longest inhibition obtained in 
 any one experiment was produced by 10 c.c. of milk in the gut. 
 In this case the inhibition lasted 30 minutes. Ordinarily neutral 
 solutions produced a longer inhibition than the mechanical stimu- 
 lation by moving the soft rubber tube in the intestinal fistula. 
 
 In the animals with the vagi and splanchnic nerves severed the 
 substances named above still caused reflex inhibition of the empty 
 stomach from the intestinal mucosa, but the latent period of the 
 inhibition was greatly prolonged, the degree of the inhibition less, 
 and the duration of it much shorter than in the normal animals. 
 
 It is therefore clear that this inhibition of the tonus and mechan- 
 ical stimulation of the intestinal mucosa involve both long or 
 central and short or local reflex paths, a situation similar to that 
 foimd in the gastric mucosa itself. 
 
 We may conclude, then, that: (i) Gastric juice, chyme, acids, 
 alkalies, water, milk, and oil introduced into the small intestiae 
 inhibit gastric hunger contractions and gastric tonus for varying 
 periods. (2) This inhibition is due partly to mechanical, partly 
 to chemical, stimulation of the intestinal mucosa. The chemical 
 stimulation produces the greatest effect. (3) This inhibition takes 
 place primarily by the "long" or central reflex path, but "short" 
 or local reflex paths in Auerbach's plexus are also involved 
 (Elsesser). 
 
 The precise r61e of these reflexes in the control of the gastric 
 hunger mechanism in the normal animal must be determined by 
 further investigation. They are probably factors in the diminution 
 or absence of hunger in cases of enteritis, intestinal obstruction, 
 constipation, appendicitis, and gallstones. 
 
CHAPTER XII 
 
 THE NERVOUS CONTROL OF THE HUNGER MECHANISM 
 
 {Continwd) 
 
 I. INHIBITION OF HUNGER BY SMOKING AND BY PRESSURE 
 ON THE ABDOMEN 
 
 --- It is generally held to be true that smoking shortly before a 
 meal leads to depression of hunger and appetite. It is also a 
 common belief that strong pressure on the abdomen ("tightening 
 the belt") decreases or relieves the himger sensation, at least 
 temporarily. We are now in position to test the correctness of these 
 behefs by decisive experiments as regards the influence of these 
 measures on the objective hunger contractions and the subjective 
 himger sensations. 
 
 Depression or inhibition of hunger by smoking is rendered 
 probable by the fact that, at least in man, anything which stimu- 
 lates the sensory nerve-endings in the mouth and in the gastric 
 mucosa inhibits the gastric hunger contractions in direct proportion 
 to the intensity of the stimulation. Smoking stimulates the nerve- 
 ending in the mouth in varying degrees, according to the kind of 
 tobacco used. Smoking frequently involves stimulation of the 
 nerve-endings in the gastric mucosa owing to the swallowing of 
 saliva containing nicotine, oils, tannic acid, ai^d other irritating 
 substances. Smoking may also act on the hunger mechanism in a 
 third way, that is, through absorption of nicotine and other products 
 of the combustion. The third possibility has not been investigated. 
 It is well established, however, that even small quantities of nicotine 
 in the blood leads to nausea and vomiting. Nausea and vomiting 
 are accompanied by atony of the gastric fundus, which insures 
 absence of hunger contractions and hunger sensations. 
 
 The effects of smoking on the gastric hunger contractions were 
 first studied on Mr. V., our young man with the permanent gastric 
 fistula. In his case smoking (cigars) leads invariably to inhibition 
 
 199 
 
200 CONTROL OF HUNGER IN HEALTH AND DISEASE , 
 
 of the hunger contractions. But Mr. V. is not a habitual smoker. 
 It is therefore possible that the results obtained on him were simply- 
 due to the condition of nausea or disgust that smoking usually 
 produces in the novice and hence were not applicable to persons 
 used to smoking. 
 
 The tests were repeated on several habitual smokers. So far 
 as smoking influences the gastric himger contractions this influence 
 is in the direction of inhibition. This inhibition appears to depend 
 on the intensity of stimulation of the nerve-endings in the mouth, 
 a cigarette or "mild" cigar causing only slight inhibition, while a 
 "strong" cigar or pipe causes complete and prolonged inhibition, 
 €ven when the gastric hunger contractions are at their maximum. 
 
 If the cigar or pipe causes very strong stimulation of the nerve- 
 endings, in the mouth, the inhibition of the hunger contractions 
 may continue from 5 to 15 minutes after the cessation of the 
 stimulation. Thus even a brief period of smoking may suppress 
 an entire hunger pe^riod. 
 
 The subjective sensation of hunger is diminished or abolished 
 parallel with the gastric hunger contractions. But it seems to 
 the authors that even a "mild" smoke diminished the sensation 
 of hunger rather more than one might infer from the slight depres- 
 sion of the contractions. This is probably due to the deviation of 
 attention, the smoking acting partly as a "counter-irritant." 
 
 Smoking inhibits the gastric hunger contractions. It is prac- 
 tically certain, even in the absence of direct experiments, that 
 moderate smoking does not inhibit the gastric movements of diges- 
 tion. The reason for this difference in the action of the same 
 condition on the empty and on the filled stomach is not clear. 
 
 The experiments with constriction of the belt were made on 
 three normal men. The tests were made with the subject standing 
 up, sitting, and lying on the back, and at all stages of the gastric 
 hunger contractions. 
 
 ^ Strong contraction of the abdominal belt leads nearly always 
 to inhibition of the gastric hunger contractions of weak or moderate 
 strength, lasting from 5 to 15 minutes. The inhibition may be 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 201 
 
 partial or complete, but in either case the hunger contractions 
 reappear despite the continued pressure of the belt. This inhibition ^ 
 is obtained even when the belt constriction is moderate, so that no 
 discomfort or pain is produced. 
 
 When the gastric hunger contractions are strong (the middle 
 of a hunger period), constriction of the belt never causes complete 
 inhibition. But so far as the increased abdominal pressure affects 
 the hunger contractions, the influence is iti the direction of inhibi- 
 tion. The individual hunger contractions are weakened without 
 suffering much change in the rate. Frequently, however, even a 
 belt constriction that caused considerable discomfort has practically 
 no influence on the hunger contractions, particularly if the subject 
 is lying down. 
 
 When the gastric hunger contractions are at their maximum in 
 rate and amplitude, as is ordinai^ily the case near the end of a 
 hvmger period, no amount of belt constriction seems to influence 
 the contractions. When this stage of the hunger period is reached 
 the hunger pangs rim their normal course in the presence of even 
 painful belt pressure. 
 
 All three subjects agreed that the belt constriction appeared' 
 to diminish or interfere with the hunger sensation to a greater! 
 extent than seemed warranted from its effect on the hunger con- 
 tractions. Several factors are probably involved in this discrepancy.! 
 (i) The belt constriction distracts the attention from the hunger 
 impulses by stimulation of nerve-endings in the viscera, especially 
 those of the peritoneimi. (2) Strong pressure on the abdomen from 
 without appears to induce, temporarily, a condition stimulating in 
 a feeble way the complex sensation of satiety. 
 
 According to R. Lennhoff,^ hunger and appetite are appeased 
 with a less quantity of food when the belt is constricted than when 
 the intra-abdominal pressure is regulated solely by the tonus of 
 the abdominal muscles. Lennhoff ascribes this to depression of 
 hunger and appetite by the pressure of the belt. His observation 
 is probably correct, but his explanation is erroneous. laa normal 
 person the actual hunger contractions and hunger sensations are 
 
 i^Juoted in Tow. Amer. Med. Assoc, LX (1913), 41- 
 
202 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 stopped by the first few morsels of food swallowed, while this may 
 actually increase the appetite through stimulation of nerve-endings 
 in the mouth and in the mucous membrane of the esophagus and 
 stomach. This appetite sensation is gradually counteracted by 
 the sensation complex of satiety, which depends in part on the 
 distension of the stomach with corresponding readjustment of the 
 tonus of the abdominal muscles. This feeling of fulness, which 
 appears to be referred to the abdomen as a whole, is probably 
 developed with less intake of food when the abdominal wall is 
 mechanically prevented from relaxing owing to the pressure of 
 the belt. 
 
 We have practically nothing but conjectures to offer in way of 
 explanation of the mechanisms involved in these inhibitions of the 
 gastric hunger contractions by strong pressure on the abdomen. 
 Strong pressure on the abdomen causes temporary inhibition of 
 the gastric hunger contractions in dogs, but the manipulation 
 greatly disturbs them, and disturbance from any cause leads to a 
 temporary inhibition of the empty stomach in dogs with the 
 splanchnic nerves intact. In dogs with the splanchnic nerves sec- 
 tioned on both sides strong pressure on the abdomen causes no 
 distinct inhibition of the gastric hunger contractions. This points 
 to the conclusion that belt constriction causes gastric inhibition, 
 not by direct pressure on the stomach, but by direct stimula- 
 tion of inhibitory nerves, or by mechanical (or sympathetic) 
 stimulation of the adrenal glands, and through long reflexes. Belt 
 constriction involves stimulation of cutaneous nerve-endings, but 
 a gentle stimulation of the tactile nerve-endings in the skin alone 
 does not lead to this inhibition. The afferent path of the reflex 
 must therefore involve abdominal proprioceptors. The splanchnic 
 nerves probably constitute the efferent path of the reflex. We 
 do not wish to be understood as denying the existence of local 
 inhibitory mechanisms that may be stimulated by mechanical 
 manipulation of the abdominal organs, but our results indicate 
 that strong belt constriction is not a sufficient stimulus for such 
 local mechanisms. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 203 
 
 II. INFLUENCE OF PHYSICAL EXERCISE AND EXTERNAL COLD 
 ON THE HUNGER MECHANISM 
 
 So far we have been unable to initiate or augment the gastric 
 hunger contractions in man or experimental animals by any sensory 
 stimulation or central nervous processes. We have seen that so far 
 as these nervous processes affect hunger it is in the direction of 
 inhibition. It is singular, indeed, that the inhibitory mechanisms 
 are so readily called into play, while motor reflexes are either 
 inaccessible or lacking, especially since the utility of some of the 
 inhibitory reflexes are open to question at present. 
 
 From the point of view of biological, adaptation we might expect 
 the vagogastric tonus to be directly affected by voluntary muscular 
 activity and by exposure to cold, since both conditions involve 
 increased oxidation and consequently increased need of food. 
 
 Muscular activity may augment the gastric hunger activity by 
 increasing the vagus tonus as well as by chemical changes in the 
 blood. The same applies to stimulation of the cold nerve-endings 
 of the skin. However, it is probable that if these conditio^s cause 
 increase in the vagus tonus reflexly, this response is more prompt 
 than that induced by the changes in the blood following the increase 
 or decrease in body metabolism due to stimulation. It is generally 
 recognized that exercise, cold climate, and cold baths increase 
 appetite and hunger. It does not follow that these conditions 
 actually augment the gastric hunger contractions. The increase 
 in hunger and appetite may be only apparent, that is, may reflect 
 a condition of increased excitability of parts of the central nervous 
 system, so that the afferent impulses that give rise to the sensation 
 of hunger and appetite produce a greater central effect. If the 
 gastric hunger contractions are actually increased, this may be 
 due to changes in the blood rather than to increased vagus tonus. 
 
 It is well known that exposure of the skin to cold (as by bathiag 
 in ice water) may induce contracture or "cramps" of the digestive 
 tract. This is especially the case during the height of gastric and 
 intestinal digestion. These cramps and contractures may be the/ 
 result of circulatory disturbances or of changes in the blood rather 
 than a direct reflex effect. Central processes are also able to induce/ 
 
204 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 contraction of the large intestine and the rectum, as shown by- 
 involuntary defecation in cases of great anxiety or fear. 
 
 I. EXPERIMENTAL PROCEDURE 
 
 1. Dogs. — Dogs with simple gastric fistulas were trained to run 
 in a treadmill. When trained to run without urging or interference, 
 records were taken of the contractions of the empty stomach so as 
 to determine (i) whether muscular activity induces hunger con- 
 tractions in the quiescent stomach, and (2) whether muscular 
 activity augments the hunger contractions of an active stomach. 
 
 The hunger contractions of the stomach of dogs were recorded 
 for 2 to 4 hours after a day's fast, the dogs being taken direct from 
 the kennel without being exercised. On other days the same dogs 
 were taken out for a 4- to 6-mile brisk walk before the 2- to 4-hour 
 recording period. 
 
 Records of the gastric hunger contractions were taken with the 
 dog lying quietly in the lap of an assistant. Then the body of the 
 animal was surroimded with an ice pack, or the dog placed directly 
 on a slab of ice. After some training the dogs do not appear much 
 disturbed by the ice pack or slab of ice. The ice pack was apphed 
 with the stomach quiescent as well as in hunger activity. 
 
 All of these procedures were used on normal dogs and on dogs 
 with the splanchnic nerves sectioned on both sides, in order to have 
 the tonus fibers of the vagi unopposed by the splanchnic inhibitory 
 influence. 
 
 2. Man. — The tests were made on the author, on Mr. V. (the 
 gastric fistula case), and on three assistants (J. H. L., S. J. O., 
 A. M. P.). 
 
 Records were taken of the gastric hunger and tonus contraction 
 with the man standiag or walking or numing in situ. Tests were also 
 made after muscular exercise (playing tennis, walking 6 to 12 miles). 
 
 The influence of exposure of the body to cold on the gastric 
 hunger mechanism was tested in the following way: (i) While 
 records of the gastric tonus and hunger contractions were being 
 taken, the man, stripped of his clothes, was subjected to cold or 
 warm showers for varying periods. The cold showers were at times 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 205 
 
 sufficiently cold or prolonged to cause intense shivermg. (2) The 
 man, stripped of his clothes in a cold room, was covered up on a 
 couch so as to feet comfortably warm. At the desired moment in 
 the gastric activity, that is, during a period of quiescence or in the 
 midst of a period of hunger contractions, the covers were removed 
 and the cold air of the room set in motion by a fan placed close to 
 the person. This brought on shivering in a few minutes. (3) The 
 man arose at 7:00 a.m. and, without the usual cold bath and 
 breakfast, proceeded to the laboratory, and records of the gastric 
 tonus and hunger contractions were taken from 8 : 00 a.m. to 12 : 00 m. 
 These served as controls. On the other days the man arose at 6 : 00 
 A.M., took a cold bath (this was prolonged until the discomfort 
 became very severe), followed by a brisk walk, when records were 
 taken from 8:00 a.m. to 12:00 m. 
 
 2. RESULTS ON DOGS 
 
 I. Effects of running in treadmill. — The initial effect on gastric 
 tonus and hunger contractions of running in the mill is always in 
 the direction of inhibition — usually complete inhibition — and if the 
 dog is started running in the midst of a period of gastric quiescence 
 there is no evidence of increased gastric tonus or beginning of 
 hunger contractions. If the dog is made to, run at high speed the 
 inhibition persists during the entire period, even if the nmning is 
 kept up for one or two hours. When the dogs ran at rather high 
 speed for an hour or more the gastric inhibition usually persisted 
 from 20 to 40 minutes after the dog stopped running. The return 
 of gastric tonus and hunger contractions in such cases is very 
 gradual. But frequently when the gastric tonus finally recovered 
 after a running period it was higher than before the dogs began 
 to run. Thus a dog showing type I or II of hunger contractions 
 when he started to run in the mill showed an increased tonus and 
 type III of hunger contractions 30 minutes after he stopped running, 
 while the running period itself was accompanied by complete gastric 
 inhibition. If the dog runs only moderately fast in the mill the 
 gastric tonus and hunger contractions reappear during the running 
 
2o6 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 period, or come on during the running, in case the dog is started 
 when the empty stomach is quiescent. 
 
 These facts indicate that the carnivorous animal in pursuit of 
 its prey must be urged on by something else than the pangs of 
 hunger, as these are inhibited by the chase. Brisk walking or 
 running leads also to inhibition of the digestion movements of the 
 stomach, according to the observations of Cohn on dogs. Bender on 
 man, and Scheunert on the horse. 
 
 2. Effects of 4- to 6-milewalk. — Eight tests (with a corresponding 
 number of controls) on two dogs failed to show any marked effect 
 of a 4- to 6-mile walk on the gastric hunger contractions either in 
 the way of increase or decrease, the records being taken during the 
 two hours following the walk. These walks certainly caused no 
 depression of the dog's hunger contractions. But the dog that 
 showed type II contractions in the control usually showed type II 
 contractions after the walk, with no definite increase either in rate 
 or intensity. This should be noted, however, that after these walks 
 both dogs showed greater restlessness than when taken from the 
 kennels directly to the laboratory. They were not so easily quieted 
 in the lap of the assistant. This rather restless conditioin of the 
 dogs may have counteracted any augmentation of gastric hunger 
 contractions due to the walk, as restlessness from any cause tends 
 in the dog to inhibit the hunger contractions. 
 
 3. Effect of intense stimulation of the cutaneous nerve-endings for 
 the sensation of cold. — When a dog is lying quietly and comfortably 
 in the lap of an assistant, surrounding the dog with an ice pack or 
 placing him directly on a slab of ice leads to struggling and rest- 
 lessness. After a number of repetitions of these procedures most 
 dogs become so accustomed to it that they pay little or no attention 
 to the change and show no restlessness or struggling. If the dog 
 is disturbed or struggles when placed on the slab of ice or surrounded 
 by an ice pack there always follows a temporary inhibition of 
 gastric tonus and hunger contractions. But this does not indicate 
 the initial or primary effect of stimulation of the cutaneous nerve- 
 endings for cold, because the same type of inhibition is induced by 
 restlessness or struggle for any cause. After the dog is trained to 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 207 
 
 these procedures strong stimulation of the cutaneous nerve-endings 
 for cold by the ice pack, by placing the dog on a slab of ice, or by 
 turning on an electric fan in a cold room after uncovering the dog, 
 has no immediate effect on the gastric tonus and hunger contrac- 
 tions. There is usually an increase in the intra-abdominal pressure 
 owing to the increased tonus of the abdominal muscles. If the ice 
 pack is apphed during a period of gastric quiescence there is no 
 immediate increase in gastric tonus or initiation of the himger 
 contractions, even though the dog starts to shiver violently in a 
 few minutes. If the ice pack is applied during the hunger contrac- 
 tions, these contractions do not change appreciably either in rate 
 or strength, at least for some time. This is true even when the dog 
 shivers considerably. It would thus seem that the vagus centers 
 governing the gastric tonus are not directly affected by even very 
 strong stimulation of the cutaneous nerve-endings for cold. 
 
 In several instances the continued application of the ice pack 
 (30 to 40 minutes), and in consequence continued shivering, led to a 
 gradually increased gastric tonus and the appearance of type III 
 himger contractions. These may be due to changes iii the blood 
 as a result of increased oxidation, or they may appear from causes 
 not connected with the stimulation of the cold nerve-endings. 
 Such change in the hunger contractions is not infrequent in dogs, 
 even when they are lying undisturbed and comfortable in the lap 
 of an assistant. ' 
 
 It is conceivable that the stimulation of the cold nerve-endings 
 in the skin does influence the vagogastric tonus centers, but the 
 stimulation acts equally on the gastric inhibitory mechanism via 
 the splanchnic nerves, so that the net result on the empty stomach 
 is nil. This possibility is cleared up by the test on dogs with section 
 of both splanchnic nerves. Tests were made on two dogs on which 
 the operation had been performed. The results were practica-lly 
 identical with those on normal dogs. The ice pack neither decreased 
 nor increased the gastric hunger contractions. It is therefore clear 
 that the nervous impulses that give rise to the sensation of cold and 
 induce increased neuromuscular tonus in general have no direct 
 action on the vagogastric tonus centers. 
 
2o8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 ); 
 1 
 
 IT 
 
 '' ''■''!';'' 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 209 
 
 Fig. 25. — A, tracing from the empty stomach of a dog. I. Dog standing in 
 treadmill, stomach showing type I hunger, contractions. At x, the dog begins to run 
 in the mill with the result that gastric hunger contractions are promptly inhibited. 
 The running was kept up for 60 minutes. II. Record from stomach of same dog 45 
 minutes after he ceased running, showing increased gastric tonus. B, tracing from 
 the empty stomach of man (A. J. C.) in standing position; beginning of a hunger period. 
 At X, the man began running, with the result that the hunger contractions were 
 promptly inhibited. C, tracing from the empty stomach of dog with section of splanch- 
 nic nerves on both sides. At x the dog is surrounded by an ice pack. D, tracing from 
 the empty stomach of man (A. J. C.) in the midst of a period of hunger contractions. 
 The man was stripped and covered up with blankets in a cold room (20° C). At x 
 the covers were removed and a fan close to the man started. Shivering began at x'; 
 showing a temporary but partial inhibition of the hunger contractions. E, records 
 of culminations of periods of gastric himger contractions of A. J. C. I. The ordinary- 
 type of ending of the hunger periods without tetanus. II. ^unger period ending in 
 incomplete tetanus three hours after intense stimulation of the cold nerve-endings 
 (bath at 10° C. for 15 minutes). 
 
2IO CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 3. RESULTS ON MAN 
 
 1. Direct effect of muscular exercise. — Standing or walking in situ 
 has no effect on the gastric tonus or the hunger contractions. But 
 running in situ promptly inhibits the hunger contractions. The 
 degree and duration of the inhibition are on the whole directly pro- 
 portional to the speed of the running. In some cases walking seemed 
 to prolong a hunger period without changing the rate or intensity 
 of the individual contractions. In no case did walking or running 
 induce hunger contractions in the quiescent stomach. The results 
 on man are thus identical with the results on dogs. In both species 
 rapid running is accompanied by inhibition of the gastric tonus 
 and hunger contractions. In the case of the dog running in the 
 treadmill, one caimot be sure that the exercise is strictly voluntary 
 and enjoyable. The inhibition may therefore be due to certain 
 emotional states (anxiety, discomfort, mild anger, or fear). This 
 possibiHty is eliminated by the tests on man. In the men the 
 conditions of the emotions when running in place were not different 
 from that when standing or walking in place. In no case was the 
 running carried to the poipt of .respiratory, cardiac, or muscular 
 distress. 
 
 2. After-effects of muscular exercise. — Moderate exercise in the 
 form of playing tennis or walking 4 to 8 miles was taken in the after- 
 noon. No supper was taken, and the motor condition of the 
 empty stomach was recorded from 8:00 p.m. to 12:00 midnight. 
 The tracings obtained on the days specific exercise was taken 
 show on the whole greater gastric himger activity than the controls. 
 The periods of quiescence become shorter. This tends to make the 
 gastric hunger contractions more or less continuous, and there 
 appears to be some increase in the rate of the contractions. A 
 typical experiment (S. J. O.) may be cited in the way of illustration. 
 
 Record of control day. — Luncli i : 30 p.m. No special exercise. No supper. 
 Period of observation 8:00 p.m to 12 midnight. 
 
 8:00 to 10:00 P.M. Stomach practically quiescent. 
 10:00 to 10:40. Strong hunger contractions, ending in tetanus. 
 
 10:40 to 11:35. Stomach quiescent. 
 
 11:3s to 12:05. Moderate hunger contractions ending in tetanus. 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 211 
 
 Record of exercise day. — ^Lunch 1:30 p.m. No supper. Tennis 4:00 to 
 5:00 P.M.; walking 6:00 to 7:00 p.m. Period of observation 8:00 p.m. to 12 
 midnight. 
 
 8 : 1 s to 9 : so p.m. Practically continuous hunger contraction ending 
 
 in strong tetanus. 
 9:50 to 10:20. Stomach quiescent. 
 
 10: 20 to II :4o. Strong hunger contractions ending in tetanus. 
 
 (Control day, 70 minutes; exercise day, 190 min- 
 utes.) Total duration of hunger periods from 
 8:00 p.m. to 12 midnight. 
 
 In some instances there was no marked difEerence between 
 records of the control and the exercise days. This is to be expected, 
 since the activity of the gastric hunger mechanism depends in part 
 on factors not understood or controlled. Exercise that brings ori a 
 degree o-f fatigue bordering on exhaustion seems to depress the 
 gastric hunger mechanism. But our experiments on this point are 
 as yet too few to permit a final conclusion. 
 
 3. Direct effect of stimulation of the cold nerve-endings of the skin. — ■ 
 The immediate effect of stimulation of the cold nerve-endings of 
 the skin by ice pack, alcohol bath, cold shower bath, or cooled air 
 is inhibition of the gastric tonus and hunger contractions, and the 
 degree of inhibition is proportional to the intensity of the stimula- 
 tion. In no instance did we observe an initial increase in gastric 
 tonus and hunger contractions. When the stimulation is continued 
 the inhibitory effects gradually diminish, even though the man 
 shivers intensely from the cold. In this way the gastric hunger, 
 contractions may return to their normal rate, intensity, and regu- 
 larity, while the man is shivering and jerking like a dog in mild 
 parathyroid tetany. It may be noted in this connection that mild 
 and in some instances fairly severe parathyroid tetany in dogs does 
 not appreciably influence the gastric hunger contractions. 
 
 Intense stimulation of the heat nerve-endings of the skin (hot 
 shower) produces practically the same initial inhibition as the 
 corresponding stimulation of the cold nerve-endings. 
 
 While it is true that on prolonged stimulation of the cold nerve- 
 endings of the skin, during a period of gastric hunger contractions, 
 the inhibitory effects gradually disappear, so that the contractions 
 
212 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 reappear in their normal intensity, these contractions are always 
 felt as weaker than the normal, or may not be felt at all. Evidently 
 the intense sensation of cold dominates consciousness to the exclu- 
 sion of the gastric htmger pangs. 
 
 It is well known that strong stimulation of the cold nerve- 
 endings of the skin causes a reflex increase of tonus of the urinary 
 bladder. In several instances we started these stomach tests on the 
 men at a time when their bladders were known to contain 50 to 
 260 c.c. of urine. This permitted us to compare the reflex effect 
 of cold on the stomach and bladder tonus without a balloon in the 
 bladder. When the cold stimulation began during a period of 
 gastric quiescence and was continued long enough to induce intense 
 shivering, a strong desire to micturate soon developed while there 
 was no evidence of increased gastric tonus. Prolonged cold stimu- 
 lation may produce so great a, tonus of the bladder that micturition 
 cannot be inhibited voluntarily. The tonus centers of the urinary 
 bladder are, the vagogastric tonus centers are not, directly in- 
 fluenced by cold stimulation of the skin. 
 
 When the cold nerve-endings of the 'skin are stimulated, as 
 described above, during a period of quiescence of the empty stom- 
 ach, the stomach remains quiescent. If there is any change in the 
 gastric tonus it is in the direction of inhibition. Nevertheless, this 
 cold stimulatibn, if not sufficiently intense to be painful, seemed to 
 induce a "sensation of emptiness" in the abdominal region, a 
 sensation that seemed to be associated with^ appetite and desire 
 for food. We record this with some hesitation, for this sensation 
 of emptiness may be purely subjective (auto-suggestion). It may 
 also be due to the increased tonus of the abdominal muscles. In 
 any event this sensation is clearly different from the hunger pangs. 
 
 4. After-effect of the stimulation of the cold nerve-endings of the 
 skin. — ^All of the tests in this group were made on one man (A. J. C). 
 A prolonged cold bath, from 6 : 00 to 7 : 00 A.M., followed by a brisk 
 walk, nearly always resulted in increased hunger activity of the 
 stomach as recorded for the period 8:00 a.m. to 12:00 m. The 
 temperature of the water varied from 5° C. to 15° C. The subject 
 remained in the water as long as was deemed safe (10 to 20 minutes) 
 despite discomfort and pain. Water at this temperature soon brings 
 
NERVOUS CONTROL OF THE HUNGER MECHANISM 213 
 
 on shivering, contracture, and at times severe headache, and it 
 requires much vigorous exercise to restore the feeling of warmth. 
 Rubbing the skin (rough towel) seems to be of little avail. A 
 typical experiment may be cited in illustration. 
 
 Control record. — ^No bath or breakfast. Observation period 8:00 a.m. to 
 12:00 M. 
 
 8:50 to 10:00 A.M. 26 fairly strong hunger contractions; no tetanus. 
 ii:ootoii:4S. 22 fairly strong hunger contractions; no tetanus. 
 
 Gastric tonus on the average 5 cm. bromoform. 
 Test period. — 6:00 to 6:15 a.m., cold bath (temperature of water 10° C). 
 No breakfast. Observation period 8:00 a.m. to 12:00 m. 
 
 8:00 to 9:00 A.M. 32 strong contractions; no tetanus. 
 9:4s to 10:25. 23 fairly strong contractions; no tetanus. 
 
 1 1 : 1 S to 1 1 : 45. 19 strong contractions ending in tetanus. 
 
 Gastric tonus on the average 8 cm. bromoform. 
 Control period. — ^48 hunger pangs; no tetanus. 
 Test period. — 74 hunger pangs; tetanus. 
 
 Under ordiuary conditions the periods of gastric hunger con- 
 tractions of the author do not end in tetanus, but the hunger tetanus 
 appears after 3 to 4 days' complete starvation. Intense stimulation 
 of the cold nerve-endings for 15 to 30 minutes thus seems to bring 
 about a condition similar to prolonged starvation. This is in har- 
 mony with the observation of Lusk that such stimulation quickly 
 renders the liver free from glycogen. This effect of cold on the 
 gastric himger mechanism is obviously an indirect one, or brought 
 about through changes in the blood, and is not a direct reflex from 
 the skin. 
 
 Lusk has shown that intense cold leads to quicker and more 
 complete oxidation of the body glycogen than prolonged starvation. 
 And it is interesting to note that the same stimulus causes not only 
 an increase in the gastric himger contractions, but also an even 
 greater increase in the subjective hunger and appetite sensations, 
 probably owing to an increased excitability of the central nervous 
 system. The increased desire to eat after a cold bath, in the case 
 of the healthy individual, is a universal experience. I have inves- 
 tigated this matter in the case of young children, with whom habit 
 or intelhgence cannot be assigned as the cause for seeking food 
 
214 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 after a cold bath. It was found that young children react in the 
 same way as adults. 
 
 While these observations include only two species (man, dog), 
 it does not seem likely that the gastric vagotonus mechanism will 
 have different reflex associations in other animals. But this opinion 
 should not stand in the way of actual investigation of the condition 
 in other vertebrates as well as in the invertebrates. In man and in 
 dogs the situation appears to be this: The vagus motor nuclei 
 in the medulla control, in part, the tonus and hunger contractions 
 of th© stomach, The tonus of the vagus nuclei, in turn, are con- 
 trolled by the condition of the blood rather than by afferent nervous 
 impulses, unless sensory impulses from the stomach musculature 
 itself play such a r61e. This possibiKty is now imder investigation. 
 
 iii. afferent or sensory paths of the hunger complex 
 
 and the question of the cerebral 
 
 "hunger center" 
 
 1. Rdle of the vagi. — The vagi nerves are the main, if not the 
 orily, afferent pathway for the gastric hunger impulses, although 
 Luciani assumes that some of the hunger impulses from the 
 stomach are carried by the sympathetic (splanchnic) fibers. If 
 the contraction of the small intestine contributes to the hunger 
 sensation, the afferent hunger impulses may involve sympathetic 
 and spinal nerves, but all sensory conduction from the stomach 
 appears to be confined to the vagi, because no central reflexes of 
 any kind can be evoked by stimulation of the stomach after section 
 of all the vagi fibers to that organ (Miller). We need not here refer 
 to the physiologists who have argued against the vagi nerves (and 
 in favor of the splanchnics) as being concerned in hunger on the 
 basis that animals will continue to eat after section of these nerves 
 or after excision of the stomach, as these objections have already 
 been considered and refuted. 
 
 2. The primary hunger center is therefore the sensory' nuclei of 
 the vagi nerves in the medulla (fasciculus solitarius). Some of 
 the more direct hunger reflexes (such as salivation, vasomotor 
 fluctuations, etc.) may be carried out via these medullary centers 
 alone. Luciani assumes also spinal hunger centers analogous to 
 
NERVOUS. CONTROL OF THE HUNGER MECHANISM 215 
 
 these sensory vagi nuclei. There is no evidence that the processes 
 of conscious hunger sensation can take place in the medullary- 
 nuclei. 
 
 3. Rdle of the optic thalami and the mid-brain. — The important 
 facts in this connection are the hunger behavior of decerebrated- 
 animals (acephalic infants, dogs, pigeons, frogs). This hunger 
 behavior has already been ascribed. These animals minus the 
 cerebral hemisphere, but with the thalamic region of the brain 
 intact, exhibit practically all the hunger behavior of normal animals, 
 except the intelligent search for and ingestion of the food. But 
 even this statement requires limitation, for, according to Ewald,^ 
 decerebrated pigeons and frogs will finally eat spontaneously if 
 kept in good condition for a sufficient time (months) after the 
 operation. 
 
 Rogers has recently made the important observation that the 
 hunger behavior of the decerebrated pigeon is completely abolished 
 on removal of the optic thalami. It is thus clear that this region 
 contains important nuclei for the elaboration of the bodily responses 
 to the himger impulses from the stomach. Whether or not the 
 processes of conscious hunger sensations are elaborated in the 
 thalamus cannot be determined on experimental animals. L. R. 
 Miiller assximes that conscious hunger sensations are evoked in the 
 mid-brain. We have seen that hunger is essentially pain, and some 
 neurologists take the position that the sensation of pain is a thala- 
 mic rather than a cortical function. This view is supported by the 
 extensive studies of Head and Hohnes on the change in the pain 
 sense in persons with thalamic lesions and intact cortex. The 
 frequent occurrence of excessive hunger or polyphagia in persons 
 with tumors of the pineal glands have by some (Schiiller) been 
 interpreted as due to a pressure stimulation of subcortical hunger 
 centers. Whether the thalamic processes caused by the gastric 
 hunger contractions are conscious or merely subconscious reflexes, 
 or whether the nuclei concerned with these processes are identical 
 with those involved in pain sensation, it is clear that the thalamus 
 
 ' Quoted from A. L. Gillespie, The Natural History of Digestion, New York, 1898, 
 286. 
 
2i6 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 is a very important reflex and relay station for the afferent 
 hunger impulses. 
 
 4. Cortical hunger centers. — Concerning these practically nothing 
 is known. There can be little doubt that conscious hunger 
 
 involves in some way , cortical 
 processes, and one might expect 
 the part of the cortex involved 
 would be contiguous with that 
 for the gustatory sense, the latter 
 being placed in the hipochampal 
 gyrus by the majority of neurol- 
 ogists and psychiatrists. Roux 
 assiunes that the cortical hunger 
 center is in the Rolandic area, 
 thus supporting Bechterew, who 
 locates the conscious taste pro- 
 cesses in the region of the Rolandic 
 area which iimervates the muscles 
 of mastication and deglutition. 
 
 To recapitulate: In the affer- 
 ent phase of the hunger complex 
 the facts clearly estabh'shed are 
 the r61e of the vagi, and the 
 sensory vagi nuclei in the medulla, 
 and the great importance of the 
 thalamus. The cortical factors^in 
 hunger are unknown, and the same 
 appUes to the detailed roles of the 
 subcortical hunger centers both 
 in health and in disease. This 
 field of the physiology of hvmger 
 is therefore mainly "gaps and 
 guesses . " It remains for the clini- 
 cal investigator to correct the guesses and fill up the gaps, as very 
 little can be done with these problems on animals below man, at 
 least vidth the methods so far available to the physiologist. 
 
 Fig. 26. — ^Diagram of the nervous 
 mechanism of the hunger sense. A , cer- 
 ebrum. B, optic thalami. C, motor 
 nuclei of the vagi nerves. D, sensory- 
 nuclei of the vagi nerves. F, medulla 
 oblongata. G, spinal cord. H, stomach. 
 I, visceral sjrmpathetic ganglia. K, 
 splanchnic nerves. L; motor fibers to 
 the stomach. M, sensory paths (hunger) 
 to cerebrum (hypothetical) . N, sensory 
 fibers from stomach in the vagi, + 
 indicates motor, — indicates inhibitory 
 effects, -» indicates direction of nerv- 
 ous conduction. 
 
CHAPTER XIII 
 THE CHEMICAL CONTROL OF THE HUNGER MECHANISM 
 
 I. ANALYSIS OF THE PROBLEM 
 
 The reader will recall from the review of the literature on hiinger 
 and appetite in chap, ii that most of the authors assume a chemical 
 control of the hunger mechanism in the sense that starvation 
 changes of. the blood stimulate the conscious hunger center in the 
 brain, the specific sensory nerves in the stomach, or sensory nerves 
 in all the tissues. We know now that the hunger sensation is caused 
 by strong contractions of the empty or nearly empty stomach. 
 This fact modifies but does not eliminate the question of chemical 
 control of the hunger mechanism. We must now determine whether 
 starvation changes in the blood influence the motor side of the 
 mechanism, while the earlier authors considered the influence of 
 the blood only on the sensory side of the hunger apparatus. 
 
 Chemical changes in the b lood may act in a positive way either 
 on the vagi tonus centers in jy]£_bram ox_directiy on the stomach 
 motortissues. The problem of chemical control of hunger is thus 
 resolved into three main queries, namely: (i) Do chemical stimuli 
 in the blood cause the increased gastric tonus of hunger ? (2) Do 
 chemical stimuH in the blood initiate the individual gastric hunger 
 contractions ? (3) Do chemical stimuli control the grouping of the 
 hunger contractions into hunger periods, separated by periods of 
 relative gastric quiescence, in species showing this grouping ? 
 
 We must also consider the possibility of chemical blood changes 
 that may depress or inhibit the hunger contractions. 
 
 The gastric hunger contractions are inhibited by mechanical an d 
 chemi ^Tstimxi la tionorthe nerve-endmgs in the m ucous memtojie 
 of tEemouth^^^jS^haiiJva^^ insures inhi- 
 
 bition of the hunger contractions during mastication and gastric 
 digestion. The gastric himger mechanism receives motor or tonic 
 innervation via the vagi, and the central connections of this tonus 
 
 217 
 
2i8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 innervation appear to be practically isolated from all normal 
 reflexes, while the inhibitory mechanism via the splanchnic nerves 
 is very readily called into activity reflexly. The foregoing facts 
 appear to have only two alternative explanations, viz: (i) The 
 gastric hunger contractions are due to a specific automatism (vagi 
 centers and stomach) primarily independent of afferent impulses 
 as well as the conditions of the blood. Such an automatism would, 
 of course, vary with the physiological condition of the automatic 
 tissues ; but if this is the mechanism we cannot speak of any physio- 
 logical nervous control of the hunger apparatus, except in the way 
 of inhibition. (2) The vagi and the gastric mechanism, concerned 
 in the genesis of the hunger contractions may be influenced in a 
 positive way by physiological changes in the blood. If this is the 
 case, we might expect such changes in the blood to be specially 
 evident in the normal animal when starving. 
 
 . Some of the facts already discussed seem to show that both of 
 \the factors named above are to be reckoned with. Lima n and dog 
 t he gastric hunger contractions usually appear as soon as the 
 stomach is empty of food^_&at is, before intestinal digestion and 
 absorption ot ttie meal are completed. Under these conditions the 
 initiation of the hunger- coatractiras must be due to a primary 
 aut omatism not oppos e d by inhibitory reflexes rathe r than to any 
 cTiaiiges in the blood such as arejgresumably involved in starvation, 
 for tiiere^is surelyTio^^uto-digestion of the body tissues or lack of 
 pabulum in the body fluids while normal intestinal digestion and 
 absorption are still in progress. In dogs with Pavlov stomach 
 pouches we may also have hunger contractions in the main stom- 
 ach while the Pavlov stomach is quiescent, or vice versa. \0n the 
 other Jiand. evressiye hemorrhage^ prolo nged starvation, ajig"pan - 
 creajic_ diabetes. which is a type of starvation, lead to increased 
 actiyit;^;__ofthe hunger mechanism, a t least up to the poin t 
 wh ere the stomach becomes directly involved in the general 
 , de pility and cache xia . The mcreasedTvigor oT the hungefapparatus 
 in normal individuals a s a n after- effect of th e greatly accelera ted 
 'metabolism caused by physical Exertion and cold, is a bit of 
 'evidSTce pointing in the same direction. 
 
CHEMICAL CONTROL OF THE HUNGER MECHANISM 219 
 
 This augmentation of the hunger contractions in starvation 
 may be due to (i) the appearance of substances in the blood stimu- 
 lating the central tonus mechanism or the peripheral hunger 
 apparatus; (2) the absence or diminution of inhibitory substances 
 in the blood; (3) the absence or depression of inhibitory reflexes; 
 (4) starvation changes in the tissues directly concerned in the 
 hunger contraction. 
 
 If it is due to the presence of stimulating substances in the 
 blood, it would seem that transfusion of the blood of starving 
 animals into normal animals- ought to augment the activity of the 
 hunger mechanism, at least temporarily. This is actually the case. 
 
 II. ACTION OF BLOOD OF STARVING ANIMALS ON THE GASTRIC 
 HUNGER MECHANISM OF NORMAL ANIMALS 
 
 Direct transfusion from the starved donor to the normal recip- 
 ient by direct union of blood vessels is not feasible, because if 
 this is done imder general anesthesia, the anesthetic itself depresses 
 the stomach, and if it is done with aid of local anesthesia only the 
 recipient is so disturbed that the stomach is inhibited reflexly. 
 But we found that good-natured and gentle dogs used to our 
 routine of recording the gastric hunger contractions were practically 
 not disturbed at all by the puncture of the saphenous vein with a 
 sharp needle and the injection of 20 to 50 c.c. fresh-drawn and 
 defibrinated blood. This technique was therefore adhered to. In 
 the preliminary training of these dogs the animal's legs were han- 
 dled in various ways (shaved, injection of salt solution, etc.), so 
 that the animal finally paid little or no attention to the handling 
 of the leg or the insertion of the needle into the vein. In some 
 cases we decreased the sensitivity of the skin over the saphenous 
 vein by the application of carbolated vaseline. 
 
 The intravenous injection of 20 to 50 c.c. of fresh defibrinated 
 blood from starving dogs into normal dogs increases the gastric 
 tonus and hxinger contractions of the latter, if their stomachs are 
 empty and if moderate tonus and hunger contractions are in evi- 
 dence in the recipient at the time of the injection of the blood. If 
 the stomach of the recipient, although empty of food, is atonic and 
 
220 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 hunger contractions are completely absent at the time of the 
 injections, the blood froni staring animals has practically no 
 action on the stomach. The stimulating action of this blood on 
 the stomach already in moderate tonus and hunger contractions 
 lasts from lo to 30 minutes, depending on the quantity of starved 
 blood injected. 
 
 The foregoing conclusion is based on 25 experiments on 4 
 gastric-fistula dogs. The blood for the transfusion was drawn from 
 animals after 5 to 12 days of starvation. 
 
 Fig. 27. — Tracings from the empty stomach of dogs. ^4, at an intravenous 
 injection of 35 c.c. blood drawn from a dog on the eighth day of starvation; showing 
 stimulation of the gastric hunger apparatus, in the change from type I to type III 
 hunger contractions (hunger tetanus). B, at an intravenous injection of 20 c.c. of 
 blood from a dog in pancreatic diabetes; showing stimulation of the gastric hunger 
 mechanism (Luckhardt and Carlson). , 
 
 The failure of starved blood to induce tonus and hunger con- 
 tractions in atonic and quiescent stomachs is probably due to the 
 fact that by the present method of transfusion it is not possible 
 to introduce enough starved blood to overcome the inhibitory 
 factors responsible for the atonic and quiescent condition. 
 
 ni. EFFECTS OF BLOOD FROM DIABETIC ANIMALS 
 
 Under the technique described above, 20 to 50 c.c. of blood 
 from animals in pancreatic diabetes and showing the typical dia- 
 betic polyphagia were transfused into normal animals. The results 
 
CHEMICAL CONTROL OF THE HUNGER MECHANISM 221 
 
 were practically identical with those from the blood of starving 
 animals, that is, a temporary stimulation of the gastric hunger 
 mechanism. 
 
 From 20 to 50 c.c. of blood from normal dogs or from dogs 
 whose digestion was at its height were transfused into dogs while 
 their gastric tojius and hunger contractions were being registered. 
 In the majority of these experiments the transfusion had no effect 
 at all on the motor condition of the empty stomach. In a few 
 cases it acted as a very slight and transient stimulus, but in no 
 instance did the blood from normal animals produce the marked 
 effects obtained from the blood of starving and of diabetic animals. 
 Hence we conclude that the latter results are due to something 
 in the blood of starving and of diabetic animals not present, or 
 present in less concentration, in the blood of normal animals. It 
 is evidently not due to the transfusion of the above-named quanti- 
 ties of defibrinated blood as such, although defibrinated blood 
 contains a substance which induces contraction in vascular and 
 intestinal muscle. The intravenous injections of 20 to 50 c.c. of 
 0.9 per cent NaCl is also without effect on the hunger mechanism. 
 
 It is well known that intravenous injections of considerable 
 quantities of fresh defibrinated blood may cause temporary vaso- 
 motor and cardiac disturbances. Lowering of the arterial blood 
 pressure is usually a feature of these disturbances. Is vasodila- 
 tion a factor in the marked results produced by blood from starving 
 and diabetic animals ? The following control tests were made: A 
 mixture of i per cent peptone in 0.9 per cent NaCl was injected 
 intravenously, and amyl nitrite was administered by inhalation. 
 If sufficient peptone or amyl nitrite is given to affect the gastric 
 tonus and hunger contractions, this effect is always in the direction 
 of inhibition and paralysis. It is not clear, however, that this 
 inhibition is due solely to the vasodilation, but the experiments 
 show that a moderate general vasodilation does not necessarily 
 lead to stimulation of the gastric hunger apparatus. 
 
 As a preliminary step in the analysis of the stimulation of the 
 gastric hunger mechanism by starved and diabetic blood, we have 
 tested the action of acetone and oxybutyric acid on the gastric 
 
222 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 hunger contractions. It is well known that prolonged starvation 
 as well as diabetes leads to acidosis, although there is practically 
 no acidosis in pancreatic diabetes in dogs (Mariott). It seemed 
 possible that the acetone bodies might be the stimulating factors 
 in the starvation and the diabetic blood. The action of the acetone 
 bodies dissolved in Ringer's solution was tested on a number of 
 animals with uniformly negative results. That is to say, the ace- 
 tone bodies in concentrations that affect the gastric hunger appa- 
 ratus at all cause inhibition and depression. No indication of any 
 primary or secondary stimulation by the acetone bodies could be 
 secured. It is therefore clear that the stimulating actio~n of starva- 
 tion and diabetic blood on the hunger mechanism is not due, at 
 least not directly, to the acetone bodies. 
 
 IV. EFFECT OF HEMORRHAGE ON THE GASTRIC HUNGER MECHANISM 
 
 Some of the blood conditions of starvation may be produced 
 temporarily by excessive hemorrhage. It is recognized, of course, 
 that hemorrhage also introduces factors not present, at least in 
 moderate starvation, such as the temporary diminution of hemo- 
 globin. Nevertheless, the results of two series of experiments with 
 the effects of excessive hemorrhage are so striking and conclusive 
 that they are reported, even though we have not worked out their 
 interpretation. The results are most conveniently stated by the 
 following brief protocols: 
 
 Dog I. Weight 6. o kg. 
 
 Types II and III gastric hunger contractions. 
 
 Type I contractions. Gastric tonus =3 cm. chloroform. 
 
 " I " " " =3 cm. 
 
 " I " " " =3 cm. 
 
 " I " « « =2|cm. 
 
 9:12 A.M., light ether anesthesia; 146 c.c. blood drawn from carotid 
 artery at 9:30 A.M. Recording of the gastric hunger contractions 
 began 10 : 08 a.m. At this time the stomach was atonic and quiescent. 
 A gradual return of gastric tonus appeared at 10:30 a.m. At ii :oo 
 A.M. the gastric tonus was 5 cm. chloroform with vigorous type III 
 hunger contractions, and this condition persisted till the end of the 
 experiment at 12 :3o p.m. 
 
 Oct. 
 
 20. 
 
 (( 
 
 21. 
 
 n 
 
 22. 
 
 " 
 
 23- 
 
 it 
 
 24. 
 
 U 
 
 27. 
 
CHEMICAL CONTROL OF THE HUNGER MECHANISM 223 
 
 Oct. 28. Type I contractions. Gastric tonus =2^ cm. chloroform. 
 " 29- " I " " " =3 cm. 
 
 " 30. " I " " " =3 cm. ' « 
 
 31- 
 
 : cm. 
 
 Control Experiment on Dog I 
 
 November 18, Ether Anesthesia for,2o Minutes 
 
 Nov. 18. Type I contractions (very feeble) . Gastric tonus 2 cm. chloroform. 
 " 19. " I contractions (feeble) . Gastric tonus 2 cm. chloroform. 
 " 21. « I « « « 3j,m_ « 
 
 " I " « " 2 cm. 
 
 " II " " " 35 cm. 
 
 Dog II. Weight 6.7 kg. 
 
 Tj^e I hunger contractions. Gastric tonus 2 cm. chloroform. 
 
 " I " " " « 2 cm. 
 
 " I and II hunger contractions. Gastric tonus 3 cm. chloroform. 
 
 " I hunger contractions. " " 2 cm. " 
 
 " I " « « " 2 cm. ■ « 
 
 9: 10 A.M., 169 c.c. blood withdrawn from carotid artery under light 
 ether anesthesia. Record of gastric contractions began at 9:45 a.m. 
 At this time the stomach was quiescent with feeble tonus. At 
 10:00 A.M. the gastric tonus began to increase. At 10:30 a.m. the 
 gastric tonus was 9 cm. chloroform with type III vigorous hunger 
 contractions. This condition persisted till the end of the experiment 
 at 11:30 A.M. 
 Nov. 7. Types II and III contractions. Gastric tonus 25 to 3 cm. chloroform. 
 " II. « Ilandlll « « " 3 to 7 cm. 
 
 " 12. Type I " " " 2§cm. 
 
 u 
 
 25- 
 
 U 
 
 26. 
 
 Oct. 
 
 30- 
 
 U 
 
 31- 
 
 Nov. 
 
 3- 
 
 ti 
 
 4- 
 
 li 
 
 S- 
 
 " 
 
 6. 
 
 Control Experiment on Dog II 
 November 18, Ether Anesthesia for 20 Minutes 
 
 Nov. 18. Types I and III contractions. Gastric tonus i to 4 cm. chloroform. 
 
 " 20. " I and III « « « 2 cm. 
 
 " 21. Type I " " « 2 cm. 
 
 ■ " 24. " I " " " 2 cm. 
 
 « 25. " III " " « 3 to 4 cm. 
 
 " 26. Types I and III " " " 3 to 6 cm. 
 
 The reader will note that in both dogs the hemorrhage induced 
 temporarily a greater gastric tonus and intensity of hunger contractions 
 
224 ' CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 than those typical for these dogs before the hemorrhage. This effect 
 of the hemorrhage disappears in less than 24 hours. The controls 
 show that the stimulation of the gastric tonus mechanism is due to 
 the hemorrhage, and is not an after-effect of the ether anesthesia. 
 That they were felt as himger contractions by the dogs was evi- 
 denced by the amount of food consumed on the hemorrhage days. 
 The foUbwing considerations might be offered, not only as a 
 possible, but also as a probable explanation. Xb^ blood is, of 
 c ourse, the purveyor of nutritive substances to all the tissues of th e 
 body. Its chemical composition is kept remarkably constant. If 
 
 Fig. 28. — A, tracing showing gastric tonus and type I himger contractions 
 characteristic of dog before hemorrhage. B, record of gastric tonus contractions of 
 dog 60 minutes after drawing 169 c.c. blood from the carotid artery; showing the 
 temporary stimulation of the gastric hunger mechanism as an after-effect of excessive 
 hemorrhage (bottom of tracing =0 mm. pressure) (Luckhardt). 
 
 now an a nimal is bled extensively. (2 to 3 per cent of body weight), 
 there is r emoved suddenly an enormous amount of pabulum, that 
 is, 6i those various substances whic h_aj e taken up by tiie different 
 tissues during circulation. T he organs and tissues deprived ' of 
 these respect ive nutritive substan ces bernme hiinp;ry (call for food) 
 by givmg u p a something (a hormonel which acts on the neuromus - 
 cul ar apparatus of the stomach to produce the htmger contractio ns. 
 We recognize, of course, that acute hemorrhage introduces 
 other factors. Some of them have been mentioned. The explana- 
 tion offered gives a simple, reasonable picture of the mechanism 
 involved. By acute hemorrhage we induce sudden acute starvation. 
 Probably all the tissues of the body give up this " hunger hormone." 
 By withholding food from the animal the blood changes appear 
 
CHEMICAL CONTROL OF THE HUNGER MECHANISM 225' 
 
 more slowly, depending for one thing on the state of nutrition and 
 reserve food supply of the animal before the period of starvation 
 is started. 
 
 V. HUNGER CONTRACTIONS OF THE STOMACH POUCH ISOLATED 
 ACCORDING TO THE METHOD OF PAVLOV 
 
 It was hoped that simultaneous record of the contractions of 
 the stomach pouch and of the main stomach would throw some 
 light on the relative importance of the tonus of the vagi, the con- 
 dition of the blood, and the physiological state of. the gastric motor 
 mechanisms in the genesis of the hunger contractions. The Pavlov 
 operation leaves the vagi connections with the stomach pouch at 
 least partially intact, so that if the hunger contractions are nor- 
 mally initiated by efferent vagi impulses we might expect a close 
 parallel between the rate and intensity of the contractions in the 
 two stomachs. The character of the blood flowing to the two 
 stomachs is necessarily the same. The amount of local nervous 
 co-ordination between the two stomachs depends on the extent of 
 the intact myenteric plexus and muscularis. The operation severs 
 hy far the greater amount of these neuromuscular connections. 
 This may diminish the local nervous co-ordination and thus per- 
 mit the development of different physiological states of the motor 
 mechanisms in the two stomachs. The work was done on two young 
 and vigorous dogs. Relatively large stomach pouches were made 
 according to the method of Pavlov. In Dog I the muscularis join- 
 ing the two stomachs was left intact for a distance of 6 cm. These 
 figures were verified by post-mortem examination at the end of the 
 experiment. 
 
 Simultaneous records of the hunger contractions in the two 
 stomachs were taken while the dogs were lying quietly and com- 
 fortably in the lap of an attendant. The balloon was passed into 
 the main stomach via the esophagus. The balloon used for the 
 stomach pouch was much smaller than that used for the main 
 stomach. 
 
 Results. — Dog I, having the 6 cm. of intact muscularis and 
 yenteric nerve plexus imiting the two stomachs, showed a familry 
 
226, . CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 close parallel of the tonus and the hunger contractions of the main 
 stomach and the stomach pouch. When the tonus of the stomach 
 was so great that the type III contractions (or incomplete tetanus) 
 were present, the synchrony appeared complete. The two stomachs 
 gave contractions of the same strength and rapidity. The con- 
 traction and relaxation phases of the individual contractions show 
 also a fair degree of correspondence. 
 
 When the gastric tonus is weaker, so that the stomach exhibits 
 the slower and stronger contractions of type II, the parallel between 
 the stomachs is still in evidence, but it is less complete. That is to 
 say, the contractions may appear simultaneously and be of corre- 
 sponding strength, they may appear simultaneotisly and be very 
 unequal in strength, or there may be considerable lack of synchrony 
 both in the beginning and in the duration of the contractions of the 
 two stomachs. At times the pouch would give two separate and 
 strong contractions during a single but more protracted contraction 
 of the main stomach. When the contractions are still slower, or of 
 type I, the co-ordination between the two stomachs is more nearly 
 perfect. 
 
 Dog II, with only 3 cm. of intact muscularis and myenteric 
 plexus uniting the two stomachs, exhibited no synchrony between 
 the two stomachs at any time. The main stomach would be quies- 
 cent, while the pouch showed vigorous hunger contractions, or 
 vice versa. But more frequently both stomachs exhibited hunger 
 rhythm at the same time, but without any synchrony in the rate 
 and the strength, of the contractions. 
 
 The Pavlov operation necessarily severs a considerable portion 
 of the vagi connection with the pouch. But it is weU known that 
 at least half of the vagus influence can be eliminated by section of 
 one vagus without any appreciable disturbance of the gastric tonus. 
 In general the hunger rhythm of the pouch in Dog II resembled 
 that of the stomach of dogs with section of both vagi. In this 
 animal (Dog II) the amount of vagi connections with the motor 
 mechanism of the pouch was not sufficient to maintain the normal 
 tonus. It is also evident that the 3 cm. bridge of myenteric plexus 
 was also insufficient for local co-ordination of the two stomachs. 
 
CHEMICAL CONTROL OF THE HUNGER MECHANISM 227 
 
 In Dog II, therefore, the two stomachs differed in the quantity of 
 innervation. The other obvious differences between the main 
 stomach and the pouch, such as the presence of saliva, the occa- 
 sional presence of intestinal juice and bile, gases and food debris, 
 hair, etc., were common for Dogs I and II. These conditions were 
 not sufficient to create inco-ordination through differences in the 
 physiological state of the motor mechanisms when the connecting 
 bridge of myenteric plexus was 6 cm. in length. The fact that in 
 Dog II the pouch would show the hunger contractions during 
 complete quiescence of the main stomach and vice versa seems 
 to show that the physiological state of the gastric motor mechanism 
 and not the character of the blood is the pri mary factor in the" 
 gen esis~or these contractions. The main stomacE and the poucBT 
 were supphed with the same blood. The character of the co- 
 ordination of the two stomachs in Dog I indicates that the himger 
 contractions are not normally caused by periodic impulses from the 
 brain via the vagi. If such were the case there should have been a 
 closer synchrony of the contraction and relaxation phases in the main 
 stomach and the pouch. A "primary vagi innervation of the con- 
 tractions would not permit a contraction in the pouch with no 
 contraction in the main stomach, the begirming of the pouch con- 
 traction during the relaxation phase of the main stomach, or 
 two distinct and strong contractions of the pouch during a single 
 contraction of the main stomach. These results are readily explain- 
 able on the basis of local genesis of the contractions and some 
 impairment of the myenteric connections between the two parts. 
 Under these conditions the physiological state of the motor mech- 
 anism of the two stomachs would not be exactly alike, and in con- 
 sequence there will be some interference with, or inhibition of, the 
 excitation wave at the isthmus joining the two parts, as well as in 
 the two stomachs themselves. Thus the excitation wave from the 
 main stomach may pass the myenteric bridge unimpeded, but may 
 reach the pouch during the refractory phase of the latter, and thus 
 produce little or no effect. And a similar interference may obtain 
 in the case of the excitation waves from the stomach pouch. Since 
 most of the myenteric plexus joining the two parts of the stomach 
 
228 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 is severed in the Pavlov operation, the local co-ordinating mechan- 
 ism is obviously imparled, although not completely destroyed. 
 And if we assume a peripheral origin of the hunger contractions, 
 this must lead to a certain degree of independent activity of 
 stomach and pouch. The results demanded by this assumption 
 of a peripheral stimulus or local axi tomatism initiating the hu nger 
 contractions~are th ose actually found in Dog I . that is, impaired 
 synchrony of the two parts. As we have seen, the s5aichrony of 
 the two stomachs is more nearly perfect the slower the contractions. 
 When the contractions come at longer'intervals there is less chance 
 for interference with the excitation wave in the region of the 
 myenteric isthmus and of collision, so to speak, with the refractory 
 state. The parallel in the activity of the two stomachs during 
 type III contractions may be only apparent or a parallel of the 
 tonus only, for when the tonus reaches a certain degree. the con- 
 tractions appear at their maximum rapidity. Hence if the main 
 stomach and the pouch have equally strong tonus they will exhibit 
 an equal niunber of contractions per unit of time, even without 
 any physiological co-ordination of the excitation waves between 
 the two stomachs. 
 
 SUMMARY 
 
 Blood from starving animals and animals in pancreatic diabetes 
 transfused into normal animals acts as a temporary stimulus to the 
 gastric hunger mechanism. 
 
 Excessive hemorrhage is followed by a temporary augmentation 
 of the gastric hunger contractions. 
 
 Prolonged starvation, pancreatic diabetes, aiid possibly exces- 
 sive hemorrhage result in some change in the bloody that acts as a 
 stimulus to the gastric hunger mechanism. 
 
 The character of the parallel between the himger contractions 
 of the main stomach ' and of the stomach pouch supports the 
 view that these contractions are caused primarily by a gastric 
 automatism and not by motor impulses via vagi nerves. 
 
 When the muscularis and myenteric isthmus joining the main 
 and the accessory stomachs is relatively narrow,, the two stomachs 
 
CHEMICAL CONTROL OF THE HUNGER MECHANISM 229 
 
 exhibit complete independence of the hunger contractions, even to 
 the point of vigorous activity of the one during quiescence of the 
 other. This fac t points to a , local a utomati sm, as a primary factor 
 rather thairthe_£onditira_of_the ^ood^ as the character of the 
 hlooS~^^mi^ ^ the main stomach and -llie.-s.t~Qmach poucK i;^ 
 necessarily the same. 
 
 VI. ACTION OF EPLNEPHRIN, PITUITRIN, ORGAN EXTRACTS, 
 AND DRUGS 
 
 The fact that the gastric huhger contractions involve essentially 
 the same motor mechanisms as the gastric digestion contractions 
 suggests that the chemical control exerted by the blood is probably 
 the same on both. Esserine and pilocarpin augment the hunger 
 contractions, while morphine produces profound inhibition (Luck- 
 hardt). Pituitrin produces an initial augmentation; epinephrin, 
 amyl nitrite, calcium chloride, etc., a temporary depression. 
 
 Substances that cause temporary augmentation of the gastero- 
 intestinal movements' can apparently be prepared from all the 
 tissues of the body. Attempts have been made to show that there 
 is a specific "motor hormone" for gastero-intestinal peristalsis in 
 the wall of the digestive tract itself. With the exception of epine- 
 phrin it is probable that all the substances so far studied in the 
 various tissue extracts are abnormal split products or artifacts 
 not present in normal blood, and hence playing no role either in 
 the normal himger contractions or in the digestion peristalsis. 
 Biedl was not able to demonstrate any favorable action of spermin 
 or testicle extracts on metabolism, appetite, or hunger. The fact 
 that a drug or a tissue extract when introduced hypodermically 
 or intravenously initiates or augments the gastric hunger contrac- 
 tions does not imply that these drugs or extracts have the same 
 effect on the sensation of hunger. The latter effect may be modi&ed 
 or abolished by other actions, peripheral and central, of these, 
 substances. 
 
 The work of Bayliss and Starling, Magnus, Cannon, and others 
 seemed to show that the gastero-intestinal contractions are pri- 
 marily local reflexes through the Auerbach's plexus or initiated by 
 
230 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 "automatic" nervous discharges from the ganglionic plexus. 
 Kieth reports the presence in the Auerbach's plexus of "nodal" 
 tissue similar to that in the heart, and he ascribes the main r61e in 
 the genesis of the gastero-intestinal movements to this nodal tissue. 
 The presence of nodal tissue in the Auerbach's plexus does not 
 materially alter the problem of the causation of the gastero- 
 intestinal movements. 
 
 The special difficulties in relating the hunger contractions of 
 the stomach to chemical changes in the blood are the periodicity 
 of the rhythm and the abrupt cessation of the contraction periods. 
 So far as we know today chemical changes or starvation changes 
 in the blood are more continuous. Of course, we do not deny the 
 possibility of a periodic secretion into the blood of some specific 
 substance or hormone having this effect on the stomach, but all 
 the evidence so far at hand is against this possibility. The fact 
 that after extirpation of the parathyroid gland there is a tendency 
 to .atonicity and motor paralysis of the gastero-intestinal tract, 
 especially when the symptoms of tetany are^severe, is no evidence 
 that the parathyroid secretion is a motor stimulus to the stomach 
 and intestines. The motor paralysis is probably due to secondary 
 causes. The only conclusion that seems warranted by the facts 
 at hand is that the gastric hunger mechanism is prima,rily a utomatic 
 or_ind,&pandent_o f^ blood changes ^as well as of central nervous 
 influences; but in the normal individuaTcEemical changes of the 
 blood as well as nervous impulses from the brain and spinal cord 
 augrnattfof'3ecrease~tIns^rmmf^^ correlate 
 
 it with the needs of the org anism. 
 
 This conclusion should not be regarded as a bar to further 
 investigation of the chemical control of the hunger mechanism in 
 health, and especially in disease. Such work is not only urgent, but 
 is certain to jdeld important results. Recent experiments by 
 Dr. Luckhardt seem to show that the gasiteicJiunger_contractions 
 in dogs are_ aug mented by inducing thej condition of phlorhizin 
 glycosuria. It is significant that all the conditions which have so 
 far proved_t o increase the hunger contractions (diabetes melUtus, 
 
CHEMICAL CONTROL- OF THE HUNGER MECHANISM 231 
 
 pancreatic diabetes, prolonged starvation, ^reat physical exertion, 
 extreme cold, phlorhizin glycosuria) h ave these two things in ' 
 conunon : (i) ^aci dosis of varying degrees , and (2) eit her inability to 
 use sugar by t he tissues or else a lessened amount of sugar fl.v a.ila.h1e 
 for the use ot the tissues because of the sugar having been oxidized | 
 or eliminated. ' '. ~ 
 
CHAPTER XIV 
 SECRETION OF APPETITE GASTRIC JUICE IN MAN 
 
 I. THE FLUID CONTfeNTS OF THE STOMACH FEEE FROM FOOD 
 
 The normal stomach, empty of food, always contains some fluid 
 and mucus. The stomach is therefore, strictly speaking, never 
 empty. This fluid in the empty stomach is made up of (i) gastric 
 juice and mucus, (2) saliva, (3) duodenal contents (pancreatic 
 juice and bile). Pancreatic juice and bile are frequently absent, 
 however. The total fluid content of the empty stomach as well as 
 the chemistry of this fluid depend on several factors, such as the 
 relative rate of gastric and salivary secretion, the tonus and con- 
 tractions of the stomach, the rate of absorption in the stomach, 
 and the rate of empt}dng of the stomach contents into the 
 duodenum. ' 
 
 According to the more recent literature the fluid content of 
 the empty stomach of normal persons varies within wide limits. 
 Verhagen found the average to be 10 to 25 c.c, but occasionally 
 as much as 50 c.c. were obtained. Moritz gives higher figures, or 
 24 to 64 c.c. Working on himself, Moritz obtained an average of 
 43 c.c. of fluid in the stomach in the morning, with an acidity of 
 o.ii per cent. Rehfus, Bergheim, and Hawk state that in normal 
 persons the fluid in the empty stomach in the morning varies, from 
 30 c.c. to 180 c.c. The average of more than two hundred- obser- 
 vations on our gastric-fistula case, Mr. V., is 20 to 25 c.c. In Mr. V. 
 the salivary factor is excluded as the esophagus is completely 
 closed. The fluid content in the stomach in the morning before 
 breakfast is greater than at noon before l;unch. This is probably 
 due to a lower tonus of the stomach in the morning. Sixty tests 
 on eight normal medical students in the author's laboratory showed 
 a variation from 10 to 120 c.c, with an average of 40 c.c. Some 
 individuals tend to run high; others are consistently low. 
 
 232 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 233 
 
 II. CONTINUOUS SECRETION OF GASTRIC JUICE IN THE EMPTY 
 STOMACH OF NORMAL PERSONS 
 
 Continued secretion of gastric juice in the absence of food in 
 the alimentary tract, and in the absence of cerebral processes 
 relating to appetite ("psychic" stimulation), is a well-known 
 phenomenon in certain types of gastric disorders, but it is generally 
 assumed by physiologists that, in the absence of psychic stimulation, 
 the gastric glands cease to secrete almost as soon as the stomach is 
 emptied of chyme, and that the glands remain quiescent up to the 
 next feeding. The quiescence is supposed to be sufficiently com- 
 plete to render the surface of the stomach alkaline, due to the 
 continued secretion of alkaline mucus. To the extent that this 
 view is anything more than an assumption, it is based essentially 
 on the studies by Pavlov and his pupils on dogs. Pavlov frequently 
 emphasizes the fact that not a drop of gastric juice flows from the 
 stomach unless there is food or other stimuli in the stomach or 
 unless the appetite is called into play. Later Boldyreff reported 
 that on continued starvation the gastric glands exhibit periodic 
 activity, and if the starvation is maintained for more than three 
 or four days the secretion of the gastric gland becomes continuous. 
 In gastric-fistula cases of normal persons no specific study has 
 been made of the continuous secretory activity of the empty 
 stomach, but in some instances (Kaznelson, Homborg) there are 
 indications of a slow, continued secretion even when the stomach 
 had been free from food for hours. 
 
 Most of our observations on Mr. V. were made between 10 : 00 
 A.M. and 4:00 P.M., the usual breakfast of coffee, milk, and biscuits 
 being taken at 7 : 00 a.m. A few tests were made between 9 : 00 a.m. 
 and 12:00 M., and on such occasions Mr. V. did not take any 
 breakfast. The rate of the continuous secretion of gastric juice 
 in the empty stomach of Mr. V. varies from a few cubic centimeters 
 up to 60 c.c. per hour. 
 
 In general more gastric juice is obtained from the empty stom- 
 ach if the stomach is emptied (through the fistula) every 5 or 10 
 minutes than if it is emptied every 30 or 60 minutes. It is therefore 
 likely that some of this secretion passes into the intestines or is 
 
234 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 actually reabsorbed in the stomach itself. It does not seem prob- 
 able that the presence of a certain amount of this juice in the 
 stomach would tend to inhibit further secretion. 
 
 If the secretion rate is low the acidity is usually not over 0.20 
 to 0.25 per cent, but the pepsin concentration is nearly, as great as 
 that of the appetite gastric juice. If the secretion rate is moderate 
 the acidity is greater and the pepsin concentration may even exceed 
 that of the appetite secretion. When the secretion rate is low the 
 juice is very thick and opalescent, owing to the great amount of 
 ropy mucin. 
 
 ■ What constitutes the stimulus to the continuous gastric secre- 
 tion ? We think it can be shown that it is not an appetite secretion. 
 To be sure, in the case of normal and vigorous persons, periods of 
 hunger and appetite are present almost as soon as the stomach is 
 emptied of food. And it is obviously difficult so to control the 
 cerebral processes of a person that the thoughts are not diverted 
 to food and eating, especially if the usual meal time has passed and 
 one's attention is at the time on the stomach. This is especially 
 true if the gastric juice is collected every 10 minutes. If the stom- 
 ach is emptied every 30 or 60 minutes and the person is kept very 
 busy with matters not pertaining to food and eating, we think this 
 factor is entirely eliminated. This was done every day for two 
 weeks at a stretch, so as to make it a mere incident or routine in 
 the day's work. Nevertheless, the continued secretion persisted 
 with the usual fluctuations in character and quantity. 
 
 Is the secretion due to a subconscious secretory vagus tonus ? 
 The vagi carry secretory fibers to the gastric glands. But we know 
 next to nothing about the reflex or tonus control of this neuro- 
 secretory mechanism. We know that the vagi send tonus impulses 
 to the gastric motor mechanism. But it does not follow that this 
 is also the situation in regard to the gastric gland. 
 
 The presence of food in the intestine may be partly responsible 
 for this continued secretion, by reflex action from the intestinal 
 mucosa (Pavlov), or by absorptions of gastric secretins into the 
 blood. In a thirty-nine-year-old man with gastric fistula Umber 
 obtained some secretion of gastric juice on rectal feeding with milk, 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 235 
 
 sugar, and eggs. Umber explains the secretion as a reflex effect 
 from the mucosa of the large intestine. We are not convinced that 
 purely psychic factors are excluded in his experiments. If a person 
 is hungry it is likely he will be led to think of food and eating by 
 the mere act of rectal feeding. Moreover, Umber's experiments 
 were not numerous enough really to establish the point. 
 
 Gastric juice itself contains mucins and proteins that are 
 digested by the pepsin-hydrochloric of the gastric juice. It is 
 highly probable that the products of this digestion yield gastric 
 secretagogues, just as in the case of some of the digestion products 
 of the food proteins. According to Bickel amino-acids given by 
 mouth cause secretion of gastric juice. Absorbed slowly in the 
 stomach or passed into the intestines to be absorbed there, the 
 products of the auto-digestion of the gastric juice probably furnish 
 chemical stimuli for a slow but continuous gastric secretion. 
 Which one of these factors is of prime importance in the continuous 
 secretion of gastric juice by the empty stomach must be determined 
 by other lines of work, especially in disease conditions where the 
 continuous secretion is greatly increased. 
 
 III. APPETITE SECRETION OF GASTRIC JUICE 
 
 I. The mere act of chewing indifferent substances and the stimu- 
 lation of nerve-endings in the mouth by substances other than those 
 directly related to food cause no secretion of gastric juice. On this 
 point our results on Mr. V. are in complete accord with those 
 obtained from dogs by Pavlov and his school, and contrary to those 
 of a number of observers on man. 
 
 In a woman with gastric fistula and esophageal stenosis Richet 
 reports secretion of gastric juice from acid stimulation in the mouth. 
 He also states that the introduction of food or sapid substances 
 into the stomach via the fistula caused saHvation. This must have 
 been a purely psychic effect, unless the procedure caused nausea. 
 The subject was evidently a hypersensitive woman. We have 
 never observed any of these effects in Mr. V. 
 
 In 1896 Schiile introduced the method of obtaining pure appetite 
 gastric juice in man by emptying the stomach by means of a stomach 
 
236 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 tube, then chewing food for 15 minutes, and again emptying the 
 stomach with the tube. He claims that the mere act of chewing 
 and the tasting of such sapid substances as oil of peppermint, slices 
 of lemon, and mustard cause secretion of gastric juice even in the 
 absence of appetite. TroUer, usiag Schiile's method, also reports 
 that slices of lemon, mustard, etc., in the mouth, as well as the 
 mere act of chewing, cause secretion of gastric juice. In the majority 
 of his experiments the secretion thus obtained was very slight (only 
 about one-fourth that obtained on chewing bread), and in some of 
 
 TABLE I 
 Gastric Juice in c.c. (Mr. V:) 
 
 TimeinMin. 
 
 Exp. 19 
 
 Exp. 7 
 
 Exp. II 
 
 Exp. 27 
 
 Nothing in mouth . 
 
 Chewing paraffin. . 
 Nothing in mouth; 
 Vinegar in mouth. . 
 Nothing in mouth. 
 Mustard in mouth . 
 Nothing in mouth. 
 Quinine in mouth. . 
 Nothing in mouth . 
 Chewing food 
 
 10 
 10 
 10 
 10 
 10 
 10 
 10 
 10 
 10 
 10 
 10 
 10 
 
 S 
 7 
 6 
 
 S 
 4 
 6 
 
 5 
 6 
 
 4 
 
 3 
 
 S 
 
 50 
 
 i.o 
 0.8 
 
 °-5 
 0.4 
 0.4 
 0.4 
 o-S 
 o-S 
 0.4 
 
 0-3 
 
 0-3 
 
 24.0 
 
 U.4 
 0.4 
 
 o-S 
 0.2 
 
 0-3 
 0.2 
 
 o. 
 o. 
 o. 
 o. 
 o. 
 17- 
 
 I 
 o 
 
 I 
 o 
 
 I 
 I 
 I 
 o 
 o 
 
 0.9 
 
 1.0 
 
 44.0 
 
 the experiments recorded in detail the acidity of the juice is so low 
 that it must have been mixed with swallowed saliva. It is probably 
 very di65cult for the average person to avoid swallowing some 
 saliva with mustard or citric acid in the mouth for 10 to 15 minutes. 
 TroUer did not adequately control the rate of the continuous 
 secretion in the empty stomach when the persons had nothing in 
 particular in the mouth. Riegel cites the case of a professional cook, 
 in whom chewing of food (beefsteak) or slices of lemon caused no 
 secretion of gastric juice. This man showed chronic digestive dis- 
 orders, however. But Riegel suggests that the absence of appetite 
 secretion was due to a kind of permanent fatigue of the taste- 
 secretory mechanism in consequence of his duties as cook. Hom- 
 borg, working on a five-year-old boy with gastric fistula and nearly 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 237 
 
 complete cicatricial stenosis of the esophagus, concluded that 
 chewing indifferent, badly tasting, or strongly tasting (lemon) 
 substances did not induce secretion of gastric juice. Umber ob- 
 tained no gastric secretion by chewing indifferent substances (pieces 
 of rubber), but in one experiment alcohol in the mouth gave a 
 slight secretion. It must be noted that Umber's subject was a 
 man fifty-nine years old, who might have been iii the habit of 
 taking alcoholic beverages with his meals. 
 
 Kaznelson and Bickel, working on a twenty-three-year-old girl 
 "with gastric fistula and complete cicatricial esophageal stenosis, 
 report that all sapid substances (quinine, asafoetida, etc.) in the 
 mouth, even those that give rise to disgust, initiate or augment 
 the gastric secretion. Kaznelson cites one experiment with quinine 
 (control e:q)eriment with water), from which she concludes that 
 bitter substances in the mouth augment the secretion of gastric 
 juice, but her actual figures show, if anything, the reverse. The 
 total secretion of gastric juice for 80 minutes with the water control 
 (sham drinking) was 43.7 c.c, while the quinine experiment jdelded 
 only 37.6 c.c. for the corresponding time. 
 
 How are these contradictory findings to be accounted for ? In 
 view of the consistently negative results of Pavlov and his students 
 on dogs, and of Homborg, and the writer on man, it is our belief 
 that the investigators who report that mechanical chewing and 
 general stimulation of the nerve-endings in the mouth cause secre- 
 ^on of gastric juice have not eliminated the factors of appetite, 
 swallowed saliva, and variations in the rate of the continuous 
 secretion of the empty stomach. In man the appetite factor is not 
 easily controlled, except by a long series of tests in which the experi- 
 mental procedure becomes a mere routine to the subject. There 
 appears to be no direct or unconditional reflex pathway from the 
 mouth to the gastric gland. Unless the stimuli in the mouth initiate 
 or augment the central processes that constitute the sensation of 
 appetite, there is no innervation of the secretory nerve-fibers to the 
 gastric gland. 
 
 2. The relatively slight and inconstant secretion of gastric juice 
 produced by seeing, smelling, or thinking of food. — Bringing a tray 
 
238 CONTROL or HUNGER IN HEALTH AND DISEASE 
 
 of palatable food into the room in sight of Mr. V. has never yet 
 caused secretion of gastric juice, no matter what the degree of 
 himger and appetite. It is probable that under these conditions 
 the primary and normal effects of seeing and smelling the food are 
 inhibited by the consciousness of the experiment, or possibly his 
 main interest was not the food, but the expiration of the experiment 
 so that he might partake of the food. In order more closely to 
 approximate normal conditions, Mr. V. was sent out to the near-by 
 cafeteria to select the lunch that he knew he would eat shortly 
 after returning with it to the laboratory. The rate of his gastric 
 secretion was measured for lo-minute periods before going for 
 the food, during the selection of, and after returning to the labora- 
 tory with it. In the majority of these tests the act of selecting the 
 ingredients for the noonday meal caused a slight and temporary 
 augmentation of the secretion rate of the empty stomach. On 
 the whole this augmentation was greater the greater the rate of 
 the continuous secretion. But on some days the augmentation 
 was absent, although Mr. V. was in good health, felt hunger, and 
 the cafeteria displayed the usual variety of food. 
 
 Pavlov reports that there are great individual variations in dogs 
 in the amount of gastric secretion induced by seeing and smelling 
 food. This, in all likelihood, is true of man, and we suspect that 
 Mr. V. belongs to the group of individuals in whom the taste of 
 the food is the all-important factor in the psychic secretion of 
 gastric juice. We have not been able appreciably to augment the 
 continuous secretion in Mr. V. by inducing the thought of food, 
 for example, during a test while he is busy with other work, by 
 arresting his attention casually, and by discussing with him the 
 taste and ingredients of his favorite dishes, v 
 
 Schiile states that seeing or smelling food causes no secretion of 
 gastric juice in normal persons. This is directly contradicted by 
 Bulawinzew. This investigator emptied the stomach by means of 
 the stomach tube, then let the subject see or smell food, and again 
 emptied the stomach. The gastric juice thus obtained had such 
 low acidity (0.2 per cent HCI) that it must either have been in the 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 239 
 
 continuous gastric secretion or the appetite gastric juice mixed 
 with sahva. There is nothing in the review to indicate that he 
 controlled the continuous gastric secretion. Homborg obtained 
 no secretion of gastric juice from -a five-year-old boy on his seeing 
 or smelling food, probably because the child always became angry 
 when not permitted to eat the food shown him. Cade and Latarjet 
 report secretion of gastric juice was induced by talking to the 
 subject about her favorite food. This subject (a young woman) is 
 exceptional in that she virtually had an accessory stomach, but 
 
 TABLE II 
 
 Secretion of Gastric Juice (Mr. V.) on Seeing, Smelling, and 
 Thinking or Food when Hungry 
 
 
 Time 
 
 IN 
 MiN. 
 
 Gastric Juice in c.c. 
 
 
 Exp. 3 
 
 Exp. 8 
 
 Exp. 12 
 
 Exp. IS 
 
 Exp. 30 
 
 Exp. 45 
 
 
 10 
 
 s 
 
 O-S 
 
 0-3 
 
 0.4 
 
 0.6 
 
 0.4 
 
 
 10 
 
 7 
 
 0-3 
 
 0.4 
 
 O-S 
 
 o-S 
 
 0-3 
 
 
 10 
 
 6 
 
 o-S 
 
 0-3 
 
 0.4 
 
 0.4 
 
 0.4 
 
 Selecting the lunch at the cafe- 
 teria 1 
 
 10 
 
 14 
 
 I.O 
 
 I.O 
 
 35 
 
 o-S 
 
 I.O 
 
 
 10 
 
 10 
 
 I.O 
 
 0.6 
 
 2.0 
 
 0.4 
 
 1.0 
 
 
 10 
 
 S 
 
 o-S 
 
 o-S 
 
 \... 
 
 0-3 
 
 1 .0 
 
 
 10 
 
 6 
 
 0-3 
 
 0.4 
 
 
 0.4 
 
 0.7 
 
 the mucosa of the isolated stomach portion was directly exposed 
 so that the collection of the secretions was rather difficult. Kaz- 
 nelson and Bickel, workuig with a twenty-three-year-old girl with 
 gastric fistula and stenosis of the esophagus, reached the remarkable 
 conclusion that anything which stimulated the olfactory sense 
 induced secretion of gastric juice in the resting stomach. Thus 
 they claim that smelling ammonia, acidic acid, and aromatic oils 
 causes secretion of gastric juice. This we are absolutely unable 
 to confirm on Mr. V. It is possible that in this young woman 
 every gustatory and olfactory stimulus when manipulated by the 
 investigators led to thoughts of food through idea associations. 
 
240 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 IV. GASTRIC SECRETION INDUCED BY TASTING AND CHEWING 
 PALATABLE FOOD 
 
 I. The secretion rate. — ^We have records of 156 tests of the 
 appetite secretion of Mr. V. during the 20 minutes' mastication 
 of the noonday meal. The particular ingredients of this meal were 
 of his own selection, and varied from day to day. The meal usually 
 included soup and some kind of meat and gravy, and always milk 
 and a dessert. Secretion of gastric juice during 20 minutes' masti- 
 cation of palatable food was: lowest, 30 c.c; highest, 156 c.c; 
 average, 70 c.c; number of experiments, 156. 
 
 
 
 
 
 / 
 
 
 
 \ 
 
 
 
 
 
 in 
 
 
 in 
 
 
 
 
 / 
 
 
 
 \ 
 
 \, 
 
 
 
 
 5 
 
 
 
 / 
 
 / 
 
 
 
 
 \ 
 
 \, 
 
 
 
 
 
 
 
 / 
 
 
 
 
 
 
 N 
 
 \ 
 
 
 Chewing food 
 
 Fig. 29. — Typical curve of secretion of gastric juice of Mr. V. on mastication of 
 palatable food for 20 minutes. The gastric juice was collected at 5-miuute intervals. 
 The rise in the secretion rate during the last 5 minutes of mastication is due to chewing 
 the dessert (fruit). 
 
 This gives an average rate of secretion of 3.5 c.c. of gastric 
 juice per minute. The maximum rate of secretion determined at 
 any time was 54 c.c. in 5 minutes, or 10.8 c.c. per minute; the 
 lowest was 7 c.c. in 5 minutes, or 1.4 c.c. per minute. The secre- 
 tion rate is proportional to the palatability of the food. Thus the 
 secretion rate is nearly always highest in the last 5-minute period, 
 when Mr. V. masticates the dessert, and on the day when the 
 highest rate of secretion was noted (156 c.c. in 20 minutes) Mr. V. 
 stated that the Ixmch was "imusuaUy fine." 
 
 Is this rate and quantity of appetite secretion of gastric juice 
 typical for normal adults ? Mr. V. is in normal health, except for 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 241 
 
 infrequent periods of headache and nervousness, the etiology of 
 which is obscure. TroUer reports 5 experiments on a person with 
 nervous dyspepsia. Chewing beefsteak for 15 minutes yielded 55 
 c.c. of gastric juice, while 3 experiments on a person with hyper- 
 acidity gave 50 c.c. gastric juice in 15 minutes. This is a secretion of 
 a rate of about 3.5 c.c. per minute. Chewing bread for 15 minutes 
 ^delded much less gastric juice. In the case of persons with hypo- 
 chlorhydria the average secretion for 15 minutes (chewing --beef- 
 steak) was only 28 c.c. In Umber's fistula case (a man fifty-nine 
 years old) two tests with chewing beefsteak for 15 minutes yielded 
 
 TABLE III 
 
 Rate of Appetite Secretion of Gastric Juice of Mr. V. 
 Detail of Typical Experiments 
 
 
 Rate op Secretion of Gastric Juice in Consecutive s-Min. Periods, c.c. 
 
 EXPERDJENT 
 
 No. 
 
 Before Starting 
 Chewing 
 
 During Chewing 
 
 On Cessation of 
 Chewing 
 
 20 
 
 31 
 
 35 
 
 55 
 
 86 
 
 94 
 
 120 
 
 150 
 
 I 
 
 o-S 
 03 
 0.2 
 
 0. 2 
 0. 2 
 0.2 
 
 0-5 
 
 0^6 
 2.0 
 0.2 
 
 0-3 
 0.2 
 
 °-3 
 
 0.8 
 
 0.7 
 30 
 0.3 
 0.2 
 0.1 
 0.2 
 
 10 
 
 II 
 
 IS 
 
 20 
 
 5 
 
 6 
 
 6 
 
 22 
 
 IS 
 18 
 16 
 22 
 20 
 II 
 28 
 54 
 
 14 
 17 
 IS 
 21 
 18 
 
 IS 
 20 
 
 35 
 
 20 
 
 23 
 18 
 
 30 
 20 
 12 
 29 
 45 
 
 s 
 
 10 
 8 
 
 IS 
 9 
 3 
 8 
 
 20 
 
 3 
 6 
 
 4 
 6 
 
 3 
 
 2 
 
 6 
 
 IS 
 
 I.O 
 
 2.0 
 
 i-S 
 6.0 
 1.0 
 
 OS 
 2.0 
 8.0 
 
 73 C.C. and 48.5 c.c. gastric juice jn 60 minutes. This low rate of 
 secretion (about i c.c. per minute) must be due to the advanced 
 age and to a malignant tumor of the esophagus. The ten-year-old 
 girl studied by Sommerfeld secreted no to 150 c.c. gastric juice 
 in 90 minutes on chewing meat or mixed food for 30 to 40 minutes, 
 a secretion rate of 2 to 2.5 c.c. per minute. The maximum secre- 
 tion rate in the twenty-three-year-old girl studied by Kaznelson 
 and Bickel was 5 c.c. per minute, the average secretion rate being 
 much lower. Homborg's five-year-old boy secreted 15 to 25 c.c. 
 in 30 minutes on chewing meat or apple pie. Chewing bread or 
 milk yielded less than half this amount. The three-year-old child 
 observed by Bogen, on chewing meat for 15 minutes, yielded 6 to 
 
242 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 22.5 c.c. gastric juice, or an average rate of less than i c.c. per 
 minute. 
 
 These data reported by previous investigators cannot be directly- 
 compared with our results on Mr. V. for the reason that the col- 
 lection of the gastric juice was not always confined to the actual 
 period of mastication of the food. The rate of the appetite secretion 
 starts to fall almost as soon as Mr. V. ceases to masticate the food, 
 and ift 15 minutes the activity of the gastric glands is in most cases 
 down to the level of the continuous secretion. The secretion rate 
 is highest during the actual tasting of the food. 
 
 In this respect there is a marked difference between man and 
 dog. In the dog, after 12 to 24 hours of starvation, sham feeding 
 with meat for 5 minutes may initiate and keep up secretion of gastric 
 juice for 3 to 6 hours (Pavlov, Rosemaim). It is obvious that in 
 these tests on dogs the starvation period was much longer and the 
 hunger and appetite more intense than in our experiments on Mr. V. 
 Another factor is probably the greater voluntary control over 
 attention and other cerebral processes in man. 
 
 It may be of interest in this connection to note the rates of 
 gastric secretion that have been obtained by sham feeding in dogs. 
 Konowaloff reports 4 c.c. per minute; Schoumow-Simanowsky 
 found a maximum of 5 c.c. per minute; and Rosemann (in a dog 
 weighing 24 kg.) gives as the average 3.4 c.c. per minute. Since 
 the quantity of gastric glands even in very large dogs is probably 
 only a third of that in the adult man, the foregoing data seem to 
 indicate that the gastric glands in dogs work with greater speed 
 than the gastric glands of man. ^ 
 
 2. The direct relation between the rate of appetite gastric secretion 
 and the palatableness of the food. — The mastication of bread and 
 butter or the taking of milk in the mouth yields much less gastric 
 juice than the chewing of meat. This is in line with results of 
 previous observers on man. The taste nerve-endings are evidently 
 stimulated more intensely by the readily diffusible sapid substances 
 in the meat. In general the desserts (pies, pudding, fruits) yielded 
 even greater secretion than meat. This was particularly noticeable 
 in the case of chewing oranges. ' Mr. V. is especially fond of oranges. 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 243 
 
 The sapid substances in the orange juice probably diffuse readily 
 and thus reach all the taste nerve-endings in marked concentration. 
 There is no question but that the mastication of a palatable dessert 
 at the end of a meal serves to augment and prolong the appetite 
 secretion of gastric juice. 
 
 3. The latent period of the gastric appetite secretion.-;— Pavlov 
 and his coworkers found that the appetite gastric secretion in dogs 
 exhibited uniformly a latent period of 5 to 6 minutes. According 
 to the literature the latent period of the appetite gastric-juice 
 secretion in man varies from 3 to 9 minutes. The latent period 
 depends primarily on the condition of the gastric glands. Thus 
 if there is a continuous gastric secretion of 2 to 6 c.c. per 10 minutes 
 at the time mastication of the food begins, the appetite secretion 
 shows practically no latent period at all. The quantity of gastric 
 juice secreted during the first 5 minutes of chewing is just as great 
 as that secreted during the second or third 5-minute periods. On 
 the other hand, if the continuous secretion is very low (0.2 to 0.3 c.c. 
 per 10 minutes) the appetite secretion shows a latent period of 2 
 to 4 minutes. It is therefore evident that with the gastric secretion 
 already in progress the appetite secretion reflex exhibits no greater 
 latent time than neuromuscular reflexes in general. 
 
 The latent period varies indirectly with the intensity of the 
 appetite stimulation. If the continuous secretion is very low, the 
 latent period of the secretion does not exceed 2 to 3 minutes, provided 
 the food is very palatable. 
 
 v. TOTAL SECRETION OF GASTRIC JUICE IN MAN ON AN AVERAGE MEAL 
 
 As stated above, Mr, V. yields appetite gastric juice at: mini- 
 mum secretion rate, 84 c.c. per hour; maximum secretion rate, 
 648 c.c. per hout; average secretion rate, 210 c.c. per hour. Does 
 this furnish us a clew to the total gastric secretion on an average 
 meal in man ? This question cannot be answered by direct meas- 
 urements, even in cases of duodenal fistula and collection of all the 
 chyme issuing through the pyloric opening, as the alimentary tract 
 of such persons is far from normal, and we still have the variable 
 factors of swallowed saliva and of direct absorption in the stomach. 
 
244 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 In the case of dogs sham feeding alone may jdeld 600 to 700 c.c. 
 of gastric juice in 4 to 6 hours. But this situation is abnormal 
 because the sham feeding does not satisfy the appetite, even though 
 the secretion inhibits the hunger. It is therefore certain that the 
 appetite secretion is much less when the food is permitted to reach 
 the stomach. But when the food is allowed to reach the stomach, 
 how can we measure the total gastric secretion ? Using large dogs 
 with fistula of duodenimi, Moritz reports that the ingestion of 
 200 gm. of meat caused a secretion of 320 c.c. gastric juice in 7 
 hours. Part of this was undoubtedly swallowed saKva, and possibly 
 some admixture of bile and pancreatic juice. With the same method 
 Tobler obtained 200 to 300 c.c. of gastric juice from feeding 100 gm. 
 meat; pari of this fluid was undoubtedly swallowed saUva. 
 
 It seems to us that we can arrive at a very close estimate of the 
 total average secretion of gastric juice in a man on the following 
 basis: Pavlov and his pupils have shown on dogs that the secretion 
 curves of the main and the accessory stomach pouch run parallel. 
 They have also shown that on a meal of meat, or a mixed meal, 
 the secretion usually reaches the maximum toward the end of the 
 first or during the second hour. Lonnquist notes particularly that 
 the secretion does not reach its maximum until toward thei end of 
 the second hour after eating. On the whole, the quantity of gastric 
 juice yielded by a dog's accessory stomach after the first two hours 
 following a moderate meal of meat, bread, or a mixture of meat 
 and bread, is about half of that secreted during the entire digestion 
 period. This is evident from experiments reported in detail by 
 Pavlov and his students, as well as from studies on dogs in our labo- 
 ratory. But this is not true if a very large quantity of food is given, 
 or if the food contains a considerable amount of fat, as in both 
 cases the secreti'on of fluid is greatly prolonged. 
 
 We can safely assume that the general relations and the relative 
 importance of the appetite and the hormone gastric juice are the 
 same in man and dog. Pflaunder supports the view that the maxi- 
 mum rate of secretion in man is reached at the end of the first or 
 the beginning of the second hour of digestion. Sick finds that 
 the maximum acidity of gasfric content is usually reached at the 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 245 
 
 end of the first hour of digestion. The same is shown by the more 
 recent studies of Rehfus, Bergheim, and Hawk, using the Ewald 
 rest meal on normal persons. 
 
 The total secretion of gastric juice in normal adult man on inges- 
 tion of the average dinner of meat, bread, vegetables, coffee or milk, 
 and dessert will, on the foregoing assumptions, be as follows: ist 
 hour, 200 c.c. gastric juice; 2d hour, 150 c.c; 3d to 5th hours, 
 350 c.c; total, 700 c.c. gastric juice. 
 
 It should be noted in this connection that Mr. V.'s noonday 
 meal is in reality the big meal or dinner. He secretes less gastric 
 juice on his evening meal, probably not more than 400 to 500 c.c, 
 and from the fact that he makes his breakfast solely on biscuits, 
 coffee, and milk it is likely that his secretion of gastric juice on the 
 morning meal does not exceed 250 to 300 c.c. This would make 
 a total of 1,350 to 1,500 c.c. of gastric juice secreted in 24 hours. 
 These figures do not include the continuous secretion in the absence 
 of food. It is of interest to note that Pflaunder arrived at practically 
 the same figures (1,500 c.c. or 25 c.c. per kg. of body weight in 
 24 hours), basing his estimate on calculations from the acidity and 
 volimie of the gastric content at varying periods after the meal. 
 
 It need not be pointed out that the foregoing figures are subject 
 to great variations, depending on the condition of the stomach and 
 the quality and quantity of the food. 
 
 SUMMARY 
 
 The fluid contents of the "empty" stomach vary from nothing 
 up to 150 c.c. The average of a number of tests varies with the 
 individual from 30 to 50 c.c. The quantity is greater in the morn- 
 ing than at noon or at 6:00 p.m. It is on the whole greater in the 
 siunmer than in the winter months. The most important factor 
 in these daily and seasonal variations is probably the tonicity of 
 the empty stomach and the rate of the continuous secretion. 
 
 The gastric glands in the normal person are never completely 
 quiescent. The continuous secretion varies from 2 to 50 c.c. per 
 hour. The higher figures are exceptional, but may obtain for 
 several days in succession, again to revert to the lower figures. 
 
246 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 ||The vagus secretory tonus is a possible and the auto-digestion of 
 I the gastricjuice iteelf is a probable fa,ctor in this continuous gastric 
 secretion. The secretion itself is rich in pepsin, but when the 
 secretion rate is very low it is poor in free hydrochloric acid. 
 
 Chewing on indifferent substances and stimulation of the nerve- 
 endings in the mouth by substances not related to food do not 
 cause secretion of gastric juice, that is, these processes do not 
 augment the continuous gastric secretion. , 
 
 Seeing, smelling, and possibly thinking of palatable food usually 
 cause a very slight and transitory secretion of gastric juice. 
 
 The rate of secretion of gastric juice on mastication of palatable 
 food is directly proportional to the palatabiHty of the food. Duriag 
 mastication the average rate is 3.5 c.c. per minute (minimum rate: 
 1.4 c.c; maximum rate: 10.8 c.c). On cessation of chewing the 
 secretion rate diminishes rapidly, so that in 15 to 20 minutes the 
 gastric glands reach the level of the continuous gastric secretion. 
 The chemistry of this appetite gastric juice is practically constant. 
 
 The latent period of this appetite secretion varies indirectly 
 with the rate of the continuous secretion, so that when the con- 
 tinuous secretion is abimdant the appetite secretion shows prac- 
 tically no latent period at all, while with the lowest rate of the 
 continuous secretion the latent period varies from 2 to 3 minutes. 
 This latent period is therefore one of the processes in the gland 
 cells, and not in the nervous mechanism. 
 
 On the basis of these experiments on Mr. V., on the reports of 
 other gastric fistula cases in man, and on the work of Pavlov on 
 dogs, it is estimated that an adult normal person secretes on an 
 average meal (dinner) 700 c.c. of gastric juice, or an average total 
 of 1,500 c.c. of gastric juice in 24 hours. 
 
 On the whole, this work on the appetite secretion of gastric 
 juice in man confirms and extends the work of Pavlov and his 
 pupils on dogs. Pavlov overlooked or ignored the continuous 
 { secretion in the absence of all food and psychic stimuli, and he 
 put too great an emphasis on the- secretion induced in a hungry 
 animal by seeiag and smelling food. The significant appetite secre- 
 tion in man is that induced by tasting and chewing good food. The 
 
SECRETION OF APPETITE GASTRIC JUICE IN MAN 247 
 
 continuous secretion does not fit in with Pavlov's general theory of 
 strict adoption of the digestion juices to the food, as it apparently 
 serves no useful purpose in digestion. 
 
 It is also clear that Pavlov ov erestim ated the importance of 
 the appetite secretion in gastric digestio n. The continuous secre- 
 tioii uiiLiaLey gasUTc" digestion in the absence of appetite juice. /^ 
 Dogs with both vagi sectioned exhibit practically normal gastric 
 digestion within a few daj^ after the operation, despite the fact ( 
 that the appetite gastric juice is eliminated. C ats may be forcib ly I 
 fed with mipalatable foo d and the stomach digestion is practically I 
 as rapid as when they eat voluntarily. And we know that in man " 
 th€ pepsin-hydrocEIonF acid of the gastric juice may be greatly 
 reduced if not entirely absent (achylia) without marked impair- 
 ment of gastric peristalsis or food utilizatipn, We have on numer- 
 ous occasions removed all the appetite gastric juice from Mr. V.'s 
 stomach before the , masticated meal was put into his stomach 
 without producing the slightest evidence of indigestion. 
 
 The signi ficance of hunger an d appetite for digestion is appar- . 
 ently not so m uch in the actual yiej.d of appej:ite gastric juice as ( 
 in^tEe~fact that when these sensation complexes are present the j 
 entS re gastero-intestinal tract, both on th e motor and JnT" the/ 
 secretory side, is in fit condition to handle the ingested food. ' 
 
CHAPTER XV 
 THE CHEMISTRY OF HUMAN APPETITE GASTRIC JUICE 
 
 j I. THE SOLIDS 
 
 The total solids of the pure gastric juice of Mr. V. vary from 
 0.48 gm. to 0.58 gm. per 100 c.c, of which 0.34 gm. £0 0.47 gtn. 
 is organic, and o.ii gm. to 0.14 gm. inorganic material. The 
 hydrochloric acid is, of course, expelled in the evaporation and 
 drying of the gastric-juice residue. 
 
 The hunger gastric juice (continuous secretion) is distinctly 
 higher than the appetite juice both in total and in organic sohds. 
 
 The gastric juice or fluid in the empty stomach is distinctly 
 more dilute than the appetite juice, although it may approach the 
 concentration of the latter in cases where the rate of the continuous 
 secretion is considerable. 
 
 The foregoing figures on Mr. V.'s appetite gastric juice are 
 slightly higher than those given by Sommerf eld for the gastric juice 
 from a ten-year-old girl, namely 0.40 gm. to 0.47 gm. Schmidt 
 found jn a human gastric-fistula case 0.58 gm. of total solids in the 
 gastric juice, of which 0.32 gm. was organic, and 0.26 gm. inorganic. 
 But Schmidt did not work with pure gastric juice. This is evident 
 from his method of obtaining the juice, as well as from the fact that 
 the acidity of the juice was only 0.20 gm'. or less than half that of 
 normal human gastric juice. Albu reports one experiment on a 
 patient with hypersecretion finding the percentage of solids only 
 0.24 gm., practically all of which (0.23 gm.) was inorganic salts. 
 He also reports one determination on normal human gastric juice 
 (pure appetite juice) in which the inorganic solids were 0.18 gm.; 
 the organic solids are not given. 
 
 Our results on Mr. V. agree closely with most of those reported 
 for the gastric juice of dogs. The total concentration of organic 
 and inorganic substances is therefore about the same in the normal 
 gastric juice (appetite juice) of man and dog. 
 
 248 
 
CHEMISTRY OF HUMAN APPETITE GASTRIC JUICE 249 
 II. SPECIFIC GRAVITY 
 
 The specific gravity of Mr. V.'s appetite gastric juice varies 
 between 1,006 and 1,009 '^th an average of 1,007. This is the 
 average of twenty tests on an equal number of gastric- juice samples. 
 It will thus be seen that 1,009 is an exceptional concentration. 
 
 The specific gravity of the continuous secretion is higher than 
 that of the fluid or juice found in the empty stomach and lower 
 than that of the appetite juice. 
 
 The specific gravity of the appetite gastric juice of the dog, as 
 reported by Schoumow-Simanowski, Konovaloff, Friedenthal, and 
 Rosemann varies from 1,002 to 1,007, "vnth. an average of 1,004. 
 This low average figure is probably due to 'the fact that in most of 
 these experiments the gastric juice was collected for several hours 
 after only a few niinutes of sham feeding. There is evidence that 
 the percentage of solids in the gastric juifce is greatest during the 
 first hours of appetite or digestion secretion. The concentration 
 of the dog's appetite gastric juice during the first 20 minutes of 
 secretion will in all probability be found identical with that of man 
 for the same period. 
 
 III. OSMOTIC CONCENTRATION 
 
 The appetite gastric juice lowers the freezing-point from 
 —0.55'* C. to —0.62° C; the continuous secretion from' —0.47° C. 
 to —0.52° C; the fluid of the empty stomach from —0.21° C. 
 to —0.41° C. The juice found in the empty stomach exhibits 
 the greatest fluctuations in osmotic pressure, the appetite and the 
 hunger juice being very constant. The hunger juice has, on the 
 whole, a lower osmotic concentration than the appetite juice. 
 
 The foregoing figures for the appetite gastric juice of Mr. V. 
 are practically identical with those reported on the pure gastric 
 juice of other human fistula cases. Sommerfeld (in a ten-year-old 
 girl) found the freezing-point to vary from —0.47° C. to — o. 65° C. ; 
 Kaznelson (twenty-five-year-old girl) reports a variation from 
 —0.46° C. to —0.54° C. Umber reports two tests on the gastric 
 juice (pure) of a fifty-nine-year-old man with cancer, finding a 
 
250 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 variation of —0.15° C. to —0.82° C. Assuming that Umber's 
 determinations are correct, the gastric juice of this cancer patient 
 was clearly not normal. We question whether the normal stomach 
 can secrete a juice with an osmotic concentration so much greater 
 than the blood as the figure —0.82° C. demands. The reader will 
 note that the figures of Sonunerfeld and Kaznelson, as well as our 
 own for Mr. V., indicate an osmotic pressure of the appetite gastric 
 juice not far below or above that of the human blood. According 
 to Bickel the gastric juice (ten-year-old child) is always hypotonic 
 to the blood. Lehman concludes that the osmotic pressure of 
 normal gastric juice (gastric content) is usually less than —0.50° C, 
 and that a concentration above this figure indicates hyperacidity 
 or other pathological conditions. This view is obviously unten- 
 able. 
 
 The osmotic concentration of the dog's appetite gastric juice 
 is practically identical with that of man. Sasaki reports a variation 
 from —0.51° C. to —0.60° C; Rosemann gives somewhat higher 
 figures, or —0.56° C. to —0.64° C. On the other hand, Bickel 
 reports extraordinary fluctuations in osmotic, concentration of 
 dogs' gastric juice (Pavlov pouch) or —0.52° C. to —1.21° C. We 
 question whether the normal stomach can secrete a juice of the 
 osmotic concentration —1.21° C, that is, twice that of the blood. 
 
 IV. TOTAL NITROGEN OF THE GASTRIC JUICE 
 
 The total nitrogen was determined by the method of Kjeldahl 
 on 9 different lots of appetite gastric juice of Mr. V. The average 
 of all our, determinations is 0.60 gm. nitrogen per 100 c.c. appetite 
 juice. The total nitrogen of the hunger juice was not determined. 
 If all the nitrogen is in the form of proteins, and if we accept the 
 figures of Nencki and Sieber, and of Pekelhaaring, namely, that 
 nitrogen constitutes 14.39 P^i" cent of the proteins of the gastric 
 juice, the appetite gastric juice of man would contain on the average 
 nearly 0.42 gm. protein per 100 c.c, or practically all the organic 
 solids in the appetite juice. 
 
 Rosemann reports nitrogen determinations in 2 lots of dog's 
 appetite gastric juice, finding 0.035 gm^and 0.054 gm. per 100 c.c, 
 
CHEMISTRY OF HUMAN APPETITE GASTRIC JUICE 251 
 
 respectively. These figures are considerably lower than ours on 
 the appetite juice of Mr. V. 
 
 V. AMMONIA 
 
 The ammonia of the fresh gastric juice was determined by a 
 combination of Fohn's aeration and the Nessler colorimetric meth- 
 ods, using I to 5 c.c. of the juice. The ammonia cannot be deter- 
 mined by the Nessler reagent directly in pure gastric juice, as 
 parallel tests on the same samples of gastric juice jdeld higher 
 figures by aeration and Nessler than by Nessler direct (using i c.c. 
 of the juice). 
 
 Ammonia in the amounts of 2 to 3 gm. per 100 c.c. is a constant 
 constituent of pure gastric juice of man and dog. The ammonia 
 appears to be slightly more concentrated in the continuous secre- 
 tion or hunger juice than in the appetite juice. The ammonia may 
 be greatly increased in gastric ulcers, and in certain normal persons 
 the ammonia may also be exceptionally high (10 to 15 mgr.). 
 
 Rosenheim and Strauss reported small amounts of ammonia in 
 the gastric content of man. Zunz, working with the gastric content 
 (test meals) on normal persons and on persons with various dis- 
 orders of the alimentary tract, also reports the presence of ammonia. 
 In the normal individuals the ammonia of the test-meal contents 
 varied from 0.7 to 5.0 mgr. per 100 c.c. In cancers of the stomach 
 the ammonia in the test-meal content was increased. The test 
 meal introduces factors (bacterial action, saliva, etc.) not present 
 in pure gastric juice. Sommerfeld, working with pure gastric juice 
 of a ten-year-old girl with complete stricture of the esophagus, 
 states that gastric juice contains no ammonia. Nepcki, Zaleski, 
 and Salaskin 'reported 4 to 5.5 mgr. ammonia per 100 c.c. pure 
 gastric juice of the dog. Rosemann reports the constant presence 
 of a small amount of ammonia in the pure gastric juice (appetite 
 secretion) in the dog. Reisner concludes that the ammonia in 
 gastric juice comes from the saliva. 
 
 What is the origin and significance of the gastric-juice ammonia ? 
 It is known that saliva contains traces of ammonia. We find that 
 the mixed saliva of man contains from 0.5 to 1.5 mgr. ammonia 
 
252 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 per loo ex. Salaskin found 2.5 gm. NH3 per 100 c.c. in the saliva 
 of the dog. But in dogs with Pavlov's stomach pouch, and in our 
 gastric-fistula case, Mr. V., no saliva can enter the stomach or the 
 part of the stomach yielding the juice. 
 
 The ammonia of the duodenal content may be a factor, as 
 Boldyreff and others have shown the frequency with which intes- 
 tinal content enters the stomach. This factor is excluded in dogs 
 with the Pavlov stomach pouch. In our human fistula case this 
 factor is readily controlled by making the ammonia determinations 
 only on those samples of gastric juice that are absolutely free from 
 admixture with bile, pancreatic juice, and succus entericus. Rose- 
 mann points out that the gastric-juice ammonia cannot be a simple 
 filtrate from the blood since normal blood contains only about 0.5 
 mgr. of ammonia per 100 c.c. , 
 
 Huber, working in the author's laboratory, found that intra- 
 venous and oral administration of ammonia salts increases the 
 ammonia concentration in the gastric juice. It is decreased on 
 low, and increased on high protein diet. But when the urine 
 ammonia is greatly decreased by taking alkalies, or greatly in- 
 creased by taking acids, the concentration of the gastric-juice 
 ammonia remains unchanged. 
 
 The question of the origin of the gastric-juice ammonia is 
 'therefore very complex, (i) It is in part an active excretion from 
 the blood. (2) It may be formed in part by deamidization of 
 amino-acids in the gastric mucosa . (3) It may be formed in the 
 process of secretion of gastric juice, or (4) by the action of the HCl 
 on the gastric-juice protein, or on the cells of the mucosa. In 
 cases of gastric ulcers of infectious origin it may come in part from 
 bacterial activity in the active focus of the ulcer. 
 
 In 1898 Nencki, Pavlov, and Zaleski found that, per unit of 
 mass, there is more ammonia in the gastric mucosa than in any 
 other tissue of the body. These findings were essentially confirmed 
 by Salaskin the same year. Huber found a greater concentration 
 of ammonia in the fundic mucosa than in the mucosa of the cardiac 
 and the pyloric ends of the stomach. These facts seem to indicate 
 some relation of the ammonia formation to the secretion process 
 
CHEMISTRY OF HUMAN APPETITE GASTRIC JUICE 253 
 
 itself and to the protein absorption, unless the higher ammonia con- 
 tent of the secreting and absorbing mucosa represents ammonium 
 chloride in the process of absorption from the gastric Juice. 
 
 VI. THE AMINO-ACIDS 
 
 When deductions are made for the ammonia nitrogen. of the 
 juice, the formol-titrable nitrogen of Mr. V.'s appetite gastric juice 
 varied from 3 to 9 gm. nitrogen per 100 c.c. The gastric juice of a 
 second fistula case (Mr. E.) gave 7 gm. per 100 c.c. Four lots of 
 dog's appetite gastric juice (Pavlov pouch) gave only i to 2 gm. of 
 amino-acid nitrogen. It thus appears that normal human gastric 
 juice contains slightly more amino-acid than ammonia nitrogen; 
 but the greater part of the gastric-juice nitrogen is associated with 
 more complex proteins. 
 
 Zunz reports that the amino-acid nitrogen (test meals) usually 
 exceeds the ammonia nitrogen, and that both substances are 
 increased in cases of gastric cancer. In three normal persons the 
 maximimi amino-acid was 10 gm. per 100 c.c. of gastric content, 
 while in several gastric cancer cases it reached 15 to 20 gm. per 
 100 c.c. of content. But these figures cannot be directly compared 
 with ours on pure gastric juice, because of the uncertain factors 
 associated with the gastric contents following a test meal. 
 
 VII. AUTO-DIGESTION OF THE GASTRIC JUICE 
 
 When fresh gastric juice is incubated at 38° C. the following 
 changes take place in the proteins and the gastric mucin: 
 
 1. Practically all the ropy mucin and mucin flocculi are dis- 
 solved. 
 
 2. The pink color of the biuret reaction is increased. In fact, 
 fresh human gastric juice gives practically a violet biuret reaction, 
 and this color is intensified and changed toward pink by the 
 auto-digestion. 
 
 3. The characteristic protein precipitation at the point of 
 neutralization is decreased. 1 
 
 4. The quantity of proteins jJrecipitated by nitric acid and by 
 heat is reduced. ' 
 
254 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 It is thus clear that the protein of pure gastric juice undergoes 
 pepsin-hydrochloric acid digestion in the stomach itself. But 
 some of the gastric juice proteins are not hydrolyzed, at least not 
 down to the peptone stage. It is an interesting fact that the pro- 
 tein of the gastric juice of man injected into guinea-pigs sensitizes 
 the animals to subsequent injections of human serum, but injec- 
 tions of even large quantities of human gastric juice into pigs thus 
 sensitized produce no anaphylaxis. This auto-digestion of the gas- 
 tric juice itself is probably a factor in the continuous secretion of 
 
 gastric juice in the way of yielding gastric secretagogues. 
 t 
 
 Vin. ACIDITY or NORMAL GASTRIC JUICE 
 
 The acidity was determined by titration with iV/40 NaOH, 
 and using dimethyl-amino-azo-benzene and phenothalein as indi- 
 cators for the free and the total acidity, respectively. During-tiie 
 4 years that Mr. V. has been under observation htuidreds of 
 determinations have been made of the acidity of the contents of 
 the "empty" stomach, of the hunger juice, or continuous secre- 
 tion, and of pure appetite juice. The reader will recall that the 
 contents of the '-'empty" stomach are taken one hour after wash- 
 ing out the stomach with 200 c.c. of water. All the cases where 
 the gastric juice or gastric content was contaminated with bile 
 (intestinal content) are excluded from the summaries given in 
 Table IV. 
 
 The second gastric-fistula case, Mr. E., was a man of twenty-six 
 years of age, healthy and vigorous. Nearly a year prior to our 
 work on him his esophagus was corroded with a solution of lye, 
 and this led to a nearly complete cicatricial stenosis, and hence 
 the gastrostomy. At the time of the observations the esophagus 
 had been dilated sufficiently to permit swallowing of any well- 
 masticated food, and the gastrostomy opening was used only in 
 the dilation processes. In this case, saliva is therefore not excluded 
 from the contents of the empty stomach, and possibly not from 
 the continuous or hunger secretion, although Mr. E. was instructed 
 and urged not to swallow any ^liva during these experiments. 
 The appetite juice was obtained by Mr. E.'s chewing palatable 
 
CHEMISTRY OF HUMAN APPETITE GASTRIC JUICE 255 
 
 food, and spitting out the chewed food, care being taken not to 
 swallow saUva or particles of food. 
 
 These results from my two gastric-fistula cases are in agreement 
 with the work of Pavlov and his pupils on dogs, and the work of 
 previous observers on pure gastric juice of normal persons. The 
 latter data have recently been brought together and discussed by 
 Boldyreff. 
 
 TABLE IV 
 Acidity of Normal Human Gastric Juice 
 
 
 Material 
 
 No. OF 
 Obser- 
 vations 
 
 AcmiTY 
 
 Person 
 
 Free 
 
 Total 
 
 
 fCont. empty stomach. 
 
 Hunger juice 
 
 [Appetite juice 
 
 f Cont. empty stomach , 
 
 Hunger juice 
 
 Appetite juice 
 
 23s 
 180 
 28s 
 
 10 
 
 8 
 IS 
 
 Low 
 
 High 
 
 Aver. 
 
 Low 
 
 High 
 
 Aver. 
 
 Mr.V... 
 Mr. E... 
 
 0. 10 
 oiS 
 0-35 
 
 0.09 
 0. 20 
 0.30 
 
 0-3S 
 °-3S 
 0.44 
 
 0.36 
 0.32 
 0.36 
 
 0.18 
 0.2s 
 0.40 
 
 0.20 
 0.2s 
 0-34 
 
 o.iS 
 0.20 
 0.40 
 
 0.18 
 0.27 
 0.36 
 
 0.40 
 0.4S 
 053 
 
 0.41 
 0.38 
 0.47 
 
 0.23 
 o'34 
 0.48 
 
 0.2s 
 
 0-33 
 0.44 
 
 Normal human gastric juice (appetite secretion) when secreted 
 above a certain minimimi rate shows a practically constant total 
 acidity of nearly 0.5 per cent HCl, or the same as the gastric 
 juice of normal dogs. Practically the same figure is obtained when 
 the acidity is determined by conductivity methods (Menten). 
 The gastric juice (appetite as well as hunger juice) secreted by the 
 normal stomach at a low rate shows lower than normal acidity 
 and total chlorides. The view of Pavlov based on experiments 
 on dogs that gastric juice is secreted at imiform and constant acidity 
 is true for man only in regard to appetite, digestion, and hunger 
 juice secreted at fairly high rate. We must take cognizance of the 
 equally important fact that the normal gastric mucosa is capable 
 of secreting a juice of submaximal acidity. 
 
 The studies of Rehfus and Hawk on the acidity of the gastric 
 content at varying periods after drinking water and ingesting an 
 
2S6 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 Ewald test meal also support the view that the normal gastric 
 juice has a fairiy constant acidity. 
 
 The reader will note that normal human gastric juice is equal in 
 total acidity to the maximum acidity reported by clinical observers 
 for so-called hyperacidity in man. So far as we are acquainted with 
 the literature, there is no evidence that the gastric glands under any 
 pathological conditions are able to or do secrete a juice of higher than 
 normal acidity. Actual hyperacidity does not occur in cases of 
 experimental ulcers in the stomach and duodenum. But there 
 may be h)rpersecretion. Moreover, the presence in the stomach 
 of gastric juice of full acid strength leads by itself and' immediately 
 to no untoward sjonptoms. > 
 
 The contents of the "empty" stomach, and the continuous or 
 hunger secretion (when the secretion rate is low) have \miformly a 
 lower acidity than the appetite juice. The total acidity of contents 
 of the "empty" stomach is 0.2 or less. The reader will note that 
 this figure is frequently given as the acidity of pure gastric juice of 
 normal persons. The acidity of the continuous or himger secretion 
 is higher, and the greater the secretion rate the higher the acidity 
 until it may equal that of the appetite juice. In no instance does 
 the acidity of the continuous secretion exceed that of the appetite 
 juice. 
 
 What is the cause of the low acidity of the continuous secretion 
 and contents of the empty stomach ? The following factors must 
 be taken into account: 
 
 I. The actual acidity of the juice as secreted may increase with 
 the secretion rate, until the maximum acidity is reached with the 
 high average rate of secretion, under conditions similar to those 
 obtaining in the case of the salivary glands where the concentration 
 of the salts and the organic materials increases with the rate of 
 salivary secretion. If this is a factor the gastric juice secreted at a 
 low rate should show a lower osmotic concentration and a smaller 
 total of chlorides than the juice secreted at high rate. The figures 
 reported by Umber for man and by Rosemann for the dog support 
 this view, the former investigator showing particularly that the 
 osmotic concentration of the gastric juice increases with the rate 
 
CHEMISTRY OF HUMAN APPETITE GASTRIC JUICE 257 
 
 of secretion. The cryoscopic data may, however, be misleading, 
 as the salts produced by the neutralization of the HCl may not 
 dissociate as freely as the acid. 
 
 2. The slower rate of secretion may give a chance for the HCl 
 to be partly neutralized by the alkaline mucus secreted by the 
 mucin cells of the gastric mucosa. This is the factor emphasized by 
 Pavlov. In fact, Pavlov takes the position that in the normal 
 animal gastric juice has practically a constant acidity, irrespective 
 of the secretion rate, but the actual acidity of the juice in the 
 cavity of the stomach is purely a matter of rate of neutralization. 
 If this is the sole factor, the total chlorides of the gastric juice 
 ought to show a greater constancy than the acidity. That the 
 hydrochloric acid of the gastric juice is in part neutralized by the 
 gastric mucus is obvious. But according to Boldyreff the alkalinity 
 of gastric mucus is only 0^05 to o.io NaaCOj. That is to say, it 
 would require 100 to 200 c.c. of gastric mucus to reduce 100 c.c. of 
 gastric juice from the normal acidity of 0.45 down to o. 2 5 by neutral- 
 ization and dilution. The importance of this factor has therefore 
 been overestimated by Pavlov. 
 
 3. When the gastric juice is collected from a Pavlov accessory 
 stomach, or from an individual with complete closure of the esoph- 
 agus, as is the case with Mr. V., the saliva cannot be a factor in 
 lowering the gastric juice acidity by neutralization and dilution. 
 When all or most of the saHva is swallowed the acidity of the gastric 
 juice is necessarily reduced in proportion to the relative rate of 
 sahvary and gastric secretion. This is effected by dilution rather 
 than by neutralization, as the titration alkalinity of sahva is low 
 (0.8 NajCOj; Neumeister, cited by Boldyreff). 
 
 According to Boldyreff, Carlson, Hicks and Visher, Rehfus and 
 Hawk, an important factor in lowering the acidity of gastric juice 
 from that actually secreted by the gland (0.5) to that usually 
 found in the cavity of the stomach (0.25), is the entrance of the 
 alkaline intestinal contents (pancreatic juice, bUe, and succus 
 entericus) into the stomach. This usually occurs, probably, when 
 the acid in the stomach moimts much above 0.25. This "mechan- 
 ism for self-regulation of the acidity of the stomach content" 
 
258 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 probably breaks down in cases of so-called "hj^jeracidity" in man. 
 In cases of "hypersecretion" the quantity of juice secreted is 
 greater than normal, and the secretion may persist in the absence 
 of all normal stimuli, but the neutralizing factors sufl&ce to reduce 
 the acidity of the juice apprcJximately to that found in the normal 
 stomach. It is purely a balance of secretion rate and of neutraliza- 
 tion capacity. Impairment of the neutralization factors or a very 
 excessive secretion rate of gastric juice, or pyloric obstruction 
 would tend to render the acidity of the gastric content equal to 
 that of pure gastric juice; in other words, produce clinical "hyper- 
 acidity." 
 
 rX. TOTAL CHLORIDES 
 
 The total chlorides of the appetite gastric juice of Mr. V. are 
 very constant, the minimimi being 0.49 per cent and the maximum 
 0.56 per cent chlorine. The continuous secretion or hunger juice 
 is more variable in chloride content, and this variation appears to 
 be directly dependent on the secretion rate and on the acidity. 
 In general, the lower the secretion rate the lower are the acidity 
 and the total chlorides. This is in agreement with the findings of 
 Foster ind Lambert on dogs. 
 
 These facts seem to point to the conclusion that the low acidity 
 of the gastric juice secreted at a slow rate is not due entirely to 
 neutralization. We have apparently a secretion of gastric juice 
 of an acidity actually lower than that of the rapidly secreted 
 appetite juice. The dependence of the actual secreted acidity on 
 the secretion rate is not a very close one, however, as we may have 
 very marked fluctuation in rate without any change in chlorides. 
 But below a certain secretion rate (25 to 30 c.c. per hour from the 
 entire stomach of the adult) an actual hj^oacid juice is secreted. 
 
 The foregoing figures for total chlorides in the normal gastric 
 juice of Mr. V. agree closely with the findings of previous observers 
 on the gastric juice of dog and of man. Rosemann gives 0.54 to 
 0.64 CI for the appetite gastric juice of the dog. The figures given 
 by Sonimerfeld for human appetite juice vary from 0.53 to 0.59 CI. 
 Umber, working on an old man (fifty-nine years) with partial eso- 
 
CHEMISTRY OF HUMAN APPETITE GASTRIC JUICE 259 
 
 phageal stenosis (maKgnant), reports total chlorides of the gastric 
 juice as varying from 0.27 to 0.60 CI. 
 
 X. CONCENTRATION OF PEPSIN 
 
 In our tests the digestion mixture was made up of i c.c. gastric 
 juice and 15 c.c. N/10 HCl. . The egg albumin in the Metts tubes 
 was coagulated in boiling water for 10 miautes. The digestion 
 time was 24 hours at 37° C. Under these conditions the pepsin 
 concentration of the gastric juice of Mr. V. showed the following 
 figures: appetite juice, 6^ to 7I mm. digestion; continuous secre- 
 tion, 6 to 7 mm. digestion; contents of empty stomach, 3 to 4 mm. 
 digestion. The results are stated in the length of albumin column 
 actually digested, because, according to Cobb, the law of Schiitz 
 does not hold for pepsin in concentrations that digest more than 
 4 to 5 mm. in 24 hours. 
 
 The appetite gastric juice of Mr. E., our second gastric-fistula 
 case, when tested as above in 14 experiments, showed a pepsin 
 concentration of 5 to 7 mm. with an average of 6 mm., a slightly 
 lower value than the gastric juice of Mr. V. The pepsin concen- 
 tration of the gastric juice of normal dogs runs somewhat lower, 
 or 2 to 5 mm. 
 
 When the Metts tubes are placed in 16 c.c. of undiluted human 
 gastric juice (appetite secretion) the digestion in 24 hours at 37° C. 
 varies from 12 to 16 mm., or only twice the quantity digested in 
 the dilution of i c.c. juice to 15 c.c. N/io HCl. This seems to 
 indicate that in normal gastric juice the pepsin is present in excess 
 of the needs or at least far in excess of that needed in economic 
 digestion. 
 
 The U.S. Pharmacopeia defines " 100 per cent pepsin as a 
 preparation capable of digesting three thousand times its own 
 weight of finely divided egg white (coagulated) in three hours." 
 The Pharmacopeia test is carried out as follows : 10 gm. of boiled 
 white of egg is macerated through a No. 40 filter and placed in 
 40 c.c. 0.3 per cent HCL, 3^ mgr. dried pepsin added, and the 
 mixture incubated at 52° C. for 3 hours, with occasional stirring. 
 After being treated in this manner, there is only a very small residue 
 
26o CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 of undissolved egg white at the end of three hours, but the procedure 
 of measuring the amount of this residue does not 3deld very accurate 
 results. ' 
 
 This test was applied to six different lots of appetite gastric 
 juice of Mr. V. Under the foregoing conditions, i to i| c.c. appetite 
 gastric juice digested lo gm. of coagulated and finely divided egg 
 white in 3 hours practically as completely as is done by 3I mgr. 
 " ICO per cent pepsin." As defined by the U.S. Pharmacopeia, i c.c'. 
 of human gastric juice must therefore contain 3I mgr. pepsin, or 
 100 c.c. of the juice, 3 5 mgr. pepsin. We have seen that the appetite 
 gastric juice of man contains about 400 mgr. organic material per 
 100 c.c. That is, according to the Pharmacopeia definition, only 
 about 10 per cent of the organic matter in the human gastric juice 
 is pepsin. 
 
 It has been shown that an adult normal person, if hungry, 
 secretes 600 to 700 c.c. gastric juice after an average palatable 
 dinner, or a total of about 1,500 c.c. gastric juice in 24 hours. That 
 is to say, there is a secretion of 240 to 250 mgr. pepsin per dinner, 
 capable under proper conditions of digesting from 630 gm. to 750 
 gm. of protein (coagulated and finely divided egg albumin) in 3 
 hours; and the total pepsin secretion in 24 hours is 525 mgr. 
 capable of digesting i| kg. proteins (coagulated^eggwhite) in 3 hours. 
 
 It is therefore clear that the normal human stomach secretes 
 pepsin far in excess of the actual needs of gastric digestion, or, more 
 precisely, far in excess of what can be used advantageously under 
 ordinary conditions of gastric digestion. When the boiled egg 
 white is broken up in larger pieces, such as occurs in ordinary rapid 
 mastication, 1 c.a of gastric juice requires 6 to 10 hours for completfe 
 digestion. 
 
 This great excess of pepsin in normal gastric juice probably 
 explains the clinical findings of great reduction in pepsin content 
 without any evidence of impaired gastric digestion. It probably 
 also explains, in part at least, the practical uselessness of conxmercial 
 pepsin as a therapeutic measure in gastric disorders. 
 
CHAPTER XVI 
 HUNGER AND APPETITE IN DISEASE 
 
 I. ANALYSIS OF THE PROBLEM 
 
 We believe all physicians will agree that the control of hunger 
 and appetite is a very important factor in the control of disease, 
 and especially of chronic disorders. The physiologist is therefore 
 assured of the co-operation of the clinics in the investigation of 
 the pathology of hunger and appetite. Such co-operation is a sine 
 qua non for progress in this field, as the final verdict in the analysis 
 of the pathology of hunger is the word and the reactions of'the 
 patient himself. 
 
 Conditions of disease in man, so far as they affect hunger, 
 usually involve a decrease or absence of hunger and appetite 
 sensations, as in fevers, anemias, cachexias, and neuroses of various 
 origin. Certain pathological states such as diabetes, brain tumors, 
 neuroses, etc., may be associated with abnormally strong hunger! 
 and appetite. In diseases of the stomach itself the hunger sensa- 
 tion may be decreased (atony, gastritis, constipation, etc.), increased 
 (hypermotility, pyloric insufficiency, vagotonia, etc.), or altered in 
 the direction of abnormal painfulness, as in gastric and duodenal 
 ulcers. 
 
 From our analj^is of the nature of the hunger mechariism, it is 
 evident that depression or absence of the hunger sensation may 
 theoretically be brought aboiat in any one of the following ■wz.ys: 
 (i) direct failure or absenc e of the tonus and h unger contractions 
 of the empty stomach; (2) pr olonged reflex in hibition of the 
 stomach; (3) interference,with^or depre ssion of th e centra l con- 
 ductjonjgaths; (4) direct depression of the cerebra l or thala mic 
 hunger^ centers; (5) interferenc e with the cen t ral conduction of 
 the hunger impulses by abnormal or unusually strong_ mipuls es 
 frqm_otiier proprioceptors. These various conditions may be 
 caused by pathologi cal changes in the bloo d, in the motor 
 
 ,261 
 
262 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 mecha nism of the s tomach itself, o r in the central conduction paths 
 and sensory centers. Pathological augmentation of hunger would 
 result from the reversal of these conditions. Th e first que stion 
 that_must be s^ettled ^ the physiologicaljp athologv of hung er is 
 whe ther or not th e abnormaljtigsa re due to changes in the gastri c 
 h unger mech anism i tself ^ j^JTh is can in every case be settled by direct 
 tests on the patient, using our balloon method. When the patho- 
 logical changed are in the central nervous system itself their analysis 
 becomes much more difficult. 
 
 II. THE LITERATURE ON HXHSTGER AND APPETITE IN 
 DISEASE IN MAN 
 
 I. Bulimia. — Abnor mally intense hunger sensation has been 
 ter med bulimia.. Some authors do, othfers do not, distinguish 
 between buljmia and polyphagia. When distinctions are made, 
 the term poly phagia is used to denote the cond ition of excessiv e 
 inges tion of foo d, that is, an absence of satietv or sensation of 
 fu]^sSj_ r ather than an abnormallv intense hunger sensation . 
 Bulimia may be temporary or chronic. It is characterized by the 
 fact that hunger comes on shortly after eating, and if it is not 
 appeased by food there follow headache, weakness, and prostra- 
 tion, just as in normal hunger in many persons, only to a much 
 greater degree. Very small quantities of food may appease this 
 himger temporarily. This sensation of hunger m ay arise bef ore 
 the stom ach is emp tyj_although in many cases of bulimia, the food 
 leaves^the s.tpmach_ more rapidly than in normal persons (Ewald, 
 Perthes, Sick, Leo, Boas). Nic^ai^onclude;! that bulimia is due 
 to hyperexcitability of the afferent himger nervfe in the stomach 
 and esophagus. Ploenius i nsists that bulimia is an augmentation 
 of normal hunger, and appears only when the stomach is empty; 
 and that it in varia bly indicates organic lesions ia±he..stQmach, such 
 as local destruction of the mucosa with pepsin-HCl corrosion of 
 the deep tissues. According to Eeo, buli mia may occ ur in exoph - 
 thalmic goitre, in gastric and duodenal ulcer, with hyperacidity , 
 in chronic gastritis, diarrhoea, tapeworms, pregnancy, excessive 
 menstruation (hemorrhage), and even in cancer and m dilation of 
 
HUNGER AND APPETITE IN DISEASE 263 
 
 the stomac h. Ewald records bulimia associated with Addison's 
 disease, syphilis, uterine diseases, and brain injuries (tumors, 
 emboli, trauma). Meyer states that excessive hunger or bulimia 
 may appear in _all tj^es of neu rosig. 
 
 This hunger has usually a very sudden onset, and is satisfied, 
 or even turned into nausea by .very small quantities of food. 
 Meyer describes another type of intense hunger accompanied by 
 headache, in" which neither the hunger nor the headache is reheved 
 by eating, and the ingestion of food does not lead to the sensation 
 of fulness or satiety. But in these patients there was evidence of 
 ■other cerebral disturbances. Meyer argues that in cases where the 
 intense hunger is satisfied or even turned to nausea with a few 
 mouthfuls of food we cannot be dealing with the mere augmenta- 
 tion of true hunger. This position is not tenable. There may be 
 increased excitability of the inhibitory reflexes from the mouth 
 and the gastric mucosa, and hyperexcitabiUty of the mucosa nerve- 
 endings would lead to nausea after ingestion of even small. quan- 
 tities of food. Me yer also rep orts excessive hunger in certain 
 persons past middle life with tendency to adiposity. Perthes 
 reports bulimia in persons with patent pylorus. In some of 
 Jerthes's patients the hunger was intense enough to wake them 
 Tip from sleep every' two hours during the night. Boas assumes a 
 type of "idiopathic" bulimia, not accompanied by any other 
 functional or organic disturbances. 
 
 The excessive hunger in pregnancy is in all probability a^rmal r 
 physiological effect^of the increased metabolism due to the growing 
 fetus^ The peculiar fl uctuation in the appetite or desire for certain, 
 kinds of food that may occur in pregnai^ involves more compjex 
 fax;tors.^ 
 
 The bulimia of hypochondriacs, and other types of neurotics, 
 may be a subjective exaggeration of normal hunger impulses. 
 
 2. "Hunger pain." — The gastric pains that appear in the empty 
 :stomach or a few hours after ingestion of a meal in persons with 
 gastric or duodenal tilc^rs, or with gall-bladder disease are desig- 
 nated by Moynihan, Hertz, and others as "hunger pains." In 
 normal persons the hunger sensation, if sufficiently strong, is painful. 
 
264 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 The patients with ulcer or hypersecretion describe these hunger 
 pains in part as continuous or persistent, in part as variable or 
 "gnawing," precisely like the normal pangs of hunger, except 
 that they are more intense or painful. Like the normal pangs of 
 hunger the pathological hunger pains are allayed by the ingestion 
 of food. Most of the German authors do not differentiate between 
 bulimia and the hunger pains of gastric and duodenal ulcers. 
 
 Following Moynihan, many clinicians regard the hunger pains 
 in ulcers as caused by hydrochloric acid stimulation of the raw 
 surfaces of the ulcer. In support of this view they cite the fact 
 that the pains are temporarily relieved by giving alkalies by 
 mouth. Hertz has shown, however, that giving strong acids by 
 mouth to ulcer patients does not cause or increase the himger 
 pains. If the acid stimulation of the ulcer gives rise to these 
 hunger pains in ulcer patients, they have a different origin from 
 the normal hunger pains, as the latter are caused by strong, con- 
 tractions of the stomach, especially of the fimdic and cardiac 
 regions. The gnawing or rhythmical character of the hunger pains 
 in ulcer cases appears to the author to show that they are due to 
 contractions. If they were caused by chemical stimulation of the 
 sensory nerves directly we should expect them to be continuous. 
 Hertz has pointed out additional facts that support the mechanical 
 or contraction origin of the pains, such as the patency of the pylorus, 
 the rapid emptying of the stomach, the hypertonicity and hyper- 
 peristalsis of the stomach, etc., in both duodenal and gastric ulcer. 
 Moreover, hypersecretion and hyperacidity is not a constant factor 
 in ulcers (Hardt), and the hunger pains in ulcers may closely 
 simulate the gastric pain in cases of gallstones, appendicitis, 
 gasteroptosis, etc., where there is no raw mucous surface to be 
 stimulated chemically, either in the stomach or the duodenum. . 
 
 Edelmann states that the gastric digestion peristalsis is directly 
 dependent on the acidity of the gastric juice. But according to 
 Eisner the condition of achylia gastrica in man has per se no 
 effect on the digestion movements. The emptying time of the 
 stomach in achylia may be normal, less than normal, or greater 
 than normal. 
 
HUNGER AND APPETITE IN DISEASE 265 
 
 The recent studies on man by Spencer, Meyer, Rehfus, and 
 Hawk have led them to conclude that weak alkalies (sodium 
 bicarbonate) in the stomach hasten the empt3dng of the stoijiach 
 by increasing the digestion peristalsis or by opening the pylorus. 
 This is opposed to the generally accepted view of the acid control 
 of the pylorus, as developed by Cannon. If their conclusion is 
 substantiated, we may have the explanation of the allaying of the 
 "himger pains" in ulcer patients by oral administration of alkalies. 
 That is, the alkalies cause relaxa^on of the tetanic spasm of the 
 pylorus and antrimi, induced reflexly from the duodenum. Glassner 
 and Kreuzfuchs state that in cases of gastric ulcer there is a pro- 
 longed tetanic closure of the pylorus when the acid chyme first 
 enters the duodenum. This is a reflex from the duodenum. The 
 body of the stomach is atonic and quiescent during this pyloric 
 spasm. The spasm itself is felt as pain. In cases of duodenal 
 ulcers similar pylorus spasms come on later in digestion and are 
 likewise felt as pains. According to these observers the hunger 
 pains in ulcers are thus due to pylorus spasm, while Hertz ascribes 
 them to contractions of the entire antrum. Pick suggests that the 
 pains are due to mechanical stimulation of the food rather than 
 to the acid stimulation of the ulcer. Ehrlich protests against the 
 view that "painful empty stomach" in ulcer patients is an evidence 
 of neurosis. According to Jacobi, the pains of gastric and duodenal 
 ulcers are due to "hypersecretion, h}^erperistalsis, or pressure." 
 
 Are the sensations of "hunger pains" identical with the normal 
 pangs of hunger except for their greater degree of painfulness? 
 This question cannot be answered from the clinical literature, and 
 probably will remain unanswered until the clinical investigator 
 himseK experiences the pain in ulcer and allied diseases. These 
 pains may lead to or be associated with nausea, but the same is 
 true in normal hunger of some persons and in prolonged starvation. 
 The "peristaltic xmrest" of Kussmaul occurs both in the filled and 
 in the empty stomach, in cases of pyloric obstruction and in cer- 
 tain forms, of neurosis. The sensations aroused by this condition 
 are said to be similar to cramps rather than to the pangs of hunger. 
 The gastralgokenosis of Boas is thought by this author to be due 
 
266 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 to the strong contractions of the pyloric part of the stomach toward 
 the end of gastric digestion. Although the pain disappears on 
 taking food, Boas does not identify it with true hunger pains. 
 The gastralgia in tabes is generally held to be of central origin, 
 but so far as we know the tonus and motor conditions of the stom- 
 ach have not been studied during the gastric crisis of this disease. 
 
 3. Polyphagia and akoria. — The term "polyphagia" is frequently 
 used in the sense of bulimia or excessive hunger. Other authors 
 confme it to excessive ingestion of food without actual augmenta- 
 tion of the hunger sensation. In this latter sense it imphes essen- 
 tially delay in or absence of the sensation of satiety. Nicola^ 
 beheved that polyphagia results from anesthesia of the stomach 
 nerves concerned in the sensation of satiety. But true akoria or 
 absence of satiety occurs mainly in hysteria and neurasthenia, and 
 has probably nothing in common with such a condition as the 
 polyphagia in diabetes. 
 
 4. Anorexia. — ^Theddnunution jQtabsencejpf ji^^ and appeti te 
 i n gastero-enteriti s, in fevers, and in caxdiejaa^ jtc., are in all prob- 
 ability associated with atony of the stomach and absence of the 
 gastric hunger contractions. The evidence for this view will be 
 presented later. The true anorexia nervosa is probably of more 
 complex origin, involving both central and peripheral factors. 
 There ma y be atony and absence of the gastric himger contractions 
 €vmjn_cases where no or ganic lesion in the stomach can be demon- 
 strate d. In some cases of anoreaaJEwald found pathological 
 changes in the mucous membrane of the moutiij suggesting disorders 
 of .the sense of taste. 
 
 When the anorexia is very marked it may be accompanied by 
 nausea, at least at the sight, smell, or taste of food, or an actual 
 fear of food and eating (sitophobia). Under other conditions a 
 mild nausea may be present synchronously with practically normal 
 hunger and appetite (Boas). ,We have seen that this may occur 
 in normal individuals in prolonged starvation. J^erv gus anorexia 
 i s more common in women than in men. Vertes^ takes the position 
 that most of the disturbances of hunger^ ajod appetite that appear 
 in pregn^cy, ovarian diseases, menstrual (Usijrders^ etc.^ are in 
 
HUNGER AND APPETITE IN DISEASE 267 
 
 re ality independent of t he latter^ while in a few cases, they are 
 reflex neuroses. The actual state of the gastric hunger mechanism 
 in these conditions is not known. 
 
 5. Parorexia. — ^This term is used to designate various types of 
 abno rmal, perverted, or depraved app etite. These conditions refer 
 exclusively to appetite, rather than to hunger, at least it has not 
 been shown that hunger is at all iavolVed. The least abnormal 
 condition appears to be the malacia, or desire for highly spiced or 
 acid foods that are sometimes seen in chlorotic girls and in preg- 
 nant womeii^ Another type — p ica — ^i s the_appetite for substances 
 that are not food, such^ asclay^ chalk, or earth. These materials 
 are eaten, especially by children, because they like the taste of 
 them. This is probably a bad habit, rather than an indication of 
 seriously perverted mental processes. Most of our domestic ani- 
 mals, even those that appear perfectly healthy, eat earth at times, 
 aside from the quantity of earth consumed with their ordinary 
 food and drink. And even with the best of care in the way of food 
 hygiene, we all consmne more or less earth, dirt, stable manure, 
 etc., with our food.- To the mind of the average adult earth has 
 become synonymous with dirt or filth, hence we abhor taking it 
 into the mouth, just as the average person loathes snakes. The 
 child, not having formed these associations, puts sand, chalk, or 
 earth into his mouth from general curiosity or in the spirit of play, 
 and may or may not like the new experience. If he likes it, he will 
 repeat it until he learns the usual social canons. Clay^atingJs-OiL 
 a par with gum chewing andjtobaccoLchewing,^ and i^-certainly less 
 injurious and.nasty than the latter habit. 
 
 6. AUotriophagia, or desire for disgusting and offensive sub- 
 tances, such as human excreta, body lice, etc., is practically confined 
 to insane individuals, or extreme degenerates. It is likely that t&e 
 habit is reached via the route of sexual depravity, at least in many 
 
 .cases. In persons with the ordinary idea-associations lost or 
 suppressed, tolerance and even liking for any kind of taste and 
 odor can apparently be cultivated. We all know that animal 
 excreta are regularly ingested by many normal animals, though 
 most of them pass by those of their own species. 
 
268 CONTROL OF^.HUNGER IN HEALTH AND DISEASE 
 
 ni. CONDITION OF THE GASTRIC HUNGER MECHANISM IN 
 DISEASE OF EXPERIMENTAL ANDIALS 
 
 1. Pancreatic diabetes. — Experimental pancreatic diabetes in 
 animals is accompanied by the excessive hunger or polyphagia of ' 
 diabetes melitus in man. Dr. Luckhardt studied the gastric hunger 
 contractions in two dogs during the entire course of fatal pancreatic 
 diabetes. With good care dogs live from 4 to 6 weeks after complete 
 pancreatectomy, showing progressive emaciation despite their exces- 
 sive intake of food. In both the diabetic dogs the gastric tonus 
 and hunger contractions were more continuous and vigorous than 
 in normal dogs or in the same dogs before they became diabetic. 
 This augmentation of the gastric hunger contractions persisted up 
 till within 24 hours of the death of the animals, despite the progres- 
 sive and finally extreme emaciation and weakness. The increased 
 food consumption of the dogs thus ran parallel with the greater 
 vigor of the peripheral hunger mechanism. And there can be little 
 doubt that the dogs felt greater htmger and consumed more food 
 because of the greater vigor of the gastric hunger contractions. 
 
 The cause of this augmented contraction of the empty stomach 
 in diabetes is still an open question. It is evidently due, at least 
 in part, to some change in the blood, for transfusion of diabetic 
 blood into normal dogs stimulates the hxmger contractions in the 
 latter. Allen states that when partial diabetes in man is controlled 
 by means of temporary starvation and dieting, so that the urine 
 becomes free from sugar and the acidosis disappears, the polyphagia 
 of the diabetic patient also disappears, but we do not know whether 
 the latter is due to a return of the gastric hunger mechanism to the 
 normal state of activity. 
 
 2. Polyphagia and augmented gastric hunger contractions in dogs 
 with' mange. — ^A number of dogs kept in the laboratory for long 
 periods in the course of certain lines of investigation became 
 afflicted with mange. Dr. Luckhardt observed that these mangy 
 dogs consumed a much greater amount of food than they did before 
 contracting or after being cured of the disease. It was also noted 
 that a dog with mange is more susceptible to cold than normal 
 dogs, as shown by their ahnost constant shivering, even in a room 
 
B 
 
 Fig. 30. — Records of the gastric hunger contractions of a dog before and during 
 fatal pancreatic diabetes (Luckhardt). Bottom of tracings,-f o pressure of bromoform. 
 A , type II contractions indicating moderate hunger in dog before rendered diabetic. 
 Four-fifths original size. B, culmination of a tetany period in the diabetic animal last- 
 ing about 20 minutes. Smaller tetany periods are likewise shown. Throughout, a 
 type III rhythm on a high tonus. Two thirds original size. C, tracing obtained from 
 the empty stomach of a diabetic dog less than 2 days before death. Throughout, 
 type III contractions on a high tonus. Dog too weak to walk. Ate 105 gm. meat — 
 the last meal before death, which followed 2 days later. Two-thirds original size. 
 
270 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 with temperature ranging from 55° to 65° F. This is probably due 
 to the loss of hair, and to interference with the normal vaso- 
 constrictor reflexes of the skin by the persistent cutaneous 
 
 Fig. 31.— Tracing from empty stomach of dog while normal (A), and after 
 developing severe mange (5); showing abnormally intense gastric hunger parallel 
 with the mange and the polyphagia (Luckhardt). 
 
 hyperemia. These conditions must involve an abnormal heat loss 
 from the skin. 
 
 The gastric tonus and hunger contractions were studied in a 
 number of these mangy and polyphagic dogs, in order to determine 
 whether the greater hunger was due to greater gastric hunger 
 
HUNGER AND APPETITE IN DISEASE 271 
 
 contractions. This proved to be the case. A dog with extensive 
 mange but otherwise healthy exhibits abnormally great gastric, 
 tonus and hunger contractions. The latter tend to become tetanic, 
 and when this is not the case, the individual contractions are abnor- 
 mally strong. The polyphagia of the mangy dogs is therefore due to 
 the greater vigor of the gastric hunger mechanism. The stronger 
 gastric contractions are probably brought about indirectly through 
 increase in muscular metaboHsm as a result of the too great loss of 
 heat from the skin, in other words, the same effects as we found on 
 exposing normal men and animals to great and prolonged cold. 
 
 3. Hunger and appetite in cases of alcoholic gastritis in dogs. — 
 Dr. Luckhardt found that whiskey or strong alcohol introduced 
 directly into the empty stomach of dogs in sufl&cient amount to 
 induce marked narcosis abolishes the tonus and hunger contrac- 
 tions of the stomach for 24 to 36 hours. During this period the 
 animal refuses food and may vomit at times. After 36 to 48 hours 
 the hunger contractions gradually return and may at times even 
 approach the condition of incomplete tetanus. The dog shows 
 interest in food, but may eat only a mouthful. Occasional vomiting 
 stiU continues. Evidently the gastric mucosa continues hyper- 
 sensitive for a much longer time than the period of motor paralysis 
 of the stomach, so that ingestion of food induces or increases 
 nausea and gastric distress, despite the fact that hunger contractions 
 and hunger sensations are present. In other words, the dog experi- 
 ences himger and nausea at the same time. That the dog actually 
 feels the contractions of the empty stomach as hunger seems to be 
 shown by the fact that he walks up to the food from time to time, 
 sniffs at the food, and may even start to eat a little. At the end 
 of several days, vomiting disappears entirely and the dog resumes 
 normal feeding. 
 
 The interesting point in these observations is the recovery of 
 strong gastric hunger contractions a considerable time before the 
 dog starts normal feeding. We think the disinclination to eat, 
 despite moderately strong hunger, is due to nausea induced from 
 the hyperexcitable gastric mucosa. After-effects of alcohol on the 
 brain may also play a role. 
 
2 72 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 fiG. 32. — Tracings from empty stomach of dog showing effect of alcoholic, 
 gastritis on the hunger mechanism (Luckhardt). A, gastric hunger contractions of 
 dog before inducing alcoholic gastritis. B, tracing showing atonic stomach of dog 24 
 hours after excessive administration of alcohol by stomach tube. Dog drinks water 
 and vomits but refuses food. C and D, moderate gastric hunger contractions of dog 
 3 and 4 days after the alcoholic debauch. Dog ate a little, and vomited frequently, 
 evidently being nauseated and feeling some hunger at the same time. E, vigorous 
 hunger contractions 8 days after inducing the gastritis; dog normal and eating 
 greedily. 
 
HUNGER AND APPETITE IN DISEASE 273 
 
 4. Paralysis of the gastric hunger mechanism in pneumonia, 
 distemper, and general peritonitis. — ^Dogs with well-advanced pneu- 
 monia or distemper refuse all food. Such dogs show complete atony 
 and absence of gastric hunger contractions. This is likely the 
 condition of the empty stomach in all acute infections of sufficient, 
 severity. The mechanism of the failure of the hunger contractions 
 in these acute infections is not known. The bacterial toxins may 
 depress the motor mechanism of the stomach directly, lower the 
 vagus tonus, augment inhibitory reflexes, or induce excessive secre- 
 tion of epinephrin. The elevated temperature may also play a 
 role. Cannon observed that infections also depress the digestion 
 peristalsis of the stomach and intestines in. cats. 
 
 5. Depression of the gastric hunger contractions in parathyroid 
 tetany. — ^Animals in parathyroid tetany show decrease or absence 
 of desire for food in direct proportion to the severity of the tetany 
 and cachexia symptoms. Is this refusal of food due to absence of 
 the gastric hunger contractions ? 
 
 Our observations were made on three dogs. The dogs were 
 observed every third day for two weeks, so as to secure the average 
 normal gastric tonus and hunger contractions before extirpation 
 of the parathyroid. All three do^s ran a t)^ical course of tetany 
 of varying severity from day to day. Dog I died in tetany on the 
 sixth day after the operation; Dogs II and III died in depression 
 on the eighth and tenth days respectively. The results were 
 practically the same in the three dogs. In this tetany there is 
 depression of the tonus and contraction of the empty stomach 
 parallel with the severity of the tetany, so that during extreme 
 tetany the stomach is practically atonic, and tonus contractions 
 and hunger contractions are completely absent. The milder stages 
 of the tetany (hyperexcitabiUty of the motor nerves, slight tremors, 
 twitchings, and some salivation) may coexist with considerable 
 gastric tonus and hunger contractions, but the hunger contractions 
 are always slower and weaker than normal. 
 
 It is well known that the course of parathyroid tetany, especially 
 in dogs, is usually more or less periodic, the animal recovering 
 spontaneously for periods varjdng from a few hours to a day or 
 
274 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 more between the tetany attacks. Dog II showed two such periods 
 of spontaneous recovery of 34 and 20 hours' duration. During 
 these periods the gastric hunger contractions and the gastric tonus 
 also returned to approximately normal conditions, the dog at the 
 same time taking normal interest in food. 
 
 The relation of these depressions of hunger and appetite to the 
 gastric hunger contraction is, nevertheless, not a direct one. Dur- 
 ing the mild stages of tetany the failure of hunger and appetite is 
 usually much greater than one would expect'on the basis of the 
 degree of depression of the hunger contractions. In strong tetany 
 there are no gastric hunger contractions and the dogs refuse food, 
 but the dog may refuse food even though fairly strong hunger 
 contractions are present in mild tetany, or if he does eat the amount 
 of food consiuned is very small. It is therefore clear that the 
 depression of hunger and appetite in tetany cannot be accounted 
 for solely on the basis of depression of gastric hunger contractions, 
 although this is unquestionably one of the factors. But we must 
 also take into account either a change in the central nervous system, 
 or a change in the character of the nervous impulses from the 
 stomach and other proprioceptor systems. 
 
 The condition of parathyroid tetany, so far as it influences the 
 stomach motor activities, depresses both the digestion movements 
 of the filled and the hunger contractions of the empty stomach, 
 but the movements of digestion show less depression than do the 
 hunger contractions. Thus moderately strong tetany may leave 
 the gastric digestion movements practically normal but completely 
 inhibit the hunger contractions of the empty stomach. The tetany 
 condition does not lead to increased motor activity, either in the 
 empty or the filled stomach. 
 
 The cause of this depression of the gastric motor activities in 
 parathyroid tetany is not determined. In the case of the digestion 
 movements it was shown not to be due to splanchnic inhibition. 
 This test has not been made in the case of the hunger movements. 
 But one factor in the depression or complete inhibition of the hun- 
 ger contraction in tetany is the increased excitability of the nerve- 
 endings in the gastric mucosa. Vomiting is a tetany symptom in 
 
HUNGER AND APPETITE IN DISEASE 275 
 
 dogs. And dogs in tetany frequently vomit with nothing in the 
 stomach but bile and saliva. In such dogs water at body tempera- 
 ture introduced into the stomach through a fistula in the fundus 
 causes vomiting. The presence of a deUcate rubber balloon in the 
 stomach or the slight inflation of the balloon causes vomiting. 
 This never occurs in normal dogs. The stimulation of the nerve- 
 endings in the gastric mucosa in normal animals (man and dog) 
 causes inhibition of the gastric hunger contractions through weak 
 and long reflexes. In parathyroid tetany these nerve-endings in the 
 mucosa become so hypersensitive that they are intensely stimulated 
 by saliva, water, bile, and gastric juice. But in addition to these 
 inhibitory reflexes from the gastric mucosa we probably also have a 
 direct depression of the automatic tissue in the stomach, for it is not 
 likely that the inhibitory reflexes, even though very strong, could 
 maintain the sustained extreme depression seen in strong tetany. 
 
 By way of sxmmiary, we conclude that parathyroid tetany in 
 dogs does not lead to increased tonus or contractions of the empty 
 stomach, but to depression of the tonus and the hunger contractions. 
 The degree of the depression of the motor activities of the empty 
 stomach is on the whole parallel with the severity of the tetany 
 symptoms, and more marked than the depression of the gastric 
 movements of the digestion. The hyperexcitability of the nerve- 
 endings in the gastric mucosa is a factor in this depression. The 
 stimulation of these nejve-endings leads, through local and long 
 reflexes, to inhibition of the tonus and the hunger movements. 
 There is probably also a direct depression of the automatic tissue 
 in the stomach through changes in the blood. The diminution or 
 lack of appetite for food in animals in tetany is on the whole greater 
 than would be expected on the basis of the degree of the depression 
 of the gastric hunger contractions. The cause of the lack of hunger 
 and appetite in tetany is therefore complex. It is due in part to 
 the depression of the gastric hunger contractions. Other factors 
 are the change in the brain, and in the character of the other 
 afferent nervous impulses. 
 
 6. Increase in gastric tonus and hunger contractions in dogs after 
 partial occlusion of the pylorus. — It is well known that pyloric 
 
276 CONTJIOL OF HUNGER IN HEALTH AND DISEASE 
 
 I 
 
 obstruction in man leads to various disturbances of the gastric- 
 digestion movements, as well as to disturbances of the hunger 
 sensation. In order to determine whether any of the latter dis- 
 turbances, and particularly the stronger gastric pains that are so 
 frequently in evidence in pyloric obstruction, are due to changes 
 in the motility of the empty stomach, the hunger contractions of 
 the empty stomach after partial occlusion of the pylorus were 
 studied in two dogs by Dr. Elsesser. 
 
 The pyloric obstruction was made in the following manner. 
 The serosa extending across the pyloric sphincter about | cm. by 
 15- cm. was scarified, care being taken to avoid injury to the larger 
 blood vessels of that region. Two rows of stitches running parallel 
 to the long axis of the bowel were made, the second folding in the 
 first, thus bringing the two scarified surfaces together and at the same 
 time partially occluding the pyloric lumen. The method has these 
 advantages, that some pyloric obstrubtion is sure to be produced 
 which will be firmly maintained by adhesions forming between the 
 two raw surfaces. Furthermore, complete occlusion and loss of the 
 animal is avoided, a termination frequently attendant upon placing 
 ligatures around the pylorus. After the animal had recovered suffi- 
 ciently from the effect of the operation — a matter of several days — • 
 records of the gastric hunger contractions were made duplicating the 
 normal ones, both as to conditions and periods of time. On one dog, 
 which we may designate as Dog A, a second operation similar to the 
 first was performed and a second series of tracings was obtained. 
 
 Dog A remained very well and active and was killed 35 days 
 after the first and 14 days after the second operation. At autopsy 
 ,the pylorus presented a lumen constricted by a hard, tough mass 
 of granulation tissue, the seat of the scarification and stitching. 
 The stomach was not distended, but showed some hj^ertrophy. 
 The gastric mucosa lay in deep folds. Dog B became somewhat 
 emaciated after stenosis, evinced a hypersensitivity of the gastric 
 mucosa by occasional vomiting of the balloon while records were 
 being made. At autopsy the pylorus was constricted, so that the 
 stomach contents would be forced through it only with difficulty. 
 The stomach itself was considerably dilated. 
 
HUNGER AND APPETITE IN DISEASE 
 
 277 
 
 Both dogs gave evidence of delayed emptying of the stomach 
 after the stenosis, in that food remnants were frequently foxmd in 
 the stomach more than 24 hours after feeding. 
 
 Fig. 33. — Tracings showing contractions of the stomach of dog ^. Dog normal; 
 tracing, taken 48 hours after feeding, represents height of a period of hunger contrac- 
 tions; B, same dog as in tracing A, 42 hours after feeding, 30 days after production 
 of partial stenosis of the pylorus, showing typical hypertonus and tetany periods of 
 the empty stomach. Chloroform manometer. Time, 15 minutes (Elsesser). 
 
278 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 After recovery from the operations the empty stomachs of these 
 two dogs showed more continuous and on the whole stronger 
 himger contractions than before the operation, with a tendency 
 for the contraction tq pass into long periods of incomplete tetanus. 
 It is thus clear that partial stenosis of the pylorus induces a hyper- 
 motility in the stomach, irrespective of the presence of food in the 
 stomach cavity. The hypermotility of the stomach during gastric 
 digestion may be a temporary condition induced by the presence 
 of the food and retardation of its passage through the pylorus, a 
 condition similar to that of the small intestine above a region of 
 obstruction. The fact that the hypermotiUty is present even in 
 the empty stomach seems to show that the piotor changes following 
 mere mechanical obstruction of the pylorus are more fundamental 
 and permanent. 
 
 The mechanism of this increased motility can as yet only be 
 conjectured. Bacterial toxins from local foci of infection are 
 excluded in these 'experiments, as the partial stenosis was produced 
 aseptically in animals with normal stomachs and without sub- 
 sequent infection. We may be dealing with nervous reflexes from 
 the pylorus involving the entire stomach. 
 
 By way of summary, we conclude that partial pyloric stenosis 
 in dogs produces hypertonicity, hypermotihty, and hyperperistalsis 
 of the empty stomach, even if of but a few days' or weeks' duration. 
 These motor phenomena are similar to those seen in the filled 
 stoma'ch in man with partial obstruction of the pylorus. The same 
 conditions which lead to h3T)erperistalsis, etc., during digestion, 
 led at the same time to increased motility of the empty stomach. 
 In other words, partial pyloric stenosis appears to produce a neuro- 
 muscular hyperactivity, independent of the presence of food in 
 the stomach. 
 
 IV. EXPERIMENTAL INVESTIGATION OF THE HUNGER 
 MECHANISM IN DISEASE OF MAN 
 
 I. Absence of gastric hunger contractions in gastritis, tonsillitis, 
 influenza, and "colds." — ^During the four years that Mr. V., the 
 gastric-fistula case, has been under observation in our laboratory 
 
HUNGER AND APPETITE IN DISEASE 279 
 
 he has had a few attacks of mild gastritis, in three cases associated 
 with nose and throat colds, with some temperature. During these 
 attacks the eingty^tomach^remained_somewha^^ 
 plete abs ence of the Hunger contractions. Mrr V. felt no hunger 
 and EaH little or no desire to eat. In fact, putting food in the 
 stomach in these conditions sometimes produced nausea. The 
 absence of hunger and depression of the appetite thus ran parallel 
 with the impairment of the gastric hunger mechanism. 
 
 Luckhardt and Hamburger have reported gastric atony and 
 absence of hunger contractions in a case of acute gastritis brought 
 on by dietary indiscretion! The author has taken records on him- 
 self in one mild attack of gastritis, lasting three days, two attacks 
 of "cold" and tonsillitis, one of which was complicated with painful 
 antrum infection. During the gastritis the empty stomach showed 
 no himger contraction. The tonsillitis, "colds," and antrum 
 infection did not completely abolish the hunger contractions, except 
 when sufficiently severe to induce elevation of the body temperature 
 to 101° or 102° F. Again, the depression or absence of the feeling 
 of hunger ran parallel with the degree of depression of the gastric 
 himger contractions. But even when no hunger was experi- 
 enced, the sight of palatable food was capable of inducing some 
 appetite. 
 
 2. Hunger in diabetes melliius. — Dr. Luckhardt studied the 
 gastric himger contractions of a man twenty-nine years of age, in 
 the last stage of diabetes. The em|)ty stomach showed abnormally 
 strong hunger contractions till within a few days of death in coma, 
 the patient at the same time complaining of great hunger. This 
 seems to show that in chnical diabetes there is an increased activity 
 of the gastric hunger mechanism similar to that demonstrated 
 in pancreatic diabetes in dogs. But more observations are needed 
 on clinical diabetes before this relation can be accepted or 
 demonstrated. 
 
 3. Gastric hunger contractions in a case of gastric cancer. — The 
 subject was an old man, considerably emaciated, but with no 
 serious obstruction at the pylorus. His hunger and appetite were 
 good and his gastric hunger contractions normal. This observation 
 
28o CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 Fig. 34. — A , normal hunger contractions of the empty stomach of a neurasthenic 
 man. The contractions gave rise to epigastric pain, not hunger pangs. B, tetanic 
 contractions of the empty stomach of a man with carcinoma of the stomach and par- 
 tial pyloric obstruction. The contractions caused epigastric distress, rather than 
 true himger. C, vigorous hunger contractions of the empty stomach of a diabetic 
 man, 5 days before death in diabetic coma, showing vigorous hunger contractions 
 associated with the diabetic polyphagia (Luckhardt and Hamburger) . 
 
HUNGER AND APPETITE IN DISEASE 281 
 
 of Luckhardt and Hamburger is in line with the fact that patients 
 with cancer of the stomach may continue to feel hunger when 
 the tumor growth is so advanced that feeding by mouth becomes 
 impossible. 
 
 4. Excessive pain produced by normal gastric hunger contractions 
 in neurasthenics. — -Dr. Luckhardt reports a case of a man who 
 sought hospital treatment for a dull ache or epigastric pain which 
 came on whenever the stomach was empty. This pain or ache 
 proved to be due to the himger contractions of the empty stomach, 
 the latter not being stronger than those observed in normal indi- 
 viduals. The patient beheved that the o])servation of his stomach 
 by the balloon method was a method of treatment. The patient 
 stated after a few days that the pain had ceased entirely, although 
 the gastric himger contractions continued normal, and he left the 
 hospital very grateful for what had been done for him. There was 
 no evidence of organic lesion in the stomach. This case presents 
 either a temporary neurosis (hyperexcitability) of the gastric hun- . 
 ger nerves so that the normal contractions actually give rise to 
 abnormally strong impulses, or else the normal impulses from the 
 stomach become exaggerated in consciousness through perverted 
 attention. 
 
 The author studied the gastric hunger contractions of a similar 
 case, a. young farmer seeking medical aid for excessive epigastric 
 pain, and some feeling of weakness and depression. No organic 
 lesions could be detected. The gastric hunger contractions were 
 strong, the periods ending in incomplete tetanus, but equally strong 
 hunger tonus and contractions have been seen in normal individuals 
 of .his age and occupation. Yet the tonus and contractions were to 
 him sufficiently painful to seek medical aid repeatedly, but no 
 treatment appeared to give permanent relief. 
 
 5. Cause of the "hunger pains" in cases of gastric and duodenal 
 ulcers. — ^Hamburger, Ginsburg, and Tumpowsky found that the 
 "gnawing" hunger pain's in duodenal and gastric ulcers are caused 
 by the hunger contractions of the empty or partly empty stomach. 
 These contractions are, on the whole, not stronger than those of 
 healthy persons in hunger, yet they are felt as much more painful 
 
282 
 
 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 •3 H 
 
HUNGER AND APPETITE IN DISEASE 283 
 
 than the normal hunger pangs. This may be due to hyperexcita- 
 bility of the sensory nerve-fibers in the stomach. These patients 
 usually feel a more or less steady and dull gastric pain besides the 
 gnawing or intermittent pains associated with the rhythmical 
 contractions. -The cause of the continuous but less sharp pain is 
 probably to be sought in the steady and strong tonus contractions 
 of some region of the stomach or duodenum. This steady but dull 
 gastric pain in ulcer patients is thus similar in origin to that felt 
 by some people in prolonged starvation. 
 
 If the theory of infectious origin of ulcers indicated by the work 
 of Rosenow is applicable in all cases, the hyperexcitabihty of the 
 gastric sensory nerves in ulcer is probably due to the local inflam- 
 matory processes. Even in ulcers of traumatic origin (chemical, 
 mechanical) secondary infection probably takes place, so that even 
 in such cases we have local inflammation. 
 
 6. Cause of gastric pain in diseases of the gall bladder. — ^We do 
 not refer to the pain definitely due to the mechanical stimulation 
 of the gall bladder or the bile duct by biHary calculi, but to the 
 epigastric pains that come on a certain length of time after a meal, 
 and closely resemble the hunger pains of ulcer, We know that 
 the rhythrnical contractions of the gall- bladder are greatly aug- 
 mented during gastric digestion, probably through reflex stimu- 
 lation of acid chyme in the duodenum. In this manner, pain from 
 the gall bladder itself may be augmented parallel with gastric 
 digestion peristalsis especially in cases of hypersecretion. 
 
 Ginsburg and Tumpowsky studied the epigastric pain in one 
 patient with gall-bladder infection, as determined by clinical diag- 
 nosis. Gastric and duodenal ulcers were excluded. In this patient 
 the pain ran absolutely parallel with the strong hunger contractions 
 of the empty or nearly empty stomach. The hunger contractions 
 were stronger than usual for a man of the patient's age. We can- 
 not be sure that the gastric contractions were the only cause of 
 the pains; there may be strong contractions of the gall bladder 
 parallel with the stomach contractions. 
 
 In this patient, too, the epigastric pain appeared greater than 
 warranted by the strength of the gastric contractions. Evidently 
 
284 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 gall-bladder infections may lead to hyperexcitability of the sensory 
 nerve-fibers of the stomach and duodenum, possibly from the 
 spread of bacterial toxins along the branches of the vagi nerves. 
 
 7. Hunger contractions of the empty stomach in infants with 
 ■ pylorospasm and congenital pyloric stenosis. — ^Pylorospasm has been 
 ascribed to a great variety of causes, including primary neurosis 
 of the local motor mechanism. The hyperperistalsis of the filled 
 stomach usually associated with spasms of the pylorus may be a 
 temporary condition due to the presence of food in the stomach. 
 On the other hand, if pylorospasm is simply an expression of pri- 
 mary hypermotility of the entire stomach, this condition of hyper- 
 tonus and hypermotility should also be in evidence when the 
 stomach is empty. A study of the motor conditions of the empty 
 stomach may thus aid in determining some of the factors involved 
 in hypercontractility of the pyloric sphincter. In infants " riimina- 
 tion" is probably always secondary to chronic vomiting, which in 
 turn may or may not be associated with pylorospasm. If the 
 vomiting is due to gastric hypertonidty and hypermotility, these 
 conditions should also be present in the empty stomach, with or 
 without the involvement of the pylorus. 
 
 We have studied the motor conditions of the empty stomach in 
 two infants, one with congenital pyloric stenosis, and one with 
 pylorospasm, chronic vomiting, and rumination. 
 
 Case I : Infant three months old; chronic vomiting and gradual 
 loss of weight. Congenital pyloric stenosis. Gastro-enterostomy 
 was made. The pylorus was found contracted, and somewhat 
 edematous and anemic. Before the operation, record of the tonus 
 and contractions of the empty stomach was made by the balloon 
 method as applied to infants. The strength of the contractions was 
 markedly greater than in normal infants. The duration of the 
 periods of contraction was also greater. This indicates a greater 
 than normal gastric tonus. There was no indication of prolonged 
 tetanic contractions. 
 
 Case 2: Infant five months old; chronic vomiting ("rumina- 
 tion"). Practically stationary body weight. Pylorospasm. A 
 number of observations were made on this infant. When the child 
 
HUNGER IN APPETITE AND DISEASE 
 
 285 
 
 if 1 \l i 
 
 
 1 
 
 
 
 M H, K 
 
 
 1 
 
 1 
 
 i hi 
 
 1 ; 1 
 
 1 
 
 1 
 1 
 
 1 
 
 ! 
 
 1 
 
 
 
 Fig. 36. — A, tracing showing a period of vigorous hunger contractions of the 
 empty stomach of a normal infant; B, tracing showing exceptionally intense and 
 practically continuous hunger contractions of a 3-months-old infant with persistent 
 pylorus spasm amounting to almost complete pyloric obstruction accompanied by 
 chronic vomiting and gradual loss of weight; C, tracing showing exceptionally intense 
 hunger contractions and periods of incomplete tetanus of the empty stomach of a 
 S-months-old infant with chronic vomiting ("rumination") and practically stationary 
 body weight. In the right half of the tracing the upward exciu-sion of the manometer 
 had to be checked mechanically to prevent the chloroform from being driven out. 
 Hence the extreme vigor of the gastric contractions is not fully registered. Chloro- 
 form manometer. Time 20 minutes. 
 
286 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 was quiet, so that all nervous inhibitory factors were eliminated, 
 the empty stomach usually showed hypertonus with periods of 
 tetanic contractions lasting several minutes, interspersed with 
 vigorous contractions of normal duration — an unmistakable con- 
 dition of hypertonicity ' and hj^permotility. If the infant was 
 asleep during the observation period the tetanic contraction of 
 the stomach invariably caused restless facial grimaces, or he would 
 wake up and cry. Such vigorous and prolonged periods of tetanic 
 contractions have so far never been observed in the empty stomach 
 of normal infants. They have been observed in adult persons and 
 in dogs after prolonged starvation. This type of contractions of 
 the empty stomach may also be seen in dogs with pancreatic 
 diabetes. ^ 
 
 The results in the cases of these two infants indicate that 
 pylorospasm and pyloric stenosis involve either primarily or 
 secondarily a condition of hypertonus and h3^ermotility of the 
 entire stomach. The excessive contraction of the pylorus may be 
 an expression of this general hypermotihty. It is known that the 
 tonus and contractions of stomachs in young mammals are greater 
 than in the adult and in the old. This may be correlated with the 
 greater tendency to hyperactivity of the pylorus in infancy and 
 childhood. In the adult these gastric contractions would cause 
 intpnse hunger pains, and it is probable that such pains are also 
 experienced by the infant. 
 
 8. Hunger in experimental fevers in man and dogs. — Dr. Rupp 
 induced temporary fever in himself and in a number of other 
 men by injections of typhoid vaccines and of sodium nucleate. 
 Records of the gastric hunger contractions were taken in the 
 usual way, and careful notes made of the subject's own feeling of 
 hunger and appetite. Fever reactions on injection of the standard 
 doses of typhoid vaccine are usually very slight and variable, but 
 with doses two or three times larger elevation of the temperature 
 up to 103° or 104° F. together with the other symptoms of fever 
 can usually be produced for a few hours. Sodium nucleate in- 
 variably brings on a temporary fever, the degree and duration of 
 the fever depending on the quantity injected. 
 
HUNGER AND APPETITE IN DISEASE 
 
 287 
 
 ^ l-i Jr tt' 
 
 • S u 1*1 g S 
 "2 o 4j 
 
 an S^ a 
 
 o O -g -M s 
 
 Ssga 3 
 
 » O S H bO 
 
 ™ .J3 tH ij 'S 
 
 B'S s a s 
 
 yp 
 
 i: d ■* SH 
 
 .s ^-5 S 
 
 K> 
 
288 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 Dr. Rupp found that when the temperature elevation reached 
 only ioo°-io2° F. the strength and duration of the gastric hunger 
 contractions showed practically no deviation from the normal. 
 But they produced a different effect on consciousness. Instead of 
 the normal hunger pangs associated with increased appetite and 
 desire for food, the gastric hunger periods during the fever pro- 
 duced headache, nausea, and an epigastric distress Uke "sick 
 stomach." More severe temperature reactions (io4°-io5° F.) 
 usually render the empty stomach atonic, and in that condition 
 there are no hunger contractions. When the subjects experienced 
 the fever chills there was always complete absence of the gastric 
 hunger contractions. 
 
 Similar results were obtained by Dr. Mayer on dogs. Sodium 
 nucleate fevers of io3°-ios'' F. lead to gastric atony and absence 
 of the hunger contractions. But temperature elevatioiis of one 
 or two degrees above the normal had little or no effect. 
 
 It must be noted that we are here dealing with very temporary 
 fever reactions. It is not unlikely that temperature elevations of 
 one or two degrees above the normal and persisting for days or 
 weeks would have a more deleterious influence on the gastric 
 hunger mechanism. 
 
 These experiments show that fever anorexia is in some cases at 
 least more complicated than the mere absence of the gastric hunger 
 contractions. In fact we may have objectively normal gastric 
 contractions parallel with the epigastric feeUng of "sick stomach," 
 nausea, headache, depression, no thought of or desire for food. 
 This anomalous condition may be due to hyperexcitability of the 
 gastric sensory nerves by action of the toxins, or due to elevation 
 of the temperature. Changes in the central nervous system may 
 also play a r61e. 
 
CHAPTER XVII 
 
 HUNGER AND APPETITE IN DISEASE— (Contintied) 
 
 I. ACTION OF BITTER TONICS 
 I ACTION ON THE HUNGER MECHANISM 
 
 The value of "bitter herbs" in disease is a current popular 
 belief, and the use of these bitters as medicine probably antedates 
 even the "medicine man" of primitive human society. Today 
 the use of bitters is, or at least should be, confined to cases of 
 impaired gastric digestion. The mechanism of this action is still 
 in the maia an open question, despite a considerable amount of 
 experimental work. The literature seems to show that the bitters 
 cause increased secretion of gastric juice. Nevertheless, Cushny 
 concludes that the favorable effects from bitters are largely sub- 
 jective. The bitters are capable of producing a considerable 
 impression on the patient, so that their effects may be due in part 
 to suggestion and not to any real action of the drug. That the 
 bitters increase appetite and hunger is a generally accepted view. 
 The bitters may produce ,these results in any or all of the following 
 ways: (i) direct inauguration or augmentation of the hunger 
 contractions of the empty stomach, or hastening the reappearance 
 of the gastric^unger contractions by facihtating gastric digestion 
 (through increased secretion or increased peristalsis), and thus 
 accelerating the emptying of the stomach; (2) augmentation of 
 appetite directly by stimulation of gustatory and other sensory 
 nerves in the mouth, esophagus, and stomach, or indirectly, by 
 accelerating gastric digestion; (3) central Bahnung or faciHtation, 
 the strong afferent impulses from the mouth (and possibly also 
 from the esophagus and stomach) may in some way bring feeble 
 htmger and appetite sensations more prominently into consciousness. 
 
 The tests were carried out on a number of normal men, and the 
 influence of the bitters in the mouth and in the stomach was tested 
 separately. The bitters were introduced through the stomach tube 
 
 289 
 
290 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 when it was desired to study the action from the stomach alone. 
 In Mr. v., and usually also in the dogs, the drugs were introduced 
 through the gastric fistula. 
 
 In order to exclude possible psychic factors, the subject was 
 frequently kept in ignorance of the nature of the substance (water 
 or drug) as well as of the time when it was given. 
 
 The following bitters were used: tinctures of gentian, quassia, 
 columba, himiulus, and condurango; elixir of quinine, strychnine, 
 and iron. 
 
 In the case of man the bitters were introduced into the stomach 
 in varying quantities up to the maximum therapeutic dose, but 
 never exceeding that. In the case of the dogs the drugs were used in 
 gradually increasing quantities until definite effects were produced. 
 
 I. Action in the stomach. — ^When used in therapeutic quantities 
 and introduced directly into the stomach so as not to come into 
 contact with the mouth or esophagus, these bitters have no, direct 
 action whatever on the hunger mechanism. If the bitters are 
 introduced into the stomach during a hunger period, the gastric 
 hunger contractions continue in their normal rate and strength 
 until the completion of the hunger period, except for a slight 
 temporary inhibition that may appear immediately on introduction 
 of the drug. This transient inhibition is not peculiar to these drugs, 
 however, since it follows the introduction of any liquid, including 
 water at body temperature, directly into the stomach. At no 
 time did we obtain an increase in the gastric hunger contractions 
 from the bitters. If the bitters are introduced into the empty but 
 quiescent stomach, that is, between two himger periods, there is 
 no immediate initiation of gastric himger contractions or hastening 
 of the appearance of the next hunger period. 
 
 The foregoing results were obtained with all the bitters both 
 in man and dogs, so that we are inclined to believe that all the 
 numerous bitters used in therapeutics are without direct action 
 (that is from the stomach) on the hunger mechanism when used in 
 therapeutic quantities. 
 
 When the bitters are introduced directly into the stomach in 
 sufficient quantities to produce demonstrable effects on the hunger 
 
HUNGER AND APPETITE IN DISEASE 
 
 291 
 
 mechanism, this action is always 
 in the direction of inhibition, 
 and the inhibition is the greater 
 the greater the quantity of the 
 drug. All the bitters tried are 
 capable of causing this inhibition 
 of hunger. It is not known what 
 ingredient in the bitters is 
 responsible for this action. The 
 alcohol in the tinctures will itself 
 produce some inhibition. This 
 inhibition is not peculiar to the 
 bitters, as previous work has 
 shown that anything which 
 stimulates the nerve-endings in 
 the gastric mucosa inhibits the 
 gastric htmger mechanism in 
 proportion to the intensity and 
 duration of the stimulation. 
 And it is of little or no interest 
 in therapeutics, as the quanti- 
 ties of the drugs required to 
 produce it are much greater 
 than that permissible in practi- 
 cal medicine. When the elixir 
 of iron, quinine, and strychnine 
 is put into the stomach in 
 quantities sufficient to affect 
 the hunger mechanism, the ani- 
 mal usually develops mild symp- 
 toms of strychnine poisoning 
 (rapid respiration, greatly in- 
 creased reflex excitability). 
 During this period of increased 
 activity of the skeletal neuro- 
 muscular mechanisms, there is 
 
292 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 not only no increase in tonus and hunger contractions of the 
 empty stomach, but the stomach is rendered even more atonic 
 than during the quiescent interval between the hunger periods in 
 the normal animal, a situation similar to that found in animals in 
 parathyroid tetany. According to Heubner and Reider, large 
 doses of bitters retard the emptjdng of the stomach in digestion. 
 
 2. Action in the mouth. — ^The experiments on dogs were unsatis- 
 factory and inconclusive, for the reason that the dogs object to the 
 bitters, even when given in minute quantities by the mouth. The 
 dogs salivate profusely, become restless, and endeavor in various 
 ways to get rid of the apparently disagreeable taste of the bitters. 
 Putting small quantities of the bitters in the mouth invariably 
 leads to prompt and prolonged inhibition of the gastric hunger 
 contractions, but inhibition of the hunger pangs in dogs accompanies 
 restlessness of the animal from any cause. The results on man 
 are not complicated by the uncontrollable factor of struggling and 
 protest. 
 
 In man the bitters acting in the mouth inhibit the gastric himger 
 contractions in direct proportion to the intensity of their stimu- 
 lation of taste sense. If the bitters are placed in the mouth during 
 a period of quiescence of the empty stomach, there is no initiation 
 of gastric hunger contractions, but so far as any effect can be 
 detected this is a temporary inhibition of the gastric tonus. The 
 temporary inhibition of the gastric tonus and himger contractions 
 by the bitters acting in the mouth is not followed by an increase 
 in gastric tonus or gastric hunger contractions above the normal. 
 That is, there is no after-effect of the nature of augmentation or 
 stimulation of the hunger mechanism. A few drops of tincture of 
 condurango on the tongue may inhibit the hunger contractions 
 for 15 to 20 minutes. 
 
 We think that a sufficient number of bitters is included in the 
 experiments above to justify applying the results to the whole 
 group of bitters, especially in view of the fact that the action on 
 the hunger mechanism is the same in aU cases. 
 
 These experiments were conducted on normal individuals, 
 while the bitters are or should be prescribed only in cases of anorexia, 
 
HUNGER AND APPETITE IN DISEASE 293 
 
 a disordered digestion, or particularly a disordered gastric digestion. 
 There remains the possibility of a more favorable action of the 
 bitters on the hunger mechanism in these pathological conditions. 
 It is desirable that direct tests be made on such material with 
 proper control. But we venture to predict that the results will be 
 the same as those reported above on normal men, as it is not likely 
 that the fundaihental reflex relations of the sensory nerves in the 
 mouth and the gastric mucosa to the hunger mechanism are so 
 readily changed by disease. 
 
 It must be noted that the reflex inhibition of the hunger con- 
 tractions from the actions of the bitters in the mouth is accompanied 
 by cessation of the conscious himger pangs. There is a complete 
 parallel between the objective inhibition and the subjective absence 
 of hunger sensation. 
 
 The foregoing results show clearly that the bitters usually em- 
 ployed in therapeutics have no favorable action on the hunger 
 mechanism. But the therapeutic use of these substances may still 
 be justified bv their direct action on gastric secretion or on the 
 appetite. 
 
 Summarizing, we conclude that in therapeutic quantities the 
 bitters, acting in the stomach alone, have no effect on the gastric 
 tonus or the gastric himger contractions or on the parallel sensation 
 of hiuiger. In greater than therapeutic doses the bitters inhibit 
 the htmger contractions and aboUsh the hunger sensations, prob- 
 ably by stimulation of nerve-endings in the gastric mucosa. Acting 
 in the mouth alone, the bitters, even in traces, inhibit the himger 
 contractions and abolish the hunger sensations in direct proportion 
 to the intensity and duration of the stimulation in the mouth, and 
 there is no after-effect in the way of augmentation of hunger 
 
 contractions and hunger sensations. 
 
 I 
 
 II. ACTION ON THE SECRETION OF GASTRIC JUICE EST 
 NORMAL MEN AND DOGS 
 
 The literature on this subject is both considerable and conflict- 
 ing. It seems pretty well estabhshed that the bitters have no action 
 on the pepsin-hydrochloric-acid digestion itself, except possibly in 
 
294 CONTROL OR HUNGER IN HEALTH AND DISEASE 
 
 way of slight retardation. This slight retarding action is of no 
 practical significance, especially when the bitters are taken 20 or 
 30 minutes before the meal, or even just before the meal, because 
 of the great dilution with gastric juice, saliva, and the fluids of the 
 food. The literature also points to the conclusion that by them- 
 selves the bitter tonics are incapable of causing secretion of gastric 
 juice, either by acting in the mouth or in the stomach. Pavlov 
 noted in dogs that the bitters acting in the mouth cause a copious 
 flow of saliva, but leave the gastric gland perfectly quiescent; and 
 not even when introduced into the stomach do they cause secretion 
 of gastric juice. 
 
 Some observers (Reichmaim, Scheffer, and others) have reported 
 that as long as the bitters remain in the stomach they depress or 
 diminish the secretion of gastric juice, and this led to giving the 
 bitters from 10 to 30 minutes before the meals. 
 
 Do the bitter tonics augment the secretion of gastric juice 
 indirectly by increasing the excitability of the nerve-endings of 
 taste in the mouth, and possibly the nerves of appetite sense in the 
 stomach ? This is the view emphasized by Pavlov, but he does not 
 adduce any experiments in its support. The work of Borissow 
 seems to confirm it, however. Borissow reports 12 sham-feeding 
 tests on one dog with gastric fistula and esophagotomy. Six of 
 these tests were made after giving the dog tincture of gentian 
 in the mouth. In both series of tests the sham feeding was con- 
 tinued for I minute and the gastric juice collected for 2 hours 
 following the sham meal. In the case of the gentian series, the 
 sham feeding was instituted as soon as the profuse salivation 
 induced by the bitters had ceased. Borissow obtained the following 
 results: 
 
 Series 
 
 Min. c.c. 
 
 Max. c.c. 
 
 Aver. c.c. 
 
 Normal or no tonic 
 
 Tincture of gentian 
 
 S9-3 
 8S.1 
 
 126. S 
 
 185.2 
 
 lOI 
 130 
 
 There was no difference in the acidity and the pepsin concen- 
 tration of the gastric juice of the two series, but the average excess 
 
HUNGER AND APPETITE IN DISEASE 295 
 
 of gastric juice in the gentian series is striking. However, it may 
 be questioned whether a short series of tests on one animal can be 
 held as conclusive, especially in view of the great individual 
 variations (over 100 per cent) within each series. 
 
 Experimental procedure on man. — It will be recalled that Mr. V. 
 has the esophagus completely restricted at the level of the upper 
 end of the sternvun, so that nothing can be swallowed from the 
 mouth and reach the stomach via the esophagus. Above the 
 constriction the esophagus is somewhat dilated so as to hold 
 about half a glass of liquid. These conditions serve admirably 
 for studying the influence of the bitters on the secretion of gastric 
 juice. 
 
 On all test days 100 c.c. of water were put into the stomach 
 120 and 60 minutes before the meal, so as to insure a completely 
 empty stomach. The tonics were introduced into the stomach via 
 the fistula 15 to 30 minutes before mealtime. In the series of tests 
 with the tonics in the mouth, these were put into the mouth and 
 swallowed into the esophageal pouch 10 minutes before the meal. 
 They usually had to be expectorated before the meal actually 
 began, because of the salivation induced by them. 
 
 In all three series of tests the gastric juice was collected in the 
 course of the first 20 minutes during which Mr. V. was chewing his 
 food in the usual way, preparatory to putting it into the stomach 
 by means of a syringe. We are therefore dealing with the appetite 
 gastric secretion only. 
 
 The stomach was invariably emptied just before Mr. V. started 
 to eat, and a record was kept of the quantity, acidity, and pepsin 
 strength of this juice found in the empty stomach, as it was thought 
 that the quantity and quality of this juice might serve to indicate 
 the physiologic condition of the gastric glands, irrespective of the 
 condition of the appetite. 
 
 The experiments were made during the period from April to 
 November, 1914. The tests with the tonics were interspersed with 
 controls without the tonics all the way, so as to eliminate as far as 
 possible the errors from variations in nutrition, appetite, etc., 
 associated with variations in climate and bodily activity. 
 
296 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 It was aimed to make these tests a mere incident in Mr. V.'s 
 daily routine. For that reason no special dietary standard was 
 fixed. The ingredients of the noonday meal Mr. V. selected for 
 himself at a nearby cafeteri^. He naturally selected what appeared 
 to him most palatable from day to day. The evening meal was 
 taken in the same boarding-house throughout the experimental 
 period. Mr. V. stated that the boarding-house meals were very 
 much the same from- week to week, and were less palatable than 
 the noonday meal. 
 
 The tonics used (in therapreutic doses) were tinctures of gentian, 
 quassia, colimiba, humulus, and condurango, and elixir of quinine, 
 strychnine, and iron. Most of the tests were made with the gen- 
 tian tincture and with the elixir. 
 
 In order to exclude all possible psychic factors, Mr. V. was not 
 
 told of the purpose of the experiments. He went about his daily 
 
 work, taking his usual food at the usual time, while now and then 
 
 a tonic was given and the appetite secretion measured. We think 
 
 it may safely be concluded that such psychic factors as faith in 
 
 the potency of or hope of improvement from the drugs was entirely 
 
 eliminated. Nor was the taking of any of these tonics by the 
 
 mouth disagreeable or loathsome, such as might induce psychic 
 
 depression. 
 
 / TABLE V 
 
 Gastric Jthce Secreted by Mr. V. nxraiNG the First Twenty 
 Minutes or Chewing Food 
 
 Meal 
 
 Tonics 
 
 No, or Ex- 
 periments 
 
 Gastric Juice in c.o. 
 
 Lowest 
 
 Highest 
 
 Average 
 
 Lunch 1 2:00-1:00 P.M. 
 Supper 6:00-7:00 P.M. 
 
 No tonics 
 
 Tonics in mouth,. . 
 Tonics in stomach. 
 
 No tonics 
 
 Tonics in mouth. . . 
 Tonics in stomach. 
 
 31 
 30 
 
 20 
 20 
 20 
 IS 
 
 3S 
 30 
 40 
 20 
 20 
 18 
 
 95 
 93 
 8S 
 50 
 48 
 47 
 
 S8.o 
 61.0 
 S8.2 
 36.0 
 330 
 30.1 
 
 Tests to the nimiber of 50 were made with bitters in the mouth, 
 and 35 with bitters in the stomach, together with 51 control tests. 
 These are summarized in tables. The lunch and supper series are 
 
HUNGER AND APPETITE IN DISEASE 297 
 
 tabulated separately, because the appetite gastric secretion was 
 uniformly less at the evening meal. This is probably due to less 
 palatable food at the evening meal (absence of variety in the food, 
 inferior cooking). 
 
 Examination of the tables shows that the bitter tonics acting 
 either in the stomach or in the mouth are without influence on the 
 quantity of the appetite psychic secretion. There is a suggestion 
 of an increased secretion with the bitters in the mouth for the 
 noonday series, but this is counterbalanced by a slightly lower 
 figure for the evening meal. The average physiologic condition 
 of the gastric glands is practically the same in all the series. 
 
 As Mr. V. is a young man in good health, the question naturally 
 arises whether the sensory nerves for the appetite sense (in mouth 
 and stomach) are not normally in a state of maximum excitability, 
 so that no further increase in excitabiUty by bitter tonics is possible. 
 This objection seems to be met by the lower secretion at the evening 
 meal. Here is a condition in which less palatable food should have 
 been rendered more palatable by contrast with the bitter tonic, or 
 by actual increase in the excitability of the gustatory nerves. The 
 results indicate no improvement by contrast. If the bitters in the 
 mouth augmented the excitabihty of the taste nerves at the evening 
 meal, this evidently caused an already unpalatable food to taste 
 still more impalatable, and hence the diminished appetite secretion. 
 
 These bitters in mouth or stomach produced no change in the 
 acidity and in the pepsin concentration of the appetite gastric juice. 
 
 A similar series of tests was made on eight dogs provided with 
 an accessory stomach pouch, according to the Heidenhain-Pavlov 
 method. Care was taken to interfere as little as possible with the 
 distribution of the vagi to the stomach pouch. 
 
 The tonics were introduced into the main, stomach by means 
 of a stomach tube, so as not to come in contact with the nerve- 
 endings in the mouth or esophagus. They were introduced into the 
 stomach pouch directly with a pipette. When introduced into the 
 mouth the bitters were soaked up in a small wad of cotton and 
 the dog was compelled to chew on this for i minute. The tests were 
 made 24 hours after the previous meal, and each dog was fed a 
 
298 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 fixed quantity of boiled lean meat. The gastric juice was collected 
 for 2 hours after the beginning of the feeding. 
 
 The tonics were put into the main and accessory stomachs from 
 20 to 30 minutes before feeding, and into the mouth 10 minutes 
 before feeding. The size of the dogs varied from 5 to 8 kg. The 
 quantity of tonics put into the stomach varied from 1.5 to 2 c.c. 
 
 Our results on the five dogs are summarized in Table VI. The 
 data in this table permit only one conclusion, namely, that these 
 bitters acting in the mouth or in the stomach have no effect on 
 the secretion of gastric juice or on the quantity of food consumed 
 by the normal dog. The shght increase that appears in the case of 
 Dog 5 would probably have been counterbalanced if a larger series 
 of tests had been made. The tonics did not produce any changes 
 in the acidity and pepsin concentration. 
 
 TABLE VI* 
 
 Dog 
 
 Tomes 
 
 No". OF Ex- 
 periments 
 
 Gastric Juice in c.c. 
 
 Lowest 
 
 Highest 
 
 Average 
 
 
 
 17 
 IS 
 IS 
 
 17 
 10 
 10 
 
 IS 
 10 
 10 
 
 6 
 6 
 
 10 
 
 9 
 8 
 
 10 
 
 13 ' 
 10 
 
 3 
 3 
 2 
 
 4 
 S 
 3 
 
 6 
 
 S 
 
 8 
 7 
 7 
 
 33 
 29 
 26 
 
 9 
 8 
 
 7 
 
 10 
 
 10 
 
 8 
 
 9 
 II 
 
 16 
 
 17 
 16 
 
 . 19.6 
 18.4 
 18.6 
 
 S-i 
 4-9 
 4.8 
 
 7.0 
 7.2 
 6,8 
 
 8.4 
 8.0 
 
 Dog I . . 
 
 ■{Tonics in mouth 
 
 
 [Tonics in main stomach 
 
 fNo tonics 
 
 Dog 2 . . 
 
 Tonics in mouth 
 
 [Tonics in main stomach 
 
 fNo tonics ... . 
 
 Dog 3.. 
 
 Tonics in mouth 
 
 [Tonics in main stomach 
 
 Dog 4.. 
 
 \Tonics in main stomach 
 
 Dogs.. 
 
 ■ Tonics in main stomach 
 
 14.0 
 14.1 
 
 
 
 
 *Dogs with accessory stomachs prepared according to the Heidenhain-Pavlov method. Record 
 of the secretion of gastric juice for the first two hours following a standard meal of lean meat. The va- 
 riation in the average quantity of gastric juice secreted by the different dogs is due mainly to difiEerence 
 in size of the accessory stomachs. " ' 
 
 The possible value of thes^ and other stomachics, especially in 
 digestive disorders, should be investigated by other methods, such 
 as the determination of the actual quantity of food consumed, the 
 
HUNGER AND APPETITE IN DISEASE 
 
 299 
 
 time required for completion of gastric digestion, etc., with and 
 without the tonics. And the final verdict cannot be given until 
 all possible tests have been applied. But as regards any favorable 
 action of these stomachics on the gastric secretory mechanism in 
 normal men and dogs our results go to show that it is nil, at least 
 when all purely psychic factors are eliminated. 
 
 m. INFLUENCE ON FOOD CONSUMPTION AND ON THE 
 GASTRIC JUICE IN EXPERIMENTAL CACHEXLA. 
 
 Hoppe reports that when bitters are given to sick dogs the 
 quantity of gastric juice is increased, and the pepsin and HCl of 
 the juice is likewise increased. No figures are presented, nor are 
 sufl&cient accounts of the method used given, so as to enable one 
 to evaluate his conclusions. Moorhead, working in the author's 
 laboratory, produced cachexia in two dogs with Pavlov stomach 
 pouch by repeated excessive hemorrhage, and studied the action 
 of the bitters on the food consumption and the appetite secretion 
 before and after inducing the chronic anemia. The dogs were bled 
 20 to 30 c.c. per kg. daily until they became permanently listless, 
 weak, and depressed, lost weight gradually, and showed little 
 interest in food or surroundings — in a word, typically cachectic. 
 During the observation period the dogs showed little or no 
 improvement. 
 
 TABLE VII 
 Quantity or Gastric Secretion in c.c, Cachectic Dogs (Pavlov Stomach) 
 
 
 No. T. 
 
 Dog I 
 
 Dog 2 
 
 
 Avr. 
 
 Mxm. 
 
 Mnm. 
 
 Avr. 
 
 Mxm. 
 
 Mnm. 
 
 tion one hour. , |.j.^^j^^ j^ ^^^^^^^ 
 
 ri-^7 after j^-l^„„„,,;:: 
 
 '^^™S [Tonics in stomach . 
 
 10 
 10 
 10 
 
 10 
 10 
 10 
 
 0.50 
 I. go 
 1.06 
 
 1-05 
 2.50 
 I. 20 
 
 2.0 
 4.2 
 31 
 
 3-9 
 
 S-o 
 3-5 
 
 0.0 
 
 o-S 
 0.0 
 
 0.0 
 0.2 
 0. 2 
 
 IIS 
 1. 14 
 1. 14 
 
 I-SO 
 31S 
 1.80 
 
 S-O 
 2.1 
 2.2 
 
 5-9 
 
 7-7 
 
 2-5 
 
 0,0 
 
 O.I 
 
 0.6 
 
 0.0 
 
 O.I 
 O.I 
 
 Before the chronic anemia was induced the bitters had no 
 influence on food consumption or on thf quality and quantity of 
 
300 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 the appetite gastric juice. During the cachexia the bitters acting 
 in the mouth appeared to increase slightly both the quantity of 
 food consumed, and the quantity and quality of the appetite 
 gastric juice (Table VII). The experiments are not numerous 
 enough to permit final conclusions, even for sick dogs. And it is 
 not clear whether the apparent action of the bitters is a direct one 
 on the appetite mechanism, or in the nature of a condition reflex. 
 The real value of bitter tonics as stimuli to appetite in disease is 
 still an open question, that must be answered by quantitative test 
 methods on the sick. 
 
 IV. ACTION ON APPETITE IN CLINICAL CACHEXIA. 
 
 Moorhead has completed an extensive series of tests with bitters 
 on five hospital patients with chronic cachexia and poor appetite, 
 using the method of weighing the food consumed, on the theory 
 that if the bitters actually increase appetite this should be revealed 
 in the food consumption. Tonic days were alternated with no-tonic 
 days, so as to exclude any progressive increase or decrease in the 
 appetite from other causes. The results are as follows: 
 
 Patient A: given tincture of gentian. The patient was told 
 that the medicine would help his appetite and digestion, and 
 said he felt that it did improve his appetite a great deal. Evidently 
 the subjective faith and hope was greater than the objective results. 
 
 Number of control or no-tonic meals 45 
 
 Number of tonic meals 87 
 
 Average food consumption, no-tonic meals . . . . 10.3 oz. 
 Average food consumption, tonic meals 11 . 3 oz. 
 
 Average increase i oz. per meal 
 
 Patient B : given elixir of iron, quinine, and strychnine. This 
 patient was not told what the medicine was given for, hence he 
 did not know that any attempts were made to improve his appetite. 
 
 Number of control or no-tonic meals 60 
 
 Number of tonic meals 48 
 
 Average food consumption, no-tonic meals . . . . 11 . 8 oz. 
 Average food consumption, or tonic meals 13 . 8 oz. 
 
 Average increase 2 oz. per meal 
 
HUNGER AND APPETITE IN DISEASE 301 
 
 Patient C : given elixir of iron, quinine, and strychnine, without 
 being told for what purpose. This patient was a chronic alcoholic 
 and cachectic, with no other definite ailment. 
 
 Number of control or no-tonic meals 33 
 
 Number of tonic meals 27 
 
 Average food consumption, no-tonic meals. . . .9.95 oz. 
 Average food consumption, tonic meals 10. 84 oz. 
 
 Average increase o. 89 oz. per meal 
 
 Patient D: given elixir of iron, quinine, and strychnine. This 
 patient had chronic myocarditis, and was anemic and cachectic. 
 
 Number of control or no tonic meals 32 
 
 Number of tonic meals 37 
 
 Average food consumption, no tonic meals. ...11.7 oz. 
 Average food consumption, tonic meals 13 . 2 oz. 
 
 Average increase i . 5 oz. 
 
 Patient E: given tincture of gentian. This patient had per- 
 nicious anemia, and was very emaciated. He was told that the 
 medicine given him would improve his appetite, and he was very 
 anxious to have his appetite improved. 
 
 Number of control or no tonic meals 22 
 
 Number of tonic meals 21 
 
 Average food consumption, no tonic meals. ... 19.4 oz. 
 Average food consumption, tonic meals 23 . i oz. . 
 
 Average increase 3 • 7 oz. 
 
 The mmiber of different kinds of bitters advocated from time 
 to time as useful in disease is a large one. They are of such varied 
 chemical composition that the only thing they have in common is \ 
 the bitter taste. Of course, in this discussion, we do not include 
 such substances as quinine or strychnine, or the bitters with alcohol 
 as the main constituent, as these substances have distinct physio- 
 logic actions not directly related to appetite, after absorption into 
 the blood. 
 
 The bitter tonics are common "home remedies" and favorite 
 "drug-counter prescriptions." They are given to convalescents 
 who would continue to improve, tonic or no tonic, and the tonic, 
 
302 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 not the recuperative power of the patient, gets the credit, or the 
 physician prescribes a more hygienic living and a tonic. The health 
 improves and both physician and patient think the tonic did it. 
 
 But even if the bitters have no direct action on gastric secretion 
 and digestion, and no appreciable indirect action on the secretion of 
 gastric juice, may they not be valuable aids in expelling worry and 
 implanting hope and good cheer in the mind of the patient ? May 
 they not be an efficient handmaid to psychotherapy? There is 
 no question that the bitter tonics coimect up with the popular 
 belief that the potency of a medicine is directly related to its 
 strong (or bad) taste. And the readiness with which these tonics 
 are dispensed nourishes the popular superstition that there is, or 
 must be, a specific drug remedy for every ailment, a superstition 
 that constitutes the chief aid of the medical quack and the patent 
 medicine vender. 
 
 The stimulation of certain nerve-endings in the mouth and in 
 the normal gastric mucosa unquestionably contributes to the com- 
 plex sensation of appetite, and these nerves are stimulated by 
 condiments and flavors of food. Apart from this, the physiologic 
 way of augmenting hunger and appetite is moderation in the food 
 intake or increasing the utilization of the food in the body by outdoor 
 living, fresh air, cold baths, and physical work. If these measures 
 do not improve appetite and hunger, the chances are that the 
 digestive tract is not in a condition to take care of the amount of 
 food deriianded by stronger hunger and appetite sensations. 
 
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INDEX 
 
 Abdomen^ effect of massage of, on hun- 
 ger, 200. 
 
 Acidity of human gastric juice, 254. 
 
 Acids, in stomach, influence of, on hun- 
 ger, 171, 175. 
 
 Age, variations in hunger with, 119. 
 
 Akoria, 266. 
 
 Alcohol: influence of, on appetite, 180; 
 on hunger, 178. 
 
 Alcoholic gastritis, hunger and appetite 
 in, 271. 
 
 Alkalies in stomach, influence of, on hun- 
 ger, 171,26s. 
 
 Allotriophagia, 267. 
 
 Ammino acids, in gastric juice, 253. 
 
 Ammonia, in gastric juice, 251. 
 
 Animal behavior, influence on, of hunger, 
 8, i34> 136, 144, 147- 
 
 Anorexia, 266, 286. 
 
 Appetite: gastric factors in, gp, 115; in- 
 heritance, factors in, 11; in disease, 
 261; in fevers, 278, 286; in prolonged 
 starvation, 134; nature of, 98; per- 
 verted, 267; relation of, to himger, 10, 
 98; relation of, to thirst, 12; (ieories 
 of, 96. 
 
 Appetite gastric juice: acidity of, 254; 
 chemistry of, 248; importance of, in 
 normal digestion, 247; secretion of, 
 23s, 240- 
 
 Bile in stomach, 132. 
 
 Bitter tonics: influence of, on hunger, 
 290; on food consumption, 300; on 
 gastnc juice secretion, 293; nature of 
 action of, 289, 302. 
 
 Boldyrefi, work of, on stomach in hunger, 
 27, 33- 
 
 Borborygmi, in hunger, 26, 82. 
 
 Boring, work of, on hunger, 25, 105. 
 
 Brain, hunger centers in, 20, 149, 215, 216. 
 
 Bulimia: in duodenal fistula, 24; in re- 
 section of stomach, 23; in various 
 diseases, 261. 
 
 Busch, work of, on hunger, 24. 
 
 Cachexia, action of bitter tonics in, 209, 
 300- 
 
 Cannon, work of, on hunger, 19, 28, 35. 
 
 Carbon dioxide in stomach, influence of, 
 on hunger, 180. 
 
 Cardia, in hunger, 77. 
 
 Chemotropism, in appetite, n, 99. 
 
 Cerebrum: influence of, on hunger con- 
 tractions, 149; hunger centers in, 216. 
 
 Cold, effect of, on hunger, 7, 9, 206, 211. 
 
 Continuous secretion of gastric juice, 233, 
 234- 1 
 
 Crop, hunger contractions of, in birds, 51. 
 
 Diabetes mellitus, hunger in, 279. 
 Diabetic blood, influence of, on hunger, 
 
 220. 
 Disease, hunger and appetite in, 261. 
 Distemper, hunger in, 273. 
 Drugs, influence of, on hunger, 229. 
 
 Emotions, influence of, on hunger, 151, 
 182. 
 
 Epigastric "emptiness," feeling of, in 
 hunger, 93. 
 
 Epinephrin, influence of, on" hunger, 229. 
 
 Esophagus: in hunger, 7, 71, 81; sensi- 
 bility of, 104. 
 
 Fevers, hunger and appetite in, 278, 286. 
 
 Gall-bladder infections, gastric pain in, 
 283. 
 
 Gastric cancer, hunger in, 280. 
 
 Gastric hunger contractions: after sec- 
 tion of stomach nerves, 141; chemical 
 control of, 217; effect of hemorrhage 
 on, 222; in dogs, 138; in infants, 40, 
 119; in man, 36, 126; in rabbits, 143; 
 inreptilia, 53; 
 
 — conditions of disease: alcoholic gastri- 
 tis, 271; diabetes mellitus, 277; dis- 
 temper, 273; fevers, 276, 286; gall- 
 bladder infections, 283; gastric cancer, 
 280; gastric ulcer, 281; gastritis, 278J 
 
 317 
 
31 8 CONTROL OF HUNGER IN HEALTH AND DISEASE 
 
 mange, 268; pancreatic diabetes, 268; 
 parothyroid tetany, 273; peritonitis, 
 273; pneumonia, 273; pylorospasm, 
 284; pyloric stenosis, 275; tonsillitis, 
 278; 
 
 — in the isolated stomach, 160; 
 
 — influence of, on circulation, 88; on re- 
 flexes, 8s; on salivation, 8g; 
 
 — influence on, by chemicals in the 
 mouth, 161, 166; chemicals in the stom- 
 ach, 171; decerebration, 149; diabetic 
 blood, 221; starvation blood, 219; 
 section of stomach nerves, 158; 
 
 — mechanism of, 169, 183; relation of, to 
 digestion contractions, 56; to feeding 
 habits, 153, 185. 
 
 Gastric juice: auto-digestion of, 235; 
 chemistry of, 248; quantity of, 243, 
 24s; secretion of, 233, 240. 
 
 Gastric mucosa: pain sensation from, 
 ;ro2; tactile sensation from, 103 ; tem- 
 perature sensation from, 104; sensa- 
 tion of nausea fr6m, 113. 
 
 Gastric tonus: relation of, to hunger, 67; 
 in prolonged starvation, 128, 141. 
 
 Gastric ulcer, hunger in, 264. 
 
 Gastritis, hunger in, 278. 
 
 HaUer, theory of, hunger,' 17. 
 
 Headache, in hunger, 92, 94, 134. 
 
 Hemorrhage, influence of, on hunger, 222. 
 
 Herbivora, hunger in, 41, 48, 50- 
 
 Hertz, work of, on sensibility of stomach, 
 103, 105, III, 264. 
 
 Hunger: cause of, 61; general phenom- 
 ena of, 7; influence of, on behavior, 8, 
 134, 136, 144, 147; in disease conditions, 
 261; in higher animals, 6, 30, 125; in 
 plants, 5; in protozoa, t; method of 
 objective study of, 31; relation of, to 
 appetite, 96; relation of, to the need of 
 food, 22, 153, 18s; theories of, 16. 
 
 Hunger centers: in cerebrum, 216; in 
 medulla, 214; in optic thalami, 215. 
 
 Hunger pains: in gastric ulcer, 263, 281. 
 
 Hunger tetanus of stomach: in dogs, 44; 
 in man, 37, 65, 212; in pancreatic dia- 
 |betes,268; in prolonged starvation, 125; 
 in pyloric stenosis, 275. 
 
 Hydrochloric acid, rdle of, in hunger pains, 
 264. 
 
 Hyperacidity, in stomach, 256. 
 
 Infants: feeding of, 121; hunger of, 40, 
 
 119. 
 Inheritance: of chemotropic elements of 
 
 appetite, n, 99; of feeding reflexes, 
 
 9, 12. 
 
 Inhibition of hunger: by bitter tonics, 
 292; by cold stimulation of the skin, 
 206,211; by disease, 261; bytheemor 
 tions, 151, 182; by heat stimulation of 
 the skin, 206; by mastication, 165; 
 by ruiming, 210; by sapid substances 
 in the mouth, 160, 167, 189, 193; by 
 smoking, 199; by stimulation of gastric 
 mucosa, 169; by stimulation of intes- 
 tinal mucosa, 194; by swallowing, 167. 
 
 Instincts, relation of, to hunger and appe- 
 tite, 9. 
 
 Intestines, contractions of, in hunger, 81. 
 
 Luckhardt, work of, on hunger, 220, 222, 
 230, 268, 271, 277, 280. 
 
 Mange, increased hunger in, 268. 
 Mastication, inhibition of hunger by, 165. 
 MeduUa, hunger centeirs in, 210. 
 Memory, in appetite, 97. 
 Moorhead, work of, on bitters, 299, 300. 
 
 Nausea: in prolonged starvation, 135; 
 
 relation of, to hunger, 7, 92, 94, 113. 
 Nicolai, work of, on hunger, 25. 
 
 Optic thalami, rdle of, in hunger, 154, 215. 
 
 Pancreatic diabetes, hunger in, 268. 
 Parathyroid tetany, hunger in, 273. 
 Paroexia, 267. 
 Patterson, work of, on hunger, 52, 120, 
 
 123. 
 Pepsin, concentration of, in gastric juice, 
 
 259- 
 Peritonitis, hunger in, 273. 
 Phagocytosis, in protozoa, influence of 
 
 hunger on, 3, 4. 
 Phlorhizin glucosuria, 230. 
 Physical exercise, effect of, on hunger, 
 
 203, 205, 210. 
 Pituitrin, influence of, on hunger, 229. 
 Plants, hunger in, 5. 
 Pneumonia, himger and appetite in, 273. 
 
INDEX 
 
 319 
 
 Polyphagia: in man, 266; in mange, 269; 
 in pancreatic diabetes, 268. 
 
 Pressure on abdomen, effect of, on hun- 
 ger, 200. 
 
 Protozoa, hunger behavior of, 2, 4. 
 
 Pyloric stenosis, influence of, on hunger, 
 '275. 
 
 Pylorospasm, hunger contractions in, 284. 
 
 Pylorus, effect of patency of, on hunger, 
 
 23- 
 
 Rectal feeding, influence of, on hunger, 
 
 Rogers, work of, on hunger, 51, 56, 143, 
 
 151, IS4, 194, 215. 
 Rumen, hunger contractions of, 50. 
 Ruminants, hunger in, 50. 
 
 Salivation, in hunger, 89. 
 
 Salt hunger, 14. 
 
 Satiety, origin of sensation of, iii. 
 
 Sleep, hunger contractions in, 150. 
 
 Smoking, influence of, on hunger, 199. 
 
 Splanchnic nerves, effect of section of, on 
 hunger, 155. 
 
 Starvation: aftgr-effects of, 137; dis- 
 comforts of, 138; gastric hunger con- 
 tractions in, 126; gastric juice in, 128; 
 gastric tonus in, 26, 141; hunger and 
 appetite in, 125, 134; literature on, 
 
 Starvation blood, influence of, on hunger, 
 219. 
 
 Stomach: action of bitter tonics on, 289; 
 digestion contractions of, 55; extirpa- 
 tion* of, in relation to hunger, 23 ; fluid 
 content of empty stomach, 232; hun- 
 ger contractions of, in ampMbia and 
 reptilia, 53; in birds, 51; in dogs, 41; 
 in herbivora, 48; in infants, 40; in 
 man, 36 ; sensibility of, to appetite, 99, 
 lis; to pain, 102; to temperature, 104; 
 to touch, 103. 
 
 Stomach pouch (Pavlov) , hunger contrac- 
 tions of, 225. 
 
 Stomach pulse, 39. 
 
 Taste sense : influence of , on hunger, 163; 
 importance of, in appetite secretion, 
 23s, 240, 247; role of, in appetite, 98. 
 
 Thirst, lack of appetite elements in, 13. 
 
 Tonsillitis, hunger and appetite in, 278. 
 
 Vagi centers, in medulla: reflex control 
 of, 169, 210, 218; tonus of, 206, 214. 
 
 Vagi nerves: effect of section of, on hun- 
 ger contractions, 156; relation to 
 hunger sense, 22, 214; role of , in gastric 
 juice secretion, 234. 
 
 Water in stomach, influence of, on hun- 
 ger, 171. 
 
 Weakness, feeling of, in hunger, 7, 92, 
 I3S. 137-