Part 17

The question of the therapeutic influence of the so-called bitters, it appears to me, bears the closest connection with that of appetite. After a long period of high repute these substances have been almost expelled from the list of pharmaceutic remedies. When tested in the laboratory, they were unable to justify their old and valued reputation; when directly introduced into the stomach, many of them were unable to produce a flow of gastric juice. Consequently, in the eyes of the clinician, they became greatly discredited, so that many were quite ready to discard their use altogether. Obviously, the simple conclusion was drawn that a weak digestion could only be assisted by a remedy which directly excites secretory activity. In this, however, it was forgotten that the conditions of the experiment possibly had not corresponded with the actual state of affairs. The whole question of the therapeutic importance of the bitters, however, acquires a different significance when we link it with another question, such, for instance, as how do bitters affect the appetite? It is the universal opinion of the earlier and later physicians that bitters increase the appetite, and if this be so everything is said. They are, in consequence, real secretory stimulants, since the appetite, as has many times been repeated in these lectures, is the strongest of all stimuli to the digestive glands. It is, however, not by any means strange that this had not previously been observed in the laboratory. The substances were either introduced directly into the stomachs of normal dogs or else injected into the circulation. But their action is chiefly bound up with their effect upon the gustatory nerves, and it was not, therefore, without some reason that this large group of remedies, consisting of substances of the most varied chemical composition, were grouped together mainly on account of a certain bitter taste common to them all. A person who suffers from digestive disturbance has, moreover, a blunted taste, a certain degree of gustatory indifference. The ordinary foods, which are agreeable to other people, and also to himself when in health, now appear tasteless. They not only arouse no desire for eating, but may even cause a feeling of dislike; there is no sense of taste, or at best a perverse one. It is necessary, therefore, that the gustatory apparatus should receive a strong stimulus in order to restore a normal sensation. As experience teaches, this object is most quickly attained by exciting sharp, unpleasant, gustatory impressions, which by contrast awaken the idea of pleasant ones. In either case there is no longer indifference, and this is the foundation upon which an appetite for this or that kind of food may be awakened, and here a general physiological law is illustrated. The light appears brighter after darkness, a sound louder after silence, the enjoyment of blithesome health more intense after illness, and so on. This explanation of the appetising effects of bitters proceeding from the mouth does not exclude the possibility of some such similar influence coming also from the stomach. As has been already stated in the fifth lecture, there is some reason for believing that certain impulses from the cavity of the stomach are likewise necessary for the excitation of appetite. It is possible that bitters not only act directly on the gustatory nerves in the mouth, but that they also act on the mucous membrane of the stomach in such a way that sensations are generated which contribute to the passionate craving for food. As a matter of fact, it has been confirmed by many clinicians that after the administration of bitters some such special sensations do arise in the stomach. The effect of these remedies consists, therefore, not merely in the generation of a simple reflex, but in the production of a certain psychic effect, which indirectly excites a physiological secretory activity. The same probably applies to other substances, such as condiments. In any case, whether our explanation corresponds to the actuality or not, the question of the therapeutic effect of bitters is settled in the affirmative the moment we acknowledge that these substances awaken appetite. The problem, therefore, of an experimental investigation of bitters consists in establishing the fact that they have an effect upon the appetite. The question is a difficult one, and has not hitherto been attempted in the laboratory. It is not sufficient to hand over clinical observations to the laboratory as experimental proofs. One must have, in addition, the assurance that the investigation has been correctly carried out; that is to say, that it dealt exactly with the point under consideration. It is interesting to observe that the connection between appetite and gastric juice is by many physicians, and in many text-books of medicine, exactly reversed. Thus it is represented that some medicinal remedy calls forth a secretion of gastric juice, and this, by its presence in the stomach, awakens an appetite. Here we have to deal with a false explanation of a true fact, and that because it was not recognised that a psychic effect could by any possibility be a powerful excitant of secretory nerves. The customs of the chief meal of the day also correspond with our physiological results. After this or that _hors d’œuvre_, perhaps also with a liqueur of brandy (especially customary in Russia), both of which are designed to awaken the appetite, the repast proper begins, and, in the majority of cases, with something hot, consisting mostly of meat broth (_bouillon_, different soups, and so on). After this comes the really nourishing food--meat of different kinds served in various ways, or, in the case of poorer people, stews made with vegetables, and therefore rich in carbohydrate material. This sequence of foods, from the standpoint of physiology, is quite rational. Meat broth, as we have already seen, is an important chemical excitant of gastric secretion. An attempt is therefore made in two ways to secure a free secretion of gastric juice to act on the chief food; first, in the excitement of the appetite juice by the _hors d’œuvre_, and secondly, in the promotion of the flow by the action of the meat broth. It is in this way that human instinct has made provisions for the digestion of the chief meal. A good meat broth can only be afforded by well-to-do people, and consequently with the poorer classes a less expensive, and, indeed, also a less effective, chemical excitant is used for awakening the early secretion. For example, _kwas_[31] serves in this way with the Russian population, while in Germany, where the price of meat is high, different kinds of soups are used, consisting of water mixed with flour, bread, etc. It is further to be borne in mind that the quantity of the digestive juices in general stands in close connection with the content of water in the organism. This has been shown by the experiments of Dr. Walther for the pancreatic juice, and by my own for the gastric juice. If this sequence of foods, therefore, holds good for healthy people, it must be even more strictly adhered to in pathological conditions. Thus, when a person has no appetite, or only a weak one, he has no psychic juice or only very little; consequently, the meal must in every case be begun with a strong chemical excitant--for example, with a solution of the extractives of flesh. Otherwise solid foods, particularly if they do not consist of meat, would remain long in the stomach without any digestion whatever. It is, therefore, in every way desirable to prescribe meat juice, strong broth, or meat extract to people who have no appetite. The same applies also to forced feeding, for instance, of the insane. It is true that the method of introduction in this case necessarily secures the presence of a chemical excitant, since the food can only be introduced in a fluid form. In any case the addition of meat extract would be very useful. If one arranged the ordinary fluid foods in descending order, according to the influence of the chemical excitants, the following would be the series: first, the preparations of the flesh, such as meat juice and the like; secondly, milk; thirdly, water.

The usual termination of the repast is also, from the physiological standpoint, easy to be understood. The chief meal is generally ended with something sweet, and everybody knows that sweets are pleasant. The meaning of this is easy to guess. The repast, begun with pleasure, consequent on the pressing need for food, must also, notwithstanding the stilling of hunger, be terminated with an agreeable sensation. At the same time the digestive canal must not be burdened with work at this stage; it is only the gustatory nerves which should be agreeably excited. After thus dealing in general with the usual arrangement of our meals, we may now speak of some special points.

Above all comes the acid reaction of the food. It is apparent that acidity enjoys a special preference in the human taste. We use quite a number of acid substances. Thus, for example, one of the commonest seasoning substances is vinegar, which figures in a number of sauces and such like. Further, many kinds of wine have a somewhat acid taste. In Russia, _kwas_, especially in the acid form, is consumed in great quantities. Moreover, acid fruits and green vegetables are used as food, and they are either of themselves acid, or made so in the preparation. In medicine this instinct is likewise often made use of, and acid solutions, especially of hydrochloric and phosphoric acids, are prescribed in digestive disturbances. Finally, Nature itself constantly endeavours to prepare lactic acid in the stomach in addition to the hydrochloric acid. The former arises from the food introduced, and is consequently always present. These facts are all physiologically comprehensible when we know that an acid reaction is not only necessary for an efficient action of the peptic ferment, but is at the same time the strongest excitant of the pancreatic gland. It is even conceivable that in certain cases the whole digestion may depend upon the stimulating properties of acids, since the pancreatic juice exerts a ferment action upon all the constituents of the food. In this way acids may either assist digestion in the stomach where too little gastric juice is present, or bring about vicarious digestion by the pancreas where it is wholly absent. It is easy, therefore, to understand why the Russian peasant enjoys his _kwas_ with bread. The enormous quantity of starch which he consumes, either as bread or porridge, demands a greater activity upon the part of the pancreatic gland, and this is directly brought about by the acid. Further, in certain affections of the stomach, associated with loss of appetite, we make use of acids, both from instinct as well as medical direction, the explanation being that they excite an increased activity of the pancreatic gland, and thus supplement the weak action of the stomach. It appears to me that a knowledge of the special relations of acids to the pancreas ought to be very useful in medicine, since it brings the gland--a digestive organ at once so powerful and so difficult of access--under the control of the physician. We could, for instance, intentionally discard digestion in the stomach, and thus transfer it to the bowel, by prescribing substances which do not excite the gastric glands. On the other hand, by lessening the acidity of the gastric juice we could reduce the

## activity of the pancreas, and these are matters which might be made use

of in various special diseases, or even in some general disturbances of the digestive apparatus.

No less instructive is a comparison of the results of our experiments upon fat, with the demands of instinct and also with the precepts of dietetics and therapeutics. Everybody knows that fatty foods are heavy, that is, difficult of digestion, and in the case of weak stomachs they are usually avoided. We are now in a position to understand this physiologically. The existence of fat in large quantities in the chyme restrains in its own interest the further secretion of gastric juice, and thus impedes the digestion of proteid substances; consequently, a combination of fat and proteid-holding foods is particularly difficult to digest, and can only be borne by those who have good stomachs and keen appetites. The combination of bread and butter is less difficult, as might _a priori_ be inferred from its wide employment. Bread requires for itself, especially when calculated per unit, but little gastric juice and but little acid, while the fat which excites the pancreatic gland insures a rich production of ferment both for itself and also for the starch and proteid of bread. Fat alone does not count by any means as a heavy food, as may be seen from the fact that large quantities of lard are consumed in certain districts of Russia with impunity. This also is comprehensible, since the inhibitory influence of the fat in this case does not prevent the digestion of any other food-stuff, and is conducive to the assimilation of the fat itself. There is no struggle in this case between the several food constituents, and therefore no one of them suffers. In harmony also with daily experience the physician, in cases of weakness of the stomach, totally excludes fatty food and recommends meat of a fat-free kind; for example, game, etc. In pathological cases, however, where an excessive activity of the gastric glands is manifested, fatty food, or fat as emulsion, is prescribed. And here medicine has empirically brought to its aid the restraining action of fat, which we have so strikingly seen in our experiments.

Amongst all the articles of human food, milk takes a special position, and this is unanimously recognised, both in daily experience and in the practice of medicine. By everybody milk is considered a light food, and is given in cases of weak digestion as well as in a whole series of severe illnesses; for example, in heart and kidney affections. The extreme importance of this substance, a food prepared by Nature itself, we can now well understand. There are three properties of milk which secure it an exceptional position. As we already know, in comparison with nitrogenous equivalents of other foods, the weakest gastric juice and the smallest quantity of pancreatic fluid are poured out on milk; consequently, the secretory activity requisite for its assimilation is much less than with any other food-stuff. In addition, milk possesses a further important property. Thus, when it is introduced unobserved into the stomach of an animal it causes a secretion both in the stomach and also one from the pancreas; consequently, it appears to be an independent chemical excitant of the digestive canal; and in this

## action it is remarkable that we perceive no essential difference in

the effect when the milk is brought unnoticed into the stomach from that which occurs when it is given to the animal to lap. Although flesh is a better chemical excitant, it is by no means a matter of indifference how it gets into the stomach. It must, therefore, be accepted that milk excites not only a really effective, but at the same time a very economic, secretion, and also that the appetite is unable to stimulate this secretion into a more active or abundant flow. The secret of the relation of milk to the secretion of the digestive juices can, unfortunately, at present be submitted to no further analysis or investigation. We are at liberty, however, to suppose that the fat on the one hand is of importance for the inhibition of the gastric glands, and the alkalinity on the other for the restraint of the pancreas. Thus the gastric glands and the pancreas, notwithstanding the presence of excitants, are maintained by milk at a certain but not too high degree of activity, a matter which is in every way desirable in consideration of the easy digestibility of its constituents. Finally, the third characteristic which is observed to belong to milk, and which is probably only an expression of the first, consists in the following. When one administers to an animal equivalent quantities of nitrogen, in the one case as milk, in the other as bread, and afterwards estimates the hourly output of nitrogen in the urine, it results that the increase during the first seven to ten hours after the milk (compared with the excretion beforehand) amounts only to from 12 per cent to 15 per cent of the nitrogen taken in, while after bread it amounts to 50 per cent. If the hourly rate of absorption and the extent to which milk and bread are respectively used up be taken into consideration, it has to be admitted that these augmentations of urinary nitrogen which appear soon after feeding must be expressions of the functional

## activity of the digestive canal itself, and that this activity in the

case of bread is three or four times greater than in the case of milk (_Experiments of Prof. Rjasanzew_); consequently, in the case of milk a much larger fraction of its nitrogen is free to be used up by the organism at large (irrespective of the organs of digestion) than in that of any other kind of food. In other words, the price which the organism pays for the nitrogen of milk, in the form of work on the part of its digestive apparatus, is much less than that for other foods. How admirably, therefore, the food prepared by Nature distinguishes itself when compared with all others!

The facts just related bring forward a new aspect from which the relative nutritive values of different foods may be judged. The older criteria must frankly make room for the new or else be displaced by them. Experiments upon the utilisation of food-stuffs, in which what remains undigested is determined as well as what is absorbed into the body fluids, cannot alone be trusted to solve the question in a satisfactory manner. Suppose, for instance, that in the digestion of a given food the alimentary canal has been given a certain work to perform; if it be in health the work will be accomplished in the best possible manner--that is to say, with complete abstraction of everything nutrient. You will thus learn how much nutrient material was contained in the food, but the question of its digestibility remains as obscure as before. In your experiment you do not know how great an effort it has cost the alimentary canal to extract all the nourishment from the food. Nor can artificial digestion experiments settle the question of digestibility, for experiments in which food is normally partaken of are quite different from those in the test-tube, where we have to deal with only one juice, and not with the interaction of different juices and different food constituents. That one must here, as a matter of fact, make a distinction is clear from the observation of Dr. Walther in our laboratory. Fibrin, which is regarded by all as the most easily digested proteid, proved, when compared with a nitrogen equivalent of milk, to be a much stronger excitant of the pancreas, although milk contains, in addition to nitrogenous substances, a good deal of other non-nitrogenous material. The digestibility and nutritive value of foods must obviously be decided by an estimation of the real work which they entail upon the digestive apparatus, both in regard to the quantity and quality of the juices poured out on a given amount of nutrient material. The energy used up in gland metabolism must be deducted from that of food taken in. The remainder will then indicate the value of the food to the organism; that is to say, will give the amount available for use by all the other organs exclusive of the digestive apparatus. From this point of view those materials must be taken as less nourishing and less digestible which are in large part used up to make good the expenditure entailed by their digestion on the part of the alimentary canal; that is to say, those food-stuffs are less useful whose nutritive value little more than covers the cost of their digestion; consequently, it is of great practical importance to compare from this aspect the same foods differently prepared--for example, boiled and roast meat, hard and soft boiled eggs, boiled and unboiled milk, etc.