Columbia Umuersritp mtfjeCitpof Jfretollork College of $f)pgtrians anb burgeons Reference Htbrarp DIGESTION AXD DIET Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/collectedcontribOOrobe COLLECTED CONTRIBUTIONS ox DIGESTION AXD DIET BY SIR WILLIAM ROBERTS, M.D. F.R.S. FORMKBLY PHYSICIAH TO TI1E MANCHESTER ROYAL INFIRMARY AND PROFESSOR OF MEDICINE I.N" THE VICTORIA UNIVERSITY PHILADELPHIA LEA BROTHERS AND CO. 1891 P E E F A C E The present volume consists mainly of a reprint of two publications by the author — namely, the Lumleian Lectures ' On the Digestive Ferments and Artificially Digested Food,' delivered before the College of Physicians in 1880, and a course of five Lectures ' On Dietetics and Dyspepsia,' given at the Owens College in 1885. These two little books, after running through two editions, were still called for; and it appeared more advisable to reissue them in conjunction than to print new editions of them separately. The opportunity seemed also a favourable one for bringing together into a collected form, convenient for reference, the other contributions of the author on kindred subjects. These include : — a paper ' On the Therapeutics of Starch Digestion,' published in The Practitioner for 187'.' ; a paper ' On the Estimation of the Amylolytic and Proteolytic Activity of Pancreatic Extracts,' printed in the Proceedings of the Royal Society for 1881 ; an address ' On Feeding the Sick,' delivered at the meeting of the British Medical Association at Cardiff in 1885 ; some observations ' On the Use of Gastric Antacids,' made before the Section of Thera- peutics at a meeting of the same Society in Leeds in VI PREFACE 1889, and, lastly, an address ' On some Practical Points in Dietetics,' delivered before the Manchester Medical Society in October, 1890. The volume therefore embraces all the contributions which the author has made to subjects relating to Digestion, Dietetics, and Dyspepsia. The matters treated of have been thrown together into four groups or sections ; and the materials have been subjected to some amount of rearrangement. By this means a certain degree of order and coherence has been given to the entire work ; but no attempt has been made to produce a systematic treatise. The articles have all been carefully revised ; and repetitions have been eliminated as far as was practicable ; but no substantial changes have been made in the subject- matter. W. E. London, April 1891. CONTENTS SECTION I. DIGESTION AND TEE DIGESTIVE FERMENTS. I. — DIGESTION IN GENERAL — THE DIGESTIVE FERMENTS — DIGESTION OF THE CARBOHYDRATES. PAGE Digestion is a faculty or function common to animals and plants . 3 Exterior digestion 4 Interstitial digestion .......... 6 General character and properties of the digestive ferments . . 9 Peculiarity of the albuminous matter contained in solutions of the proteolytic ferments 13 On nomenclature . . . . . , . . ,15 Preparation of artificial digestive juices 10 Boracic solution ......... 17 Dilute spirit 17 Chloroform-water 18 Diastasic ferments and the digestion of starch 1'.) Theory of starch transformation . . . . . .21 The respective shares of saliva and pancreatic juice in the digestion of starch 27 When can starch be said to be fully digested ? .... 29 Absolute energy of diastase 31 Digestion of cane-sugar - the invereivc ferment .... 36 Vlll CONTEXTS II. — DIGESTION OF PROTEIDS — THE MILK-CURDLING FERMENT THE EMULSIVE FERMENT. PAGE Pepsin and trypsin — digestion of proteids . . . . . . 39 Nature of the acid of gastric juice ....... 40 The effect of gastric juice on the salivary and pancreatic ferments 43 Digestive proteolysis .......... 47 Characters of peptones ......... 48 Comparison of the action of pepsin and trypsin . . . . 51 Peptogens ........... 54 The milk-curdling ferment ........ 56 Curdling ferment of the pancreas ...... 50 What is the function of the milk-curdling ferment ? . . . 58 Emulsive ferment — the digestion of fats ..... 59 Opinions and observations of Bernard . . . . . Author's observations ........ 61 Briicke's and Gad's observations . . . . . . 62 III. — THE ESTIMATION OF THE ACTIVITY OF PANCREATIC EXTRACTS. Preliminary observations ........ 60 Diastasimetry ........... 08 Standard starch mucilage 69 Effect of quantity and time 70 Effect of temperature ........ 73 Mode of proceeding 74 Mode of calculating and expressing the diastasic value . . 70 Diastasic value of the pancreas of the pig, ox, and sheep . . 78 Diastasic value of saliva and malt 79 Trypsimetry ........... 80 Metncasein reaction ........ 80 Effect of quantity and time . . . . . . . 83 Effect of temperature ........ 84 Mode of proceeding ......... 87 Mode of calculating and expressing the tryptic value . . 88 Comparison of the enzymic values of the pancreas of the pig, ox, and sheep 89 CONTENTS IX SECTION II. DIETETICS. I. — INTRODUCTORY — ON DIETETICS IN GENERAL. Dyspeptic troubles more common in man than in animals Causes of this — complexities of the human dietary . Basis of scientific dietetics — dietetic customs On the use of meat ........ On the use of alcoholic beverages ...... On the use of tea, coffee, and cocoa ..... Dietetic habits of the two sexes ...... Dietetic habits of infants and children- and of the aged . Personal and family idiosyncrasies ..... Effect of the quality of the food on nutrition and vital habits High feeding and low feeding ....... Comparison of bodily and mental qualities of high-fed and low classes and races ....... fed PAGB 93 94 96 98 99 101 103 104 105 106 108 109 II. — EFFECT OF FOOD-ACCESSORIES ON SALIVARY DIGESTION. Preliminary remarks . . . . . . . . . . 112 Method of experimentation . . . . . . . .114 Effect of alcoholic beverages 11.3 Proof spirit, brandy, whisky, and gin 115 Wines 117 Acids 118 Malt liquors . . 119 Effervescent table waters 119 Effects of tea, coffee and cocoa, &c. . . . . . . 120 Tea — tannin 121 Coffee and cocoa 124 Beef-tea, salt, and sugar 125 III. — EFFECT OF FOOD-ACCESSORIES ON PEPTIC DIGESTION. Method of experimentation 127 Varying quantities of hydrochloric acid 130 Varying quantities of pepsin 131 a X CONTENTS I'AGK Effect of alcoholic beverages 132 Proof spirit, brandy, whisky, gin 132 Sherry and port wine ......... 133 Claret, hock, and champagne 135 Malt liquors 136 Effervescent table waters 137 Effects of tea and coffee 138 Beef-tea and whey 140 IV. — EFFECT OF FOOD-ACCESSORIES ON PEPTIC DIGESTION. CONTINUED — THEIR EFFECT ON PANCREATIC DIGESTION. Causes of the retarding effects of food-accessories on peptic digestion 143 In the cases of beef-tea and whey ....... 144 Retarding effects of salts of the organic acids .... 146 Retarding effects of inorganic neutral salts . . ... 146 Effects of superacidulation 147 Effects of dialysis 149 The alkaloids and volatile oils of tea and coffee .... 150 Has retardation of gastric digestion a beneficial purpose ? . . . 153 Use of salt 156 Effects of food-accessobies on pancreatic digestion . . . 156 Effects of food-accessories on pancreatic diastase .... 157 Effects of food-accessories on tryptic digestion ... . . 158 V. — ON SOME PRACTICAL POINTS IN DIETETICS Preliminary remarks .... Proper basis for the study of dietetics Man strictly subject to biological laws Double aim of diet ..... What is a luxury ? Diversity of our diet .... Useless restrictions on the choice of food Office of the palate in the choice of food Beneficial effect of change of diet Better to lessen than to forbid The neurotic or hysterical stomach . Mid-life revision of diet .... How to restrict the intake of food Concluding remarks .... 160 162 163 163 164 164 165 166 168 169 170 171 173 173 CONTEXTS XI SECTION III. PREPARATION OF FOOD FOR INVALIDS. I. — PREPARATION OF ORDINARY FOODS FOR INVALIDS. PAG] Effects and purposes of cooking 177 Clinical relations of gastric and intestinal digestion . . . 180 Feeding the sick with liquid food 182 Milk 183 Beef-tea and other meat decoctions ....... 184 Cold-made infusions of meat 185 Beaten-up eggs 18(5 Fortified gruels 187 Different kinds of farinaceous flours . 188 Commercial ' foods ' for invalids 188 Apparatus and ingredients required for the preparation of foods in the sick room and nursery 190 II. — PREPARATION AND USE OF ARTIFICIALLY DIGESTED FOOD. Introductory remarks . 192 Pancreatic digestion of milk 190 Modified casein or metacasein 198 Directions for the preparation of peptonised articles of food . . 200 Peptonised milk 200 Peptonised gruel 202 Peptonised milk-gruel 203 Peptonised soups, jellies, and blancmanges . . . . 204 Peptonised beef-tea 205 Nutritive value of peptonised food ....... 206 Experimental evidence ......... 207 Clinical experience of peptonised food 213 In urasmic vomiting 214 Gastric catarrh .......... 214 Crises of cardiac disease ........ 214 Pernicious anaemia 215 Gastric ulcer . . 215 Pyloric and intestinal obstruction 216 The use of pancreatic extract as an addition to food shortly before it is eaten . . 217 Pancreatic extract a- an addition to nutritive enemata . . . 218 Xll CONTENTS III. THE USE OF MALT, AND ESPECIALLY OF MALT INFUSION, FOR THE PREDIGESTION OF STARCHY FOOD. PAGE Various kinds of diastase ......... 219 Conditions in which starch digestion is defective .... 221 Preparations of malt .......... 222 Malt extracts 223 Malt infusion 224 Note on the antiseptic properties of chloroform .... 225 Administration of malt preparations with food ..... 226 Predigestion of starchy food ........ 227 Liebig's method 228 The use of malt infusion ........ 229 Clinical experience ......... 230 SECTION IV. DYSPEPSIA. ON THE ACID DYSPEPSIA OF HEALTHY PERSONS. General description 235 Symptoms 237 The acid residuum . . . . ' 238 Nature and source of the acid 239 Particular symptoms 242 Pain 242 Depression 243 Acid eructations and heartburn 244 Flatulence 244 Gastric cramp or paroxysmal pyrosis ..... 247 Diagnosis of acid dyspepsia 249 Further incidents of acid dyspepsia 250 Treatment 250 By antacids 251 By provoking salivation 255 INDEX 259 Section I DIGESTION AND THE DIGESTIVE FERMENTS I. DIGESTION IN GENERAL— THE DIGESTIVE FERMENTS DIGESTION OF CARBOHYDRATES. (First Lumlcian Lecture.) Summary : — Digestion is a faculty or function common to animals and plants— Exterior digestion — Interstitial digestion — General characters and properties of the digestive ferments — Preparation of artificial digestive juices — Diastasic ferments and the digestion of starch — Theory of the process — The respective shares of saliva and pancreatic juice in the digestion of starch — When can starch be said to be fully digested ? — Absolute energy of diastase — Digestion of cane-sugar, and the inversive ferment. Digestion has been usually regarded as the special attribute of animals. They receive into their alimen- tary canal the food which they require for their sus- tenance in a crude form. It is there subjected to the action of certain ferments which transmute its elements, by a peculiar chemical process, into new forms which are fitted for absorption. Looked at in this restricted sense, plants have no digestive function. They possess no alimentary canal, nor any vestige of a digestive apparatus. But when the matter is examined more profoundly, it is seen that plants digest as well as animals, and that the process in both kingdoms of nature is fundamentally the same. In order to understand this generalisation — which was first propounded by Claude Bernard, and constitutes i: 2 4 EXTERIOR DIGESTION one of the most important fruits of his splendid labours ' — it is necessary to recognise digestion under two types or conditions — namely, a digestion which takes place exteriorly at the surface of the organism, and a digestion which takes place interstitially in the interior of the organs and tissues. Exterior digestion is that common process with which we are familiar as taking place in the alimentary canal of animals, by which the crude food introduced from without is prepared for absorption. Interstitial digestion, on the other hand, is that more recondite process by which the reserves of food lodged in the interior of plants and animals are modified and made available for the purposes of nutrition. These two types of digestion are essentially alike both as regards the agents and the processes by which they are carried out — and although one type of digestion is more developed in the animal kingdom and the other type more developed in the vegetable kingdom, both types are represented in the two kingdoms— and bear witness to the fundamental unity of the nutritive opera- tions in plants and animals. I shall only be able to indicate in outline the facts and arguments on which Bernard sought to establish these propositions. EXTERIOR DIGESTION. We all know that the alimentary canal is simply a prolongation of the external surface ; that the skin is continued, at either extremity, without a break, into the alimentary mucous membrane. Accordingly the pro- 1 Claude Bernard, Legons sur les phenom&nes de la vie, T. II.. Edited after his death by Dastre. Paris, 1879. EXTERIOK DIGESTION 5 cesses which take place in the digestive tube are, strictly speaking, as much outside the body as if they took place on the surface of the skin. Upon this inner surface, if I may so call it, are poured out the digestive juices, charged with the ferments which are the special agents of the digestive processes. This is the common con- dition of exterior digestion as it occurs in animals — but it is not the only condition. Among some of the lowest members of the animal series a permanent alimentary canal does not exist. In the amoeba any portion of the exterior is adapted for the reception of food. The morsel sinks into a depression formed on the surface at the point of impact — it is digested in this improvised stomach, and the indigestible portions are expelled through an improvised anus. Among plants exterior digestion is a much less prominent feature than among animals, but examples of its occurrence and evidence of its importance are not difficult to point out. In the lowest orders of plants — fungi and saprophytes, which are devoid of chlorophyll — exterior digestion is probably a function of prime necessity. In all likelihood their carbon-containing food is only absorbed after undergoing a process of true digestion. The transformation of cane-sugar by the yeast plant is a striking example — though a distorted one — of exterior digestion. Cane-sugar is a crude form of food both to plants and animals, and requires to be transformed into invert-sugar (a mixture of equal parts of dextrose or grape-sugar and lrevulose or fruit-sugar) before it can be made available for nutrition. The yeast plant is no exception to this rule ; and when placed in a solution of cane sugar it is under the necessity of trans- forming that compound into invert-sugar before it can use it for its profit in fermentation. This transforma- G INTEKSTITIAL DIGESTION tion is effected by a soluble ferment attached to the yeast cell, which can be dissolved from it by water. We shall see later on that a similar ferment exists for a similar purpose in the small intestine of animals — having the same property of changing cane-sugar into invert -sugar. Even among the higher plants exterior digestion is not quite unknown. The function may be said to be foreshadowed in the excretion of an acid fluid by the rootlets of some plants which serves to dissolve and render absorbable the mineral matters in their vicinity. But genuine and most remarkable examples of this type of digestion occur among the so-called insectivorous plants, of which Mr. Darwin has given so interesting an account. In the sundews, the plant, by a peculiar mechanism provided on its foliage, seizes the insects which fortuitously alight on its leaves. A stomach is extemporised around the prey, into which is poured out a digestive fluid. The prey is digested, and the products absorbed, in essentially the same manner as in the gastric digestion of animals. INTERSTITIAL DIGESTION. Both animals and plants lay up reserves, or stores, of food in various parts of their tissues for contingent use, so that if you suddenly withdraw from them their food supplies neither animal nor plant immediately dies — it lives for a certain time on its reserves. But before these reserves can be made available for the operations of nutrition they must first be converted from their inert and mostly insoluble state into a state of solution and adaptability to circulate in the nutritive fluid which constitutes the alimentary atmosphere of the proto- INTERSTITIAL DIGESTION 7 plasmic elements. This conversion of inert store-food into available nutriment is brought about certainly in some, presumably in all cases, by the same agents and processes as the digestion which takes place in the alimentary canal of animals ; and it is this identity in the agents and the processes which Bernard insisted on as the proof of the fundamental identity of the two kinds of digestion. The storing up of food is carried on to a larger extent in the vegetable than in the animal kingdom, owing to the intermittent life of most plants. In their seed, tubers, bulbs, and other receptacles are laid up stores of albumen, starch, cane-sugar, and oil — designed primarily for the growth and nutrition of the plant or its offspring — but which are largely seized on by animals and utilised for their food. Owing to their more con- tinuous life animals store up food less than plants. Nevertheless, they accumulate stores of fat in various parts of their body — of animal starch (glycogen) in their livers and elsewhere — and of albumen in their blood. Birds also store up large quantities of albumen and fat in their eggs. The transformation of store food has been followed out most completely in regard to starch and its congener glycogen, and cane-sugar. Bernard worked out this subject with marvellous minuteness and success. It has long been known that the transformation of starch into sugar in germinating seeds was effected by diastase ; and that a similar ferment, existing in saliva and pan- creatic juice, performed the same office on the starchy food of animals. It has also been proved that the stores of starch laid up in the tuber of the potato and in various parts of other plants are changed at the periods of budding and growth in the same way and by the 8 INTERSTITIAL DIGESTION same agent. Bernard showed that animal starch or glycogen is stored up largely not only in the liver but in a variety of other situations, and especially that it is widely distributed and invariably present in large quan- tities in embryonic conditions. In juxtaposition with the glycogen is found a diastasic ferment which trans- forms it into grape-sugar, as it is required for the active operations of growth and nutrition. The stores of cane-sugar which exist in the beet-root and in the sugar-cane are transformed or digested in like manner into invert-sugar when the plants enter on the second phase of their life — the phase of inflorescence and fructification. Here, again, it has been proved that the converting agent is a soluble ferment — the same ferment which, as already mentioned, is attached to the yeast cell — and the same ferment which exists in the small intestine of animals for a similar purpose. The transformation of store proteids and fats has not been followed out with the same success as that of starch and cane-sugar. But the evidence, as far as it goes, and analogy, point to the conclusion that the stores of albuminous and oily matters contained in the seeds, bulbs, and other receptacles of vegetables are subjected to a digestive process before they are made available for the nutritive operations of the plants, and that the changes thus effected are of the same nature and accom- plished by the same agents as those which take place in the digestion of proteids and fats in the alimentary canals of animals. I have, I think, said enough to show the scope of the evidence and the analogies from which Bernard deduced certain far-reaching generalisations, which I have ven- tured to summarise in my own language in the following propositions : — DIGESTIVE FERMENTS il (1) Digestion, or the process by which crude food is changed into available nutriment, is a function or faculty of capital importance in every form of active life. (2) This function is exercised partly on food brought into proximity with the surface of the organism (exterior, chiefly intestinal digestion) and partly on reserves of food laid up in the interior of the organism (interstitial digestion). (3) The agents concerned in this function and their mode of action are essentially the same whether the organism be a plant or an animal — and whether the action take place in the interior of the tissues, — or on the general r intestinal surfaces. GENERAL CHARACTERS AND PROPERTIES OF THE DIGESTIVE FERMENTS. The essential work of digestion is carried out by a remarkable group of agents, called soluble or unorganised ferments. These are found dissolved in the several digestive juices or secretions, which are thrown out on the path of the food as it travels along the alimentary canal. The physical and mechanical processes to which food is subjected in the mouth and stomach are all purely introductory, or preparatory, and are solely in- tended to facilitate the essential work of digestion, which consists in the action of the digestive ferments on the alimentary principles. The number of distinct ferments employed in the digestion of the miscellaneous food used by man is not accurately known, but there are at least seven or eight of them. The accompanying table presents in one view a scheme of the several digestive secretions or juices — and the ferments which they contain — together with an 10 DIGESTIVE FERMENTS indication of the action of each ferment on the several alimentary principles. Table of the Digestive Juices and their Ferments. Digestive Juices Ferments contained in them Action on Food Materials Saliva . Salivary diastase or ptyalin Changes starch into dextrine and sugar. o.,,,. { a. Pepsin . b. Curdling ferment . Changes proteids into peptones in an acid medium. Curdles the casein of milk. Pancreatic juice -/ \ a. Trypsin b. Curdling ferment . c. Pancreatic diastase d. Emulsive ferment. Changes proteids into peptones in alkaline and neutral media. Curdles the casein of milk. Changes starch into dextrine and sugar. Emulsifies and partially saponifies fats. Bile 9 Assists in emulsifying fats. Intestinal juice \ \ a. Invertin b. ? Curdling ferment Changes cane-sugar into invert-sugar. Curdles the casein of milk. An examination of the table shows that a long and complicated series of ferment-actions is required to accomplish the digestion of our food. Starch is attacked at two points — in the mouth and in the duodenum — by two ferments, salivary and pancreatic diastase, which are substantially identical. Albuminous matters are also attacked at two points — in the stomach and in the small intestine — but here the two ferments, pepsin and trypsin, are certainly not identical. The ferment, of which the DIGESTIVE FERMENTS 1! only known characteristic is to curdle milk, is found in the stomach and in the pancreas — and I think also in the small intestine. The bile is not known to possess any true ferment-action, but it assists, by its alkalescent reaction and by its physical properties, in emulsifying and promoting the absorption of fatty matters. The ferment which transforms cane-sugar, strange to say. is not encountered until the food reaches the small in- testine. The known digestive ferments all belong to the class of soluble or unorganised ferments. They are sharply distinguished from the insoluble or organised ferments, of which the type is yeast, in not having the power of self-nutrition and self-multiplication. All living or- ganisms possess this power either in a dormant (poten- tial) or in an active (kinetic) state. Soluble ferments cannot therefore be said to be alive — but they are exclusively associated with living organisms and take an essential part in their vital operations. The digestive ferments are all the direct products of living cells, and may be regarded as detached repositories of cell-force. The}' are quite unknown in the domain of ordinary chemistry. Their mode of action bears no re- semblance to that of ordinary chemical affinity, and has a distinctly physiological character. They do not derive their marvellous endowments from their material sub- stance. They give nothing material to, and take nothing material from, the substance acted on. The albuminoid matter which constitutes their mass is evidently no more than the material substratum of a special kind of energy — just as the steel of a magnet is the material substratum of the magnetic energy — but is not itself that energy. This albuminoid matter of the ferment may be said to become charged, at the moment of elaboration by the 12 DIGESTIVE FERMENTS gland-cells, with potential energy of a special kind — in the same way that a piece of steel becomes charged with magnetism by contact with a pre-existing magnet. The potential energy of the ferment is changed into the active form (i.e. becomes kinetic) when it is brought into contact with the alimentary substance on which it is designed to act. The chemical and physical characters of the digestive .ferments appear to be tolerably uniform. In composi- tion they resemble proteid substances, and contain car- bon, oxygen, hydrogen, and nitrogen in the same or somewhat similar centesimal proportions as albumen. But as not one of them has yet been obtained in a state of absolute isolation and purity, this is, strictly speaking, a matter of inference rather than an ascertained fact. They are all soluble in water ; they are all diffusible, though with great difficulty, through animal membranes and parchment paper. They are also capable (all those I have tried) of passing through porous earthenware by nitration under pressure ; but some of them pass through readily, and others with the utmost difficulty and only in the smallest proportions. They are precipitated from their watery solutions by absolute alcohol — but, unlike other proteids (peptones ex- cepted), they are not truly coagulated by alcohol. When the alcohol is removed the ferments are still found to be soluble in water and to retain their activity unimpaired. They are rendered permanently inert by the heat of boiling water ; and when in solution they are coagulated and destroyed by a heat of about 160° Fahr. (71° C). There is a curious point in regard to the proteolytic ferments which requires elucidation. Liquid prepara- tions of these ferments invariably contain a considerable amount of unchanged — that is to say of undigested — DIGESTIVE FERMENTS 13 albumen, which is precipitated by the addition of nitric acid or by boiling. This is the case both with pancreatic extracts and with solutions of pepsin acidulated with hydrochloric acid. It is evident that this substance can- not be any one of the ordinary forms of albumen — otherwise it would long since have undergone digestion — it would, in fact, have been transformed into peptone by the trypsin or pepsin associated with it in the solution— and in that condition would of course have been in- capable of being precipitated by nitric acid or boiling. All this leads up to the inference that the albuminoid matter which constitutes the organic substratum of pep- sin and trypsin is an altogether special form of albumen — and that one of its peculiarities is that it is unsuscep- tible of the proteolytic transformation which we call digestion. Its relation to ordinary albumens would re- semble that of an unfermentable sugar in regard to ordinary sugars. It further suggests itself to one's mind that the undigested remnant which is invariably found as a residuum in the artificial digestions of proteids — and which goes by the name of ' dyspeptone ' — is not, as has been thought, a bye-product of the digestive process, but that it is simply an admixture of this variety of non- digestible albumen. Each digestive ferment has its special correlative alimentary principle, or group of principles, on which alone it is capable of acting. Diastase acts exelu>ivtly on amylaceous substances. Pepsin and trypsin act only on the azotised principles — the emulsive ferment of the pancreas is only capable of acting on fatty bodies — the inversive ferment of the small intestine has no activity except on cane-sugar. The changes impressed on alimentary principles by the digestive ferments are not, chemically speaking, of a 14 DIGESTIVE FERMENTS profound character — and they affect much more the physical state of these principles than their chemical composition. In the main they are processes of de- duplication and hydration — and the result is to render the substances operated on more soluble and more dif- fusible — to diminish their colloidal state and to make them approach or even to reach the crystalloid state. This does not appear to be invariable, however. Cane- sugar is a marked exception — it is converted in the small intestine into invert-sugar (a mixture of equal parts of grape-sugar or dextrose and fruit-sugar or lsevulose), but invert sugar, though more highly hydrated than cane- sugar, is neither more diffusible nor more soluble. It does not appear to be absolutely true that all food requires digestion before it can be absorbed. Fat is largely taken up by the lacteals in its unaltered state — except in so far that it is finely divided or emulsified. Grape-sugar (dextrose) is not known to suffer any diges- tive operation, but to be absorbed unchanged. Perhaps it would be more correct to say that grape-sugar is an article of food predigested for us by the agency of plants. Although the mode of action of digestive ferments is special and peculiar, the results of that action are not peculiar, but can be obtained in other ways by ordinary chemical forces. By long continued boiling in water — and more rapidly by boiling with acidulated water — starch is converted into dextrine and sugar, and albumen is changed into a substance resembling peptone. The peculiarity of the action of ferments consists in this : that the ferments are able, swiftly and without violence, to produce changes which, by ordinary chemical agencies, can only be produced either by strong reagents or by long-continued and very slow action of weaker reagents. DIGESTIVE FERMENTS 15 It is interesting to remark that the changes produced in food by digestion are, in their ultimate results, very similar to, if not identical with, those produced by pro- tracted cooking. It is becoming evident that the active work which is prosecuted in many quarters on the action of ferments demands the introduction of some new words. The word ferment is still commonly applied to both organised and soluble ferments, although the necessity of referring these groups of agencies to separate categories is univer- sally recognised. Kuhne has proposed to designate the soluble ferments as ' enzyms,' and we may conveniently adopt the word into English, with a slight change of orthography, as ' enzymes.' May we not also designate the organised ferments as ' zymes ' ? If this suggestion were adopted, a great deal of paraphrase might be avoided by coining from these two roots the cognate words which we are in want of for clear expression and concise description. The words ferment and fermentation have been so associated from old time with yeast and alcoholic fermen- tation, that the application of the same words to the pro- cesses by which milk-sugar is changed into lactic acid and alcohol into acetic acid, and to those more complex transformations which we call decomposition and putre- faction, appears strange to us. And yet it is now well known that all these transformations are produced by the action of minute organisms and that they belong strictly to some category as alcoholic fermentation. Still more strange to us is it to apply the same terms to the silent transmutations which take place in the action of diastase on starch and the action of pepsin and trypsin on albumen. If all organised ferments became known as ' zymes,' 16 ARTIFICIAL DIGESTIVE JUICES and all soluble ferments as ' enzymes,' then the process in which zymes are engaged might be called ' zymosis ' — and the process in which enzymes are engaged might be termed ' enzymosis.' The action of the former might be described as ' zymic,' and that of the latter ' enzymic' It would also follow that in scientific description the verb to ' ferment ' would be displaced by the verb to ' zymose,' or to ' enzymose,' as the case might be. THE PREPARATION OF ARTIFICIAL DIGESTIVE JUICES. The study of the digestive ferments has been im- mensely facilitated by a method first introduced by Eberle. Eberle discovered that an aqueous infusion or extract of the digestive glands possessed the same pro- perties as the natural secretions or juices of those glands. The reason of this is that the glands which secrete the digestive juices contain within them a reserve stock of their respective ferments. Accordingly when the glands are infused in water their reserve stock of ferments passes into solution. These infusions or extracts then constitute artificial digestive juices which operate in a flask or beaker in the same way as the corresponding glandular secretions act in the alimentary canal. Solu- tions of organic matters are, however, extremly perish- able — they pass quickly into putrefaction. In order to obviate this inconvenience, and to obtain an extract which is always handy for use, various preservative means have been employed. Bernard used carbolic a.cid — others have used glycerine ! or common salt. 1 Glycerine is one of the best solvents of the digestive ferments, especially for the preparation of solutions designed for experimental purposes. Bullock's acid glycerine of pepsin is used medicinally very largely, and is one of the most active preparations in the market. ARTIFICIAL DIGESTIVE JUICES 17 These preservatives, although perfect for the purpose intended, have a pronounced taste which it is impossible to get rid of. I have made a good number of experiments on this point. As the ultimate object I had in view was to obtain a solution which could be administered as a medicine by the mouth — or which could be employed in the preparation of artificially digested food — I sought for a preservative which either had little taste and smell, or one which was volatile and could be got rid of by vapori- sation. After a good many trials I adopted the three following solutions as on the whole the best suited for the purpose. i. Boracic Solution. This solution contains three or four per cent, of a mixture of two parts of boracic acid and one part of borax. An extract of the stomach or of the pancreas made with this solution keeps perfectly, and has little taste and no smell. For experimental purposes this extract is, I believe, all that can be desired — it is neutral in reaction and is chemically inert. It answers well also for administration by the mouth when the dose does not exceed one or two tea-spoonfuls. But when larger quan- tities are required for the preparation of artificially digested food, and when food thus prepared has to be used day after day in quantity sufficient to sustain nutrition, larger quantities of boracic acid and borax are taken into the stomach than that organ can always comfortably tolerate. ii. Dilute Spirit. The second solution is water mixed with twelve or fifteen per cent, of rectified spirit. 1 This solution makes 1 This proportion of spirit is not enough for perfect preservation in summer weather. The water should contain 20 to 25 per cent, of C 18 ARTIFICIAL DIGESTIVE JUICES a most excellent extracting medium, and the quantity of spirit in it is so small as rarely to he an objection to its use. In the preparation of artificially digested food a final boiling is usually requisite, and in this final boiling the alcohol is dissipated. On the whole, this is the most generally useful of the three solutions. in. Chloroform Water. Chloroform dissolves in water in the proportion of about one in two hundred — these are the proportions employed in the preparation of the Aqua Chloroformi of the British Pharmacopoeia. This forms a perfect solvent for the digestive ferments, and its keeping qualities are unrivalled. But though the quantity of chloroform dis- solved is so minute (about two and a half drops in a fluid ounce), it communicates a somewhat powerful smell and taste to the solution. This taste and smell are agree- able to most persons, but not to all. It is, however, quite easy to get rid of the chloroform. If the dose to be used be first poured into a wineglass or saucer and left exposed to the air for three or four hours, the chloro- form passes off almost entirely in vapour, and leaves behind a simple aqueous solution of the ferments. Or, if the solution is employed for the preparation of arti- ficially digested food, the chloroform, being very volatile, disappears in the final boiling. It is perhaps well to mention that chloroform water has the property of re- ducing Fehling's solution, and that this property has to- be taken into account in making experiments on digestion which involve testing for sugar. rectified spirit. The solvent properties of the medium are not in the least deteriorated by this additional proportion of spirit — at any rate in regard to malt-diastase and the pancreatic enzymes. DIASTASIC FERMENTS 1!> Alimentaiy substances fall naturally into three well- marked groups, namely, Carbohydrates, Proteids, and Fats. I propose to consider the digestion of the three groups in the order here indicated. I have, however, no intention of dealing systematically with these subjects, but rather to take up certain points and questions in regard to which I have myself made observations, or which have a bearing on the preparation of artificially digested food and its administration to patients. I shall treat the digestive transformation of starch in some detail, because this has been worked out almost to com- pleteness, and because it probably furnishes a type which will hereafter be of service as a guide to the study of the more complex problem of the digestion of proteids. DIASTASIC FERMENTS — DIGESTION OF STARCH. The importance of starch as an article of human food has, perhaps, scarcely been duly recognised. If we re- gard the enormous proportion in which the seeds of cereals and leguminous plants and the tuber of the potato enter into our dietary, and the immense percentage of starch in these articles, it is probably not too much to say that fully two-thirds of the food of mankind consists of starch. In the raw state starch is to man an almost indi- gestible substance ; but when previously subjected to the operation of cooking it is digested with great facility. Diastase has only a feeble action on the unbroken starch granule, even at the temperature of the body. In the lower animals, and in germinating seeds, the starch granule is probably attacked in the first instance by some other solvent, which penetrates its outer mem- branes, and thus enables the diastase to reach and act c 2 20 TRANSFORMATION OF STARCH on the starchy matter contained within. By the aid of heat and moisture in the process of cooking, the starch granule is much more effectively broken up. Its con- tents swell out enormously by imbibition of water, and the whole is converted, more or less completely, into a paste or jelly or mucilaginous gruel. It is in this gela- tinous form exclusively, or almost exclusively, that starch is presented for digestion to man. The digestion of starch is accomplished partly by the saliva and partly by pancreatic juice, both of which are rich in diastase. Diastase also exists abundantly in the liver, and in smaller quantities in the intestinal juice, in the blood, the urine, and apparently in all the interstitial juices. Diastase from all these diverse sources appears to act substantially in the same manner on starch, changing it by a progressive hydrolysis into dextrine and sugar. If the action of a fluid containing diastase— say saliva or extract of pancreas — on starch paste be watched, the first effect observed is the liquefaction of the paste and the production of a diffluent solution. This change is effected with great celerity — in two or three minutes the stiff paste becomes a watery liquid. This is evidently a distinct act — and antecedent to the saccharifying process which follows. By operating with small proportions of diastase and large proportions of pure starch paste, it is possible to hit on a moment when liquefaction is com- plete and saccharification is not yet begun. At this moment the solution yields a pure starch reaction, and no reaction of dextrine nor of sugar. The process of sac- charification follows immediately on the heels of lique- faction ; and in ordinary manipulations the one process runs into the other. The speed of the action depends primarily on the TRANSFORMATION OF STARCH 21 proportion of the diastase. By adjusting the propor- tions of diastase and starch in such degrees that sac- charification will be completed in about a couple of hours, the successive steps of the process can be leisurely followed by applying from time to time the appropriate tests. If you test as soon as liquefaction is complete you get a pure blue with iodine and a slight reaction of sugar with Fehling's solution. In a few minutes the sugar reaction becomes more decided; and, although you still get a pure blue with iodine in the ordinary way of test- ing, you will get, by greatly diluting the blue solution and then adding more iodine, a deep violet tint — show- ing the presence of erythro-dextrine mixed with starch. The next step is the total disappearance of the blue reaction with iodine, and the substitution for it of an intense reddish-brown coloration of erythro-dextrine. By and by the reddish- brown colour is replaced by a yellowish-brown — indicating the preponderating presence of a different kind of erythro-dextrine. Meanwhile the sugar reaction goes on increasing. The next step is the entire disappearance of any kind of coloration with iodine. But the action is still very far from complete — the pro- portion of sugar goes on increasing for a considerable time after iodine has ceased to tint the solution. At length, however, matters come to a standstill, and the proportion of sugar ceases to increase. The explanation of this series of reactions is impossible on the old view of the constitution of the starch. Until recently it was supposed that the starch molecule was re- presented by the comparatively simple formula C,. 2 H., O lo and that under the influence of diastase this molecule was resolved by hydration into two molecules — one of dextrine and one of grape-sugar. 22 TRANSFORMATION OF STARCH The researches of Musculus and 0' Sullivan 1 have shown that this is not a correct account of the trans- formation. In the first place it was found that the sugar produced was not grape-sugar (dextrose), but another kind of sugar called maltose. It was also found that the dextrines first produced, and which were coloured red or brown by iodine, were progressively changed, with simultaneous production of sugar, into a series of dex- trines of a lower type, which did not yield any coloration with iodine. To these latter kinds of dextrine the term achroo-dextrines has been applied. As maltose is now ascertained to be the kind of sugar which is mainly produced in the digestion of starch by diastase, this body assumed a new and considerable importance in physiological chemistry, and it will not be out of place here to give some description of its proper- ties. Maltose is a fermentescible, crystalline sugar of the saccharose (cane-sugar) class, having very little sweetening power, and possessing one atom less water than grape-sugar. Its formula is C 12 H 22 O n . It possesses more rotatory power on polarised light than grape-sugar, but has considerably less power of reducing cupric oxide. The rotatory power of maltose is + 150, that of grape- sugar + 58. The reducing power of maltose is 61 com- pared to that of grape-sugar as 100. Maltose can be hydrolysed into grape-sugar by prolonged boiling with dilute acids. Malt-diastase does not possess this power, but we shall presently see that the diastasic ferments of the small intestine are able slowly to effect the same change. 1 O'Sullivan's papers are published in the ' Journal of the Chemical Society,' from 1872 to 1876. A full account of these researches is given in a paper in the same Journal for September, 1879, by T. H. Brown and J. Heron. TRANSFORMATION OF STARCH 23 The researches of Musculus and O'Sullivan have rendered it necessary to assume that the molecule of soluble or liquefied starch is a composite molecule, con- taining several members of the group C 12 H 20 O 1(1 — which is to be regarded as the constituent radical of the compo- site starch molecule. The starch molecule must in the future be represented by the formula //(C 12 H 2o O 10 ) — the value of n not being yet definitely agreed upon. Two able chemists of Burton-on-Trent, H. T. Brown and J. Heron, have extended these researches, and fully confirmed the main conclusions of Musculus and O'Sullivan. In an elaborate publication (' Journ. Chem. Soc.,' Sep., 1879) they have for the first time presented a fairly complete scheme of the succession of changes undergone by starch under the action of diastase. These chemists assume tfiat the molecule of soluble starch consists of ten members of the group C 12 H 20 O, and that its formula should be written 10(C 12 H. 20 O 10 ). This view greatly facilitates the comprehension of the progressive hydrolysis of starch by diastase. We have seen that starch in the condition of paste or jelly is distinguished sharply by its physical properties from liquefied or soluble starch. There is therefore in all probability some difference of molecular aggregation between starch in these two states— and it Mill not be a very bold assumption to suppose that starch in the gelatinous state consists of still more complex molecules than soluble starch — and that several molecules of soluble starch are grouped together to form the molecule of starch in the gelatinous state. On the ground of these assumptions we may represent the successive steps of the digestion of gelatinous starch by the following series of equations. The molecule of gelatinous starch is first resolved 24: TRANSFORMATION OF STARCH into its component molecules of soluble starch. The molecule of soluble starch is then resolved by progres- sive de-duplication and hydration into dextrine and maltose by the following succession of steps : — One molecule of soluble starch = 10(C 12 H. 20 O 10 ) + 8(H 2 O) = 1. Erythro-dextrine a 9(C 12 H 20 O 10 ) + (C 12 H 22 O n ) maltose 2. Erythro-dextrine 8(C 12 H 20 O 10 ) + 2(C,.,H,,,O n ) 3. Achroo-dextrine a 7(C 12 H 20 O, ) + 3(C,.,H.,,0 11 ) 4. Achroo-dextrine j3 6(C 12 H 2o O 10 ) + 4(C 12 H 22 0„) 5. Achroo-dextrine y 5(C )2 H 20 O 10 ) + 5(C,._,H...,O u ) (5. Achroo-dextrine 5 4(C,,H, O 10 ) + 6(Ci 2 H.,,O u ) 7. Achroo-dextrine e 3(C 12 H 20 O 10 ) + 7(C 12 H 22 O n ) 8. Achroo-dextrine 6 2(C 12 H 20 O 10 ) + 8(C 12 H 22 O 11 ) The final result of the transformation is represented by the equation 10(C ia H ao 10 ) + 8H a O = 8(C la H aa O u ) + 2(C la H 20 O 10 ). Soluble Starch. Water. Maltose. Achroo-dextrine. In order to render this array of equations more easy of comprehension to those who are unaccustomed to read complex chemical formula;, the transformation may be represented by the subjoined diagram. We will assume that the molecule of gelatinous starch consists of an aggregation of five molecules of soluble starch, and that the molecule of soluble starch consists of an aggregation of ten groups of the radical C 12 H 20 O 10 . Each of these radicals is represented in the diagram by the shaded dots. The open circles represent the atoms of maltose which are set free at each stage of the trans- formation. The first act is the breaking up of the large molecule of gelatinous starch into its component mole- cules of soluble starch. Then follows the progressive disintegration of the latter molecules into dextrine and maltose. TRANSFORMATION OF STARCH 25 /'"''•'''-A Molecule of IKBJ$ \P3<^M Gelatinous Starch \ /^©^\/g^^- Molecule of /0^\ r Soluble Starch g@©|) + 8 atoms of water 1 Ervthro-dextrine « (@@@@> O maltose 2 Erythro-dextrine (|,©&) "0° 3 Achroo-dextrine « (T©^- nOn " 4 Achroo-dextrine |3 p©^) o *^rP » 5 Achroo-dextrine y ©©a OP qO " 6 Achroo-dextrine S ^ 0°oO 7 Achroo-dextrine e ^) 0°qOO » 8 Achroo-dextrine 5 (gj\ OaOo " °o We must conceive that the energy of the ferment is exercised in gradually pulling asunder the component groups or radicals of the unstable molecule of soluble starch — detaching one after another from the parent molecule — each radical as soon as detached assuming an atom of water and becoming an atom of maltose. At each detachment the parent molecule draws its remaining groups together to form a new kind of dextrine. As the process 26 TRANSFORMATION OF STARCH goes on the dextrine molecule becomes smaller and smaller — that is, contains fewer and fewer component radicals — the higher dextrines giving a red or brown coloration with iodine, but the lower dextrines giving no reaction with iodine. It is to be noted that after the transformation has reached its final term there still remains a portion of achroo-dextrine unconverted into maltose. Upon this remnant diastase has only a very slow action. The percentage result, when the reaction is completed, gives, in round numbers, 80 parts of maltose and 20 parts of achroo-dextrine. The eight varieties of dextrine indi- cated in the above table of equations have not all been obtained in the separate state, but there is strong evi- dence of the existence of at least several of them as distinct bodies. The account just given of the transformation of starch has been deduced from a study of the action of diastase derived from malt. The question arises — -physiologically an important question — whether the action of salivary and pancreatic diastase is identical with that of malt- diastase. The researches of Musculus and V. Mering ' gave an affirmative answer to this question. These observers found that saliva and pancreatic extract act on starch paste in the same way as malt-diastase, the final products in all cases being achroo-dextrine and maltose, and not dextrose (grape-sugar). At my suggestion Mr. H. T. Brown was good enough to submit the question to a fresh examination in regard to pancreatic extract. His results fully confirm the conclusions of Musculus and V. Mering. He found, however, that there was a slight difference in the results when the action of pancreatic extract and malt-diastase on starch were continued a 1 Maly's ' Jahresbericht fur Thier-Chemie ' for 1878, p. 40. SALIVARY AND PANCREATIC DIASTASE 2 7 long time. The pancreatic ferment, in addition to the power, which it shares with malt-diastase, of slowly con- verting the lowest achroo-dextrine into maltose, exhibited a power of slowly changing maltose into dextrose (grape- sugar) which is not possessed in any degree by malt- diastase. Mr. Brown also informs me that there is in the small intestine a ferment which possesses similar properties. 1 THE RESPECTIVE SHARES OF SALIVA AND PANCREATIC JUICE IN THE DIGESTION OF STARCH. The respective shares of saliva and pancreatic juice in the digestion of our farinaceous food is probably variable and perhaps not quite identical. As all our farinaceous, food is eaten after being cooked, the starch in it is more or less completely gelatinised ; it is, therefore, probable that one of the chief uses of sali- vary diastase in man is to liquefy starch jelly. A very brief contact suffices for this, and it is manifest that the accomplishment of this change is an important advan- tage in the subsequent operations in the stomach. Our gruels, blanc-manges, puddings, and similar farinaceous dishes owe their thick pasty condition to starch in the gelatinous state, and nothing can be imagined more resistent to the rapid permeation of a meal by the gastric juice, and to the pulping of it into a uniform chyme, than the presence of coherent masses of starch paste. If the saliva performed no other service than this, it would furnish an important aid to the digestion of a meal. There has been considerable dispute as to whether, and how far, the saccharification of starch goes on in 1 Sec a paper by Brown and Heron on the ' Hyclrolytic Ferments of the Pancreas and Small Intestine,' in the 'Proceedings of the Royal Society ' for 1880, p. 393. 28 SALIVARY AND PANCKEATIC DIASTASE the stomach. My own observations lead to the con- clusion that this depends on the degree of acidity of the contents of the stomach ; and it is known that this varies within very wide limits. When a meal is swal- lowed it takes some time for the gastric juice to perme- ate the mass, and the acidity of the gastric contents is for some time feeble. As digestion proceeds the contents of the stomach tend to become more and more acid. This is a point which each one can observe for himself. The stomach is by no means reticent of its doings. The posseting which we see in infants goes on in a less degree in the adult ; and we are perforce made aware, some- times inconveniently so, by our palates, of the ascending scale of acidity in the stomach as digestion advances. Saliva acts energetically in neutral and in slightly acid media, but its activity is checked and finally arrested when the acidity becomes pronounced. When digestion is proceeding comfortably and normally a certain interval elapses before the acidity of the stomach becomes con- siderable, and during this interval the salivary diastase continues active, and has time to accomplish a good deal of work. But we must remember that our farinaceous food is, for the most part, not in the most favourable condition for rapid digestion. It is not generally in a state of mucilage — but in the form of a solid paste as in bread, puddings, and pastry. A good deal of it, too, is imperfectly cooked. Consequently, the larger part of our starchy food reaches the duodenum still unchanged, or only partly changed, and this larger part of the work is consummated by the pancreatic juice in the alkaline medium of the small intestine. I shall have to return to this point in speaking of gastric digestion. It has been noted as curious that the saliva of man possesses more diastasic power than that of almost any DIGESTION OF STARCH 29 other animal. Among the herbivora, which are such large consumers of starch, the saliva has comparatively little diastasic power ; and in some, as in the horse, it is almost or altogether wanting. I apprehend that this is due to the fact that man alone has learnt to cook his starchy food, and that the diastasic power of his saliva has become developed with the opportunity for its exer- cise. Diastasic power would be thrown away in the saliva of the horse, because he eats his food in the raw or uncooked state, and saliva is almost without action on raw starch. WHEN CAN STARCH BE SAID TO BE FULLY DIGESTED ? Seeing that in the digestion of starch a number of intermediate products are evolved — the question arises when can the digestion of starch be said to be accom- plished ? Is maltose the only product absorbed, or are not the dextrines, especially the achroo-dextrines, also absorbed ? The dextrines, even those coloured by iodine, are highly diffusible, and pass freely through parchment paper in dialysis. In this respect they contrast strongly with starch jelly, and even with liquefied (or soluble) starch, both of which are undialysable. It seems not improbable that the lower dextrines are largely absorbed. Because if we follow the history of starch after it has been transformed by digestion, and absorbed, we are confronted with the remarkable fact that after absorption the products of starch digestion, or at least a large por- tion of them, undergo a reconversion in the liver into a substance closely resembling undigested starch. Glyco- gen, in its essential features, is an exact counterpart of soluble starch. It forms an opalescent solution in water ; it is undialysable, and it is transformed by diastase into dextrine and sugar. 30 DIGESTION OF STARCH It appears reasonable to suppose that it would be an advantage to the economy if that portion of our starchy food which is destined to be stocked in the liver as glyco- gen, should be absorbed at an early period of its diges- tion, because the less removed the digested product is from starch at the moment of absorption the fewer steps it will have to retrace in recovering the amylaceous state after absorption. The annexed diagram will render my meaning clear. It represents, on one side of the dividing line of the ab- sorbent membrane, the descending steps of the digestive process — and on the other side the ascending curve of the reconstructive process. Soluble Starch .V X "DEXTRINE. SUGAR. Absorbent Surface Liver Glycogen It is not necessary to suppose that the ascending steps of the reconversion are identical with the descend- ing steps of digestion, but it is probable that they are fundamentally alike, seeing the close similarity of the products at the two ends of the journey. At any rate there is no warrant in the present state of know- ledge for the opinion that sugar is the only absorbable product of starch digestion. ENERGY OF DIASTASE 31 ABSOLUTE ENERGY OF DIASTASE. The notion that the energy of diastase is not con- sumed in action seems, on a priori grounds, to be quite untenable — such a notion contravenes a general principle in physics that energy in performing work is expended and finally exhausted. It is easy to show experimentally that diastase is no exception to this rule. Payen and Persoz estimated that malt-diastase was able to convert two thousand times its weight of starch into sugar. My own experiments with extract of pancreas indicate a much higher power than this. The following experi- ment illustrates at the same time the enormous diastasic power of pancreatic diastase and the fact that this power is strictly limited. A quantity of starch mucilage was prepared, contain- ing one per cent, of pure potato starch — 100 cubic centi- meters of this mucilage contained exactly one gram of dry starch. The pancreatic extract employed was pre- pared in the following manner : — Fresh pig's pancreas, freed from fat, was rubbed up with an equal weight of fine sand until it became a smooth uniform pulp. This pulp was spread out very thinly on sheets of glass, and allowed to dry in the open air for a fortnight. It was then scraped off with a knife and formed a rough shreddy sort of powder. 125 grams of this mixture of pancreas and sand were infused, at the temperature of the room, in 1,000 cubic centimeters of saturated chloroform water, with a little more chloroform added to ensure against decomposition. The mixture was allowed to stand for four days with occasional agitation, and the product was then filtered clear through paper. The extract of pan- creas thus prepared proved a very serviceable prepara- 32 ENERGY OF DIASTASE tion, and most of my observations on pancreatic diges- tion were made with it. This extract was found to be so extremely active that it was necessary to dilute it largely in order to bring the quantities of starch operated on within due compass. Accordingly a dilution was made of one cubic centimeter of the extract in 1,000 cubic centimeters of water. Five numbered phials were then severally charged with 100 cubic centimeters of the prepared starch mucilage — so that each phial contained exactly one gram of dry starch. One cubic centimeter of the diluted pancreatic extract was added to phial No. 1 — two cubic centimeters to No. 2 four cubic centimeters to No. 3 — six cubic centi- meters to No. 4 — and eight cubic centimeters to phial No. 5. The phials were then corked and placed in the warm chamber, where the temperature was steadily maintained by a Page's regulator at 100° F. (38° C.) At the end of twenty hours the contents of the phials were examined. All of them were perfectly transparent, and had entirely lost the opalescent appearance of the original starch mucilage, and not a vestige of sediment existed in any of them. The following reactions indicated the progress of the transformation. No. 1 gave an intense blue coloration with iodine — and when the blue solution was largely diluted and more iodine added, it developed a violet tint which showed the presence of erythro-dextrine — it also reduced the cupro- potassic solution freely. No. 2 gave a strong blue reaction with iodine, and by diluting and adding more iodine, the colour changed to a deep claret-red, indicative of abundance of erythro- dextrine. This and all the rest gave a strong sugar reaction with Fehling's solution. ENERGY OF DIASTASE 33 No. 3 yielded no blue reaction with iodine, but an intense port-wine coloration of erythro-dextrine. No. 4 gave no blue reaction with iodine, and only the faintest possible brown coloration with that reagent, showing only traces of erythro-dextrine. No. 5 exhibited not a vestige of reaction with iodine. It contained neither starch nor erythro-dextrine, but it yielded a strong sugar reaction. The transformation of No. 5 might be regarded as complete, but the rest still contained starch or erythro- dextrine, or both. -Nos. 1, 2, 3, and 4 were restored to the warm chamber, and re-examined at the expiration of seven hours. No. 4 no longer gave the slightest reaction with iodine, but Nos. 1, 2, and 3 showed only slight signs of further alteration, anc\ were returned to the warm chamber. At the end of forty-eight hours from the commence- ment of the experiment, Nos. 1, 2, and 3 were examined again. No. 1 showed a strong blue coloration with iodine, and also a strong reaction of erythro-dextrine. No. 2 no longer gave any blue tint with iodine, but it exhibited an intense erythro-dextrine reaction. No. 3 only gave a yellowish brown reaction with iodine of moderate intensity. After a further sojourn of seventy hours in the warm chamber the contents of the three phials were not found to be sensibly altered — they gave exactly the same reactions as before. It was evident that in these phials the diastasic action had run its course to an end within the period of forty-eight hours, and that the solutions had then come to a state of rest — the ferment had liberated all its energy — the limits of its power had been reached — and the task allotted to it was left un- 34 ENERGY OE DIASTASE finished. Nevertheless it had accomplished an amount of work which, considering its infmitesiinally minute mass, appears marvellous. We shall now endeavour to measure approximately the amount of this work as indicated by the above experiments. The original pancreatic extract, when evaporated to dryness on a water-bath, was found to leave a residue of 1*5 per cent, of organic matter. This organic matter included, besides diastase, a quantity of proteolytic ferment (trypsin) and a certain quantity of the milk- curdling ferment. It also included a certain quantity of digested proteid matter — for in making an extract of the pancreas there is always accomplished some self-diges- tion of the glandular tissue. Taking into account these various admixtures, it would appear a very liberal allowance to estimate the diastasic ferment as amounting to one-fourth of the total organic matter. This would give us for the original extract a proportion of diastase in round numbers of 0*4 per cent., and for the diluted extract of 0*0004 per cent. The proportion of diastase added to phial No. 4 seems to have hit off with precision the limit of quantity required to transform one gram (15-5 grams) of starch in forty-eight hours at a temperature of 100° F. (38° C). The amount of diluted extract added to this phial was 6 cubic centimeters, and on the basis of the above esti- mate this represents a quantity of net diastase amount- ing to 0-00024 gram. This yields us by an easy calcu- lation the astounding result that pancreatic diastase is able to transform into dextrine and sugar no less than 40,000 times its own weight of starch. 1 1 Marvellous as these numbers are, Mr. Horace Brown (whose joint paper with Mr. Heron, already referred to, has been my chief guide in ENERGY OF DIASTASE 35 The speed at which a given quantity of starch is transformed by diastase depends essentially on the pro- portion of ferment brought to act upon it. In the above experiments the proportion of diastase was very minute in comparison with the amount of starch, and the action went on slowly for forty-eight hours. But if we reverse these proportions and mix a small amount of starch with a large amount of diastase, the transformation is instantaneously accomplished. If a test-tube be half filled with an active extract of pancreas and a few drops of starch mucilage be quickly shaken therewith, you cannot detect the reaction of starch or dextrine in the mixture, however prompt you may be with the testing— the transformation has followed on the admixture as instantaneously as the explosion of the charge follows the fall of the trigger. Between these extremes there are all gradations. This mode of action differs entirely from what is seen in the operation of ordinary chemical affinity. If you add a drop of acid to an excess of alkali, the acid is instantly neutralised and the action comes to an end ; and, conversely, if you add a drop of alkali to an excess of acid, the action is equally instantaneous ; the affinity of the two bodies for each other is a mutual affinity. But this is not the case with the action of diastase on starch. The starch ap- pears to be entirely passive in the process ; all the energy is on the side of the diastase, and this energy can only be liberated gradually. There is something in this strikingly suggestive or reminiscent of the action of living organ- isms. To illustrate my meaning, let us compare the trying to work out the theory of starch digestion) informs me in a private communication that he has arrived at numbers still more wonder- ful in estimating the transforming power of malt-extract on the higher dextrines. d 2 36 INVERSIVE FERMENT particles of the ferment to a band of living workmen whose function is to scatter little heaps of stones. If the heaps are few and the workmen many, all the heaps will be scattered at once, and the energy of the workmen will still remain sensibly unimpaired. But if the heaps are millions and the workmen hundreds, and if the work- men are doomed to labour on until they fall exhausted at their task, the scattering of the heaps will go on for a comparatively long time and the process of exhaustion will be a gradual one. I may here mention that the diastasic ferment does not exist in the saliva and pancreatic juice of young suckling animals — except in minute proportions. Its quantity increases when the teeth are cut. In the human infant diastase does not appear to exist in suffi- cient abundance to digest starchy matters effectively until about the sixth or seventh month. Until this period it is therefore not advisable to administer fari- naceous food to infants. DIGESTION OF CANE-SUGAR — INVERSIVE FERMENT. Bernard ' first called attention to the fact, already mentioned, that cane-sugar (saccharose) required diges- tion both in animals and plants before it could be used in nutrition. The cane-sugar stored up in beet-root and in the sugar-cane is changed by ferment-action into in- vert-sugar before it is permitted to circulate in the sap, and take part in the nutritive operations of the plant. He found also that an analogous transformation was requisite before cane-sugar could be assimilated by animals. He states that when cane-sugar is injected 1 Claude Bernard, Ler s mis stir les ph&nom&nes de la vie, T. II., p. 36. Paris, 1879. INVERSIVE FERMENT 37 into the blood it circulates therein as an inert body, and is in no degree used as nutriment by the tissues, but is eventually entirely removed, unchanged, with the urine. Cane-sugar is, however, an important article of food, and is consumed by us in large quantities every day. And we know that when thus consumed it does not behave like an inert matter — circulating awhile in the blood, and then being eliminated by the kidneys as a waste product. It is evidently absorbed and assimilated, and must therefore, somewhere or other, be transformed or digested in animals as it is in plants. Reasoning in this way, Bernard sought for an inversive ferment for cane-sugar in the alimentary tract ; and after searching in the saliva, in the stomach, and in the pancreas in vain, he at length discovered it in the small intestine. In the small intestine he found that cane-sugar was transformed into invert-sugar, and by a similar ferment with that destined for analogous purposes in yeast, in beet-root and in the sugar-cane. The transformation of cane-sugar into invert-sugar is represented by a very simple equation : — 2C 12 H 22 11 + 2H 2 = C 1 oH 24 12 + C 12 H 24 Oj 2 Saccharose. Water. Dextrose. La'vulose. The inversive ferment was detected by Bernard in the small intestine of dogs, rabbits, birds, and frogs. Balbiani found it in the intestine of the silk-worm. It was recognised by myself in an extract of the small in- testine of the pig, the fowl, and the hare. It does not exist in the large intestine. But although my observations on this subject coincided in the main with those of Bernard, I noted two points which I think merit further attention. The first was that while a piece of small intestine infused in water 38 INVERSIVE FERMENT yielded a mixture which was capable of inverting cane- sugar, the same infusion when filtered through paper until it was perfectly clear had no such power. It seemed as if the inversive ferment did not pass freely, if at all, into true solution, but remained attached to some of the formed elements contained in the intestine. The second point I noticed was the extreme slowness of the action. When cane-sugar was added to the unfiltered infusion of intestine, and the mixture maintained at blood heat, it generally took a couple of hours before a reducing effect with the copper test could be obtained. Both these circumstances reminded one of the action of formed ferments, and I could not help thinking that there was here something which required clearing up at some future time. 39 II. DIGESTION OF PROTEIDS— THE MILK-CURDLING FERMENT— THE EMULSIVE FERMENT. (Second Lumleian Lecture.) Summary : — Pepsin and trypsin and the digestion of proteids — Nature of the acid of gastric juice — Effect of gastric juice on the salivary and pancreatic ferments — Digestive proteolysis — Characters of peptones ■ — Comparison of the action of pepsin and trypsin — Peptogens — The milk-curdling ferment — The emulsive ferment and the digestion of fats. PEPSIN AND TKYPSIN — DIGESTION OF PROTEIDS. Various kinds of albuminous or proteid substances are used by mankind as food. The most important of these are muscular flesh, the casein of milk, and egg- albumen from the animal kingdom — and gluten, albu- men and legumin from the vegetable kingdom. Proteids are attacked by the digestive ferments at two points in the alimentary canal, by pepsin in the stomach and by trypsin in the small intestine. Between these two acts of digestion there is a complete break in the duodenum, owing to the abrupt change of reaction from acid to alkaline which occurs at that point. Gastric digestion is, in all creatures, an essentially acid digestion ; but the most varied opinions have been entertained as to the nature of the acid. It has been supposed in turn to be hydrochloric acid, lactic acid, acid phosphate of lime, butyric, and even acetic acid. 40 ACID OF THE GASTRIC JUICE Much of this confusion has arisen from not distinguish- ing between the acid of pure gastric juice as secreted into an empty stomach, and the acid of the gastric contents during the digestion of a meal. A good deal of light has been thrown on this subject by the recent researches of C. Eichet. 1 This observer found himself in exceptionally advantageous circumstances for the study of the gastric juice. He had under observation a young man on whom Verneuil had successfully per- formed the operation of gastrotomy for the relief of impermeable stricture of the oesophagus, the result of swallowing inadvertently a quantity of caustic potash. The complete occlusion of the oesophagus enabled Eichet to obtain and examine the gastric juice in a pure state, uncontaminated with saliva. All food had to be ad- ministered through the fistulous opening left after recovery, and the observer could at any moment — as in the famous case of Alexis St. Martin — withdraw portions of the gastric contents for examination. Eichet also took advantage of the new method of separating the various organic and mineral acids from one another made public by Berthelot in 1872. 2 Berthelot had found that if you shook up an aqueous solution of any acid with ether, and then allowed the two fluids to separate, that a part of the acid passed into the ether, and that the remainder clung to the water, and that the ratio between these two parts was a constant quantity. He called this ratio the coefficient of ])artage, and found that its value was a fixed character- istic for each particular acid. Solutions of the mineral acids were found to yield nothing, or almost nothing, to ether when agitated with it — but organic acids were 1 Du Stic Gastrique, by Ch. Eichet. Paris, 1878. • Ann. de Chimie et de Physique, 4'' serie, t. xxvi., p. 396. ACID OF THE GASTRIC JUICE 41 found to pass into the ether in considerable, though very variable, quantities — the proportion varying in a constant ratio according to the nature of the acid. Testing pure gastric juice, uncontaminatud with food or saliva, by this method, Eichet found that almost all the acid was retained by the water, and that only a small proportion — about one in twenty- two — passed into the ether. This showed that the acid of pure gastric juice was almost entirely a mineral acid, with only a minute admixture of organic acid. The organic acid (tested by the same method) exhibited a coefficient of partage closely corresponding with that of sarcolactic acid. The nature of the mineral acid was determined by a method similar to that employed by C. Schmidt, and yielded the same result — namely, undoubted evi- dence that the mineral acid of pure gastric juice was hydrochloric acid. But Eichet found that this mineral acid did not behave in the presence of salts of the organic acids quite in the same way as free hydrochloric acid does. The observations of Berthelot had shown that when free hydrochloric acid is added to a solution of acetate of soda, or other similar organic salt, the mineral acid attaches the base entirely to itself, and throws the whole of the organic acid free into solution — so that the mixture when tested by the method of coefficient of partage behaves exactly like an unmixed solution of the organic acid. "When pure gastric juice was put to this test it was found that, although it liber- ated the organic acid largely, it did not do so to the same extent, by a good deal, as if the mineral acid con- tained in it had been entirely free. It behaved, rather, as hydrochloric acid does when united with a feeble organic base, such as leucin or peptone — and, on the ground of what appear to be very careful experiments, 42 ACID OF THE GASTEIC JUICE Eichet came to the conclusion that this feeble base was probably leucin, derived from the gastric mucus, and that the acid of pure uncontaminated gastric juice was hydrochloric acid in loose combination with leucin. 1 Eichet next proceeded to examine the free acid actually existing in the stomach during the digestion of a meal in his patient with gastric fistula. He found, as might have been expected, that this differed from the acid of pure unmixed gastric juice — in this respect, namely, that it contained a very much larger proportion of organic acids, in comparison to the mineral acid, than pure gastric juice. It was evident that the mineral acid had to a large extent seized upon the bases of the acetates, malates, lactates, butyrates, and other organic salts always present in the food, and had set free their organic acids. The real work of digestion then, so far as the acid constituent is concerned therein, is largely performed by various organic acids thus set free from the articles of food which are undergoing digestion. Eichet found that the acidity of the contents of the stomach during digestion, although it varied through considerable limits, had a marked tendency to maintain the normal average. If acid or alkali was added to the digesting mass the mean was presently restored auto- matically — the stomach in the former case ceasing to secrete acid, and in the latter case secreting an increased quantity of acid. 1 There are other proofs that the acid of the gastric juice is not free hydrochloric acid. It was shown by Bernard that free hydrochloric acid, even in the proportion of one in a thousand of water, dissolves oxalate of lime — but gastric juice possesses no such power. Blondlot likewise proved that gastric juice does not decompose carbonate of lime — whereas the feeblest dilutions of free hydrochloric acid do so. EFFECT OF GASTRIC JUICE OX OTHER FEEMENTS 43 THE EFFECT OF GASTRIC JUICE ON THE SALIVARY AND PANCREATIC FERMENTS. The observations of Berthelot on the power of a mineral acid to set free the acids of organic salts, and to take their place with the bases — and the further observations of Eichet, showing that the acids actually free in the gastric contents during digestion were organic acids, have led to the re-examination of a point of some importance, namely — as to whether the salivary and more especially the pancreatic ferments were or were not destroyed by the acid contents of the stomach. The matter has a practical interest in this way. If the gastric acid destroys these ferments, it is evidently use- less to administer pancreatic preparations by the mouth during digestion, because they would be rendered inert by the acid contents of the stomach. On the other hand, if they are not destroyed in passing through the stomach, but merely lie dormant and recover their activity in the alkaline medium of the small intestine, then we can administer pancreatic preparations during digestion with every prospect of their passing uninjured through the pylorus and proving useful in assisting digestion in the small intestine. A series of experiments bearing on this question were submitted by T. Defresne to the Academic de Medecine and the Academie des Sciences towards the close of 1879, and have attracted some attention. On the ground of these experiments Defresne arrived at the following con- clusions — namely, that saliva continued its action on starch in the stomach without interruption — that the pancreatic ferments in like manner preserve their activity in the presence of the gastric acid — that the acids of the chyme, being organic acids, did not really destroy these 44 EFFECT OF GASTRIC JUICE ON OTHER FERMENTS ferments, but merely reduced them to a state of tempo- rary inertness ; so that when the acidity of the chyme was neutralised in the duodenum, they recovered their powers and exhibited undiminished activity both on starch and proteids. As the question had a direct bearing on the medi- cinal administration of pancreatic preparations, and indirectly on the administration of malt-diastase and malt-extract, I thought it desirable to repeat some of Defresne's experiments, and to put the question raised by these experiments to the test in other ways. One of Defresne's (apparently) most convincing experiments was the following, which I give nearly in the words of the abstract of the paper published in the Proceedings of the Academie de Medecine for Nov. 4, 1879. When 20 grams of dilute hydrochloric acid, having twice the acidity of the normal chyme (which is estimated as 2 per 1000 of HC1), are mixed with 20 grams of egg- albumen — what follows ? The acidity of the medium is no longer due to free hydrochloric acid, but to the lactic and phosphoric acids of the white-of- egg which have been set free. In presence of these acids pancreatine may be digested for two hours in the warm chamber with impunity. And if, at the end of this period, the acidity of the mixture be neutralised, digestion is accelerated and the pancreatine peptonises 38 times its weight of albumen. I repeated this experiment in the following manner : 40 grams of boiled and chopped white-of-egg were mixed with 40 cubic centimeters of dilute hydrochoric acid of the strength of 4 per 1000. This mixture was subjected to a preliminary digestion of two hours in the warm chamber at 40° C. The object of this preliminary diges- tion was to allow the hydrochloric acid a sufficient time EFFECT OF GASTRIC JUICE OX OTHER FERMENTS 45 to seize on the bases, and to set free the organic acids of the white-of-egg. At the end of this time, 5 cubic centi- meters of an active extract of pancreas were added to the mixture. A second experiment was arranged in exactly the same way, except that filtered saliva was substituted for extract of pancreas. The mixtures were kept in the warm chamber for a further period of one hour, and were then filtered and carefull v neutralised. On testing the neutralised filtrates, I obtained approximative^ the same results as Defresne. The diastasic and proteolytic ferments of the pancreatic extract were found active, but not so active by a good deal as if the extract had been diluted to the same extent with simple water. In the second experiment with the filtered saliva, the ptyalin had preserved its activity quite unimpaired. These experiments, however, involve a fallacy which vitiates the deductions intended to be drawn from thorn. White-of-egg has a highly alkaline reaction, and although the acid used in the experiment possessed double the strength of the normal gastric juice, it was found that the mixtures, at the end of two hours' digestion, had only a comparatively feeble acidity — in fact, only one- seventh of the normal acidity of the gastric contents. It has long been known that the salivary and pancreatic ferments are able to resist a feeble acidity, but the ques- tion really at issue is : can these ferments resist the average acidity of the contents of the stomach, when, moreover, this acidity is rendered still more destructive to them by the presence of pepsin ? I tested the question in this way. A distinction is drawn, and rightly, between acidity due to free hydro- chloric acid, and a similar degree of acidity due to an organic acid. Now, lactic acid is a typical organic acid, and it is also an acid which is often, if not always, pre- 46 EFFECT OF GASTRIC JUICE ON OTHER FERMENTS sent in the contents of the stomach during digestion. I prepared a solution of lactic acid corresponding in satu- rating power to the normal gastric acid (2 per 1000 HC1). To 50 cubic centimeters of this dilute lactic acid I added 5 cubic centimeters of a solution of pepsin and 5 cubic centimeters of an active extract of pancreas. I prepared a second similar experiment, but substituted filtered saliva for pancreatic extract. The mixtures were then placed in the warm chamber for one hour. At the end of this period the solutions were exactly neutralised and tested. They were both found to be absolutely inert. Not a vestige of amylolytic nor proteolytic power had escaped destruction. I had an opportunity of trying the same question in a still more satisfactory way. While I was examining the throat of a patient suffering from an ailment which did not affect his general health, a portion of the con- tents of the stomach was ejected, and fortunately caught in a clean vessel. This was immediately filtered, and about 10 cubic centimeters of clear acid solution were obtained. The period of digestion was three hours after breakfast. One half of this was devoted to testing its saturating power. It was found to possess an acidity very nearly corresponding with that of normal chyme. To the remaining portion five drops of extract of pancreas and five drops of filtered saliva were added, and the mix- ture was placed in the warm chamber for one hour. At the end of this time it was exactly neutralised, and divided into two equal portions. One portion was tested with a drop of starch-mucilage, and found to be abso- lutely devoid of amylolytic power. The other portion was added to an equal volume of milk rendered slightly alkaline with bicarbonate of soda, and was then placed DIGESTIVE PROTEOLYSIS 47 in the warm chamber. Not the slightest digestive action was produced on the milk in twelve hours. I may mention that in the above experiments I used milk as the test of proteolytic activity. 1 had become thoroughly familiar with the behaviour of milk with pancreatic preparations during a long course of observa- tions, and was therefore able to detect the slightest signs of pancreatic action. With this evidence before me, I am unable to accept the conclusions of Defresne and others in Paris who allege that saliva and pancreatic preparations can resist the normal acidity of the stomach in full digestion, and who recommend the administration by the mouth of pancreatic preparations during the period of chymifi- cation. I will in my next lecture point out the time, and the method in which these preparations may, I believe, be administered by the mouth with some pro- spect of success. DIGESTIVE PROTEOLYSIS. The changes undergone by albuminoid substances in digestion are still very imperfectly understood. It is, however, known that the chief end-product of the trans- formation is peptone. It is also known that between any native proteid — egg-albumen, muscle-fibrin, casein, or legumin — and the end-product peptone there are intermediate grades and bye products, which have hitherto proved difficult to define and isolate. The con- stitution of the proteid molecule is still unknown to chemists. That it is a highly complex aggregation is certain ; and it can scarcely be doubted that the wa}' to a better knowledge of its constitution lies in a persever- ing study of the action on it of the digestive ferments. It has been already seen that in the case of starch the 48 CHARACTER OF PEPTONES action of diastase furnished the key to the constitution of the starch molecule — and, similarly, it is not un- reasonable to expect that the mystery of the proteid molecule will be finally solved by a study of the action on it of pepsin and trypsin. Attention has hitherto been too exclusively directed to peptic digestion, which is complicated by the inter-action of an acid. Pancreatic digestion is, in this respect, a simpler process — inasmuch as it requires the interference neither of an acid nor of an alkali, but is a reaction, pure and simple, between the ferment and the proteid. This, however, is a question of the future. Character of Peptones. — The end-product peptone has been fairly isolated and its characteristics defined. If the filtered product of a pancreatic digestion of egg- albumen be evaporated to dryness in a watch-glass at a temperature of 104° Fahr. (40° C.) there remains a glassy straw-coloured residue resembling dried gum. With the point of a penknife this can be chipped off in shining scales, which may be easily reduced to a fine whitish powder — this is nearly pure peptone. This sub- stance is extremely soluble in water : and its solutions even when highly concentrated by evaporation betray no jehying, and no viscosity, but continue diffluent almost to the moment of desiccation — only just before drying up do they assume a slightly syrupy consistence. When the latter point is approached the solution deposits beautiful white crystalline sheaves of tyrosin and spheres of leucin. From the constancy with which these crystal- line bodies make their appearance in pancreatic digestion it may be inferred that they constitute an essential por- tion of the final products of the transformation. The reactions of peptone are mostly of a negative character. Its solutions give no precipitation with nitric CHARACTERS OF PEPTONES 49 acid, nor with boiling, nor with ferrocyanide of potassium and acetic acid. The behaviour of peptone with alcohol is peculiar. When a strong peptone solution is dropped into absolute alcohol, the peptone is precipitated as a white sediment, but it is not truly coagulated into an insoluble modification, as all the other proteids are, for when the alcohol is removed the deposit is found to have preserved its solubility in water — even after prolonged contact with the alcohol. Solutions of peptone are pre- cipitated by those metallic salts which throw down other proteids, also by tannin when the solutions are neutral. When the solutions are rendered alkaline, the cupro- potassic test (Fehling's solution) added in very small quantity produces a rose-red coloration, whereas other proteids produce a violet tint. Physiologically, by far the most important reactions of peptone are its extreme solubility in water and its diffusibility through organic membranes. With regard to the latter point contradictory statements have been made by different investigators. Otto Funke rated the diffusibility of peptone through the membrane of the small intestine higher than that of common salt. On the other hand, Y. Wittich concluded that peptones did not pass through parchment paper more rapidly than unaltered albumen. My own observa- tions support the view that peptone is incomparably more diffusible through parchment paper than the native pro- teids. In the case of milk the effect of digestion is very marked in regard to its behaviour in the dialyser. When milk was dialysed for forty-eight hours into twice its volume of water, not a trace of proteid matter could be detected in the diffusate ; but when milk had been pre- viously digested for a couple of hours with pancreatic extract, an abundant reaction with tannin and Fehling's solution was obtained after dialysing it for eight hours. E 50 CHARACTERS OF PEPTONES My results with egg-albumen were equally striking. I prepared a solution by agitating white-of-egg with nine times its bulk of water, and straining the product through muslin. When this solution was dialysed into twice its volume of water for thirty-two hours it yielded absolutely no reaction with tannin nor with the cupro-potassic test. But when the same solution was previously digested, either with pepsin and acid — or with pancreatic extract — and then dialysed, it gave in five hours a slight but distinct reaction, both with tannin and with Fehling's solution, and in sixteen hours a most abundant reaction. The theoretical views held by physiologists in regard to the intimate nature of the transformation undergone by proteids in the presence of pepsin and trypsin are still unsettled, but recent opinions converge towards the idea that the process is, in the main, one of progressive de-duplication with hydration, similar in type to the transformation of starch by diastase. This view receives a positive support from the recent analyses of Henninger. By operating on highly purified albumen, fibrin, and casein, Henninger J succeeded in obtaining peptones in a state of great purity. An analysis of peptones so obtained indicated that they contained less carbon and nitrogen, and proportionately more hydrogen, than their original proteids. The differences were, it is true, small, but they pointed distinctly in the direction of the conclusion that there was a fixation of the elements of water by the proteid in the course of its transformation into peptone. Henninger also believes that he has succeeded in reversing the process, and in reproducing an albuminous substance from peptone by operating on it with dehy- drating agencies. He found that when fibrin-peptone 1 A. Henninger, Be la Nature et du Rule Physiologique dcs Peptones. Paris, 1878. ACTION OF PEPSIN AND TRYPSIN 51 •was heated with anhydrous acetic acid at 80° C, or was maintained for an hour at the temperature 160" to 180° C, it yielded a body which agreed closely in its reactions with syntonin. The intermediate products which are generated in the course of proteid digestion, and stand between the original proteid and the end-product peptone, are very imperfectly understood. The laborious researches of Meissner and Kiihne have shown that several such inter- mediate bodies are produced, but these have not yet been adequately isolated and defined. COMPARISON OF THE ACTION OF PEPSIN AND TRYPSIN. The action of pepsin and trypsin, although similar in the main results, is certainly not identical. There is a markedly larger production of leucin and tyrosin in tryptic than in peptic digestion. Moreover, the action of the two ferments on different proteids appears to vary both in character and in energy. Milk is much more readily digested by pancreatic extracts than by artificial gastric juice ; but in the case of egg-albumen the advan- tage lies decidedly with the gastric juice. The study of the digestion of egg-albumen by the two methods yielded some interesting results. I employed for this purpose a dilution of egg-albumen (obtained from fresh-laid eggs) with water, in the proportion of one in ten. This remains uncoagulated after being boiled in the water-bath, and furnishes a favourable medium for studying the digestion of albumen — more favourable in some respects than the chopped boiled white-of-egg usually employed. It per- mits the ferment to be at once brought into uniform and intimate contact with the particles of the albumen, thus obviating the irregularity and want of constancy which 52 ACTION OF PEPSIN AND TRYPSIN necessarily attends the operation of a solvent acting on solid pieces of variable size, which can only be attacked progressively from their surfaces. In the raw state this, solution is digested with extreme slowness by artificial gastric juice; and pancreatic extract is nearly inert on it ; but after being boiled it is attacked with energy by both the gastric and the pancreatic ferments. 1 When the boiled solution was treated, in the warm chamber,, with pepsin and hydrochloric acid, the transformation of the albumen went on rapidly and without interrup- tion to its close. In the earlier periods of the action the mixture gave a dense precipitate with nitric acid and with ferrocyanide of potassium, but this precipitation became progressively less and less pronounced, until at the end of two or three hours these reagents only pro- duced a slight haze. The albumen was now completely digested, or at least as nearly so as could be reached,, for this remnant of a reaction persisted even after a further digestion of twenty-four hours. When the same solution was treated with pancreatic- extract the progress of events was different. For an hour or two (the time varying with the quantity of extract added) there was no apparent change— but at the end of this time the mixture lost its diffluent con- dition, and became converted into a gelatinous mass, exactly resembling a thin starch jelly. By and by the gelatinous matter broke up into little masses, which floated in a transparent liquid. At this point the action seemed to be arrested. The floating masses of jelly 1 In cooking this solution it is advisable to use the water-bath, for otherwise some of the albumen coagulates and cakes on the bottom of the vessel, and the liquid froths up in an inconvenient manner. If the eggs from which the albumen has been obtained are not freshly laid some coagulation will occur on boiling the solution. The addition of a drop of ammonia obviates this. ACTION OF PEPSIN AND TRYPSIN 53 remained almost undiminished in quantity after twenty- four and even forty-eight hours. When the mixture was filtered the liquid portions came through perfectly trans- parent, and the jelly-like matter was left on the filter. The nitrate was found to be a rich and nearly pure solution of peptone — uncontaminated with any un- digested or half-digested albumen. The jelly-like matter was found to be insoluble in water, hot or cold, but it dissolved readily in acids, and was rapidly digested by pepsin and hydrochloric acid. If a large amount of pancreatic extract was used, a considerable proportion of the jelly-like matter was slowly dissolved — but the main result was always the same — the pancreatic ferment was only able to convert a part of the albumen into peptone, whereas the gastric ferment converted the entire quantity, with the exception of an insignificant residuum. In the case of milk, the relation of the two ferments is reversed. Tryptic digestion of milk is rapid, and leaves only a very slight residue — whereas peptic digestion is slow, and leaves a large residue. I have some further observations to make on the digestion of milk by trypsin, but it will be more convenient to take up the subject when I come to the use of pancreatic extract for the preparation of artificially digested food. 1 The primary function of the pepsin-acid of gastric juice is evidently to get the albuminoid matters into solution rather than to peptonise them. Bernard ranked pepsin low as a peptonising agent. He looked on gastric digestion as a hasty preparatory process, introductory to 1 Most observers have noticed the occurrence of this indigestible residuum (named Dysjwptonc by Meissner) in the artificial gastric diges- tion of protekls. I have noticed the same in the digestion of milk by pancreatic extract. 54 PEPTOGENS the more perfect intestinal digestion. This seems to me a truthful view. The rapidity with which boiled egg- albumen is dissolved by an active preparation of pepsin is very striking — but the matter in solution is not, as is well known, really digested — it is merely liquefied, and is nearly all re-precipitated by neutralisation. The later stages of digestion — those which approach or reach up to peptone — appear to be performed by pepsin very slowly and as it were with difficulty. The case is quite other- wise with trypsin. The action of trypsin on solid albuminoid masses is exceedingly slow and imperfect — but its action on liquid casein, as it exists in milk, is marked by a rapidity and completeness of which there is no parallel example in the case of pepsin. PEPTOGENS. I may here advert to a singular view advanced by Schiff in regard to the production and secretion of pepsin and trypsin. Schiff found that when an insoluble aliment such as boiled white-of-egg (or fibrin, or meat which had been deprived of its soluble portions) was introduced into the stomach of a fasting animal no pepsin was secreted, and the albumen remained undigested ; but if with the albumen certain soluble aliments were introduced into the stomach, then pepsin was produced, and diges- tion immediately began. To these substances, which had the power of pro- voking the formation and secretion of pepsin, Schiff gave the name of pcjitogens. Among the most effective peptogens were found to be solutions of dextrine, extract of meat (or soup), infusion of green peas, bread (which contains dextrine), gelatin, and peptones. On the other hand solutions of grape-sugar, soluble starch, fat-emul- sion or gum had no peptogenic effect ; and milk and PEPTOOENS 00 coffee had not much. Schiff further found that pepto- genic substances were just as effective when they were injected into the blood, or into the cellular tissue, or introduced as enemata into the rectum, as when they were introduced directly into the stomach. On the other hand when peptogens were injected into the small in- testine their influence was not observed — their effect seemed to be annulled by some action of the mesenteric glands, or by some change induced in them in their passage along the thoracic duct. On the ground of these experiments — and they were numerous and oft repeated, and gave constant and de- cisive results — he concluded that the absorption into the blood of these soluble aliments was a necessary pre- liminary of proteid digestion —that no pepsin nor trypsin was secreted unless these substances existed beforehand in the blood. The first act, according to Schiff, of gastric digestion was the absorption from the constituents of a meal of these soluble peptogens by the veins of the stomach. On this followed immediately the secretion of pepsin and the commencement of digestion proper. 1 These views and experiments of Schiff have not been allowed to pass without challenge, but they have not yet been overturned. If they should be substantiated they will give, curiously enough, a scientific sanction lo the prevailing custom of commencing dinner with soup. 1 See Legons sar la Physiologie de la Digestion, Paris, 1867, t. ii., p. 200 ct seq., where the experimental evidence on which he relies is set forth at length. 56 MILK-CURDLING FERMENT THE MILK-CURDLING FERMENT RENNIN. You all know that one of the most striking properties of gastric juice is to curdle milk. This property is utilised on a large scale in the industrial art of making cheese. Rennet, which has been used for that purpose from remote antiquity, 2 is simply an infusion of the fourth stomach of the calf in brine. The curdling of casein by rennet does not depend upon the acid of the gastric juice, for it takes place when the milk is neutral or even faintly alkaline. It has until lately been believed that this property was an inherent attribute of pepsin, but this opinion is no longer tenable. Briicke succeeded, by a process I need not particularise, in producing pepsin which had an energetic action on proteids, but which did not possess, except in the feeblest degree, the power of curdling milk. Mr. Benger also found that an extract of pig's stomach in saturated brine, while it possessed energetic action as a milk-curdler, had comparatively only feeble proteolytic powers. We must, therefore, regard the agent in gastric juice which curdles milk as a distinct substance from pepsin. In the course of my experiments on pancreatic extract, I made the unexpected observation that the pancreas also contained an agent capable of curdling milk. I found this property in the pancreas of the pig, the sheep, the calf, the ox, and the fowl. In whatever way the extract of the gland was made, whatever solvent was used, this 1 The name ' Rennin ' for the milk-clotting ferment has been pro- posed by A. S. Lea and W. L. Dickinson. Joarn. of Physiology, 1890, p. 307. 3 Cheese was in use among the ancient Hebrews. When Jesse sent David to visit his brethren in the camp of Saul, and to bring them corn and bread, he also instructed him to ' carry these ten cheeses unto the captain of their thousand.' — 1 Sam. xvii. 18. MILK-CURDLING FERMENT 57 property of curdling milk was present in it ; but the brine extract exceeded all others in curdling capacity. If a few drops of extract of pancreas be added to some warm milk in a test-tube, the milk becomes a solid ■coagulum in a few minutes. Some minutes later the whey begins to separate from the curd. In short, the action resembles exactly that of calf's rennet ; and, so far as I know, you could make cheese with pancreatic rennet as perfectly as you can with gastric rennet. There is, however, not an absolute identity of the two agents. I said just now that gastric rennet produced curdling in neutral and even in faintly alkaline milk ; but if the alkali exceed a very small proportion, ordinary rennet •does not curdle milk. I found that an alkalescence exceeding that produced by one grain of bicarbonate of soda to an ounce of milk altogether prevented the milk being curdled by gastric rennet. But this is not so with pancreatic rennet. You may add two, three, or four grains of bicarbonate of soda to each ounce of milk, and still the pancreatic rennet will induce curdling with undiminished energy. Milk is likewise curdled by pan- •creatic extract when quite neutral, and even when very faintly acid. Indeed, it appeared to me that a very faintly acid milk curdled more actively with pancreatic extract than neutral milk, but not so actively as alkaline milk. That the curdling agent of the stomach and pancreas is a true ferment, and not some inorganic chemical agent, seems to be proved by the fact that boiling or even heat- ing to 160° F. (70° C.) instantly destroys its power. I found, moreover, that, like other soluble ferments, it is precipitated, but not truly coagulated, by alcohol — for it recovers its solubility and activity when the alcohol is removed, even after a contact of several weeks. 08 MILK-CURDLING FERMENT The curdling ferment of the pancreas is a distinct body from trypsin, as the following experiments show. (1) Some brine extract of pancreas (which was known to possess strong proteolytic energy) was acidulated with hydrochloric acid in the proportion of 1 per 1,000, and then placed in the warm chamber at a temperature of 104° F. (40° C.) for a period of three hours. It was then carefully neutralised with bicarbonate of soda. When thus treated, the extract was found to have lost its proteolytic power, but its curdling action on milk was almost as energetic as ever. (2) A portion of the same brine extract of pancreas was filtered under vacuum pressure through porous earthenware. The filtered product was found to possess an undiminished faculty of curdling milk, but it had almost no power of dissolving the curds. The curdling ferment had evidently traversed the earthenware freely, but only traces of trypsin had passed through. What is the real function of the curdling ferment ? Seeing its striking reaction with milk, one's first idea is that it must have something to do with the digestion of casein. But a little consideration shows that this idea is altogether improbable. Although all mammalia start life on a milk diet, milk does not form a part of the normal diet of any adult creature except man. Nor can its universal presence in the mammalian digestive organs be regarded as a vestigial phenomenon — a 'memory ' of the suckling phase of their existence — for the same curdling property is found in the stomach and pancreas of the fowl which never at any period of its life fed on milk. Moreover, it may be doubted whether the ferment in question is the actual agent which curdles milk on its passage into the stomach — for the acid of the gastric juice, which also curdles milk, would probably be beforehand EMULSIVE FERMENT — DIGESTION <>F FATS 59 with it, inasmuch as its action is a good deal more prompt than that of the ferment. In the pancreatic digestion of milk, the occurrence of curdling has appeared to me to be a distinct hindrance to the process. Has this ferment any true digestive functions'? I think this is quite open to doubt. Its action on milk is apparently akin to that of the fibrin-ferment on blood — and it may likewise have some kindred purpose — but what that purpose may be I am unable to conjecture. EMULSIVE FERMENT — DIGESTION OF FATS. The digestive change undergone by fatty matters in the small intestine consists mainly in their reduction into a state of emulsion, or division into infinitely minute particles. In addition to this purely physical change, a small portion undergoes a chemical change whereby the glycerine and fatty acids are dissociated. The fatty acids thus liberated then combine with the alkaline bases of the bile and pancreatic juice, and form soaps. The main or principal change is undoubtedly an emulsi- fying process, and nearly all the fat taken up by the lacteals is simply in a state of emulsion, and not of saponification. It is however quite certain that both these processes do take place in the small intestine, though in very unequal degrees. The only question in connection with the digestion of fat which I propose to examine is :— "Whether these changes are produced by the operation of a soluble ferment, or by some other and different agencies. In his latest utterances on this subject, Bernard ' insisted that the digestion of fat, like the digestion of starch and proteids, consisted in the 1 Claude Bernard, Lccojis sur les Ph&nomAnes de la Vic, t. ii., p. 34G. Paris, 1879. 60 EMULSIVE FERMENT DIGESTION OF FATS action of a soluble ferment, which he named Ferment Emulsif. This ferment, he alleged, first emulsified and then saponified fats. In the intestine the change scarcely went beyond emulsion — in this condition fat was found in the contents of the lacteals. Saponification took place almost exclusively further on, and later in the blood. It is certainly established that the pancreatic juice exercises a marked influence on the digestion of fats, and it is in the pancreas, according to Bernard, that the emul- sive ferment is to be found. Bernard demonstrated that healthy pancreatic juice has quite a special faculty of emulsifying fats. Pancreatic tissue has also the same property. If a portion of fresh pancreas be rubbed up with fatty matter and water, you get an emulsion which is quite persistent. I have not had an opportunity of examining the behaviour of pancreatic juice with fatty matter, and cannot therefore speak of its properties : but it is singular if, as alleged, the effect of pancreatic juice and pancreatic tissue on fat be due to the pre- sence of a soluble ferment, that the extracts of pancreas possess none of the same power. I have made extracts of pancreas in various ways — with simple water, with chloroform-water, with dilute spirit, with solutions of boracic acid, of borax, and of both combined, with glycerine and water, with brine, and with solution of salicylic acid, and of salic}date of soda ; and yet I could not satisfy myself that any of these extracts possessed any special power of emulsifying fats, nor of liberating the fatty acids and inducing saponification. Paschutin l states that the emulsive ferment of the pancreas can be extracted by a solution of bicarbonate of soda. An extract of pancreas made by myself with a two per cent, solution of bicarbonate of soda was indeed found to have 1 Hoppe-Seyler, Physiolugischc Chemie, p. 257. Berlin, 1878 EMULSIVE FERMENT DIGESTION OF FATS fil a very marked emulsifying power, but it had the sam< power, even in an enhanced degree, after being boiled, which showed that its emulsifying properties could not depend on the presence of a soluble ferment. I was equally unsuccessful in my attempts to verify the alleged power of extracts of pancreas, and of crushed pancreatic tissue, to liberate the fatty acids. When fresh pancreas, finely triturated with sand, was digested with milk in the warm chamber, I could not obtain satisfactorv evidence of the development of free acid from the decom- position of the fat of the milk by a soluble ferment. The pancreas itself yields a slightly acid solution when infused in water, and a mixture of milk and pancreatic tissue always showed a slight acid reaction ; but when this primary acidity was neutralised, no further production of acid took place until such a time had elapsed as was sufficient to permit the development of organised ferments and the origination of the lactic fermentation. If the development of organised ferments was prevented by the addition of antiseptics — such as chloroform or a combina- tion of boracic acid and borax — a mixture of milk and crushed pancreas remained neutral for several days. The same results followed when I operated on emulsions made with crushed pancreas and lard or olive oil. In my numerous observations on the digestion of milk with various pancreatic extracts, I never could detect the pro- duction of an acid reaction, unless organised ferments were permitted to intervene. I obtained similar negative results with almond emul- sion. Bernard attributed the formation of an emulsion when almonds (or other oily seeds) were rubbed up with water to the presence in the seeds of a soluble ferment. But I found, to my surprise, that almonds which had been boiled for seven hours still produced a perfect 62 EMULSIVE FERMENT DIGESTION OF FATS emulsion. As all known soluble ferments are destroyed by boiling, this result seems irreconcilable with Bernard's view. I also found that almond emulsion kept in the warm chamber for six or eight hours at a temperature of 100° F. (88° C.) showed not the slightest evidence of an increase of its original faintly acid reaction. It ap- peared to be more probable that the fatty matter in the almond existed in the seed in the condition of a solid emulsion, and that the formation of a fluid emulsion by trituration with water was due simply to the liberation of the minutely divided oil particles, rather than to the intervention of a soluble ferment. It is with considerable hesitation that I venture to place myself even in apparent contradiction with so great an observer as was Claude Bernard ; and I by no means pretend that these observations traverse the main con- clusions for which he contended as to the digestive trans- formations of fat in plants and animals. The views which Bernard developed on the digestive process are based on inductions so wide, and observations so multi- plied, that I feel satisfied that their substantial accuracy will be ultimately established in regard to fat, as they have already been established in regard to starch and cane-sugar. Some observations made by Briicke promise to throw a fresh light on the digestion of fat. Briicke found that oils and fats which contained an admixture of free fatty acids — in other words, which were more or less rancid — were emulsified by a slight agitation with a weak solution of carbonate of soda. J. Gad extended these observations, and showed that even simple contact of a rancid oil with the alkaline solution was sufficient to effect a mechanical division of the oily matter. I have repeated these observations, and the results are certainly remarkable. EMULSIVE FERMENT — DIGESTION OF FATS 63 The different behaviour of two specimens of the same oil, one perfectly neutral and the other containing a little free fatty acid, is exceedingly striking. I have here before me two specimens of cod-liver oil — one of them is a fine and pure pale oil, such as is usually dispensed by the better class of chemists ; the other is the brown oil sent out under the name of De Jongh. I put a few drops of each of these into these two beakers, and pour on them some of this solution, which contains two per cent of bicarbonate of soda. The pale oil, you see, is not in the least emulsified ; it rises to the top of the water in large clear globules ; the brown oil, on the con- trary, yields at once a milky emulsion. The pale oil is a neutral oil, and yields no acid to water when agitated with it — in other words, it is quite free from rancidity; but the brown oil, when treated in the same way, causes the water with which it is shaken to redden litmus paper. I was surprised to find that olive oil (salad oil), which appeared quite sweet, and had not the slightest taste or smell of rancidity, gave a milky emulsion with the soda solution. This oil did not yield any acid reaction to water when agitated therewith. Nevertheless it evidently contained a little free fatty acid (probably oleic acid, which is insoluble in water, and therefore does not acidif} 7 water shaken up with it), for when a portion of this oil was washed with a strong solution of carbonate of soda, and then allowed to separate, the oil thus freed from acid no longer gave an emulsion with the weak soda solution. It would appear that an admixture of only a very small proportion of free fatty acid is sufficient to induce emulsification — a quantity so small as not to cause any appreciable rancidity to the senses of smell or taste. This specimen of almond oil is to all appear- ance perfectly sweet, but it communicates a rather sharp 64 EMULSIVE FERMENT DIGESTION OF FATS acid reaction to water shaken up with it, and it gives, as you see, an instantaneous and perfect emulsion with the soda solution. The bearing of these observations on the digestion of fat is plain. When the contents of the stomach pass the pylorus they encounter the bile and pancreatic juice, which are alkaline, from the presence in them of carbo- nate of soda. So that the fatty ingredients of the chyme, if they only contain a small admixture of free fatty acids, are at once placed in favourable circumstances for the production of an emulsion without the help of any soluble ferment, the mere agitation of the contents of the bowel by the peristaltic action being sufficient to effect the purpose. This view of the matter renders it necessary that fresh inquiries should be made into the effect of gastric digestion on fats. It has hitherto been supposed that fatty and oily substances undergo no change in the stomach, but it is quite possible that something may have been overlooked. It was noted by Eichet in the patient with a gastric fistula that the fatty matters were detained a long time in the stomach, and that they only passed through the pylorus with the last portions of the meal. It is also a familiar experience to most dyspeptics that rancid eructations are a frequent occurrence in the later stages of gastric digestion. If it should turn out that among the complex operations taking place in the stomach there occurred some slight decomposition of the neutral fats, and a liberation of a small quantity of free fatty acid, such a result would supply the necessary condition for the emulsification of the neutral fats in the duodenum. In speculating on this subject it is difficult to shut one's eye to the possibility of the intervention of formed or organised ferments in the digestive process. It is well known that fatty acids are liberated in the de- EMULSIVE FERMENT DIGESTION OF FATS 65 composition of neutral fats by bacteroid ferments (zymo- phytes), and the presence of ferments of this class in the living stomach has been so repeatedly observed that it may well give rise to the suspicion that they are a nor- mal ingredient of the gastric mucus, and have a normal function to perform in the digestion of some portions of our food. It is not, however, desirable to push specula- tions of this kind in advance of observed facts, and I only mention them as hints for further inquiry in regard to the digestion of fat. 66 III. ON THE ESTIMATION OF THE AMYLOLYTIC AND PROTEOLYTIC ACTIVITY OF PANCEEATIC EXTRACTS. (From the Proceedings of the Royal Society for 1881.) Summary : — Preliminary observations — Diastasimctry— Standard starch mucilage — Effect of quantity and time — Effect of temperature— Mode of proceeding— Mode of calculating and expressing the diastasic value — Diastasic value of the pancreas of the pig, ox, and sheep — Trypsimetry— Metacasein reaction — Effect of quantity and time — Effect of temperature — Mode of proceeding — Mode of calculating and expressing the tryptic value — Comparison of the enzymic values of the pancreas of the pig, ox, and sheep. The degree of activity possessed by preparations of the soluble ferments cannot be ascertained by direct weighing and measuring. The agents to which they owe their power have in no case been obtained in a state of isolation and purity. These agents are known to be indissolubly united with some form of albuminoid matter, and we are constrained to speak of them as if they really were albuminoid bodies. But their mode of action suggests an affinity with the imponderable forces, and points to the conclusion that the relation which these agents bear to their organic substratum is analogous, or at least comparable, to the relation subsisting between a mass of protoplasm and the vital endowments with which it stands possessed. The activity of preparations of the soluble ferments can only be gauged by their capacity for work. But in- NATURE OF SOLUBLE FERMENTS 67 asmuch as there is in them no power of growth and multiplication, the amount of energy with which they are endowed is strictly limited, 1 so that when the capacity for work existing in a given liquid or solid preparation of one of these ferments has been ascertained, and has been put into due expression, the amount of energy in a certain quantity of the preparation can be counted in grams or cubic centimeters like that of any other chemical agent. The term ferment has, up to this time, been applied in common to two groups of agents, which, although nearly allied both in their origin and in their mode of action, belong to essentially distinct categories. The organised or formed ferments, of which yeast is the type, are independent organisms with powers of growth and reproduction ; and the transformations which constitute their special characteristics as ferments are inseparably associated with the nutritive operations of these orga- nisms. The ferment-power cannot be separated from the ferment-organism by any method of nitration, nor by any solvent. The soluble-ferments, on the other hand, pass freely into solution in water — their action is dissociated from the life of the gland-cells which pro- duced them — and they are wholly devoid of the power of growth and reproduction. Kiihne has proposed to distinguish the group of soluble ferments by the name of ' enzyms.' I would suggest the desirability of adopting this term into Eng- lish, with a slight change of orthography, as ' enzymes,' and also of coining from this root the cognate words which are requisite for clear and concise description. The action of an enzyme may be designated enzymosis, and the nature of the action may be spoken of as enzymic. 1 For proof of this sec p. 31, et seq. 68 DIASTASIMETRY In the present paper I shall venture to employ these terms in the sense here indicated. The pancreas is known to be the source of two fer- ments or enzymes, of capital importance in the digestion of food, namely, an amylolytic enzyme, pancreatic diastase, and a proteolytic enzyme, trypsin. It is also known that the pancreas takes an important share in the digestion of fats, but it is doubtful whether its power in this re- spect is due to an enzyme or to an agency of a different character. The present paper concerns itself solely with the amylolytic and the proteolytic functions of the pan- creas. ESTIMATION OF THE AMYLOLYTIC ACTIVITY OF PANCREATIC EXTEACTS — DIASTASIMETRY. Probably the most accurate mode of estimating the activity of a diastasic solution is to ascertain the amount of sugar produced when a given quantity of the solution is made to act on a given volume of a standard starch mucilage, for a fixed time and at a fixed temperature. This method has already been recognised by Mr. H. T. Brown and Mr. J. Heron in their paper on the transfor- mation of starch by malt infusions. 1 Kjeldahl has de- veloped this method to a further point, and has used it to measure the comparative activity of malt infusions and of saliva. 2 In the method about to be described, a simpler and speedier proceeding was employed, and the results were so brought out as to indicate absolute as well as com- parative values. In principle the method consists in ascertaining the quantity of starch mucilage of known 1 Journal of the Chemical Society, September, 1879. ■ Compte Rendu des Travaux du Laboratoire de Carlsberg, 1879r p. 129. STANDARD STARCH MUCILAGE 69 strength which can be transformed, by a unit measure of a diastasic solution, to the point at which it ceases to give a colour reaction with iodine, in a unit of time, and at a fixed temperature. When starch mucilage is treated with extract of pancreas, or with any other diastasic solution, the mix- ture progressively loses its property of giving a colour reaction with iodine. First the blue reaction of un- altered starch passes away, then the brown and yellow reactions of dextrine successively disappear. It is not difficult to fix, with a fair amount of accuracy, the vanishing point of this reaction. This point may, for our present purpose, be called the achromic point. The extract of pancreas employed in these observa- tions was prepared by digesting fresh pancreas, freed from fat and chopped up, in four times its weight of dilute alcohol, containing 25 per cent, of rectified spirit (sp. gr. 0-838). The digestion was continued for four or five days, with occasional agitation. The mixture was then filtered through paper. Filtration is much facilitated by the addition to the solvent of 0*02 per cent, of acetic acid (containing 28 per cent, dry acetic acid). The standard starch mucilage was made from potato starch. Owing to the large size of its granules, potato starch is easily obtained in a state of great purity, by re- peated levigation with water, and afterwards drying the product at 40 3 C. 1 The mucilage was made of the strength of 1 per cent., and in the following manner: 5 grammes of starch were well stirred up into a thin mud with 30 cubic centimeters of water, and then poured in a slender stream into 470 cubic centimeters of briskly boiling water. The 1 The so-called pure starch of the shops is worthless for the purposes of diastasimetry. A supply of pure potato starch may be obtained from Mottershead & Co., chemists, Manchester. 70 EFFECT OF QUANTITY AND TIME mixture was stirred and allowed to boil for a few seconds. Thus prepared the mucilage is perfectly smooth and uniform, and is so diffluent that it can be measured out like an ordinary liquid. This is known in the present paper as the standard starch mucilage. It should be used fresh, for it is apt to change in a few days, and to lose its opalescent appearance, and slight mucilaginous con- sistency. When thus changed it is found to contain sugar. So long as it maintains its slight opalescence and slight mucilaginous character it is fit for use. The iodine solution used in the testing was composed of 1 part of the liquor iodi of the British Pharmacopoeia, diluted with 200 parts of water. In determining the data on which is based the method of diastasimetry here proposed, it was necessary to ascertain the mutual relations in regard to the anxio- lytic process of three factors, namely, the quantity of pancreatic extract set in action, the time required to reach the achromic point, and the temperature at which the enzymosis was carried on. Quantity and Time. — The amount of arnylolytic work done by a given sample of pancreatic extract is strictly proportional to the quantity of it set in action — in other words, the amount of the standard starch mucilage which can be changed to the achromic point in a given time and at a given temperature varies directly as the quantity of the extract employed. This law of propor- tionality may probably be regarded as fundamentally applicable to the action of all enzymes, which, having no power of growth or multiplication, conform in this respect to the common law which governs the action of ordinary chemical agents. The rule is, however, liable to interference if the products of the enzymosis accumu- late in the solution to such a degree as to hamper the EFFECT OF QUANTITY AND TIME 71 action. In the conditions observed in the following experiments this interefrence did not arise. The starch mucilage operated on was exceedingly dilute, and con- sequently the sugar and dextrines produced in the trans- formation never accumulated to such a degree as to check the enzymosis. In the action of all enzymes the element of time is an essentially important factor. An enzyme liberates its energy gradually, in successive portions, and it takes a comparatively long time to exhaust itself completely. I found that pancreatic diastase, in the presence of excess of starch mucilage, took not less than forty-eight hours to completely exhaust itself at the temperature of 40° C. {see p. 33). The fundamental rule which governs the mutual relations of quantity and time in the action of an en- zyme is that of inverse proportion. That is to say, double the quantity of an enzyme will do a given amount of work in half the time, and that half the quantity will require double the time. This rule, however, is ap- parently controlled by another rule, namely, that an enzyme liberates its energy at a progressively retarded rate If we conceive an enzyme as a body in a state of tension, charged with a certain amount of dormant energy, we can further conceive that in action it will discharge this energy gradually, and also at a rate which is con- tinually diminishing. Such a conception will, I think, enable us to understand some features in the action of diastase and trypsin which are otherwise difficult to explain. In regard to the action of pancreatic extract on starch mucilage, the rule of inverse proportion between quantity and time was found to hold good within con- siderable limits, as the following experiments show : — 72 EFFECT OF QUANTITY AND TIME Table I. — Experiments showing the inverse proportion between quantity and time in the action of Pancreatic Extract on Starch Mticilage. The quantity of the standard mucilage acted on in each experiment was 10 c.c. diluted with water up to 100 c.c. Temperature 15° C. The ' calcu- lated ' time in the third column was obtained by taking the middle obser- vation in each set as a standard of comparison. Time in which the Achromic Point was reached Quantity of Pancreatic Extract employed Found Calculated ( 0-02 c.c. 34 minutes 36 minutes 0-04 „ 18 18 „ I. . . 0-08 „ 9 9 0-10 „ 7 7| „ 1 0-20 „ 3 3* „ 1 0-4 „ 4f » 5 II. . •I 0-2 „ 10 10 0-05 „ 40 40 „ In both sets of observations the inverse time-rate is seen to come out true with almost mathematical accuracy. When, however, a relatively small quantity of pan- creatic extract was employed, and the time required to reach the achromic point was, in consequence, con- siderably lengthened, it was found that the advent of the achromic point was postponed beyond the term indi- cated by the rule. If the period occupied in reaching the achromic point fell within the compass of an hour, and the temperature was low, as in the observations above recorded, the inverse time-rate came out true, but when the period of action extended to several hours and the temperature stood higher, the departure from the rule was undoubted. The annexed table gives the results of experiments made with a view of testing this point. EFFECT OF TEMPERATURE 73 Table II. — Experiments showing the postponement of the Achromic Point when the action is protracted. The quantity of standard mucilage acted on in each case was 10 c.c diluted with water up to 100 c.c. Temperature 40° C. The 'calculated' time in the third column was obtained by taking the first observation, which was several times repeated, as a standard of comparison. Quantity of Pancreatic Extract employed Time in which the Achromic Point was reached Found Calculated 005 c.c. 0-005 „ 0-004 „ 0-002 „ 0-0005 „ 10 minutes 115 140 300 1,380 100 minutes 125 „ 250 1,000 It need scarcely be said that when the enzymosis is very slow it is not possible to fix the vanishing point of the colour reaction with the same precision as when the action is more rapid and the change more abrupt. Not- withstanding this source of error, I think the conclusion indicated by these experiments may be relied on. The postponement of the achromic point shown in the table may be explained, as has been suggested, on the as- sumption that the enzyme liberates its energy at a continually retarded rate. In the case of trypsin, we shall see evidence of a precisely parallel phenomenon. Temperature. — The action of pancreatic diastase on starch mucilage was found to increase in energy (or speed) from zero up to 30° C. From this point to 45° the rate of action continued steady, showing a range or platform of indifferent temperature extending from 30° to 45°. Above 45° the action became less and less energetic, and finally ceased between 65° and 70°. The following table exhibits the results obtained at various temperatures between 5° and 70° C. 74 MODE OF PROCEEDING Table III. — Showing the effects of Temperature on the action of Pancreatic Diastase. The amount of the standard mucilage acted on in each experiment was 10 c.c. diluted with water up to 100 c.c. The quantity of pancreatic ex- tract employed in each experiment was 01 c.c. Temperature Achromic point reached in 3—5° C 36 minutes. 10° 15° 20° 25° 30° 40° 45° 50° 55° 60° 65° 70° 18 12 8 6 „ 5 5 ,, 5 7 10 40 Very slow action. No action. These results, thrown into the form of a curve, are shown in the subjoined diagram. The ordinates indi- cate the diastasic value, or D, as calculated by a method to be presently explained ; the abscissa? represent the temperatures. Curve illustrating the effect of temperature on the action of pancreatic diastase. Mode of proceeding. — In testing the activity of a sample of pancreatic extract, it was found on the whole more convenient to operate on a fixed quantity of the standard mucilage, and to vary the quantity of extract MODE OF PROCEEDING 7") added to it, than to proceed contrariwise. The bulk of liquid operated on was thus kept constant. The ordinary proceeding was as follows : 10 cubic centimeters of the standard mucilage were mixed in a beaker with 90 cubic centimeters of water. The mixture was then warmed to 40° C, or at least to some point well within the range of indifferent temperature extending from 30° to 45° C. This was done in order to eliminate the disturbing influence of temperature. The next step was to add the deter- mined quantity of the extract to .be tested to the diluted mucilage, and to note the exact time. Then, at short intervals, a drop of the enzymosing liquid was placed on a white slab, or plate, with a drop of the iodine solution. The time and result of each testing was noted. When the achromic point was reached the time was marked, and the interval from the commencement of the experi- ment was computed. If at the end of three minutes the mixture still gave the blue reaction of unaltered starch, a new experiment was made, using two, three, or four times the quantity of extract. If, on the other hand, the achromic point was reached in less than two minutes, a new experiment was made, using a smaller quantity of the extract. Two or three experiments generally suf- ficed to determine the quantity of extract required to bring the achromic point within a period ranging from two to ten minutes. A final control experiment enabled the operator to fix the achromic point somewhere between four and six minutes. The accuracy of the method depends chiefly on the sharpness and precision with which the occurrence of the achromic point can be determined. If it occur earlier than two minutes, the transition is too rapid for exact observation and record. On the other hand, if it occur later than fifteen or twenty minutes, the transition is too gradual for precise 76 EXPRESSING THE DIASTASIC VALUE limitation. The most satisfactory results are obtained when the achromic point falls between four and six minutes. The following example will serve as an illustration of the way in which the experiments were carried out, noted, and expressed : — Table IV. — 10 ex. standard Starch Mucilage + 90 ex. water + 0-1 ex. Pancreatic Extract — at 40° C. Time Reaction with Iodine 10.30 A.M. . Commencement of experiment 10.31 „ Blue. 10.32 „ Violet. 10.33 „ Brown. 10.34 „ Yellowish -brown. 10.35 „ Pale yellow. 10.36 „ No reaction — achromic point. 6 minutes. Achromic point reached in 6 minutes. The result of the experiment was expressed in the first instance as follows : 0*1 cubic centimeter pancrea- tic extract + 10 cubic centimeters standard mucilage = 6 minutes at 40° C. From this somewhat incongruous expression it is, however, easy to extract by a simple formula, in the manner to be now explained, a correct and convenient ex- pression for the diastasic value of any amylolytic solution. MODE OF CALCULATING AND EXPRESSING THE DIASTASIC VALUE. The principle of the method consists, as already stated, in ascertaining the amount of starch mucilage of known strength which can be transformed by a unit measure of the diastasic solution to the point at which EXPRESSING THE DIASTASIC VALUE 77 it ceases to give a colour reaction with iodine, in a unit of time and at a given temperature. In reducing this principle to a definite formula it was necessary to choose arbitrarily a unit of measure of the diastasic solution and a unit of time. The unit of measure fixed on was 1 cubic centimeter, and the unit of time five minutes. These selections seemed, on the whole, the best adapted for furnishing a convenient scale. On these bases the formula took the following form : the diastasic value of any solution — or, D — is expressed by the number of cubic centimeters of the standard starch mucilage which can be transformed to the achromic point by 1 cubic centimeter of the solution to be tested in a period of five minutes at a given temperature. In the process of testing, the quantity of the standard mucilage was made constant, namely 10 cubic centi- meters, and the quantity of pancreatic extract and the time were made variable. In order to get the value of D the results must be so transformed as to make the quantity of extract and the time constant, and the quantity of the standard mucilage variable. This is accomplished by increasing or reducing the quantity of pancreatic extract employed to 1 cubic centimeter, and increasing or diminishing the standard mucilage in the same proportion. The product thus obtained is again in- creased or reduced in the same proportion as is requisite to increase or reduce the time found to five minutes. Taking the example above given (Table IV.), the value of D is obtained by the following formula : Let p signify the quantity of pancreatic extract employed, and m the number of minutes found requisite to reach the achromic point, then : — 10 5 n — x = D, p in 78 DIASTASIC VALUE OF PANCREAS and in the above example — D = 10 ^x 5 n = 83at40°C. 0-1 6 The value of D, as already explained, signifies the number of cubic centimeters of the standard starch mucilage which can be changed to the achromic point by 1 cubic centimeter of the diastasic solution in five minutes at a given temperature. As the standard mucilage contains 1 per cent, of dry starch, the value of D divided by 100 gives us the same value in terms of dry starch, and the result of the above experiment may be read as follows : — D = 83 = 0-83 grm. of dry starch. This method of diastasimetry is equally applicable to saliva and malt-diastase. It may also be applied to the estimation of the diastasic agent which is present in urine, and presumably to all diastasic solutions. In the case of solid preparations containing diastase — like malt or glandular tissue — a solution in known proportions must first be prepared ; and from the ascertained activity of such solution the proportionate activity of the solid substance can be easily calculated. I may here mention some of the results which this method has already yielded. Pancreatic Tissue. — The pancreatic tissue of the pig (obtained from animals killed for the market in the fasting state) yielded an extract which, when made on the large scale, possessed a mean diastasic value of 100. This extract is sent out by Mr. Benger, of the firm of Mottershead & Co., chemists, Manchester, under the name of 'Liquor Pancreaticus,' and is made in the pro- portion of one part of pancreatic tissue to four of solvent (water containing 25 per cent, rectified spirit). This DIASTASIC VALUE OF SALIVA AND MALT 79 value indicates that 1 grin, of the moist pancreas of the pig is capable of transforming 4 grins, of dry starch to the point at which it no longer gives a colour reaction with iodine, in five minutes, at a temperature of 40° C. The pancreatic tissue of the ox and sheep yielded an extract (made in the same proportions) which was of far inferior activity. The ox extract had a diastasic value of about 11 and that of the sheep of about 12. These numbers indicate that in point of diastasic activity the pancreas of the pig has ten times the value of the pancreas of the ox and sheep. This extraordinary difference is probably linked with the diversity of their food. The pig is fed largely upon potatoes and meal, which are rich in starch ; the ox and sheep, on the other hand, feed on grass, which is poor in starch. "We shall presently find that there is no such difference in regard to tryptic activity in the pancreas of these animals. Human Saliva. — Filtered saliva was found to have a diastasic value varying from 10 to 17 at 40° C. Its action was influenced by temperature exactly in the same manner as that of pancreatic extract. Saliva increased in energy up to about 30° C, and continued steady from this point to about 45° ; above this point its activity de- clined, and was finally extinguished between 65- and 70°. Malt Diastase. — Infusions of malt made in the pro- portion of one part of crushed malt to four parts of water, exhibited a diastasic value of 4 to 5 at 40 : C. But malt diastase did not attain its maximum activity at this temperature. It continued to increase in energy up to about 60° C, when it showed a diastasic value of 10. Above 60° the action diminished in energy, but did not come to a full stop until the temperature approached 80° C. Human Urine. — Several specimens of healthy urine 80 TEYPSIMETRY were tested by this method. They showed a diastasic value varying from 0-03 to 0'13 at 40° C. The effect of temperature thereon was not examined. ESTIMATION OF THE PKOTEOLYTIC ACTIVITY OF PANCREATIC EXTRACTS — TRYPSIMETRY. The writer had found in previous inquiries that when milk is subjected to digestion with pancreatic extract, a striking change takes place in it at an early stage of the process — the milk acquires the property of curdling when boiled. The onset of this reaction occurs at an earlier or at a later period according to the activity of the extract and the quantity of it employed ; and it is possible to fix the time of its advent with con- siderable accuracy— sufficient accuracy to serve as the basis of a method of measuring the proteolytic activity of pancreatic extracts. The reaction in question depends on the production, as a first step in the pancreatic digestion of casein, of a modified form of that body which I have named oneta- casein. This substance resembles casein in being curdled by acetic acid in the cold ; but it differs from casein in being also curdled by simple boiling. These two reac- tions together distinguish metacasein from other proteid bodies. The property of curdling when boiled, which may be called the metacasein reaction, continues observable in milk undergoing tryptic digestion until near the termi- nation of the process ; it then disappears semewhat abruptly, and the milk, when boiled, remains fluid just as it did at first. We may, therefore, speak of the onset iwint of the metacasein reaction, and of the vanishing point of the METACASEIN REACTION 81 metacasein reaction. These two points mark respec- tively the initial and the terminal limits of the principal phase in the digestion of milk by pancreatic extract. Before the onset point of the reaction — that is, dis- tinct and undoubted curdling on boiling — is actually reached, its approach is indicated by an appearance of soiling of the sides of the test-tube in which the milk has been boiled. This appearance is due to incipient coagulation, which presently developes into pronounced curdling, and is a useful sign in testing to indicate the coming on of the metacasein reaction. The following typical experiment may serve to give the reader a clear notion of the succession of events — so far as they concern us here — which occur when milk is submitted to digestion with pancreatic extract. Table V. — 4. c.c. Pancreatic Extract added to 50 ex. Milk diluted with water to 100 c.c. Temperature, 18 c C. Reaction on Boiling No change. Slight soiling of the sides of the test-tube. More soiling. Distinct curdling — onset point of the metacasein reaction. More pronounced curdling. Pronounced curdling. Diminished curdling. Slight curdling. Xo change; vanishing point of the meta- casein reaction. The length of time during which the successive steps of the transformation may continue observable depends on the energy of the action ; and this, in its turn, depends on the activity of the preparation and the quantity of it added to the milk; it is also greatly in- fluenced by temperature. By using an excess of an active pancreatic extract, and witli a favourable tempera- Time 2 minutes . 3 „ 4 ,, 5 „ 6 to 80 ii 90 „ 95 „ 100 » 82 MILK AS A TEST FLUID ture, all the steps of the process may be crowded almost into an instant of time ; with converse conditions the action may linger on for many hours. Although milk is a secretion of somewhat variable composition, the oscillations which it exhibits, when it is the product of a dairy, and is not intentionally adulte- rated, do not materially vitiate it for the purposes of a test fluid such as is here required. The milk delivered at my house presented very little variation. It had a density of 1030— seldom varying more than a degree from this point — and the results obtained with the milk of different days showed a remarkable uniformity. Milk from different dairies, and at different seasons of the year, would no doubt present greater irregularities. Milk should, however, be used fresh, for if it have become slightly acid, as it is apt to do in keeping, the results obtained are untrustworthy. If milk be diluted with water the occurrence of the metacasein reaction is postponed ; and the degree of postponement varies with the degree of dilution. For example, if 50 cubic centimeters of pure milk are changed to the onset point of the metacasein reaction in three minutes, the same quantity of milk diluted with an equal volume of water will take six minutes to reach the same point — other conditions being equal. There are, however, several advantages in using diluted milk instead of pure milk as the experimental fluid. The in- equalities of the milk are thereby minimised. The ' strike ' of the reaction is more sharply defined, and the required quantity of pancreatic extract can be included in the water of dilution. This last is an important advantage, because if the extract to be tested is feeble, a considerable quantity of it requires to be added, and this, if pure milk were employed, would seriously alter EFFECT OF QUANTITY AND TIME 83 the degree of dilution, and thereby vitiate the results. In the following experiments, milk diluted with an equal bulk of water was invariably employed : and if the quantity of pancreatic extract to be added exceeded 3 .cubic centimeters for every 50 cubic centimeters of milk, this was always included in the water of dilution. In principle the method of trypsimetry here pro- posed consists in ascertaining how many cubic centi- meters of milk can be changed to the onset point of the metacasein reaction, in five minutes, by 1 cubic centi- meter of the extract to be tested, at a given temperature. In settling the data on which the method is based, it was necessary, as in the case of diastase, to. determine the relations of tryptic action to quantity, time, and temperature. Quantity and Time. — The rule of inverse relations between quantity and time which was found to be valid within a wide range in the case of diastase and starch, Ts~only reliable in the case of trypsin and milk within narrow limits. "When the time of action exceeds 8 or 10 minutes the advent of the metacasein reaction is post- poned beyond the term indicated by the rule of inverse proportion, and this postponement increases as the time of action is lengthened. The following two sets of observations may be taken as samples of the results obtained by experiment in regard to this point. If the vanishing point of the metacasein reaction was taken as the test of comparison, the results approxi- mated a little more nearly to the requirements of the rule of inverse proportion than when the onset point was taken, especially at low temperatures; but still the evidence in either case pointed in the same direc- tion, and indicated that trypsin, like diastase, exhausts itself in action at a progressively retarded rate. 84 EFFECT OF TEMPERATURE Table VI. — Showing undue postponement of the Metacasein Reaction when the Enzymosis is slow. The quantity of milk acted on in each experiment was 50 c.c. diluted with water up to 100 c.c. The ' calculated ' time in the third column was obtained by taking the first observation in each set as the standard of comparison. Quantity of Pancreatic Extract added Onset Point of the Metacasein Reaction Found Calculated Set I.— Temperature 40° C. 1-0 c.c. 0-8 „ 0-6 „ 0-4 „ 0-2 „ 3 minutes 4 9 30 3f minutes ' 2 » 15 Set II.— Temperature 16° C. 4-0 c.c. 2-0 „ 1-0 „ 0-5 „ 0-25 „ 6 minutes 16 39 105 280 12 minutes 24 48 96 From the numerous experiments which were per- formed with a view of elucidating this point, I arrived at the conclusion that when the onset point of the metacasein reaction fell between 3 and 6 minutes the inverse time- rate gave a reliable basis of calculation, but not beyond these limits. Temperature. — Tryptic enzymosis is exceedingly sensitive to temperature. The action of trypsin on milk increases in energy from zero to 60° C. Above this point there is a rapid fall, and the action is finally arrested between 75° and 80° C. There is not, a,s with diastase, any range or platform of indifferent temperature. The following table exhibits the degrees of activity from 10° to 80°. In order to obtain the utmost uniformity of results, the quantities of pancreatic extract employed EFFECT OF TEMPERATURE 85 were so adjusted as to bring the time of the occurrence of the metacasein reaction within a period ranging from 4 to 6 minutes. Table VII. — Showing the effects of Temperature on Tryptic Enzymosis. The quantity of ruilk employe! in eaeli experiment was 50 c.c. diluted with water up to 100 c.c. In the fourth column the degree of tryptic activity, or T, was calculated by a method to be presently explained. Temperature Quantity of Pancreatic Extract employed i >nset point of the Metacasein Reaction Trvptic Value- -orT 10° c. 60 c.c. 5 minutes 8 15° 4-0 „ 5 12 20° 30 „ 4 21 30° 1-0 „ H „ 45 40° 0-6 „ 76 50° 0-4 „ Of >! 119 60° 0-3 „ 5^ „ 150 65° 0-4 „ 5 125 70° 0-8 „ 4 78 75° 2-0 „ 6 ., 21 80° 4-0 „ No action In the subjoined diagram these results are thrown into the form of a curve. The ordinates indicate the Curve illustrating the effect of temperature on the tryptic digestion of milk. degrees of tryptic activity (or, T), and the abscissae indicate the temperatures. In another series of experiments the effect of tempe- 86 EFFECT OF TEMPERATURE rature was gauged by the length of time required to reach the onset or the vanishing point of the meta- casein reaction when constant quantities of pancreatic extract were used. The results obtained in this series are tabulated in Table VIII. In the first set the onset point of the reaction was taken as the index of tryptic activity ; in the second set the vanishing point of the reaction was employed for the same purpose. The results brought out by these experiments correspond pretty closely with those given in Table VII. Table VIII. — Showing the effect of Temperature by the length of time required to reach the Metacasein Reaction, when constant quantities of Pancreatic Extract are used. I Set. 0*4 c.c. Pancreatic Extract -with 100 c.c. Diluted Milk 11 Set. 4 c.c. of Pancreatic Extract with 100 c.c. Diluted Milk Temperature Onset Point of the Meta- casein Reaction Temperature Vanishing Point of the Metacasein Reaction 2 to 5° C. 312 minutes 10° 168 10= c. 180 minutes 15° 120 — — 20° 70 „ 20° 75 „ 30° 25 30° 26 40° 12 40° 12 50° 6 „ 50° 6 60° 4 60° 4 65° 6 70° / I action suspended, but resumed on cooling An examination of the table shows how very nearly the results correspond, whether the onset point or the vanishing point of the metacasein reaction be taken as a measure of tryptic activity. This correspondence sub- stantiates the conclusion that the onset point of the reaction furnishes a trustworthy index of the activity of MODE OF PROCEEDING 87 tryptic digestion. The proportionate quantity of pan- creatic extract added to the milk in the experiments recorded in Set II. of Table VIII. was ten times as great as in those recorded in Set I.; and it is seen that, by using these proportions, the vanishing points and the onset points fell out in nearly the same times in both sets of experiments. Mode of Proceeding. — In testing the tryptic activity of a sample of pancreatic extract, the following proce- dure was adopted : — 50 cubic centimeters of fresh milk were diluted with 50 cubic centimeters of water, less the quantity of extract intended to be added. The diluted milk was then warmed to 40° C, and maintained exactly at that temperature until the close of the experiment. The intended quantity of the pancreatic extract, say 1 cubic centimeter, was then added, and the time exactly noted. At the end of each minute a portion of the digesting milk was withdrawn, and boiled for a few seconds in a test-tube, inclining the test-tube to one side after the boiling in order to observe the effect. The result was at once noted down. As soon as distinct curdling occurred on boiling, the experiment was con- sidered finished ; the time was recorded, and the number of minutes which had elapsed from the commencement of the experiment were reckoned. The result came out in the following form : — 1 c.c. pane, extract + 50 c.c. milk = 4 minutes at 40° C. If no signs of incipient curdling (soiling of the sides of the test-tube) occurred within 3 minutes, a new experiment was made, using two, three, or four times as much pancreatic extract. If, on the other hand, distinct curdling occurred in 2 minutes, or less, a fresh experiment was made, using half or quarter the quantity 88 EXPRESSING THE TRYPTIC VALUE of extract. Three or four such experiments usually sufficed to enable the operator to fix the onset point of the reaction somewhere between 4 and 6 minutes. Mode of Calculating and Expressing the Tryptic Value. — The object of the experiment was to ascertain how many c.c. of milk can be changed to the onset point of the metacasein reaction by 1 c.c. of extract in a period of 5 minutes, at the temperature of 40° C. The tryptic value, or T, was calculated from this first expres- sion of the results of an experiment in exactly the same way as for diastase. If p be made to signify the quantity of pancreatic extract added to the milk, and m the number of minutes which were required to reach the onset point of the metacasein reaction, then the value of T was obtained by the following formula : — 50 5 m x =T p m ' and taking the experiment above given the value of T came out as follows : — T = ^x^ = 62-5 at40°C. In judging the practical value of this method of trypsimetry, one must have regard to the inherent diffi- culty of estimating the activity of preparations of the proteolytic enzymes. I venture to think that we have in this method a means of estimating the activity of trypsin preparations which is superior in ease and pre- cision to any we possess for the evaluation of pepsin preparations. What may be the limits of error arising from inequalities in the composition of milk I am unable to say, but with the same specimen of milk the limits of error do not certainly exceed 6 to 8 per cent. ENZTMIC VALUES OF PANCREATIC TISSUE 89 The tryptic value of pancreatic extract from the pig, made on the large scale, was found to range from 40 to 70 at 40° C. The pancreatic tissue of the ox and sheep yielded an extract which possessed ahout the same tryptic activity as that of the pig. Extracts prepared from single glands presented very considerable variations both in regard to their diastasic and their tryptic activity. The following table shows the enzymic values of twelve samples of pancreatic extract prepared with single glands from four pigs, four oxen, and four sheep, killed for the market. Table IX. All the observations were made at 40° C. D stands for diastasic value, and T for tryptic value. Pig Ox Sheep „ - ID = 166 No.l | T = 64 „ | D = 100 Iso - 2 \T = 83 - o 1 D = 100 JNO. < rp_<79 x - , |D = 100 No. 4 [ T = 64 v . fD=8 Ud \T-64 No. 6 | T = 5Q xo.7{?: 4 9 2 No - 8 {?:J3 No - 9 {t = 125 XT t „rD = i2 No.l0| T = 83 v „ | D = 14 No.ll| T = 64 No 12 n Pancreatic Diastase. The action of alcohol on the pancreatic digestion of starch was found to be identical with its effect on salivary 158 FOOD-ACCESSORIES AND TRYPTIC DIGESTION digestion (see p. 116). In regard to wines and beer, it was found, as explained in a preceding lecture, that their inhibitory influence on the action of salivary diastase was entirely due to the acidity of these beverages. The same is the case with their action on pancreatic diastase — and as this acidity is removed by the alkaline juices of the duodenum, these beverages are without any effect on the pancreatic digestion of starch. In the case of tea the reaction of the medium also governs the result. For, although tea is highly inhibitory of pancreatic, as of salivary, amy lory sis, this inhibitory action is removed (or almost removed) by changing the reaction from neutral or faintly acid to alkaline. When therefore tea passes into the alkaline atmosphere of the duodenum, it ceases to have any effect on the pancreatic digestion of starch, or at least any effect of practical significance. Effectof Food-accessories on Tryptic Digestion. — I tested experimentally the effect on tryptic digestion, of milk, of alcohol, and of tea and coffee. Alcohol had a distinctly retarding influence when its proportion in the digesting mixture rose to 5 per cent, of absolute alcohol (10 per •cent, of proof spirit), but the effect was comparatively slight. The digestion of milk (other conditions being equal) was delayed by 10 per cent, of proof spirit from the normal of twelve minutes to eighteen minutes. Even with twice this proportion of alcohol, digestion went on without any embarrassment, but the time of its comple- tion was prolonged from the normal of twelve minutes to forty-five minutes. When we consider how rapidly alcohol is absorbed from the stomach, it is obviously almost impossible that the chyme in the duodenum should ever contain anything like these proportions of alcohol, so that we may consider that alcohol as used -dietetically never interferes with tryptic digestion. FOOD-ACCESSORIES AND TRYPTIC DIGESTION 159 Nor did I find that tea or coffee, even in the pro- portion of 50 or 60 per cent, of the digesting mixture, had any effect worthy of note. A slight retardation was observed, but not the slightest sign of embarrassment. The results obtained with milk were controlled by experi- ments made with bread, with meat, and with fish-fibre — all of which yielded conformable results. It may. there- fore, be concluded that with regard to pancreatic digestion the effects of food-accessories are practically nil. In no case did I find evidence of the possibility of that em- barrassment and arrest which occurred in so many instances in the case of salivary and peptic digestion. 160 V. ON SOME PRACTICAL POINTS IN DIETETICS. (An Address delivered at the Opening of the Session, of the Manchester Medical Society, October 1890.) Summary : — Two groups of cases require advice on diet, the seriously sick and the substantially healthy — Contradictory advice given to the latter — The proper basis of dietetics is a study of the food-habits of mankind — Man strictly subject to biological laws — Double aim of diet, one to subserve the needs of general nutrition, the other to subserve the needs of the brain and nervous system — What is a luxury ? — Diversity of our diet — Useless and punitive restrictions on the choice of food — Office of the palate in regulating the choice of food — Beneficial effect of change of diet — Better to lessen than to forbid — The neurotic or hysterical stomach — Mid-life revision of the diet — How to restrict the intake of food -Conclusion. Our advice is sought in the matter of diet in two different sets of cases. In one set the patient is seriously ill, and dis- abled more or less completely from pursuing his ordinary avocations ; or he is suffering from some disease which requires a special dietetic treatment, such as diabetes or gastric ulcer. In the other set the patient is only troubled with some slighter ailment or indisposition which does not incapacitate him from taking his part in the world's work, nor necessitate any deviation from his usual habits. In the former class of cases the diet often requires to be entirety transformed, the customary routine has to be abandoned, and the order, quality, and quantity of food have to be rearranged to suit the exigencies of the morbid TWO GROUPS OF CASES 1 (J 1 state, with an almost complete abandonment of an}- thought as to what might be most suitable in health, and might best promote the success of the individual as an agonist in the struggles and competitions of life. When a man is struck down with fever, or is smitten with some organic disease, we need not consider what diet is best fitted to bring out his physical and mental powers ; the business in hand is to advise what is best to keep body and soul together until the fever storm be passed, or what is best to minimise the incidence of the organic trouble, and to lengthen out existence to the utmost possible span. But the case is far otherwise with the second group, which forms the larger proportion of those who seek our advice, and who question us anxiously as to what they shall eat, drink, and avoid. These have no organic disease, and go about their business or pleasure as usual. They complain perhaps of some dyspeptic trouble, some bodily discomfort, or mental worry or weariness ; or of a want of a sense of tranquil and vigorous life ; or they are getting on in years, and feel the premonitions of old age ; or they belong to that class of neurotics who imagine themselves ill — persons who ponder over their sensations, and give excessive thought as to what they shall eat and what they shall drink. Most of these require of us what aid we can give them by a judicious management of their diet, not only to keep well and live long, but also to maintain that health with maximum vigour, both of body and brain. Now, with regard to the first group, the advice tendered by us on points of diet displays a fair degree of unanimity. We do not differ much as to the dietetic management of a case of fever, or of diabetes, or of gastric ulcer, or, indeed, of any of the more serious forms M 162 THE SCIENTIFIC BASIS OF DIETETICS of sickness. But, in regard to the second group, in the case of persons who are substantially healthy — and it is of these alone that I propose to speak — the advice ten- dered by different practitioners is apt to show a lament- able want of consonance, or even a total contradiction. Many patients of this group are persistent seekers after medical advice, and they go about from one adviser to another. The tales some of these have to tell of their dietetic adventures are not pleasant hearing to a medical ear, and are calculated to leave the impression on the public that our notions on dietetics are little better than a farrago of whims and fancies. All this confusion is, I believe, to be traced mainly to a want of appreciation of the right method of investigating questions relating to diet. I have on previous occasions spoken on this point ; but it cannot be too often nor too urgently insisted on that the only true basis of a scientific knowledge of dietetics is to be found in a painstaking and unprejudiced objective study of the food customs and habits of mankind. These customs and habits are as much sober unsophisticated facts of natural history as are the food habits of wild animals. They have grown up by the free play of natural instincts, under the regu- lating force of universally acting biological laws — under the pressure of the sleepless vigilance of the law of the survival of the fittest and the sure incidence of the laws of heredity. Neither physician nor physiologist has had anything whatever to do with their formation ; and, among European communities, and especially among English-speaking communities, the bungling hand of authority has not materially interfered with their normal development. Some persons appear to think that civilised man is, to a large extent, a denaturalised creature, and they CIVILISED MAN IS XOT DENATURALISED 1G3 speak of civilisation as if it were the antithesis of Nature. No conception could be more fallacious ; for, after all, strictly speaking, civilisation is but a branch of natural history. We can no more withdraw ourselves from the incidence of biological laws than we can from the inci- dence of physical laws. Biological, like physical, laws are absolutely inexorable, and all the apparatus of our civilisation and all the influences which flow from the initiative of our reason and the action of our intelligence can only modify the conditions under which they operate. I contend, therefore, that we have in our generalised food habits and customs a natural dietetic standard or model —as truly natural as the food habits of the squirrel, the blackbird, or the trout ; and, further, that we are war- ranted in concluding beyond all reasonable doubt that there lies in each main feature of this standard some im- portant beneficial purpose. Considerations of this order, if fully realised by us, would, I think, give greater steadi- ness and coherence to our notions on dietetics, and bring more uniformity into our rules of practice. If these views are sound, the office of the medical adviser in matters of diet may be broadly defined to be to adjust the national standard of diet to the special peculiarities and the changing needs of the individual ; and in carrying out this adjustment it is his duty to adhere, as far as is practicable, to the main features of that standard. An attentive examination of the dietetic customs of civilised races reveals very clearly that there are two distinct indications aimed at : one is to subserve the needs of general nutrition, and the other is to subserve the needs of the higher functions of the brain and nervous system. It may be said that bread and other cereal articles, leguminous seeds, the various products of the 164 VARIETY OF DIET dairy, fruits and vegetables, the harvest of the sea, and meat, are designed to minister to the former purpose ; and that tea and coffee, and the various forms of alcoholic beverages, are designed to minister to the latter purpose. With this second group should also be classed tobacco ; for although tobacco cannot be regarded as food, its use must be ranked with our dietetic customs. Strictly speaking meat, or at least some kinds of meat, should probably find a place in both categories, for it possesses certain stimulating properties which distinguish it from vegetable and dairy products. Tea and coffee and alco- holic beverages are sometimes branded as luxuries. What is a luxury ? You cannot rightly class as luxuries — meaning thereby something that has no solid utility to the species— articles that are in general use among a successful and ascendant community. The very fact that these articles have attained this position is, to a naturalist, evidence sufficient that in some way or other the community as a whole, and in the long run, benefits by their use. The struggle for existence — or rather, for a higher and better existence — among civilised men is almost exclusively a brain struggle ; and these brain- foods, 1 as they have been not inappropriately termed, must be regarded as a very important part of the equip- ment for that struggle. One of the most characteristic features of our national dietary is its variety or diversity. Not only are our several daily meals framed on a different plan, but the meals of one day differ more or less from the corre- sponding meals of another day. We may be quite sure that this diversity serves some useful end. In drawing up schemes of diet we are not, therefore, justified in 1 Of course, this term is used not in a literal, but in a figurative, sense. PUNITIVE RESTRICTIONS ON DIET 165 neglecting this feature and in reducing the diet list to a dead level of monotonous uniformity. A want of atten- tion to this point leads us unwittingly to needlessly torment and worry our patients by placing unnecessary restrictions on their choice of food. Some of those commonly imposed are difficult to understand. There is to be observed a sort of fashion running through these restrictions, yet I know not on whose authority they repose. I do not think it is any medical authority. My impression is that most of them derive their origin from some crude notions floating through the lay press, and unconsciously lodged in the medical mind. Why, for example, should tea and coffee be so frequently for- bidden without any evidence that they disagree with the patient? Or why should the bland, innocuous, and easily digested potato be so ruthlessly proscribed? Sometimes prohibition takes a wider sweep, and fruit and vegetables are included in one general condemna- tion. Nor are the rules laid down always self-consistent. Sugar is forbidden while farinaceous matters are per- mitted, although, as is well known, these latter are all transmuted into sugar in the course of the digestive operations. Mutton is sanctioned, while beef (of which certain parts are quite as digestible) is denied ; or both beef and mutton are condemned, while poultry and game are recommended. These kinds of restrictions are, fur the most part, quite unmeaning; they stand on no ground of science nor of experience, and are gratuitously punitive to our patients. Some patients, I admit, seem to derive a sort of grim satisfaction from then- dietetic fetters, and come to regard them almost as a mark of distinction ; but to most persons these restrictions are very irksome, or even unendurable; and, indeed, many patients break through them, and may sometimes be 166 INDICATIONS OF THE PALATE heard complacently relating how they profited by their rebellion. I remember, some years ago, an amusing instance in point, where I was myself one of the incrimi- nated parties. A fine old gentleman in this neighbour- hood, on account of some vesical trouble, had his port wine, to which he was very partial, entirely cut off. His convalescence proved tedious and halting, and still the port wine was withheld. On some special occasion — I forget what — his powers of resistance gave way, and out came the port wine ; and he used to recount with glee that he never looked behind him after. I hope I have learnt some useful lessons since then. Now there is, I think, one very good rule in regard to the regulation of the diet in cases where there are no special indications to fulfil, and that is to put two ques- tions to the patient when he inquires whether he may take this or that article of food — namely, Do you like it ? and, Does it agree with you ? If the answer be in the affirmative, there is no intelligible reason why the use of that article should not be sanctioned. Such a rule is so plain and simple, and so obviously consonant with good sense, that it might scarcely appear worth while, or even dignified, to make formal mention of it, and I would not have done so had I not been satisfied, from actual experience, that it is constantly violated. The indications of the palate are of great importance in the regulation of the diet, and should always be inquired into and carefully considered. The palate is placed like a dietetic conscience at the entrance gate of food, and its appointed function is to pass summary judgment on the wholesomeness or unwholesomeness of the articles presented to it. It acts under the influence of a natural instinct, which is rarely at fault. This instinct represents an immense accumulation of experi- EULOGIUM OF THE PALATE 167 ence, partly acquired and partly inherited. It is, of course, not infallible — no instinct is, but so close and true are the sympathies of the palate with the stomach and the rest of the organism, that its dictates are entitled to the utmost deference as those of the rightful authority in the choice of food. I am of course aware that the palate — or, rather, the civilised palate — is not always credited with these solid good qualities. Some persons there are — not medical authorities — who dis- trust its office, and regard its indications with suspicion, as if they were the suggestions of some frivolous and wanton agency, tempting men to a vain gratification of the senses, rather than as those of an honest and skil- ful guide in the choice of food. This puritanical view of the palate is wholly unscientific ; it moreover implies, to speak figuratively, a gross slander on a responsible and rarely endowed organ which has performed in the past, and still performs, most difficult and most com- plicated functions with conspicuous success ; for who shall venture to say, that in the evolution of the human animal from the short-lived, immoral, and stupid savage, with his diet of wild fruit, roots, raw flesh, and unfiltered water, to the status of civilised man, the promptings of the palate have not played an important and even indis- pensable part ? "We are apt to forget that there is no such a thing as an absolutely good or an absolutely bad flavour to the animal palate. Sweet things are indifferent to the palate of the carnivora ; and, conversely, the taste of flesh has no attraction for the herbivora. Each animal has its own gustatory standard, which is accu- rately adjusted to the wants of its particular economy. It must, however, be admitted that this eulogium applies rather to the typical or general palate than to the particular palate. Man is the most individual of all 168 CHANGE OF DIET creatures, and his palate fully shares in this character- istic. And while it is true that the normal or average palate indicates automatically and correctly, not only the due quality, but also the due quantity, of the eating and drinking, there are other palates that require more or less of the control of reason to steady their indica- tions. Then there are eccentric or misfitting palates that appear — if one might so express it — as if they be- longed to somebody else — palates which are not in- herently defective, but which stand, in one or two par- ticulars, in sharp discord with the organism to which they are attached. And, lastly, there are palates which are altogether perverse and depraved ; that habitually betray their hosts, and lead them into endless digestive and other troubles. It is the business of the medical adviser to diagnosticate these eccentric or vicious palates, and to assist their owners by judicious counsel how best to neutralise their evil promptings, and to train them if possible — for the palate is, to a certain extent, an educ- able organ — to a more wholesome and more harmonious performance of their functions. The next point to which I would call your attention is the advantage to be gained from change of diet. A readjustment of the quality of the meals has often the happiest effect. Change of diet is as refreshing as change of air. The gratifying results are sometimes credited to the skill of the medical adviser in making an improved selection of food when they are really due to the change itself. A course of two or three weeks of vegetarian regimen occasionally proves most grateful, especially in the case of habitually heavy feeders — and, similarly, a course of total abstinence from alcoholic beverages is often highly salutary, and, most of all, for those whose daily potations are on a liberal scale. The BETTER TO RESTRICT THAN TO FORBID 169 good effect of men change of diet is, I think, deserving of more attention than it has hitherto received. There need not be such a departure from the general plan as is involved in vegetarianism or total abstinence. Slighter alterations are often of signal benefit — changes from tea to coffee or cocoa — from one kind of alcoholic beverage to another — from one sort of bread to another. Again, a revision of the order and times of the meals is some- times beneficial. I have seen more than once an altera- tion from a mid-day dinner to a late dinner or substan- tial supper effective in removing a troublesome insomnia. In carrying out plans of change of diet it should ever be borne in mind that the effect is temporary, and that its benefits are exhausted in two or three weeks, or a month or two at the most, and that then a return to the old diet or a new change may be desirable. Another point of practical interest is this : when certain articles disagree, it is better to lessen the quantity than to forbid. If fruit and vegetables prove difficult of digestion, it is certainly unwise to prohibit them alto- gether. It will generally be found that if the quantities are reduced to a certain level they can be tolerated and enjoyed. The antiscorbutic properties of fruit and vegetables cannot be safely foregone ; and a very small proportion suffices to fulfil this indication. I may again refer to the use of potatoes. People do, no doubt, some- times unduly stuff their stomachs with potatoes, which the organ finds difficult to deal with. But many persons •cannot enjoy, or scarcely eat, their dinners without potatoes, and to abstain from them is a great privation. Nor is this necessary ; a reduced allowance solves the dilemma perfectly. Then, again, some persons are ab- normally sensitive to tea or coffee or alcoholic beverages, and suffer discomfort from the quantities usually taken. 170 THE HYSTERICAL STOMACH But abnormal sensitiveness is not a proof that the incriminated article is unserviceable ; and a diminution of the quantity may prove a better remedy than total prohibition. Your late distinguished townsman, Dr. Angus Smith, was hypersensitive to tea, but he did not abstain from it. He was in the habit of taking a table- spoonful or two of ordinary tea, and filling up the cup with water ; and he used to declare that he derived as much cheer and refreshment from this weak dilution as other people did from their stronger concoctions. While on this subject I may mention a useful suggestion which we owe, I believe, to Sir Andrew Clark — namely, that sensitive persons should take their tea infused for a very short time, only for one or two minutes. There are, as is well known, idiosyncrasies in which some particular article cannot be tolerated even in the smallest propor- tions ; prohibition is then a necessity. Much more common are the instances in which there is defective self-control as to quantity. This is especially the case with alcoholic beverages. Self-control is indispensable for the salutary use of these articles ; and in the absence of this quality there is no safety except in total abstinence. I animadverted awhile ago on the practice of impos- ing punitive restrictions on the choice of food ; but there are cases in which a certain amount of coercion is salu- tary, and even necessary. In neurotic and hysterical persons the stomach sometimes shares in the general nerve instability, or it may even be the chief offender. This kind of stomach, if indulged in its whims, is apt, like other pampered beings, to give itself airs — it won't have this and it won't have that — and it may even grow proud of its eccentricities. I have known such stomachs reduce their hosts, by successive acts of self-inflicted MID-LIFE KEVISION OF THE DIET 171 restrictions, to a diet of dry toast and watergruel — with what results of depressed vitality von can easily imagine. In this group of cases the medical adviser may with advantage insist on a gradual return to ordinary diet ; and he will often find that the stomach, after a certain recalcitrancy, will submit, and consent to digest ordinary food, perhaps to the astonishment of the patient, and certainly to the common advantage of the organism. Patients of this class should be given to understand that there are some things worse than an aching stomach — namely, impoverished blood, failing strength, and en- feebled brain and nerve. Moreover, the lower the vitality is reduced by insufficient feeding the more prone is the stomach to neuralgic pains. An enforced adminis- tration of more and better food is often the surest as well as the shortest road to deliverance from gastric hyperesthesia. The last point I shall advert to is the necessity for a revision of the diet to meet those changes in the type of nutrition which naturally take place as tlic individual travels on from youth to age. Senescence invades the several organs and tissues in a varying order of time ; and this want of synchronism is sometimes a source of trouble. When the hair falls off or turns grey before its time, our vanity but not our health is touched. When the teeth decay prematurely, we find succour in the in- valuable art of the dentist. But if the prime organs and functions of the body age with unequal steps, the matter is more serious and less easily remedied. As years roll over us the balance of nutrition alters ; the exchange of material shrinks, and the organs concerned therein be- come correspondingly less active and less capable. In the normal course the palate and appetite adjust them- selves automatically to these altered conditions, and there 172 MID-LIFE KEVISION OF THK DIET is a lessened intake of food. But sometimes this adjust- ment lags behind. The power of taking food continues unaltered, while the assimilative powers are on the wane : you have the palate and appetite of thirty with the liver and kidneys of sixty. Some form of nutritive disorder necessarily follows. In most of these cases, but not in all, there is a tendency to stoutness. There are indica- tions of digestive difficulties and of engorgement of the abdominal organs, and signs of that vague condition which is termed latent or undeveloped gout. The early recognition of this condition is very important, for there- upon depends the prevention or postponement of de- generative processes which hereafter prove formidable. In this conjuncture the observant medical adviser may render invaluable service in detecting the maladjustment, and in taking timely steps for its correction. The most obvious indication is to lessen the quantity of food, and this is a task of varying difficulty. In many cases of this class — perhaps the majority — the maintenance of an undiminished ingestion of food rests on the force of habit. The accustomed quantity of food and drink is taken, though with a somewha,t flagging appetite and lessening gusto. The still small voice of the dietetic con- science is unheeded ; or even there may be a little forcing in of the supplies, from a mistaken notion that a falling off might prove disadvantageous, or of evil augury. In these cases an authoritative hint from the medical adviser is sufficient, and is readily accepted and acted on. Full feeders are rarely aware that they eat too much. People constantly delude themselves on this point. I do not know how it is ; men often are aware and acknowledge that they drink too much, but they hardly ever allow that they eat too much. They will tell you that they eat much less than most other men they meet with, and LESSENING THE INTAKE OF FOOD 173 insist that they consider themselves to he moderate, or even small, eaters ; and it is difficult or impossible to persuade them to the contrary. Possibly they are apt unconsciously to compare themselves with younger men. The medical adviser must in this matter rely mainly on his own judgment and on collateral evidence. In sonic cases, however, there is much more difficulty in control- ling the intake of food. The appetite is really strong, and the powers of digestion — at least of gastric digestion — are abnormally active. Unsatisfied hunger is a pain- ful and an urgent guest, and, with plenty at hand, is hard to resist. The less concentrated forms of food are here a useful resource — green vegetables, salads, and thin soups which help to fill the aching void without adding materially to the albuminoid and fatty ingredients of the meal. Tea and coffee are also serviceable in allaying an unseasonable craving for food. A stiff cup of tea or coffee shortly before dinner certainly takes the edge off a troublesome appetite. It is, however, well to proceed cautiously and tentatively in this direction, for the promptings of Nature, however apparently to us mis- directed, are not to be lightly set aside. The effects of a contracted diet should be carefully and patiently watched, with an open mind for every sign or suggestion, whether of warning to retreat or of encouragement to advance. I need hardly add that in regard to this middle-life revision of the dietary, as it may be termed, particular attention should be given to the quantity of alcoholic- beverages. As a very general rule the tolerance for these articles diminishes with advancing years, and it is necessary nearly always with persons who have used them freely to reduce their quantity when middle age is reached. In regulating the diet of substantially healthy per- 174 BEWARE OF HARD-AND-FAST LINES sons, it is imperative to beware of hard-and-fast lines. Cases of this group are very diverse ; scarcely any two are exactly alike, and their management is complicated often by moral and social considerations which are dim- cult to justly estimate. We can only hope to avoid serious errors by a patient investigation of each par- ticular case, and by bringing to bear upon it a full know- ledge, combined with a large infusion of common sense. Section III PREPARATION OF FOOD FOR INVALIDS 177 I. PREPARATION OF ORDINARY FOODS FOR INVALIDS. (Abstracted chiefly from an address on 'Feeding the Sick,' delivered before the British Medical Association at Cardiff in 1885.) Summary: Effects of cooking — Clinical relations of gastric and intes- tinal digestion — Feeding the sick with liquid food — Milk — Beef-tea and other meat decoctions — Cold-made infusions of meat — Beaten-up eggs — Fortified gruels— Different kinds of farinaceous flours — Com- mercial ' foods ' for invalids Apparatus and ingredients requisite for the preparation of foods in the sick-room and nursery— 'Whole- meal ' flour. EFFECTS OF COOKING ON FOOD. The process of cooking fulfils far more important ends than that of improving the savour of food — far more important even than the mechanical disintegration which generally attends the process. It produces certain chemical changes in several of the most important ali- mentary principles which render them incomparably more susceptible to the action of the digestive ferments than in the uncooked state. The discovery of the use of fire-heat in the preparation of his food must indeed have constituted one of the earliest and most important steps in the process by which man has emerged from the ranks of the dumb creation. The stores of proteid and farina- ceous nutriment contained in the seeds of cereals and leguminous plants, and in the bulbs, tubers, roots, and N 178 EFFECTS OF COOKING ON FOOD succulent stems of certain vegetables are, in the raw state, nearly altogether beyond his powers of digestion. By the discovery of the art of cooking these immeasur- able stores were at one stroke laid open to him. It is moreover chiefly by the same art that he has been enabled to take his food at intervals, in separate meals, and has thereby been for ever relieved from the necessity which is imposed on all animals in the wild state of having to spend almost the entire of their waking hours either in seeking after their food, like the carnivora, or in con- suming their food like the vegetable feeders. This im- munity secured to him the untold advantage of possess- ing the leisure requisite for the cultivation of his higher faculties. The practice of cooking is not equally necessary in regard to all articles of food. There are important differ- ences in this respect, and it is interesting to note how correctly the experience of mankind has guided them in this matter. The articles of food which we still use in the uncooked state are comparatively few ; and it is not difficult in each case to indicate the reason of the ex- emption. Fruits, which we consume largely in the raw state, owe their dietetic value chiefly to the sugar which they contain ; but sugar is not altered by cooking. Salads may be regarded more as a relish for other food, and as having a quasi-medicinal purpose, rather than as a substantial source of nutriment. Milk is consumed by us both cooked and uncooked, indifferently, and experi- ment justifies this indifference ; for I found on trial that the digestion of milk by pancreatic extract was not ap- preciably hastened by previously boiling the milk. Our practice in regard to the oyster is quite excep- tional, and furnishes a striking example of the general correctness of the popular judgment on dietetic questions. EFFECTS OF COOKING OX FOOD 170 The oyster is almost the only animal substance which we eat habitually, and by preference, in the raw or un- cooked state ; and it is interesting to know that there is a sound physiological reason at the bottom of this pre- ference. The fawn-coloured mass which constitutes the dainty of the oyster is its liver, and this is little else than a heap of glycogen or animal starch. Associated with the glycogen, but withheld from actual contact with it during life, is its appropriate digestive ferment — the hepatic diastase. The mere crushing of the dainty be- tween the teeth brings these two bodies together, and the glycogen is at once digested without other help by its own diastase. The oyster in the uncooked state, or merely warmed, is, in fact, self- digestive. But the ad- vantage of this provision is wholly lost by cooking, for the heat employed immediately destroys the associated ferment, and a cooked oyster has to be digested, like any other food, by the eater's own digestive powers. With regard, however, to the staple articles of our food, the practice of cooking them beforehand is univer- sal. In the case of farinaceous articles cooking is actually indispensable. When men under the stress of circum- stances have been compelled to subsist on the uncooked grain of the cereals, they have soon fallen into a state of inanition and disease. By the process of cooking, the starch of the grain is not only liberated from its protect- ing envelopes, but it undergoes a chemical change, by which it is transformed into the gelatinous condition, and this immensely facilitates the attack of the diastasic ferments. A change of ecmal importance seems to be induced in the proteid matter of the grain. I found that the gluten of wheat was greatly more digestible, by both artificial gastric juice and by pancreatic extract, in the cooked than in the uncooked state. In regard to flesh s -2 180 GASTRIC AND INTESTINAL DIGESTION meat the advantage of cooking consists chiefly in its effects on the connective tissue and the tendinous and aponeurotic structures associated with muscular fibre. These are not merely softened and disintegrated by cook- ing, but are chemically converted into the soluble and easily digested form of gelatin. I made some instructive observations on the effects of cooking on the contents of the egg. The change induced by cooking on egg albumen is very striking. For the purpose of testing this point, I employed a solution of egg albumen made by mixing white-of-egg with nine times its volume of water. This solution when heated in the water-bath does not coagulate nor sensibly change its appearance, but its behaviour with the digestive ferments is completely altered. In the raw state this solution is attacked very slowly by pepsin and acid, and pancreatic extract has almost no effect on it ; but after being cooked in the water-bath, the albumen is rapidly and entirely digested by artificial gastric juice, and a moiety of it is rapidly digested by pancreatic extract. CLINICAL RELATIONS OF GASTRIC AND INTESTINAL DIGESTION. In forming a plan of dietary for the sick, distinction must be made between gastric and intestinal digestion. In healthy persons, and invalids of the slighter sort, we must have regard mainly to gastric digestion ; but in the seriously sick the stomach becomes often inoperative, and digestion becomes almost exclusively intestinal. The sympathy of the stomach with the general condition of the system is much more active and close than that of the intestine ; the former organ approximates more nearly to the animal life of the body, the latter more nearly to FEEDING THE DUODENUM 181 the vegetative life. The seriously sick, and especially th< febrile sick, are often quite unable to take solid food. When the appetite and power of taking food fails, it fails first with regard to meat, which is, so to speak, the speciality of the stomach, and next in regard to bread. Patients are then reduced to the use of liquid food. In this latter condition the stomach loses its normal office, and becomes merely a conduit to pass on the liquid food to the duodenum — a continuation, as it were, of the oesophagus. Not perhaps that there is, except in ex- treme cases, an absolute abeyance of gastric secretion and gastric action, but they are reduced to so low an ebb that they count for practically nothing hi the work of digestion. In this state of things, when patients are unable to take airy solid food, it is quite wonderful to observe, in many cases, that persons who in health were unable to digest milk, or only to digest it with pain and difficulty, are able during illness to take milk m any quantity. The reason of this is obvious. In a state of health milk must be dealt with in the stomach, and the casein is curdled into solid masses ; these masses have to be broken up and to be more or less dissolved in the gastric juice before they can traverse the pylorus. In tbe seriously sick, with an almost paralysed stomach, milk is not meddled with in that viscus. There is neither pepsin nor acid to curdle it, and it passes as a flowing liquid into the duodenum. Arrived there it encounters the secretion of the still active pancreas, and milk is especially amenable to the action of the pancreatic juice. In feeding the sick our first consideration, therefore, should be whether we are aiming at feeding the stomach or feeding the duodenum. In the former case, when the patient can take solid food — and this is the diagnostic indication that the stomach still posse^--- digestive 182 LIQUID FOODS activity — our aim must be to administer meat, bread, eggs, &c, in a state most favourable for peptic digestion. The meat should be well cooked — by preference boiled. It should be finely comminuted either by perfect mastica- tion in the mouth, or (if this be impossible) by pounding in a mortar or beating to a paste with a spoon, as in the preparation of potted meat. Beef-tea and soups should be used sparingly, as should likewise be tea, coffee, and alcoholic beverages. And of these last, the best adapted for weak stomachs are regulated quantities of ardent spirits or of the stronger wines or champagne. FEEDING THE SICK WITH LIQUID FOOD. In a considerable number of conditions, our patients are unable to take solid food, and are reduced to the necessity of using food which can be administered in the liquid form. This is usually the case in the febrile state and in serious organic disease, especially of the ab- dominal organs, and in the terminal stages of almost all diseases. There are other conditions in which, although the patient may have the ability to take solid food, it is not desirable that such food should be administered to him. In narrowing of the pylorus or other part of the digestive tract, in ulceration of the intestinal mucous membrane, it is obviously undesirable to administer articles of food which are capable of forming lumps or masses which may block up the narrowed parts of the intestinal tube, or irritate the ulcerated surfaces. There is thus a large field for the employment of liquid food ; and one of the most embarrassing tasks in clinical diete- tics is to devise food of this form in sufficient change and variety, and having at the same time an adequate nutritive value. Our resources in this state of things consist of MILK 183 milk, beef-tea, and other meat-decoctions, cold -made meat-infusions, beaten-up eggs, and the various gruels. I propose to make some remarks on each of these articles. Milk. — By far the most serviceable liquid food we possess is milk. Milk contains, in almost equal propor- tions, proteid, saccharine, and fatty matter, and is capa- ble alone, as we know, of sustaining life. All plans of feeding the sick on liquid food centre round milk. It can be given alone, or mixed with tea, coffee, or cocoa, or with lime water, soda water, ardent spirits, or with farinaceous gruels of various sorts, or as buttermilk, koumiss, or whey. Were it not for the necessity of change and variety, we should, in a large number of cases, want nothing but milk. It should, however, be remem- bered that milk is by no means a perfect kind of liquid food. In the course of its digestion in the stomach, milk is coagulated into solid masses, and these masses have to be redissolved before they can be absorbed. Not unfrequently, if milk be given too freely, or when there is excess of acid in the stomach, these curdy masses fail of being dissolved ; and they are discharged by vomiting, or they pass down the intestine more or less unchanged, and are ultimately voided with the stools. In this way milk may become an objectionable form of liquid food ; these curds may block up a narrowed part of the in- testine, or they may undergo putrefactive changes, and thereby irritate the tender or ulcerated mucous mem- brane. To obviate this drawback we are in the habit of combining milk with an antacid. By this means the formation of curds in the stomach is restrained or wholly prevented. The most common practice is to mix the milk with one-third or one-fourth of its bulk of lime water, and often with the happiest results. But in many instances the symptoms are not thus allayed, and the 184 BEEF-TEA milk is still discharged in hard and sour curds. Failure in these cases is often solely due to the feeble antacid capacity of lime water. The saturating potency of lime water is in reality very low. Quicklime dissolves in water only to the extent of about half a grain to the fluid ounce. This is only equivalent in saturating power to one grain of chalk or to a grain and a half of bicarbonate of soda. To reach a full antacid effect lime water requires to be given in very large quantities — quantities which are altogether impracticable. Six ounces of lime water are only equal to a single ordinary antacid dose of chalk or bicarbonate of soda. I have repeatedly observed in cases of feeding with milk and lime water, that failure was simply due to the feebleness of the antacid charge, and that when a solution containing five or ten grains per ounce of bicarbonate of soda was substituted for lime water as an admixture with milk a favourable result was at once obtained, and the discharge of hard curds arrested. Beef-tea and other Meat-Decoctions. — Next to milk, in frequency of use and in high esteem, come beef-tea and other meat-decoctions. Long experience has satisfied us in this country of the usefulness of these preparations in feeding the sick. Beef-tea and its congeners (mutton- tea, veal and chicken broth), however, take rank as restoratives and stimulants, rather than as nutrients. They contain no albuminous matter in solution, and the small quantity of gelatin contained in them can- not be of much account. There is a wide-spread mis- apprehension among the public in regard to the nutri- tive value of beef-tea. The notion prevails that the nourishing qualities of the meat pass into the decoction, and that the dry hard remnant of meat-fibre which remains undissolved is exhausted of its nutritive pro- perties ; and this latter is often given to the cat or dog, COLD-MADE MEAT INFUSIONS L85 or even, as I have known, thrown away as useless rub- bish into the midden. A deplorable amount of waste arises from the prevalence of this erroneous notion in the households of many who can ill afford it. The proteid matter of meat is, as you know, quite insoluble in boiling water, or in water heated above 160° Fahr. The ingredients that pass into solution are the sapid extractives and salines of the meat, and nothing more, except some trifling amount of gelatin. 1 The meat- remnant, on the other hand, contains the real nutriment of the meat ; and, if this be beaten to a paste with a spoon, or pounded in a mortar, and duly flavoured with salt and other condiments, it constitutes not only a highly nourishing and agreeable, but also an exceedingly digestible, form of food. Cold-made Infusions of Meat. — The defect in nutri- tious value of beef-tea led Liebig to suggest the use of cold-made infusions of meat. He recommended that minced beef should be infused in cold water acidulated with a few drops of hydrochloric acid. An infusion so prepared differs essentially from beef-tea in the fact that it contains, in solution, a large amount of albumi- noid matter. The addition of the acid is, according to my observations, a needless complication of the process. Infusions quite as rich in albumen were obtained when simple water was used as when the water was acidulated with hydrochloric acid. Infusions made from minced meat with half its weight of water, and allowed to stand for two hours, and then pressed through cloth, were found, on analysis, to contain over four per cent, of dry albumen. This amount of proteid is equivalent to that 1 These remarks on beef-tea apply equally to Liebig's Extract of Meat, Brand's Essence of Beef, and Valentine's Meat-Juice, all of which give only a slight reaction of albumen with nitric acid. 186 BEATEN-UP EGGS contained in cow's milk. The nutritive value of such infusions is, therefore, very high. When heated to the boiling point, they coagulate into a solid jelly. Made from beef or mutton, the product has an unpleasant bloody appearance ; but, when made from veal, the coloration is much paler. The best preparation, how- ever, is made from the meat off the breast of a chicken. This meat is nearly white, and it yields an infusion which is almost colourless, and which sets, on heating, into a solid white jelly, of very agreeable appearance. Cold-made meat-infusions cannot be heated above 114° Fahr. without becoming turbid from commencing coagu- lation of albumen. It is, therefore, impossible to cook them without destroying their liquid character. The objection to these infusions is their raw flavour, which to many is highly disagreeable — though some invalids take them without the slightest objection. The best way of covering the raw taste is to add some ordinary beef-tea or a little of Liebig's Extract of Meat. Some prefer a flavour communicated by a slice of lemon, or by the addition of a little claret. 1 Beaten- iq) Eggs. — Another highly nutritive form of liquid food is supplied by raw eggs. The yolk, or white, or both together, are beaten up in various ways and com- binations which are well known. Eggs are more easily digested by the stomach in the cooked than in the un- cooked state; but, when the stomach is weak and unable to digest solid food, beaten-up eggs pass through it into the duodenum without being meddled with, and are slowly digested in their passage down the intestine. They are incapable of forming lumps or masses, and are, therefore, well adapted for cases of narrowing or ulcera- tion of an}' part of the digestive tract. 1 Cold-made meat-infusions keep badly. They should be preserved in a cold cellar, or, still better, on ice. FOBTIFIED GRUELS 18" Fortified Gruels. — A very important kind of liquid food is furnished by gruels made with the several kinds of cereal or leguminous seeds. Gruels are not by them- selves an agreeable kind of food ; they lack flavour ; but, mixed with milk or beef-tea, they constitute a valuable addition to our resources in feeding the seriously sick. When prepared from the cereal flours in the usual May, they can only be made of feeble nutritive power, if their liquid character is to be preserved. These flours are very rich in starch, and gruels made from them be- come thick and pasty if the proportion of flour used in their preparation rise to four or five per cent., and a gruel of this strength does not contain more than one- half per cent, of proteid matter. But, if the meal be mixed beforehand with one-eighth of its weight of ground malt, you can prepare from these flours gruels of much higher nutritive value, and still preserve their liquid character. The diastase of the malt acts upon the thickening starch as the heat rises, and converts it into soluble starch and dextrine. These fortified gruels can be made with as much as 20 per cent, of meal, and still maintain the fluid state. 1 Such gruels contain about two per cent, of proteid matter, and about 14 per cent, of carbo-hydrates, and are admirably adapted, combined with milk or beef-tea, to supply a varied kind of liquid food of highly nutritious character. Mixtures of this 1 This mode of preparing fortified gruels requires a somewhat nice adjustment of temperature for complete success ; and without the use of a thermometer, and some practice in the operation, is apt to yield an unsatisfactory result. A better and easier method is to prepare the gruels in the usual way with the unmixed flours, and to thin them after- wards when cool by the addition of a previously prepared malt-infusion. This method is fully described in a subsequent article on ' The use of malt, and especially of malt-infusion, in the predigestion of starchy food.' See p. 219. 188 USE OF FARINACEOUS FLOURS class seem especially suited for the nourishment of cases of typhoid fever. Use of the various kinds of Farinaceous Flours. — A matter of interest, in designing food for the sick-room and nursery, is the consideration of the special pro- perties of the several kinds of cereal and leguminous substances used as food. In point of chemical composi- tion, the several kinds of cereal grains are closely allied ; still, there are differences between them, and these differ- ences may be of importance. The proteid of wheat is not quite identical with that of oats or barley. On the other hand, leguminous seeds differ importantly in com- position from the cereal grains. Taking the lentil as a type of the leguminous group, it is to be observed that lentil-flour contains twice as much proteid matter as wheat or oat flour, and almost twice as much lime. Moreover, the proteid of the leguminous seeds differs materially from that of wheat or oats. These differences are probably of not a little importance in feeding the sick and the young ; and, if we had more knowledge and experience in their use, we could perhaps utilise with advantage these several cereal and leguminous products, and combine them in varied ways to meet the indications and necessities of different cases. You must all have observed how there has grown up in these latter years an enormous trade in prepared ' foods ' for infants and invalids. The very success of this trade is some evidence of the usefulness of these articles. Their composition is generally made more or less of a secret, but whatever secret there be must be hidden within a very narrow compass. The several possible flours out of which these ' foods ' are mingled can be easily counted — wheat, barley, oat, maize, pea, lentil, and one or two others. These are the ingre- ADVANTAGES OF SICK-BOOM COOKERY L89 clients— with malt-flour in some cases — out of which they are all compounded. Now, I cannot help thinking that it would be an advantage both to ourselves and to our patients, if we knew more precisely what we were about in this matter, and if we were in a position to prescribe for infants and invalids the several kind- of farinaceous aliments in proportions known to us, instead of blindly using some mixture of which we know not the exact composition. It is impossible for us to make progress in dietetics on such a path. I can quite believe that these flours have their special excellences, and that they are severally adapted for different cases and condi- tions. In the first place, they have distinctive flavours, and thereby may be made to contribute to the important end of providing change and variety for the invalid. Moreover, the faculty of ' agreeing' of the different flours, in reference to the individual idiosyncrasy, is a point of not a little significance. Lastly, the difference of chemi- cal composition between the cereal and leguminous flours must have an important bearing on the dietetic uses ol these two groups of aliments. It is, I repeat, a serious disadvantage that the control of the preparation of food for the sick-room and nursery should pa>s from the hands of the medical attendant to those of the pur, In the matter of drug-giving, all enlightened practitioners are chary of prescribing secret remedies. Such a prac- tice, it is felt, must be fatal to the intelligent use of drugs. So it is with providing food for the sick. What we want is to have at our disposal a supply of the several articles of food in their simple state, and suitable appliances in connection with the sick-room or nursery for cooking and combining them in various ways according to the exigencies of our patient-. 190 THE SICK-ROOM KITCHEN APPARATUS AND INGREDIENTS REQUIRED FOR THE PREPARATION OF FOODS FOR INVALIDS. If I were asked to enumerate the ingredients and apparatus which are necessary for the cuisine of the sick- room and nursery, I think I could do so very briefly. In addition to the resources of the domestic kitchen and larder, the sick-room kitchen should contain a sup- ply of the following flours : oat, maize, malt and lentil flours in a finely pulverised condition, and freed from bran. It should be provided with a solution of sodium bicarbonate, containing twenty grains to the ounce ; this would be of use to add to milk when necessary, and to assist in the preparation of peptonised articles of food. Next to these would come a reliable pan- creatic extract, and a preparation of pepsin, or rennet, for the production of whey. The associated apparatus should include an enamelled rod thermometer, wherewith the nurse could, when desirable, heat up cold-made in- fusions of meat to a proper temperature, and regulate the warmth required in the predigestion of food. A double-cased saucepan would form an indispensable item ; this makes an admirable hot- water bath for the preparation of beef-tea and fortified gruels. A pair of scales and glass measures would complete the list. Finally, there should be, for the service of the nurse, a card or sheet containing plain directions for the prepara- tion of the various kinds of liquid food. Given these simple appliances, I see no difficulty, in these days of skilled nursing, in the medical attendant being able to prescribe almost any kind of liquid food for his patients in any combination, and having it served up for the invalid in the most suitable possible manner. There is no difficulty on the part of the miller in produc- WHOLE-MEAL FLOUR 191 ing meals from malt, oats, or lentils, freed from bran and coarser particles, and in nearly as fine a state of prepa- ration as wheaten flour. 1 In this state, these meals are susceptible of much more rapid and perfect cooking than when roughly ground. I have little sympathy with much that has been said of the advantages of whole meal and decorticated flour. It has been alleged that the too complete separation of the outer parts of the grain deprives the flour of its mineral matter. If we lived on bread alone, there would be some force in this objection ; but as that is not so, and that we find in milk, meat, fish eggs, soups, and fresh vegetables, a superabundant provision of mineral matter, and have, moreover, always at our elbows a supply of salt, there can never be any lack of saline materials in our food. The branny matter of the flour is both indigestible and irritating to the prima; vias ; and although it may not injure, or may even be useful, to the strong and healthy, it is quite an unfit element in food designed for the weak and tender membranes of the invalid and infant. 1 Flours of this class can now be readily obtained through any of the large druggists. 192 II. PREPARATION AND USE OF ARTIFICIALLY DIGESTED FOOD. {Third I/umleicm Lecture.) Summary : — Introductory Remarks — Pancreatic digestion of milk — Modi- fied casein or metacasein — Directions for the preparation of peptonised articles of food — Peptonised milk — Peptonised gruel — Peptonised milk-gruel— Peptonised soups, jellies, and blancmanges — Peptonised beef-tea — Nutritive value of peptonised food— Clinical experience of peptonised food — In uraamic vomiting — In gastric catarrh — In the crises of cardiac disease — in pernicious anaemia — In gastric ulcer — In pyloric and intestinal obstruction — Use of pancreatic extract as an addition to food shortly before it is eaten — pancreatic extract as an addition to nutritive enemata. The suggestion to administer to invalids artificially digested food appears at first sight a somewhat startling proposal. So great an interference with the order of nature would seem to go beyond the legitimate province of art. But when we reflect how largely art already interferes in the preparation of our food, the taking of this further step will appear less surprising. The practice of cooking is in reality as complete a departure from the ways of untutored nature as artificial digestion would be. Among the almost countless species of animals, not one of them, except man alone, cooks his food, insomuch that man has, not inaptly, been defined as the cooking animal. My previous remarks on the effects of cooking (see p. 177, et seq.) go to show that the changes impressed on FLUID MEAT 193 food by cooking form an integral part of the work of digestion — a part which we of the human race get done for us by the agency of artificial heat — but a part which the lower animals are compelled to perform by the labour of their own digestive organs. It must also be borne in mind that the digestive process carried on in the alimentary canal is, strictly speaking, executed on a doubling of the exterior surface, and not in the true interior of the body. If we take these considerations into account, it will appear, I think, not unnatural that we should try to help our invalids by administering their food in an already digested, or partially digested, con- dition. We should thereby only be adding one more to the numberless artificial contrivances with which our civilised life is surrounded. Dr. Pavy 1 was, I believe, the first to carry into actual practice the idea of preparing an artificially digested food. At his suggestion, Messrs. Darby and Gosden in- troduced a preparation which consisted of meat reduced to a fluid state by artificial digestion. The formula for this preparation has not, so far as I know, been made public. It is still in the market, 2 and is sent out and advertised by Savory and Moore under the title of ' Darby's Peptonised Fluid Meat.' A specimen of this preparation is on the table before me. It has the appear- ance of a light brown very thick treacle. It has a strong salt taste and an agreeable meaty flavour, without any bitterness. It is mostly soluble in water. The solution does not precipitate on boiling, nor with nitric acid, and it gives a strong reaction of peptone with Fehling's solu- tion, and with tannin. I have also before me a specimen of artificially digested 1 A Treatise on Food and Dietetics. 2nd ed., p. 559. 2 This was written in 1880. 194 THE GASTRIC METHOD meat prepared by Mr. Benger. It is a greyish-looking extract, with a pleasant meaty flavour, and is quite devoid of bitterness. It dissolves mostly in water, and the solution gives the usual reactions of peptone in great intensity. Mr. Benger informs me that it is made by operating, at a temperature of about 140°Fahr., on finely triturated raw beef with pancreatic extract and a little carbonate of soda. The solution thus obtained is neu- tralised with hydrochloric acid, and then evaporated at 212° Fahr. to the consistency of a solid extract. Both of these preparations appear to me to be much superior in value to any of the meat extracts hitherto introduced. But however useful preparations of this class may prove to be, in a limited range of circumstances, it is pretty evident that if artificially digested food is to be employed on a large scale, and among all classes, means must be found to bring the preparation of it within the range of culinary operations and the apparatus of the kitchen and sick-room. The difficulty hitherto encountered in the production of an artificially digested or peptonised ' food suitable for invalids, is mainly owing to the use of the gastric method in its preparation. If you subject any native article of food — say milk, bread, egg, or meat — to artificial diges- tion with pepsin and hydrochloric acid, you destroy more or less completely the grateful odour and taste, and the inviting appearance, which made it desirable as food, and convert it into an unsavoury mess, from which the human palate turns away with disgust. The unsavouri- ness of artificially digested food is, however, not due to any ill taste or smell inherent in the products of diges- tion — which, when purified, are both odourless and free 1 I may be permitted to use the word ' peptonised ' as a convenient abbreviation for the phrase ' artificially digested.' THE PANCREATIC METHOD 195 from any unpleasant flavour — but to a number of bye- products of various kinds, which accumulate as digestion proceeds. One of these bye-products is a substance with a pure bitter flavour, which seems to be a constant ac- companiment of gastric digestion. It is also developed in some cases in the later stages of pancreatic digestion. I have not observed this bitter substance, except in the digestion of proteids. It is evidently a normal educt of the process, and its presence probably accounts, in most cases, for the bitter flavour of the eructations of which dyspeptics complain, and which is generally attributed to the regurgitation of bile. It would be interesting to know more about this subject. My own efforts to produce a palatable peptonised food have been chiefly directed to the pancreatic method. The pancreas excels the stomach as a digestive organ, in that it has power to digest the two great alimentary principles, starch and proteids ; and an extract of the gland is possessed of similar endowments. This double power is a manifest advantage in dealing with vegetable aliments, which contain both starch and proteids. Any extract of pancreas may be used for the prepara- tion of artificially digested food, but the most suitable are those prepared with dilute spirit or chloroform water. The extract sent out by Mr. Benger, under the name of 1 Liquor Pancreaticus,' l is an almost faultless pharma- ceutical preparation. It is made by extracting perfectly fresh and finely chopped pancreas with four times its weight of dilute spirit. By some ingenious devices, Mr. Benger has succeeded in overcoming the mechanical difficulties of the manufacture, and has produced an ex* tract which possesses the diastasic and proteolytic pro- perties of the pancreas in a highly concentrated degree. 1 Sent out by Mottershead & Co., chemists, Manchester. o 2 196 PANCREATIC DIGESTION OF MILK It is a nearly colourless solution, with very little taste or smell beyond that of the spirit used to preserve it. It is of this preparation that I must be understood to speak in what I have now to say on the production of artificially digested food by pancreatic extracts. My attention was first turned to the artificial diges- tion of milk, and I soon found that it was possible, by means of pancreatic extract, to digest this important article of food with comparatively little disturbance of its taste and appearance. Milk contains all the elements of a perfect food, adjusted in their due proportion for the nutrition of the body. Two out of its three organic con- stituents — namely, the sugar and the fat— exist already in the most favourable condition for absorption, and require little, if any, further assistance from the digestive fer- ments. It is therefore obvious that if we could change the casein of milk into peptone without materially alter- ing the flavour and appearance of the milk, such a result would go far towards solving the problem of supplying an artificially digested food for the use of the sick. PANCKEATIC DIGESTION OF MILK. When milk is subjected to the action of pancreatic extract, at a temperature of 100° F. (38° C), in an open glass vessel, a series of changes take place in it which are highly interesting to watch. The first thing that arrests the observer's notice is that the tough wrinkled skin which quickly forms on the surface of warm milk when exposed to the air is either not produced at all, or is only produced in a very imperfect degree. In its stead there forms a slight brittle and perfectly smooth pellicle of quite a different appearance. The next thing noticed is that the milk becomes more or less softly curdled. By-and-bye the curds begin to redissolve, and the milk PANCREATIC DIGESTION OF MILK 197 gradually rcassumes its originally diffluent condition. A portion of the curd is, however, very resistent, and re- mains undissolved for many hours. If the milk be diluted beforehand with one-third or one-fourth of its bulk of water, this curdling phase is altogether omitted, or is only observed as a slight and transient thickening. Next follows a very curious change of aspect. The milk loses its glossy white appearance, and gradually assumes a dull yellowish-grey shade which is characteristic, and the degree of which enables the practised eye to judge with considerable precision how far the peptonising pro- cess has advanced. This change of aspect is, however, by no means conspicuous, and would scarcely be remarked in a cursory observation, except by comparison with un- altered milk. While these changes are proceeding, the milk gradually loses its proper flavour, and at length develops a pure bitter taste, which is to many palates not disagreeable. No really unpleasant flavour is pro- duced unless the process be allowed to go on to incipient decomposition. The progressive transformation of the casein into peptone, of which these outward signs are the indica- tions and accompaniments, may be followed by testing the milk from time to time with acetic acid. At first the addition of the acid causes an abundant precipita- tion of curdy matter, but this reaction progressively diminishes in intensity until at length it ceases alto- gether. When this point is reached the transformation may be regarded as complete. All the casein has been changed into peptone — even nitric acid no longer causes a precipitate. The time occupied in the transformation (supposing the temperature and the activity of the preparation to be constant) depends on the quantity of pancreatic extract added, and may be made to vary from 198 METACASEIN a few minutes to several hours. In the ordinary opera- tion of preparing peptonisecl milk for invalids, two or three teaspoonfuls of the liquor pancreaticus are added to one pint of milk diluted with a third of its bulk of water. With these proportions, and at a temperature of 100° Fahr., the process is usually completed in from two and half to three hours. Modified Casein or Metacasein. — The conversion of casein into peptone does not take place by a direct trans- formation of the one body into the other. You all know that milk does not curdle or coagulate in the least degree on being boiled, but when milk is subjected to the action of pancreatic extract (provided no alkali be added) it speedily loses this negative property, and curdles abun- dantly on boiling. This coagulation on boiling is most intense soon after the addition of the extract, and it very gradually diminishes in intensity as the action goes on, and ceases altogether about the same time that acetic acid ceases to cause a precipitate. It was, moreover, found that if the milk was boiled at the period of the greatest intensity of this reaction, and thrown on a filter, the whole of the albuminoid matter of the milk was caught on the filter in the form of curds, and the filtrate showed not the slightest reaction of casein. These re- actions revealed the interesting fact that in the transfor- mation of casein into peptone by pancreatic extract, the first step in the process is the conversion of casein into an intermediate body, and that it is this intermediate body which is subsequently gradually changed into pep- tone. This body may provisionally be called metacasein, signifying thereby that it is still casein, but in a modified condition. Metacasein is characterised by two reactions, which, taken together, serve to distinguish it from other proteid bodies — it is coagulated by boiling in neutral METACASEIN 199 media, and it is precipitated in the cold by acetic acid. The conversion of casein into metacasein in pancreatic digestion takes place almost suddenly, as is shown by the following experiment : — 5 cubic centimeters of pan- creatic extract were added to 100 cubic centimeters of milk, diluted with one-fourth of its bulk of water, and maintained at blood-heat. The first slight, almost doubt- ful, evidence of coagulation on boiling was perceived in three minutes ; in five minutes coagulation on boiling was pronounced ; and in nine minutes it had reached its maximum. From this point coagulation on boiling, and precipitation on the addition of acetic acid, dimi- nished in intensity pari passu very gradually for a period of two hours, when both reactions finally ceased. Taking these observations and reactions together, it is evident that the conversion of casein into metacasein constitutes a first and distinct step in the transformation of casein by trypsin, and that this step is antecedent to the further and slower changes by which metacasein is transmuted into peptone. It is impossible not to see in this a striking analogy with the sudden transformation of gelatinous starch into soluble starch under the action of diastase, as described on a previous page (p. 20). "When milk is rendered slightly alkaline by the pre- vious addition of a little bicarbonate of soda, no precipi- tation on boiling occurs during its digestion by pancreatic extract. But the metacasein is nevertheless produced, and its presence may be detected by carefully saturating the alkali, and then boiling. For although metacasein is precipitated on boiling when the solution is neutral, it is not precipitated when the solution is even slightly alkaline. This is the reason why, in preparing pepto- nised milk for the sick, it is desirable to add to it a small quantity of bicarbonate of soda. 200 PEPTONISED MILK The foregoing account of the behaviour of milk with pancreatic extract will greatly facilitate the comprehen- sion of the practical rules which must be followed in preparing peptonised dishes for invalids. DIRECTIONS FOE, THE PREPARATION OF PEPTONISED ARTICLES OF FOOD. Peptonised Milk. — A pint of milk is diluted with a quarter of a pint of water, and heated to a temperature of about 140° F. (60° C). Two teaspoonfuls of liquor pancreaticus, together with twenty grains of bicarbonate of soda, are then mixed therewith. The mixture is then poured into a covered jug, and the jug is placed in a warm situation in order to keep up the heat. At the end of an hour or an hour and half the product is raised to the boiling point. It can then be used like ordinary milk. The object of diluting the milk is to prevent the curdling which would otherwise occur and greatly delay the peptonising process. The addition of bicarbonate of soda prevents coagulation during the final boiling, and also hastens the process. The purpose of the final boil- ing is to put a stop to the ferment action when this has reached the desired degree, and thereby to prevent certain ulterior changes which would render the product less palatable. The degree to which the peptonising change has advanced is best judged of by the develop- ment of the bitter flavour. The point aimed at is to carry the change so far that the bitter taste is faintly perceived, but is not unpleasantly pronounced. As it is. impossible to obtain pancreatic extracts of absolutely constant strength, the directions as to time and quantity must be understood with a certain latitude. The extent of the peptonising action can be regulated either by in- creasing or diminishing the dose of the liquor pancre- PEPTONISED MILK 201 aticus, or by increasing or diminishing the time during which it is allowed to operate. By skimming the milk beforehand, and restoring the cream after the final boil- ing, the product is rendered more palatable and more milk-like in appearance. Preparation of Peptonised Milk in the Cold. — The action of pancreatic extract on milk goes on at the ordi- nary temperature of the air exactly in the same way as at blood-heat — except that it is slower, and requires a longer time for completion. The cold method has, how- ever, a convenience and simplicit}* which recommends it for general use in the sick-room. I have accordingly drawn up the following directions for the preparation of peptonised milk at a temperature of 60° to 65° Fahr., which may be regarded as the ordinary degree of warmth maintained in rooms occupied by invalids. In the winter season it will be necessary to slightly warm the ingre- dients beforehand in order to bring them to the due tem- perature, but in the warmer seasons the operations can be carried on without any preliminary heating. A pint of milk is diluted with half a pint of lime-water 1 — or with half a pint of water containing twenty grains of bicarbonate of soda in solution. To this are added three teaspoonfuls of liquor pancreaticus. The mixture is then set aside in a jug or other convenient vessel, in the sick-room, for a period of three or four hours. At the expiration of this time the milk is far advanced in the process of digestion, and has developed a slightly bitter taste. It is now ready for use. It may be used cold, either alone, or with soda-water, which covers the bitter- ish taste remarkably well — or it may be warmed and sweetened for administration to infants. 1 I owe the suggestion to use lime-water to Dr. Watkins, of Newton- le-Willows. 202 PEPTONISED GRUEL If milk thus prepared be consumed at the period in- dicated — that is to say, at the end of three or four hours, it need not undergo any final boiling — it is better, indeed, to use it without boiling, because the half-finished pro- cess of digestion will still go on for a time in the stomach. But if milk thus prepared has to be kept much longer, it is advisable to raise it for a moment to the boiling point, so as to bring the action of the ferment to a ter- mination, and thus to prevent those ulterior changes which render the product disagreeable to the palate. The process can be regulated with the utmost nicety by occasionally tasting the mixture, and watching the development of the bitter flavour — and it can be perma- nently arrested at any moment by heating the product to the boiling point. Peptonized Gruel. — Gruel may be prepared from any of the numerous farinaceous articles which are in com- mon use — wheaten flour, oatmeal, arrowroot, sago, pearl barley, pea or lentil flour. The gruel should be very well boiled, and made thick and strong. It is then poured into a covered jug, and allowed to cool to a lukewarm temperature. Liquor pancreaticus is then added in the proportion of two teaspoonfuls to the pint of gruel. At the end of three hours the product is boiled and strained. The action of pancreatic extract on gruel is two-fold — the starch of the meal is converted into sugar, and the albuminoid matters are peptonised. The conversion of the starch causes the gruel, however thick it may have been at starting, to become quite thin and watery. The bitter flavour does not appear to be developed in the pancreatic digestion of vegetable proteids, and peptonised gruels are quite devoid of any unpleasant taste. It is difficult to say to what extent the proteids are peptonised in the process of digestion by pancreatic extract. The PErTONISED MILK-GRUEL 203 product, when filtered, gives an abundant reaction of peptone ; but there is a considerable amount left of un- dissolved material. Most of this, no doubt, consists of insoluble vegetable tissue, but it also contains some on- liberated amylaceous and albuminous matter. Peptonised gruel is not generally, by itself, an acceptable food for invalids, but in conjunction with peptonised milk (pep- tonised milk-gruel), or as a basis for peptonised soups, jellies, and blanc-manges, it is likely to prove valuable. Peptonised Milk-gruel. — This is the preparation of which I have had the most experience in the treatment of the sick, and with which I have obtained the most satisfactory results. It may be regarded as an artificially digested bread-and-milk, and as forming by itself a com- plete and highly nutritious food for weak digestions. It is very readily made. First, a good thick gruel is pre- pared from any of the farinaceous articles above men- tioned. The gruel, while still hot, is added to an equal quantity of cold milk. The mixture will have a tem- perature of about 125° F. (52° C). To each pint (550 cubic centimeters) of this mixture, two teaspoonfuls of liquor pancreaticus, and twenty grains of bicarbonate of soda are added. It is then set aside in a warm place for two or three hours, and finally raised to the boiling point and strained. The bitterness of the digested milk is almost completely covered in the peptonised milk-gruel; and invalids take this compound, if not with relish, with- out the least objection. Since the first publication of these lectures, pepto- nised milk-gruel has found favour with many practi- tioners, and has come into considerable use among their patients. I find, however, that some persons fail to pep- tonise milk-gruel so as to make it acceptable to the palate and stomach of the invalid. This is entirely due to 204 PEPTONISED SOUPS AND JELLIES allowing the peptonising process to go on too far. Arti- ficial digestion, like cooking, must be regulated as to its degree ; and it is easy to regulate the degree of artificial digestion by the length of time during which the pro- cess is allowed to go on. It must be remembered that liquor pancreaticus (and every other form of pancreatic extract) is more or less variable in its activity, just as the fires used in cooking vary in their intensity, and that allowance must be made for this variability. If the liquor pancreaticus is very active the slight bitterness, whereby it is known that the process has been carried far enough, is developed in an hour, or less ; but if the preparation is not so active two or three hours may be required to reach the same point. It must further be borne in mind that the warmer the temperature at which the process is carried on the quicker is the action of the ferment. The practical rule for guidance is to allow the process to go on until a faintly perceptible bitterness is developed, and not longer. As soon as this point is reached the milk-gruel should be raised to the boiling point, so as to put a stop to further changes. Peptonisecl Soups, Jellies, and Blanc-manges. — I have sought to give variety to peptonised dishes by preparing soups, jellies, and blanc-manges containing peptonised aliments. In this endeavour I have been assisted by a member of my family, who has succeeded beyond my expectations. She has been able to place on my table soups, jellies, and blanc-manges containing a large amount of digested starch and digested proteids, pos- sessing excellent flavour, and which the most delicate palate could not accuse of having been tampered with. Soups were prepared in two ways. The first way was to add what cooks call ' stock ' to an equal quantity of pep- tonised gruel, or peptonised milk-gruel. A second and PEPTONISED BEEF-TEA 205 better way was to use peptonised gruel, which is quite thin and watery, instead of simple water, for the purpose of extracting shins of beef and other materials employed for the preparation of soup. Jellies were prepared simply by adding the due quantity of gelatin or isinglass to hot peptonised gruel, and flavouring the mixture according to taste. Blanc-manges were made by treating pepto- nised milk in the same way, and then adding cream. In preparing all these dishes it is absolutely necessary to complete the operation of peptonising the gruel or the milk even to the final boiling before adding the stiffening ingredient. For if pancreatic extract be allowed to act on the gelatin, the gelatin itself undergoes a process of digestion, and its power of setting on cooling is utterly abolished. Peptonised Beef -tea. — Half a pound of finely minced lean beef is mixed with a pint of water and 20 grains of bicarbonate of soda. This is simmered for an hour. When it has cooled down to a lukewarm temperature, a tablespoonful of the liquor pancreaticus is added. The mixture is then set aside for three hours, and occasionally stirred. At the end of this time the liquid portions are decanted and boiled for a few seconds. Beef-tea pre- pared in this way is rich in peptone. It contains about 4*5 per cent, of organic residue, of which more than three-fourths consist of peptone — so that its nutritive value in regard to nitrogenised materials is about equiva- lent to that of milk. When seasoned with salt it is scarcely distinguishable in taste from ordinary beef-tea. The extreme solubility of digested products — whether •of starch or of proteids — detracts from their acceptability to healthy persons. To them the}- appear thin and watery — they miss the sense of substance and solidity which is characteristic of their ordinary food. But to the weak 206 NUTRITIVE VALUE OF PEPTONISED FOOD invalid without appetite this sense of substance or thickening is generally objectionable, and he takes with more ease an aliment which he can drink like water. The jellies and blanc-manges, on the other hand, give to invalids of more power that sense of resistance and solidity which is desired by those of stronger appetite. NUTEITIVE VALUE OF PEPTONISED FOOD. At the outset of this inquiry we are met with the question : Is it certain that the ultimate products of digestion are of equal nutritive value to the mixed transi- tional products which are produced in succession, and probably absorbed as the food is gradually transformed in the alimentary canal ? — in other words, are maltose and peptones alone as valuable to the economy as a mixture of these substances with the several dextrines and hemipeptones which are presented to the absorbent surfaces in the course of natural digestion ? With regard to the products of starch-digestion, no direct experiments have been made on the nutritive value of maltose, and we can do little more than conjec- ture that the intermediate dextrines have a usefulness of their own. That they are absorbed seems proved (as might have been expected from their known diffusibility) , for they have been detected in the blood, and especially in the blood of the portal vein. With regard to peptones, we have more information. It was naturally assumed by the earlier observers who identified peptone as the chief ultimate product of diges- tion that this was the form under which proteids were taken up by the absorbents, and introduced into the blood for the nutrition of the tissues. But some twenty years ago doubts were cast on this conclusion. It was alleged by Briicke and Voit that the nutrition of the tissues was NUTRITIVE VALUE OF PEPTONISEB FOOD "207 maintained not by peptone, which was unfitted for this purpose, but by soluble albumen, which was absorbed in the undigested state from the primse viae, and that the office of peptone was a subordinate one, resembling that of gelatin, and consisted in aiding to preserve the tissue- albumen from too rapid destruction. Direct observa- tions on the nutritive value of peptones have, however, shown this paradoxical view to be untenable. As the point is one of importance, I will endeavour to lay before you the proofs which have been already adduced cf the food-value of peptones, and I will supplement these by some observations made by myself. P. Plosz 1 was the first to put this question to the test of direct experiment. He fed a puppy dog weighing 1,302 grams with an artificial compound made of fat and sugar, in imitation of milk, but in which the casein was replaced by artificially digested fibrin. In the course of eighteen days of this diet the dog grew and increased 501 grams in weight. E. Maly 2 performed a similar experiment on a pigeon. He first fed the pigeon for several days on a regulated quantity of wheat until he had ascertained the quantity requisite to keep the bird in a state of nutritive equili- brium, in which it neither gained nor lost weight. He then made an artificial corn from starch, fat, gum, salts, and water, but in which the gluten was replaced by fibrin-peptone, and fed the pigeon on the same quantity of this artificial corn as he had before given of the natural corn. Under this novel diet the bird, after a short ap- prenticeship, not only maintained its weight, but actually put on flesh. This experiment seemed to show that pep- tone was even superior to natural gluten as a nutriment. 1 Pfluger's Archiv f. cl. ges. Physiologic, 1874, p. 323. - Ibid. p. 585. 208 NUTRITIVE VALUE OF PEPTONISED FOOD It was, however, objected to these experiments that they did not rigorously prove that peptone could build up the tissues, inasmuch as the increase of weight might have been due to an excessive accumulation of fat or of water, and that there might have been not an increase, but a decrease of the structural elements which contained nitrogen. To meet these objections, Plosz and Gyergyai l insti- tuted a third set of experiments on a dog weighing 2,753 grams. The dog was brought down by a diet of simple water to a weight of 2,531 grams. He was then fed on a mixture composed of sugar, starch, and fat, and contain- ing, in addition, 5 per cent, of purified peptone. Of this mixture about 400 grams were daily administered to the animal for a period of six days. In these six days the dog took in with his food 14-45 grams of nitrogen, but the total of the nitrogen excreted by the urine and faeces only amounted to 13*46 grams, so that nearly one gram of nitrogen had been retained in the body of the animal, which had increased in weight 259 grams. This experiment went to prove that peptone served to repair the wear and tear of the nitrogenised structural ele- ments, and even contributed something to the increase of weight. Adamkiewicz, 2 by a still more rigorous method, in a laborious series of experiments on a dog which was fed on a diet wherein the only possible source of nitrogen was peptone prepared from blood-fibrin, arrived at the con- clusion that peptone supplied nitrogen to the solid tissues, and that it possessed a nutritive value equal to albumen, or even slightly superior ; and that therefore it could not be looked on as a bye-product of digestion, 1 Pfliiger's Archiv, Bd. x. 1875, p. 536. 2 Natur und Nahriucrth des Peptons. Berlin, 1877. EXPERIMENT WITH PEPTONISED .MILK 209 but as the chief resultant of the transformation of pro- teids in the alimentary canal. The experiments above cited seem sufficient to settle definitely the question raised by Briicke and Yoit, and to establish the nutritive value of peptone as a source of nitrogen to the tissues. It seemed, however, desirable to obtain direct proof of the nutritive value of peptonised milk as compared with the natural article. My observa- tions led me to the conclusion that it was easier to get a supply of peptonised aliment suitable for invalids by the artificial digestion of milk by pancreatic extract than by any other method. But in so important a matter as the feeding of invalids, inference and conjecture seemed hardly a sufficient basis for actual practice. The questions I proposed to myself were — (1) Is arti- ficially digested, or peptonised, milk alone sufficient to sustain nutrition? and (2) is it as efficient in this respect as natural milk ? For the purpose of answering these questions I procured four kittens, of the same brood, eight weeks old. Kittens at this age thrive perfectly on an exclusively milk diet. Two of the kittens were fed on natural milk, and the other two on milk previously digested by pancreatic extract. The digestion of the milk in the latter case was carried out to full completion — that is to say, until the milk became greyish and bitter, and no longer gave any precipitate with acetic acid, nor even with nitric acid. The animals were per- mitted to have as much of their respective foods as they could consume. The experiment was continued for a period of twenty days. The quantity consumed by each pair was as nearly as possible the same. All four con- tinued in perfect health, and took their nutriment greedily. I was surprised to find that the pair fed 021 peptonised milk showed no repugnance to the bitter taste p 210 EXPERIMENT WITH PEPTONISED MILK of their food, but appeared to relish it quite as well as their companions did their natural milk. The following table exhibits the gain in weight at the end of twenty days by each of the four kittens. The weights are given in grains, and in round numbers. Diet t •*■ nv; u Weight at the Initial Weight end | f20days Increase of Weight Increase of Weight per cent. Natural milk ] Fully pepton- I ised milk \ No. 1—338 514 „ 2—558 835 „ 3—403 626 „ 4—374 562 176 280 223 188 52 50 55 50 The table shows that the percentage increase of weight was very nearly alike in all four animals. No difference could be perceived in the sleekness of their coats nor in the vivacity of their gambols. The experiment proves that peptonising the milk in no degree spoils its nutritive value. It also shows, as might have been expected, that in healthy animals with abundance of digestive power there is no advantage to be gained from the administra- tion of food in a predigested state. The quantity of food which is taken and absorbed appears to be regulated not so much by the quantity which can be digested as by the quantity which can be assimilated. This experiment had an interesting sequel. After Nos. 3 and 4 had been fed on full if peptonised milk for a period of twenty days, they were fed for a period of ten days on partially pep- tonised milk. By using a less quantity of the pancreatic extract in proportion to the milk, and by allowing the process of artificial digestion to go on for not more than half the time allowed in the previous experiment, only a partial conversion of the casein was effected. As nearly as I could judge by the precipitate caused with acetic acid, the casein was digested to about the extent of one EXPERIMENT WITH PEPTONISED MILK 211 half. Under these circumstances I certainly expected that Nos. 3 and 4 would gain weight as before, and would continue to thrive as well as Nos. 1 and 2. It might have been anticipated that under these new con- ditions the proper digestive powers of Nos. 3 and 4 would come into play and complete with ease the unfinished work of the artificial process. But events did not pass exactly as I anticipated. The annexed table shows the actual results. The weights, as before, are given in grams. Diet Initial Weight Weight on 3rd day Weight on 5th day Weight on 7th day Weight on 10th day Natural milk - Half-pepton- ( ised milk \ No. 1—514 „ 2—833 „ 3—626 ., 4—562 551 — sain 37 900— .. 62 693— .. 67 645— . 570— gain 19 936— „ 36 687— loss 6 638— .. 7 593— gain 23 993— „ 57 681— loss 6 648— gain 10 618— gain 25 1063— „ 70 693— .. 12 683— „ 35 No interval was allowed to elapse between the two sets of experiments, so that the initial weights in the second set are the same as the terminal weights in the first set. The abrupt alteration in the diet of Nos. 3 and 4 produced a marked disturbance in their nutrition. But there was no declension in their general well-being, and they con- tinued to take their modified diet with the same avidity as before. In the first three days Nos. 3 and 4 showed an unusual increase of weight — an increase quite out of proportion to that of their companions. Then came a check; in the next four days they not only showed no gain, but showed even a slight loss of weight. In the last three clays they began to gain weight again, and were evidently recovering from the temporary check caused by their change of diet. The explanation of this series of events which has presented itself to my mind is the following, but I by no means wish to lay stress on its accuracy. It seemed as if the enforced rest imposed on p 2 212 DEDUCTIONS FROM THE EXPERIMENT the digestive organs for a period of twenty days, during the use of fully predigested food, had temporarily diminished their natural vigour — just in the same way as the disuse of a limb diminishes for a time the strength of its muscles. During this first period, immediately following the change of diet, the unemployed digestive powers were suddenly called upon to resume their wonted activity ; but, owing to their enfeeblement from disuse, they were unable to respond to the call with due prompt- ness, and undigested materials accumulated in the intes- tines. This accumulation accounted for the unusual increase in weight during the first period. During the next period the digestive embarrassment made itself felt, and gave a check to the processes of growth and nutri- tion, and the animals ceased to grow and gain weight. During the last period the temporary enfeeblement of the digestive organs was passing away, in proportion as renewed exercise was restoring them to their original vigour, and growth and increase of weight again com- menced. Whether this explanation be trustworthy or not, the lesson indicated by it is probably a true one — namely, that except in extreme cases, when the digestive power is wholly lost or in complete abeyance, it is more advan- tageous to use a food which has been subjected to partial artificial digestion than food in which the process has been carried out to completion. If the patient possess any digestive power at all, it is better that that power should be kept in exercise than that it should be per- mitted to deteriorate still further from total disuse. This is in agreement with the rule we apply in other cases of enfeebled function, according to which we endeavour to combine partial rest with moderate exercise. CLINICAL EXPERIENCE 213 CLINICAL EXPERIENCE OF PEPTONISED FOOD. The extreme difficulty of arriving at reliable conclu- sions in regard to the effect of therapeutical agents is well known to every sober-minded inquirer. The diffi- culty is not less, but probably greater, in judging of the effects of dietetic means. I have now had a consider- able experience, extending over a period of two years, 1 of the use by invalids of peptonised milk and peptonised milk-gruel, and it would be an easy task for me to recite a string of cases in which improvement and recovery followed the use of these articles of diet. But evidence of this sort would be wholly delusive unless checked by such an analysis of the circumstances of each case as would enable me to isolate the influence of the dietetic means. In the immense majorit}* of cases such an ana- lysis would be obviously impossible, the conditions to be taken into account would be too numerous, and their relative influence too difficult to determine. In a ques- tion of this kind one is obliged, in a large degree, to fall back on general impressions, and on deductions based on physiological considerations. Nevertheless there are certain cases — most of them cases of incurable disease — in which the conditions are sufficiently simple to per- mit direct trustworthy conclusions to be drawn. I found that peptonised milk-gruel was generally preferred, as being more agreeable to the palate, to simple peptonised milk ; and by far the larger number of my observations were made with the former prepara- tion. I was also soon satisfied that, with most rare ex- ceptions, peptonised milk-gruel was perfectly acceptable to the invalid's stomach, and that a diet composed exclu- sively of this article could be used for many consecutive weeks without the slightest Bign of failure of nutrition. 1 Written in 1880. 214 CLINICAL EXPERIENCE The cases in which the use of peptonised aliment appeared to produce the most striking benefits were those in which complete anorexia prevailed, and those in which the stomach was intolerant of food, and immediately re- jected every form of nutriment. A brief review of the results obtained in cases of this kind will, I think, prove instructive. Urcemic Vomiting. — In advanced Bright 's disease in- cessant vomiting is sometimes a distressing and intract- able symptom. In some cases of this class I have seen the vomiting at once and permanently allayed by the use of peptonised milk-gruel. The downward course of the disease may not have been a moment checked, but the relief to the dying patient was great. Gastric Catarrh. — That form of gastric catarrh which is the Nemesis of alcoholic excess often yields immedi- ately to the use of peptonised food. In the later periods of cirrhosis there frequently prevails severe intolerance of every kind of food — the stomach rejecting even beef- tea and diluted milk in the smallest quantities. The relief afforded by the use of peptonised milk-gruel in some of these cases is most striking — the vomiting ceases almost from the first, and the intolerable sense of dis- tension diminishes. Crises of Cardiac Disease. — Persons suffering from dilatation and valvular incompetency usually encounter one or more crises which are susceptible of relief before finally succumbing to their disorder. These crises are marked by a general venous stagnation with severe con- gestion of the lungs, liver, and kidneys, and rapidly rising dropsy. Associated with these symptoms, there is generally almost complete inability to take food, and sleeplessness. In this condition I have seen marked relief follow the use of peptonised aliment. I have long CLINICAL EXPERIENCE 215 observed, as I doul >t not have many of you, that the condition here described is often alleviated in the a striking manner by the use of exclusively liquid nourish- ment — such as milk or milk-gruel, given in small por- tions sub-continuously, or Bippingly, as it were, through- out the waking hours — the patient being never permitted to take a distinct meal, nor a particle of solid food. A- my practice has been to direct, in cases of this class, the administration of the peptonised aliment in this sipping fashion, the gratifying results noted have been partly due to the mode of administration ; but I have been convinced by more than one example, when the same liquid nourishment, in the natural and in the predigested condition, has been used in succession, that there was a distinct superiority in the predigested article. Pernicious Anaemia. — In the earlier periods of this singular disorder, I am inclined to hope that predigested aliment may prove a valuable resource. In cases where the disease, although fully declared, was still of com- paratively recent origin, I have, in the last eighteen months, seen the symptoms checked under the use of peptonised milk-gruel. In one case, owing to the irrita- bility of the stomach, the milk- gruel was at first adminis- tered per rectum with pancreatic extract, but was after- wards tolerated by the stomach. In three of these cases the amelioration went on to complete restoration. In cases of longer standing I have failed by the same means to obtain the slightest improvement. Gastric Ulcer. — The use of an exclusively liquid nourishment given sub-continuously, in the manner before indicated, is a well-known and most efficacious mode of treatment in these cases. But since adopting the plan of giving peptonised milk-gruel, I think I have perceived that the results were distinctly better than 216 CLINICAL EXPERIENCE before, especially in cases associated with epigastric pain. The almost absolute rest procured by this food for the ailing organ appeared to be an additional advantage. I may be permitted to mention one case. The patient had suffered from copious and repeated haematemesis, and from severe epigastric pain. The irritability of the stomach was such that the simplest nourishment, given in the smallest quantities, was immediately rejected. Peptonised milk-gruel -was, however, tolerated at once ; vomiting only occurred two or three times during the two first days of the treatment, and then ceased, as did likewise the epigastric pain. This patient used no other food for a period of six weeks, and took daily from two to three quarts — with steady recovery of flesh and strength. Pyloric and Intestinal Obstruction. — Peptonised ali- ment would appear to be especially suitable for use in these cases, but, so far, I have been somewhat disap- pointed in the results. The vomiting has generally been effectually controlled, but I have not been able to con- vince myself, in cases of pyloric stricture, that the fatal event was delayed even a single day. When the obstruc- tion has been temporary, and due to a removable cause, the results have been of course more satisfactory. I should be glad to see a further trial made of peptonised, or partially peptonised, milk in the gastric and intestinal catarrh of infants. In one severe case of this class a favourable result was immediately obtained ; in another case there was greater tolerance of food, and more comfort after it, than with the use of simply diluted milk. It would be interesting also to have ex- perience of the use of peptonised aliment in typhoid fever and in old age. The greater variety which can now be given to this form of food by the preparation of PANCREATIC EXTRACT [JSED \\" I II I FOOD 21 i peptonised soups, jellies, and blanc-manges will serv< to obviate the monotony sometimes complained of under the continuous use of peptonised milk-gruel. THE USE OF TANCREATIC EXTRACT AS AX ADDITION 10 FOOD SHORTLY REFORE IT IS EATEN. The administration of pancreatic extract with, or im- mediately after, a meal can, I think, have only a limited utility. On entering the stomach the pancreatic extract would encounter the acid of the gastric juice, and when this rose above a certain point the activity of the ferments would be destroyed. Still a not inconsiderable interval of time must elapse before this point is reached, and during this interval the pancreatic ferments would ac- complish a certain amount of work. I have repeatedly administered pancreatic extract in this way, but I am unable to say positively that I have seen benefit from this mode of administration. There is, however, a modi- fication of this plan, which I have lately put in practice. that promises better results. It is to add the extract to the food fifteen or twenty minutes before it is eaten. Certain dishes commonly used by invalids — farinaceous gruels, milk, bread-and-milk, milk flavoured with tea or coffee or cocoa, and soups strengthened with farinaceous matters, or with milk — are suitable for this mode of treatment. A teaspoonful or two of the liquor pancrea- ticus should be stirred up with the warm food as soon as it comes to table. And such is the activity of the pre- paration that even as the invalid is engaged in eating — if he eat leisurely as an invalid should do — a change comes over the contents of the cup or basin — the gruel becomes thinner, the milk alters a shade in colour, or perhaps curdles softly, and the pieces of bread soften. 218 WITH NUTRITIVE ENEMATA The transformation thus begun goes on for a time in the stomach, and one may believe that before the gastric acid puts a stop to the process the work of digestion is already far advanced. This mode of administering pancreatic preparations is simple and convenient. No addition of alkali is re- quired, and, of course, no final boiling. The only pre- caution to be observed is that the temperature of the food, when the extract is added, shall not exceed 150° F. (65° C). This point is very easily ascertained, for no liquid can be tolerated in the mouth, even when taken in sips, which has a temperature above 140° F. (60° C). If therefore the food is sufficiently cool to be borne in the mouth, the extract may be added to it without any risk of injuring the activity of the ferments. Pattern/tic Extract as an Addition to Nutritive Erie- in at a. — Pancreatic extract is peculiarly adapted for ad- ministration with nutritive enemata. The enema may be prepared in the usual way with milk-gruel and beef- tea, and a dessert-spoonful of liquor pancreaticus should be added to it just before administration. In the warm temperature of the bowel the ferments find a favour- able medium for their action on the nutritive materials with which they are mixed, and there is no acid secretion to interfere with the completion of the digestive process. I have now had some experience in this method of alimentation, and have been satisfied with its success. In one case a patient suffering from postpharyngeal abscess, which entirely occluded the oesophagus, was nourished exclusively for a period of three weeks (until the abscess broke) on enemata of milk-gruel mixed with pancreatic extract. 219 III. THE USE OF MALT, AND ESPECIALLY OF MALT INFUSION, FOR THE PREDIGESTION OF STAKCHY FOOD. (From • The Practitioiur t ' December 1879.) Summary : — Various kinds of diastase — Conditions in which starch digestion is defective — Preparations of malt — Malt extracts — Malt infusion — Its mode of preparation, properties, and preservation — Note on the antiseptic properties of chloroform Administration of malt preparations with food— Predigestion of starchy food — Liebig's method — The use of malt infusion — Clinical experience. The digestion of starch consists, as is well known, in its conversion into dextrine and sugar. By this change starch becomes soluble and diffusible, and thereby adapted for absorption from the alimentary canal. It is further known that this conversion is effected partly by the saliva and partly by the pancreatic juice, and that the actual agent of the transformation is a special ferment contained in these secretions. As regards saliva, the ferment goes by the name of ptyalin, and is held to be identical with the diastase of malt. The correspond- ing pancreatic ferment has not received a distinctive name ; indeed, until recently it was not thought to be a separate body ; it was rather supposed that the pancrea- tic juice contained a single ferment which possessed manifold powers, and was able at the same time to pep- tonise proteids, to emulsify fats, and to convert starch into sugar. It is now, however, ascertained that these 220 ACTION OF DIASTASE several powers correspond to separate ferments. The question has, as yet, been scarcely raised as to whether the diastasic agents of the saliva of the pancreas, and of malt, are one and the same ferment, or whether there are not more than one, perhaps several, modifications, all capable of doing similar work. It may be regarded as probable, in view of certain recent observations, that the latter supposition will turn out to be correct. As regards the pancreas, I have obtained evidence, which I need not here particularise, that its diastasic agent is a distinct body from that of saliva and malt. Until further inquiry it will be convenient to use the word ' diastase ' as a common term, signifying an anxio- lytic ferment, that is to say, a ferment having the power of resolving the starch molecule into more diffusible bodies of the dextrine and sugar class ; and we may con- veniently designate diastasic agents according to their local source as malt diastase, salivary diastase, pancrea- tic diastase, and so forth. 1 Before diastase can exercise its power the cellulose investment of the starch granule must be ruptured. This is accomplished for the human subject by the art of cook- ing. In boiling and baking the starch-granules break up under the combined influence of heat and moisture, and the liberated starch swells out enormously by imbibition of water into a mucilage or jelly-like mass. Unless starch is previously changed into this gelatinous state it is acted on very slowly by the diastasic ferment. It is a matter of capital importance, therefore, in the sick room, to make sure that gruels, puddings, and other farinaceous dishes prepared for the invalid are thoroughly cooked. 1 These three by no means exhaust the list of local diastases. There is a diastase in the urine, in blood-serum, in the liver, and several other tissues of the body ; indeed, diastase seems to be one of the most widely diffused of all the soluble ferments, both in plants and animals. DEFECTIVE DIASTASIC POWER 221 Having premised so much, 1 pass to the consideration of the means we possess of artificially aiding the digestion of starch in cases where that process is defective from deficient diastasic power in the saliva and pancreatic juice. Unfortunately, our knowledge of the defect which it is proposed to remedy is very incomplete. Something, however, we do know with fair precision. We know that in infants under three or four months old the saliva has but a feeble diastasic power. I have further ascertained the significant fact that the pancreas of suckling calves is inert on starch, and the inference is strong that the pancreas of the infant at the breast is in the same pre- dicament. It is not probable that the diastasic power is wholly wanting in sucklings, seeing how r widely this power is distributed ; but it appears certain that it does not exist in sufficient amount to be available for the digestion of sensible quantities of starchy food. 1 This being so, it is obvious that farinaceous articles are unfit food for young infants unless artificial means are used to assist their digestion. With regard to older children and adults, we possess very little exact knowledge re- specting defective secretion of salivary diastase, and none at all respecting defective secretion of pancreatic diastase. We may nevertheless pretty safely conclude that when- ever the mouth is dry there is diminished supply of salivary diastase. In the febrile state, in advanced stages of most organic diseases, after alcoholic excesses, and in 1 The earlier opinion that the saliva of young infants was wholly wanting in diastasic power is not supported by recent researches. Both Schiffer and Korowin found that the secretions of the mouth of infants had a certain power of converting starch into sugar. Zweifel also found that the extract of the parotid (but not the submaxillary) glands of still- born children and of infants dying a few days after birth possessed this power, though apparently in feeble degree. Kxtract of the pancreas in I be same subjects was found inert. (Zweifel, Untersuchungen ilberden Vcrdauungscuppa/rat dcr Neugeborenen.) 222 MALT DIASTASE a multitude of niorbid conditions of various kinds, the mouth is dry and the saliva is scanty ; and it is reason- able to infer that we shall be doing an important service to our patients so suffering by remedying this defect by artificial means. In malted barley we have at command an unlimited supply of diastasic power, and it is not surprising that many eyes have been turned in this direction, and that many efforts have been made to utilise this resource as a means of assisting the digestion of starchy food when the supply of natural diastase is deficient. Of late re- newed interest in the subject has been created by the introduction into pharmacy of a new class of malt pre- parations, which, under the name of ' malt extracts,' are now challenging the attention both of the profession and the public in a very prominent manner. It will be worth while to inquire into the real value of these preparations which have suddenly become so popular. The task is made easy by the opportune appearance of a valuable report on malt extracts by W. E. Dunstan and A. F. Dimmock, published in the Pharmaceutical Journal for March 9, 1879. There is also a simpler and cheaper preparation of malt, namely, the cold-water infusion, which I desire to bring under notice. This latter pre- paration has not yet been formally introduced into medical practice ; but its diastasic action on starch has been minutely studied by Mr. 0' Sullivan, and by Messrs. Brown and Heron, in an important series of papers pub- lished in the Journal of the Chemical Society. 1 I propose to say something about both these preparations. Malt Extracts. — These articles are now manufactured 1 ' Contribution to the History of Starch and its Transformations,' by Brown and Heron, Journ. of the Chem. Soc, Sept., 1879. The papers of O'Sullivan are published in the same journal for the year 1872 and subsequent year. MALT EXTRACTS 223 on an enormous scale. No less than three limited com- panies exist whose sole business appears to he to make and sell malt extract. The best brands— those that appear to command our English market — are Corbyn's, Kepler's, Trommer's, and the variety called 'Maltine' : and the remarks I am about to make apply exclusively to these four articles, which may be regarded as practi- cally identical in character and merit. Malt extracts are essentially infusions of malt concentrated by evaporation to the consistency of a thick treacle. In order to preserve the activity of the diastase, which is destroyed by a heat exceeding 170° Fahr., the evaporation is conducted at a low temperature, in vacuo, by the aid of costly machinery, and this accounts for the high price of these preparations. Malt extracts thus prepared are of a dark-brown colour, very thick and viscid, and possess an agreeable, sweetish taste. Chemically they consist (besides water) of about 70 per cent, of a variety of sugar called 'maltose,' 2 per cent, of salts, a varying quantity of diastase, and about 6 per cent, of nitrogenised compounds. The exact condition of the nitrogenised matter is not known. Some of it, no doubt, exists as albuminoid material, but this does not seem to be in true solution, for I find that when malt extract is diluted with three or four times its bulk of water a copious precipitate falls, and the supernatant liquor shows only slight traces of albumen when tested with nitric acid. From these facts it may be gathered that the value of malt extract as a food is but little more than so much syrup, and that the statements made on this point in the advertisements are ridiculous exaggerations. These preparations have, however, important uses as vehicles — especially as a vehicle for cod-liver oil — which they suspend in the most perfect manner, and render acceptable to some stomachs which cannot tolerate the '224 MALT INFUSION oil in any other guise. But the proper medicinal value of malt extracts must be held to depend entirely on the amount of diastase which they contain, and in this respect I found that the four brands already named were highly active, but not all equally so. Malt Infusion. — The cold-water infusion of malt is an energetic diastasic agent, and trials of its action on various farinaceous gruels have led me to believe that it may with advantage be added to our list of malt pre- parations. I have adopted the following method and proportions as yielding a pharmaceutical preparation of convenient standard strength. Three ounces (or three piled-up table-spoonfuls) of crushed malt are thoroughly well mixed in a jug with half a pint of cold water. The mixture is allowed to stand over night — that is to say, for ten or twelve hours. The supernatant liquor is then carefully decanted off from the sediment, and strained through two or three folds of muslin until it comes through fairly clear and bright. The above quantities yield about six ounces of product. Malt-infusion thus prepared has a light-brown colour like sherry, a faint sweetish taste, and the odour of beer-wort. It is slightly acid in reaction, and its sp. gr. is about 1025. It is rendered cloudy by nitric acid, showing that it contains albumen. Its chief solid constituent is maltose, and it is rich in diastase. I was surprised to find that the action on starch of the above standard malt infusion was quite as powerful as that of average specimens of malt extracts. This shows that, in spite of all the precautions used in the manufacture of malt extract, an enormous amount of the unstable diastase is rendered inert and lost in the process of concentration. 1 Malt infusion is very prone 1 This loss, 1 have mason to believe, depends on increase of acidity during concentration. The malt infusion has an acid reaction, and the ANTISEPTIC PROPERTIES OP CHLOROFORM 225 to fermentation, and it must either be prepared fresh for each day's consumption, or means must be used to pre- serve it from decomposition. This may be easily accom- plished by adding a few drops of chloroform to the infusion, and keeping it in a well-corked bottle. 1 If the acid to which this reaction is due is not volatile. The proportion of acid, therefore, increases as evaporation proceeds. All acids, even organic acids, except in very minute proportions, are highly destructive to diastase. 1 Note ox the Antiseptic Properties of Chloroform. — The anti- septic properties of chloroform have recently been brought up in Germany as something new (see Lancet, Dee. 20, 1890, p. 1343). It is, however, no novelty at all. I have used chloroform for the preservation of all kinds of organic liquids constantly for the past fifteen years, and have incidentally mentioned the fact in several of my published papers. I derived the hint from Claude Bernard's observations on the narcotic effects of ether and chloroform on vegetable organisms. The antiseptic power of chloroform, according to my observations, is suspensive, and not destructive. It acts really rather as an anaesthetic than as a true antiseptic. It does not kill bacteroid organisms and their spores ; it only renders them dormant. It has, therefore, no permanent sterilising power, and is not adapted for the preparation of sterilised culture fluids in bacteriological experiments. In the case of milk, blood-serum, and urine, for example, chloroform when present in excess and in corked phials preserves these fluids perfectly ; but when the corks are removed, and the chloroform is allowed to exhale, putrefactive changes set in just as if no preservative had been used. My experiments on the use of chloroform for the preparation of culture media were performed in the following manner : — Long-necked flasks were charged with milk, blood- serum, or other organic liquid, and a few drops of chloroform were added, taking care that more chloroform was used than the liquids could dissolve. The necks of the flasks were then tightly plugged with cotton wool, and firmly corked. Treated and kept in this way the liquids remained unchanged. But if at the end of a month or six weeks the corks were withdrawn, while the cotton wool plugs were left undisturbed to prevent the access of fresh germs, the volatile chloroform soon escaped, and putrefactive changes, with abundant growth of bacteria, commenced in a few days, showing that the germs originally present in the liquids were not dead but sleeping. At one time I used chloroform as a digestive antiseptic, but as my observations multiplied I discontinued the practice as being obviously Q 226 MODES OF USING MALT INFUSION taste and odour of chloroform thus communicated to the infusion be objected to, this may be obviated by pouring out the intended dose into a wide-mouthed wine-glass or a saucer two or three hours beforehand, and allowing the vessel to stand on the mantelpiece or other warm place. The chloroform soon flies off in vapour, and the infusion is restored to its original taste and smell. Preparations of malt may be utilised for their dias- tasic property in two ways : either they may be admin- istered with a meal, so as to perform then mission during and for a short period after the ingestion of the food, or they may be mixed with the food beforehand with a view to predigest the starchy matters before they enter the mouth. I shall consider these two methods separately. 1. Administration of Malt preparations with Food. — The labels on the malt extract bottles usually direct one or two dessert-spoonfuls to be taken after a meal. This is obviously a bad mode of utilising the diastasic powers of the preparations. A meal is often a long affair ; the earlier portions may be in full digestion before the final portions have passed the mouth, and it must be borne in mind that diastase is rendered permanently inert by the acid of the stomach, and that as soon as the meal is penetrated by the acid gastric juice the conversion of futile. Chloroform must be present in considerable proportion to exer- cise an appreciable antiseptic or antifermentive effect, and it could not be safely introduced into the stomach in sufficient quantity for this purpose ; besides, fermentive processes do not occur in the stomach with such speed or to such an extent as to disturb its function, except in cases of pyloric obstruction. This proposition seems to be proved by the observations recorded in the next section, p. 242. As to any effect of chloroform on intestinal putrefactive changes, as supposed by Salkowski and Kirchner, it is quite inconceivable that a substance so volatile and absorbable could, in the warm atmosphere of the body, survive to reach the small intestines in sufficient quantity to exercise any antiseptic influence. MODES OF USING MALT INFUSION 'I'll starch is arrested, and no further progress is made therein until it starts afresh in the small intestine under the influence of the pancreatic juice. When a malt prepara- tion is administered after a meal the dose is not properly- mingled with the food, nor is it mingled at the right time. The better plan is to direct the patient to sip his dose of malt extract or of malt infusion, as the case may be, during the progress of the meal. The object in view is to supplement the action of the saliva, and the artificial substitute should, like the natural secretion, be mingled with the food in the mouth so that it may have due op- portunity for the performance of its destined work before its energies are checked by the rising tide of the gastric acid. Malt extract is taken in doses of one or two dessert-spoonfuls diluted with water or milk. Malt infu- sion may be taken in similar quantities, and in the same way ; or it may be added to the beverage which happens to be used with the meal, for it has little taste of its own. I may mention that malt extracts, from their syrup-like consistence and flavour, are suitable for spreading on bread or toast, or for sweetening any kind of farinaceous pudding, gruel, or porridge. An effectual commingling of the ferment with the food is thus ensured. 2. Predigestion of Starchy Food by Malt preparations. Some years ago Liebig pointed out with great force the advantage — or rather the necessity — of predigesting the starchy aliments given to young infants, and sug- gested a method of preparing a farinaceous ' food for infants ' by an ingenious process which was designed to completely transform its starchy ingredients into dextrine and sugar before the food was administered to the infant. This proposal of Liebig's is historically interesting, as the first successful attempt to provide human beings with food not only previously cooked, but also previously u 2 228 liebig's food for infants digested. Liebig's plan and principle is this : ground malt and wheat-flour are mixed together with a due quantity of milk and a little water to form a gruel. This mixture is heated over a very slow fire until it thickens, which occurs when the temperature approaches 150° F. At this temperature the starch granules swell out and burst, and the starch is gelatinised. At the same time the diastase is dissolved out of the malt, and acts energetically on the gelatinised starch. The gruel is now diligently stirred for some time without increasing the heat, until at length, from the conversion of the starch into sugar, it becomes quite thin and diffluent, It is then raised to the boiling point, and when cool is ready for use. 1 This method is easy to the chemist in his laboratory, who proceeds thermometer in hand. But it is otherwise when the operator is a cook or nurse, and the apparatus a saucepan and an open fire. The starch does not begin to gelatinise until the heat rises above 140° F. Below this point the granules remain intact — at least, for a long time — and the diastase cannot attack them in this state. On the other hand, should the tem- perature rise much above 160° F., the diastase is destroyed by the heat, and the starch conversion is arrested in mid-career. If, therefore, this narrow range of some 20° F. be overpassed on either side, the desired result is not fully attained ; and to keep within this narrow range is too much for the rough chemistry of the 1 Liebig also added a few grains of bicarbonate of potash, in order to render the product more exactly equivalent to mother's milk. This is a needless complication, and may be regarded as an example of Liebig's passion for chemical symmetry, and his habit of looking at physiological questions too exclusively from a laboratory point of view. The diastasic action goes on perfectly well without the alkali, whose presence is more likely to hamper than to assist the further stages of digestion in the stomach. IMPKOVED METHOD 229 kitchen. This is the reason why this admirably-conceived method has failed to obtain a more firm footing in the sick rooms and nurseries of this country. 1 All the difficulties, however, disappear if, instead of using the crude malt, we use the standard malt infusion of which I have spoken. By this means Liebig's idea can be carried out to completion with perfect ease, and a much wider application can be given to it than seems to have been contemplated by its illustrious author. The mode of proceeding with the malt infusion is as follows : — A suitable gruel is prepared from wheat, or from oatmeal, groats, pearl-barley, arrowroot, or any other farina. The gruel may be made with water alone, or, as is more usual, with the addition of milk or some kind of meat broth. In either case the gruel should be well boiled, and strained to separate the lumps. When the gruel is cold, or at least sufficiently cool to be tolerated in the mouth, the malt infusion is added. One tablespoonful (well mixed therewith) is sufficient to digest half a pint of gruel. The action is very rapid ; in a few minutes the gruel becomes thin from the conversion of the starch. When this point is reached the food is ready for use. The only pre- caution to be observed in the process is to make sure that the gruel is at least sufficiently cool to be borne in the mouth before the malt infusion is added. It is not of the least consequence if the temperature be below this point, for the transformation goes on just as well, though not so rapidly, when the gruel is cold as when it is warm ; whereas too high a temperature endangers the activity 1 Efforts have been made to evade these difficulties in some of the ' foods for infants ' sent out by manufacturing druggists, but without much success ; and some of the so-called improved methods are a good deal worse than the original plan. 230 ADVANTAGES OF MALT INFUSION of the ferment, which is rendered inert at 170° F. The product of the action of malt on starch is not cane- sugar nor grape-sugar, but maltose, 1 and maltose has very little sweetening power. This is the reason why gruel thus digested suffers little change of taste ; so little, indeed, that the addition of it to milk or broth produces scarcely any appreciable alteration of flavour. Malt extracts are less suited than malt infusion for the predigestion of farinaceous aliments. Malt extracts have a somewhat strong sweetening power, and they communicate a dingy brown colour to the food ; whereas the malt infusion adds neither adventitious taste nor colour. Malt infusion has also an enormous advantage in point of price. Malt extracts cost three shillings a pound — the infusion can be made for three farthings a pound. The trials I have made, in actual practice, of food thus predigested have been highly satisfactory. Since the above paper was written I have had an extended experience of the use of malt infusion as an aid to the digestion of farinaceous food, and I can speak with confidence of its efficiency and agreeableness. Although inferior in diastasic power to an active pancreatic extract, malt infusion has the great advantage of not imparting to the food any unpleasant flavour ; and its deficiency in strength is easily compensated by the use of larger doses, which is a facile point with a substance so bland and cheap. Malt infusion should be regarded as a 1 According to the observations of Brown and Heron, 100 parts of starch are transformed by malt infusion, when the reaction has reached its ultimate terms, into 80 parts of maltose and 20 parts of dextrine. (Journ. Chem. Soc, Sept., 1879.) The products of the action of salivary and pancreatic diastase on starch are, according to Musculus and v. Mering, absolutely identical with those of malt diastase. (Maly's Jahres bericht for 1878, p. 49.) ADVANTAGES OF MALT INFUSION 23] household remedy. Crushed malt can be obtained at any provender shop, and the preparation of the infusion may be entrusted to the housewife or nurse. In the digestive and intestinal troubles of infancy, when milk cannot be tolerated, a strong gruel predigested with malt infusion mixed with an equal volume of beef tea or other meat decoction, constitutes, as I have often proved, an exceed- ingly valuable resource. Section IV DYSPEPSIA 235 OX THE ACID DYSPEPSIA OF HEALTHY PERSONS (Fifth Lecture of the Owens College Course.) Summary : — General description — Symptoms — The acid residuum — Nature and source of the acid — Particular symptoms — Pain— Depres- sion — Acid eructations and heartburn — Flatulence — Gastric cramp or paroxysmal pyrosis — Diagnosis of acid dyspepsia — Further inci- dents of acid dyspepsia — Treatment — By antacids— By provoking salivation. The dyspepsia of substantially healthy people may be broadly divided into the atonic form and the irritative or acid form. In the former there is defect of digestive power — that is to say, deficiency of gastric juice, and deficiency of muscular action in the stomach. In the latter there is an undue secretion or an undue accumu- lation of acid in the stomach, especially towards the later stages of digestion. The former, or atonic dyspepsia, scarcely merits the name of dyspepsia ; it is rather an oligopepsia, or apepsia ; it is a defect rather than a disorder of digestion, and is often painless. It generally constitutes a part of some general ailment or debility, and is met with in the anaemic and in persons of low vitality, with feeble appetite, and slender powers of taking food. Acid dyspepsia, on the other hand, is often seen in persons of strong constitution and good health, who work hard, are never laid up, and who live as long and 236 GENERAL DESCRIPTION are as good lives as their non-dyspeptic brethren. This. form of dyspepsia is apt to trouble those who lead studious or sedentary lives ; but it is by no means un- common among farmers and those who lead an open-air life, especially if they belong to gouty families. Acid dyspepsia is often, perhaps generally, associated with undue sensitiveness of the stomach (gastrodynia) ; hence there is frequently a certain commingling of symptoms — of symptoms due to mere hyperesthesia and of symptoms due to disorder of the digestive process. Neurotic and hysterical individuals, both male and female, are very liable to gastric pains ; although their digestion may be normal, their ' neurotic centre,' if I may be allowed the expression, is in their epigastrium ; and their symptoms imitate those of true acid dyspepsia. In these cases of ' false dyspepsia,' as they may be termed, there is generally much complaint of flatulent distension, with noisy demonstrative eructation of gas,, but without any real excess of acid in the stomach. The acid dyspepsia of healthy persons consists essen- tially in a tendency or predisposition of an enduring character, the tendency being towards a generation or accumulation of excess of acid in the later stages of gastric digestion. The tendency is more or less per- manent, and lasts with many persons from youth to age. It is rare in boyhood and girlhood, and tends to diminish in old age. It prevails at its maximum during the flush of manhood, and is distinctly more common among men than women. To a certain extent acid dyspepsia may be regarded as an ill-directed vigour of digestive action, as is well illustrated by the following incident. A habitual dyspeptic, who regularly suffered from painful excess of acid after each meal, on one occasion partook of an unusually heavy dinner, which proved too much SYMPTOMS 237 for his digestive powers. After some hours of discomfort the meal was expelled with violent vomiting. This attack was followed by marked prostration of the gastric powers. During the ensuing forty-eight hours there was a Btate of oligopepsia, with diminished appetite, but each meal was digested with perfect comfort and without the least excess of acid. At the end of two days the appetite and digestive vigour returned, and with their return came also the dolorous incidents of acid dyspepsia. With most dyspeptics their trouble is not altogether continuous. They have then good periods and their bad periods. During their good periods they may for weeks or months go on digesting their meals with the same comfort as their more fortunate brethren. Then again for weeks or months their condition is one of almost incessant and severe suffering. It may even become serious, and lead to loss of appetite, inability to take due quantity of food, and to consequent emaciation and loss of strength. But as a rule the dyspeptic, in spite of his torments, maintains his flesh and bodily vigour unimpaired. Symptoms. — The subject of acid dyspepsia generally takes his food with appetite, sometimes even with voracity. The early periods of digestion are also gene- rally easy and comfortable, but after a while there is felt a weight and aching at the pit of the stomach, which often increases to a severe pain. Then succeed a sense of fulness and tightness in the epigastrium, repeated and copious discharge of flatulence, with eructations of sour liquid into the mouth, and tendency to nausea or, more rarely, actual vomiting. These symptoms come on earlier after a hght meal than after a heavy meal. After breakfast the symptoms often appear very speedily — in half an hour or an hour — whereas after dinner they are 238 SYMPTOMS usually postponed for one, two, or three hours. In very sensitive dyspeptics a glass of sherry or a basin of soup will appear to ' turn sour ' in fifteen or twenty minutes. There is generally with dyspeptics of this class an im- pression that their digestion is abnormally slow. I doubt whether this is really so. I think that digestion in these cases is, often at least, hurried, and consequently im- perfect ; and that, after the main act of digestion is over, there remains in the stomach a large residuum of an acid mucus, mixed with remnants of food, chiefly com- posed of fatty matter. This sour mass seems difficult to dispose of ; it lingers long in the stomach, and gives a feeling of unpleasant fulness and distension, which does not really correspond with any actual excess in the bulk of the gastric contents. At length, however, this re- siduum is got rid of, and the stomach becomes empty and at rest ; the pain and discomfort wear off, and there is peace for the dyspeptic until after the next meal ; then comes a repetition of the same events. Not unfrequently the acid residuum is not entirely got rid of when the next meal-time arrives, and hence sour eructations may be experienced immediately on takmg the new meal, confusing the symptomatology. In this case the sour mucus, for a short space of time, floats on the surface of the new meal, and the eructations are con- sequently acid to the taste ; but presently it mingles with the meal, and the degree of acidity of the total gastric contents is thereby reduced (by dilution), and the eruc- tations cease to be sour. Hence it is that the ingestion of a meal sometimes relieves the dyspeptic for a while ; and this often happens with an accidental ' fit ' of acid dyspepsia in persons who are not habitually predisposed thereto. They are cured, much to their surprise, by taking a full meal — the fact being that the new meal DEGREE OF ACIDITY 2o9 gives the surplus acid work to do — and so ends the attack. The secondary or sympathetic symptoms associated with acid dyspepsia are sometimes very puzzling to the in- experienced, and apt to lead him astray in regard to their real nature. There are pains of a neuralgic character and abnormal sensations in various parts of the body — in the gums, in the head, in the bowels, or indeed anywhere — cold feet, flushings of the face, lassitude, abnormal sleepiness, palpitation of the heart, and so forth. The Acid of Acid Dyspepsia: its Nature and Source. — Being myself subject to occasional periods of acid dys- pepsia, in typical form, I have had several opportunities of examining the sour residuum which accumulates in the stomach toward the later stages of digestion. "When this is thrown on a filter a perfectly clear pellucid acid liquor comes through, not containing any trace of organisms. The degree of acidity was found to vary through a considerable range. The results of analysis on six several occasions gave the following degrees of acidity, expressed in terms of dry hydrochloric acid (HC1):- 0T5 per cent. HC1 0-30 per cent. HC1 0-26 per cent. HC1 0-31 per cent. HC1 028 per cent. HC1 0*36 per cent. HC1 These numbers indicate a considerable excess in degree of acidity of the gastric contents. 1 Pure gastric juice (human) is estimated to have an acidity of 0*2 1 Reichmann found in cases of acid dyspepsia still higher degrees of acidity than those recorded above ; namely 0-34 per cent, and 0-45 per cent. HC1. On the other hand, Dr. McNaught found lower degrees- ranging from 0-09 per cent, to 0-2 per cent. HC1.— Medical Chronicle vol. i. pp. 420 and 330. 240 NATURE OF THE ACID per cent. HC1, but this is considerably higher than the actual acidity of the contents of the stomach during normal digestion. According to the observations of Eichet on a young man with gastric fistula (made arti- ficially for the relief of impassable stricture of the oesophagus) the mean acidity of the gastric contents during the entire period of digestion was 0-17 per cent. HC1. But the variations were very great, and oscillated between 0*07 per cent. HC1 on the one side and 0'3 per cent. HC1 on the other. 1 The nature of the acid in the sour residuum is not always the same. It seems to be a variable mixture of hydrochloric and diverse organic acids in varying propor- tions. The kind and proportion of the organic acids must depend mainly on the composition of the preceding meal. Lactic and butyric acids are probably the organic acids most commonly present. The latter is certainly often present, and can be recognised by its peculiar acrid smell and taste. The discrimination of the organic acids from hydrochloric acid, when both are present together in a solution containing proteid compounds, is very difficult ; and the tests in vogue (shaking up with ether, tropseolin, and methyl-violet) are by no means trustworthy. As this point is of interest and under inquiry, I may relate how I convinced myself that the acid of the sour residuum of acid dyspepsia was not (in the sample examined) unmixed hydrochloric acid. In the course of my inquiries I had occasion to investigate the effects of acids on diastasic action ; and I found that organic acids had considerably less inhibitory power on starch digestion than mineral acids of the same satu- rating equivalence. Now, on comparing the inhibitory effect of pure dilute hydrochloric acid with that of the 1 Eichet, Du Sue Gastriqtie. Paris, 1878. SOURCE OK THE ACID 241 acid contained in the sour residuum, it was found that for the same saturating equivalents hydrochloric acid had mere than double the inhibitory power of the acid of the sour residuum. The sourer of the acid in acid dyspepsia has been much debated. I have long since come to the conclusion that it is exclusively derived from excessive secretion or accumulation of gastric juice, and not from any fer- mentive process. The sort of windy turmoil which goes on in the stomach of the dyspeptic has led observers too hastily to the analogy of vinous fermentation. A more precise examination of the incidents of acid dyspepsia lends no support to this view. Fermentive processes, whether toruloid or bacterial, cannot, I think, take place in the stomachs of healthy persons to an extent sufficient to have a practical bearing ; they can only take place to this extent in cases of pyloric obstruction or of chronic dilatation, when the food is detained in the viscus for a very long time — for twenty- four or forty-eight hours, or longer. Fermentive changes are altogether too slow to ac- count for the rapid development of acidity and flatulence in cases of acid dyspepsia. The two following experi- ments show how very gradual is the development of acid in bacterial fermentation :— (a) Two ounces of the sour eructation from a typical case of acid dyspepsia were carefully neutralised with caustic soda, and then set aside in the warm chamber at blood-heat. After four hours only the feeblest acidity — amounting to 0'018 per cent. HC1 — was developed. Bacteria were found under the microscope in scanty numbers, evidently only beginning to swarm. {b) Two fluid drachms (7 cubic centimeters) of the same sour eructation were mixed with twelve ounces (340 B 212 PARTICULAR SYMPTOMS PAIN cubic centimeters) of warm bread and milk. The whole mixture was now faintly acid =0*012 per cent. HC1. In two hours the acidity had not appreciably altered. In five hours the acidity had increased to 0*015 per cent. HC1, and at the end of twenty-four hours (during the whole of which period the mixture had been maintained at blood-heat) the acidity had only risen to 0*035 per cent. HC1. In neither case was there any appreciable production of gas. The presence of organic acids in the acid residuum is easily accounted for without calling in aid the agency of fermentation. For, as has been ex- plained in a previous lecture, salts of the organic acids, present in the articles of food, are decomposed by the hydrochloric acid of the gastric juice — chlorides of the bases are formed, and the organic acids are set free (see ante, p. 145). In this way the occurrence of lactic, butyric, tartaric, malic, and other organic acids in the sour residuum is easily and naturally accounted for. Particular Symptoms.— The most common and cha- racteristic symptoms of acid dyspepsia are pain, depres- sion, at'ul eructations and heartburn, flatulence , and gastric cramp or paroxysmal pyrosis. To each of these symptoms I propose to devote a few words. Pain. — The dolorous sensations about the epigastrium, which often extend upward to the lower sternal regions, are essentially due to the irritating action of the acrid and acid residuum on the mucous membrane of the stomach. This is the main and true explanation of the pain. But in the subjects of acid dyspepsia, especially during their bad periods, the stomach is unusually sen- sitive ; and a residuum which would not be felt during their better periods, nor in non-dyspeptics, causes acute sensations. The severity of the pains (apart from vary- ing sensitiveness of the stomach) depends (a) on the DEPRESSION 243 degree of acidity ; the sourer the residuum is, the greater is the smarting caused by it; (/>) on the proportion of butyric acid contained therein; for butyric acid is much more acrid than so much lactic or hydrochloric acid ; (r) on the quantity or volume of the residuum. If the quantity be small — only one or two ounces — there may be no pain though the acidity be high; on the other hand, if the residuum be large it may cause pain though it- acidity be not excessive; because the extent of mucous surface brought into contact with the irritating fluid affects the degree of sensation produced. Just as with the impression of hot water on the skin, the dolorous sensation varies proportionately to the extent of surface exposed ; the finger can easily tolerate immer- sion in water at a degree of heat which would be quite unbearable to the whole arm. During the bad periods the pain and aching at the epigastrium linger after the stomach is empty, so that the discomfort is almost continuous. Depression. — There is often a pronounced sense of depression. In neurotic individuals this is spoken of in exaggerated language. It is described as a horrid tor- ment ; they say that their life is made miserable, and not worth living. This constitutes what has been known of old as hypochondria. The pain and physical discom- fort in the epigastrium appear to me quite sufficient to account for this depression, without invoking the aid of any poisonous alkaloid, formed during the digestive process. There is a peculiar bitter principle, produced during both the gastric and pancreatic digestion of proteids ; l but this is a normal product, and there is not the least evidence that it possesses poisonous properties. ' I called attention to the production of this bitter principle in my Lumleian Lectures (see ante, p. 195). 244 HEARTBURN Acid Eructations and Heartburn. — These are usually prominent symptoms of acid dyspepsia, but are not invariably present. There is a regurgitation into the mouth of sour liquid from the stomach with discharge of flatulence. The savour of the eructation may be simple sourness, like that of lactic or hydrochloric acids, but often it has a burning, acrid quality — this occurs when butyric acid is contained in the residuum. Butyric- acid is volatile, and rises in acrid fumes, which affect the cardia and oesophageal orifice of the stomach and cause a persistent feeling of heat and horrification, with a nauseating tendency. This constitutes true heartburn. The occurrence of heartburn with the presence of butyric- acid requires no intervention of butyric fermentation to explain it. Milk, butter, cheese, and other fatty food, all contain more or less butyric acid, either free or in com- bination. The butyrates are decomposed (as previously explained) by the hydrochloric acid of the gastric juice, and butyric acid is liberated in the free state. But how, therefore, it may be asked, is not heartburn a more con- stant incident of acid dyspepsia '? The reason probably is, that, to produce a sensible quantity of butyric acid the butyrates must be present in the meal in considerable amount, as in rancid butter and other rancid fats often used in cooking, and secondly that the acid in excess must be hydrochloric acid, and not merely lactic or other organic acid — otherwise the butyrates are not decom- posed — and the proportion of mineral to organic acid in the sour residuum varies a good deal. Flatulence. — This is an invariable accompaniment of acid dyspepsia. The accumulation of gas in the stomach causes a sense of fulness and distension and an impor- tunate desire to get rid of the accumulation by upward dis- charge. This importunity is intensified by the hypersensi- FLATULENCE 245 tiveness of the stomach, which isimpatient of an amount of gas which would not incommode it, nor require upward discharge, but would be otherwise disposed of, perhaps through the pylorus, if the stomach were less sensitive. The occurrence of butyric acid also aggravates the gastric discomfort. The vapour of this acid, when it is largely present in the residuum, must be always rising into acrid fumes in the warm atmosphere of the stomach. But apart from hypersensitiveness of the organ, and apart from the vapour of butyric acid, there is undoubtedly an abnormal generation or accumulation of gas in the stomach in acid dyspepsia. What is its source? The fermentation theory, as already explained, is wholly in- adequate to account for it, and we are driven to other modes of explanation. My impression is that the ac- cumulation of gas in acid dyspepsia may be traced to three sources, (a) Swallotved air. There is a large amount of air entangled and swallowed during the de- glutition both of food and of saliva. The air engulfed with food is not larger in acid dyspepsia than in non- dyspeptics, but in regard to that swallowed with saliva there is a difference. During the existence of exc< — acid in the stomach there is a certain amount of un- conscious salivation going on, and a larger amount of air is thereby carried down than in the normal state. (b) Liberation of carbonic acid in the stomach. The saliva secreted during the period of surplus acid in the stomach is much more alkaline (from carbonate of soda) than when the contents of the stomach are neutral or only moderately acid. I have found this to be constantly the case: sometimes the alkalescence of the saliva is so high as to occasion visible effervescence on the addition of an acid. "When the stomach is empty and neutral the saliva then secreted barelv turns the colour of litmus 246 FLATULENCE paper, but when the organ contains excess of acid I have found the alkalescence of the saliva equal to O04 per cent. HC1. When this alkaline saliva, secreted in un- usual profusion, descends into the stomach, it encounters the acid residuum, and is neutralised thereby with libera- tion of a certain amount of carbonic acid. I shall return to this point when I come to the treatment of acid dyspepsia, (c) Regurgitation of carbonic acid from the duodenum. This is a third probable source of gas in the dyspeptic. When the chyme passes through the pylorus it encounters the secretions of the liver and pancreas, both of which are alkaline from carbonate of soda. The collision must liberate carbonic acid. We may regard it as probable that when the contents of the stomach are super-acid the biliary and pancreatic secretions are, as in the case of the saliva, super-alkaline, and that conse- quently a larger disengagement of carbonic acid occurs in the duodenum under such conditions than in tranquil digestion. The gas thus generated would unduly distend the duodenum, and would probably push its way partly upwards through the pylorus into the stomach, and partly downwards into the jejunum. It has been suggested, as a partial source of gas in acid dyspepsia, that carbonic acid is exhaled from the blood through the mucous membrane of the stomach (as in the process of respiration through the pulmonary membranes), but I do not see why this should occur in a larger degree in dyspeptics than in other healthy persons. I can, however, easily believe that in regurgitant heart disease and in general emphysema, when there is severe venous stasis in the stomach, and a cyanotic state of the blood, such exhalation of carbonic acid through the gastric mucous membrane may take place, and that this accounts for the distressing flatulent distension which is PAROXYSMAL PYROSIS l> I 7 so common in these affections. But in acid dyspepsia the blood is not surcharged with carbonic acid, and there is no venous stasis in the stomach. Gastric Cramp or Paroxysmal Pyrosis. — The course of acid dyspepsia is sometimes diversified by the occurrence of a very peculiar and characteristic symptom, which, though brief in duration, is very distressing, and even alarming to the uninitiated. This symptom consists in a paroxysm, of which the chief features are sudden cramp of the stomach with sudden profuse salivation. The attack only lasts half a minute or a minute, but to the sufferer the time appears long. I would suggest that the word pyrosis be confined to these essentially paroxys- mal attacks. Writers on dyspepsia exhibit confusion in the use of the term pyrosis, and give it a mixed description, which includes partly these paroxy>ms and partly the ordinary symptoms of acid dyspepsia and heartburn. The gush of saliva into the mouth is often misunder- stood, and is described as a regurgitation from the stomach or from the lower part of the cesophagus. Paroxysmal pyrosis is essentially an abortive and incomplete act of vomiting. Complete vomiting consists of the following succession of events: — Gastric Bpasm, profuse salivation, convulsive spasm of the abdominal muscles, sudden downward thrust of the diaphragm, closure of the glottis, opening of the cardia, and finally ejection of the contents of the stomach. The abortive act which constitutes a paroxysm of pyrosis falls short of the complete act in the absence of the downward thrust of the diaphragm, and of the opening of the cardia ; moreover, the contraction of the abdominal muscles is either absent altogether or is cramp-like rather than convulsive ; the voice is reduced to a whisper, but is not altogether sup- pressed, so that the closure of the glottis is not absolute : 2-18 PAROXYSMAL PYROSIS and there is no ejection of the contents of the stomach. Occasionally, however — but this is quite exceptional — the paroxysm does culminate in actual vomiting. The sense of nausea is imperfectly developed in these attacks. The gush of saliva is something tremendous — often greater than incessant swallowing efforts can dispose of — and the surplus flows out abundantly from the mouth. Some persons are not conscious of swallowing any of it, and believe that they let it all flow out at the mouth. A paroxysm of this kind only occurs during the presence of surplus acid in the stomach, and on its conclusion there is a sensible relief (for a time) to the previously existing epigastric pain and other symptoms of acid dyspepsia. I have had several opportunities of examining the fluid that gushes into the mouth in paroxysmal pyrosis, both in my own case and in that of patients. It in- variably possesses the character of true saliva, differing only in its unusual degree of alkalescence. I will give two examples. The first is from my own person. During a typical attack of gastric cramp I succeeded in collecting some of the fluid which flowed in an abundant stream into the mouth. Its alkalinity was equal to 0*125 per cent. HC1 ; it effervesced distinctly with acid. In dia- stasic power it was more active than average healthy saliva — in the proportion of 12 to 8. The second ex- ample was from a patient who was subject to recurrent and severe attacks of paroxysmal pyrosis. On closely questioning this patient he insisted that the fluid which came into, and flowed out of, his mouth during the paroxysms came from the stomach. He was quite sure that it was not a rush of fluid into the mouth from the sides of the mouth itself. I requested him to send me on the next occasion some of the ejected fluid in a bottle. DIAGNOSIS 249 He did so. I found it, as I had expected, to possess all the properties of true saliva, with excess of alkali. Its alkalinity was equal to 0*15 per cent. HC1, which cor- responds very closely with the grade of acidity of the gastric contents daring tranquil digestion. Its diastasic activity was fully equal to that of fresh normal saliva, as tested hy standard starch mucilage in the manner previously described (see p. 114). I cannot therefore doubt that the gush of fluid in par- oxysmal pyrosis is purely and exclusively a gush of saliva. The relief which commonly follows a paroxysm is obviously due to the large quantity of alkali introduced into the stomach with the gulped saliva. The paroxysms of pyrosis occur quite irregularly — rarely more than once in one day, more generally once in two or three days, sometimes only once a week, or once a month, or even once a year. Some dyspeptics never experience these paroxysms. They occur exclu- sively during the presence of excess of acid in the stomach, but they are not infrequently provoked by an impression of cold, or a chill. Diagnosis of Acid Dyspepsia. — The diagnosis of acid dyspepsia is in principle perfectly simple. If the dolorous sensations at the epigastrium are relieved by a dose of carbonate of soda, or any other alkali, the case is one of acid dyspepsia. Such a dose, as habitual dyspeptics know well, infallibly gives relief. The relief may not be quite complete, but it is always marked and speedy. If no such relief is given the case is certainly not simply one of acid dyspepsia. In neurotic and hyste- rical individuals the diagnosis is not always so easy. because such persons give a confused, often discrepant, account of their sensations, and are poor subjects for this kind of crucial experiment. 250 TREATMENT AYhen the dyspeptic takes a dose of soda early after a meal the relief is only temporary, and does not serve until the next post-cibal emergency ; but if he takes his dose later on the relief lasts until after the next meal, and the subsequent eructations are perceived to have lost their sour and acrid taste. Further Incidents of Acid Dyspepsia. — Slight meals are sometimes more provocative of acidity than full ones. A meal taken at an unusual hour, or a full meal eaten at an hour when usually a light meal is taken, is also very apt to provoke acidity. Surplus acidity is provoked by anything that renders the meal more difficult of digestion, such as imperfect mastication or hurried eating. As a rule, careful ' dieting ' is of no avail, or only of partial avail, in acid dyspepsia. Constipation of the bowels dis- tinctly intensifies the symptoms. Almost all habitual dyspeptics have their special lredantia and juvantia, and to none is the old proverb more applicable that ' one man's meat is another man's poison.' Some cannot take sugar, others can take it freely ; the same with eggs, with soup, with various wines and beer, with tea, coffee, some kinds of meat, with potatoes, and so forth. Fatty matters disagree very generally. The dyspeptic stomach is peculiarly capricious and peremptory, and, as a rule, there is very little use in arguing with it in regard to its likings and dislikings. The appetite is usually good ; dyspeptics often enjoy their meals and ' could eat more ' were it not for fear of the consequences. Sometimes the appetite is voracious : sometimes, on the contrary, the appetite is weak or capricious. Treatment. — The treatment of cases of habitual acid dyspepsia divides itself into — (a) means which are directed to obtain relief from present discomfort ; and (/>) means TREATMENT BY ANTACIDS 251 which aim at raring the disorder, or at least at shorten- ing the had periods. The bias or tendency lb, as I have hefore remarked, more or less enduring ; but if yon can cut short the had periods, this is nearly as good as complete cure, because the ailment can thereby be con- trolled and. practically, nullified. (<() Treatment by Antacids. — For immediate relief there is nothing better than a dose of carbonate of soda. Five or ten grains of bicarbonate of soda dissolved in water almost at once allay the suffering by saturating the gastric acid. A copious upward discharge of carbonic acid follows such a dose. Other alkaline substances are equally effective — magnesia, chalk, or carbonate of potash. But by far the most advantageous modi of administering antacids in these cases is in the guise of the lozenge. A lozenge properly used should he deliber- ately sucked, and not roughly chewed and swallowed. The process of sucking induces a plentiful flow of alka- line saliva, and the presence in the stomach of this bland demulcent secretion is soothing to the angry mucous membrane. The compilers of the British Pharmacopoeia have provided us with two. and only two. antacid lozenges — namely, the troch. sod. bicarb, and the troch. bismwthi. The former contains 5 grains of bicarbonate of soda in each lozenge. It is an effective antacid, hut it is not a favourable example of pharmaceutical art. It has a peculiar nasty, soapy taste, which makes the suck- ing of it a penance : and this. I presume, is the reason why it has not hecome popular with dyspeptics. The hismuth Lozenge is in every way a hetter article. It owes its antacid properties to :U grains of chalk and 2£ grains of carbonate of magnesia. These quantities are. in saturating power, equal to 10 grains of bicarbonate of soda. This i- a full antacid dose, and the chalk and 252 TREATMENT BY ANTACIDS magnesia are practically tasteless, and this is a distinct advantage in regard to the active ingredients of a lozenge. The subnitrate of bismuth, to which this lozenge owes its name, has no antacid properties, and is probably inert. It imparts, however, a slight metallic taste, and communicates to the breath a somewhat disagreeable taint ; so that its presence in the lozenge may, I think, be regarded rather as a tribute to the decaying art of polypharmacy than as a really useful addition. The bismuth lozenge has won its way into favour with dyspeptics by sheer merit, and incmiries which I have caused to be made among druggists and lozenge-makers show that the sale of this lozenge is steadily and largely increasing all over the country. A bismuth lozenge without the bismuth would be a nearly perfect antacid lozenge, and I would venture to suggest that some such lozenge should be introduced at the next revision of the British Pharmacopoeia.* Besides these officinal articles, there are largely sold in the shops a variety of lozenges and tablets for the use of dyspeptics. None that I have examined fulfil the condi- tions of a perfect antacid lozenge. The compressed tablets of carbonate of soda and the soda-mint tablets, although effective as antacids, are so unpalatable that they cannot be properly sucked without disgust, and, indeed, those who use them generally swallow them whole in haste — and thus miss the concurrent flow of saliva, which is distinctly helpful to dyspeptics. Some of the antacid lozenges sold in the shops are flavoured with pungent spices to conceal the taste of the soda. All such 1 This suggestion has been carried out by several manufacturing druggists. Some have added 1 grain of sodium chloride to each lozenge ; this addition pleasantly sharpens its flavour, but has the disadvantage of rendering the lozenge hygrometric in very damp weather. TREATMENT BY ANTACIDS 253 adjuncts are obviously a mistake. Pungent spices have a strong tendency to provoke acidity in the Btomach : and, moreover, any pronounced flavour is objectionable in an article which is used frequently. The alkaline Baits of the Vichy springs have been made into very agreeable lozenges, which are sold in this country in sealed box< -. They owe their antacid properties chiefly to carbonate of soda, but partly also to carbonate of potash and to the carbonates of lime and magnesia. They contain besides a small quantity of sodium chloride, which pleasantly sharpens their flavour. These lozenges have a compara- tively feeble saturating power, but owing to their full sapid qualities, they provoke an abundant flow of alka- line saliva, and this renders them effective for the relief of gastric acidity. Were it not for their costliness, I believe these Vichy lozenges would soon get into favour with dyspeptics. As to the comparative merits of the several antacids employed in acid dyspepsia, there is, perhaps, on the whole not much to choose. Certain differences may. however, be noted. The alkaline bicarbonate- have a nauseous taste, and if taken in excess they leave an alka- line residuum in the stomach. This is at least abnormal, and perhaps embarrassing, in an organ which requires the presence of an acid to perform its functions. The earthy carbonates, on the other hand, are tasteless, and, owing to their insolubility, they cannot, when taken in excess, cause the neutral line to be over-passed. Perhaps the most advantageous course would be to vary and change the antacid from time to time. The question may now be put — Is there any harm in the practice of habitually using antacids for the relief of acid dyspepsia? J)o dyspeptics purchase present ease at the cost of some future detriment ? My attention has :25-± TREATMENT BY ANTACIDS been directed to this point for some year-. I have, naturally, regarded a practice so artificial with con- siderable misgivings. But the more extended my experi- ence has become the more I have been satisfied that, with due precaution.-, the practice is harmless — and I know of no valid evidence from any other quarter to justify a contrary conclusion. My own experience has been mostly gained from the use of the bismuth lozenges, which I have largely prescribed for a considerable Length of time. I have, however, invariably enjoined the follow- ing strict rules in regard to their use: — They were not to be used at or near meal times — not sooner than three- quarters of an hour or an hour after breakfast, nor sooner than an hour or an hour and a half after dinner ; they were not to be used regularly and systematically, but only as the occasion arose, that is to say. when gastric pain was distinctly present, and was producing more discomfort than a man could be reasonably ex- pected to bear who had the easy means of relief ready to his hands ; lasth . the use of the lozenges was to be dis- continued if their employment did not cut short the pain. This last injunction leads up to the remark that an antacid dose is sometimes a useful means of diagnosis in cases of gastralgia. It is often impossible to decide from a patient's statements what may be the real nature of the pains complained of. In such a case, if an effective antacid does fail to give relief, it is sure evidence that the pains are not due to gastric acidity. A useful notion of the relative antacid potency of the several articles hi common use as gastric antacids (as .sold in the shops) may be obtained from an inspection of the following table. Ten grains of bicarbonate of soda are taken as a standard antacid dose ; and the cpiantities given of the other articles correspond in saturating value PROVOKING SALIVA IH )N 25o to tliis standard dose. The results were obtained by direct alkalimetrical determinations, and are here shown in round numbers : — ■ Table of Antacid Equivalents. 10 grains sod. bicarb. = 12 grains pot. bicarb. ,, .. = 6 .. creta precipit. ,. .. -- 6 .. carb. magnesia. „ .. .. = :; .. light calcined magnesia. ,, ., „ = (i fluid ounces lime water. „ „ „ = 2 fluid drachms liq. pota: ., = 1 bismuth lozenge B.l'. ,, ., = 2| Wyeth's soda-mint tablets. ., ,, .. = 5 Vichy lozenges. Treatment by provoking Salivation. — The use of antacids, although adequate for immediate relief, has not much permanently beneficial effect in cases of habitual acid dyspepsia. The symptoms are apt to return with unabated severity after the next meal. It seemed, therefore, desirable to find some more curative method than that of exhibiting endlessly recurrent doses of alkaline substances. Having found that during the prevalence of surplus acid in the stomach there coincided an increased flow of saliva, and that this saliva possessed an unusual degree of alkalescence, I was led to the idea that the saliva was the natural antacid of the stomach. On several occasions I was able to measure synchronously the alkalinity of the saliva and the acidity of the stomach ; and I found that the proportion between them was such that six to eight volumes of the saliva would saturate one volume of the gastric acid. There does not, at first sight, appear to be much prospect of relief from this small proportion of salivary alkali. Nevertheless, when it is considered that complete saturation of the gastric acid is by no means necessary to procure relief, and that all that is required is that the acidity should 1m reduced as to bring it within the limits of the normal 256 PROVOKING SALIVATION acidity in tranquil digestion, the prospect looks much more promising. If the acidity in the stomach could be reduced one-fourth or one-third, these normal limits would be usually attained. And I think it highly pro- bable that, in the usual course of events in acid dyspepsia, the descending stream of alkaline saliva does fulfil an important purpose. When the stomach contains an ex- cessive quantity of sour residuum we may suppose that the pylorus is closed against its passage into the duodenum. This may be regarded in the light of a con- servative act, and designed to prevent disturbance of the alkaline digestion in the duodenum by an overwhelming influx of acid from the stomach. But by the steady, con- tinuous downward flow of alkaline saliva the excessive acidity in the stomach is gradually lessened, and at length brought down to the normal grade, and then the refractory pylorus opens, and the stomach is relieved. This train of ideas led me further to the notion that if the flow of this alkaline saliva could be increased, effective relief might thereby be given in acid dyspepsia, and that by acting in this way we should be operating more closely after nature's indications than by giving alkalies of extraneous source. We should be making the blood itself the source of the alkali, instead of taking it from the shop. And on trial I found the results con- formable with the theory. Anything that increased the flow of saliva was found to abate the pangs of acid dys- pepsia. Lozenges of all sorts promote a flow of saliva, but especially lozenges which contain a stimulating in- gredient like ginger or cayenne. A very sensible relief is given to the dyspeptic by the use of these lozenges ; and this is probably the secret of the habit of some country dames, who carry in their capacious pockets a root of ginger, to which they apply when the stomach aches. A step further led me to the use of simple gum-lozenges. PROVOKING SALIVATION L ; ."m The sucking or chewing of any kind of lozenge will pro- mote salivation; the turning round with the tongue, and the mastication of the little morsel, sets the Balivary glands to work. Lumpy ' tears' of gum arabic, .such as maybe picked out from the druggist's stock, do not make bad lozenges for this purpose. The ' glycerine juji of the shops likewise consist of nearly pure gum, and these are somewhat more palatable than the gum I and answer equally well, or better, as provokers of salivation. The sugar contained in them is, however, objectionable to some stomachs. I think a lozenge com- posed of gum, with the addition of a little pyrethrum, might be a valuable addition to the resources of the dyspeptic. By the use of lozenges, and especially of gum lozenges, I have obtained in the treatment of acid dys- pepsia distinctly more curative results than by the use of alkalies. The advent of the bland gummy solution in the stomach probably acts topically as a soothing application to the irritated mucous membrane, allays its abnormal sensitiveness, and thereby disposes it to a more normal performance of its functions in dealing with the succeeding meal. If the surplus acid is great, and the torment severe, a dose of alkali must be ad- ministered; but the milder means here suggested will give adequate relief in many instances, and will greatly promote the abbreviation of the bad periods. ^Vith regard to the regulation of the diet of the dyspeptic, the removal of habitual constipation, the due mastication of the food, the avoidance of hurried citing, the use of exercise in the open air, and the adoption oi other hygienic precautions, I have nothing to add to the rules laid down on these matters in your manuals and in special treatises on dyspepsia. s INDEX ACHKOMIC Acrrr.oMic point, 69 Acid dyspepsia, 235 — of gastric juice, 40 — of acid dyspepsia. 235 Acids, effects of, on salivary diges- tion, 118 Alcoholic beverages, effects of, on digestion, 115, 132, 157 use of, 99 Antacids, in acid dyspepsia, 251 ■ with milk, 183 Artificially digested food, 192, 227 Beef-tea, 184 effects of, on digestion, 125, 140 peptonised, 205 Beer, see Malt liquors Blancmanges, peptonised, 204 Boracic solution, 17 Butyric acid in dyspepsia, 240 Cane-sugab, digestion of, 36 Casein, digestion of, 197 Chloroform as an antiseptic — note, 225 — water, as a solvent for digestive ferments, 18 Cocoa, effects on digestion, 120, 139 Coffee, use of. 101 — effects on digestion, 120, 138 Cooking, effects of, on food, 177 Cramp, gastric, 247 FARINACEOUS Dialysis, of food accessories, 149 Diastase, action of, 19 — various kinds of, 219 Diastasimetry, 68 Diet, change of, 168 — diversity of, 164 — double aim of, 163 — mid-life, revision of. 171 — useless restrictions on, 165 Dietetic customs, 'J 7 Dietetics, scientific basis of, 96, 162 Digestion, exterior, 4 — in general, 3 — interstitial, 6 — of cane-sugar, 36 fats, 59 milk, 196 proteids. 39 starch, 19 Digestive ferments, 9 Dyspepsia, acid, 235 — symptoms of, 237 — treatment of, 250 Effervescent waters, effects of, 119, 137 Egg-albumen, digestion of, 51 Eggs, beaten-up, 186 Enemata, peptonised, 218 Enzymes and Enzymosis, 15, 16 Farinaceous flours, different kinds of, 188 ^S^