HX64102122 QP1 45 .R54 1 897 Collected contributi Digestion AND Diet Sir William Roberts. m.d.. h r.s. intlieCitpotlfttjgork THE LIBRARIES iHelJical Hibrarp M; ' -> vr-. // //. >/' Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/collectedcontrib1897robe COLLECTED CONTEIBUTIONS ON DIGESTION AND DIET WITH AN APPENDIX ox THE OPIUM HABIT IN INDIA 15Y SIK WILLIAIu ROBERTS, M.D., F.R.S. J'OK.MKRLV PHY.-iriAN TO THE J1A>X'HESTEI: ROYAL INFIRMAllY AND PROFrSSOR OF MKniCtSK IN' THK VICTORIA UXIVKRSn'Y SECOND EDITION LONDON SMITH, ELDER, & CO., 15 WATERLOO PLACE 1897 [All riphts reserved] PREFACE 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 1879 ; a paper * On the Estimation of ) the Amylolytic and I'roteolytic Activity of Pancreatic Extracts,' printed in the Proceedings of the lutijal 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. The present edition is enlarged by the addition, in the form of an appendix, of an article on the Opium Habit in India. This article first appeared as an ' annexure " to the Eeport of the Pioyal Commission on Opium, published in 1895. It is here reproduced as a contribution to our knowledge of a group of quasi- dietetic substances, which includes alcohol, tobacco, tea and coffee, concerning the true significance of which we are still greatly in need of enlightenment. W. E. London : I'cbrnary 1897. CONTENTS SECTION I. DIGESTIOX AND THE DIGESTIVE FERMENTS. rAiiK H 4 (> I. DIGESTIOX IX GKXERAL — THE DIGESTIVE FERMENTS DIGESTIOX OF THE CAKBOHYDEATES. Digestion is a faculty or function common to animals and i^lauts . Exterioi' digestion .......... Interstitial digestion General character and properties of the digestive ferments . Peculiarity of the albuminous matter contained in solutions of the proteolytic ferments . . . . . . . . 13 On nomenclature ......... 15 Preparation of artificial digestive juices 1(> Boracic solution ......... 17 Dilute spirit .......... 17 Chloroform-water ......... 18 Diastasic ferments and the digestion of starch . . . . . I'.t 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 ? . . . . 2!( Absolute energy of diastase . . . . . . . 31 Digestion of cane-sugar — the inversive ferment .... 36 Vlll CONTEXTS II. DIGESTION OF PROTEIDS — THE MILK-CUKDLING FERMENT — THE EMULSIVE FERMENT. PARK 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 56 What is the function of the milk-curdling ferment '.' . . . 58 Emulsive ferment — the digestion of fats 59 Opinions and observations of Bernard . . . . . 60 Author's observations ........ 61 Briicke's and Gad's observations . . . . . . 62 III. THE ESTIMATION OF THE .ACTIVITY OF PANCREATIC EXTR.\CTS. Preliminary observations 66 Diastasimetry 68 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 . . 76 Diastasic value of the pancreas of the pig, ox, and sheep . . 78 Diastasic value of saliva and malt 79 Tryjisimetry ........... 80 Metacasein 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 CONTEXTS IX SECTION II. DIETETICS. I. — INTKODUCTOKY — ON DIETETICS IX GENERAL. PA(i K Dyspeptic troubles more common in man than in animal^^ . . 9H Causes of this — complexities of the human dietary . . . . 94 Basis of scientific dietetics — dietetic customs .... ll(» On the use of meat . . 9H On the use of alcohoUc beverages ....... 99 On the use of tea, coffee, and cocoa . 101 Dietetic habits of the two sexes . 10;> Dietetic habits of infants and children — and of the aged . . . 104 Personal and family idiosyncrasies ...... 105 Effect of the quality of the food on nutrition and vital habits . . 10(! High feeding and low feeding ....... 108 Comparison of bodily and mental qualities of high-fed and low-fed classes and races 109 II. EFFECT OF FOOD-.A.CCESSORIES ON SALIVARY DIGESTION. Preluninary remarks ... ...... 11*2 Method of experimentation ........ 114 Effect of alcoholic beverages ........ 115 Proof siJirit, brandy, whisky, and gin ..... 115 Wines . . . ' 117 Acids 118 Malt liquors 119 Effervescent table waters ........ 119 Effects of tea, coffee, and cocoa, &c 1'2() 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 X CONTEXTS I'ACB Effect of alcoholic beverages ........ 132 Proof spirit, brandy, whisky, gin ...... 132 Shei'ry 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 whev ......... 140 IV. — EFFECT OFFOOD-ACCESSOKIES ON PEPTIC DKiESTIOX, CONTINUED — THEIR EFFECT ON P.\NCRE.\TIC DIGESTION. Causes of the retarding effects of food-accessories on jieptic digestion ........ In the cases of beef-tea and whey ...... Retarding effects of salts of the organic acids Retarding effects of inorganic neutral salts .... Effects of superacidulation ....... Effects of dialysis ......... The alkaloids and volatile oils of tea and coffee Has retardation of gastric digestion a beneficial purpose ? Use of salt Effects of Foon-.\ccEssoRiEs on p.iXCRE.\Tic digestion Effects of food-accessories on pancreatic diastase . Effects of food-accessories on tryptic digestion .... 143 144 146 146 147 149 150 153 156 156 157 158 V. — ON SOME PR.\CTIC.VL 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 CONTENTS XI SECTION III. PREPAJIATION OF FOOD FOR INVALIDS. I. — PKEPARATIOX OF ORDINARY FOODS FOR INVALIDS. PAGE Effects and purposes of cooking 177 Clinical relations of gastric and intestinal digestion f . . 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 ... ........ 186 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. — PREP.\RATION AND USE OF ARTIFICIALLY DIGESTED FOOD. Introductory remarks 192 Pancreatic digestion of milk ........ 196 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 blanc-manges . . . . 204 Peptonised beef-tea . 205 Nutritive value of peptonised food ....... 206 Experimental evidence ........ . 207 Clinical experience of peptonised food . . . . . . 213 In ur»mic vomiting ........ 214 Gastric catarrh .......... 214 Crises of cardiac disease ........ 214 Pernicious anajmia . 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 as an addition to nutritive euemata . . . 218 XU CONTENTS III. — THE USE OF MALT, AND ESPECIALLY OP MALT INFUSION, FOR THE PKEDIGESTION 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 antisejitic properties of chloroform .... 225 Administration of malt preparations with food . . . . 220 Predigestion of starchy food ........ 227 Liebig's method .......... 228 The use of malt infusion ........ 229 Clinical expei-ience 230 SECTION IV. DYSPEPSIA. ON THE ACID DYSPEPSIA OF HEALTHY PERSONS. General description 335 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 CONTENTS XIU APPENDIX. A MEMORANDUM OX THE GENERAL FEATURES AND THE MEDICAL ASPECTS OF THE OPIUM HABIT IN INDIA. TAOE Introductory — Euphoric agents 2G1 (1) The opium habit proper ........ 263 Distribution and prevalence ...... 264 Tolerance and susceptibility ...... 269 Age and sex .......... 271 Dosage .......... 272 Increase of dose and excess ....... 274 Stopping the opium habit ...... 27r> The opium habit and food . . . . . . . 277 Effect on health and longevity ...... 27H „ „ insanity ........ 281 „ „ suicide ........ 282 Effect on the generative functions ... . . 284 (2) Opium as a household remedy in India ..... 285 (3) Opium as remedy and prophylactic against malaria . . 288 Prevalence of malaria in India ..... 290 Composition of Indian opium . . . . 291 Anarcotine as an antiperiodic ...... 292 Opium-eaters and malarial infection . . ... 294 Plurality of malarial infection ...... 296 (4) The practice of giving opium to infants ..... 298 Prevalence and dosage 299 Why given 300 General effect of the practice ...... 301 Opium marasmus ........ 303 (5) Use of opium on occasions of ceremony ..... 304 (6) Opium-smoking in India ........ 310 Madak-smoking ........ 310 Chandu-smoking ......... 311 Opium pipe ......... 314 Prevalence of opium-smoking in India . . . . 314 Effect on health 315 What the chandu-smoker inhales . . ... 31(> INDEX 319 Section I DIGESTION AND THE DIGESTIVE FERMENTS I. DIGESTION IN GENEEAL— THE DIGESTIVE FERMENTS- DIGESTION OF CAEBOHYDEATES. (First Lumleian Lecture.) SDMM.VRY : — 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 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- ' Claude Bernard, Lerons sur les Phinmiines de la Vie, t. ii. Edited after his death by Dastre. Paris, 1879. EXTERIOR DIGESTION O 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 m 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-containmg 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 laevulose 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- formmg that compound into invert-sugar before it can use it for its profit in fermentation. This transforma- 6 INTERSTITIAL 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. INTEKSTITIAL 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 / 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 i^lace 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 graj^e- 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 fa,ts 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 m my own language in the following propositions : — DIGESTIVE FERMENTS 9 (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 or intestinal surfaces. GENERAL CHAKACTERS 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 U) DIGESTIVE FERMENTS indication of the action of each ferment on the several ahmentary principles. Table of the Digestive Juices and their Ferments. Digestive Juices Ferments contained in Action on Food Materials : Saliva . . . Salivary diastase or Changes starch into ptyalin dextrine and sugar. / 1 a. Pepsin . Gastric juice -j , b. Curdling ferment . i Changes proteids into peptones in an acid medium. Curdles the casein of • milk. Pancreatic juice -l a. Trypsin i , 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 . ? . . . . 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 U 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. They 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 EERMENTS 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 filtration 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 a,mount of unchanged — that is to say of undigested — DIGESTIVE FERMENTS 13 albumen, which is precipitated by the addition of nitric acid or by boiHng. 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 w^ould 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 unsus- ceptible 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 j)roteids — and which goes by the name of ' dyspeptone ' — is not, as has been thought, a by-product of the digestive process, but that it is simplj' 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 exclusively 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 ]4 DIGESTIVE FERMENTS profound character — and they affect much more the j)hysical 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 laevulose) , 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. Kiihne 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 caU 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, extremely 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 acid — others have used glycerine ' or common salt. ' 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 Sim'it. The second solution is water mixed with twelve or fifteen per cent, of rectified spirit.^ This solution makes ' 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 be 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. III. 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 he 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 19 Alimentary 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 w'hich 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 FEKMENTS — 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 TRANSFOEMATION 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 jDure 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 TKAXSFORMATIOX 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 mtense 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 iodme. 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 Ci.,H,,oO„„ 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 O'SulHvan' 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 thekind 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 CigHg^Oi,. 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. ' O'Sullivan's papers are published in the ' Journal of the Chemical Society ' from 1872 to 187G. A full account of these researches is given in a paper in the same Journal for September, 1879, by H. T. Brown and J. Heron. TRANSFORMATION OF STARCH 23 The researches of Muscuhis and O'SuUivan 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,2Ho(,0,o — 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,oH.,oOi(,) — 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'SuUivan. In an elaborate publication (* Journ. Chem. Soc.,' Sep., 1879) ihey 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 that the molecule of soluble starch consists of ten members of the group C,.2H2oOio, and that its formula should be written 10(C,2H2oOio). This view greatly facilitates the comprehension of the progressive hydrolysis of starch by diastase. We have seen that starch m 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 aggi-egation between starch in these two states — and it will 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 TKANSFORMATION 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,,H,oO,o)-f-8(H,0) = 1. Erythro-dextiine o 9(C,oH„oOio) + (C,„H„._,0,,) maltose 2. Erythro-dextriiie /3 8(C,,H3„0,„) + 2(C,,H,.p„) 3. Achroo-dextrine a 7(C,,H2„0,„) + 3(C,,H,„0,,) 4. Achroo-dextrine ;8 6(C,,H,„0,„) + 4(C,,H.,,0„) 5. Achroo-dextrine y 5(C,„H2„0,|,) -t-5(C,oH.„0„) 6. Achroo-dextrine S 4(C,2H,,„0,„) -i- 6(C,,H,,0„) 7. Achroo-dextrine f 3(C,oH„„0, j + 7(C,,H2,0„) 8. Achroo-dextrine 6 2(C,,H,„0„,) +8(C,,H,,,0„) The final result of the transformation is represented by the equation lOiC.^H^oO.o) + SH^O = 8(C,2H,20„) + 2(C,,H,,0,o). Soluble Starch. Water. Maltose. Achroo-flextrine. In order to render this array of equations more easy of comprehension to those who are unaccustomed to read complex chemical formulae, 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 CigH^^Oio, 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 Molecvile of Gelatinous Starch Molecule of Soluble Starch + 8 atoms of water 1. Erythro-dextrme a ffS)- O maltose 2. Erythro-dextrine (i@f) .^^ 3. Achroo-dextrine a (©©I*) OOq " 4. Achroo-dextrine /S (©^) O *^P " 5. Achroo-dextrine y ^^ - .OPo^ t< 6. Achroo-dextrine 8 ^ O^nO 7. Achroo-dextrine e @- O^qQO 8. Achroo-dextrine (9 ^ "^^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 obtamed 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 sahvary 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 ' Maly's Jahresbericht filr Thier-Chemie for 1878, p. 40. SALIVAKY AND PANCREATIC DIASTASE 27 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.' THE RESPECTIVE SHARES OF SALIVA AND PANCREATIC JUICE IN THE DIGESTION OF STARCH. The respective shares of saHva 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 ' See a paper by Brown and Heron on the ' Hydrolytic Fennents of the Pancrtas and Small Intestine ' in the Proceedings of tJie Royal Society far 1880, p. 393. 28 SALIVARY AKD PANCREATIC 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 per- meate 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 speakmg 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 opportunitj^ 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 S.AID 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 % X ■"-.. ~^--. "v-e. _^°««00-DEXTRINE. SUGAR. Absorbent Surface Liver Glycogen It is not necessary to suppose that the ascendmg 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- 32 ENERGY OF DIASTASE creas thus prepared proved a very serviceable prepara- 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 steadilj^ 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 perfectlj" transjDarent, 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 ervthro-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- dextrme, or both. Nos. 1, 2, 8, and 4 were restored to the warm chamber, and re-examined at the expii-ation of seven hours. No. 4 no longer gave the slightest reaction with iodine, but Nos. 1, 2, and 3 show^ed only sHght signs of further alteration, and 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 erj-thro-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- D 34 ENERGY OF DIASTASE finished. Nevertheless it had accompHshed an amount of work which, considering its infinitesimally 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 grains) 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 sugai* no less than 40,000 times its own weight of starch.' ' 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 6D The speed at which a given quantity of starch is transformed hy 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. 36 INVERSIVE FERMENT particles of the ferment to a band of living workmen whose function is to scatter little heaps of stones. If the heajDs 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 3'oung 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 ' Claude Bernard, Legons sur les Phinomenes de la Vie, t. ii., p. 36. I'aris, IbT'J. 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, m the stomach, and in the pancreas in vam, 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 : — ^^I2^22^n + 2H20 = C,2H240i2 + Ci2H240,2 Saccharose. Water. Dextrose. Laevtilose. 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 recogiiised 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 11. DIGESTION OF PROTEIDS— THE MILK-CUEDLING FEEMENT— THE EMULSIVE FEEMENT. {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 sahvary 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 TRYPSIN — 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 legumen 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 hi 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.' 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.- Berthelot had found that, if you shook up an aqueous, solution of any acid with ether, and then allowed the two fluids to separate, 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 ■parta(ie, 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 ' Die Sue Gastrique, by Ch. Richet. Paris, 1878. ■* Ann. de Chimie et de Physique, 4" s6rie, t. xxvi., p. 396. ACID OF THE GASTRIC JUICE 41 found to pass into the ether in considerahle, though very variable, quantities — the proportion varying in a constant ratio according to the nature of the acid. Testing pure gastric juice, uncontaminated with food or sahva, 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 libe- rated 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 GASTRIC 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 leucm.' Eichet next proceeded to examine the free acid actually existing in the stomach durmg 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 — m this resj)ect, namely, that it contained a very much larger proportion of organic acids, in comparison to the mineral acid, than pure gastric juice. It was e^adent that the mmeral 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. ' 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 GASTKIC JUICE ON OTHER FERilENTS 4o THE EFFECT OF GASTKIC JUICE OX 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 Richet, 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, namel}' — as to whether the salivary and more especially the pancreatic ferments were or were not destro3'ed ])y 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 alkalme 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 Academic des Sciences towards the close of 1870, and have attracted some attention. On the ground of the 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 acti\dty in the presence of the gastric acid — that the acids of the 44 EFFECT (^F GASTRIC JUICE ON OTHER FERMENTS chyme, being organic acids, did not really destro}' these 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 waj's. One of Defresne's (apparently) most convincmg experiments was the following, which I give nearly in the words of the abstract of the paper published in the ' Proceedings of the Academic 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 HCl), are mixed with 20 grams of egg-albumen — what follows ? The acidity of the medium is no longer due to free hj'drochloric 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 hydrochloric 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- EFFECT OF GASTRIC JUICE ON OTHER FERMENTS 45 tion was to allow the h\-drochloric acid a sufficient time 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 carefully neutralised. On testing the neutralised filtrates, I obtained approximatively 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 them. 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, 46 EFFECT OF GASTRIC JUICE ON OTHER FERMENTS and it is also an acid which is often, if not always, pre- sent in the contents of the stomach during digestion. I prepared a sohition of lactic acid corresponding in satu- rating power to the normal gastric acid (2 per 1000 HCl). 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 wdth 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 eqxisd 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 sHghtest 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 proteolj'tic activity. I 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 ch^^mifi- 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 pros- pect 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 by-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 way 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 ah'eady seen that in the case of starch the 48 CHARACTERS 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. Characters 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 jellying, and no viscosity, but continue diiHuent 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 -10 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, contradictor}^ 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, V. 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. "\Mien 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. 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 shght 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 ' 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 ' A. Henninger, De la Nature et du Rule PJujsiologique cles Peptones. Paris, 1878. ACTION OF PEPSIX AND TRYPSIN ol 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. COMPAEISON 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.' 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 ' 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 filtrate was found to be a rich and nearly pure solution of pei3tone — 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.^ 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 ' Most observers have noticed the occurrence of this indigestible residuum (named Dijspeptone by Meissner) in the artificial gastric diges- tion of proteids. I have noticed the same in the digestion of milk by pancreatic extract. 54 TEPTOGENS 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 slowl.y 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 Schifif 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 i)ortions) was introduced into the stomach of a fasting animal no pepsin was secreted, and the albumen remahi 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 j^^ptogens. 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 PEPTOGENS 5.) coifee had not much. Schiff further found that pepto- genic substances were just as effective when they were injected into the blood, or into the ceUular 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.' 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 to the prevailing custom of commencing dinner with soup. ' See Logons sur la Physiologic dc la Digestion, Paris, 1867, t. ii., p. 200 et seq., where the experimental evidence on which he relies is set forth at length. 56 MILK-CURDLING FERMENT 1 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 utiHsed on a large scale in the industrial art of making cheese. Rennet, which has been used for that purpose from remote antiquity,'^ 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. Brilcke 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 ' The name ' Rennin ' for the milk-clotting ferment has been jn-o- posed by A. S. Lea and W. L. Dickinson. Journ. of Physiology, 1890, p. 307. - 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-CUEDLING FERMENT 57 property of curdling niilk 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, hke 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. 58 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 pro- duct 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 OF 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 occm'rence of curdling has apj)eared 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 api^arently akin to that of the fibrin-ferment on blood — and it may hkewise 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 infinitel}^ 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 ' Claude Bernard, Legcms sur les PMnoinines dc la Vie, t. ii., p. 346. 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 be3'ond 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 salicylate 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 ' 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 ' Hoppe-Seyler, Physiologische Chemie, p. 257. Berlin, 1878. EMULSIVE FERMENT DIGESTION OF FATS 61 a very marked emulsifying power, but it had the same 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 satisfactory 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. (38° 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 ELEMENT DIGESTION OF EATS G3 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 (probabl}' oleic acid, which is insoluble in water, and therefore does not acidify 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 61 EMULSIVE FERMENT DIGESTION OF FATS acid reaction to water shaken up witli 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 chj^me, 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 sulficient 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 Richet 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. 6Q III. ON THE ESTIMATION OF THE AMYLOLYTIC AND PROTEOLYTIC ACTIVITY OF PANCREATIC EXTRACTS. (From the Proceedings of the Royal Society for 1881.) Summary : — Preliminary observations — Diastasimetry — 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 sheeii — 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 FEKMEXT8 67 asmucli as there is in them no power of growtli and muhiphcation, the amount of energy with which they are endowed is strictly limited,' 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 then* 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 organ- isms. The ferment-power cannot be separated from the ferment-organism by any method of filtration, 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. Kuhne 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 en zymosis, and the nature of the action may be spoken of as enzymlc. ' For proof of this see p. 31 et seq^. 68 DIASTASIMETRY In the present paper I shall venture to employ these terms m 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, j^anc re at ic 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 EXTRACTS DIASTASIMETRY. Probably the most accurate mode of estimating the activity of a diastasie 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.' 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.'^ 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 ' Journal of the Chemical Society, September, 1879. '^ Compte Rendu des Travaux dit Lahoratoirc de Carlsberg, 1879, 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 sta)idard 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° C The mucilage was made of the strength of 1 per cent., and in the following manner : 5 grams 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 ' The so-called pure starch of the shops is woi'thless for the pui*poses 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 nmeilaf/e. 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 amylo- Ij^tic 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 en zymosis was carried on. Quantitij and Time. — The amount of amylolytic 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 w'hich 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 interference 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° G.{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 j^roportion. 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 ijrogressively 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 diflficult to explain. In regard to the action of pancreatic extract on starch mucilage, the rule of inverse proportion between ([uantity 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 shotoing the inverse proportion between quantity and time in the action of Pancreatic Extract on Starch Mucilage. The quantity nf 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 Poiut — Quantity of Pancreatic Extract employed was reached Found Calculated 0-02 c.c. 34 minutes 36 minutes 0-04 „ 18 „ 18 I. . 0-08 „ 9 9 0-10 „ 7 7 J, 0-20 „ 3 3* ( 0-4 „ 4| „ 5 II. . . 0-2 „ 10 „ 10 1 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 quantitj^ 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 TEMPEEATUKE i Table II. — Experiments slwwitig the postponement of tlie Achromic Point iclien the action is protracted. The quantity of staudarJ mucilage acted uu iu each case was 10 c.c. (liluted with water up to 100 c.c. Temiitrature 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 Time in which the Achromic Point was reached Extract employed Found 1 Calculated 0-05 c.c. 0-005 „ 0-004 „ 1 0-002 „ ! 0-0005 „ 10 minutes — 115 „ 100 minutes 140 „ 125 300 „ 250 1,380 „ 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 precisel}^ 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 PEOCEEDING Table III.- — Shoici7ig the effects of Tcmperatiirc on the action of Pancreatic Diastase. The amoimt of the standard mucilage acted on in each experiment was 10 c.c. dihjted with water up to 100 c.c. The quantity of pancreatic ex- tract employed in each experiment was 0-1 c.c. Temperature Achromic Point reached in 3—5° C 36 minutes. 10° 18 „ 1.5° 12 „ 20° 8 . „ 25° T) „ 30° 5 „ 40° 5 „ 45° 5 „ 50° 7 „ 55° 10 „ 60° 40 „ 65° Very slow action. 70° No action. These results, thrown mto 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 abscissae represent the temperatures. Mode of Proceedwfi. — 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 75 added to it, than to proceed contrariwise. The bulk of Hquid 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 ■yvas 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 DIASTA.SIC VALUE limitation. The most satisfactory results are obtained when the achromia 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 c.c. standard Starch Mucilage + 90 ex. water + 0*1 ex. Paiicreatic 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. Ac hromic po int 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 adaj)ted 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 lY.), 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 p. p in 78 DIASTASIC VALUE OF PANCREAS and in the above example — D = ^^ X ^ = 83 at 40° 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 alreadj?- 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 DI AST ASIC VALUE OF SALIVA AND MALT 79 value indicates that 1 grm. of the moist pancreas of the pig is capable of transforming 4 grms. of dr}- 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 jjancreas 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 b}^ 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 j)oint 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 TRYPSIMETRY were tested by this method. They showed a diastasic value varying from 0-03 to 0-13 at 40° C. The effect of temperatm-e 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 mcta- casein. This substance resembles casein in being curdled by acetic acid in the cold ; but it differs from casein in being also curdled l)y 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 somewhat abruptly, and the milk, when boiled, remains fluid just as it did at first. We may therefore speak of the onset point of the metacasein reaction, and of the vanishing j^oint of the METACASEIX REACTIOX ' soluble starch . I no action no action neutralised 4 minutes 4 minutes Action of Acids on SaUraiij Digestion. — This is a question of considerable interest — not only because we are in the habit of using acid wines and malt liquors with our food, but also vinegar and pickles and lemon- juice ; and eat puddings and jjies containing acid fruits or acid rhubarb stalks. The annexed table shows the effect of table vinegar on salivary digestion : — Table III. — Effect of Table Vinegar on Saliranj Digestion. 10 c.c. standard stixrcli niucilage+ varying quantities of vinegar + water np to 100 c.c. + l c.c. filtered saliva. Prcriortion of Vinegar contained in the digesting Mixture 0-02 per cent. = 1 in -5,000 O-O-") „ =1 in 2,000 0-1 „ =--1 in 1,000 0-2 „ = 1 in .500 Time in which the achromic point was reached (Normal, 4 minutes) 6 minutes 14 30 no action EFFERVESCENT WATERS 119 The table shows that the hindeiing effect of vinegar is very powerful. Even so small a proportion as 1 in 5,000 sensibly delayed the action ; with a proportion of 1 in 1,000 the action was very slow, and it was altogether arrested when the proportion of vinegar rose to 1 in oOO. The bearing of these results on the use of salads is evident. Salads are usually highly seasoned with vinegar, and they are commonly eaten with a liberal use of bread. The acid may perhaps assist in the digestion of the salad ; but it is obvious that it w^ould altogether prevent any salivary action on the bread eaten with it. This, of course, is a matter of no moment to a eupeptic individual, who has abundant digestive resources ; but those of weak digestion would do well to be sparing in the use of acid salads and other sour dishes. Malt Liqiinrs. — Malt liquors were found to hamper salivary digestion exactly in proportion to their degree of acidity. Sound English beers have not nearly so much acidity as wines — and they interfere comparatively little with the digestion of starch ; but ' turned ' beer is highly inhibitory. Ejf'en-cscoit Table Waters. — The examination of these yielded some odd results. A pure aerated water, charged merely with carbonic acid, exhibited considerable inhibi- tory power on salivary action. ^Vlien the digesting mix- ture contained 50 per cent, of a carbonated water the diastasic action was wholly arrested, and even so small a proportion as 10 per cent, postponed the achro- matic point from the normal of four minutes to thirty minutes. But the effervescent table waters of com- merce — soda water, potash water, seltzer water, Apol- linaris water, &c. — are all more or less charged with alkaline carbonates ; and this charge of alkali altogether 120 EFFECT OF TEA, COFFEE, AND COCOA I'pmoves their inhibitory effect on salivary digestion. These waters are, as you know, extensively used both here, and still more on the Continent of Europe, as an addition to wines — to claret, hock, and sherry esjDecially. And the effect of this addition is to greatly mitigate, or wholly to obviate, the retarding influence of these wines on the digestion of starch. The use of these waters as an addition to wines is, therefore, highly commendable. TEA, COFFEE, AND COCOA. The effect of tea and coffee on salivary digestion pre- sented a strong contrast, for while tea exhibited an intense inhibitory action, coffee — and with it id ay be ranged cocoa — had only a subordinate effect. As this is the first time I have had occasion to speak of experimental inquiries into the effect of these beverages, I must enter into a little explanation. There is no standard strength of tea and coffee, but from information gathered in the social circle, and observations on the beverages put un my own table, I have learnt that the medium strength of tea is from 4 to 5 per cent., that is, four or five parts by weight of the dry leaf to a hundred parts of boiling water. Strong tea runs up to about 7 per cent., and weak tea goes down to 2 per cent. Coffee is generally used in a stronger infusion than tea. Medium coffee has a strength of about 7 per cent., and strong coffee — the black coffee or ' Cafe noir ' of our French neigh- bours — has a strength of about 12 or 15 per cent. Cocoa, on the other hand, is usually made weak ; the printed directions given on the packets of cocoa indicate a strength of only about 2 per cent. This is probably one of the reasons why cocoa has a higher reputation as an aid to digestion than tea or coffee. EFFECT OF TEA 12 Table IV. — Effect of Tea and Coffee on Salivary Digestion. 10 c.c. standard starch mucilage + varying qaantities of tea and coffee (both of 5 per cent, strength ) + \v.iter to 100 c.c. + 1 c.c. filtered saliva. Both beverages were infused for ten minutes and then filtered. Time in which the achr omic point was reached (Normal, 4 minutes) 1 'roportion of Tea or Coffee coiitaineil in tlie Digesting Jlixturo Tea--5 per cent. Coffee- -5 per cent. strength strength 1 1 per cent. 8 minutes 4 minutes 2 30 4 ,, 3 50 4 ,j 5 180 4 10 ( no action beyond i 4 i soluble starch • " 20 no action 4 ij 40 — 10 60 — 20 " Tea. — The table shows that tea is a powerful retarder of salivary digestion. When the digesting mixture con- tained even so small a proportion as 1 per cent, there was a perceptible retardation, and as the proportion increased the inhibitory effect was rapidly intensified. With a proportion of 2 and 3 per cent, the achro- matic point was delayed from the normal of four minutes to thirty and fifty minutes respectively ; with 5 per cent, it was delayed to three hours, and above this proportion there was practically no digestion of starch. A specimen of high-class Assam tea was found to retard salivary digestion somewhat more powerfully than a good China tea. A very cheap low-class tea costing Is. 6(L per lb., such as is supplied to the poorest classes, had very little retarding effect. It was probably an adulterated article. What is the cause of the inhibitory action of tea on salivary digestion ? It seems to be entirely due to the large proportion of tannin contained in tea. Black 122 EFFECT OF TANNIN China tea contains, according to the analyses of Jauke, an average of 8 per cent, of tannin ; ' and, as the following table shows, tannin is highly inimical to the digestion of starch. Table V. — SJiows the effect of Tannin on Salivary Digestion. 10 CO. standard staroli mucilage + varyiug quantities of tannin + water to 100 o.e. + l CO. filtered saliva. Proportion of Tannin in the | Time in which the achromic point was Digesting Mixtnre reached ( Normal, 4 minutes) 0-002 per cent. = 1 in -50,000 . ! 10 minutes 0-005 „ =1 in 20,000 . 40 „ 0-01 „ - 1 in 10,000 . no digestion beyond soluble starch 0-02 „ =lin 5,000 . I no digestion On comparing the results obtained with tea and those obtained with tannin, and calculating the amount of tannin which would be contained in a 5 per cent, infusion of tea, the conclusion is arrived at that the tannin contained in tea fully accounts for its inhibitory €tfect on salivary digestion. For if the tea operated with contained 8 per cent, of tannin, and three-fourths of this were taken up in the infusion, it would yield a solution containing 0-3 per cent, of tannin, and the ■effect of such a percentage of tannin would correspond very exactly with the results shown by experiment to be produced by the tea employed. It appears that tannin exists in two conditions in the tea-leaf. One, the larger, portion is in the free state, and is easily extracted by hot water ; but about one-fourth is fixed and remains undissolved in the fully exhausted tea- leaves. Some persons have supposed that by infusing tea for a very short time— only two or three minutes — the passing of tannin into the infusion could be avoided. This is ' Walter Blyth, Foods, their Composition and Analysis, p. 334. TANNIN IN TEA 12o a delusion ; you can no more have tea without tannin than you can have wine without alcohol. Tannin, in the free state, is one of the most soluble substances known. If 3'ou pour hot water on a little heap of tannin it instantly dissolves like so much pounded sugar. Tea-leaves when treated with hot water expand at once into thin broad laminae, presenting a highly favourable condition for the rapid extraction of their soluble consti- tuents. Tea infused for two minutes was not found sensibly inferior in its retarding power on salivary diges- tion to tea infused for thirty minutes. The deteriora- tion of the flavour of tea by long infusion appears to depend on the slower taking up of a bitter principle, which is less soluble than tannin, and which, apparentl^y, does not interfere with diastasic action. If you wish to minimise the inhibitory action of tea on starch digestion you should direct, not that it be infused for two or three minutes, but that it should be made very weak and used very sparingly, and that it should be drunk, not with the meal, but after the meal has been swallowed. There is a curious difference in the practice of different persons in the way in which they imbibe beverages with their meals. Some drink and eat at the same time : others eat first and drink afterwards. The latter are the wiser if it be an object to facilitate their salivary digestion. There is another device by which tlie inhibitory effect of tea on salivary digestion may be obviated, and which may be recommended to persons of weak digestion. The introduction of a pinch of bicarbonate of soda into the teapot completely removes the deterrent effect of tea on starch digestion. This is a practice I have seen followed in some households under the idea that the soda helps to extract the virtue of the tea. 1 found on experiment that the addition of so small a proportion as 1 per cent. 124 EFFECT OF COFFEE of bicarbonate of soda to the weight of the diy tea-leaf greatly mitigated the inhibitory effect of the infusion on starch digestion, and that twice this quantity (2 per cent.) almost entirely removed it. This latter proportion corresponds roughly to about ten grains of soda (as much as will stand on a threepenny-piece) to an ounce of the dry tea-leaf. A darker coloured infusion is obtained thereby, but the flavour is not sensibly altered, nor is there an alkaline reaction produced — for tea-infusion, like most other vegetable infusions, is slightly acid to test paper ; and the quantity of soda here mentioned is only just sufficient to neutralise that acidity. But is the inhibitory effect of tea on starch digestion injurious to healthy people ? Is not this retarding effect really one of the objects which we unconsciously aim at in using this beverage ? I will return to these questions later on when I come to consider the effects of our food-accessories on peptic digestion. The peculiar alkaloid of tea — theine or caffein, for the two bodies are identical — and the volatile oil which gives it aroma, seem to have no part in the inhibitory effect of tea on digestion. I made direct experiments with citrate of caffein, and found it indifferent, at least in such proportions as it could ever be present in our tea infusions. I tested the effect of theine and the volatile oil in another way. I sprinkled some dry tea-leaf on a plate and exposed it for four hours to a temperature of 212° Fahr. (100-^ C). This would suffice to drive off both the alkaloid and the volatile oil. Tea so treated was found to have lost none of its inhibitory effects on starch digestion. Coffee. — Coffee was found to have a far less inhibitory action on salivary digestion than tea (see Table lY.). Operating on a 5 per cent, infusion of a high-class coffee, bp:ef-tea, salt, and sugar 125 it was found that up to a proportion of 20 per cent, in the digesting mixture there was no appreciable retard- ing effect. "With 40 per cent, the achromic point was delayed from the normal of four minutes to ten minutes. Above this point the retarding effect increased somewhat ; but even when the digesting mixture contained 90 per cent, of coffee digestion still went on with considerable speed. In coffee, tannin is replaced by a modification of that substance called caffeo-tannic acid, and this accounts for the marked difference in the effect of the two beve- rages on salivary digestion. Cocoa resembles coffee in its effect on starch diges- tion, and it may be regarded as practically indifferent. We may therefore infer from these observations that the use of coffee and cocoa, in so far as concerns their influence on salivary action, is more to be recom- mended to persons of feeble digestion than the use of tea. Beef-tea, Salt, and Saorti(in of Hock, Claret or Chatnpasne in the Digesting Mixture 10 per cent. . 20 „ . . 40 „ . . 60 „ . . Time in which Digestion was completed (Normal, 100 minutes) Hock Claret Champagne 90 minutes 100 130 180 100 minutes 115 „ 150 embarrassed 100 minutes 140 180 embarrassed We observe again that the retarding effect of these wines is out of proportion to the alcohol contained in ihem. These wines are estimated to contain from 10 to 12 per cent, of absolute alcohol (20 to 24 per cent, of 136 MALT LIQUORS proof spirit), so that, however freely they might be used dietetically, the amount of alcohol so introduced, even if they were used up to 80 per cent, of the total contents of the stomach, would scarcely produce an appreciable effect on peptic action. We must, therefore, again here re- cognise the presence of some other retarding agent besides alcohol. The table shows that champagne has a markedly less retarding effect than hock and claret. Indeed, in the proportion of 10 per cent., champagne had a distinct, though slight, accelerating effect. This superiority of champagne is due probably, as we shall presently see reason to believe, to the mechanical effects of its effervescent qualities. If we consider the copious proportions in which hock and claret are used dietetically, it becomes evident that their retarding effect on peptic digestion is often brought into play. A pint of claret or hock is a common allow- ance with dinner for robust eaters — and such a propor- tion, as the table shows, would not be without consider- able effect. When French and Italian peasants use freely, as they do, a wine akin to claret with their meals, which are mainly composed of In'ead and other farinacea, the effect must be highly retarding on digestion. On the other hand, the more sparing use of these wines, a glass or two, with dinner or luncheon would evidently not produce any appreciable retardation of peptic action, but would, like corresponding doses of sherry, act as pure stimulants. In both these instances, as in some others, it seems to be indicated that by adjusting the quantities we may elicit diverse effects. With large (|uantites we may obtain retardation, with small quantities we may obtain acceleration of gastric digestion. Malt Liquors. — The malt liquors experimented on EFFERVESCENT WATEKS 137 were bottled Burton ale, a light sparkling English table beer, and Lager beer. Table Xl.—Shoius the effect of Malt Liquors on Gastric Digestion. 2 grams of dried beef -fibre+ 0-15 HCl + l c.c. glycerine-extract of pepsin -(-varying quantities of malt liquors -1- water to 100 c.c. Proportion of Malt Liquors contained in the Time in which Digestion was completed (Normal, 100 minutes) Digesting Mixture Light English ,urt„n ale -^^j^ ^ "^^ Lager boer 10 per cent. . .. | 115 minutes 100 minutes 20 „ . . 140 „ 115 40 „ . . 200 „ 140 60 „ . . 1 embarrassed 180 „ The retarding effect of malt liquors is (as is the case with wines) altogether out of proportion to their per- centage of alcohol. These beverages contain only from 4 to 6 per cent, of alcohol (8 to 12 per cent, of proof spirit), so that the alcohol contained in them could scarcely ever, on its own account, produce any effect. Their retarding influence must, however, often come into operation. These beverages are used very freely with meals, and the digesting mass in the stomach must often contain them in the proportion of 50 or 60 or sometimes even 80 per cent. Such proportions would act as powerful retardants, especially on the digestion of bread and other articles of farinaceous food. In more moderate quantities — a tumbler or so — especially of the lighter beers, the effect would evidently be rather to promote than to retard gastric digestion. It was found experimentally that beer when ' well up ' was distinctly more favourable to quick digestion than the same beer when ' flat.' Efen-esceiit Table Waters. — Simple carbonated water 138 TEA AND COFFEE distinctly hastened peptic digestion ; but the favourable effect was quite subordinate — and it was better brought out with proportions of 10, 20, and 40 per cent, than with larger proportions. I attributed the slight accele- ration observed entirely to the mechanical operation of the escaping gas in causing an additional stirring up of the digesting mixture. The ordinary commercial effer- vescent table waters — soda- and potash- water, seltzer and Apollinaris waters — all contain, as before stated, a certain quantity of an alkaline carbonate. This would have necessarily a certain neutralising effect on the acid of the gastric juice. But I was surprised to find, even in a laboratory experiment — wherein, of course, there could not be, as w^ould be the case in the living stomach, any compensating secretion of fresh acid— that these waters had, even in the proportion of 90 per cent., only a very slight and insignificant deterrent effect on peptic digestion. In smaller proportions their action was quite inappreciable. It may be inferred from these observations that the sparkling wines (as indeed was found experimental!}' to be the case with champagne) are less hindering to digestion than the still wines ; and that, when used in moderate proportions, they may act, not only as stimulants to the secretion of gastric juice and to the muscular activitj' of the viscus, but may, at the same time, slightly accelerate the speed of the chemical process in the stomach. Tea and Coffee. — The effect of these important beverages is of great interest, in view of their wide diffusion and copious use. A large number of obser- vations were made with the object of testing their influence on j)eptic digestion. The mean results are indicated in the following table : — TEA AND COFFEK 1 3i> Table Xll.— Shows the effects of Tea and Coffee on Gastric Digestion. 2 grams of fined beef-fibre+0'15 HCl + l c.c. glyccrine-extnict of i)ei)siii + varying proportions of tea aud coflEee+ water to 100 c.c. Proportion of Tea or Coffee coutaiiied in the Digest- Time in whieli digestion was completed (Normal, 100 minutes J ing Mixture Tea-5 per cent. ! Coffee— 6 percent. Coffee— 15 per strength strength . cent, strength 10 per cent. . lOo minutes lOo minutes 160 minutes 20 „ . . 140 „ 140 ,, embarrassed 40 „ . . 180 „ I 180 ,, almost no action 60 „ . . embarrassed embarrassed — It is seen that both tea and coffee exercise a powerful retarding effect on peptic digestion. "With infusions of equal strength there was no appreciable difference between the two beverages ; but inasmuch as coffee is usually made of greater strength than tea, its effect, as dieteticallyused, is more potent. Cocoa was found, with infusions of equal strength, to possess nearly as much retarding effect as tea or coffee ; but as it is usually made with a strength of only about 2 per cent., its inhibitory effect scarcely comes into play in the customaiy use of this beverage. Strong coffee, the ' cafe noir ' of France, is seen to have a very powerful inhibitory effect. Even so small a proportion as 10 per cent, of this strong coffee in the digesting mixture abated the speed of digestion very considerably, and with 20 per cent, diges- tion was greatly embarrassed. Considering the copious proportions in which we use tea and coffee with our meals, it is obvious that the retarding effect of these beverages is commonly brought into operation in gastric digestion. I could not detect any appreciable difference between the effect of tea infused for 2 or 3 minutes and tea infused for 15 or 30 minutes. If you wish to mini- mise the retarding effects of tea, in persons of weak diges- 140 BEEF-TEA AND WHEY tion, you should give instructions either that the heverage be made weak or that it be used in sparing quantities.' The effect of tea on gastric digestion is enhanced, in regard to bread and other farinaceous articles, by its j)owerful inhibitory action on salivary digestion ; so that, speakipg of these two phases of digestion together, tea must rank much higher as a retarding agent than coffee and cocoa. In the case of alcoholic beverages, their stimulating influence on secretion, and on the muscular activity of the stomach, operates as a partial set-off" against their retarding effect on the chemical process of peptic digestion ; but in the case of tea and coffee there is not, so far as is known, a corresponding compensation. Tea and coffee are probably pure re- tarders of the digestive process in the stomach ; and the question will presently arise as to whether this is an evil or a good. Bccf-tea ami JJ'hei/. — Beef-tea may be regarded as the representative type of the various soups and broths which are so largely used as accessories to the more solid ingredients of our meals. And the unexpected effects of ' A good deal has been said of the injurious effects on gastric digestion of the tannin contained in tea. I question whether the statements made with reference to tliis matter are worthy of attention. It has been alleged that meat-fibre is hardened by tea, and that the coats of the stomach are liable to be injured by this beverage. These views are entirely theoretical. Leather is no doubt a very tough, indigestible substance, but meat-fibre is not gelatine, and the coats of the living stomach are not dead membrane. Meat-fibre does not, as a matter of fact, harden in tea ; on the contrary, it swells nearly as freely in acidulated tea, of medium strength, as in simple acidulated water. And the same is true of a half per cent, solution of pure tannin. The effect of tannin on peptic action is com- paratively slight ; and its presence in tea only partially accounts for the inhibitory power of tea on the digestion of proteids in the stomach. The acid reaction of the gastric contents importantly modifies the reaction of tannin on albuminoid solutions, and largely obviates the precipitation of proteids which is occasioned by it in neutral media. EFFECT OF BEEF-TEA AND WUKY 141 beef-tea on peptic digestion led to an examination of the effects of whey, and of infusions or decoctions of other articles of food — bread and fruit, and also of fruit juices. The results obtained with beef-tea and whey are chronicled in the following table. The beef-tea was made by gently boiling or simmering lean minced beef with an equal weight of water for thirty minutes, and filtering. The whey was made b}- coagulating warm milk with the peptic extract and then straining and filtering. Table XIII.— Shoivs the effect of Beeef-tea and Whejj on Peptic Digestion. 2 grams of dried beef-fibre + 0'15 HCl + l c.c. glyeerine-extract of pepsiu + varying quantities of beef-tea or whey -f water to 100 c.c. Proportiou of Beef -tea or Whey in the Digesting Time in wMcU Digestion was completed (Normal, 100 minutes) Mixture Beef-tea Whey 10 per cent. 20 „ . . 40 „ . . 60 „ . . 115 minutes 140 embarrassed almost no digestion 105 minutes 130 150 embarrassed It is seen from the table that beef-tea has a power- fully retarding effect on peptic digestion — about equal to that of a five-per-cent. tea. Whey retarded sensibly less — about equal to hock. With the single and trifling exception of aerated (carbonated) water, I found that none of the various accessories which we use with food aided pej^tic digestion. The most favourable conditions for rapid digestion were obtained with hydrochloric acid, pepsin, and simple water. Even minimal quantities of alcohol, wines, tea, or coffee did not give the least assistance to the chemi- cal process. Some of the substances tried were found to be indifferent ; or their retarding effect was so slight that in the quantities in which they are generally used 142 EFFECT OF DECOCTIONS OF BREAD AND FRUIT dietetically the retardation could not be regarded as having an 3' practical importance. Among these were cane-sugar up to a proportion of 10 per cent., glycerine up to the same proportion, strong decoctions of bread, ripe apple, and pear, and the expressed juice of the grape and the orange. In regard to the two last, however, it was found that when their proportion in the digesting mixture amounted to 50 per cent, or over a very considerable retardation occurred : grape juice had a more potent effect than orange juice. So large a proportion as 50 per cent, of these juices could, however, only occur in the gastric contents when these fruits were taken im- moderately, as sometimes happens with children.^ ' Dr. W. J. Eraser has published, in vol. xviii. of the Journal of Anatomy and PJu/siologT/, a very interesting paper — based on a large number of elaborate experiments — dealing with the effects of tea, coffee, and cocoa on peptic digestion. The results obtained by Dr. Fraser coincided generally with those recorded above ; he found that these beverages in nearly every instance retarded peptic digestion. The plan of the experiments diifered so widely from that followed by myself that it was not found possible to bring the results of the two sets of experi- ments into useful comparison. 143 IV. EFFECT OF FOOD-ACCESSORIES ON PEPTIC DIGESTION CONTINUED— THEIR EFFECT ON PANCREATIC DIGESTION. {Fourth Lecture of the Owens College Course.) Summary : — Causes of the retarding effects of food-accessories on peptic digestion — In the cases of beef -tea and whey — Action of salts of the organic acids - and of chlorides of potassium and sodium — Effect of superacidulation and dialysis in removing the retarding effects of food-accessories — Retardation of peptic digestion probably beneficial in purpose — Argument on this question. Effect of food-accessories on pancreatic digestion — On pancreatic diastase — On tryptic digestion. The general results of the experiments described in the preceding lecture appeared to me not a little remark- able. I was particularly surprised to find that beef-tea and whey, which, as meat-juice and milk, are common articles of food, and which are given to invalids, should rank with alcohol, wines, tea, and coffee — and even, in the case of beaf-tea, rank high — as retarders of peptic digestion. And nothing struck me more than the com- parative feebleness of alcohol in this respect. Proof spirit, whisky, and brandy had no more retarding effect than so much beef-tea, and we have previously seen that alcohol is still more feeble as a retarder of salivary digestion. What is the cause of tliese retarding effects '? On inquiring into this (juestion it was speedily seen that the cause was different in different cases. In the case 144 CAUSES OF EETAKDING EFFECTS of proof spirit the cause must, of course, be due directl}- to the alcohol contained in it ; and the same is true of whisky, brandy, and gin, in regard to which it was found that their retarding effect was proportional to the quantity of alcohol they contained. But in regard to wines and malt liquors, their percentage of alcohol did not account for nearly their full effect ; and with tea, coffee, beef-tea, and whey, alcohol had, of course, no part in the retarding effect produced by them. These latter are all highly complex fluids containing various ingre- dients of widely different nature. The wines, besides alcohol, contain ethereal compounds and saline and ex- tractive matters ; and malt liquors contain, in addition to a small dosage of alcohol, the extractive matters of hops, dextrines, and salines. Tea and coffee contain the alkaloid theine (or caffeine), an essential oil, salines, and a bitter principle. Tea contains a large percentage of tannin, and coffee a still larger percentage of caffeo-tannic acid. Beef-tea and whey are rich in organic salts and other saline matters, besides very complex extractives. It is not surprising, therefore, that inquir}^ into the causal agent of retardation should reveal profound differences in this respect. I have by no means mastered this subject, but I have obtained a certain amount of light, which has both a positive and a negative bearing. It will facilitate matters if I take first the cases of beef-tea and whey. I think I have made out in both these instances that their retarding effect on peptic digestion is due to the presence in them of salts of the organic acids and of neutral inorganic salts ; namely, to the lactates and sarcolactates, and to the chlorides of potassium and sodium which they contain. It has been shoN^n by Berthelot that salts of the SALTS OF THE ORGANIC ACIDS 145 organic acids are decomposed in the presence of tlie mineral acids, just as the carbonates are — with this difference only, that in the latter case the carbonic acid, being gaseous, escapes with effervescence, whereas in the former case the organic acids which are set free remain in the solution. Therefore, when lactate or tartrate of potash is mixed in solution with free hydrochloric acid, there is immediately formed chloride of potassium, and free lactic or tartaric acid. And this is exactly what occurs in the stomach with beef-tea and whey, for the hydrochloric acid of the gastric juice seizes on the alkaline bases of the lactates contained in these liquids, forming therewith chlorides of sodium and potassium, and setting free the organic acid ; and although the acidity of the gastric contents is not thereby diminished, this acidity no longer consists of hydrochloric acid, but partly of that and partly of lactic acid : and if the quantity of beef-tea be considerable, all the hydrochloric acid may disappear, and only lactic acid be left free in the solution. The effect of this substitution is immense, for the organic acids have only a very feeble digestive power as compared with hydrochloric acid. On comparing experimentally lactic and tartaric acids with hydrochloric acid, I esti- mated that for equal saturating power the organic acids had not more than one-eighth or one-tenth of the diges- tive power of the mineral acid. In order to test the actual effect of an organic salt on peptic digestion I made some observations with the neutral tartrate of potash. Varying quantities of this salt were added to the usual digesting mixture. The fol- lowing table exhibits the results obtained : — 146 INORGANIC SALTS Table XIV. — Shoiuing the effects of Salts of the Organic Acids on Peptic Digestion — Neutral Tartrate of Potash. 10 grams moist eg-g-albiimen + 0-2 HCl + 2 c.c. glycerine-extract of pepsin + varying quantities of neutral tartrate of potasli + water to 100 c.c. Proportion of Tartrate of Potash in the Digesting Mixture Time in which Digestion was complcti'il (Normal, 100 minutes) 0-05 per cent. = 1 in 2,000 . 0-125 „ =1 in 800 . 0-25 „ = 1 in 400 . 0-5 „ = 1 in 200 . 115 minutes 160 embarrassed almost no digestion It is seen from the table that even so small a pro- portion of the tartrate as 1 in 2,000 retards digestion appreciably, and that 1 in 800 retards it considerabl3\ To obtain an idea of the effect of this in the living stomach, let us suppose that the total gastric contents during digestion amounted to two pounds (14,000 grains), then so small a quantity as seven grains of the tartrate of potash would slightly prolong digestion, and eighteen grains would retard it considerably. But the mere substitution of the organic for the mineral acid is not all — the presence of the newly formed chlorides in the digesting mixture is an additional cause of embarrassment to the digestive process. The annexed table exhibits the effects of the chlorides of sodium and ]3otassium on peptic digestion. Table XV. — Showing the effects of Sodium and Potassium Chlorides on Peptic Digestion. 10 grams moist egg-alhumen + 0'2 HCl+2 c.c. glyct-rine-extract of pepsin + varying quantities of sodium and potassium chlorides + water to lOo c.c. Proportion of NaCl or KC'l in the Digesting Jlixture Time in which Digestion was completed (Normal, luO minutes) Sodium Chloride Potassium Chloride 0-1 per cent. = 1 in 1,000 0-25 „ = 1 in 400 0-5 „ =1 in 200 1- „ = 1 in 100 115 minutes 150 embarrassed almost no digestion 108 minutes 130 „ 1 150 embarrassed EFFECT OF SUPEKACIDULATIOX 147 The table shows that sodium chloride has a very considerable power of retarding peptic action. Even in the proportion of 1 in 1,000 it has an appreciable effect ; and with 0-5 per cent, (or 1 in 200) the effect is so great as almost to bring the process to a standstill ; the potassium salt has very distinctly less retarding effect, as the table indicates, than the sodium salt.' These observations yield presumptive evidence that the lactates and neutral mineral salts known to exist in beef-tea are the real retarding agents of that liquid, and that probably kindred salts contained in whey, beer, and wines may account, at least in part, for the retarding effects of these beverages. Now, if this explanation be correct, we ought to find that by increasing the hydrochloric acid in a digest- ing mixture containing beef-tea the retarding effect is mitigated. For if the lactates of beef-tea cause occulta- tion of a portion of the free mineral acid, and thereby retard the speed of digestion, we should expect to find that the addition of more of the mineral acid, so as to compensate for this loss, would parth' obviate the retard- ing effect ; and this is precisely what occurred on experi- ment. The effect of siqieracidulation was tested not only with beef-tea, but also with whey, coffee, tea, wines, and malt liquors. The results obtained, however, only fully answered expectation in the cases of beef-tea and whey. ' The powerful inhibitory effect of sodium chloride on peptic diges- tion has probably some bearing on the old debated question of why the stomach does not digest itself. The blood-serum contains just O-o per cent, of sodium chloride, and this proportion is seen by the table to in- hibit peptic digestion. No doubt, as Dr. Pavy pointed out, the jirincipal obstacle to the self-digestion of the stomach during life is the alkaline reaction of the blood-serum ; but the presence in it of the sodium chloride constitutes an additional and very interesting security against such a disaster. l2 148 EFFECT OF SUPERACIDULATION In regard to the other beverages named the results were either nil or very sHght. The observations tabulated in Table VI., page 130, indicate that the rate of digestion of beef-fibre is sensibly the same with an acidulation of 0-16 per cent. HCl and with an acidulation of 0'3 per cent. HCl. Accordingly comparison was made with these two grades of acidulation in digesting mixtures containing an inhibi- tory proportion (that is to say, a proportion which would approximately treble the normal time of digestion) of beef-tea, whey, coffee, tea, wines, or malt liquors. The results obtained are chronicled in the following table : — Table XVI. — Shoiving the effect of Superacidulaticm on Digesting Mixtures containing Inhibitory Quantities of various Beverages. 2 grams of dried beef-fibre + 2 c.c. peptic-extract + inhibitory quantities of beef-tea, whey, tea, coffee, wine, or malt liquor -f water to 100 c.c. Addition to the Digesting Mixture Time in winch Digestion was completed (Noi-mal, lUO minutes) 0-15 per cent. HCl 0-3 percent. HCl Beef-tea 40 per cent. Whey 50 Coffee 50 Tea 50 Claret 50 Hock 50 Burton ale 50 „ Sherry 20 Port 30 300 minutes 300 300 „ 300 300 300 300 300 300 „ 120 minutes 130 200 240 300 300 300 330 330 „ It is seen that with beef-tea superacidulation acted powerfully in obviating the retarding effect, in fact almost nuUifying it altogether. With whey the increased acidity also acted powerfully in the same direction — not nearly so much, but still considerably, with coffee — much less with tea — find not at all with the lighter wines and Burton ale. With sherry and port superacidula- EFFECT OF DIALYSIS 149 tion distinctly intensified the inhibitory effect of these beverages.' The conchisions were therefore arrived at that the inhibitory etfects of beef- tea and whey were largely due to the salts of the organic acids contained in them, that the same explanation applied only partially to the effects of coffee, and still less with regard to tea. In the case of wines and malt liquors, it was evident that their inhibitory effects must be otherwise accounted for. Further light on the retarding effects of these several food-accessories was sought by subjecting them to dia- lysis, whereby a rude and imperfect but suggestive idea could be obtained of the effect on them of absorption through the walls of the stomach. In each case 100 cubic centimeters of the liquid to be tested were dialysed for six hours into 3,000 cubic centimeters of water ; and the retarding effect of the dialysed product was compared with that of its undialysed counterpart. The results are recorded in the following table : — Table XVII. — Shoiving the effects of Dialysia." 2 grains drietl beef-fibre + 0'15 HCH-2 c.c. peptic extract-!- varying quantities of dialysed and uudialysed beef-tea, whey, coffee, tea, light wines, or Bui-ton ale -(-water to 100 c.c. Addition to the Digesting Mixture Time in which Digestion was completed (Normal, 100 minutes) Undialysed Dialysed for 6 hours 1 Beef-tea 40 per cent. 300 minutes Whey 50 „ 300 Coffee 50 „ 300 Tea 50 „ 300 Claret 50 „ 1 300 ' Hock 50 „ 300 ; Burton ale 50 „ 300 1 120 minutes 135 210 240 210 210 195 ' I take this to be due to the large proportion of alcohol contained in sherry and port ; for I found that with proof spirit also superacidu- lation acted adversely on the speed of peptic digestion. - The increase of the i^roduct in the dialyser varied a good deal. In 150 CAUSES OF EETARDATION The results of dialysis, as shown in the above table, yield the same indications as superacidulation, and lead to the conclusion that in regard to beef-tea and whey the retarding agents are the crystalloids contained in these liquids, and which dialyse with rapidity. Coffee and ale were also considerably affected by dialysis, but tea and the light wines were only slightly affected by dialysis for six hours. I found that by dialysis for twenty-four hours the retarding power of all these beve- rages was almost entirely removed. From these observations on superacidulation and dialysis it was inferred that with beef-tea and whey the saline matters contained in them are wholly answerable for their retarding effect on peptic digestion, \yith regard to coffee, the retarding effect is partially due to saline matters, perhaps chiefly to the caffeo-tannate of potash contained in that beverage. In the case of ale it would also seem that the saline ingredients contained therein account for a considerable portion of its retard- ing effect ; and it would further appear, from a com- parison of the effects of superacidulation on the one hand and dialysis on the other, that the retarding salines of ale are not salts of the organic acids, but neutral mineral salts — probably chlorides and phosphates of potash and soda. In the cases of tea and coffee there arose the question ■whether the alkaloid, theine or caffeine, contained in these beverages contributed anything to their retarding effect on peptic digestion. Direct experiments gave a negative answer to this question. It was found that the case of beef-tea, whey, the wines, and beer the increase amounted to about 10 per cent. ; in the case of coffee to 4 per cent. ; and in the case of tea to only 1 per cent. Allowance was made in the experiments for these differences. CAUSES OF RETARDATION 151 citrate of caffeine, up to a proportion of 1 per cent, in the digesting mixture, had no appreciable effect — and this is a far larger proportion of the alkaloid than ever gets into solution in our ordinary infusions. Neither has the volatile oil contained in tea and coffee any effect. Tea and coffee which had been heated on a plate at 100° C. for a period of four hours — whereby both the volatile oil and the alkaloid would be driven oft' — yielded infusions which had not appreciably lost any of their retarding effects. The tannin of tea accounts for a portion of the retarding power of this beverage, but only for a portion. I found experimentally that the tannin con- tained in tea accounted for about one-half of the retard- ing effect of that beverage on peptic digestion. With regard to wines, I am unable to account for their retarding effect on peptic digestion. Neither super- acidulation nor dialysis gave support to the idea that it was due to their saline ingredients. The retardation caused by these l)everages was wholly out of proportion to the alcohol contained in them. In the case of sherry it was found that when this wine was briskly boiled for five minutes, and the loss by evaporation afterwards made up by the addition of water, its mhibitory effect was lessened by fully one-half. This showed that the high retarding power of sherry was largely due to its volatile constituents. Speaking generally, we may infer that the retarding effects of beef -tea and whey are due to conditions which are easily obviated in the living stomach — either through the rapid absorption of their saline ingredients by the gastric capillaries, or through an increased secretion of gastric acid. But in regard to coffee, tea, the wines, and malt liquors, their retarding agency would appear to be less easily re- movable, and would therefore exercise a more persistent 152 USE OF SOUP influence on gastric digestion. The retarding po^Yer of beef-tea and whey is, hoAvever, worth bearing in mind : it accounts perhaps for the difficulty and discomfort \Yhich some persons notoriously experience in the digestion of soups and milk ; and points to the desirabihty of restricting the amount of these fluids in persons of weak digestion. The practice of taking soup at the beginning of dinner is so ^Yidespread that it must be credited with some beneficial purpose. The object of the practice probably is to awaken the stomach to its work.' Taken on an empty stomach, the salines of the soup would be rapidly absorbed, and in passing through the coats of the stomach they would pro- voke both the glandular and the muscular activity of the organ. Taken in due quantity this would probably be the only effect, but taken in large quantity soup would un- doubtedly display its retarding power on the chemical act of peptic digestion ; it should therefore be partaken of sparingly- by persons of feeble digestion. This rule, I apprehend, accords perfectly with common experience. I shall have occasion to explain further on why beef- tea and milk, notwithstanding their retarding effects on the chemistry of gastric digestion, are nevertheless often suitable aliments for sick persons. I come now to a curious and interesting question. What is the meaning of all this retarding eifect ? Why should the practice be almost universal among civilised races of taking with their meals beverages which retard digestion ? And, considering the copious libations - of tea, coffee, beer, or light wines which health}^ persons associate with their meals, it is quite evident that an ' See also remarks on peptogens, p. 54. - This, however, only applies to persons in health. These agents figure quite differently in the dietetic habits of invalids. They are either altogether omitted from their dietary or used sparingly, or very diluted. IS r.ETARDATIOX AX EVIL? 15S important retardation of gastric digestion is thereby frequently produced. Is this retardation wliolly, or even at all, evil ? Do we healthy people take tea, coffee, wines, or beer with our meals for some collateral good, and in spite of their un- toward retarding effect on the chemistry of digestion, or is there really some good in this retardation itself ? and do we unconsciously use these beverages partly for this very purpose of abating the speed of gastric action '? It requires perhaps some courage to set forth and to defend a proposition apparently so paradoxical as that men take these beverages in part with the unconscious purpose of retarding their digestion. This is, however,^ what I propose doing, and I am countenanced in this speculative course by some words of Darwin. * False facts,' he says, ' are highly injurious to the progress of science, because they often endure long ; but false views, if supported by some evidence, do little harm, because everyone takes a salutary pleasure in proving then- false- ness ; and when this is done one path of error is closed and the true path is often at the same time opened.' ' The view I am about to suggest concerning digestive retarda- tion may be true or false, and must submit to the test of criticism ; but the facts indicated b}' the experiments stand equally fast whether that view prove true or false. It does not really require much ingenuity to show cause why retardation of gastric digestion may not be regarded in the healthy and strong as having a beneficial purpose. We must bear in mind that among civilised races the preparation of food for the table is carried to a high degree. The cereal gi-ains which are employed to make bread are first finely ground and sifted from the bran by ' Descent of Man, chap. xxi. 154 BENEFICIAL PUHPOSE OF RETARDATION the miller ; the flour is then subjected, with the aid of moisture and artificial heat, to a cooking process; the meats and fish we eat are boiled or roasted ; the vegetables we use are carefully deprived of their coarser parts, and then are boiled : all this preliminary preparation and cooking renders our food highly digestible, and easy of attack by the digestive juices. But this is not, I apprehend, the sole object in view. The preliminary preparation and cooking not only renders our food more digestible, but makes it also more capable of being thoroughly exhausted of its nutritive qualities. These two objects are not quite the same. Even as it is, and with all this careful pre- paration, some waste occurs ; and the faeces always con- tain considerable remnants of undigested food. But it is obvious that, if food be rendered too easy of digestion, there arises a risk that the meal will pass too quickly, and wastefully, into the blood, and on through the tissues into the excretory organs, and so out of the body, before it has been made fully and economically available for the sustenance of the slow nutritive processes. Moreover, a sudden irruption into the blood of large quantities of newly digested aliment would tend to disturb the chemical equilibrium of that fluid, and so interfere with the tran- quil performance of its functions. It would also tend to produce hepatic and other congestions, to the general disadvantage and discomfort of the economy. A too rapid digestion and absorption of food may be compared to feeding a fire with straw instead of with slower burn- ing coal. In the former case it would be necessary to feed often and often, and the process would be wasteful of the fuel ; for the short-lived blaze would carry most of the heat up the chimney. To burn fuel economicall}', and to utilise the heat to the utmost, the fire must be damped down, so as to ensure slow as well as complete USES OF RETARDATION 155 combustion. So with human digestion, our highly pre- jjared and highly cooked food requires, in the healthy and vigorous, that the digestive fires should he damped down in order to ensure the economical use of food. In the plan of the dietary of the civilised races, arrived at slowly as the result of an immense experience, we seem therefore to detect two apparently contradictory aims — namely, on the one hand, to render food by pre- paration and cookmg as digestible as possible ; and, on the other hand, to control the rate of digestion by the use of certain accessory articles with food. In reality these objects are not contradictory but co-operative to a beneficial end. For, to express the problem in another way, it may be said that we render food by preparation as capable as possible of being completely exhausted of its nutrient properties ; and, on the other hand, to prevent this nutrient matter from being wastefully hurried through the body Ave make use of agents which abate the speed of digestion.' This combination of appliances renders our plan of feeding more elastic, more adaptable to variety of individual health and constitution, and to variety of external conditions. - During the early periods of life retardation of diges- tion is less required than in the adult state, because the growing organism can more fully utilise, in the work of the building up of the framework, any excess of food ' A slow digestion is quite a different thing from an imperfect diges- tion ; indeed, it has seemed to me that dyspeptics sometimes suffer not from a too slow but from a too hurried digestion. - The practice of the Irish peasant to underboil his potato, so as to leave a ' stone,' as it is said, in the middle of it ; and the practice of the Scotch peasant to undercook his oatmeal — for he makes his ' brose ' not by boiling, but simply by pouring boiling water on the meal -both these practices seem designed to check the speed of digestion, and thereby to enable the meal to ' stay ' the stomach for a longer period. 15G USE OF SALT which is poured into the blood. Accordingly we observe that retarding agents (tea, coffee, and alcoholic beverages) are not used at all, or only used sparingly. In- infants and children. If this view of digestive retardation in the stomach be well founded, the stomach becomes in some degree a storage organ for food — like the crop of birds, the paunch of ruminants, the dilatable cheeks of monkeys, and the l)Ouch of the pelican. Use of Salt. — Why do we use so much salt with our food ? Animals in a state of nature require none. They find (with most rare exceptions) all the salt they require in their natural food ; but cooks are always adding salt in their culinary operations, and we have it nearly alwaj's on our plates. This habit is probably dejDendent on the elaborate preparation and cooking to which Y>e subject our food. In the preparation of flour the wheat is robbed of its outer coating, or bran, which contains the larger part of the saline matters of the grain. Potatoes and green vegetables are boiled in large quantities of water, and are therefore deprived of their saline ingredients. Meat and fish are boiled or roasted, and thereby lose some of their mineral constituents. Salt must therefore be supplied artificially to make up the defect, and to restore to the food so treated that sapidity and salinity of which it has in part been deprived. It has been remarked that tribes and races which subsist chiefly on a vegetable diet have more need of salt than meat-eating communities. EFFECT OF FOOD-ACCESSORIES ON PANCREATIC DIGESTION. The effects of the food-accessories on pancreatic digestion must obviously be less important, and also more FOOD -ACCESSORIES AND PA^'CREATIC DIASTASE 157 difficult to estimate, than in the case of saHvary and peptic digestion. These accessories undergo changes in the stomach ; alcohol and saline matters are largely absorbed in that viscus, so that the beverages containing them are considerably modified by the time they reach the duodenum. And not only are the accessories altered by their sojourn in the stomach, but the articles of food are also profoundly altered. Digestion is already half accom- plished, the solid proteids are partly reduced to a state of solution, and the entire gastric mass is converted into a more or less homogeneous chyme. When this enters the duodenum it encounters the alkaline secretions of the liver and pancreas. A large part of the dissolved matter is reprecipitated b}^ the neutralisation which then occurs, and the whole digesting mixture becomes alkaline in re- action. The digestion of starchy matters, suspended in the stomach, is now actively resumed ; the digestion of the midissolved proteid matters which came through the pylorus, and of the neutralisation precipitate, recom- mences and proceeds to its final termination. Pancreatic digestion appeared in my experiments, except in the cases of milk and farinaceous matters, to be essentially slower than gastric digestion. On meat- and fish-fibre and on egg-albumen pancreatic extract acted with extreme slowness, but on milk the action was extremely rapid — so likewise on bread. The agency of the stomach seems especially necessary for the digestion of all kinds of meat. In considering the effect of food-accessories on pan- creatic digestion we have to distinguish between the diastasic and tryptic action of pancreatic juice. Effect of Food-accessories onPancrearably 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- munit^y 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 179 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 gram 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 equal 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 N 'i 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 cookmg 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 DUODENU.M 181 the vegetative life. The seriously sick, and especially the febrile sick, are often quite unable to take solid food. When the appetite and power of taking food fails, it fails iirst with regard to meat, which is, so to speak, the speciality of the stomach, and next in regard to Ijread. 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 (esophagus. Not perhaps that there is, except in ex- treme cases, an absolute abej'ance of gastric secretion and gastric action, but the}' are reduced to so low an ebb that they count for practicalh' nothing in the work of digestion. In this state of things, when patients are unable to take any solid food, it is quite wonderful to observe, in many cases, that x^ersons who in health were iniable to digest milk, or only to digest it with pain and difficulty, are able during illness to take milk in any (juantity. 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 the 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 especiall}^ amenable to the action of the pancreatic juice. In feeding the sick our first consideration, therefore, should be w^hether 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 possesses 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 masticii- 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 ] 80 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 farmaceous 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 lic^uid 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-TKA 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 oilier Meat-decocti