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ON TUfi DEVELOPMENT OF PHYSIOLOGICAL CHEMISTEY AND ITS SIGNIFICANCE FOR MEDICINE: AN ADDRESS DELIVERED AT THE CELEBRATION OF THE OPENING OF THE NEW INSTITUTE FOR PHYSIO- LOGICAL CHEMISTRY OF THE IMPERIAL UNIVERSITY OF STRASSBURG, FEBRUARY 18, 1884.* By Pbofessoe FELIX IIOPPE-SEYLER. Translated by T. WESLEY MILLS, M. A., M. D., DEMONSTRATOR OF PHYSIOLOGY, MC GILL UNIVERSITY, MONTREAL, CANADA. The mere opening of another large and elegant struc- ture in connection with Strassburg University can in itself have no great interest, as of these there are already so many. This is, however, the first building erected by a German university for the investigation and teaching of the ecience of physiological chemistry. Allow me, then, to * Any views of Professor He ppe-Seyler's on the relations of physio- logical chemistry must attract attention in every quarter of the world. This translation has been undertaken in the hope of bringing the mat- :er of his recent address within reach of a larger number. While the first few pages have been rendered freely and somewhat condensed, a closely literal translation has been given of the remaining ones, owing to the importance, originality, and extreme interest, alike to biologists, chemists, and physicians, of the opinions they contain. The admira- tion and gratitude of the pupil have rendered the task pleasant. — The Translator. ■ '> (►N TlIK l)KVE!X)l'.VIKNT OF give tlie objects for wliicli this l)iiil(liiig has l)een erected, afterward a short sketch of the liistory of i)hysiohjo"ieal chemistry, and finally to indicate what the plan and arranj>-e- nients of the structure itself are. For hundreds of years liave able physicians zealously interested themselves with the chemical investio'ation of the composition of the organs of the luinian body and its life-processes, the knowledge of wliich seemed of great value in determining the causes, course, and treatment of disease. J'revious to the discov- ery of oxygen by Priestley and Scheele, and to the time when the penetrating Lavoisier, with experiments of pre- viously unknown accuracy, gave clicmistry a surer founda- tion, very little came out of this investigation. Especially such discoveries as that of the composition of water, of carbon dioxide, and of other important compounds of a simple kind, are to be noted in this connection. It would be wholly wrong to suppose that the brilliant discoveries of the last quarter of the eighteenth century were the results of this period ah>ne ; in fact, the way had been already pre- pared, and other important discoveries made. Among oth- ers, the numerous and valuable discoveries of Scheele, the accurate measurings and weighings of Lavoisier, and his proposed antiphlogistic theory, gave alike an invaluable foundation for the science of chemistry, and also a point of observation for its organization. Already these beginnings of sci entitle chemistry had shown themselves fruitful for physiology. The investiga- tions of Scheele, Lavoisier, and Van Ingen-llousz on the respiration of animals, sprouting seeds, green plants, etc., gave physiology a deep insight into the chemical relations of organisms to the surrounding atmosphere. Scientitic chemistry and physiological chemistry have here alike a common origin. But, though by Scheele and many others, especially French chemists, many important substances of I'lIYSIOLOGICAL CHEMISTRY. 3 the animal and plant world wore brono-ht to liii'lit, yet or- ganic chemistry, and with it physiology, remained far in the rear of the advancing knowledge of inorganic snbstances. The limitation of the attention to the inorganic part of chemistry was authorized, inasmuch as it was to furnish that knowledge which for all time would remain a certain basis. Tn the second decade of our centurv chemistry aijain began to grow and to be the food of physiology. Organic chemistry remained as vet almost identical with animal and plant chemistry. The labors of Chevceul on the fats, of Prout, Tiedemann, and Gmelin on digestion, of Prevost and Dumas on the composition of the blood and the forma- tion of urea, which belong to this ])eriod, wonderfully en- riched our knowledge of life-processes. In 1828 Wiihler accomplished the synthetic formation of urea from cyanic acid, previously discovered by him, and ammonia. For the first time, here was a si(hstance, ivhich had been previously known only as a normal j^roduct of the processes of life, formed out of its inorganic elements. Soon after, Berzelius and Liebig greatly increas.'d the existinor knowled<''e of oro-anic substances. A theoretical war of thirty years' duration sprang up, but it proved fruit- ful in investigation, especially of the organic realm. ()r- ganic synthesis, together with the explanation of theoretical points ; the rearrangement of groups on physical and chemi- cal grounds; the mechanical theory of gases and vapors, which first gave a foundation for the estimation of the rela- tive weiii'ht of molecules and the number of tlie atoms con- tainod therein ; the relation of atoms in molecules ; and the theory of organic cliemistry in its essentials, founded on the atfinities of the carbon atoms — offering many points diffi- cult of solution and still controverted — all was the fruit of this period. It would be difficult to enumerate all the chemists to ON THE DEVELOrMENT OF whom this profj^ress was due, but the names of Laurent and Kekule are the foremost. It could justly be said, as Lothar Meyer said in 1864, that already for a long period the controversy over the systematic arrangement of chemis- try had ended. In consequence of this controversy, how- ever, physiological chemistry had in general been over- looked, though Liebig was not one of those who neglected it. From 1830 till old age, though engaged in almost every controversy of the time, he labored to advance it. lie had himself worked out excellent methods of determina- tion, and had made investigations into the constitution of flesh ; and his keen insight gave to his pupils correct meth- ods of research for the accomplishment of decided results. The pregnant ideas of his writings prompted numerous valu- able researches. His investigations of the relation of food to life-processes and to muscle-work are especially noteworthy. They have directly or indirectly led to researches of wide application to agriculture, medicine, and hygiene, and espe- cially in the last ten years. Though the hypothesis relating to the formation of fat within the organs from albuminous matters has proved erroneous, the results of the work of this period in their practical worth remain uncontroverted. Important advances were made in other directions. Fer- ments acting on diastase and starch were discovered in the saliva, and afterward in the pancreatic secretion. Schwarm extracted pepsin from the mucous membrane of the dead stomach with dilute hydrochloric acid ; and the action of this artificial digestive fluid on albumin was ascertained. C. Bernard subsequently discovered the emulsifying action of the pancreatic juice on fat, and the remarkable formation and changes of carbohydrates in the animal body, especially in the live;, as dependent on the method of feeding ; and various other influences were recognized. The composition and conditions of secretion of the various digestive fluids PHYSIOLOGICAL CHEMISTRY. in their main outlines were ascertained. With new and ex- cellent methods and apparatus, rnd by very numerous and varied researches, was the interchange of gases in the respi- ration of animals of different classes, under varying condi- tions of nutrition and many other circumstances, investi- gated by Regnault and Reiset. New substances were found in the organs of men and animals in health and disease. With the noted researches of Liebig on flesh may be ranked the labors of Strecker on the biliary acids ; of Strecker and Scherer on xanthin, hypo- xanthin, and guanin ; of Frerichs and Stiideler on leucin, tyrosin, etc. The investigation or the composition of the blood in health and disease was at this period the subject of numer- ous researches in Germatiy and France. C. Schmidt's re- search "On the Characteristics of Epidemic Cholera" de- serves special mention. Nor have these researches remained without fruit, though the over-zealous opposition of the Prague-Vienna school against bloodletting had an injurious influence, which has not yet been wholly removed. Of enci'mous value for physiology was the discovery of Magnus that from the blood, when subjected to a good vacuum, together with carbon dioxide and a little nitrogen, oxygen also was given off, and, in fact, more from arterial than from venous blood. Few then anticipated, with Jo- hannes Miiller, the enormous consequences of Magnus's discovery, and, in fact, able chemists were at once ready to controvert it. The researches of Schonbein on the peculiarities of oxygen in different conditions ; the formation of ozone, hy- drogen superoxide, etc., did not receive generally the atten- tion they deserved. Liebig fully understood their value. To the casual observer, looking from a distance, nothing very striking in the development of physiological chemistry 6 ON THE DEVELOPiMENT OF may seem to ha\ ^ occurred in the last twenty or twenty-five years. It has, however, been i.i good fortune. Tlie general advance of chemistry, especially since 1850, and in particu- lar the improved methods of gas analysis due to Bunsen — the improvement in apparatus, spectrum analysis, etc. — have all contributed to the advance of physiological chemistry. The publication in the second half of the fifth decade of this century of Virchow's " Cellular Pathology," to- gether with the researches of Max Schultze on the structure of animal cells, which soon followed, though of no direct hearing on physiological chemistry, yet afforded new points of view. The researches of Pasteur and his pupils and op- ponents, from the beginninjj of the sixth decade onward, have had a notable influence on physiological chemistry. These researches, though as yet abounding in obscuri- ties and uncertainties, have still given results of the highest value for the technique and for medicine. The treatment of wounds to the exclusion of infection, the relation of sepsis to operative surgery, and the discovery of micro-organisms of definite character in the blood in certain diseases, are of a value well recognized. There is no limited region of natural science which at the present time attracts zealous investigators in so great numbers as the microscopic determination of the conditions of life and propagation of these micro-organisms. Botanists, chemists, physiologists, normal and pathological anatomists, surgeons, pathologists, and hygienists contend in the race in this realm of investiga- tion. Difficult is it to separate the chaff from the wheat. Owing to the extreme minuteness of these organisms, their anatomical investigation and certain separation are very diffi- cult. But the difficulty is greatly increased, owing to the power many of them possess, according to the conditions under which they are found, of developing into entirely r '9 PHYSIOLOGICAL CHEMISTUY. 7 different forms, and at the same time oocasioninjjj entirely different clieniical processes, accordinfj as the elieniical and physical conditions siirroundinij thein vary. Physiological chemistry partakes of a far p:rcater share of difficulty than the microscopic investigation, which, npart from the method, now much used, of impregnation with coloring matters (which also leads to manifold deception), without simultaneous chemical investigation with sutti- cieut certainty, can not make great advances. This investi- gation, as I shall soon liave occasion to illustrate, brings greiit gain to physiology itself. I must abstain from giving you a complete outline of the advances physiological chemistry has made with refer- ence to the composition of the organs and iiuids of the human body, and the processes taking place in them, ef- fected in ^he last two decades. Allow me to sketch the manner in which, in the most recent period, the science has advanced. With great ' -encc, and not without success, the pro- cesses of the digestion of all the most important constituents of fo-^id in the alimentary canal, with the sole exception of the part played by the bile (which, indeed, does not seem essential, and which is wanting in invertebrates), have been studied, and it has been ascertained that these processes in all their phases may be carried on outside the organism, and the products of their action isolated and investigated. Medicine and hygiene in this case, as well as physiology, have become possessed of treasures of knowledge the practical value of v'hich already abundantly appears, but /ar short 0/ the extent to which it must appear in the diagnosis and treatment of dis- eases of the alimentary tract especially. Our kiiowledge of the composition of the blood and its changes under the influence of certain physiological pro- cesses has been essentially advanced in the line referred to • 8 ON THE DEVELOPMENT OF and the chemical functions of the red corpuscles in respira- tion, especially the influence of the coloring matter in refei- ence to the absorption of oxygen from the air in the lungs, its transportation to the cells of the organs, and their proxi- mate causes, are so well known that, in a given case, it is merely a question of reckoning to determine the total quan- tity of oxygen appropriated in a given period by definite extents of surface, etc. With reference to the life-processes within organs, such as muscles and glands, the passage of the free, indifferent oxygen of the air into these organs has been demonstrated with certainty. The chemical structure of numerous sub- stances already known which arise in the organism has been determined, and their formation by synthesis accomplished ; others have been discovered and to some extent artificially formed, and many general laws in regard to their formation and behavior with reference to the peculiarities of their chemical structure discovered, and, above all, the interesting formation and processes of change of the aromatic bodies in their characteristic combinations with sulphuric acid, gly- cocoll, glycuronic acid, and cystin. By the last-mentioned investigation have the methods and results of the new theoretical chemistry become of great value for physiology, while interesting new material for chemistry has appeared. Even with more and more clearness during the course of these investigations has the fact become recognized that the substances which iorm the organs, out of which they build themselves up and are regenerated, belong to a class which may be included under the term onhydrides, and which have the common property that, under treatment with alkalies and acids, many of them also, through fer- ments, can be changed or split up with the addition of the elements of water, thereby, as it is said, becoming hydrates. PHYSIOLOGICAL CHEMISTRY. 9 These anhydrides show mostly in striking chemical af- finities, swell in water or dissolve generally with difficulty in it ; they withstand the action of the atmospheric oxygen, and, so far as it can yet be made out, have very large molecules. ^iv» Animals and plants are, as regards these substances in general, not different, though certain substances, as albu- minous matters, fats, and inosit, appear in both ; others, as cellulose, starch, cane-sugar, tannic acid, and malic acid, only in plants ; others, again, as glycogen, less in plants than in animals ; finally, certain substances, as gelatin, urea, and creatin, are formed only in animals. The line of demarkation which it was once thought could be drawn in regard to chemical * structure and life- processes between pV.nts and animals has been, in conse- quence of recent investigations, more and more obliterated. The discovery of inosit, glycogen, and allantoin in plants; the establishment of closer relations between the caffeine and theobromine of plants and the jranthin and guanin of animals, especially the presence, without excep- tion, of globulin substance, lecithin, cholesterin, nuclein, and potassium in all cells formed under normal or pathological conditions so far as yet investigated, vvhethc" \i\ man or in the highest or lowest animals and plants — all these consid- erations must bring us to the conviction that definite funda- mental chemical formations and changes are common to all living beings, and that the life-processes common to them all, ^especially their growth through formation of their own sub- stance and their propagation without limit under conditions peculiar to them, must be formed in the presence of those chemical constituents ; that also in the further processes of change, often appearing so different in the different classes, orders, and families of animals and plants, many processes can take place according to a conformable fundamental type; and that finally in the life-processes of man these parallels 10 ON THE DEVELOPMENT OF are again foundj whose simplest manifestation we, perhaps, follow with the least difficulty in the lowest organisms. We are thus brought to a definite unity in the original chemical structure and processes of living existence, a point which the microscopico-anatomical investigation of the mor- phological development has already reached. The chemical characters are, however, much more within our ken than the microscopic, since the latter take cognizance of the simplest forms of existence, as plastic, variable, or irregularly formed little masses. When the chemical components of "the cells or the pro- toplasm, or any formed organ of animals or plants, is spoken of, it is, of course, to be observed that we yet have no right to speak of the constituents of living cells, but only of the products of their chemical decomposition. A series of ob- servations of different kinds points in the direction of the conclusion that the change which simple protoplasm, as well as complicated organs, undergoes on the entrance into the death state, arises from the chemical addition of water. If the water essential for all life-processes be removed, life is indeed suspended, but death does not, in consequence of this alone, follow. Plants, insects, amphibians (e. g., tritons), and frogs can for a long period remain hard frozen ; their life is thereby fully suspended ; after being slowly thawed out, the organs take on again all their life-functions. The noses, ears, hands, and feet of men act similarly when frozen by a degree of cold not too intense. But such frozen or- gans die at once if thawed out too quickly, inasmuch as the melting ice-crystals injure the cells in juxtaposition to them. Carefully dried seeds of plants — e. g., peas — can be kept heated for hours at 100° C. without their vitality disappear- ing. They sprout, after cooling, when placed in water or moist earth just as quickly as undried and unheated peas, and develop to perfectly healthy plants. If the seeds are not PHYSIOLOGICAL CHEMISTRY. H carefully and fully dried before the heating, they perish un- ler 60 °C. If now, from these and many other experiences, it is to be concluded that the death of protoplasm arises from assumption of water, then must it be assumed that the forms of living protOj^laoiii conduct themselves in respect to the sub- stances found in the dead forms of the same as anhydrides do to their hydrides or decomposition products^ unless some fur- ther insight into this matter is forthcoming. In the most recent times different hypotheses bearing on the chemical structure and peculiarities of living proto- plasms have been published ; they do not, however, taken together, agree with the known facts. Their mechanical and chemical behavior, so far as they have as yet been in- vestigated, force us to the supposition that one and the same protoplasm^ according to the influences which from without are brought to bear upon it, may form [darstellen^ two en- tirely different bodies — different in chemical structure and in action on other organic substances which come into rela- tion with the same, and also in attraction for water. The protoplasms further effect chemical changes through which, on the one hand, fermentative decompositions, and, on the other, anhydrides, are formed. Both processes stand in such decided opposition to each other that they can not proceed at the same time from one and the same substance. In the plants and animals of higher organization we can ascribe to one cell the one function, and to another the other. In the lowest unicellular organisms this is not possi- ble : in these, both processes must go on in the same proto- plasm; they form albuminous substances, fats, glycogen, or cellulose, and such like, and also break up these sub- stances. It would appear that it is observation of just these lowest, simplest forms of life that enables us to form the clearest conceptions. • 12 ON THE DEVELOPMENT OF Beer yeast-cells in a saccharine fluid change grape-sugar into alcohol and carbon dioxide in the complete absence of free oxygen, and can continue these processes for months without either growing or multiplying themselves, when, indeed, the food-supply is abundantly present and the tem- perature favorable. According to certain observers, the yeast-cells do grow and multiply, but there is no doubt that it must he admitted that growth and multiplication are in- significant. A portion of the same yeact-cells, brought into a sac- charine fluid in the presence of oxygen, forms little or no alcohol, separates some carbon dioxide, with absorption of oxygen, grows, and, moreover, multiplies abundantly under similar conditions of temperature and nourishment. The bacteria "f decomposition \Fdulnisshacterien\^ brought into watery xtracts of flesh in the presence of oxy- gen, decompose albuii. lous matters, creatin, sugar, and lac- tic acid into leucin, hydroparacumarsic acid, indol, skatol, ammonia, carbon dioxide, hydrogen, and sulphureted hy- drogen. They are motionless and do not multiply ; however, the latter is denied by some observers. The same bacteria, under precisely similar conditions but with oxygen present, form no hydrogen, no organic decomposition products ; only carbon dioxide, water, and ammonia ; they multiply abundantly and are in lively motion. The formation of anhydrides, to be recognized in the growth of organisms and their multiplication, happens either only, in the main, in the presence of oxygen, or, at least, much more abundantly than without it. However, oxygen can neither of itself form anhydrides nor be the sole cause of the movements of the bacteria. Though oxygen is of itself powerless to act as an oxi t PHYSIOLOGICAL CHEMISTRY. ^ 13 dizer in such cases, yet, in the presence of nascent hydro- gen, it does possess such power ; and this latter is always the case in putrefactive processes. There is an opinion, as yet very widely diffused, that these lower organisms comport themselves throughout otherwise than the higher plants and animals. Differences not a few are to be ob- served, but, just as these lower organisms contain the same substances in their protoplasm as the highest (globulin substance, lecithin, cholesterin, nuclein, and potassium) so do they in their chemical processes show a remarkable agree- ment in the fundamental types. If we suppose (and there is no fact opposing it) that also in the highest organisms indifferent oxygen in the same manner as in the lowest suc- ceeds in oxidizing, so might the general protoplasmic phe- nomena in plants and animals be thus fornmlated : Distinction must he made between (1) the protoplasm in- capable of stimulation^ as it continues to be in the absence of oxygen, acting with a ferment-like decomposing power on albuminous matters and many other substances, and (2) the protoplasm capable of stimulation, of less density than the first, of greater capacity for attracting water and not inciting fermentation. In the presence of water the second is changed into the first, through addition of the elements of loater in chemical combination, in consequence of the weaker or strong- er shocks of the so-called stimulation, through different modes of motion — electrical, thermal, chemical, or mechanical mo- tion. The first protoplasm is again changed into the second BY" THE PRESENCE OF OXYGEN, sincc, by the decomposing ac- tion of the first protoplasm, oxygen is rendered active, and through the active oxygen the second anhydrated protoplasm arises. If, under such circumstances, substances present them- selves which can be easily anhydrated, they pass over into anhydrides. The anhydride formation happens, accordingly, through the reformation of anhydride protoplasm in conse- 14 ON THE DEVELOPMENT OF If It quence of the influence of active oxygen on the protoplasm with ferment-like action. It would lead too far into details to demonstrate the agreement of these hypotheses with all the results of ob- servation on them in the entire realm of the orgaiJc world which they include. Let it suffice to choose from very dif- ferent classes of organisms individual representatives, and demonstrate their agreement. What I have already said of beer yeast-cells and bac- teria is in unison with the hypotheses, so I will not re- peat. The muscles of men and vertebrates, through stimula- tion, change in density, break up glycogen, and form lactic acid ; the latter is, however, in the presence of oxygen, oxi- dized ; carbon dioxide and water are formed in the propor- tion the carbohydrates furnish, and in correspondence with the strength and duration of the stimulation. The change into the stimulated condition follows also in the absence of oxygen. The removal of oxygen calls into existence last- ing tetanus (poisoning by hydrocyanic acid, rapid death by bleeding, hanging, etc.). On the other hand, under normal presence of oxygen, in order to maintain a stimulated con- dition in some measure lasting, continuous repetition of the stimulus is necessary, since the active oxygen at once forms the anhydrated protoplasm. In glands, in consequence of stimulation, a secretion of a watery fluid follows, which can have only chemical, not physical, causes, in that it is independent of the blood- pressure, and the fluid secreted does not contain those salts which, in all the transudations, pass over from the blood in definite proportions. With this secretion abundant formation of carbon di- oxide and of warmth takes place at the same time. Very clearly were these conditions observed in the secretions of i PHYSIOLOGICAL CHEMISTRY. 15 the insect-eating plants, as so admirably described by Charles Darwin. Mechanical phenomena of motion \^Bewegungserschei- nungen] in plants, especially the remarkable movements of the petioles of Mimosa pudica, are of the same nature as the secretion of water from protoplasm, in consequence of the stimulation already mentioned. That the vacuole for- mation in numerous protoplasms, also in the Amoeba itself, arises from a similar secretion of watery solution from the protoplasm in consequence of stimulation, is highly proba- ble. The mechanical movements of Amoeba, etc., toward A the point of stimulation is explicable only through these hypotheses. Numerous and very different in kind are the observa- tions on higher, especially warm-blooded animals, which have afforded the demonstration that with the prevention of the access of oxygen to the organs the stimulative ca- pacity sinks, while, in consequence of this hindrance, the extent of the decomposition of tissue and of chemical in- terchange rises. When a stream of blood containing oxygen is conducted through the living kidneys, the union of glycocoll and ben- zoic acid which takes place has been shown to be an anhy- drating process. The opposite process, however — viz. : the splitting up of hippuric acid and similar compounds under addition of water in the living organs — is observed. Presumably the last process takes place also without the presence of oxygen, and can be effected in the proto- plasm incapable of stimulation. Let these Intimations suffice to indicate how in one realm of physiological chemistry — and that the largest — results unite to induce further investigation of problems becoming ever more comprehensive ; and how, further^ all living beings, of form and life-phenomena the most widely 16 ON THE DEVELOPMENT OP different, appear to owe their fundamental structure to an original chemical orffanization, u)ith properties common to them all. In the preface to his " Animal Chemistry," Liebig, in 1842, said: "The new chemistry has, with all its discover- ies, furnished only insignificant service to physiology and pathology, and no one can deceive himself as to the causes of this failure who takes into consideration that all the methods introduced into the realm of inorganic chemistry, the knowledge of the behavior of the simple bodies, and the compounds that might be made in the laboratory, could be brought into no sort of relation with the living animal body and the character of its components." Since that time this has been changed ; but it would be vain to reckon on a further advance in physiology from the side of the chemist when the questions of biology lie so very far away from him — questions whose answers bring for the theoretical chemist but very little profit. While theoretical chemistry and chemical technique are closely linked with one another — while the one derives great advantage from the other — the relation to physiology and to the whole of medicine is entirely different. But even the technique has found it necessary to take the solution of certain problems in hand, with what good or ill luck might follow. For the chemical manufacture of dye-stuffs, for the sugar industry, for beer and brandy manufacture, there now exist special, and in part excellently directed, laboratories, in which for special objects these branches are practiced and partially taught. In all civilized countries there are now laboratories for the objects of agriculture. Physiological and pathological chemical laboratories have also been estab- lished, but, with very few exceptions, they have restricted means and no independence. The importance of chemistry for the development of physiology and pathology did not t rilYSIOLOGICAL CHEMISTRY. 17 escape Virchow's sharp ken. He establislied in 1856 the first better-endowed and tolerably independent laboratory in his new pathologicalinstitute in Berlin. In Munich, through Liebig's influence, a series of diligent researches was made on food and nutrition [^Erndhrung und Stojfwechsel]. In Tubingen the laboratory for applied chemistry was restricted almost exclusively to the subject of medical chcmi<=try. Sev- eral of the ablest physiologists, such as Briicke and Pfliiger, applied themselves with lively interest to the solution of the problems of physiological chemistry, and encouraged and advanced this science. In the Physiological Institute of the Berlin University, opened a few years ago, there is a suitable laboratory for physiological chemistry, which has already done good ser- vice alike to teaching and to science. Though, after the example of Frerichs, several clinicists fostered physiological and pathological chemical investiga- tion, yet in most German universities the chemistry of physi- ology has not received the consideration and advancement it deserves. It can be said in praise of the physicians of all times, and not in small n ambers of those of the last ten years, that they, with much attention for the objects of the diagnosis and treatment of disease, sought to apply what science and the technique supplied. Astonishing nmst it be then, that the great majority of the physicians in the most recent times felt coldly enough over the advance of chem- istry in general — much more so than was the case at an ear- lier period, and that within my recollection — while a small minority kept their eyes fixed on it with great interest. One or another will perhaps say that these advances may be of really great significance for the science of medi- cine, but of little applicability to the practice of medicine. With regard to numerous results of the anatomical and 18 ON THE DEVELOPMENT OF physico-physiological investigations, and such as have been spoken of above by myself, bearing on tlie cliemical behavior of living cells in general, it is not to be expected that they should have a direct bearing on practice. But quite differ- ent is it with very many results of the most recent investi- gations of physiological chemistry. So can T not under- stand how at the present day a physician can recognize, follow in their course, and suitably treat, diseases of the stomach and alimentary canal, of the blood formation and decomposition, of the liver, kidneys, and urinary passages, and the different forms of poisoning — how he can suitably regulate the diet in these and in constitutional diseases — without the knowledge of the methods of physiological chemistry and of its decisions on questions offering them- selves for solution, and without practical training in their application. Is it possible we must conclude that there is an over- burdening of the medical student while following out the curriculum, and that this is the cause of the insufficient at- tention in general paid to the chemical problems of medi- cine ? I am far from denying an overburdening ; it exists, in fact, in high degree, and the lengthening of the term of study (one semester) now in force does not suffice to obvi- ate it. This overburdening, however, is not the only cause, nor is it distributed uniformly over the different depart- ments of study. The principal cause of this unsym metrical distribution lies in the form which the medical curriculum has taken in the last ten years. The really valuable results in the great field of normal and pathological investigation which have been achieved through the improved microscopes of the last four decades ; the triumphant victory won by the microscope for pathology in the direction of pathological anatomy over the % PHYSIOLOGICAL OHEMISTUV I!) i earlier prevailinj^ but iiisuflieiently groinided philosophical physiolojxy ; the insight into the significance of the lowest fungi, also achieved through the microscope — have in medi- cine lent to the anatomical method of demonstration and investigation undue weight, which, at first useful in explana- tion of obscuriti'^s, becanie gradually more and more press- ing, even crushing, on the reuuiining branches of the medi- cal curriculum. The skeptical fanaticism of the injudicious champions of the Vienna school, which sought to rob the physician of all belief in tradition, has also in its after-working exerted a paralyzing influence on chemical and therapeutical efforts. Amid this sea of doubts the anatomical facts appeared to be the only thing that remained firm. On this was joined the transformed but very meager pathology. For inde- pendent clinicists this state of things could not suffice ; the sterility ensuing through this sovereignty of morphology could not remain hidden from the penetrating. Manychmg with lively interest to the means which the researches on nutrition \^S tojf'wechsel] furnished for the solution of clini- cal problems. But insight into the hidden springs and pro- cesses of life remained veiled. That they are chemical pro- cesses we know right well, but their solution requires the most painstaking work. We trust well to the certain funda- mentals of chemical investigation ; but only slowly, and con- tending against the most diverse hindrances, can we pene- trate into the fine machinery which in healthy and in diseased beings determines life \das Leben ausmacht]. On other than chemical paths do we not advance. Who will deny that ? We should not object that pathological investigation and not the physician's practice has to do with this. Every observing physician must admit that in this relation there exists no difference. 'F 20 TIIK I)KVKF,(»PMKNT ()V PHYSIOLOGICAL CIIKMISTKV. The conmiLTcial pliysicijin [reat value which in recent ti.nes, certainly rightly, is attributed to hygiene and the very numerous necessary relations which this reahn of investigation and teaching have in common with physiologi- cal chemistry, cause it the more fitly to appear that, for its practical study, space and arrangement should be made in this institute, as in great part the subjects not Avholly mi- croscopic or technical belong also to physiologi'^al chem- istry, and so can never be better managed than in an insti- tute set apart for the latter science. To avoid collision in instruction, separate rooms for work in physiological chem- istry and in hygiene are provided. * W. Leube, " On the Sij;nificance of Chemistry in Medicine," Ber- lin, 1884. \ \ \ The lew York Medical Journal, A WEEKLY REVIEW OF MEDICINE. PoBLIsnED BY 0. Appleton & Co. EOITKP BT Frank P. Foster, M.D. The ^bw York MfenroAL JotniiTAi., now in tho twentieth ycnr of it* publication, is published every Saturday, each number containing twcntv- eim private practice. EDITORIAL ARTICLES aro numerous and carefully written, and we am able to give timely consideration to passing events. MINOR PARAGRAPHS.— Under this beading are given short comments and notes on passing events. NEWS ITEMS contain the latest news of interest to the profession. OBITUARY' NOTKS announce the death's which occur in the ranks of the profes- sion, with a brief history of each individual when practicable. SOCIETY PROCEEDINGS are given promptly, and tboso of a great number of societies figure. At the samo time wo select for publication only such as we think proflrable to our readers. 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