Popular Science Monthly/Volume 53/August 1898/The Life and Work of Felix Hoppe-Seyler
IN the summer of 1895 the world lost two men, each of whom, in his own way and in his own country, had exerted an unusual influence on the development of science. They were born and they died within a few months of each other. Each was endowed by Nature with the gift of seeing the relationship of apparently unrelated phenomena; each passed through a medical training; each devoted time, much against his will, to dissection and anatomy; each was a fighter for what he believed true; each was gifted with a winning personality that attracted friends from all sides; each was a great teacher, having a ready sympathy for young students, and each was remarkable for the breadth of his knowledge and the keenness of his insight. One was Thomas H. Huxley, an Englishman, the other Felix Hoppe-Seyler, a German. LIFE AND WORK OF FELIX HOPPE-SEYLER. 543
Very similar in natural gifts though Huxley and Hoppe-Seyler were, the different environments under which they were placed de- termined their development in radically different paths. Huxley, though possessing a strong natural tendency toward physiology, was forced to become an anatomist, and from a very early date his great controversial powers were called into such requisition that his name became almost a household word among the English peoples. Hoppe- Seyler, on the other hand, while still very young, was given a decided impetus toward the study of the chemistry of organism, and, as a pioneer in a new science, was little known outside the immediate circle of his personal friends and scientific colaborers.
Felix Hoppe-Seyler deserves to be remembered by mankind not only for the valuable contributions he made to our knowledge of the chemical processes of life, not only for the impetus he gave to the development of a new science, physiological chemistry, but also for the influence he exerted on the minds of his pupils and colaborers. Great investigator though he was, and lasting though his influence on the development of biochemistry will be, he probably served mankind best in his capacity as a teacher. As there has not appeared in any English or American journal a just account of the value of the life and work of this illustrious man, a brief sketch of one to whom the world in the future will probably consider itself indebted, not less indeed than to Jenner, Pasteur, Koch, and Lister, may be of interest, and some recognition, insufficient though it be, of his lifelong services.
Ernst Eelix Imisiandel Hoppe, better known as Eelix Hoppe- Seyler, was born in Ereiburg in Thuringen, on the 26th of December, 1825, and died suddenly of heart disease at his summer home on Lake Constance on the 10th of August, 1895. He was the tenth child of the Pastor Ernst Hoppe and Frederike Nitzsch. He came of a long line of school teachers and ministers. His mother died when he was six years old, and his father three years later. The lad re- ceived a temporary home with his brother-in-law. Dr. Seyler, but soon entered the orphan asylum at Halle, where he attended the gymnasium.
His stay in Halle exerted a great influence on his later life, for the regime at the institution which was his home was of Spartan- like simplicity and rigidity. He came under the influence here, also, of the old apothecary of the institution, who took great delight in introducing young Hoppe to the mysteries of chemistry, in which he soon acquired considerable proficiency. He was dismissed from the gymnasium as a diligent student in 1846, with a preference for the natural sciences and mathematics, and in the autumn of the same year was matriculated in the medical faculty of the University
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of Halle. Here he passed mucli of tlie time of his year's stay in the pharmaceutical laboratory of Sternberg.
One of the inheritances he received from his boyhood and which he carried with him to the end was a great liking for an active out- door life. In the summer vacations he would frequently take long pedestrian tours, and in the course of one of these he met the cele- brated Weber brothers, Ernst and Eduard, of Leipsic, with whom there thus began a long friendship. Influenced by his new friends, Hoppe, the next year, betook himself to Leipsic and entered the classes of W. Weber in physics, E. H. Weber in physiology and anatomy, and of Eduard Weber in nerve and muscular physiology. He attended, also, Erdmann's lectures in organic chemistry and Lehmann's in physiological chemistry and pharmacology. In the spring of 1850 he went to Berlin, and the same year took his doc- torate, with a thesis entitled On the Structure of Cartilage and on Chondrin. This thesis and Hoppe-Seyler's subsequent work in the same direction, which confirmed previously expressed views of Vir- chow, attracted the favorable notice of the great pathologist, who thereafter became to young Hoppe a helpful friend.
He was approved as practicing physician in 1851, spent some time in Prague in the study of obstetrics, returned to Berlin, and entered practice. He found little liking for this, and in 1854 was appointed prosector in anatomy in Greifswald, where he became later Privatdocent. His personal relations here not proving to be of the pleasantest, and the outlook for the future being anything but promising, Hoppe resolved to go to America, and wrote Virchow to that effect. The latter, however, induced him to remain, promised him a position in his new laboratory, and soon had him appointed assistant. Here his time at first was so taken up by students that he was only able to carry on his chemical studies on Sundays. Again Virchow came to the rescue, had a second assistant appointed, and put Hoppe in charge of a laboratory of pathological chemistry. He was appointed extraordinary professor in 1860, and his laboratory quickly became the center of physiological chemistry in the world. To it came Klihne, Alexander Schmidt, v. Recklinghausen, Leyden, Wilson Fox, Botkin, and many others.
In 1861 he was called to the chair of applied chemistry at Tubingen, where he was shortly made full professor. His laboratory here was of the most primitive description. It was located in the former kitchen of the old castle on top of the hill. The big chimney place, and the spits, were converted into appliances for chemical research. Here began a most fruitful period of Hoppe-Seyler's career; from this laboratory appeared much of his best work. Among the students who gathered about Hoppe-Seyler here were Miescher,
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Baumann, Froriep, Gaelitgens, Parke, Salkowski, Zalesky, Lobiscli, Tolmatsclieff, Polz, Diakonow, Liebreicli, Lubavin, Manassien. Here lie remained for ten years, until in 18Y2 lie went to Stras- burg to take tlie cliair of physiological cbemistry, the first and only professorship of its kind in Germany. In Strasburg he spent the remainder of his life, and here, as in Tubingen, many students came to him, among whom were Kossel, Hoffmeister, Neumeister, Frederiq, v. Jaksch, Ledderhose, v. Mering, Mauthner, v. Udransky, Popoff, Rajewsky, Sokoloff, Howath, Ilerter, and Giacosa.
In 1864 Hoppe was formally adopted by Dr. Seyler, and there- after took the name of Hoppe-Seyler. In 1858 he married Agnes Franziska Maria Borstein, by whom he had one son, Georg Hoppe- Seyler, now professor of medicine in Kiel. In appearance Hoppe- Seyler was an erect, vigorous, active man, above medium height. Although at the time of his death nearly seventy years of age, his hair was not yet gray, his step was still youthful and elastic, and he appeared yet to have many years of life before him. He was eminently what the Germans call " liebenswurdig " — kindly and sympathetic, especially toward his pupils, whom he made his friends. With all his kindliness, however, Hoppe-Seyler, like Huxley, had little patience with half truths or errors, and he possessed a sharp pen, v/hich, in truly German fashion, told the whole truth about one unfortunate enough to incur his displeasure.
The scientific work of Hoppe-Seyler extended over forty years. His contributions to science are embraced in some hundred and forty-six separate papers. He was the author of a handbook of physiological and pathological chemical analysis, which has had six editions, and is still the best book of its kind extant. In the years 1877 to 1881 he published his celebrated text-book of physiological chemistry, which still remains as a monument to his industry, to the wide scope of his knowledge, his keenness of perception, and his power of correlating facts. Though many of the conclusions con- tained in the work have been modified by more recent investigation, the book stands unique among similar productions as the most ex- haustive treatise on the chemistry and chemical changes of the animal and plant kingdom ever attempted.
The range of subjects in which Hoppe-Seyler published observa- tions, outside his biochemical work, is remarkable, and includes botany, mineralogy, geology, chemistry, and physical diagnosis. He detected the presence of the newly discovered element, in- dium, in wolframite, and he devised a spectroscopic test for manganese, which is one of the most delicate known, and is still called Hoppe-Seyler's manganese test. Throughout his life he took a keen interest in mineralogy and geology. In 1865 he
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made tlie not unimportant discovery that gypsum, heated with sodium chloride to 130° C, was converted into the crystalline anhy- dride, and in 18T5 he published a series of researches on the forma- tion of the dolomite masses of Germany, which did much to elucidate the problem, indicating, as they did, the formation .of dolomite by the action of sea water on calcium carbonate. His works on percussion and the pulse were valuable contributions to physical diagnosis.
In biochemistry his work is remarkable not only for his dis- coveries, but also for the great number of ingenious methods of re- search devised by him. Our methods of examining pathological transudations, pus, the blood, are derived in large part from him. He was quick to jDerceive the value of the spectroscope in the study of the chemical changes in the pigments of blood, urine, bile, exu- dations, and elsewhere in the animal and plant kingdom, and he applied the method with particular success to the study of the blood pigment and chlorophyll. He seized upon the Soleil-Ventzke im- proved polariscope as a valuable means of estimating the albumin and sugar contents of urine, blood serum, transudations, and milk. He studied the circumpolarizing action of gelatin and the - sub- stances contained in gall, together with their decomposition prod- ucts. By means of these methods he rendered great service to physiological chemistry.
In the chemistry of the organism he broke ground in a great variety of places, but left the further development of nearly all the paths thus indicated to his students. His earliest work was done upon the chemistry of cartilage and the relation of cartilage to bone, work which bore closely on Kolliker's discoveries on the genesis of bone, and showed the essential similarity, in a chemical way, of the great group of connective tissues, first classified by Yirchow.
He made extended analyses of the enamel of teeth, showing its essential identity with the rock apatite, and that the enamel of the teeth of fossil and living animals was identical in chemical com- position. During his stay in Berlin he published a number of treatises on the composition of transudates, and later compared the effect on the composition of transudations of frequent drawings off of the fluid. He compared the transudations derived from various parts of the body, and endeavored to refer the differences in chemical composition found to differences in the capillary network and blood pressure. He demonstrated the presence of soaps in the blood and lymph, at that time commonly denied, and studied the presence of indican in the urine, a body the true significance of which as a measure of the putrefaction in the alimentary canal was shown by his pupil Baumann. One of the last most important of his discoveries was that of " chitosan," a decomposition product of chitin, the dis-
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coverj of whicli threw light on the chemistry of this important animal substance. Hoppe-Seyler's main work, however, to which we may direct attention, was done upon the red pigment or hasmo- glohin of the blood, npon processes of oxidation in the organism, upon the chemistry of fermentation, and upon chlorophyll.
It is not too much to say that if all work but Hoppe-Seyler's upon haemoglobin should be obliterated, we would still have nearly all that is known of that important substance. It was Hoppe-Seyler who gave the name haemoglobin, it was he who discovered that it was this substance in the red blood-corpuscles that gave them their power of carrying oxygen, and that hsemoglobin was a definite chemical compound. He discovered the difference between haemoglobin and oxyhsemoglobin. The absorption bands in the spectra and the differ- ence in the spectra of hsemogiobin and oxyhsemoglobin were also dis- covered by him, and he did more than any other one man to apply the spectroscope to the study of the blood pigment. It was Hoppe- Seyler who found that the oxygen combined with and was given up from the hsemogiobin in a molecular and not an atomic form ; he showed that carbonic oxide enters into a stable combination with haemoglobin, and thus explained the peculiarly poisonous nature of this gas. He discovered and named the decomposition products of haemoglobin, methasmoglobin, and hsemochromogen. He showed that haemin was simply the hydrochlorate of hEematin, and pointed out how the hsemogiobin molecule could be taken to pieces and built up by reduction. On the chemistry of haemoglobin he pub- lished no less than thirty papers.
An interesting discovery made by him was the cause of the sudden death to which men were subject who, after working under compressed air, suddenly returned to the ordinary atmosphere. He showed that under such circumstances the dissolved gases of the blood quickly escaped from solution with fatal results. This dis- covery indicated the proper manner of avoiding such disaster by a gradual return to the normal atmosphere, and has been the means of saving many lives.
One of the greatest discoveries of Hoppe-Seyler was that the tissues and not the blood are the seat of the oxidations of the body. This was still more convincingly shown later by Pfliiger. By this dis- covery Hoppe-Seyler's attention was attracted to the respiration of protoplasm, with what results we shall shortly see.
His work on hsemogiobin led Hoppe-Seyler in two directions: one was toward the composition of cells, the other toward respiration. Both paths have been followed with good results. In examining the composition of the red blood-corpuscles of mammals, Hoppe-Seyler discovered that the percentage of phosphoric acid contained in the
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residue of tlie alcoliolic extract was too liigli for tlie body to be protagon, as bad previously been supposed. He put bis pupils Manassien and Diakonow on tbis problem. Tbe former quickly found tbe substance to be not protagon, but lecitbin, a peculiar nitrogenous pbospborized fat, and tbe latter laid bare tbe cbemical nature of tbis substance. Hoppe-Seyler bimself proceeded to ex- amine otber cells for tbe presence of lecitbin and cbolesterin, and soon recognized tbat tbese substances, as well as tbe albumins, potas- sium pbospbate, and glycogen, must be considered ever-present con- stituents of protoplasm. Hoppe-Seyler furtber sbowed tbat tbe lecitbin generally existed in tbe cell, not free, but in combination witb albumin. Tbis fact drew Hoppe-Seyler's attention to similar compounds wbicb are formed by albumin combined witb otber sub- stances, and he proposed for sucb bodies tbe name " proteids," a name wbicb tbey bave subsequently borne.
Tbe discovery of lecitbin drew attention to tbe organic compounds of pbospborus in protoplasm. Tbere were many indications tbat tbe nuclei contained sucb a substance, altbougb tbe difficulties in its isolation bad bitberto been insurmountable. His pupil Miescber was placed on tbis problem, and discovered tbe " nucleins," probably tbe most important constituents of protoplasm tbus far recognized. Hoppe-Seyler bimself discovered " vitellin," tbe first of tbe pseudo- nucleins, and casein was soon sbown to bave a similar pbospborized
In tbe cbemistry of respiration Hoppe-Seyler was personally active, and formulated a bypotbesis of tbe cbemical nature of respiration and living matter wbicb is practically tbe only well- grounded tbeory of its kind extant, and one wbicb bas seldom been surpassed for brilliancy. By a stroke of genius be correlated tbe newly discovered reducing powers of protoplasm witb its oxidizing powers, and recognized tbe essential identity of tbe processes of life and putrefaction. Tbis idea tbrew ligbt on many pbases of cellular metabolism. It was first briefly mentioned in tbe IlediciniscJie- chemische Untersuchungen in 18Y1. It was clearly stated in volume xii of Pflliger's ArcUv fur die gesammte Physiologie some years later, and forms tbe kernel of most of bis subsequent work.
Tbe oxygen of tbe air, as is well kno^vn, is in a molecular or inert state, and not in an atomic form. It is unable, in tbis form, to carry out tbe oxidations of protoplasm. To do tbis it must be first made "active," eitber by conversion into ozone or by having its molecule split. Hoppe-Seyler's tbeory of respiration turns on the fact tbat in protoplasm and in putrefying masses, reducing substances are formed wbicb are able to split tbe oxygen mole- cule, setting free atomic oxygen. In this manner, if only air
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have access, putrefying fluids, like protoplasm, are able to oxi- dize completely tlie most resistant substances, side by side mth strong reductions. Hoppe-Seyler noticed that if animal sub- stances be allowed to putrefy in vessels deprived of air, intense reduc- tions ensue, hydrogen gas is often set free, and the whole chemical transformation is entirely different from that which the same sub- stances undergo if a current of air be constantly forced through the fluid. In the latter case the transformations are oxidations, and finally are of a most complete kind, little else than nitrates, car- bonates, and sulphates being left. If a putrefying fluid be allowed to stand exposed to air, Hoppe-Seyler discovered that at the surface the most intense oxidation ensued, while in the depths there were equally intense reductions. He found, further, in studying the fer- mentation of fibrin and calcium lactate, as well as other substances, that if no oxygen were present large quantities of hydrogen gas were evolved, if air were present no hydrogen was evolved. He imme- diately recognized in nascent hydrogen a reducing agent capable of causing the strong reductions and of splitting the oxygen molecule, thus indirectly causing oxidation. He suspected that nascent hydro- gen would combine with one atom of the oxygen molecule to form water, setting the other atom free, and experiment fully confirmed this hypothesis. If palladium be heated in a stream of hydrogen, it combines with the latter. If it now be brought into water, the hydrogen is liberated in the atomic state. Hoppe-Seyler found that palladium loaded with hydrogen would carry out oxidations and reductions similar to those of putrefying fluids. H such a palladium mass be half immersed in water containing benzol, haemoglobin, potassium iodide, or indigo, in the depths of the fluid strong reduc- tions ensue, with at the surface equally violent oxidations. In such circumstances oxyhemoglobin at the surface is transformed into methseglobin, benzol to phenol, indigo to indigo white at the bottom and indigo yellow at the surface, and iodine is liberated from its potassium combination. Hoppe-Seyler believed that in protoplasm a substance was present which acted somewhat like potassium hydrate or the ferments in the putrefying masses, causing a saponifi- cation, and at the same time a transference of an oxygen atom from a hydrogen to a carbon atom, with the liberation of nascent hydro- gen, or other reducing substance. The nascent hydrogen, in the man- ner already indicated, caused both intense reductions as well as oxida- tions. In this manner, as is well known in chemical processes outside of the cell, many syntheses and poljnnerizations can be brought about, and it would seem necessarily to result, in protoplasm, in just such a constant rearrangement of molecules as is imagined constantly to be transpiring there. Hoppe-Seyler believed that the oxygen
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would cause the formation in living matter of a great number of s}Titlieses bj tlie building of anhydrides with the formation of water. The cliief difference between living and lifeless protoplasm was about the difference between an anhydride and an acid. When death ensued, oxidation no longer took place, but the saponification con- tinued until complete.
Although this hypothesis is necessarily difficult of proof, many facts indicate its possible truth. That protoplasm is the seat of reduction and oxidation no one will probably deny, and that by a process of alternate reduction and oxidation many of the transforma- tions of substances by the organism may be repeated outside the cell is also undoubted. Thus Drechsel, by a rapidly alternating electric cuiTent, has succeeded in producing urea from albumin. It is also well recognized that many of the best-known syntheses effected by the organism are formed by a dehydration. This is true of the formation of fat, of the ethereal sulphates, of hippuric acid, of the camphor-giycuronic acid, and of the chondroit-sulphuric acid of cartilage. In this manner, too, as Hoppe-Seyler discovered, fatty acids of many carbon atoms may be synthesized from comparatively simple compounds. It seems not improbable that Hoppe-Seyler thus obtained a glimpse of that promised land toward which the physiological chemist has been patiently work- ing for the past forty years, where the mysteries of protoplasm shall be made clear. Whatever may be the exact details of the process of respiration, certainly Hoppe-Seyler's discovery that reducing substances in the presence of air may induce powerful oxidations is one of the most brilliant and suggestive made in bio- chemistry.
Impressed by the similarity of living and fermentative processes, Hoppe-Seyler devoted much time to the chemistry of the latter. He made the first classification of fermentations, distinguishing those in which a simple hydration or saponification takes place, as in the digestive fermentations, from those characterized by the trans- ference of an oxygen atom from a hydrogen to a carbon atom, with the liberation of hydrogen. To a certain extent he made clear the chemical processes of fermentation, and his researches serve as a solid and suggestive basis for further work. Hoppe-Seyler was throughout a strenuous upholder of the Liebig view of the essential identity of fermentations, whether induced by chemical bodies or living germs. His position has been justified by the recent brilliant discovery that the alcoholic fermentation of sugar by yeast, long believed to be dependent on the life of the yeast cell, is due to a substance which may be isolated from the living yeast. Hoppe- Seyler contributed also to our knowledge of the fermentation of
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cellulose into carbonic anhydride and marsli gas, wliich, as he showed, was due to a bacterium resembling or identical with the Bacillus amyldbacter.
As might be expected, Hoppe-Seyler devoted considerable time to chlorophyll. He discovered and named the " chlorophyllan," a crystalline derivative of chlorophyll. He devised an ingenious method for showing that chlorophyll, in the sunlight, liberated oxygen in a molecular and not an atomic state. If a green plant be brought into a glass tube in water, a little putrefying blood added, and the tube hermetically sealed and placed in the dark, all oxygen is consumed and the tube shows the spectrum of haemoglobin. If the plant be brought into the direct sunlight, the haemoglobin is trans- formed by the oxygen liberated by the chlorophyll bodies into oxyhaemoglobin, which gives a characteristic spectrum. If the oxy- gen were liberated in an atomic state, the spectrum of methaemo- globin would appear.
Let us now glance briefly at Hoppe-Seyler's influence upon physiological chemistry. He may be called the father of this sci- ence, for, although the beginnings of biochemistry were identical with those of organic chemistry, both taking their origin in La- voisier's experiments on oxidation, Regnault and Renard's on respira- tion, Chevreul's on the fats, and Liebig's and "Wohler's on urea, muscle, and animal metabolism, yet in the early half of the century the interest of the purely chemical analysis and synthesis of organic bodies had almost completely absorbed the attention of chemists. It was Hoppe-Seyler's great merit to perceive and to emphasize, with all his might, the great importance of physiological chemistry in the arts, in industries, and in medicine. His clear glance perceived that a knowledge of the chemical constitution and chemical processes of organisms in health and disease must underlie any proper treatment or understanding of disease, a fact which in the world at large to-day is becoming better and better recognized.
To further the development of this science, whose importance he perceived, he saw that it must have an undivided attention; that it must be divorced from physiology and pathology on the one hand, and from chemistry on the other, and given an independent position in the university faculty. In this contention Hoppe-Seyler met with fierce opposition in Germany, particularly from Pfliiger and other physiologists and chemists, so that to-day there is but one pro- fessorship of physiological chemistry in Germany — namely, that at Strasburg. In other countries Hoppe-Seyler's idea received more favorable attention, and he lived to see such professorships established in Sweden, ISTorway, Switzerland, Austria, Russia, and America.
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Hoppe-Seyler should be gratefully remembered by posterity for his service in thus putting on its feet and starting in motion a sci- ence the future of which man can but guess at, but which is perhaps fuller of promise for the alleviation of suffering, for the betterment of the conditions of existence of mankind, than any other science or group of sciences, for it holds somewhere within it the keys of the riddles of life, disease, decay, and death.
In no one way did Hoppe-Seyler set the science further forward than in the founding of a journal, the Zeitschrift filr pJiysiologische Chemie, devoted exclusively to biochemistry. The journal received at the outset both hearty support and hearty opposition, but it still remains as the official organ of publication of biochemical works. Previous to the establishment of this paper, works treating of the chemistry of organisms were scattered in agricultural, chemical, physiological, pathological, and medical journals, just as they are in the English language to-day. They thus lost largely in effective- ness. Hoppe-Seyler brought all biochemical efforts to a focus, with admirable result.
Hoppe-Seyler as a teacher could be known only by his immediate pupils. Baumann and Kossel have written of him that " with untir- ing patience he introduced the beginner to practical chemistry; no ignorance, no lack of skill exhausted his forbearance." He may be judged, however, by us through the men who were his pupils. 'Ro test of a man's mind is more certain than the influence he exerts upon those who associate with him, particularly his pupils. Judged by this test Hoppe-Seyler must rank very high indeed. Whether it is that a man of his type naturally attracts to him the most promising of the rising generation, or whether even an ordinary man absorbs from such a teacher an amount of light which, like a fluorescing sub- stance, he is enabled thereafter to emit, certain it is that Hoppe- Seyler's pupils include an extraordinary number of men of ability. His pupils and his pupils' pupils are the principal workers in physio- logical chemistry to-day, and a mere enumeration of their achieve- ments would be a history of the development of the science in the last forty years.
As a teacher Hoppe-Seyler strongly resembled Ludwig, his great contemporary physiologist. Brooks, of Johns Hopkins, AgassLz, and Liebig, the chemist. He offers a striking contrast in this respect to Claude Bernard, whose great genius affected the science of physi- ology principally by its own extraordinarily keen and suggestive re- searches, and when it died left no heirs.
Such was Hoppe-Seyler — a winning personality, a courageous upholder of what he believed true, a keen investigator, a far-sighted, broad-minded, kind-hearted man.
- In part adapted from an article entitled Zur Errinnerung an Felix Hoppe-Seyler. By E. Baumann and A. Kossel. Zeitschrift für physiologische Chemie, Bd. xxi, 1895.