COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCES STANDARD HX641 05938 R507.P26 H44 1904 The influence of Pas l^On MEDICAL SCIENCE ^ HERTER RECAP m^ Columbia (Bnitiewttp THE LIBRARIES ifWebical TLibvavp I\ THE INFLUENCE OF PASTEUR ON MEDICAL SCIENCE THE INFLUENCE OF PASTEUR ON MEDICAL SCIENCE fore t\)t ^peuical ^t\)oo\ of 3|ot)ns J^opbins? mnitjer^it^ BY CHRISTIAN ARCHIBALD HERTER, M. D. NEW YORK DODD, MEAD & COMPANY M C M I V Copyright, 1904, By Christian Archibald Herter en on THE INFLUENCE OF PASTEUR ON MEDICAL SCIENCE '*«»*^ i^ THE INFLUENCE OF PASTEUR ON MEDICAL SCIENCE TO one who treasures mem- ories of student days spent in your patholog- ical laboratory, when each member of a small and fa- vored group worked under the personal guidance of the great teacher whose unselfish labors have done so much for science in this country, it is indeed an ex- ceptional privilege to address those who represent the School of Medicine that has grown since then to be the model for many an older institution. Yet I am con- scious that this very privilege en- tails a risk, — proportioned to the THE INFLUENCE OF PASTEUR largeness of the opportunity, — of using unworthily the precious moments which fortune has be- stowed on me. My choice of subject has not, I fear, lessened this hazard, for I have chosen to speak to you of one of the most significant men of the past cen- tury, whether we consider him as a person, as an investigator or as a public benefactor. I pray you, therefore, deal gently with the shortcomings of an undertak- ing so difficult and ambitious as that of estimating the influence of a great career on the advance of medical science. Louis Pasteur first saw the light of day on December 27th, 1822, in an humble dwelling in the little town of Dole in the Franche Comte. His parents had small means and limited social oppor- tunities, but through the exercise ON MEDICAL SCIENCE of forceful character and unusual fidelity to elevated ideals of life managed to give him a fair ele- mentary education. The father, earnest, industrious and intellec- tually ambitious, instilled into his son the desire to become a useful and respected member of society, shielded him by constant com- panionship from the vulgar temp- tations of youth, and fired him with a love of country which a long and honorable career as a soldier of Napoleon had strongly fortified. The mother of young Pasteur was prevented by house- hold cares from sharing closely the intellectual interests of her only son, but showed the depth of her affection by making many a little sacrifice to further his edu- cation. She was a spirited wo- man, possessed of lively imagina- tion and quick intelligence, and THE INFLUENCE OF PASTEUR it is reasonably clear that the un- usual artistic perceptions of Pas- teur mark the perpetuation of these maternal gifts. Although the school days of Pasteur appear to have given little indication of an exceptional future, the lad showed some qualities which dis- tinguished his work in later life. In his daily tasks, at which he workedfaithfully and deliberately, he showed the most scrupulous accuracy and truthfulness, attri- butes which are the more note- worthy for the reason that they belonged to a temperament en- riched with a strong vein of ro- manticism , which for a time found expression in a fervid devotion to poetic literature. Moreover, Pas- teur showed while still in his teens a pronounced capacity for por- traiture. During his three years of instruction at the College Royal ON MEDICAL SCIENCE of Besanf on, which he entered at eighteen years of age, the young student was more absorbed in literature and art than in science, and impressed his colleagues as being surely destined for an artis- tic career. The courtesy of Mr. Philip B. Marcou of Cambridge has made it possible for me to examine closely two fine exam- ples of Pasteur's work at the end of this Besanf on period. Although these portraits disclose the man- ual hesitancy of the imperfectly trained craftsman, they bear an unmistakable air of distinction and are executed with a respect for detail which is highly remark- able. Anyone who sees these youthful works is likely to feel that eyes so sensitive to these minutest particularsof form would be apt to see many things which others had failed to notice; and it THE INFLUENCE OF PASTEUR is noteworthy that Emil Fischer, whose calm judgment is well known, has expressed his belief that Pasteur's crystallographic discoveries were facilitated by his artistic perceptions. The years at Besan^on were followed by a highly important course of study at the Ecole Nor- male of Paris, during which Pasteur formed the determination to de- vote himself to science. For the first time in his life the gifted, im- pressionable young man found himself under the influence of a creative scientific mind of the highest order — a mind which has left a large and permanent mark upon the history of chemistry, and which could not fail power- fully to mould the plastic intelli- gence of Louis Pasteur. Jean Baptiste Dumas, who had already discovered the great principle of ON MEDICAL SCIENCE substitution, united to his genius as an investigator the charm of a finished and spirited delivery. His Sorbonne lectures fairly cap- tivated the young student and gave definite and lasting direction to his study and fancy, and, later, to his researches. Other teachers of a superior order contributed to lead Pasteur into the promising and fascinating paths of physics and chemistry. The attractive Balard, to whom bromine had first surrendered the secret of its ex- istence, reinforced the chemical teachings of Dumas, and the ad- mirable lectures of Delafosse aroused an enduring interest in the subtle beauty of crystalline forms. But it is to the strong intellect of Dumas that Pasteur owed his first grasp of the great principles of science and that en- thusiasm for work which made it THE INFLUENCE OF PASTEUR possible to ignore the harsh and depressing material conditions that prevailed at the Ecole Nor- male. The recognition by young Pasteur of the importance of cor- relation in the physical sciences is an impressive feature of his mind at this period of close asso- ciation with great chemical inves- tigators. Evidences of this recog- nition exist in a singularly fine letter, full of enthusiasm for sci- ence, which he wrote to his col- league, Jules Marcou, then enter- ing on his distinguished career as a geologist.* ''Before finishing your letter," says young Pasteur, *' I had already regretted that your studies in chemistry were incap- able of responding to what geol- * Mr. Philip B. Marcou has permitted me to read a large number of unpublished letters written by Pas- teur to his father. The letter above quoted is dated June ID, 1845, and is one of a very small number be- longing to this period. 10 ON MEDICAL SCIENCE ogy will often ask of them." . . . 'M know very well that many distinguished geologists have no broad conception of chemistry, but I believe this to be a great pity, and I think that geology has not often enough turned to chem- istry." The chemist of twenty- three summers held a point of view which was destined very soon to aid him in a memorable research. It was in the field of crystal- lography that Pasteur, led by an interest in the ingenious and deli- cate methods of the science, first showed his exceptional capacity to observe minutely things and processes, and to correlate and interpret his observations. He began by carefully repeating a series of crystal measurements on tartaric acid, racemic acid and their salts, shortly before pub- II THE INFLUENCE OF PASTEUR lished by Provostaye. During the study of the recrystallized salts of tartaric acid he observed one very important but unobtrusive thing which the distinguished physicist had overlooked — regular evi- dences of hemihedral facets. All the tartrates showed a weak kind of isomorphism, which is appar- ently forced on them by the tar- taric acid group, whatever other element may exist in the com- pound. Guided, as he tells us, first, by the observation of Biot that tartaric acid and its compound rotate the plane of polarization; secondly, by a relationship be- tween the crystalline form of quartz and the direction of rota- tion ; and, finally, by Delafosse's conception that hemihedrism de- pends on definite crystallographic laws, Pasteur concluded that there is a relation between the hemi- 12 ON MEDICAL SCIENCE hedrism of the tartrates and their optical activity. An unexpected discovery soon proved this to be true in a conclusive and beautiful manner. One day, in the dark library of the Ecole Normale, Pas- teur's eyes lighted on a remarka- ble paragraph from the writings of the Berlin chemist and crystal- lographer, Mitscherlich, relative to two different saline combina- tions of tartaric acid, the tartrate and the paratartrate (or racemate) of sodium and ammonium. This note stated that these two types of double salts have the same chemical composition, the same crystal form with equal angles, the same specific gravity, the same double refraction, and that in consequence of this their opti- cal axes form the same angles. Their water solutions have the same refraction. The dissolved 13 THE INFLUENCE OF PASTEUR tartaric acid salt rotates the plane of polarization and the racemic salt is indifferent, as had been found by Biot for the whole series of salts. '' But," continues Mit- scherlich^ *'the nature and the number of atoms, their arrange- ment and their distance from one another are the same in both bod- ies." The contradiction expressed here upset all Pasteur's physico- chemical ideas and persisted for months in his mind like an inter- rogation point. But the day came when experience cleared up the mystery by demonstrating that there is really a difference between the tartrates and the racemates which Mitscherlich had not no- ticed. The former bore hemi- hedral facets on the right side and always rotated the plane of polar- ization to the right; the latter bore facets both on the right and on «4 ON MEDICAL SCIENCE the left sides and did not rotate polarized light at all. Moreover, it later appeared that this inactive racemic acid may be caused to crystallize in such a way that the crystal mass consists of equally numerous dextro-rotary and levo- rotary crystals, the former pos- sessing hemihedral facets on the right side, the latter hemihedral facets on the left side. Both kinds of crystals were isomorphous, but the isomorphism was that of two asymmetric crystals, of an object to its reflected image. The weighty and surprising discovery had been made that indifferent racemic acid crystallizes into equal quantities of ordinary dextro-rotary tartaric acid and the newly observed levo-rotary tartaric acid. This research on the tartrates, culminating in 1848 with the dis- covery of the nature of paratar- »5 THE INFLUENCE OF PASTEUR taric or racemic acid, proved that Pasteur had already made him- self master of the experimental method. Three distinct practical results followed in the train of this re- search as a consequence of con- tinued studies of crystallographic problems. In the first place there came to light numerous fresh ev- idences of a relation between mo- lecular constitution, crystalline form and the property of rotat- ing the plane of polarization. It is true that Pasteur seriously enter- tained some ideas of a highly spec- ulative nature regarding the ope- ration of dissymmetry in nature, ideas which involved him in fruit- less experiments ; but on the other hand the tangible and positive re- sults of his work must be recog- nized as forming the basis of the modern doctrine of the asym- i6 ON MEDICAL SCIENCE metrical carbon atom, which has so illuminated our ideas of the spatial arrangements of the atoms within the molecules of organic substance ; Secondly, the research on the tartrates led Pasteur to the recognition of a series of optically inactive compounds, including in- active malic acid and inactive am- yl alcohol. Finally, the crystallo- graphicresearcheswere the bridge over which the far-seeing investi- gator passed on the way to lay the foundation of a new biological sci- ence, a science which has effected a veritable revolution in our con- ceptions of medical problems. Cagniard-Latour, Schwann and Katzing, by knowledge gained in theirexperiments on alcoholic fer- mentation, held one pass to the great secret, but saw not the fields of discovery to which it might have led them. Pasteur made his '7 THE INFLUENCE OF PASTEUR way thither by a singularly trust- worthy intuition. Greatly im- pressed with the circumstance that optically active substances like the sugars, the tartrates, the malates, the citrates, the gums and the proteids, seemed to be confined to the organic world and were not to be found outside the tissues of plants and animals, Pas- teur made a simple yet decisive experiment. To some pure crys- tallized inactive ammonium para- tartrate he added fermenting albu- minous material. After a time the fluid was examined with the po- lariscope. It rotated strongly to the left. This levorotation was obviously due to the fact that the dextrorotary constituent of the paratartrate had been decom- posed. An optically inactive fluid had been converted into an opti- cally active fluid. According to i8 ON MEDICAL SCIENCE Pasteur's theoretical views this striking change indicated the me- diation of living matter. The ac- tivity of unorganized purely chem- ical ferments could not, in his judgment, explain the facts ; mi- cro-organic life must be in some way concerned. Fortunately the rnind in which this conception was born was also capable of testing its correctness by the most rigid methods of investigation. Fortu- nately, too, the external condi- tions favored a studious excursion into the processes of fermentation , for Pasteur was called in 1854 to a Professorship at Lille in a region of distilleries which involved the training of young men to profici- ency in industrial chemistry, and made it essential to get new light upon the various kinds of fermen- tation. At this period of Pasteur's career »9 THE INFLUENCE OF PASTEUR the prevalent doctrines of fermen- tation were singularly unsatisfac- tory anduncontrolled by searching experimentation. The versatile Spallanzani had nearly a century before taken the important step of showing that putrescible liquids can be permanently protected from the processes of fermentation and decomposition by boiling and ex- clusion of air. Then Gay-Lussac, inspired by the revolutionary but constructive work of Lavoisier, made his clever attempt to show that the results of Spallanzani were due to the exclusion of the oxy- gen of the air from the decompo- sible materials, and the ingenious French cook Appert put this erro- neous idea to important practical use in his widely employed meth- od of canning perishable foods. Thus in the early days of the nine- teenth century people were con- 20 ON MEDICAL SCIENCE tent to think of alcoholic fermen- tation as purely a chemical pro- cess. The first great blow to this widely accepted doctrine came from Theodor Schwann's incisive studies of the yeast plant in its relation to alcoholic fermentation. Very clearly did Schwann show that oxygen does not suffice to initiate the fermentation of sugar, and that the necessary condition is the presence of something which is destroyed by heat — a liv- ing organism. Unfortunately, he failed to maintain aggressively the new doctrine of the dependence of fermentation on micro-organic life. The result was that the new vitalistic hypothesis failed to make any important advance in the face of the sharp criticism and ridicule of so active and influential a teacher as Justus Liebig, whose word was nearly everywhere re- 21 THE INFLUENCE OF PASTEUR ceived as final in matters chemi- cal and physiological. To Liebig and to many others it seemed a retrograde step to as- sume that a living organism like the yeast plant is the cause of al- coholic fermentation, for the most advanced scientific thinkers were eagerly striving to explain the phenomena of life by physical and chemical laws, and the role of '' vital force " was being success- fully restricted almost from day to day. Liebig pointed effectively to the fact that sugar undergoes other kinds of fermentation than alcoholic, such as lactic and buty- ric, but that nothing like a yeast organism was to be seen in these allied types of decomposition. It seemed to him that these various kinds of decomposition had one feature in common — the presence of a small quantity of nitrogenous 22 ON MEDICAL SCIENCE substance. This dead material operated as the real ferment, by communicating a kind of shock to the molecules of sugar or beef ex- tract with which it came in con- tact, which resulted in the frag- mentation of the molecule into smaller molecules, the essence of fermentation and putrefaction. To Pasteur the position of Lie- big was wholly unintelligible be- cause it rested on prejudice much more than on experimental evi- dence. He resolved to investi- gate the subject of fermentations from the standpoint which he had reached by observing the fermen- tation of the paratartrates — that is to say, with the preconceived idea that fermentation depends on the mediation of living organisms. The first notable paper in the long series which solved one of the most pressing questions in biology 23 THE INFLUENCE OF PASTEUR deals with lactic acid fermenta- tion. * It might, perhaps, have been anticipated that Pasteur's first important utterance on the nature of fermentation would deal with the alcoholic form which has so great a commercial importance. He discovered, however, in lactic * During the years 1858 and 1859 Pasteur did highly important work on alcoholic fermentation. His views as to the significance of molecular dissym- metry had already led him to regard the levo-rotary action of amyl alcohol as an indication that this reg- ular product of alcoholic fermentation is formed by the mediation of living organisms. It was, in fact, his study of amyl alcohol (1855) together with the ex- periment on inactive ammonium paratartrate that in- cited Pasteur to undertake researches on the method of fermentative processes. His superior chemical train- ing under Dumas was used to great advantage in all the researches on fermentation. In the case of alco- holic fermentation Pasteur showed that the acid formed is neither acetic nor lactic acid, but that suc- cenic acid and glycerine are regular and not unim- portant products. Lavoisier and Gay-Lussac repre- sented the sugar in alcoholic fermentations as splitting wholly into alcohol and carbon dioxide, but the work of Pasteur showed that five or six per cent, of all the sugar is not decomposed in this way. 24 ON MEDICAL SCIENCE fermentation an admirable field on which to contest the ideas of Liebig and his followers, who were constantly pointing out that in lactic fermentation, so like the alcoholic form, there is nothing at all like a yeast ferment. This research ended, as is well known, in the discovery of a specific lac- tic acid organism or ferment, and in the cultivation of this and other organisms in an artificial medium free from albuminoids. Pasteur was not slow in forming the hy- pothesis that different types of fermentation are dependent on dif- ferent types of micro-organisms, and this idea of specificity, soon established in relation to the or- dinary decompositions, ultimately became the basis of our modern knowledge of the infectious dis- eases. The research of lactic acid fer- THE INFLUENCE OF PASTEUR mentation thus gave the coup de grace to the chemical theory of fermentation at the sametime that it marked the birth of the promi- sing science of bacteriology. The development of a method de- signed to secure pure cultures from fluid media, the use of cul- ture media of known composi- tion, and the careful chemical study of products of decomposi- tion all belong to this early period of Pasteur's life, and were achieve- ments of the deepest significance for the future of the great depart- ment of knowledge which has re- vivified the biological sciences. Another research on fermenta- tion deserves more than passing notice on account of the extraor- dinary discovery which appears as its almost accidental by-pro- duct. This is the investigation on butyric acid ferments (1861). This 26 ON MEDICAL SCIENCE research brought to light the fact that there are motile organisms ca- pable of inducing a decomposition of sugar with the production of butyric acid. In the course of this research Pasteur saw that these organisms (whose motility was most puzzling on account of its suggesting animal life) behaved very differently according to their position with reference to thecover glass, those at the centre being ac- tive, while those at the periphery and exposed to the air were checked in their movements.* From this casual observation came the fundamental conception of anaerobic life. All physiologists recognize to-day '' a class of be- ings possessing such vigorous re- spiratory power, "as Pasteur aptly * Pasteur fell into the error of describing the buty- ric acid organisms as infusorians, and thought he had shown that animal life can exist without oxygen. 27 THE INFLUENCE OF PASTEUR says, ' ' that they are able to live without the influence of the air by taking oxygen from certain com- pounds, thus occasioning in the latter a slow and progressive de- composition." That Pasteur's original and searchingexamination of the prob- lem of fermentation would one day lead him into a controversy over the unsettled question of spontaneous generation might al- most have been predicted. The long discussion with Pouchet and Bastian, containing something of bitterness and not a little of the ridiculous, is a dramatic and ani- mated chapter in the life of a peace- able but truth-loving man. As students of the influence of Pas- teur on medical science we need not pause to review this controv- ersy, for its fruits are to be found in all his subsequent work on the 28 ON MEDICAL SCIENCE specific nature of the infectious diseases. Yet this discussion, pro- longed over nearly twenty years, and replete with instruction and entertainment, is worthy of a per- manent place in the memories of scientific men. After a public victory over Pou- chet in 1862, which brought in its train the honor of election to the Academy of Sciences, Pasteur turned his attention toward two subjects of much practical interest which seemed closely connected with the phenomena of fermenta- tion. One of these was the man- ufacture of vinegar, the other the diseases of wine. The study of vinegar led to the recognition of the micro-organic nature of the vinegar film or mycoderma, and brought acetic fermentation into line with lactic and butyric fer- mentations. It led also to the dis- 29 THE INFLUENCE OF PASTEUR covery that the oxidation of alco- hol through the agency of the vin- egar organisms may be carried too far, acetic acid being lost by oxi- dation to water and carbon diox- ide. Then again, Pasteur was able to aid the makers of vinegar by teaching them that the indispen- sable film formation can be facili- tated by the actual transfer of the living ferments to the surface of the vinegar. In the study of the diseases of wine Pasteur achieved even more helpful practical re- sults, for after recognizing the de- pendence of sour, bitter and mud- dy wines on the presence of defi- nite types of living ferments, he was able to suggest a simple and efficient way of controlling these disturbing agencies by the use of moderate heat. From this recom- mendation has sprung the use of the widely employed method of 30 ON MEDICAL SCIENCE sterilizing which we call Pasteuri- zation. In Pasteur's growing interest in these works of practical utility we can detect a tendency which was destined to bear rich fruitage in medical science — the inclination to employ the gifts of which he could no longerfail to be conscious in a manner likely to be directly helpful in relieving the needs of his fellow men. It was this atti- tude which made it possible in 1865 to lead Pasteur, not without regret, away from his studies of fermentation to a wholly new sphere of endeavor. In that year the mortality among the silk- worms of northern France was so great that the silkworm industry was threatened with total extinc- tion, and grievous famine was making its appearance in a land where comfort and contentment 3» THE INFLUENCE OF PASTEUR had long reigned. Dumas, acting for a Senate Committee, selected Pasteur to solve the mystery of the plague. To Pasteur's remon- strance that he knew nothing of the subject and had never seen a silkv/orm Dumas ansv^ered: ''So much the better. You v^ill not have any ideas except those that come to you through your own observations. " There were many unfriendly comments on this ap- pointment, forsome scientific men could not understand why achem- ist should be chosen to cope with an obscure zoological problem. But Dumas knew his man and confidently relied on the great gifts he saw in him. It was quickly evident that his faith was not mis- placed. Only twenty days after his arrival at Alais, Pasteur pre- pared a note in which he outlined a method of breeding from the 32 ON MEDICAL SCIENCE eggs of silkworms free from dis- ease. Unlike his predecessors he made the moth the center of the efforts to regenerate the race of silkworms. 'Mf the butterfly is sick, reject all its eggs.*' It re- quired five years of Pasteur's most devoted attention, five years be- set with uncertainties and disap- pointments, to establish this al- most clairvoyant conception on an incontestable scientific basis. At the end of this period Pasteur and his highly skilled assistants had shown that there were two dis- tinct diseases from which the silk- worms died, pebrine or corpuscle disease, and flacherie, a bacterial affection of intestinal origin. The former was proved to be a specific disease due to the psorosperm Nosema bombycis ; the latter was believed by Pasteur to depend on a specific bacterium, but can prob- 33 THE INFLUENCE OF PASTEUR ably be excited by several distinct varieties of bacteria. The pebrine disease, which was the chief scourge of the industry, was erad- icated through the use of a care- ful system of breeding from eggs shown by microscopical exami- nation, to be free from infection. The immense practical importance of this method sociologically as well as financially can be better left to the fancy than expressed in dollars and cents. But these im- mediate practical results do not adequately express the far-reach- ing effects of the great silkworm research, which marks the entry of Pasteur into the realm of animal pathology, and is thus the vesti- bule of modern medicine. For it is true that the laws governing the propagation and development of the flacherie disease have the most striking analogies to those of the 34 ON MEDICAL SCIENCE diseases of man. The varying sus- ceptibilities of different individ- uals to the same micro-organisms, the influence of the path of infec- tion and the fact that flacherie or- ganisms acquire increased viru- lence after passage through the bodies of living silkworms fore- shadow discoveries in human pa- thology. The two volumes deal- ing with the diseases of silkworms, and dated 1870, are works whose contents should be familiar to every independent student of the infectious diseases. The researches on the silkworm diseases had one practical effect of considerable importance for Pas- teur's later career. The success with which Pasteur had solved his intricate and widely known prob- lem made it natural that French investigators of animal pathology should in future turn to him as the 35 THE INFLUENCE OF PASTEUR man most likely to help them in their work, and this brought to him new opportunities for fresh successes. It is likely that excessive work and mental stress in some degree contributed to the onset of the se- ries of paralytic seizures which in October, 1868, threatened the life of Louis Pasteur. During the crit- ical period of his illness many of the most distinguished scientific men of France vied with each other to share with Mme. Pasteur the privilege of nursing the man they loved so well, and of rescuing the life that had already placed science and a nation under endur- ing obligation, through discover- ies which were either of the great- est practical utility, or appeared susceptible of almost unlimited development. Had Pasteur died in 1868 he would have left a name 36 ON MEDICAL SCIENCE immortal in the annals of science. Others would in some degree have developed his ideas. Al- ready inspired by the researches on fermentation Lister would have continued to develop those life- saving surgical methods which will forever be associated with his name. But we may well question whether investigations in biology and medicine would not have been, for a time at least, conducted along less fruitful paths. Who shall say how soon the great prin- ciple of experimental immunity to pathogenic bacteria, the central jewel in the diadem of Pasteur's achievements, would have been brought to light ? When Pasteur recovered suffi- ciently to resume work it was soon clear to apprehensive frieads that he had no intention of leav- ing his ideas to be worked out by 37 THE INFLUENCE OF PASTEUR other men. The miseries of the Franco-Prussian war deeply af- fected him, and could not fail to inhibit his productiveness, but after a time the unquenchable love for experimental research was once more ascendant, and there began a new epoch, the epoch of great discoveries relating to the origin and cure or prevention of the infectious diseases of man and the domestic animals. As in the case of Ignatius Loyola^ it seems as if the lamp of genius shone with a larger and more luminous flame after the onset of bodily infirmity, in defiance of the physical mech- anism which is too often per- mitted to master the will. The hostility of Pasteur to Ger- many and all things Teutonic was greatly intensified by the events of the Franco-Prussian war, and has left a somewhat regrettable 38 ON MEDICAL SCIENCE impression on his scientific work. Desiring to contribute to the re- habilitation of his unhappy coun- try, he was led to improve the processes of brewing, with a view to increasing the wealth of France, and at the same time lessening the yearly tribute to the despised people beyond the Rhine. It was easily shown that some of the dis- eases of beer are due to the action of bacteria allowed to take part in the process of fermentation. But it soon became clear that the mere exclusion of these micro-orga- nisms does not insure a brew of good beer. The problem was con- siderably complicated by the dif- ficulty of deciding what consti- tutes excellence in beer, and this situation was not helped by the fact that Pasteur, who disliked the German drink almost as much as he disliked Germans, could not 39 THE INFLUENCE OF PASTEUR distinguish one brew from an- other. Nevertheless, after many discouragements, he succeeded in establishingmethods which much improved the character of French beers, methods involving the aeration of beer-wort by sterilized air, and the abandonment of open coolers. The results were far from satisfactory owing to the circum- stance that Pasteur quite over- looked the part played by the un- desirable forms of yeast— so called wild yeasts — in the production of abnormal fermentations. In fact it is doubtful if he could have sep- arated the different types of yeast by the methods at his command, for even in so late a work as the fa- mous '' Etudes sur la Biere," bear- ing the date 1876, we are struck with the inadequate character of Pasteur's devices for obtaining pure cultures of micro-organisms. 40 ON MEDICAL SCIENCE This work, with its tender ded- ication to the memory of Pasteur's father, was a highly important contribution to bacteriology in spite of its many botanical defects. It is really a bacteriological pot- pourri bringing together the writ- er's views on many questions, rather than a strict treatise on the diseases of beer. Besides chapters on the causes of bad beer and improved methods of brewing, the volume treats of the origin of ferments and furnishes conclusive experimental evidence against that plastic doctrine of the trans- formation of species around which the friends of the spontaneous generation fallacy were hopefully rallying. But by far the most striking and original chapter in this notable volume is that in which Pasteur formulated his physiological theory of fermenta- 4» THE INFLUENCE OF PASTEUR tion — the startling theory that the essential characfferistic of fermen- tation is life without air, life with- out free oxygen. This theory, if not entirely upheld by other biol- ogists, has at least proved a pow- erful stimulus to new studies of this unexplored aspect of life. Pasteur's life was prolonged a quarter of a century after the close of the war with Germany, and during a large part of this long period his mind dwelt almost un- ceasingly on two phases of the great biological and practical problems which it was his for- tune to develop so fruitfully. One of these was the investigation of the etiology of disease as related to the activity of micro-organisms. The other was the experimental study of the amazing phenomena of immunity to the action of spe- cific viruses or virulent micro- 42 ON MEDICAL SCIENCE organisms. These two affiliated phases of bacteriological research culminated in one of the most re- markable discoveries of all time —remarkable for its practical re- sults, but even more striking as an example of the use of the im- agination in science. It is well worth while to consider the chief events that ultimately led to the discovery of a method of immun- ization against the virus of hydro- phobia. The idea that some diseases are due to living micro-organisms was suggested by Boyle two hun- dred years before the days of bac- teriology. From time to time thoughtful men took up this idea as worthy of discussion, but it received no substantial confirma- tion until Schoenlein, with the aid of the microscope, made his ad- mirable discovery of the infectious 43 THE INFLUENCE OF PASTEUR nature of ring worm. This was in 1839. Within a few years Henle, the gifted anatomist of Gottingen, proposed an ingenious explana- tion of the infectious diseases which assumed the agency of micro-organisms, but the theory, though based on thoughtful clin- ical considerations, was deficient in experimental data and had little practical influence on medicine. It is scarcely surprising that the leading scientific minds of the epoch should have been hostile to any mere hypothesis of conta- gion by germs, for in their strug- gle against the ancient conception of a vital force they regarded the idea of a contagium vivum exactly as Liebig had regarded Schwann's and Pasteur's doctrine of fermen- tation. Even the illuminating-cell doctrine of Virchow was not es- pecially favorable to the idea that 44 ON MEDICAL SCIENCE living organisms from outside can excite disease by fixing them- selves and developing in the body. Pasteur's training and tem- perament and genius admirably fitted him not merely to detect the great central truth of etiology, but to force it, in spite of stub- born opposition, upon a doubting v/orld half stunned at the bold- ness of the new doctrine. But while he took a large part in com- pelling this revolution in the con- ception of disease, the way was prepared by others, and especially by the fine observations of the biologist, Casimir Joseph Da- vaine, and the accurate and in- genious experimental methods of Robert Koch. Davaine, while assisting the clinician, Rayer, in the study of the devastating anthrax plague in 1850, observed little thread-like 45 THE INFLUENCE OF PASTEUR bodies in the blood of animals dead of this disease. Ten years later Delafond observed these lit- tle threads to be living organisms w^ith the power of multiplying outside the body. Thirteen years after his first observations, Da- vaine, incited by Pasteur's sug- gestive work on the butyric acid ferment, reopened his study of anthrax and confidently pro- claimed that the organisms he had found were the cause and the only cause of anthrax. But it required the superior technique of Koch, unquestionably, to ob- tain the anthrax organisms in pure culture, to follow the cycle of their development in the ani- mal body, and thus to place the important discovery of Davaine on an impregnable scientific foun- dation. Pasteur, entering this field a little later, independently 46 ON MEDICAL SCIENCE worked out some of the most striking features of the etiology of anthrax, and convinced the best scientific minds of France of the relationship between the ba- cilli of Davaine and the perpetu- ation of the anthrax plague. Very closely associated with Pasteur's work on anthrax is the admirable research in which the master, aided by Joubert and Chamberland, discovered the or- ganism known to us as the bacil- lus of malignant oedema, but de- scribed by its detectors as the vibrio septique, in the same year (1877) in which the well-known publication on anthrax appeared. Of the many excellent features for which this research is dis- tinguished there are two that de- serve especial mention. First, the recognition of the septic vi- brio in the blood of animals not 47 THE INFLUENCE OF PASTEUR newly dead of anthrax was an extremely important service in clearing up the gravest objections to Davaine's doctrine of the etiol- ogy of anthrax. Secondly, the observation that the septic vibrio is anaerobic affords the earliest example of a pathogenic organism which in its vegetative form is inhibited by the presence of oxy- gen — a discovery which we may reasonably attribute to the expe- rience gained sixteen years before with the butyric ferment. In looking for fresh proofs of the bacterial origin of disease, Pasteur made some visits to the hospitals of Paris, and thus came into closer relations with the prac- titioners of medicine and surgery. The alert and intellectually honest minds bade him welcome and gave him every help to pursue his studies ; the conservatives 48 ON MEDICAL SCIENCE looked at him askance, confi- dently set up their time-worn theories against his experimental proofs, and lost no occasion to ridicule the germ theory of the origin of disease. To-day it is difficult for us to picture the in- credulity and amazement of many prosperous and self-satisfied prac- titioners on hearing Pasteur's an- nouncement that he had found the same pus-exciting micro-or- ganisms (probably the staphylo- coccus pyogenes aureus) in the pus from a series of boils and in the pus from osteomyelitis, and that these conditions, so different in clinical character, are identical as regards etiology. Very soon a second bomb of the same nature fell into the conservative camp, with the confident and even fervid declaration that child-bed fever is a septicaemia commonly due to a 49 THE INFLUENCE OF PASTEUR COCCUS in chains (streptococcus),* which could be detected in the cavity of the uterus, in the blood of the uterine sinuses, and in the blood of living patients. The far- reaching practical results of this investigation^ to which Pasteur devoted only one short publica- tion, are so well known to you that they call for no comment here. Not long after the beginning of the anthrax study the attention of Pasteur was directed to a dis- ease which was destined to play a remarkable part in leading to the great goal toward which the researches of the master were carrying him — the discovery that it is possible experimentally to * Pasteur's description of the organism found in puerperal septicaemia is not enough to make it cer- tain that he was dealing with pure cultures of the streptococcus pyogenes. 50 ON MEDICAL SCIENCE induce immunityto disease caused by virulent micro-organisms. Per- roncito of Turin and Toussaint of Toulouse had reached the con- clusion that an organism detected by the former is the cause of chicken cholera, but neither had the requisite bacteriological train- ing actually to establish the cor- rectness of this contention. Pas- teur was consulted on the sub- ject, and, bringing to bear his superior knowledge and technical skill, succeeded in growing the organism outside the animal body and in experimentally inducing chicken cholera by means of these cultures grown in vitro. Return- ing to the laboratory after a short absence, he found that his cultures of the bacilli of chicken cholera had failed to grow or had grown only feebly. To increase the ac- tivity of these micro-organisms, 51 THE INFLUENCE OF PASTEUR they were now inoculated into normal fowls — a procedure sug- gested by previous experiments with other bacteria. The results were disappointing, for the inoc- ulated animals showed no signs of the disease. This made it nec- essary to isolate and grow actively pathogenic bacteria from animals with chicken cholera. Having done this, it occurred to Pasteur that it would be of interest to inoculate with fresh and virulent bacilli the animals already treated with the attenuated strain of chicken cholera organisms. This was done without delay, and to his surprise nearly all of these prepared animals resisted the vir- ulent germs. They had been immunized by means of the at- tenuated cultures and a new prin- ciple had come into medicine. By experimental study and long re- 52 ON MEDICAL SCIENCE flection on the work of Jenner, the mind of Pasteur had been prepared to grasp the immense practical significance of this dis- covery. It appeared probable that what had been accomplished for chicken cholera could be extended to other diseases. One special consideration made Pasteur feel hopeful as to the possibility of immunizing sheep and cattle against anthrax. He had noticed that certain sheep long exposed to anthrax through grazing on in- fected pastures did not die after experimental inoculation with a virulent anthrax culture, whereas previously unexposed animals of the same herd died promptly after such inoculation. Moreover, he knew from experience that fowls can be immunized against chicken cholera by feeding them the spe- cific germs of that disease, and 53 THE INFLUENCE OF PASTEUR this fact strongly suggested a similar explanation for the anthrax immunity which he had noticed. With this analogy in mind, Pas- teur took the first step toward the preparation of a vaccine against anthrax. As in the case of chicken cholera, he strove to attenuate the specific organisms of the dis- ease. This he tried to do in the way that had succeeded so well in the case of chicken cholera — that is, by exposing anthrax cul- tures to an abundance of oxygen at the body temperatures. But Pasteur found that under these conditions the anthrax organisms retain their virulence, owing, he believed, to their capacity to pro- duce resistant spores. To check this growth of the anthrax spores he successfully resorted to the procedure of growing his cultures at a temperature of 42° — 43° C. 54 ON MEDICAL SCIENCE in the presence of oxygen. By varying the procedure somewhat he was able to prepare a series of anthrax vaccines of different de- grees of activity, the use of a mild vaccine being followed by that of a stronger one in the course of immunization. The announcement by Pasteur, Chamberland and Roux of a method of protecting animals against the anthrax scourge ex- cited great public interest, but was in many quarters received with skepticism and derision. Pasteur was invited to make a large-scale public test of his claims near Melun, at the farm of Pouilly- le-Fort. He accepted the chal- lenge gladly, and on May 5, 1881, began a series of public inocula- tions which will always be mem- orable in the annals of medical science. The publicity with which 55 THE INFLUENCE OF PASTEUR the unique experiment was per- formed, the unconcealed hostility and suspicion of many of the on- lookers, and the alternating hopes and fears of Pasteur, have been most entertainingly described by M. Vallery-Radot. The outcome was a convincing demonstration of the practicability of Pasteur's method of immunizing against anthrax in sheep. Nevertheless, two years later, in an ill-natured at- tack on Pasteur's work, Koch at- tributed the discovery of vaccina- tion against anthrax to Toussaint, and pointed to a paper in which the latter had reported some ex- periments describing the immuni- zation of dogs and sheep by means of anthrax bacilli which had been heated at 55° C. for ten minutes. While it is true that Toussaint thus immunized animals against virulent anthrax organisms, his 56 ON MEDICAL SCIENCE method of obtaining a vaccine was unreliable and unsuited for practical use. The fact is that Toussaint, stimulated by Pas- teur's discovery of a method for immunizing against chicken chol- era, prepared a vaccine which sometimes protected against the disease, but which was danger- ous, owing to uncertainty as to the number and condition of the living anthrax organisms which it contained. His publication ap- peared six months after that of Pasteur, who, although greatly interested in the observation of Toussaint, criticised the methods of the latter and ultimately pre- pared a safe vaccine consisting of definitely attenuated anthrax or- ganisms. The crude experiments of Toussaint were wholly based on the epoch-making immuniza- tion to chicken cholera. 57 THE INFLUENCE OF PASTEUR On March 15, 1882, Louis Thu- illier, the earnest and gifted but ill-fated young assistant of Pas- teur, discovered in the blood of swine dead of erysipelas (rouget de pore) an organism which ap- peared to be the active agent of this plague — an organism which Klein in his elaborate investiga- tion had quite overlooked, but which was independently discov- ered by Detmers of Chicago. Pas- teur had inspired this fine research of Thuillier and stood ready to develop it. By carrying the sus- pected organism through many generations on veal bouillon, and finally introducing it into hogs, the true swine erysipelas was readily induced. The real prob- lem, however, was to make an attenuated virus for the purpose of immunizing against the dis- ease. Pasteur succeeded in ob- 58 ON MEDICAL SCIENCE taining a virus capable of protect- ing certain races of hogs for a period of a year or more, and this important practical success is ren- dered especially noteworthy by the method that was followed in attenuating the rouget organisms. In 1887 he had found in the saliva of rabid dogs an organism highly virulent for rabbits (micrococcus of rabbit septicaemia).* Adult guinea pigs were immune, but >oung guinea pigs quickly died after inoculation. By passing the organism through a series of young guinea pigs it gained in virulence until it grew fatal for adult guinea pigs. But the modi- fication which especially im- pressed Pasteur was that the bac- teria which had thus gained in pathogenic qualities for guinea * Micrococcus lanceolatus. 59 THE INFLUENCE OF PASTEUR pigs had at the same time be- come attenuated for rabbits. The memory of this singular observation now came to his aid in the rouget research. After pass- ing the rouget bacteria through a series of pigeons (which are nat- urally susceptible), it was found that the blood from the last pig- eon had become much more path- ogenic for swine than blood from hogs dead of swine erysipelas. On the other hand, Pasteur dis- covered that while the passage of the rouget organisms through a series of rabbits (which are not naturally susceptible) permitted these bacteria to grow more read- ily in the blood of rabbits and to become more highly pathogenic for them, they became definitely and permanently diminished in virulence for swine. Thus, after inoculation with modified organ- 60 ON MEDICAL SCIENCE isms, hogs became ill, but did not die. On their recovery they were immune to fatal rouget. The genius of Pasteur thus gave to biological science a definite method of permanently modify- ing the pathogenic characters of certain micro-organisms. This contribution is recorded in a paper w^hich won the applause of the Academy of Medicine, and which even to-day excites admiration for its mingling of experimental skill and scientific imagination. So far back as 1880, in the midst of the exacting anthrax investi- gation, Pasteur had found time to begin a new research on the pro- tective action of attenuated virus. From modest beginnings this re- search grew in the hands of the master to be the crowning work of his life, in the sense of em- bodying the fullest and in some 61 THE INFLUENCE OF PASTEUR respects most original expression of his ideas on the use of experi- mentally enfeebled viruses for the mitigation of infectious processes. The transmission of rabies thro ugh bites made probable the infectious nature of the disease and encour- aged a hope that it would not be very difficult to isolate the specific organism from the saliva of rabid dogs. But the most systematic efforts to isolate such an agent were rewarded only by failure. To this disappointment was added a second, even more disconcert- ing. It was found that the ex- perimental transmission of the disease by means of saliva is a matter of great uncertainty. More- over, the uniformly fatal outcome of hydrophobia made it impossi- ble to form any opinion as to whether the unknown virus was capable of conferring immunity. 62 ON MEDICAL SCIENCE Many an investigator would have been deterred from the prosecu- tion of an enterprise so unprom- ising, but the interest of Pasteur had been fully enlisted before he realized the difficulties of the problem, and the tenacity of his nature urged him to keep pa- tiently on his course. He saw clearly that a reliable way must be found to communicate rabies experimentally, and acting on a suggestion made by Dr. Dubue of Pau, that the disease is essen- tially one of the central nervous system, Pasteur took small bits of nervous tissue from animals dead of rabies and placed them under the skin of experimental animals. This method was no considerable improvement on similar inoculations of saliva from rabid dogs, but it served as the clew to a notable advance. This 6) THE INFLUENCE OF PASTEUR was the introduction of rabic nerve-tissue directly into the cen- tral nervous system of the animal to be infected, a procedure based on the idea that since rabies be- haves like a disease of the nerv- ous system the micro-organisms causing it would be likely to find in the nervous system a living culture medium highly favorable to their growth. The acute in- telligence of the masterful experi- mentalist is strikingly illustrated by the fact that failure to isolate specific micro-organisms had not shaken his faith in the testworth- iness of his preconceived idea. Hence, when he found that hy- drophobia regularly followed sub- dural inoculation with rabic nerv- ous material, he was more pleased than surprised. The first dog thus inoculated showed unmistakable signs of rabies after fourteen days, 64 ON MEDICAL SCIENCE and other animals gave similar results. Moreover, on bringing into practice the experience he had gained in studying swine ery- sipelas, Pasteur found that he could increase the pathogenic properties of the virus by carry- ing it subdurally through a series of rabbits or reduce it for dogs by carrying it subdurally through a series of monkeys. He thus had at his command three different viruses — a virus of natural strength, a virus of increased virulence and an attenuated virus. Later experiments showed that a safer virus could be prepared by drying over caustic potash, at 21° C.,the spinal cords of rabbits dead of rabies. By injecting subcutaneously first a weak virus and subse- quently a stronger one into parts with very few nervous structures, 65 THE INFLUENCE OF PASTEUR Pasteur succeeded in immunizing dogs against otherwise fatal sub- dural inoculations. This success suggested the possibility of im- munizing human beings. The rel- atively long duration of the period of incubation, which is commonly about forty days, made the outlook for human immunization peculiar- ly promising. The opportunity for trying the method soon appeared in the person of the little Alsatian lad Joseph Meister, who came to Paris with fourteen wounds in- flicted by a rabid dog. Pasteur courageously resolved to make an effort to rescue the bitten child from the certain death to which he was doomed, by making suc- cessive injections of rabbit viruses of increasing strength. The result is known to all the world ; the ef- fort to utilize the long period of incubation quickly to establish im- 66 ON MEDICAL SCIENCE munity through repeated inocula- tions, proved a success, not only in the case of little Meister, but in many thousand other instances. The great research on rabies fit- tingly marks the culmination of Pasteur's long career as an inves- tigator. In that investigation can be seen the same technical skill, the same respect for minute detail, and the same pertinacity that had distinguished so many earlier re- searches, but there can be seen also a degree of originality and a fertility of resource that excel nearly all previous exhibitions of these powers. The accumulated experience of a quarter century of original study of micro-organic life served as liquid intellectual capital on which Pasteur drew for guidance at every turn in the ex- traordinarily intricate and perplex- ing study of rabies. And it seems 67 THE INFLUENCE OF PASTEUR wholly clear that this new discov- ery could never have been made without such a treasure of experi- mental experience. One who looks only at the re- sults of Pasteur's far-reaching work is apt to overlook his mis- takes and shortcomings, and to forget that he made some serious errors not only in the interpreta- tion of experimental data, but sometimes also in experimental technic. To pathologists of the present day Pasteur's conception of acquired immunity appears so crude that it is difficult to believe he ever entertained it seriously. His work on chicken cholera na- turally led him to form a theory to account for the immunization which he observed, and this the- ory was that immunity arises from the inability of a pathogenic or- ganism to grow in a medium in 68 ON MEDICAL SCIENCE which it has previously devel- oped. Animals thus become im- mune because the necessary nu- trient material for the multiplica- tion of the specific organisms has been used up, just as an organism w^ill after a time cease to grow in vitro in an old culture medium. it seems strange that he did not test this theory by trying to grow the organisms outside the body in the blood and serum of both the immunized and normal animals, and so learn that he was in error. The short and usually inadequate descriptions of micro-organisms which Pasteur has given in his terse publications have aroused much criticism from bacteriolo- gists, and it cannot be denied that he underrated the importance of minute morphological andcultural studies — studies without which some of the most important mod- 69 THE INFLUENCE OF PASTEUR ern advances could not have been made. Nor is it easy to explain the reluctance with which he adopted the improved bacteriological tech- nique of other investigators. Koch's method of plating bac- teria, Weigert's and Ehrlich's methods of staining and certain important nutrient media found their way into his laboratory only after long delay, and through the efforts of assistants. Pasteur's comparatively faulty technique for obtaining pure cultures of bac- teria is doubtless responsible for many of the disheartening results reported by foreign observers who used his vaccines. Nevertheless his methods in the main served their purpose well, and we should remember that the most finished instruments cannot belong to the pioneer who makes his own tools. Fortunately Pasteur was greatly 70 ON MEDICAL SCIENCE favored by the circumstance that in many of his etiological studies he made cultures from the blood, where the specific micro-organ- isms often existed in pure cul- ture. Although even the plainest nar- rative of Pasteur's individual achievements is proof enough that his work holds a unique position in the history of biological sci- ence, it is worth while to consider in more general terms what it was that the consummate experiment- alist added to the science of med- icine. Such a consideration gives us a more just measure of his in- fluence than the most detailed re- cital of specific investigations. If we would understand the influ- ence of Pasteur on medical science we must recognize that his exam- ple as the apostle of an almost un- tried method of approaching the 71 THE INFLUENCE OF PASTEUR problems of medicine has been no less enlightening than his actual discoveries. Emerson has said : '' Great men exist that there may be greater men." The recent his- tory of medicine in the United States as well as in Europe, plainly shows that the seed of example sown by Pasteur has already fal- len on receptive soil, from which have sprung new combinations of human faculties powerful for the amelioration of human life. Our country has no greater cause for satisfaction than the knowledge that the ideality as well as the methods of Pasteur, has inspired a growing circle of original inves- tigators in medical science who labor for the common welfare. Let us hope that this circle will be continually widened, in the future as in the past, by accessions from the students of this University, 72 ON MEDICAL SCIENCE where the best idealsof work have been so richly nurtured. Perhaps the most deeply signif- icant feature of Pasteur's contri- butions to medicine is their direct dependence on the principles of physics and chemistry, the scien- ces that so often lie at the heart ofreal advances in biology. Med- ical men trained alongthe conven- tional semi-scholastic lines had often dabbled with these funda- mental sciences, and sometimes the superficial contact had yielded creditable or even important re- sults. In many instances, also, truly great advances had come from the labors of men who like Malpighi, Bichat and Johannes Miiller were wide awake to the fact that sound medicine must rest on sound biological conceptions. But despite the activity of nu- merous gifted medical men of 73 THE INFLUENCE OF PASTEUR broad scientific sympathies, the medical profession at the begin- ning of Pasteur's career was dully followinga well trodden but nearly blind road, in the hopeless strug- gle to solve the intricate problems of human pathology and physiol- ogy by minute observations and experiments confined largely to the most complex representatives of animal life. Then for the first time there appeared in the biolog- ical sciences a man profoundly trained in the methods of chem- istry and physics, and inspired, moreover, with a firm confidence in the applicability of these sci- ences to the solution of biological and medical problems. Triply armed with a sound method, a lofty imagination, and a strong will to serve his country, Louis Pasteur entered the wide arena of medical research, to win there the 74 ON MEDICAL SCIENCE triumphs that have reconstituted medicine, and have secured him an undying fame. Step by step, with rigid logic and unfaltering determination, he passed from the early crystallographic discoveries to the new conception of fermen- tation, and from this to the crucial discoveries relative to etiology and immunity for which the med- ical sciences had waited so long. To have fought the long battle of life with unwavering constancy to the loftiest ideals of conduct, toiling incessantly without a thought of selfish gain ; to have remained unspoiled by success and unembittered by opposition and adversity ; to have won from nature some of her most precious and covert secrets, turning them to use for the mitigation of human suffering :— these are proofs of rare qualities of heart and mind. 75 THE INFLUENCE OF PASTEUR Such full success in life did Louis Pasteur attain, and from the con- sciousness of good achieved, his noble nature found full reward for all his labor. Of the children whom fortune has endowed with splendid gifts, there are few whose lives have affected so profoundly and so be- neficently the fate of their fel- lows, few who have earned in equal degree the gratitude and reverence of all civilized men. Al- though not many can hope to en- rich science with new principles, all of us may gain from Pasteur's life the inspiration to cultivate the best that is in us. Let us keep living in our memories the inspir- iting words which the master spoke on the seventieth anniver- sary of his birthday: ''Young men, young men, devote your- selves to those sure and powerful 76 ON MEDICAL SCIENCE methods, of which we as yet know only the first secrets. And I say to all of you whatever may be your career, never permit your- selves to be overcome by degrad- ing and unfruitful scepticism. Neither permit the hours of sad- ness which come upon a nation to discourage you. Live in the se- rene peace of your laboratories and your libraries. First ask your- selves, what have I done for my education ? Then as you advance in life, what have I done for my country ? So that some day that supreme happiness may come to you, the consciousness of having contributed in some manner to the progress and welfare of hu- manity. But, whether our efforts in life meet with success or failure, let us be able to say when we near the great goal, ' I have done what I could.' " 77 E DATE 1992 NCV2 5199l> Printed in USA COLUMBIA UNIVERSITY LIBRARIES 0037525271 .y^d