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Fritz Pregl: The work and personality of a nobel laureate
YOLo VI, PAGES 5-16 (1962)
MICROCHEMICAL JOURNAL
Fritz Pregl The Work and Personality of a Nobel Laureate
The late Professor Dr. E. Philippi had been invited to address the Vereinignng del' N oiurunssenschaftler uiul M ediziner of l nnshruck, Tyrol, on occasion of the commemoration of Pregl's death. The reminisr-ences are of specia! interest since he was associated with Pregl for twenty-four years. Dr. Philippi considered the -peech to be a farewell tribute to his teacher and friend to whom he will be indebted forever for guidance and inspiration.
Fritz Pregl, born September 3, 18G9, came from what may be designated as approximately the lower middle class. He was the only son of a railroad official of middle rank, * who was stationed in Laibach, today called Lublijana, Yugoslavia. The name Pregl is of Slavic origin and means pickax or mattock. Since he retained through his life a slightly nasal accent, I [the speaker] asked him once whether he was of Slavic descent. HiR answer was definitely negative, and he told me that his family came from the surroundings of Nurnberg, Bavaria. He always considered himself of German nationality and, as we shall see, felt and acted as a patriotic Austrian. When his father died, Pregl had just finished Gymnasium. He inherited 7000 Austrian florins, about $;'~400, while his mother received a modest pension. The young Pregl considered the above-enumerated fortune ample for the completion of advanced studies. He went to Graz and enrolled in the medical school of the University. The subjects which mainly attracted him turned out to be physiology and chemistry, and Alexander Rollet, the physiologist, provided him with an assistantship in his Institute. There Pregl carried out his first scientific investigations together with the slightly older Oskar Zoth, with whom he kept a dose friendship to the end of his life. The investigation dealt with the active ingredients of gland (e.g., testes) extracts, i.e., with hormones, the action of which they studied on themselves with the use of an ergograph. *According to Hans Lieb [Mikrochemie, 35, 128(1950)], the father was an official of a 'savings bank. (Translator) 5
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After a few years Pregl exchanged this position for an assistantship with Professor Hofmann at the Institute for Medical Chemistry of the University in Graz. Thus, at the turn of the century, he was one of the many assistants one meets in university laboratories. Industrious application to work and several publications had gotten him the venia legendi, the privilege of lecturing to students, but nothing indicated the mark of greatness which the future held in store for him. Quite gradually, however, two facets of his personality emerged, which were characteristic of him and contributed decisively to his success. He showed a quite unusual liking and ability for exacting experimental work, and he developed an urge to escape from the narrow confines of daily routine and to see the famous masters at work. Slowly, he arrived at the somewhat painful decision to forget his dignity as Privatdozent and, at the age of 34 years, go as a student and apprentice for two or three semesters to Germany. He took a leave of absence; whether he received a stipend is not known. The first star that attracted him was Wilhelm Ostwald in Leipzig. It seems, however, that physical chemistry did not appeal to him, for soon he moved on, as Pregl himself said, "to learn from the old master Hufner something real: photometry and optical methods." This, too, however, did not hold him for long. He was attracted by organic chemistry with ramifications into physiology. It was just the time when Emil Fischer in Berlin had brought to culmination his classical investigations on the proteins. He had, at that period, the cooperation of a large group of very gifted students, among whom Abderhalden-a few years younger than Pregl-had one of the leading roles and later became spiritual heir and successor of the great investigator. It was the time of the protein hydrolyses and the syntheses of polypeptides which brought Emil Fischer the Nobel award. This research community attracted Pregl, but it was not easy for an unknown man-a description which still fitted him at that stage-to be admitted among the close associates of the master. Pregl frequently recalled that time. The great chief contemplated with obvious suspicion the no longer quite young Pregl who wanted a research task assigned to him. He would have to see first that a new student have the ability to perform a neat and decent job before he could assign him a problem. He would have to make a few substances which are described in the literature. In Pregl's own words, "As a suspicious Austrian, I received a regular MICROCHEMICAL JOURNAL, YOLo YI, ISSUE 1
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student's locker in the organic laboratory and the order to prepare four substances. First, I cleaned the place, put the reagents and solvents in good order, and got the apparatus ready for work. It cost me considerable trouble and time to purchase the various types of flasks and connectors for vacuum distillation so that they all would take the same size of stopper. I also collected glass tubing and condensers of uniform width and selected corks and rubber stoppers of the very best quality. On the fourth day, I was finally so far that I could start. Emil Fischer, who visited the laboratory every day, had always watched me only from a distance. Probably he also thought me lazy since I was frequently absent because of the many errands. On this fourth day, he finally asked me whether I had a substance prepared and ready. 'Not yet, but tomorrow I shall start,' was the answer which probably just confirmed his unfavorable estimate. Four more days later, I had excellent yields of the substances neatly assembled and ready for delivery to the severe master. Fischer came, saw, and assigned me a work space next to Abderhalden in the laboratory for the 'select few.' " Two publications remain as lasting evidence of Pregl's stay in Berlin. He also won the friendship of Emil Fischer. After his return to Graz, Pregl spent a few quiet years with teaching, the care of Hofmann's institute, and an exacting experimental study of the bile acids and the cholesterin. When I met Pregl in 1906, he had the title of Professor Extraordinary and lectured on physiological chemistry with gusto and much devotion. After the lecture and during evenings in the coffeehouse, he liked to elaborate on his lectures for the benefit of interested students among whom I found myself at the age of eighteen. His experimental work was carefully reasoned and performed with superior skill, but reaching a successful conclusion would have required the cooperation of a large number of able research workers, something that was out of question. The desire to save time and energy led Progl to design an automatic combustion furnace which used a clockwork to move the burner at three different speeds, depending on the behavior of the substance. The innovation did save time and was approved and adopted by Skraup, Emil Fischer, and other leading organic chemists, but for obvious reasons it was not a satisfactory solution of the problem. At that time, Pregl received a call to the Veterinary University of Berlin as successor to Abderhalden who was transferring his activity to
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Halle. This, as all other important events, was discussed by Pregl with his young "friends" in the coffeehouse since, "only the company of youth keeps one young and prevents premature ossification." The Prussian Ministry of Education offered him an assured income of R.M. 12000.00 per annum, which was several times the amount he received in Graz and appeared most acceptable to me. Pregl, however, was less materialistic and declined, for-as he put it-"he did not want to become an administrative tool but rather preferred to remain a poor devil and pursue scientific work." A kind fate allowed it that just at that period Section Chief Kelle of the Ministry of Education, who later used to claim to have been the first to "discover" Pregl, had been placed in charge of Personnel. He made the decision easier for Pregl by creating for him the position of a professor extraordinary. Thus, in 1909, Pregl, at the age of forty, functioned as a young Extraordinarius at the side of the aging Hofmann in an institute of medium size, and probably did most of the administrative work. For scientific accomplishments, he had little to show: a few early publications in the field of physiology, the two papers of the time in Berlin, and about a dozen publications on the bile acids. The latter were purely experimental studies free from unwarranted speculation. In addition, he held no monopoly concerning the bile acids. They were being studied by several other investigators, among them Professor Furth and a very young but promising chemist, Windaus. Counting everything, Pregl did not occupy a glamorous position, nor had he accomplished anything unusual. Only those people closest to him recognized in Pregl something more than just an average Dozeni: they noticed his quite unusual enthusiasm for his calling and his undeviating desire to improve his skill and technical ability toward perfection. His mind did not work like that of an Extraordinarius at 40; Pregl acted more like a student. At times when work in the laboratory became inefficient with all help on vacation, the Herr Professor decided that it would be more profitable to work as an apprentice with some good craftsman. He went out and worked with a locksmith, a glass blower, a fine mechanic, and a carpenter. He spent days at the lathe and at the carpenter's bench; he learned how to bind books; and he demonstrated an absorbing interest in every kind of skill. It remained his hobby through life to find ways for performing any kind of task to perfection. His students also were trained along these lines. Like a good nurse in kindergarten, he never got tired MICROCHEMICAL JOURNAL, VOL. VI, ISSUE 1
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Pregl's railroad passport of 1913; photograph was taken in 1910.
explaining, during the day in the laboratory and at night in the coffeehouse, how to hold a test tube, how to filter, how to remove the mother liquor and to dry, how to use the Buchner funnel, how to stir, how to shave properly, how to make mayonnaise and vinegar, how to eat a lobster, how to treat cigarets properly and how to make them; in general, how to use the intellect in performing any task so as to get the very best results in the most elegant manner. The year 1910 brought two events whieh proved important for Pregl. His work on the bile acids came to a point where continuation became simply impossible. The poor yields of degradation products left two ways for a fresh attempt: either he could try a new start with ten to one hundred times more material, or he would have to refine the analytical methods to become applicable to ten to one hundred times smaller samples. HI' chose the latter alternative and began the preliminary trials which subsequently lead to his oustanding work on the micro analysis of organic substances. At the same time, fate caught up with him. He was called to head the Institute for Medical Chemistry at Innsbruck, a position which had become vacant after Lobisch. Also about this phase of his life, later I was repeatedly, and
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in detail, informed by Pregl himself. Th e posit ion in Inn sbru ck carried with it the ran k of an Ordinarius, which he could not afford t o decline. Consequently, he accepted but asked Section Chief Kelle for permission to see the I nstitu te in person so t hat he would be able to formu late his wishes concern ing changes and repairs since it was known to him (Pregl) t hat the insti tu te was in every aspect in a desolate condition. T he local evidence by far surpassed Pregl's worst expectations. The night afte r his return from In nsbru ck to Vienna, for t he conclusion of t he discussion with t he Ministry of Educati on, he spent with his friend Abderhalden, on a bench in t he little park in front of t he Votivkirche. He repeatedly showed me that bench with th e words,"Here I was sitting, and I carried on like a baby and kept saying : 'No, I cannot do it, I cannot stick it out in that rundown hovel, I cannot work th ere, I would go to pieces. I shall decline tomorrow and rather remain assistant and E xtraordinarius in an In stitu te where I am able to work." The next day, Abderhalden accompa nied him to the door of Section Chief Kelle's office and forcefully impressed on him not to commit a stupid act. Thus it happ ened that Pregl appeared in t he fall of 1910 in Inn sbru ck, sta rted to reorganize his Insti tu t e, and began with t he development of the micro analysis of organic substances, which is one chapte r in the history of chemistry to which t he Austrians will always point wit h prid e. There is no intention of lecturing on Pregl's meth ods of micro ana lysis. It must suffice to point out some of the main features, their meaning, and how they came about. Above all, the micrometh ods are not mere miniature copies of the analytical procedures of Liebig and Dumas. Before t he scale of work could be reduced, it was necessary to establish a secure basis for t he accurate weighing and measuring of small amounts of mat erial. The starting point was th e balance which Dr., h.c., Kuhlmann t ried to improve, on the insistence of Pregl. Then arrived th e main difficulty of the carbon and hydrogen determination, the constancy of weight of the ab sorpti on tubes. Even the first apparatus was given t he shape of pencils, but a 50% solution of potassium hydroxide on glass wool still served as th e absorbent. It was difficult to wash t he ti p of t his apparatus. Later, Pregl added bulbs and capillaries to assure constancy of weight . The final shape of his absorption tubes came into being as follows. The summer had MI CR OCH E MI CAL JO UR NAL, VOL. VI , I SSUE 1
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been unusually hot , which is liable to upset combust ion analyses as any experienced micro analyst would expect. The absorption tubes did not want to remain constant in weight, and it was necessary to time th e work painstakingly to get correct results. Pr egl felt played out, and decided on one of those quick t rips around I taly which he enjoyed. As usual, the time of return was left indefinite. After a few days, however, he was back ; an idea had come to him in Trieste. Withou t wasting a word or taking off his straw hat , he just shoved it far back on his head, he stepped up to the glass blowing ta ble, made th e first absorption tub e of th e familiar shape, filled it , and gave it to his assistant with the words, "Weigh it in half an hour and then again after two hours. I am going out to eat and to have black coffee." When he returned after two and one-half hours, the weight of th e apparatus had remained nearly constant. In the evening of th e same day, again at peace with himself, he boarded th e train for Trieste to resume his trip. One by one, the many other difficulties were overcome: the tube filling, the mercury gasometer, the rubber tubing, and the lead dioxide. Whoever want s to be informed about th is chapter or want s to know how many little devils are hidden in every cubic centimeter of t he apparatus for microcombustion is invited to read t he account of our colleague Lindner on th e causes of error. It happened in the fall of Hl11 that Pregl faced for t he first t ime a large audience with a report on his new method s. Th is happ ened in Berlin, and his assista nt Max De Crinis, now professor of neurology in Graz, demonstrated t he determination of carbon and hydrogen during the one-hour lecture. Up to that time, a carbon and hydrogen determina tion had required at least three hours. In December 1911, Pregl came for two weeks as guest to the Second Chemical Institute of th e University of Vienna to introduce his methods in the laboratory of Professor Goldschmied. I had been assigned for his personal adjutant, and I recall vividly how it all started. Pr egl appeared at 9 o' clock on th e dot; at 10 o'clock, th e balance and apparatus had been unp acked and stood ready for use. My chief, Professor Goldschmied, had told me to give Pregl for the demonst rat ion a very nasty substance which he probabl y had never tri ed before. In compliance with orders, I selected 2-met hyl-3-brompropanal. Pregl introduced a weighed sample into the combustion tube and moved the burn er into the proper position for a sta rt. There
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was a mild flash and the whole tube was filled with soot, tar, and bromine vapor. Pregl gave me a brief look which I shall never forget and then turned pleasantly to Goldschmied : "Your assistant has done a very good job; I am pleased to be able to show you how one gets the better of such substances." At 11 o'clock, the tube was clean again and a new determination was proceeding; and at 12 o'clock, we were able to convince ourselves that the carbon content was correct within 0.02%. "You acted like a dirty rat, but at least your subsubstance was pure," was Pregl's approving comment in my direction. On the 9th of January, 1912, Pregl demonstrated his methods in Vienna before the Chemisch physikalische Gesellschaft. On that occasion, I had the honor of demonstrating the carbon and hydrogen determination and could approach the theory within 0.06 and 0.07%, respectively. The final victory, however, was won during the meeting of the Vereinigung deutscher Naiurjorecher und Aerzte in 1913 and also in Vienna. Pregllectured, Lieb performed the molecular weight determination, Breygant did the nitrogen, and I determined carbon and hydrogen. Everything went fine. After the lecture, Emil Fischer, who presided, came over to me and asked permission to check the weight of the carbon dioxide absorber. After he had done it, he offered me his hand and said, "Now I believe it." This was one of the most beautiful moments of my life. We all felt, "Now we have done it." As a fact, from that day on the micromethods began to replace the customary procedures of combustion analysis. The advantages of Pregl's micromethods are economy: destruction of only small amounts of valuable research substance, economy of time, and economy of effort. Just one example may suffice. Talking in Konigsberg with Nobel laureate Hans Fischer, I raised the question whether he could have concluded his investigations on hemin without the help of the Pregl methods. After brief consideration, he said, "I believe yes, but it would have taken me two or three years longer." One has to fully contemplate what two to three years mean in the instance of Hans Fischer with his 25 assistants and coworkers. Finally, Fischer directs only one of the many research centers which are aided by organic micro analysis. In 1913, organic elementary analysis had been brought to a state of tentative perfection when Pregl returned to Graz as successor to his teacher Hofmann. His Organic Quantitative Micro Analysis was not yet published, but he was already a well-known man. He received the Lieben prize, and his Institute had visitors from all parts of the MICROCHEMICAL JOURNAL, VOL. VI, ISSUE 1
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Fritz Pregl in his microchemical laboratory, around 1920.
globe since it had gotten around that the impossible was practiced in Graz: analyses with a few milligrams in one-fourth of the usual time. When I visited him at Easter in 1914, I met in his laboratory Dr. Schroder from Heidelberg, Yllner from Stockholm, Sernagiotto from Bologna, Cornubert from the Sorbonne, and an Englishman whose name has escaped my memory; truly an international company. In 1912 he had given in to his students and written a brief account of his methods for Abderhalden's IIandbuch der biochemischen Arbeiismethoden, He did not like to break into print prematurely and later once berated me for having helped to talk him into it. At the close of 1916 his well-known book appeared, which had one edition after another. During the First World War Pregl did his utmost to keep research and teaching alive. In 1917, he became Dean of the Medical School and, as such, he became involved with the development of agencies for the students' welfare. The ministry of defense sent him to Berlin to take part in the study of gas warfare; he performed experiments concerning the lethal quantities, tested gas masks, and developed a palladium test paper for the detection of carbon monoxide. After the war, in 1921, he was elected Rector of the university and again hc was able to contribute significantly to development of welfare institutions. During these years, he developed the solutio Pregl,
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Vacationing on the Island of Lussin in the Adriatic.
which in analogy to Dakin solution contains hypoiodite as the active agent. It is a powerful antiseptic whIch may be intravenously injected in large quantities. He kept the preparation and the composition a secret. The Riesswerke, who belong to the Hospital of the Province Styria, became the sole manufacturers. This gave him the assurance that any profits would benefit his homeland. Pregl's scientific contributions of that time can only be estimated by those who were close to him. He published relatively little, but he was very active. He just happened to be the "Pregl," the handy consultant for his faculty and for practically anybody who asked for his advice. Visitors came and went, and the telephone rang about fifty times a day. The Dental Clinic was on the wire; they were trying something new with the solutio Pregl. Neurology needed advice; they were trying Abderhalden's ninhydrin test for pregnancy. The surgeon Haberer was developing a diagnosis of kidney ailments by means of chemical tests. Also Gynecology and Pharmacology would consult with him, and frequent interchanges with the medical examiner were a necessity since Pregl was the County Toxicologist, a duty which went with his position as head of the Institute of Medical Chemistry. Pregl was also quite busy outside of his strictly scientific activity. MICROCHEMICAL JOURNAL, YOLo YI, ISSUE 1
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Clipping from an Austrian (? ) newspaper , 1929. Th e caption read : "T he Austrian Nobel prizewinner University Professor Dr. Friedri ch Pregl has been made a ll Honorary Cit izen of t he City of Graz, capital of Styria, on th e occasion of his sixt ieth birthday." Taken in front of th e Medical Chemical Insti tute.
He tried his best in t he interest of ju stice to promote able and promi sing people. In thi s respect he did not want to compromise, and he could be tough and was not swayed by app eals for sympathy. How much good he has done along th ese lines is unknown even to his closest. associates, but an example may be given. When he left Innsbru ck, he had to fight a pit ched battle to get for his s..icccssor the young Windau s, who was his most dangerous competitor in th e field of th e bile acids. Wagging ton gues would have it that Pregl did it to please his own vanity. The indispu table fact s arc th at Windau s was awarded the Nobel prize in 1928 and that Windaus' successor Hans Fischer was given th e same recognition in 1930. What ever Pregl's motive may have been, we Innsbruckers owe it to him that three Nobel laureates worked ill succession at the Medical Chemical Institute of our University. In his private life, Pr egl was very simple. He never was married , and his personal desires wore modest. When he celebrated his 60th birthday by taking th e driver 's test, he permitted himself t he luxury of acquiring a Stcyr automobile, :I produ ct of Austrian industry. Right after that, however, he placed 20000.00s. at the disposal of th e
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Academy of Sciences in Vienna. The interest was to provide annually a cash prize for the best work in microchemistry performed in Austria or done by an Austrian. Much time and possibly some money he gave to his adopted child, the journal Mikrochemie, at that time published by Emil Haim in Vienna. Some of his apparent generosity resulted from the clear understanding that money may be well spent if it frees of petty worries. Once I was present at the inventory taking which showed a deficit of 8000.00s. "What are you going to do?" I asked him.-"What I am going to do? I shall chip in, that's what I am going to do. It's better to have one bloodletting than bother the whole year with petty saving." When his Institute was going to be enlarged, he offered to the Ministry of Education to contribute one half of the expenses. What finally happened, I do not know. Many a token of esteem was paid to him, but he also received some slights. He took both in his stride. He was still young when he was given the title of H ofrat, the honorary degree of a doctor of philosophy of the University G6ttingen, the Nobel prize, the dignity of an honorary citizen of City of Graz, and finally the large medal for meritorious service to the Republic. The Academy of Sciences in Vienna elected him a corresponding member, and he had three separate invitations for a transfer to Vienna, all of which he declined. Pregl was never active in the political field, for party interests were alien to his innermost nature. He just strove, by consistent effort, to increase the reputation and the well-being of his people and his country. Apparently this was not well received by his contemporaries. During his opening address in Innsbruck, there was a demonstration by the Catholic students; the liberal faction made a disturbance at the torch parade of the whole student body celebrating his Nobel award; and the socialist representatives of the City Council were conspicuous by their absence from his funeral in spite of the fact that it was an honorary citizen being conveyed to his last resting place. The translator was acquainted with Fritz Pregl for nine years, 1920-29. The translation is frequently far from literal but, it is hoped, correct in the idea and mood to be conveyed. The whole flavor of intimacy could not be preserved when turning to a far larger audience, and the lapse of time has suggested some minor changes to accommodate the change in perspective.
A. A. Benedetti-Pichler MICROCHEMICAL JOURNAL, VOL. VI, ISSUE 1
MICROCHEMICAL JOURNAL
Fritz Pregl The Work and Personality of a Nobel Laureate
The late Professor Dr. E. Philippi had been invited to address the Vereinignng del' N oiurunssenschaftler uiul M ediziner of l nnshruck, Tyrol, on occasion of the commemoration of Pregl's death. The reminisr-ences are of specia! interest since he was associated with Pregl for twenty-four years. Dr. Philippi considered the -peech to be a farewell tribute to his teacher and friend to whom he will be indebted forever for guidance and inspiration.
Fritz Pregl, born September 3, 18G9, came from what may be designated as approximately the lower middle class. He was the only son of a railroad official of middle rank, * who was stationed in Laibach, today called Lublijana, Yugoslavia. The name Pregl is of Slavic origin and means pickax or mattock. Since he retained through his life a slightly nasal accent, I [the speaker] asked him once whether he was of Slavic descent. HiR answer was definitely negative, and he told me that his family came from the surroundings of Nurnberg, Bavaria. He always considered himself of German nationality and, as we shall see, felt and acted as a patriotic Austrian. When his father died, Pregl had just finished Gymnasium. He inherited 7000 Austrian florins, about $;'~400, while his mother received a modest pension. The young Pregl considered the above-enumerated fortune ample for the completion of advanced studies. He went to Graz and enrolled in the medical school of the University. The subjects which mainly attracted him turned out to be physiology and chemistry, and Alexander Rollet, the physiologist, provided him with an assistantship in his Institute. There Pregl carried out his first scientific investigations together with the slightly older Oskar Zoth, with whom he kept a dose friendship to the end of his life. The investigation dealt with the active ingredients of gland (e.g., testes) extracts, i.e., with hormones, the action of which they studied on themselves with the use of an ergograph. *According to Hans Lieb [Mikrochemie, 35, 128(1950)], the father was an official of a 'savings bank. (Translator) 5
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After a few years Pregl exchanged this position for an assistantship with Professor Hofmann at the Institute for Medical Chemistry of the University in Graz. Thus, at the turn of the century, he was one of the many assistants one meets in university laboratories. Industrious application to work and several publications had gotten him the venia legendi, the privilege of lecturing to students, but nothing indicated the mark of greatness which the future held in store for him. Quite gradually, however, two facets of his personality emerged, which were characteristic of him and contributed decisively to his success. He showed a quite unusual liking and ability for exacting experimental work, and he developed an urge to escape from the narrow confines of daily routine and to see the famous masters at work. Slowly, he arrived at the somewhat painful decision to forget his dignity as Privatdozent and, at the age of 34 years, go as a student and apprentice for two or three semesters to Germany. He took a leave of absence; whether he received a stipend is not known. The first star that attracted him was Wilhelm Ostwald in Leipzig. It seems, however, that physical chemistry did not appeal to him, for soon he moved on, as Pregl himself said, "to learn from the old master Hufner something real: photometry and optical methods." This, too, however, did not hold him for long. He was attracted by organic chemistry with ramifications into physiology. It was just the time when Emil Fischer in Berlin had brought to culmination his classical investigations on the proteins. He had, at that period, the cooperation of a large group of very gifted students, among whom Abderhalden-a few years younger than Pregl-had one of the leading roles and later became spiritual heir and successor of the great investigator. It was the time of the protein hydrolyses and the syntheses of polypeptides which brought Emil Fischer the Nobel award. This research community attracted Pregl, but it was not easy for an unknown man-a description which still fitted him at that stage-to be admitted among the close associates of the master. Pregl frequently recalled that time. The great chief contemplated with obvious suspicion the no longer quite young Pregl who wanted a research task assigned to him. He would have to see first that a new student have the ability to perform a neat and decent job before he could assign him a problem. He would have to make a few substances which are described in the literature. In Pregl's own words, "As a suspicious Austrian, I received a regular MICROCHEMICAL JOURNAL, YOLo YI, ISSUE 1
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student's locker in the organic laboratory and the order to prepare four substances. First, I cleaned the place, put the reagents and solvents in good order, and got the apparatus ready for work. It cost me considerable trouble and time to purchase the various types of flasks and connectors for vacuum distillation so that they all would take the same size of stopper. I also collected glass tubing and condensers of uniform width and selected corks and rubber stoppers of the very best quality. On the fourth day, I was finally so far that I could start. Emil Fischer, who visited the laboratory every day, had always watched me only from a distance. Probably he also thought me lazy since I was frequently absent because of the many errands. On this fourth day, he finally asked me whether I had a substance prepared and ready. 'Not yet, but tomorrow I shall start,' was the answer which probably just confirmed his unfavorable estimate. Four more days later, I had excellent yields of the substances neatly assembled and ready for delivery to the severe master. Fischer came, saw, and assigned me a work space next to Abderhalden in the laboratory for the 'select few.' " Two publications remain as lasting evidence of Pregl's stay in Berlin. He also won the friendship of Emil Fischer. After his return to Graz, Pregl spent a few quiet years with teaching, the care of Hofmann's institute, and an exacting experimental study of the bile acids and the cholesterin. When I met Pregl in 1906, he had the title of Professor Extraordinary and lectured on physiological chemistry with gusto and much devotion. After the lecture and during evenings in the coffeehouse, he liked to elaborate on his lectures for the benefit of interested students among whom I found myself at the age of eighteen. His experimental work was carefully reasoned and performed with superior skill, but reaching a successful conclusion would have required the cooperation of a large number of able research workers, something that was out of question. The desire to save time and energy led Progl to design an automatic combustion furnace which used a clockwork to move the burner at three different speeds, depending on the behavior of the substance. The innovation did save time and was approved and adopted by Skraup, Emil Fischer, and other leading organic chemists, but for obvious reasons it was not a satisfactory solution of the problem. At that time, Pregl received a call to the Veterinary University of Berlin as successor to Abderhalden who was transferring his activity to
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Halle. This, as all other important events, was discussed by Pregl with his young "friends" in the coffeehouse since, "only the company of youth keeps one young and prevents premature ossification." The Prussian Ministry of Education offered him an assured income of R.M. 12000.00 per annum, which was several times the amount he received in Graz and appeared most acceptable to me. Pregl, however, was less materialistic and declined, for-as he put it-"he did not want to become an administrative tool but rather preferred to remain a poor devil and pursue scientific work." A kind fate allowed it that just at that period Section Chief Kelle of the Ministry of Education, who later used to claim to have been the first to "discover" Pregl, had been placed in charge of Personnel. He made the decision easier for Pregl by creating for him the position of a professor extraordinary. Thus, in 1909, Pregl, at the age of forty, functioned as a young Extraordinarius at the side of the aging Hofmann in an institute of medium size, and probably did most of the administrative work. For scientific accomplishments, he had little to show: a few early publications in the field of physiology, the two papers of the time in Berlin, and about a dozen publications on the bile acids. The latter were purely experimental studies free from unwarranted speculation. In addition, he held no monopoly concerning the bile acids. They were being studied by several other investigators, among them Professor Furth and a very young but promising chemist, Windaus. Counting everything, Pregl did not occupy a glamorous position, nor had he accomplished anything unusual. Only those people closest to him recognized in Pregl something more than just an average Dozeni: they noticed his quite unusual enthusiasm for his calling and his undeviating desire to improve his skill and technical ability toward perfection. His mind did not work like that of an Extraordinarius at 40; Pregl acted more like a student. At times when work in the laboratory became inefficient with all help on vacation, the Herr Professor decided that it would be more profitable to work as an apprentice with some good craftsman. He went out and worked with a locksmith, a glass blower, a fine mechanic, and a carpenter. He spent days at the lathe and at the carpenter's bench; he learned how to bind books; and he demonstrated an absorbing interest in every kind of skill. It remained his hobby through life to find ways for performing any kind of task to perfection. His students also were trained along these lines. Like a good nurse in kindergarten, he never got tired MICROCHEMICAL JOURNAL, VOL. VI, ISSUE 1
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Pregl's railroad passport of 1913; photograph was taken in 1910.
explaining, during the day in the laboratory and at night in the coffeehouse, how to hold a test tube, how to filter, how to remove the mother liquor and to dry, how to use the Buchner funnel, how to stir, how to shave properly, how to make mayonnaise and vinegar, how to eat a lobster, how to treat cigarets properly and how to make them; in general, how to use the intellect in performing any task so as to get the very best results in the most elegant manner. The year 1910 brought two events whieh proved important for Pregl. His work on the bile acids came to a point where continuation became simply impossible. The poor yields of degradation products left two ways for a fresh attempt: either he could try a new start with ten to one hundred times more material, or he would have to refine the analytical methods to become applicable to ten to one hundred times smaller samples. HI' chose the latter alternative and began the preliminary trials which subsequently lead to his oustanding work on the micro analysis of organic substances. At the same time, fate caught up with him. He was called to head the Institute for Medical Chemistry at Innsbruck, a position which had become vacant after Lobisch. Also about this phase of his life, later I was repeatedly, and
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in detail, informed by Pregl himself. Th e posit ion in Inn sbru ck carried with it the ran k of an Ordinarius, which he could not afford t o decline. Consequently, he accepted but asked Section Chief Kelle for permission to see the I nstitu te in person so t hat he would be able to formu late his wishes concern ing changes and repairs since it was known to him (Pregl) t hat the insti tu te was in every aspect in a desolate condition. T he local evidence by far surpassed Pregl's worst expectations. The night afte r his return from In nsbru ck to Vienna, for t he conclusion of t he discussion with t he Ministry of Educati on, he spent with his friend Abderhalden, on a bench in t he little park in front of t he Votivkirche. He repeatedly showed me that bench with th e words,"Here I was sitting, and I carried on like a baby and kept saying : 'No, I cannot do it, I cannot stick it out in that rundown hovel, I cannot work th ere, I would go to pieces. I shall decline tomorrow and rather remain assistant and E xtraordinarius in an In stitu te where I am able to work." The next day, Abderhalden accompa nied him to the door of Section Chief Kelle's office and forcefully impressed on him not to commit a stupid act. Thus it happ ened that Pregl appeared in t he fall of 1910 in Inn sbru ck, sta rted to reorganize his Insti tu t e, and began with t he development of the micro analysis of organic substances, which is one chapte r in the history of chemistry to which t he Austrians will always point wit h prid e. There is no intention of lecturing on Pregl's meth ods of micro ana lysis. It must suffice to point out some of the main features, their meaning, and how they came about. Above all, the micrometh ods are not mere miniature copies of the analytical procedures of Liebig and Dumas. Before t he scale of work could be reduced, it was necessary to establish a secure basis for t he accurate weighing and measuring of small amounts of mat erial. The starting point was th e balance which Dr., h.c., Kuhlmann t ried to improve, on the insistence of Pregl. Then arrived th e main difficulty of the carbon and hydrogen determination, the constancy of weight of the ab sorpti on tubes. Even the first apparatus was given t he shape of pencils, but a 50% solution of potassium hydroxide on glass wool still served as th e absorbent. It was difficult to wash t he ti p of t his apparatus. Later, Pregl added bulbs and capillaries to assure constancy of weight . The final shape of his absorption tubes came into being as follows. The summer had MI CR OCH E MI CAL JO UR NAL, VOL. VI , I SSUE 1
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been unusually hot , which is liable to upset combust ion analyses as any experienced micro analyst would expect. The absorption tubes did not want to remain constant in weight, and it was necessary to time th e work painstakingly to get correct results. Pr egl felt played out, and decided on one of those quick t rips around I taly which he enjoyed. As usual, the time of return was left indefinite. After a few days, however, he was back ; an idea had come to him in Trieste. Withou t wasting a word or taking off his straw hat , he just shoved it far back on his head, he stepped up to the glass blowing ta ble, made th e first absorption tub e of th e familiar shape, filled it , and gave it to his assistant with the words, "Weigh it in half an hour and then again after two hours. I am going out to eat and to have black coffee." When he returned after two and one-half hours, the weight of th e apparatus had remained nearly constant. In the evening of th e same day, again at peace with himself, he boarded th e train for Trieste to resume his trip. One by one, the many other difficulties were overcome: the tube filling, the mercury gasometer, the rubber tubing, and the lead dioxide. Whoever want s to be informed about th is chapter or want s to know how many little devils are hidden in every cubic centimeter of t he apparatus for microcombustion is invited to read t he account of our colleague Lindner on th e causes of error. It happened in the fall of Hl11 that Pregl faced for t he first t ime a large audience with a report on his new method s. Th is happ ened in Berlin, and his assista nt Max De Crinis, now professor of neurology in Graz, demonstrated t he determination of carbon and hydrogen during the one-hour lecture. Up to that time, a carbon and hydrogen determina tion had required at least three hours. In December 1911, Pregl came for two weeks as guest to the Second Chemical Institute of th e University of Vienna to introduce his methods in the laboratory of Professor Goldschmied. I had been assigned for his personal adjutant, and I recall vividly how it all started. Pr egl appeared at 9 o' clock on th e dot; at 10 o'clock, th e balance and apparatus had been unp acked and stood ready for use. My chief, Professor Goldschmied, had told me to give Pregl for the demonst rat ion a very nasty substance which he probabl y had never tri ed before. In compliance with orders, I selected 2-met hyl-3-brompropanal. Pregl introduced a weighed sample into the combustion tube and moved the burn er into the proper position for a sta rt. There
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was a mild flash and the whole tube was filled with soot, tar, and bromine vapor. Pregl gave me a brief look which I shall never forget and then turned pleasantly to Goldschmied : "Your assistant has done a very good job; I am pleased to be able to show you how one gets the better of such substances." At 11 o'clock, the tube was clean again and a new determination was proceeding; and at 12 o'clock, we were able to convince ourselves that the carbon content was correct within 0.02%. "You acted like a dirty rat, but at least your subsubstance was pure," was Pregl's approving comment in my direction. On the 9th of January, 1912, Pregl demonstrated his methods in Vienna before the Chemisch physikalische Gesellschaft. On that occasion, I had the honor of demonstrating the carbon and hydrogen determination and could approach the theory within 0.06 and 0.07%, respectively. The final victory, however, was won during the meeting of the Vereinigung deutscher Naiurjorecher und Aerzte in 1913 and also in Vienna. Pregllectured, Lieb performed the molecular weight determination, Breygant did the nitrogen, and I determined carbon and hydrogen. Everything went fine. After the lecture, Emil Fischer, who presided, came over to me and asked permission to check the weight of the carbon dioxide absorber. After he had done it, he offered me his hand and said, "Now I believe it." This was one of the most beautiful moments of my life. We all felt, "Now we have done it." As a fact, from that day on the micromethods began to replace the customary procedures of combustion analysis. The advantages of Pregl's micromethods are economy: destruction of only small amounts of valuable research substance, economy of time, and economy of effort. Just one example may suffice. Talking in Konigsberg with Nobel laureate Hans Fischer, I raised the question whether he could have concluded his investigations on hemin without the help of the Pregl methods. After brief consideration, he said, "I believe yes, but it would have taken me two or three years longer." One has to fully contemplate what two to three years mean in the instance of Hans Fischer with his 25 assistants and coworkers. Finally, Fischer directs only one of the many research centers which are aided by organic micro analysis. In 1913, organic elementary analysis had been brought to a state of tentative perfection when Pregl returned to Graz as successor to his teacher Hofmann. His Organic Quantitative Micro Analysis was not yet published, but he was already a well-known man. He received the Lieben prize, and his Institute had visitors from all parts of the MICROCHEMICAL JOURNAL, VOL. VI, ISSUE 1
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Fritz Pregl in his microchemical laboratory, around 1920.
globe since it had gotten around that the impossible was practiced in Graz: analyses with a few milligrams in one-fourth of the usual time. When I visited him at Easter in 1914, I met in his laboratory Dr. Schroder from Heidelberg, Yllner from Stockholm, Sernagiotto from Bologna, Cornubert from the Sorbonne, and an Englishman whose name has escaped my memory; truly an international company. In 1912 he had given in to his students and written a brief account of his methods for Abderhalden's IIandbuch der biochemischen Arbeiismethoden, He did not like to break into print prematurely and later once berated me for having helped to talk him into it. At the close of 1916 his well-known book appeared, which had one edition after another. During the First World War Pregl did his utmost to keep research and teaching alive. In 1917, he became Dean of the Medical School and, as such, he became involved with the development of agencies for the students' welfare. The ministry of defense sent him to Berlin to take part in the study of gas warfare; he performed experiments concerning the lethal quantities, tested gas masks, and developed a palladium test paper for the detection of carbon monoxide. After the war, in 1921, he was elected Rector of the university and again hc was able to contribute significantly to development of welfare institutions. During these years, he developed the solutio Pregl,
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Vacationing on the Island of Lussin in the Adriatic.
which in analogy to Dakin solution contains hypoiodite as the active agent. It is a powerful antiseptic whIch may be intravenously injected in large quantities. He kept the preparation and the composition a secret. The Riesswerke, who belong to the Hospital of the Province Styria, became the sole manufacturers. This gave him the assurance that any profits would benefit his homeland. Pregl's scientific contributions of that time can only be estimated by those who were close to him. He published relatively little, but he was very active. He just happened to be the "Pregl," the handy consultant for his faculty and for practically anybody who asked for his advice. Visitors came and went, and the telephone rang about fifty times a day. The Dental Clinic was on the wire; they were trying something new with the solutio Pregl. Neurology needed advice; they were trying Abderhalden's ninhydrin test for pregnancy. The surgeon Haberer was developing a diagnosis of kidney ailments by means of chemical tests. Also Gynecology and Pharmacology would consult with him, and frequent interchanges with the medical examiner were a necessity since Pregl was the County Toxicologist, a duty which went with his position as head of the Institute of Medical Chemistry. Pregl was also quite busy outside of his strictly scientific activity. MICROCHEMICAL JOURNAL, YOLo YI, ISSUE 1
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Clipping from an Austrian (? ) newspaper , 1929. Th e caption read : "T he Austrian Nobel prizewinner University Professor Dr. Friedri ch Pregl has been made a ll Honorary Cit izen of t he City of Graz, capital of Styria, on th e occasion of his sixt ieth birthday." Taken in front of th e Medical Chemical Insti tute.
He tried his best in t he interest of ju stice to promote able and promi sing people. In thi s respect he did not want to compromise, and he could be tough and was not swayed by app eals for sympathy. How much good he has done along th ese lines is unknown even to his closest. associates, but an example may be given. When he left Innsbru ck, he had to fight a pit ched battle to get for his s..icccssor the young Windau s, who was his most dangerous competitor in th e field of th e bile acids. Wagging ton gues would have it that Pregl did it to please his own vanity. The indispu table fact s arc th at Windau s was awarded the Nobel prize in 1928 and that Windaus' successor Hans Fischer was given th e same recognition in 1930. What ever Pregl's motive may have been, we Innsbruckers owe it to him that three Nobel laureates worked ill succession at the Medical Chemical Institute of our University. In his private life, Pr egl was very simple. He never was married , and his personal desires wore modest. When he celebrated his 60th birthday by taking th e driver 's test, he permitted himself t he luxury of acquiring a Stcyr automobile, :I produ ct of Austrian industry. Right after that, however, he placed 20000.00s. at the disposal of th e
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Academy of Sciences in Vienna. The interest was to provide annually a cash prize for the best work in microchemistry performed in Austria or done by an Austrian. Much time and possibly some money he gave to his adopted child, the journal Mikrochemie, at that time published by Emil Haim in Vienna. Some of his apparent generosity resulted from the clear understanding that money may be well spent if it frees of petty worries. Once I was present at the inventory taking which showed a deficit of 8000.00s. "What are you going to do?" I asked him.-"What I am going to do? I shall chip in, that's what I am going to do. It's better to have one bloodletting than bother the whole year with petty saving." When his Institute was going to be enlarged, he offered to the Ministry of Education to contribute one half of the expenses. What finally happened, I do not know. Many a token of esteem was paid to him, but he also received some slights. He took both in his stride. He was still young when he was given the title of H ofrat, the honorary degree of a doctor of philosophy of the University G6ttingen, the Nobel prize, the dignity of an honorary citizen of City of Graz, and finally the large medal for meritorious service to the Republic. The Academy of Sciences in Vienna elected him a corresponding member, and he had three separate invitations for a transfer to Vienna, all of which he declined. Pregl was never active in the political field, for party interests were alien to his innermost nature. He just strove, by consistent effort, to increase the reputation and the well-being of his people and his country. Apparently this was not well received by his contemporaries. During his opening address in Innsbruck, there was a demonstration by the Catholic students; the liberal faction made a disturbance at the torch parade of the whole student body celebrating his Nobel award; and the socialist representatives of the City Council were conspicuous by their absence from his funeral in spite of the fact that it was an honorary citizen being conveyed to his last resting place. The translator was acquainted with Fritz Pregl for nine years, 1920-29. The translation is frequently far from literal but, it is hoped, correct in the idea and mood to be conveyed. The whole flavor of intimacy could not be preserved when turning to a far larger audience, and the lapse of time has suggested some minor changes to accommodate the change in perspective.
A. A. Benedetti-Pichler MICROCHEMICAL JOURNAL, VOL. VI, ISSUE 1