Thierfelder, Hans
THIERFELDER, HANS
(b. Rostock Germany, 22 February 1858; d. Tübingen Germany, 11 November 1930)
physiological chemistry.
Thierfelder, best known for his isolation of the brain substance cereborn (phrenosin) and for his chemical studies of this and other cerebrosides was born into a medical family. His father, Theodor Thierfelder, was a university professor and director of a medical clinic in Rostock. After graduating from Rostock Gymnasium. Thierfelder studied medicine (1876–1881) at Rostock, Tübingen, Heidelberg, Munich and Freiburg. His instructors in physiology included Carl von Voit at Munich and Wilhelm Kühne at Heidelberg, both of whom were influential teachers with special interests in physiological chemistry. After passing his state examinations in Freiburg, Thierfelder worked for a year with Otto Nasse at the latter’s Institute for Pharmacology and Physiological Chemistry in Rostock. Under Nasse’s direction Thierfelder took his M. D. in 1883 with a dissertation on the chemical processes involved in the formation of milk sugar and casein, a study that became the basis of his first publication.
Drawn to science rather than to medical practice, Thierfelder applied to Felix Hoppe-Seyler at Strassburg and in 1884 was appointed assistant in HoppeSeyler’s Institute for Physiological Chemisary. Later Thierfelder’s student and collabroator Ernst Klenk would describe him as “one of the last outstanding physiological chemist to come out of the old HoppeSeyler school,” and there is no doubt that the more than six years that Thierfelder spent in Strassburg left an impression on his subsequent work. In Hoppe-Seyler’s institute, where he habilitated in 1887, Thierfelder continued his training in the problems and methods of physiological chemistry, the chemical analysis of body substances, and the study of the changes these substances undergo in the body. Here he also absorbed Hoppe-Seyler’s view that physiological chemistry constituted a field of research distinguishable from the anatomical and physical aspects of physiology, a field that could best be pursued in an institutionally distinct setting. One expression of that view was Hoppe-Seyler’s Zeitschrift für physiologische Chemie, founded in 1877, Most of Thierfelder’s work was published in this journal, and he served for the greater part of his career as one of its editorial consultants. Another indication both of the identify of the field and of the continuity of Thierfelder’s work with that of his teacher was Hoppe-Seyler’s Handbuch der physiologisch und pathologisch-chemischen Analyse, Thierfelder collaborated with Hoppe-Seyler in preparing the sixth edition (1893) and kept the classic text up to date after the latter’s death with editions in 1903, 1909, and 1924.
Another effect of Thierfelder’s time in Strassburg was his association with several young workers in physiological chemistry. Among them was Joseph von Mering, with whom Thierfelder collaborated in a study of the behavior of a series of tertiary alcohols in the animal organism. They found that administration of the alcohols, like other substances previously studied, could lead to the appearance of paired glucuronic acids in the urine, but that the outcome varied depending on the species of animal used. This work led Thierfelder into further investigations on the formation of glucuronic acid in the fasting animal and on the constitution of that acid. In the latter studies he was able to give evidence of the aldehyde nature of the acid and of its close relationship to glucose. Prompted in part by Hoppe-Seyler’s interest in brain chemistry, Thierfelder undertook other research at Strassburg that resulted in the identification of brain sugar with galactose.
In 1891 Thierfelder left Strassburg to join the physiologist Max Rubner at the Hygiene Institute at the University of Berlin. The new setting encouraged different kinds of investigations. Thierfelder resumed his study of milk and its constituents. With Carl Günther he showed that, contrary to prevailing opinion, the milk acid isolated from sour milk was not always the optically inactive acid but frequently the dextrorotatory form. Günther and Thierfelder were able to isolate a substance that, inoculated into sterilized milk, always produced dextrolactic acid.
With George H. F. Nuttall, Thierfelder began to address experimentally Pasteur’s view that the microorganisms of the intestinal canal played an important role in the life of the organism. In technically difficult studies, Nuttall and Thierfelder kept guinea pigs born by cesarean section completely sterile. When the animals remained healthy and behaved normally, the two investigators concluded against Pasteur. While at the Hygiene Institute, Thierfelder met Email Fischer, and with him conducted tests on the behavior of a series of natural and synthetic sugars in relation to purebred varieties of yeast.
In 1895 Thierfelder was named director of the chemical department of the Physiological Institute at the University of Berlin, as successor of Albrecht Kossel. In 1896 he became extraordinary professor at the institute. He held both positions until 1909. Shortly after the first appointment, in 1895, Thierfelder married Luise von Beseler; they had two sons and two daughters.
On two occasions Thierfelder was offered a chair of physiology, first at Marburg in 1901, as successor of Albrecht Kossel, then at Göttingen in 1905, as successor of Georg Meissner. He declined both offers, on the grounds that physiological chemistry, as a field with its own research problems and methods, required its own institutional locale. This requirement was met when, in 1909, Thierfelder was called to the chair of physiological chemistry at the University of Tübingen, vacated by the death of Carl Gustav von Hüfner. He remained at Tübingen, as director of the Physiological-Chemical Institute for the rest of his career.
In 1900 Thierfelder and his collaborator Email Wörner reported the isolation of cerebron (later called phrensosin), the first of a group of substances known as cerebrosides to be obtained in unequivocally pure form. This work marked a breakthrough in the sense that it opened the way to determination of the chemical nature of these compounds and their relationship to other substances found in the brain. In taking over leadership of this field, Thierfelder carried forward Hoppe-Seyler’s interest in brain chemistry and his own earlier studies on brain sugar and its sources.
Except for the decade between 1913 and 1923 Thierfelder’s work on the cerebrosides and related problems occupied him for the rest of his life. Working with several collaborators, he established reliable methods for preparing cerebron and cerasin, the second cerebroside to be isolated, and obtained more exact descriptions of decomposition products of these two substances. Thierfelder showed that cerebronic acid, obtained from cerebron, is an α-hydroxy acid, and that the fatty acid of cerasin is not a hydroxy acid but another acid of formula C24H48O2, later identified as lignoceric acid by Phoebus A. Levene and Clarence J. West. On the basis of studies of the acetyl products of cerebron and cerasin, Thierfelder advanced structural formulas for these compounds that were accepted with minor modifications by the time of his death. In the course of his work on the cerebrosides, Thierfelder repeatedly encountered phosphatides, fatty substances that could hinder the purification of cerebrosides because of their chemical and physical similarities to the later. Several studies on the phosphatides were carried out by Thierfelder, his collaborators, and his students; and in the last years of his life he turned to research on the group of phosphatides closest to the cerebrosides, the sphingomyelins.
The slow, painstaking nature of the work in brain chemisty called forth Thierfelder’s finest qualities as an investigator. Not only capable of, but also preferring, long hours in the laboratory, he worked with great intensity on the problems he chose to pursue. A skillful experimenter, he demanded of himself the greatest exactitude, and of his results of the highest possible reliability. To the recalcitrance of his research problems Thierfelder opposed what his collaborator Ernst Klenk called on “iron diligence and tough perseverance,” and the conviction that his work was necessary if new knowledge was to be gained of the brain, which he regarded as one of the most obscure areas of physiological chemistry.
The same qualities may be observed in Thierfelder’s studies of the fate of several foreign substances in the animal body, problems to which he turned between 1913 and 1923. In one set of investigations he showed that after administration of phenylacetic acid and related substances to humans, phenylacetylglutamine appeared in the urine. This finding led Thierfelder to try to determine whether glutamine is present in protein and to conduct a study of the constitution of glutamine. In other research he examined the behavior of aliphatic-aromatic ketones and of hydrocarbons in the animal body, and was able to propose rules for the oxidative decomposition of these substances.
After an illness and operation in 1927. Thierfelder returned to his work with difficulty, but before his death he was able, with Ernst Klenk, to finish a monograph on the cerebrosides and phosphatides. Serious, kindly, and modest. Thierfelder was a conscientious teacher and a valued colleague. As a physiological chemist he made his influence felt not only through his own publications but also through his work on Hoppe-Seyler’s Handbuch, his service to the Zeitschrift für physiologische Chemie, and his association with numerous collaborators and students.
BIBLIOGRAPHY
I. Original Works. There is no single comprehensive bibliography of Thierfelder’s publications. A nearly complete list may be compiled by consulting Index Medicus, 5 (1883)–21 (1898–1899); Bibliographia Medica [Index Medicus], 1 (1900)–3 (1903); Index Medicus, 2nd ser., 1 (1903)–5 (1907); Royal Society Catalogue of Scientific Papers (1884–1900), XIX (Cambridge, 1925), 75–76; and Chemical Abstracts1 (1907)–19 (1925), with decennial indexes for 1907–1916, 1917–1926, and 1927–1936.
Thierfelder’s dissertation was “Beiträge zur Kenntniss der Entstehung einiger Milchbestandtheile” (Rostock, 1883). An abbreviated version was published as “Zur Physiologie der Milchbildung,” in Pflüger’s Archiv für die gesamte Physiologie, 32 (1883), 619–625. The study with Joseph von Mering appeared as “Das Verhalten tertiärer Alkohole im Organismus,” in Hoppe-Seyler’s Zeitschrift für physiologische Chemie, 9 (1885), 511–517. Among Thierfelder’s papers on glucuronic acid are “Über die Bildung von Glykuronsäure beim Hungerthier,” ibid., 10 (1886), 163–169; and “Untersuchungen über die Glykuronsäure,” ibid., 11 (1887), 388–409, and 13 (1889), 275–284. His early publication on brain sugar was “Über die Identität des Gehirnzuckers mit Galactose,” ibid., 14 (1889), 209–216. With Carl Günther, Thierfelder published “Bacteriologische und chemische Untersuchungen über die spontane Milchgerinnung,” in Archiv für Hygiene und Bakteriologie, 25 (1895), 164–195. Thierfelder’s research with George H. F. Nuttall appeared as “Thierisches Leben ohne Bakterien in Verdauungskanal,” in Hoppe-Seyler’s Zeitschrift für physiologische Chemie, 21 (1895), 109–121, 22 (1896), 62–73, and 23 (1897), 231–235. His work with Emil Fischer was published as “Verhalten der verschiedenen Zucker gegen reine Hefen,” in Berichte der Deutschen chemischen Gesellschaft, 27 (1894), 2031–2037.
Thierfelder’s isolation of cerebron was announced in his paper with Emil Wörner, “Untersuchungen über die chemische Zusammensetzung des Gehirns,” in Hoppe-Seyler’s Zeitschrift für physiologische Chemie, 30 (1900), 542–551. Other publications with various collaborators in the same field include “Über das Cerebron,” ibid., 43 (1904), 21–31, 44 (1905), 366–370, 49 (1906), 286–292 (with F. Kitagawa), 68 (1910), 464–470 (with H. Loening), and 77 (1912), 511–515 (with K. Thomas); “Phrenosin und Cerebron,” ibid., 46 (1905), 518–522; and “Untersuchungen über die Cerebroside des Gehirns,” ibid., 74 (1911), 282–289, 77 (1912), 202–217 (with H. Loening), 85 (1913), 35–58, 89 (1914), 236–247, 248–250, and 91 (1914), 107–114. With Ernst Klenk, Thierfelder published the monograph Die Chemie der Cerebroside und Phosphatide (Berlin, 1930).
His publications related to foreign substances in the body include “Phenylacetylglutamin und seine Bildung im menschilchen Körper nach Eingabe von Phenylessigsäure,” in Hoppe-Seyler’s Zeitschrift für physiologische Chemie, 94 (1915), 1–9; “Über glutaminhaltige Polypeptide und zur Frage ihres Vorkommens im Eiweiss,” ibid., 105 (1919), 58–82, with E. von Cramm; and “Die Konstitution des Glutamins,” ibid., 114 (1921), 192–198.
Thierfelder published two appreciations of his teacher: “Zur Erinnerung an Felix Hoppe-Seyler,” in Berliner klinische Wochenschrift, 32 (1895), 928–930; and “Felix Hoppe-Seyler” (Stuttgart, 1926), an address to the Natural Science Faculty of the University of Tübingen, 17 December 1925.
II. Secondary Literature. Two notices on Thierfelder, which appeared at the time of his death, are Ernst Klenk, “Hans Thierfelder†,” in Hoppe-Seyler’s Zeitschrift für physiologische Chemie, 203 (1931), 1–9; and Percy Brigl, in Berichte der Deutschen chemischen Gesellschaft63, pt. A (1930), 176–177.
John E. Lesch