MIESCHER, JOHANN FRIEDRICH II

(b. Basel, Switzerland, 13 August 1844; d. Davos, Switzerland, 26 August 1895)

physiology, physiological chemistry.

Shortly after his birth Miescher (who was known as Fritz because his father bore the same names) was taken with his family to the Bernese Emmental, where his father had just been appointed professor of pathological anatomy at the University of Bern. When local canton politics caused the elder Miescher’s resignation in 1850, the family returned to Basel, where Miescher excelled at the Gymnasium and in the musical circle to which his father and his uncle, Wilhelm His, Sr., belonged, together with the famous chemist C. F. Schönbein.

Apart from a semester spent at Göttingen Mieseher remained in Basel, where he qualified in 1868. He then did research on the composition of pus cells, working in Hoppe-Seyler’s laboratory at Tübingen (from 1868 to 1869). From there he went to Carl Ludwig’s physiological institute in Leipzig (from 1869 to 1870), and finally returned to Basel for the Habilitation. In 1871 he was appointed to the chair of physiology at the University of Basel, which had been vacated by his uncle. There he worked to isolate nuclein from the sperm heads of Rhine salmon and to solve the mystery of the fasting-reproductive stage of the male. His resources were meager, and working conditions poor. When the effects of tuberculosis necessitated treatment in a sanatorium, Miescher used the opportunity to study the effects of altitude on the constitution of the blood and observed the increase in the blood count of erythrocytes with increasing altitude. In 1885 the university built an institute for him, the Vesalianum, where he was joined by Bunge.

Miescher was an unimpressive teacher and an often obscure writer. His subtle mind demanded caution and qualifications; his indecision over the rival claims of physical and of chemical reductionism, coupled with his distrust of cytology, prevented him from unifying that subject with chemistry, as he had sought to do. Miescher nonetheless had an eye for a good problem and for appropriate research material; he was observant and painstaking, and if he sought to achieve more than the best techniques of his day could allow, he established a method for physiological chemistry that his successors eagerly exploited.

Miescher’s first and most important discovery was a new class of compounds rich in organic phosphorus and forming the major constituent of cell nuclei. He rightly concluded that these “nucleins,” as he called them, were as important a center of metabolic activity as the proteins. The product he obtained from the pepsin digestion of pus cells in 1869 was nucleohistone; five years later he isolated a purer form of nuclein from salmon spermatozoa and demonstrated the saltlike union between its two major constituents, an acid fraction (“pure nuclein,” or DNA) and a basic fraction (which he called “protamine” and regarded as an alkaloid, rather than a protein). He left to others the task of establishing the detailed chemical constitution of these compounds, and his own knowledge of them was limited to their solubility characteristics, elementary components, and reactions with histochemical tests.

Instead Miescher preferred investigating the formation of large amounts of nuclein by the male salmon during the fasting period. He concluded that this activity is achieved only at the expense of the trunk muscles of the fish, and suggested that these muscles are progressively decomposed or “liquidated” because of reduced oxygen supply. He further attempted to trace these changes at the chemical level, thereby providing a remarkable early example of the “dynamic biochemistry” that F. G. Hopkins later advocated. (Miescher’s effort was, however, unfortunate in that it encouraged others in persistent attempts to show that nucleic acids are derived from proteins; these researches in turn fostered a false view of nucleic acids as compounds formed between proteins and phosphoric acid.)

In histochemistry Miescher established a clear chemical distinction between the nucleus and cytoplasm, based on the presence of nuclein in the nucleus, a distinction that supporters of the chemical theory of staining gladly embraced. Miescher’s own parallel studies of the staining reactions of the spermatozoa were in conflict with the results achieved by Walther Flemming and P. Schweigger-Seidel, however, and thus lent credence to those who, like Albert Fischer, sought to discredit the chemical theory of staining altogether.

Miescher’s interpretation of fertilization vacillated between the extreme physicalist reductionism of his uncle and the chemical theory that his own work suggested. He was never able to accept the notion that the structures revealed by cytological staining are themselves carried by the sperm into the egg to contribute to the structure of the embryo. Miescher saw this morphological theory, as Hertwig called it, as flying in the face of the reductionist program to which he was committed.

Miescher died of tuberculosis before he had completed his last paper on nuclein. A full account of his studies on this was compiled and published by Ostwald Schmiedeberg.

BIBLIOGRAPHY

I. Original Works. All of Miescher’s papers and a selection of his letters will be found in Die histochemischen und physiologischen Arbeiten von Friedrich Miescher. Gesammelt und herausgegeben von seinen Freunden (Leipzig, 1897), His paper on the isolation of nuclein from pus is “Ueber die chemische Zusammensetzung der Eiterzellen,” in F. Hoppe-Seyler’s Medisch-chemische Untersuchungen, IV (Berlin, 1871), 441–460. His first publication on salmon nuclein is “Die Spermatozoen einiger Wirbelthiere. Ein Beitrag zur Histochemie,” in Verhandlungen der Naturforschenden Gesellschaft in Basel, 6 (1874). 138–208; his last and posthumous paper was ’Physiologisch-chemische Untersuchungen über die Lachsmilch von F. Miescher, nach den hinterlassenen Aufzeichnungen und Versuchsprotokollen des Autors und herausgegeben von O. Schmiedeberg,” in Archiv für experimentelle Pathologie und Pharmakologie, 37 (1896), 100–155.

II. Secondary Literature. The clearest account of Miescher’s work on the chemistry of the nucleus is by A. Mirsky, “The Discovery of DNA,” in Scientific American, 218 (1967), 78–88. Biographical information is in M. de Meuron-Landot, “Friedrich Miescher, l’homme qui a découvert les acides nucléiques,” in Histoire de la médecine, 15 (1965), 2–25. Earlier studies include the following: K. Spiro, Zur Erinnerung an Schönbein, Miescher und Bunge (Basel, 1922), originally published in Basler Nachrichten, 12 and 19 Feb. 1922; J. P. Greenstein, “Friedrich Miescher, 1844–1895. Founder of Nuclear Chemistry,” in Scientific Monthly, 57 (1943), 523–532. The best obituary notice is A. Jaquet, “Professor Friedrich Miescher Nachruf,” in Verhandlungen der Naturforschenden Gesellschaft in Basel, 11 (1897), 399–417. Further information is contained in F. Suter et al., Friedrich Miescher, 1844–1895. Vorträge gehalten anlässlich der Feier zum hunderte Geburtstag von Professor Friedrich Miescher in der Aula der Universität Basel am 15 Juni 1944 (Basel, 1944); and in Helvetica physiologica et pharmacologica acta, supp. 2 (1944).

Robert Olby