Kossel, Karl Martin Leonhard Albrecht

(b Rostock, Germany, 16 September 1853; d. Heidelber, Germany, 5 July 1927)

nucleoprotein chemistry.

Kossel, the only son of Albrecht Kossel, a merchant and consul, and of the former Clara Jeppe, was a keen botanist as a schoolboy in Rostock. Only his father’s influence persuaded him to read medicine, but Kossel chose to go to Strasbourg in order to attend the lectures of the mycologist Anton de Bary. There he came under the influence of Germany’s foremost physiological chemist, Felix Hoppe-Seyler, to whom he returned as assistant in 1877 after passing the state medical examination at Rostock. His Habilitations-schrift was accepted in 1881, and in 1883 du Bois-Reymond appointed him director of the chemical division of the Berlin physiological institute, where he became an assistant professor in 1887. After ten years in Berlin, Kossel received the chair of physiology and directorship of the physiological institute in Marburg. In 1901 he succeeded Willy Kuhne in the chair of physiology at Heidelberg. On his retirement in 1924 he directed the new institute for the study of proteins at Heidelberg.

Kossel married Luise Holtzmann in 1886. He received the Nobel Prize in physiology or medicine in 1910, as well as many honorary degrees. He was survived by his son, Walther, professor of theoretical physics at Kiel, and a daughter. Among his students were W. J. Dakin, A. P. Mathews, and P. A. Levene.

After studying salt diffusion and the pepsin digestion of fibrin, Kossel turned in 1879 to the nucleins (nucleoproteins) discovered by J. F. Miescher in 1869, taking the chemical characterization of these compounds to a much deeper level than had Miescher. Between 1885 and 1901 Kossel and his students discovered adenine, thymine, cytosine, and uracil. He demonstrated that these, together with xanthine, hypoxanthine, and guanine (sarcine), are breakdown products of nucleic acids, which can be used to distinguish between the true nucleins of the cell nucleus and the spurious nucleins found in milk and egg yolk, which he termed “paranucleins.” His suggestion that hypoxanthine is a secondary product of adenine, and therefore not a primary constituent of nucleic acid, was correct; and his belief in the presence of a hexose sugar in nucleic acid from the thymus was not far from the truth (2-deoxyribose). In 1893 he also suggested, correctly, that the carbohydrate in yeast nucleic acid is a pentose.

Kossel’s invaluable distinction between true nucleins and paranucleins gained acceptance only slowly; its impact was rendered less decisive by his advocacy of the mistaken view that in the synthesis of nucleins the xanthine bases are simply added to preexisting paranuclein molecules, such as are abundant in the egg yolk. Kossel’s recognition of chromatin as nucleic acid with varying proportions of histone (1893) did not lead him into the discussions current at that time on the identify of the hereditary substance.

From physiological studies Kossel correctly concluded that the function of nuclein is neither to act as a storage substance nor to furnish energy for muscular contraction; rather, it must be associated with the formation of fresh tissue. He found embryonic tissue to be especially rich in nuclein. Also from physiological studies he showed that uric acid is more closely associated with the breakdown of nucleins than with that of proteins. Although he believed that the nuclein molecule consists of some twelve subunits, or a multiple of twelve, he left the task of formulating its structure to others.

In 1884 Kossel turned to the basic component of nuclein; and from the nuclei of goose erythrocytes he isolated a substance like Miescher’s protamine, which he named histone. He regarded it as a peptone and demonstrated that the amino acids leucine and tyrosine are among its decomposition products. When he examined the basic component of fish spermatozoa —Miescher’s protamine—he found that, like histone, it is protein in character and on decomposition yields arginine, Iysine, and a new amino acid, which he named histidine. Using his own quantitative methods, Kossel made comparative studies of the protamines of the sperm of various fish species which showed varying proportions of monoamine and diamino acids. He tried to formulate sequences of amino acids with the aid of his identification of decomposition products as small as arginylarginine.

Always anxious to unite chemical description with physiological function, and seeking to move from the static world of protein chemistry to the dynamic world of physiology, Kossel formulated a scheme of protein synthesis based on the idea that all proteins possess a nucleus of the diamino acids to which monoamino acids are added progressively during embryogeny. In the reverse process of gametogenesis, diamino acids from protein breakdown are selectively utilized to form the nuclear protamine of the gametes. He followed this process quantitatively in the male salmon.

As one of Hoppe-Seyler’s most successful students, Kossel continued to develop the tradition of physiological chemistry in Germany. He was reserved, modest, unexcitable, very conscientious, an unimpressive speaker, and dominated by the vision of a biological meaning for his chemical discoveries. Thus he believed that the reactivity of proteins depends upon that of the residues in exposed positions on the molecule. In a given reaction of a protein certain characteristic groups will be involved. In his Herter Foundation lecture (1912) Kossel clearly recognized the potential diversity of polypeptides and saw in the structure of proteins the chemical basis of biological specificity. The inadequacy of the techniques then available to him prevented him from carrying these essentially modern ideas further.

BIBLIOGRAPHY

I. Original Works Kossel’s papers up to 1900 are listed in the Royal Society Catalogue of Scientific Papers, XII, pp. 404–405, and XVI, p. 427. His later papers are in his book The Protamines and Histones (London, 1928), also in German as Protamine und Histone (Leipzig–Vienna, 1929).

He also wrote Leitfaden für medicinisch-chemische Kurse (Berlin, 1888; 8th ed., 1921). His Heidelberg vice-rectoral address appeared as a booklet, Die Probleme der Biochemie (Heidelberg, 1908). With W. Behrens and P. Schiefferdecker he wrote Das Mikroskop und die Methoden der mikroskopischen Untersuchungen, which is vol. I of their Die Gewebe des menschlichen Körpers und ihre mikroskopische Untersuchung (Brunswick, 1889). He also contributed an essay, “Beziehungen der Chemie zur Physiologie,” to E. von Meyer, ed., Die Kultur der Gegenwart ihre Entwicklung und ihre Ziele: Chemie (Leipzig–Berlin, 1913), pp. 376–412.

Kossel’s early interest in proteins is found in “Ein Beitrag zur Kenntniss der Peptone,” in Pflüger’s Archiv für die gesamte Physiologie, 13 (1876), 309–320; “Ueber die Peptonoe und ihre Verhaältniss zu den Eiweiisskörpern,” ibid., 21 (1888), 179–184. His interest in the clinical aspects of his chemical researches is found in “Dosage de I’hypoxanthine et de la xanthine,” in Jouranl de pharmacie, 7 (1883), 325–326.

Many of his papers on nucleins appeared in the journal he edited for over thirty years, Hoppe-Seyler’s Zeitschrift für physiologische Chemie, including “Ueber das Nuclein der Hefe,” 3 (1879), 284–291, and 4 (1880), 290–295; “Ueber die Herkunft des Hypoxanthins in der Organismen,” 5 (1881), 152–157; “Ueber Guanin,” 8 (1883–1884), 404–410; “Ueber einen peptonartigen Bestandtheil des Zellkerns,” ibid., 511–515; “Weitere Beitraäge zur Chemie des Zellkerns,” 10 (1886), 248–264; “Ueber das Adenin,” 12 (1888), 241–253; with A. P. Mathews he publilshed “Zur Kenntniss der Trypsinwirkung,” 25 (1898), 190–194; with F. Kutscher, “Beiträge zur Kenntniss der Eiweisskörper,” 31 (1900), 165–214; with H. Steudel, “Ueber einen basischen Bestandtheil thirerischen Zellen,” 37 (1902–1903), 177–189.

Most of his opublications on nuclein in the Berichte der Deutschen chemischen Gesellschaft concern adenine and thymine: “Ueber eine neue Base aus dem Thier-Körper,” 18 (1885), 79– 81; “Ueber das Adenin,” idid., 1928–1930, and 20 (1887), 3356–3358; “Ueber eiine neue Base aus dem Pflanzenreich,” 21 (1888), 2164–2167; and two papers with A. Neumann—“Ueber das Thymin, ein Spaltungsproduct der Nucleinsäure” 26 (1893), 2753–2756; and “Darstellung und Spaltungsproducte der Nucleinsäure (Adenylsäure),” 27 (1894), 2215–2222. His important comparisons of true nucleins anb paranucleins are fouond in “Ueber des Nuclein im Dotter des Hühneries,” in Archiv für Anatomie und Physiologie (1885), 346–347; “Ueber die chemische Zusammensetzund der Zelle,” ibid. (1891), 181–186; and “Ueber die Nucleinsäure,” ibid. (1893), 157–164.

Kossel’s Nobel Prize lecture, “Ueber die Beschaffenheit des Zellkerns” (1910), is translated in Nobel Lectures Including Presentation Speeches and Laureates’ Biographies: Physiolsogy or Medicine 1901–1921 (Amsterdam, 1967), pp. 394-405. His best general lectures are –The Chemical Composition of the Cell,” in Harvey Lectures (1911–1912), 33–51; and “Lectures on the Herter Foundation” in John Hopkins Hospital Bulletiin23 (1912), 65–76.

II. Secondary Literature. The best souorce of biographical information is S. Edlbacher, “Albrecht Kossel zum Gedächtnis,” in Hoppe-Seyler’s Zeitschrift für physiologische Chemie, 177 (1928), 1–14. For a more up-to- date assessment of his work, Kurt Felix’s centenary essay should be consulted: “Albrecht Kossel: Leben und Werk,” in Naturwissenschaften, 42 (1955), 473–477. The greater part of this essay has been translated in Eduard Farber, ed., Great Chemists (New York—London, 1961), pp. 1033—1037. Obituary notices are ion Science66 (1927), 293; Deutsche medizinische Wochenschrift, 53 (1927), 1441; Journal of the American Medical Association, 89 (1927), 524–525; Nature,120 (1927), 233; and Berichte der Deutschen chemischen Gesellschaft, 60 (1927), A159–A160.

Kossel’s portrait appears in the 60th anniversary vol. of Hoppe-Seyler’s Zeitschrift für physiologische Chemie, 130 (1923), and also in 169 (1927). For a personal account of research in Kossel’s institute which is far from complimentary to Kossel as a director of research, see Sir Ernest Kennaway, “Some Recollections of Albrecht Kossel, Professor of Physiology in Heidelberg, 1901–1924,” in Annals of Science, 8 (1952) 393–397. The best reviews of Kossel’s work on the nucleic acids are P. A. Levene and L. W. Bass, in Nucleic Acids (New York, 1931), ch. 8; and R. Markham and J. D. Smith, “Nucleoproteins and Viruses,;rdquo; in H. Neurath and K. Bailey, eds., The Proteins: Chemistry, Biological Activity, and Methods (New York, 1954 [1st ed. only]), IIa, ch. 12 . For brief critical comments on Kossel’s contribution to protein chemistry, see J. M. Luck, “Histone Chemistry: The Pioneers,”, in J. Bonner and P. Ts’o, eds., The Nuchleohistoones (San Francisco, 1964), ch. 1.

Robert Olby