2 J. N. DAVIDSON AND E. CHARGAFF 



By this time Miescher had returned to Basel in his native Switzerland 

 where he found a more congenial and convenient source of nuclear material 

 in the sperm heads of the Rhine salmon. From these he isolated a high- 

 molecular-weight nuclein and a basic material less complex than known 

 proteins which he called "protamine" and which could be extracted from 

 the defatted sperm with dilute acid leaving the "nuclein" in the residue. 

 This nuclein had a phosphorus content of 9.59 % and gave analytical figures 

 corresponding to what is now known as nucleic acid. Indeed Miescher's 

 many preparations of nucleins from a variety of sources, carried out at low 

 temperatures under the most exacting conditions, would be regarded by 

 present day standards as highly satisfactory. In subsequent work he showed 

 that the nucleins of the salmon sperm were synthesized at the expense of 

 the musculature of the fish, which do not eat during the period of gonadal 

 development in fresh water. 



After Miescher's death his friends, in particular His, organized the publi- 

 cation of a collected edition of his works including many of his letters.^ 

 His work was continued by his successors. For example, Altmann,^ who first 

 used the term nucleic acid, developed methods for the preparation of pro- 

 tein-free nucleic acid from yeast as well as from animal tissues, while Kossel 

 and Neumann^ described a method for its preparation from thymus glands. 

 These methods of preparation were subsequently improved and developed 

 by Neumann.^ 



The discovery of the purine bases in nucleic acids was made by Piccard,® 

 who at Miescher's suggestion extracted salmon sperm with boiling hydro- 

 chloric acid and isolated guanine and hypoxanthine. But the most outstand- 

 ing work on the purine bases was carried out by Kossel,^ who for several 

 years from 1879 onwards was actively engaged in this field and was respon- 

 sible for the isolation of xanthine and adenine. 



Miescher had isolated from the products of the hydrolysis of nucleic acid 

 a base which we now know to have been thymine, but this pyrimidine was 

 not properly identified until the work of Kossel and Neumann in 1894.^ 

 Cytosine was isolated and identified in 1902-03 by Kossel and SteudeP 



2 "Die histochemischen und physiologischen Arbeiten von Friedrich Miescher," 

 2 vols. F. C. W. Vogel, Leipzig, 1897. 



3 R. Altmann, Arch. Anat. u. Physiol, Physiol. Abt. 1889, 524. 



* A. Kossel and A. Neumann, Ber. 27, 2215 (1894). 



* A. Neuman, Arch. Anat. u. Physiol., Suppl. 1899, 552. 

 8 J. Piccard, Ber. 7, 1714 (1874). 



7 A. Kossel, Z. physiol. Chem. 3, 284 (1879) ; 5, 152 (1881) ; 6, 422 (1882) ; 7, 7 (1882-3) ; 

 8, 404 (1883-4); 10, 248 (1886); 12, 241 (1888). 



8 A. Kossel and H. Steudel, Z. physiol. Chem. 37, 177 (1902-3). 



