THE MITOTIC CYCLE 



percentage of phosphorus ; it was only very slowly attacked by gastric 

 juice. An account of this research was submitted to Hoppe-Seyler in 

 1869, but so startling were the nature of these conclusions that 

 Miescher's^ paper was not published until 1871, by which time other 

 colleagues had confirmed these observations on different types of 

 material.' In that year, Miescher returned to his native city of Basle and 

 became interested in the biology of the Rhine salmon, the sperm of 

 which provided new material for investigations on nuclear chemistry. 

 The acid nuclein of the sperm head was shown to be united with a 

 nitrogenous base, to which Miescher gave the name protamine. He 

 did not regard this as a protein, for it gave no reaction with the Millon 

 reagent. 



The first instance in which the results of Miescher were applied to a 

 histochemical investigation is provided by the work of Zacharias,*^ 

 who sought to determine whether the nuclei of several types of cell 

 consisted of nuclein, by testing if they were resistant to peptic digestion, 

 and whether they would swell or gelate in strong sodium chloride, as 

 did Miescher's nuclein. Zacharias applied these tests to a number of 

 animal and plant cells and found that the behaviour of their nuclei 

 suggested that they also contained nuclein. This research Flemming' 

 had in mind when in his classical ^ellsubstanz, Kern und ^elltheilung he 

 gave a definition of the substance which forms the 'framework' of the 

 nucleus : 



which, in virtue of its refractile nature, its reactions, and above all, its affinity for 

 dyes, is a substance which I have named chromatin. Possibly chromatin is identical 

 with nuclein, but if not, it follows from Zacharias' work that one carries the other. 

 The word chromatin may serve until its chemical nature is known, and meanwhile 

 stands for 'that substance in the cell nucleus which is readily stained'. 



Although this definition was framed with respect to the resting 

 nucleus, Flemming clearly describes in the following section of the book 

 how the 'Kerngeriiste' of the resting nucleus is directly transformed into 

 the 'chromatischen Kernfigur' during mitosis, the individual loops of 

 which were not given a special name until Waldeyer^ first used the 

 term 'chromosome'. 



By the eighteen-seventies, there were available a number of the azo 

 dyes which are still used by histologists, and Flemming in 1882 lists 

 those which he had employed in studying the nucleus throughout its 

 stages. It was not long afterwards that Ehrlich drew attention to the 

 difference in staining properties between those dyes in which the colour 

 group was acidic or basic (see for instance Ehrlich^). 



Meanwhile,^ advances in the chemical study of the nucleus were in 

 progress and the presence was being recognized of one type of constitu- 

 ent unit, the purine bases, then known as the 'alloxuric bases'. Such 

 investigations were begun by Piccard, and continued by Kossel. At 



