438 ANNUAL REPORT SMITHSONIAN INSTITUTION, 195 7 



There were very few microscopes in America, and microscopists were 

 even scarcer. Thus the principal advances were made in Germany 

 where the dye industry was being developed at a rapid pace and where 

 research, both academically and industrially, had already progressed 

 from amateur to professional status. 



A technical development of considerable importance came in 1869 

 when Boettcher and, later, Fleming (both of Germany) in 1875 devel- 

 oped the principle of alcoholic differentiation. By overstaining and 

 then removing the excess dye with alcohol it was found possible to 

 control with great accuracy the end result. It was this method of 

 differentiation which led Fleming to develop some years later his 

 famous triple stain. The method of producing double and triple 

 staining effects had very important consequences in another direction 

 to which we shall come in a moment when we consider the work of 

 Paul Ehrlich. 



In the field of biology the advent of the new dyes made possible new 

 knowledge concerning the internal structure of cells and a better 

 understanding of the phenomena of cell division. The stains provided 

 the roots for such fundamental terms in cytology as chromatin and 

 chromosomes, referring to the ability of these structures to take 

 up dyes. 



In pathology the new stains helped to improve diagnostic techniques 

 and were invaluable tools in the solution of many problems. Thus in 

 1869 Julius Cohnheim of Breslau began his classical studies of in- 

 flammation, the nature of which was scarcely understood. Even 

 Virchow had misconstrued the process since he argued that inflamma- 

 tion was a local cellular response manifested by cells at the site of 

 injury. However, there were some who believed that other cells, 

 especially white corpuscles of the blood, were also involved. In a 

 brilliant series of experiments Cohnheim showed that this was so by 

 tagging leucocytes with aniline blue and then following their course 

 to the seat of an inflammatory process. 



But useful as the aniline dyes were to pathology in increasing our 

 understanding of the seats of diseases, they played an even more signifi- 

 cant role in revealing the causes of infections and parasitic diseases and 

 even in their cure. 



One of the most important applications of the new dyes was in the 

 field of bacteriology, then in the process of becoming a science. It will 

 be recalled that Leeuwenhoek had first seen bacteria in 1676. He did 

 not, however, associate these minute organisms with infectious dis- 

 eases. Indeed it was 200 years after bacteria were first seen before 

 their role in the etiology of disease was conclusively proved. There 

 were, of course, many reasons for the delay. The solution of the prob- 

 lem had to wait upon improvements in the microscope, improvements 



