442 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1957 



of malaria. Variants of these stains are known by the names of 

 Leishman, Giemsa, Wright, Hastings, and others. 



Shortly after coming to Berlin, Ehrlich contracted tuberculosis and 

 went to Egypt to recuperate. After 2 years, the disease arrested, he 

 returned to Germany and began work on the standardization of 

 antitoxic sera, especially those against diphtheria and tetanus. His 

 studies, although directed toward a very practical purpose, produced 

 results of the highest theoretical significance, since they led him to 

 evolve his famous side-chain theory of immunity. It would lead us 

 too far afield to discuss this here, but it should be mentioned that the 

 basic concept was derived by Ehrlich from his work on the specificity 

 of staining reactions. From the very beginning of his investigations, 

 he had been obsessed with the idea that the basis of staining reactions 

 was the ability of specific cells or parts of cells to fix or have an affinity 

 for specific stains. He generalized this idea in his motto "Corpora 

 non agunt nisi fixata" — bodies do not react unless they are fixed — 

 and from this Ehrlich derived his idea for a search for a "magic 

 bullet" or drug effective against the specific agent of specific diseases. 

 The "magic bullet" was no mere whimsey or figure of speech. It 

 derives from an ancient theme in Germanic folklore and in fact 

 provides the motif in von Weber's opera, Der Freischutz. 



With this notion, Ehrlich created the modern science of chemo- 

 therapy. He began from the observation that methylene blue seemed 

 to have a special affinity for nerve cells. He was curious about the 

 reason for the unique specificity. He therefore suggested to chemists, 

 notably Caro of the Badische Analin and Sodafabrik, that certain 

 modifications of the dye be prepared which might provide a clue to 

 its selective action on nervous tissue. In the course of these investi- 

 gations a new coal-tar intermediate was discovered which provided 

 the basis for synthesizing a whole new series of commercially im- 

 portant dyes, the rhodamine series. Here we have an example of 

 how a purely biological research proved useful to industry and 

 commerce. In the meantime Ehrlich had discovered that methylene 

 blue was a very effective stain for malaria parasites. This was in 

 1891 and it led to some trials on patients. The results were not too 

 promising but were not completely negative since they pointed the 

 way later to the synthesis of some really effective antimalarial drugs. 

 Ehrlich next attempted to find a drug effective against trypanosomes, 

 one type of which causes African sleeping sickness. The first result 

 was the synthesis of a tetrazo dye, trypan red. This was found to be 

 effective against Trypanosoma equinum, the causative agent of mal 

 de caderas, a disease of horses. Trypan red worked in mice infected 

 with this organism and was the first example of a specific drug syn- 

 thesized to be effective against an experimental infectious disease. 



