446 ANNUAL REPORT SMITHSONIAN INSTITUTION, 194 5 



TYROTHRICIN, TYROCIDINE, AND GRAMICIDIN 



Tyrocidine hydrochloride was first termed graminic acid. A crys- 

 talline neutral substance was found to be gramicidin, while gramidinic 

 acid later was found to consist of gramicidin and tyrocidine, and was 

 called by the term now employed, "tyrothricin." All were markedly 

 bactericidal in vitro against gram-positive micro-organisms but 

 tyrothricin and tyrocidine were also effective against organisms of 

 the gram-negative group. 



Gramicidin proved to be most effective, but caused serious toxic 

 reactions. However, the highly bactericidal effect of gramicidin when 

 injected into experimental animals previously inoculated with cul- 

 tures of various organisms revived interest in Fleming's penicillin. 



Accordingly, Florey, the biochemist, and his Oxford associates, men 

 whose names have since become renowned for their outstanding work, 

 began the systematic study of the new substance, penicillin. Abraham 

 and Chain, and Heatley, all chemists, together with Lady Florey, a 

 physician of competence who was the major contributor to studies on 

 local use of penicillin, all reported on phases of the work. 



THE CULTURE 



The crude fluid first prepared as an extract of the culture broth of 

 penicillin showed remarkable properties. One part in several hundred 

 thousand and even up to one in a million dilution inhibited growth in 

 vitro and in vivo, of a number of organisms. It was apparent that 

 here was a potent new agent with, to quote Florey in 1941, ". . . the 

 bacterostatic power ... as great as, or greater than, that of the most 

 powerful antiseptics known, such as the heavy metal compounds, the 

 acridine derivatives, etc." The causative agents of anthrax, gon- 

 orrhea, pneumonia, meningitis, gas gangrene, and a host of other 

 diseases and infections one by one yielded to this new miraculous 

 substance. 



PROBLEMS 



As yet, the product was not ready for use in the treatment of disease 

 in humans. Two problems confronted the research workers. How 

 should the active substance be extracted? How should it be stand- 

 ardized ? 



The identification of the physical and chemical nature of the active 

 principle could await the satisfactory resolution of these two earlier 

 perplexing problems, even though the analysis and synthesis of the 

 principle was a task which was of terrific magnitude. 



THE OXFORD UNIT 



A test for potency was ingeniously worked out by Heatley, under 

 Florey's direction. Fleming's original serial dilution method, similar 



