14 



THK ACTIN()MYCETP:S, Vol. I 



aerobic Nocardia species was now becoming 

 definitely established. 



Numerous investigations were made, dur- 

 ing this period, on the actinomycetes con- 

 cerned with the causation of plant diseases. 

 It is sufficient to mention the work of Mil- 

 lard and Burr, Lutman et al., Schaal, and 

 Goss. The organisms concerned in the causa- 

 tion of potato scab were found to belong to 

 the genus Streptomijces. The sail and the 

 fresh-water actinomycetes, belonging largely 

 to the genera Streptumijces and Micromono- 

 spora, were also studied extensively. That 

 the importance of actinomycetes as causative 

 agents in human diseases was not neglected 

 is shown by the publications of Colebrook, 

 Henrici (1930), and numerous others. With 

 the introduction of the sulfa drugs as anti- 

 bacterial therapeutic agents, attention was 

 also directed toward the chemotherapy of 

 diseases caused by actinomycetes. 



4. The Biochemical or the Antibiotic 

 Period (1940-1958) 



The most recent period in the history of 

 actinomycetes has been characterized by a 

 unique development, that of formation and 

 utilization of antibiotics and of certain other 

 biochemical products, notably vitamins. 

 Since the introduction of penicillin as a 

 chemotherapeutic agent, no other group of 

 microorganisms have contributed so much 

 to the field of human and animal therapy as 

 the actinomycetes. Beginning with actino- 

 mycin announced in 1940, a large number 

 of chemical compounds ha\'e been isolated 

 from cultures of these organisms. Screening 

 programs, initiated in the previous period by 

 a group of Russian investigators and devel- 

 oped by the writer and his associates (1942), 

 found ext(Misiv(> applications. 



Considerable attention has also been paid, 

 during this period, to the general problems 

 bearing upon the physiology and biochemi- 

 cal activities of the a(^tinomycctes, especially 

 metabolic processes, enzymatic systems, and 



biogenesis of antibiotics. Many new species 

 ha\'e been described, and a \'ariety of differ- 

 ent metabolic reactions investigated. Since 

 this field is so new and since the work done 

 in this connection is so extensive, it is diffi- 

 cult to summarize or to classify the numer- 

 ous contributions in any sort of chronological 

 order. It is much simpler to divide the period 

 on the basis of certain antibiotic groups that 

 have received the greatest consideration or 

 application. These contributions need not 

 correspond to any particular date or lab- 

 oratory, since fretiuently the same active 

 substance has been isolated almost simul- 

 taneously in several different laboratories in 

 different countries of the world. 



The writer has contributed a number of 

 reviews dealing with the historical back- 

 ground of the development of our knowledge 

 of the antagonistic effects of microorganisms 

 and the production of antibiotics. The first 

 review was published in 1937; it was largely 

 concerned with the antagonistic activities 

 of the organisms themselves, especially with 

 organic matter decomposition and their pos- 

 sible role in soil processes. The second and 

 third reviews were published in 1940 and 

 1941, and were more concerned with the 

 potentialities of the antagonistic microor- 

 ganisms as producers of antibiotics. This was 

 followed (1945, 1947) by a comprehensive 

 survey of organisms and their antibiotics in 

 a volume entitled Microbial Antag()nis7ns 

 and Antibiotic Substances. Later another \'ol- 

 ume was published in collaboration with 

 Lechevalier on Actinomycetes and Their An- 

 tibiotics (1953). 



Numerous other reviews and ^'olumes were 

 publishetl d(>aling with antibiotics as a whole 

 or with certain chemical forms in particular. 

 Only ('(M'tain of these need he mentioned 

 here: 1, the monumental \-()lumes on .1/)/?'- 

 biotics by 11. W. Florey, K. Chain, and their 

 associates; 2, the volume Aclinomijcetes — 

 Antai/onists and Antibiotic Stil)stances by 

 Krassiliiiko\'; 3, the general n^xiews by 



