300 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1955 



the attempt to produce penicillin on a large scale, one serious difficulty 

 was met. The highest-yielding strains of the mold Penicillium would 

 grow only on the surface of the culture medium in the great vats, and 

 strains that grew well when submerged were poor penicillin producers. 

 Applying the methods of inducing mutations already known to genet- 

 icists at the time, Milislay Demerec and his coworkers at the Cold 

 Spring Harbor Laboratory of the Carnegie Institution of Washington 

 undertook to irradiate with high doses of X-rays some Penicillium 

 strains that grew well when submerged, and to look for mutations that 

 would permanently affect the yield of penicillin. Among 504 selected 

 products, one was found that doubled the production of penicillin over 

 that in the original strain. This high-jnelding strain became the basis 

 of the enormous production of penicillin that within the last 10 years 

 has contributed so much to our national health. 



Even more significant than the production of this strain, however 

 valuable, was the insight gained in the studies by Demerec and others 

 into the fluctuating relations between virulent, disease-causing bac- 

 teria and viruses and those agents that may be used to combat them. 

 It was discovered that the infectious agents have powers of mutation 

 too; and among the mutations that can be induced by X-rays or by 

 chemical compounds, or among those that are always arising spon- 

 taneously in any large population of organisms, there are some muta- 

 tions that confer resistance to the sulfonamide drugs, to penicillin, to 

 streptomycin, in fact, to the killing effects of radiation itself. Learn- 

 ing this, geneticists at once made dire predictions about the conse- 

 quences of an overenthusiastic use of the wonder drugs and the anti- 

 biotics. But it seems that their medical colleagues failed to understand 

 the danger, while the clamor of those who were ill led to the widespread 

 use of such agents even for the common cold. Millions of doses were 

 given to soldiers as mere jjrophylaxis, in the hope of warding off some 

 possible infection. The result, now well known, was a near-disaster. 

 People began to say, "The miracle drugs don't work any more. Peni- 

 cillin has lost its punch. Streptomycin is no good." T\Tiat had hap- 

 pened was exactly what the geneticists had predicted. Mutant strains 

 of infectious germs had arisen that were now resistant to our drugs and 

 antibiotics, just like the now all -too-common liouseflies that seem to 

 thrive on DDT. As a matter of fact, there is in existence at least one 

 bacterial strain that actually requires a supply of streptomycin in 

 order to grow. 



New kinds of antibiotics had then to be discovered and put into mass 

 production. Yet the race was a losing one, for the mutational powers 

 of the infectious organisms seem virtually unlimited and permit 

 change far more rapidly than scientists can discover and produce new 

 agents. 



