Glass 



Genetics in the Service of Man 



247 



enormous wartime effort that went 

 into the attempt to produce penicilhn 

 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 peni- 

 cillin producers. Applying the methods 

 of inducing mutations already known 

 to geneticists at the time, Milislav 

 Demerec and his coworkers at the Cold 

 Spring Harbor Laborator}' of the Car- 

 negie Institution of Washington under- 

 took to irradiate with high doses of x- 

 ravs some Penicillium strains that grew 

 well when submerged, and to look for 

 mutations that would permanently af- 

 fect 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-yielding strain became the basis 

 of the enormous production of penicil- 

 lin that within the last nineteen years 

 has contributed so much to our na- 

 tional health. 



Even more significant than the pro- 

 duction of this strain, however valu- 

 able, was the insight gained in the 

 studies by Demerec and others into 

 the fluctuating relations between viru- 

 lent, disease-causing bacteria and 

 viruses and those agents that may be 

 used to combat them. It was dis- 

 covered 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 

 spontaneously in any large population 

 of organisms, there are some mutations 

 that confer resistance to the sulfona- 

 mide drugs, to penicillin, to strepto- 

 mycin, in fact, to the killing effects 

 of radiation itself. Learning this, ge- 

 neticists at once made dire predictions 

 about the consequences of an over- 

 enthusiastic use of the wonder drugs 



and the antibiotics. But it seems that 

 their medical colleagues failed to un- 

 derstand the danger, while the clamor 

 of those who were ill led to the wide- 

 spread use of such agents even for the 

 common cold. Millions of doses were 

 given to soldiers as mere prophylaxis, 

 in the hope of warding off some possi- 

 ble infection. The result, now well 

 known, was a near-disaster. People be- 

 gan to say, "The miracle drugs don't 

 work any more. Penicillin has lost its 

 punch. Strcptom\cin is no good." 

 What had happened 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 houseflies that seem to 

 thrive on DDT. As a matter of fact, 

 there is in existence at least one bac- 

 terial 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 un- 

 limited and permit change far more 

 rapidlv than scientists can discover and 

 produce new agents. 



Here again the geneticist may inter- 

 pose a prediction. The simultaneous 

 coincidence of two mutations, say to 

 penicillin resistance and to streptomy- 

 cin resistance, is of an order of proba- 

 bility so low (about 10-^«) as to be 

 trulv negligible. Start out with two 

 antibiotics to which the infectious 

 agents have never been exposed, and 

 use them together; and use a high 

 enough initial dose to leave no sur- 

 vivors—except, of course, your patient. 

 In this way the antibiotics may con- 

 tinue to serve mankind in the future. 

 But meanwhile, penicillin and strcp- 

 tom^•cin must be given a rest. 



In recent decades the shade of Mal- 

 thus has once again risen to trouble us. 



