tually exclusive, since the latter could conceivably give rise to the former. 

 In its broader sense, of course, mutation covers not only gene change 

 and chromosome alteration but also change in any self-perpetuating 

 extranuclear particle. An hypothesis long held by Otto Warburg is that 

 the key particle involved is the mitochondrion, which becomes impaired 

 and leads to a shift from aerobic to anaerobic respiration. This shift is 

 presumed to favor mitosis rather than differentiation, though definitive 

 evidence for this point of view seems to be lacking. The hypotheses men- 

 tioned have stressed intracellular change but, so far, no one has excluded 

 the possibility that cancer initiation may be intercellular by virtue of 

 differential destruction of component cells of a tissue, thus leading to 

 disorganization and loss of control. Certainly all the causal agents men- 

 tioned are capable of acting in this fashion. The problem of intercellular 

 relationships in an organized tissue, therefore, becomes an area of con- 

 cern in cancer research. 



Drug Effects: Another aspect of cytological studies which is of more 

 or less direct concern to medicine involves the modification of cellular 

 morphology and function by drugs and drug-related substances. Within 

 the confines of this book no extensive discussion of this particular prob- 

 lem is possible. However, the point should be made that ingestion of a 

 drug will inevitably lead to some alteration, temporary or permanent, in 

 the metabolism of some component cells of the organism. For example, 

 there is good evidence that certain antibiotics, most notably, Chloromy- 

 cetin, terramycin, and aureomycin interfere with protein synthesis, though 

 the exact mechanism is not clear. Likewise, tranquilizers of the chlor- 

 promazine type have been shown to inhibit the succinic oxidase system 

 in brain and liver mitochondria. Many drugs appear to interfere with 

 carbohydrate metabolism in one way or another, though the exact mode 

 of action in most cases is unknown. Such drugs include cortical steroids 

 such as corticosterone, antimalaria amidines, anesthetics of the dibucaine 

 type, and other compounds commonly used for some therapeutic pur- 

 pose. Such effects are not necessarily directly related to therapeutic value, 

 though they may often be related to undesirable "side-effects." 



Taxonomy 



In recent years the field of biosystematics on both the plant and ani- 

 mal side has been making increasing use of cytological analysis as a 

 major clue to taxonomic relationship. The most commonly used cytologi- 

 cal characteristic is comparative chromosome constitution and behavior. 

 Stebbins has noted that the chromosomes, because they are the bearers 

 of hereditary factors, should be considered as somewhat more funda- 



GENERAL REMARKS / 273 



