SOME CATALYTIC ASPECTS OF DISEASE AND DRUGS 243 



tris betachloroethyl amines) are nitrogen analogs of sulfur mustard 

 (bis-betachloroethyl sulfide). Several enzymes, including hexokinase, 

 are highly sensitive to nitrogen mustards. "However, the fact that 

 there has been little correlation between the susceptibility of enzyme 

 systems in vitro and in vivo has delayed the acceptance of the enzyme 

 inactivation theory of nitrogen mustard intoxication." 



Enough has been said to show the extensive and basic importance 

 of the catalytic aspect in disease, in disease-producing agents, and 

 in drugs helpful in curing disease. While an understanding of 

 the underlying physicochemical basis of disease is not in itself a 

 remedy, it should be helpful in efforts to avoid, ameliorate, and 

 cure diseases, and it may light the way for research. However, 

 we should always be ready to recognize and accept the unexpected 

 and the unsuspected actualities. 



When a drug irreversibly damages some essential catalyst of an 

 invading organism, the organism dies. If the damage is reversible, 

 the activities of the organism may be only temporarily inhibited. 

 Where the catalysts affected are not vital ones, the organism may 

 carry on what, for it, may be considered an abnormal life, and its 

 usual forms may be modified. In this connection the facts re- 

 garding Mycobacterium tuberculosis and the closely allied M. 

 leprae are of interest; their classical forms are the acid-fast rods 

 which stain red in the Ziehl-Neelson technique (carbolfuchsin 

 followed by acid-alcohol). Dr. Eleanor Alexander-Jackson of 

 Cornell University 62 developed a differential triple stain for 

 demonstrating and studying non-acid-fast forms of the tubercle 

 bacillus in sputum, tissue and body fluids. The non-acid-fast 

 forms, including hitherto undemonstrated zoogleal and globoid 

 forms, are clearly brought out by this triple staining method, 

 which can be summarized as follows: 



The Ziehl-Neelson technique is first followed, including flooding of 

 the slide with Loeffler's methylene blue counterstain; but the power 

 of this blue stain is increased by mixing in, on the slide, 8 small drops 

 of normal NaOH, and allowing this to remain not over one minute. 

 The entire slide, apart from the acid-fast forms (if present) is stained 

 deep blue. The washed slide is then flooded with a freshly made 

 solution of sodium hydrosulfite (250 mg in 50 cc water), which removes 

 the blue from all but the non-acid-fast tubercle forms. The slide is 

 quickly washed and then counterstained with an acid green, and 

 against the green background acid-fast red and non-acid-fast blue 

 forms stand out clearly. 63 



