R. D. HOTCHKISS 



done blindly, and it is possible that it may always have to be done 

 empirically. For, on the one hand, although many visible sti'uctural 

 differences have been described between different cells, these can 

 hardly ever be described in terms of function, chemical reactivity or 

 vulnerability. On the other hand, it is safe to say that those few 

 chemical differences which have been detected probably reside in the 

 proteins, polysaccharides, or other macromolecules of the cells. Almost 

 the only agents with specificity great enough to show qualitatively 

 different behavior with different cells are the antibody and enzyme 

 proteins or organized agents like the viruses. Less complex chemical 

 agents sometimes behave differently in a quantitative sense in staining 

 or penetrating diverse cells, but even here we seldom find the desired 

 situation, viz-, that the reactivity of one type of cell far overshadows 

 that of any other type. 



Chemical substances of low molecular weight are, however, not 

 devoid of specific affinities and are even capable of "biological" dis- 

 crimination. Enzymes are enzymes only if there are corresponding 

 substrates, and these latter are in many cases well-defined simple 

 substances. If the enzyme is credited with specificity in its action 

 upon substrates, it is perhaps only fair to ascribe specificity to the 

 substrate when it seeks out an active spot on the enzyme surface and 

 enters there into a transitory enzyme-substrate complex. Statistically 

 speaking, it is the rapidly moving substrate molecule and not the slug- 

 gish protein which does most of the hunting. However, we must 

 remember that there is virtually no evidence to indicate how many 

 "false complexes" the substrate enters into, at other sites on the enzyme 

 or other proteins, which do not result in chemical change, and there- 

 fore pass unnoticed. We cannot say that a key which fits many locks 

 is specific merely because most of the locks it fits will not work. 



With antibody proteins, too, simple substances have a discrimi- 

 natory ability to inhibit the combination with, and precipitation of, 

 the specific antigens. Indeed large parts of the precipitating capacity 

 of the antibody proteins can be directed toward relatively simple 

 associations of chemical groups contained in the huge antigen particle. 

 Nevertheless, it is just when we turn to the smaller molecules and to 

 the phenomena of "specific inhibition" which they show that we begin 

 to find the broadest overlapping of reactivity shown by distantly 

 related structures. For example, an antibody can be sometimes more 



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