1 102 CHEMOTHERAPY OF BACTERIAL DISEASES 



the former and a minimum of the latter, i.e., with the highest range or greatest 

 chemotherapeutic index. 



The index is subject, however, to wide variations and fluctuations according to the 

 test animal and particular strain of micro-organism employed. 



To explain the mechanism of parasitotropism and organotropism Ehrlich evolved 

 his "theory of chemo-receptors," similar to the side-chain theory of immunity, accord- 

 ing to which chemical agents cannot act upon either parasites or body cells unless they 

 are first fixed by suitable chemo-receptors {corpora non agunt nisifixata). Therefore, 

 when arsenic is administered, it is "fixed" by the arseno-receptors of certain cells; 

 mercury in turn is "fixed" by other receptors, and so on through an interminable 

 list. Ehrlich thought that the basic principle of chemotherapy was the possibility of 

 producing chemical substances carrying side-arms capable of being fixed by the re- 

 ceptors of parasites to a much greater extent than by the body cells. Presumably it 

 is not necessary that the whole molecule of a chemical agent possess a combining 

 affinity for certain receptors; if one or more atom groups become attached, it is pre- 

 sumed that it carries with it the remainder of the molecule. Moreover, that atom 

 group which is anchored or is responsible for the anchorage of the entire molecule need 

 not possess any of the properties of the entire molecule or of any part thereof. 



But chemotherapy has developed into a far more complex subject since complex 

 chemical and physico-chemical forces are involved in the effects of a chemical agent 

 on both body cells and invading parasites, and the matter of selective destruction of 

 parasites in the tissues would appear to be one of chemical or physico-chemical inter- 

 action between the chemical agent and protoplasmic constituents of the parasites, just 

 as the specific immunological processes of the body are being gradually placed on the 

 same basis. 



Instead of conceiving a remedy killing invading organisms by direct union through 

 the agency of theoretical chemo-receptors, a broader and more comprehensive con- 

 ception is required to explain the observed phenomena, as a remedy not acting as 

 such, but in virtue of the formation from it in the body of some directly toxic product, 

 either by a modification of its structure or by its union with some tissue constituent; 

 of modifications of virulence and a reduction of resistance with increased susceptibil- 

 ity to destruction by the body's natural defenses, the mechanism of parasiticidal 

 activity calling into play any one or several of the following factors depending upon 

 circumstances: 



1. A direct chemical interaction between the compound or drug as administered 

 or after some transformation in the body, with some protoplasmic constituent of the 

 parasite, resulting in the death or crippling of the latter by interference with its vital 

 processes as those of alternate oxidation and reduction (internal respiration). 



2. A physical or physico-chemical interaction with the protoplasmic colloids of 

 parasites involving precipitation, coagulation, changes in electrical charge, etc., suffi- 

 cient for destruction or crippling. 



3. The possible production of new compounds in the tissues capable of chemical 

 or physico-chemical interaction with protoplasmic constituents of invading parasites 

 rather than the production of these effects by the compound direct as administered. 



