850 CHEMOTHERAPY 



destruction of trypanosomes by an arsenical preparation has not been 

 complete, and if the antibodies produced by the body-cells do not suc- 

 ceed in destroying the remainder, there is a strong probability that a 

 new strain will now develop that will be resistant not only to the par- 

 ticular arsenical preparation used, but will also be proof against the 

 serum antibodies. This new strain may now cause a relapse of the 

 disease. Another chemical is now injected, but if this likewise fails to 

 kill all the trypanosomes, the remainder will generate still another 

 strain " resistant" to the preparation and the antibodies. This may 

 continue as long as the parasite is able to produce new receptors; when 

 this limit is reached, its nutrition will be impaired and the serum anti- 

 bodies, alone or aided by another chemical substance, may finally 

 destroy all trypanosomes, the infection " dying out, "so to speak, or 

 proving completely vulnerable to a chemical agent. 



These considerations have an actual experimental basis, and natural 

 examples of acquired serum-resistance or " fastness" are to be found in 

 relapsing fever, syphilis, sleeping sickness, and possibly malaria. No- 

 guchi and Akatsu 1 have recently succeeded in rendering different strains 

 of spirochetes "drug-fast" to various compounds of arsenic and mercury 

 in vitro. In relapsing fever the clinical course of the disease would indi- 

 dicate that only three or four serum-fast strains can be produced, and we 

 accordingly find that, after a patient has withstood a number of relapses 

 corresponding to the number of antibody-fast strains that the spirillum 

 may produce, spontaneous recovery occurs, there being then antibodies 

 that the strain cannot resist, and the infection "dies out," due in part to 

 destruction of the antibodies and in part to starvation of the parasite 

 because the number of receptors is insufficient to carry on nutrition. 

 In the mean time, however, the patient may succumb to the disease 

 before the spirillum has "played its last card." 



In syphilis conditions are different, and the phenomenon of "resis- 

 tant races" further explains many conditions not previously understood. 

 The spirochete is apparently capable of repairing its receptors to a re- 

 markable degree, especially after injury received from the antibodies pro- 

 duced by body-cells, and, further, is able to maintain its nutrition with 

 a number of different food-stuffs, so that in the untreated person re- 

 lapse follows relapse, the offensive forces of the spirochete being held in 

 abeyance by the defenses of the host over long periods of time (latent 

 periods), but the vital parts of the host being gradually damaged and 

 the defenses weakened so that death or serious symptoms may supervene 



1 Jour. Exper. Med., 1917, xxv, 349 and 363. 



