458 CORYNEBACTERIUM 



the injection of 2 ml. of a virulent culture ; oedema, of varjdng degree, was present at the 

 site of inoculation in 94 per cent, of the animals ; the adrenals were abnormal in all and 

 are noted as pink in 4 per cent., red in 22 per cent., and deep red in 74 per cent. ; a pleural 

 exudate was present in 44 per cent. 



For details of the histological changes associated with these lesions, reference may be 

 made to the monograph pubUshed by the Medical Research Council. We may, however, 

 note a few points which have a direct bearing on diphtheria as it occurs in man. Mollard 

 and Regaud (1895) recorded the occurrence of degenerative changes in the myocardium in 

 experimental diphtheria, and Flexner (1897) noted that fatty degeneration of the cardiac 

 muscle was almost constantly present in animals which died within a short time after 

 inoculation. There has been some discussion as to whether these changes are primary, or 

 are a sequel to an initial reaction in the interstitial tissue, or to a primary lesion of afferent 

 nerve fibres. The careful and detailed studies of Dudgeon (1906) gave a clear answer to 

 this question, and afforded strong experimental support to the suggestion of Bolton (1905), 

 that the direct action of diphtheria toxin on the cardiac muscle is the most important 

 cause of acute cardiac failure in human diphtheria. Examining a large series of guinea- 

 pigs, killed or dying in various stages of acute diphtheritic toxaemia, Dudgeon demonstrated 

 the occurrence of fatty degeneration of the diaphragmatic muscle within 4 hours after 

 inoculation, and of the cardiac muscle within 16 hours. Similar results have since been 

 recorded by Jaffe (1920). 



We may note also, since this method is now frequently employed in the identification 

 of a toxigenic strain of C. diphtherice, that the intradermal injection of toxin, or of living 

 baciUi, leads to a localized erythematous lesion, followed bj^ necrosis (Romer 1909). This 

 effect, as also the lethal action of the subcutaneous injection of larger doses, can, of course, 

 be specifically neutraUzed by an antitoxic serum. 



Although the production of this filtrable toxin, with its characteristic action 

 in the guinea-pig and its property of being specifically neutralized by the homologous 

 antitoxin, is one of the most important characters by which C. diphtherice is identified, 

 there exist strains of bacilli that, while conforming in all other respects with the 

 diphtheria bacillus, fail to form this filtrable toxin. These strains are commonly 

 classed as non-toxigenic, or avirulent, diphtheria bacilli. Whether they should 

 in all cases be assigned to this species is perhaps doubtful ; but there can be no 

 reasonable doubt that many of them, at least, are actually non-toxigenic variants 

 of C. diphtherice. We have noted above that certain avirulent strains can be shown 

 to be antigenically related to typical toxigenic strains, and the actual emergence 

 of an avirulent variant from a virulent organism, under laboratory conditions, has 

 been recorded by several observers. 



Thus Crowell (1926), starting from a single-cell culture of a fully virulent strain, 

 derived from this parent culture a series of daughter strains, one of which was 

 entirely avirulent. All attempts to raise the virulence of this variant were without 

 result. Cowan (1927) records the derivation of avirulent variants from 2 strains 

 of virulent C. diphtherice, one of them the classical " Park 8 " which has yielded 

 toxin to most laboratories in the world. These variants were " rough," in the 

 sense that they formed small, raised, dense and granular colonies, and gave increased 

 deposit in broth, with an absence of pellicle formation. 



The diphtheria bacillus is not the only species of Corynebacterium that is patho- 

 genic under natural conditions. C. ovis, C. murium, C. pyogenes, C. equi and 

 C. renale certainly fall into this category. So probably does C. acnes. 



A great variety of diphtheroid organisms have, at one time or another, been 

 isolated from various tissues in man and animals. Sometimes the tissue from which 

 the diphtheroid bacillus was isolated has been the site of some obvious lesion ; 



