810 



SCIENCE. 



[N. S. Vol. XVI. No. 412. 



things, but also of chemical substances and 

 of disease. 



The resemblances and the differences 

 thus revealed are doubtless fundamentally 

 of a physico-chemical nature, but in many 

 instances they transcend the powers of the 

 microscope or of ordinary chemical tests 

 to detect. 



The results already attained by the 

 method of serum diagnosis*— using this 

 expression in its widest sense — are not only 

 of interest and importance to the biologist, 

 phj^siologist and chemist, but of great prac- 

 tical value to the bacteriologist and the 

 physician. As this is not an aspect of my 

 subject, broad and important as it is, iipon 

 the details of which I propose to dwell, it 

 must suffice to present, by way of illustra- 

 tion, examples of the diagnostic application 

 of different kinds of specific serums. 



The only certain means of detecting tox- 

 ins of the class of diphtheria or tetanus 

 toxin, snake venom and certain vegetable 

 poisons of the same category is their neu- 

 tralization by the corresponding antitoxic 

 serums. Occasion may arise where such 

 detection is of practical and even medico- 

 legal importance, as has been exemplified 

 in India, where the criminal use of cobra 

 venom is not unknown. 



* The general procedure followed in the produc- 

 tion of specific serums is the injection into a suit- 

 able animal at intervals of time repeated doses of 

 toxins, bacteria, foreign cells, or other material 

 against which the antibody is desired. For ex- 

 ample, if a specific precipitating or a hoemolytlc 

 serum for human blood is wanted, an animal, say 

 a rabbit, is injected subcutaneously or intraperi- 

 toneally at intervals of three or more days with 

 five or six doses of human serum or Imman red 

 blood corpuscles. At the end of this time the 

 rabbit's serum has acquired the property of pre- 

 cipitating human serum in strong dilutions, or 

 of dissoh-ing human red blood corpuscles, if these 

 were used for the injection. Within limits the 

 less closely related the two species of animals 

 the more powerful is the antagonistic effect of 

 the specific serum. This is true especially in the 

 case of cytotoxic serums. 



The application of serum diagnosis which 

 is most familiar to physicians is the agglu- 

 tinative test for typhoid fever. The prin- 

 ciples of the agglutinative reaction were 

 worked out in the laboratory of Professor 

 Gruber in Vienna by himself and Durham, 

 and were there first applied to the diagnosis 

 of typhoid fever by Griinbaum, who was 

 anticipated in his publication by Widal, 

 who has made a thorough clinical study of 

 the subject. The method is of great value, 

 not only in the diagnosis of disease, but 

 also in the identification of bacterial species 

 and the recognition of relationships be- 

 tween species. Durham, to whom we owe 

 important contributions to this subject, has 

 given an ingenious hypothetical explana- 

 tion of mutual agglutinative reactions, the 

 main features of which are paralleled in 

 Ehrlich and Morgenroth's doctrine, based 

 upon experiments, relating to the multi- 

 plicity of cell receptors and of amboceptors 

 concerned in hfemolysis.* 



We have found the agglutinative reaction 

 an indispensable aid in the study of the 

 series of eases of paratj'phoid fever which 

 have come under observation in Dr. Osier's 

 wards at the Johns Hopkins Hospital, 

 and which otherwise it would have been 

 scarcely possible to have separated from 

 tj^hoid fever, f The occurrence of para- 

 typhoid fever as a distinct disease affords 

 an explanation of a certain proportion 

 of the failures of the serum from supposed 

 typhoid fever patients to clump typhoid 

 bacilli. Not less valuable is the serum test 

 in the diagnosis of Bacillus dysenterice 

 Shiga and of the diseases caused by it. 

 This microorganism has been shown by 

 Flexner and his pupils, Vedder and Duval, 



* Durham, Journal of Experimental Medicine, 

 January 15, 1901, Vol. V., p. 353. Ehrlich and 

 Morgenroth, Berl. klin. Woch., May 27, 1901, p. 

 570. 



t See papers on paratyphoid fever, by Johnston, 

 Hewlett and Longcope in American Journal of 

 Medical Sciences, August, 1902. 



