TOXINS AND ANTITOXINS 63 



proper doses will produce marked, often bloody, diarrhea, wasting, 

 paresis, or even paralysis of extremities, and death. The autopsy 

 shows marked inflammation, often hemorrhagic, particularly severe 

 in the cecum, but also involving the large intestine and lower 

 ileum. Monkeys, cats, and dogs are also susceptible, but fowl, pigeons, 

 and guinea-pigs are resistant. Antitoxin can be produced in horses 

 and goats. There is considerable difficulty in standardizing such a 

 serum, owing to the variation in individual susceptibility of ani- 

 mals. Kraus and Doerr have shown that the immune serum first 

 shows a capacity to neutralize toxin in vitro, then in vivo (simul- 

 taneous injection of toxin and antitoxin into opposite ear veins), 

 and finally it attains a definite curative value as demonstrated by 

 primary injections of toxin followed after certain time intervals by 

 antitoxin. A serum must have a high curative value before it is 

 acceptable and is used in doses of cubic centimeters rather 

 than units. 



Therapeutic Use of Anti-dysentery Sera. After the discovery of 

 the dysentery bacillus by Shiga in 1898 it was found that the sepa- 

 rate types of this organism vary greatly in their power to produce 

 toxic substances. The most toxic varieties are those of Shiga and 

 Kruse, and their toxins are not only endotoxic but also exotoxic in 

 nature, a fact clearly established by the work of Todd, Liidke, 

 Kraus, Doerr, and Rosenthal. Shiga was the first to immunize 

 horses with killed cultures of his organism and produced highly 

 protective sera capable of saving guinea-pigs injected with six 

 times the lethal dose of living bacilli. This specific anti-bacterial 

 serum was used by Shiga with encouraging results during a dysen- 

 tery epidemic in Japan, the mortality among cases treated with 

 Shiga's serum being one-third of that among cases treated by the 

 usual routine procedures. Not only was the mortality greatly re- 

 duced, but the total period of illness decreased from forty to twenty- 

 five days. A similar serum was prepared by Kruse and its use 

 reduced the mortality among Kruse's cases from n to 5 per cent. 

 Kraus and Doerr also obtained favorable results from the use of 

 their serum, which was mainly an antitoxic serum produced by the 

 injection of filtrates of young cultures into horses. Vaillard and 

 Dopter treated a large number of cases with a serum prepared by 

 themselves and possessing both antibacterial and antitoxic prop- 

 erties and reported highly encouraging results with a mortality of 

 2 per cent., while the mortality otherwise would have been between 

 ii and 25 per cent. More prompt effects were obtained when the 

 serum was given at the earliest moment in the course of the disease. 

 Vaillard and Dopter used 20 to 30 c.c. in moderate cases and from 

 40 to 80 c.c. in grave cases. In late cases serum injections were 

 often of value. Graham more recently has added a valuable contri- 

 bution to the serum therapy in bacillary dysentery, his studies being 

 made during the campaign in Macedonia. Graham used a serum 

 prepared at the Lister Institute and gave intravenous injections of 



