When a child is suffering from diphtheria, its throat constitutes the flask in which the bacillus is growing and elaborating its toxin. The toxin filters through the walls of the pharynx into the blood. The physician in jects under the skin of the child the serum of the immunized horse which he calls anti toxin, and this passes into the blood of the child and neutralizes the toxin absorbed in the throat. Thus, the acid and alkali are brought together and a harmless product results. The toxin being neutralized as fast as it is absorbed from the throat, does not attack or injure the body cells of the child. It must be evident that the earlier in the infection the neutralizing agent can be used, the more satisfactory is the result. Here, hours count. It has been shown that when the antitoxin is injected into the child on the first sign of the disease the per centage of recoveries is 100. Out of cases studied by Hilbert the percentage of deaths varied with the day on which the anti toxin was administered as follows: According to Wernicke the saving of lives during the first year of the use of diphtheria antitoxin in Germany amounted to 20,000, and if the agent were promptly and properly used the saving of lives would amount in that coun try to 45,000 annually. The value of diphtheria antitoxin is even greater than is indicated by the lowering in the death rate from this disease. For every sick child treated with antitoxin, on an average five are saved from being sick. While the curative value of antitoxin is great, its preventative value is still greater. The physician called to a family in which one child has diphtheria gives a curative dose of anti toxin to the sick child and immunizing doses to the others. Even when the sick child has been neglected so long that the curative value of the antitoxin is lost, its preventive value in the others is still potent. Diphtheria antitoxin has lowered not only the mortality rate hut still more the morbidity rate. In 1880, before the discovery and employment of this agent, deaths from diphtheria in the registered area of the United States amounted to 112.6 per 100,000; in 1913, after the general employment of diphtheria antitoxin, it was 18.8. Certainly it is no axaggeration that the discovery of diphtheria antitoxin is one of the most benef icent of all agents, and it could not have been made without animal experimentation. The pre paration of this agent necessitates the annual sacrifice of the lives of hundreds of guinea pigs, and it leads to the saving of the lives of thousands and tens of tholiands of children.
State and municipal laboratories are em ployed in the detection and recognition of diphtheria, and antitoxin is. furnished free to those who cannot afford to pay for it. When a physician sees a case which he suspects to be diphtheria he makes a swab from the throat of the child and transfers this in a sterilized test tube to the municipal laboratory. Here a culture is made and after 12 hours a positive statement can be furnished as to the nature of the disease. Even this delay is unnecessary if the physician is sufficiently confident that he has a case of diphtheria to deal with. Under proper precautions there is no danger in the administration of this agent. In the more en lightened communities school medical inspec tors are constantly on the watch for the first evidence of this disease and the child of the poorest citizen is transferred and treated in a municipal hospital with as much skill and care as the richest can secure. Since diphtheria
toxin has not been obtained in a pure state, its nature, so far as its chemistry is concerned, remains unknown. There is still doubt as to in just what group it should be classified. Usu ally it gives at least some of the general protein color tests, but preparations have been secured which do not respona, altogether at least, to these tests. The molecular weight of the toxin is much less than that of the antitoxin be cause the former filters readily through porcelain and diffuses quickly through gelatin, while the antitoxin is largely removed from solution by filtration through porcelain and does not diffuse through gelatin. From these facts it is inferred that the molecule of the anti toxin is much larger than that of the toxin. The toxin is highly susceptible to heat, a tem perature of 60°C. being sufficient to markedly reduce, although it does not wholly destroy its toxicity. A like effect is induced by the pres ence of both mineral and vegetable acids. Even lactic and tartaric acids speedily render it inert and its toxicity is reduced, although not completely destroyed, by borax and boric acid. It is highly susceptible to the action of oxidizing agents such as potassium perman ganate, chlorine, iodine, etc. It diffuses through parchment but does not pass through animal membranes or collodion sacs. It is in soluble in alcohol, and prolonged contact with this agent destroys its toxicity. It is also robbed of its virulence by the digestive fer ments present in the alimentary canal, and therefore is harmless when taken into the mouth, provided there is no break in the con tinuity of the mucous membrane. From solu tion it is carried down mechanically on the addition of calcium chloride, which precipitates calcium phosphate. In this respect diphtheria toxin closely resembles the enzymes. There are other respects in which this resemblance is evident. Some of these are as follows: (1) It is destroyed by heat; (2) in its purest preparation it does not respond to all the tests characteristic of proteins; (3) it is active in high dilutions; (4) it is a product of cell activity; (5) when introduced into the body there is a period of incubation before the de velopment of its effects; (6) when introduced into animals in progressively augmented doses it leads to the production of an antibody.
The chief objection to accepting the theory that toxins are enzymes or ferments lies in the fact that in their action on animals and in their reactions with their antibodies their effects may be measured mathematically and follow the law of multiple proportion. In other words, the toxins do enter into the reactions and are ex hausted or neutralized in doing so. On the other hand, the weight of evidence is that enzymes or ferments do not enter into the reactions caused by their presence and that they are not consumed in such reactions. For in stance, the hydrolytic enzymes, such as diastase and pepsin, cause starch and protein to take up water and pass over into sugar and peptone while the enzyme itself does not enter into the reaction and is not consumed in the process. It might be stated differently as follows: An enzyme changes the tempo of a reaction which would more slowly occur without its presence, while a toxin combines with its antibody much as an acid combines with an alkali.