HORMONES, DRUGS, AND TOXINS 729 



evidence goes, toxins have the property of producing, when injected into the living 

 organism, certain substances which have the power of neutralising their action. 

 These are known as antitoxins, or, in general, as antibodies, and those substances 

 capable of exciting their production are called their antigens. Statements have 

 been made that substances other than proteins may act as antigens ; we have 

 seen (page 3 16) that there is no satisfactory evidence that enzymes can act thus, 

 although some lipoids and glucosides have been said to do so ; the evidence, 

 however, that the preparations were free from protein is not sufficiently clear. 



The mechanism by which "specific" antitoxins are produced is not yet under- 

 stood. Very complex colloidal reactions are certainly involved. Two cases may 

 be mentioned. The blood of the crayfish injected into a mouse makes it immune 

 against scorpion toxin ; but the crayfish itself is more sensitive to the toxin than 

 the mouse is, and its blood does not protect another crayfish. Rabbits can be 

 immunised against tetanus by inoculation with tetanus bacilli in repeated small 

 doses. Yet their serum has no effect in neutralising the toxin in vitro. 



The reader is recommended to consult the papers by Gengou (1908) for various facts to 

 be taken into consideration. The "side-chain" theory of Ehrlich has now ceased to be 

 of much help, otherwise than in the invention of new names, valuable as it has been in 

 the past. 



ANAPHYLAXIS 



It was found by Portier and Richet (1902) that a toxin could be prepared from 

 the tentacles of the sea anemone which caused intense vascular congestion in the 

 viscera of dogs, leading to death after some hours. They found also that, if 

 a dose insufficient to cause death was given, so that the animal recovered, a 

 second dose of only one-twentieth the amount of the first, if given subsequently, 

 caused extremely severe symptoms, vomiting, diarrhoea, paralysis, and so on. 



This effect was obtained only if a certain minimum number of days (eight to 

 twelve) had elapsed between the first and second injections. It will be remembered 

 that, in the usual process of immunisation to a toxin, injections are given at 

 intervals of about four days, without the appearance of severe symptoms, so that 

 the manifestation of this supersensitive state, called by Richet, " anaphylaxis" 

 is prevented by the development of the ordinary state of immunity. We shall 

 see presently that the two processes are intimately connected. 



A remarkable fact is that non-toxic substances, such as egg-white, are also 

 able to produce severe symptoms of anaphylaxis. But a necessary condition seems 

 to be that of the colloidal state ; a similar condition applies to the property of 

 acting as antigens, in general. 



What evidence have we as to the nature of this interesting phenomenon ? 

 The monograph by Richet (1912) gives a good general account of the subject, 

 but the most important experimental work is that of Dale (1912). The value of 

 these investigations consists in the fact that they were made chiefly on an isolated 

 organ, the virgin uterus of the guinea-pig, so that the conditions could be 

 accurately controlled ; the results are of great importance, not only in the 

 interpretation of anaphylaxis, but in the theory of immunity in general. 



It is evident, to begin with, that some change is produced in the blood, by 

 which the tissue cells are affected. In different animals, the actual symptoms 

 vary according to the particular organ most sensitive to these changes in the 

 blood. In the guinea-pig, the bronchial muscle is most affected, in the dog, the 

 liver and intestine. We have seen that a considerable time is necessary for 

 these changes to be produced in the blood, but, once produced, the blood of 

 a sensitised animal can bring about anaphylactic shock in a normal one, 

 immediately, as was shown by Manwaring (1910). At the same time, the 

 anaphylactic substance, or influence, becomes fixed or adsorbed on the tissue 

 cells, so that, as Dale shows, the excised and washed uterus of an anaphylactic 

 animal, suspended in Ringer's solution, is itself sensitive to the antigen. Fig. 258 

 shows the effect, together with the striking " specificity " of the reaction. The 

 organ was taken from a guinea-pig, sensitised by an injection of horse serum, 

 fourteen days previously. It gives no response to a small dose of the serum of 



