Some science behind the scenes
Anaphylaxis - and soluble proteins
Charles Robert Richet - Nobel Lecture - December 11, 1913 on Anaphylaxis
It should be understood that the term alimentary anaphylaxis does not signify anaphylaxis by alimentary substances but anaphylaxis by the introduction of the anaphylactizing substance by way of the digestive channels. Alimentary anaphylaxis is characterized by the antigen, whether alimentary or not, being introduced into the organism by means of the digestive tube. Introduction by the rectal duct is not included, as the essential feature of alimentary ingestion is absent, which is the modification of the antigen by the digestive juices.
Alimentary anaphylaxis has been studied on various hands since Rosenau and Anderson, but the results are not so far constant nor uniform. I have tried to tackle the problem from another angle, that is to see under what conditions substances introduced into the stomach can pass into the blood. I used a reagent that is extremely sensitive, namely leucocytosis.
A dog is given cooked meat: no leucocytosis results. A dog is given raw meat, even one fifth in quantity compared with the cooked meat, then in three or four hours time, leucocytosis results. The most likely and simplest explanation is that when cooked meat is ingested, all the proteins have become non-soluble and can not be made soluble except by the action of digestive juices: pepsin, trypsin and erepsin. The products of the break-up of the protein that are formed are non-toxic and do not induce the leucocytic reaction. It is therefore not surprising that cooked meat should be ingested without affecting the leucocytes, for no soluble protein has been introduced into the stomach, and the only proteins which can pass it are those that have been modified, transformed and homogenized by the digestive juices.
Now if muscle serum or raw meat is ingested, then soluble proteins are introduced into the stomach. The digestive juices have powerful action, but it is probable that part of the protein escapes and certain particles pass into the circulation, thus effecting a true antigen injection, which can thus set off the leucocyte reaction.
It follows that each time soluble protein is introduced by the digestive channels, anaphylactic reaction may result, as it is equivalent to an antigen injection.
This may explain away the divergences of opinion among physiologists in respect of alimentary anaphylaxis, for following the introduction of a protein, depending on whether it is soluble or not, whether it is absorbed or not, whether it is resistant to the action of the ferments or not, it will or will not penetrate into the blood system.
I have indicated that there are three methods of alimentary anaphylaxis. Let us call the alimentary ingestion A, and the parenteral injection P. The following combinations are possible:
- A preparatory, A releasing;
- A preparatory, P releasing ;
- P preparatory, A releasing.
Even in the first of these three cases (A + A) where the anaphylaxis is strictly alimentary, for the initial ingestion as well as the subsequent ingestion, there is no doubt about anaphylaxis having taken place. When a dog ingests crepitin for the first time, he never vomits. When he ingests it for the second time, some three weeks later, he always vomits. This is the anaphylactic protective vomit. In the second case (A + P), the preparatory ingestion being alimentary and the releasing injection parenteral, the results are clearer still. In effect the anaphylactic shock is violent and plainly proves that a small quantity of crepitin must have escaped the digestive juices at the first ingestion and passed to the blood, as the lasting leucocytosis to be found in animals that have ingested crepitin also shows.
I have observed in this connection a remarkable fact: a period of one year between the initial ingestion and the subsequent parenteral injection. A dog ingested in June 1911 a strong dose of crepitin and survived. (Whatever the dose, it is not possible to poison dogs by ingesting crepitin.) After one year had passed, in June 1912, this dog had a harmless crepitin injection and died within an hour and a half as if struck by lightning. The death of a dog at this speed from anaphylactic shock is very rare indeed.
To these experiments, I must add the work of Gideon Wells and Thomas Osborne. In January 1911, they made a close study of the anaphylactizing and immunizing action of vegetable proteins.
The general conclusion is as expected but nevertheless necessary to be shown:
(1) through the digestive mucous membranes never passes more than tiny amounts of colloids, but sometimes it does pass them;
(2) these minute amounts are enough on occasion to cause the anaphylactic state either preparatory or unleashing;
(3) the amounts of colloids that pass into the digestive juices are weak enough to give immunity rather than anaphylaxis, especially if it be remembered that most are cases of ingestion repeated and increased at various intervals: all which conditions favour anti-anaphylaxis immunity rather than true anaphylaxis.
These findings in the field of alimentary anaphylaxis are perhaps not without importance to clinical medicine. It may be that many cases of dyspepsia are nothing more than light attacks of anaphylaxis. Doctors have long found that regular diet on strictly uniform lines was to be preferred to all other regimens. It is as if by the repeated ingestion of one some protein substance the organism had accustomed itself to it and had immunized itself against this usual antigen.