Besides those basic compounds known as leucomaines and ptomaines, certain toxic albuminous substances (tox-albumins) are found already formed, or are artificially created. They are now usually called toxins, because possessed of active toxic properties. Of those formed in the course of the physiological activity of organs are the various snake-poisons, and abrin, from the abrus precatorius, commonly known as "jequirety," and ricin, from the castor-oil bean (Ricinus communis). Besides the toxalbumins, or toxins, there are also formed principles that protect the organism against the effects of toxins, and are hence known as antitoxins. Toxins are the products of bacterial actions. Among the more familiar are the anthrax protein produced by the anthrax bacillus, toxopeptone and toxoglobulin produced by the cholera bacillus, and toxomucin (tuberculin) produced by the tubercle bacillus. Some organisms are provided with an albuminous substance which has the power to destroy pathogenic bacilli, or to antagonize the toxin which they form. The condition of exemption thus created is known as immunity. It is now believed that pathogenic bacteria produce each a poison peculiar to itself, and an albuminous substance which, if injected into the tissues of another animal, protects it against the action of the poison. An animal thus protected is said to be immune, and if the blood-serum of such immunized animal is injected into the system of another animal, this also becomes immune.

We owe especially to Behring, of Berlin, and Roux, of Paris, the demonstration of the methods by which immunization and the formation of antitoxins are produced. Taking the diphtheria toxin and antitoxin as models, we find that the first step consists in the formation of an active toxin by cultivation of the germs in an artificial medium. From a number of such cultures a specially virulent one is selected. The activity of this toxin is ascertained by injecting it into guinea pigs. If it is ascertained to have sufficient virulence or toxic power, it is then used to secure the immunization of the horse, which is found to be the most suitable animal for the purpose. As there are great differences among horses in regard to their susceptibility to the effects of the toxin, a small dose is first employed. Beginning with ½ c. c, the strength of the injection is rapidly increased until it reaches 200 to 250 c. c. The injection is practiced once in eight days, and consequently three or four months are occupied in producing immunization, so that at length as much as 250 c. c. can be injected without producing any reaction. The result is, the injection of toxins develops antitoxin in the blood-serum of the horse. To procure the antitoxin in a form available for administration, the blood is drawn off under suitable precautions, and the serum is separated from it by a process of aseptic filtration. Patience in the whole proceeding, care at every step, and minute attention to the horse's health, are necessary to secure the best result. The physician should only make use of serum that has been carefully tested and that conforms to the highest standard.

The foregoing remarks on the immunization of the horse are based on the administration of the toxin by subcutaneous injection. If, however, the toxin is injected directly into the horse's veins, and the process of immunization is conducted over a longer period of time, the resulting product will have considerably greater power. The strength of antitoxin solutions must, it was early seen, be expressed in terms of a uniform standard that may be universally conformed to. A unit being agreed upon, the other terms of the scale follow—that is, an immunity unit in which the amount of antitoxin serum sufficient to save from fatal results a guinea pig weighing 500 grammes, to which the minimum fatal dose of diphtheria toxin has been given. Ten times more is required for the human subject than for the guinea pig, is a close estimate.

The first therapeutical employment of antitoxin in disease was by Behring, soon followed by the clinical observations of Roux. Behring ascertained that active cultures of the bacillus of diphtheria were ren-dered inactive by mixing them with the blood-serum of immunized animals. The serum was then used as a vaccine to prevent the poison of diphtheria (toxin) developing in susceptible subjects, and to neutralize or inhibit it when the disease was in process of evolution. Roux carried out the same method at Paris with equally promising results, and at the present time this plan of preventing diphtheria or of arresting it has been taken up in all civilized countries.

The units of strength of any preparation of serum should be known before making use of it. The quantity injected varies from 1/1000 to 1/100 of the body weight, the latter rarely. About 20 c. c. is probably the average of the various serums in the market. The frequency of the injection varies with the severity of the case, and is once or twice in the twenty-four hours. Some redness, and not infrequently erythematous rashes and urticaria, appear near the site of the injection. If suitable antiseptic precautions are observed, nodules followed by sup- puration can hardly occur. The earlier the serum is injected the more favorable the result. It can hardly be expected that cases of many days' standing, with extension of the local process to the larynx, and with general diffusion of the poison, will prove as amenable to the action of the antitoxin as recent examples of the disease; but it has happened. Some cases of the worst type have been most favorably acted on. The injection of antitoxin when it acts well reduces temperature, abates dyspnoea, and favors detachment and expulsion of the false membrane.

Tetanus is now known to be produced by a special bacillus. Cultures of the bacillus by the method of Behring develops in animals by repeated injection a state of immunity, and immunized animals furnish a blood-serum containing the antitoxin. When the serum is added to the poison the latter loses its activity and is harmless. Many successful cases of tetanus treated by the antitoxin have been published. When a sufficient quantity of the serum of immunized animals has been injected, the severity of the disease is lessened, the spasms become less frequent, the temperature falls, sleep occurs, the general state improves, and the duration of the disease is shortened.

Pneumonia is one of the specific maladies which has been subjected to the action of an antitoxin. Animals are rendered immune by repeated injections of cultures of the pneumococcus, and the serum of immunized animals was found to be effective against pneumonia. These experiments proved so successful that Neisser and Klemperer then proceeded to make use of the serum of human subjects convalescent from pneumonia. In accordance with the principles already enunciated, it was supposed that an attack of pneumonia developed the antitoxin in the blood-serum of the individual affected. In the trials in pneumonia that have been made, it was found that the antitoxin serum lessened the violence of the disease, the crisis occurred early, and with the decline in temperature to the normal there ensued a corresponding abatement in the physical signs. The trials that have been made in this country, if not altogether favorable, have at least given promise of future success when all the conditions are properly complied with.

The treatment of hydrophobia by antitoxins is associated with the name of Pasteur. Although his theory is not accepted by all, and his results are questioned, there can be little doubt that his method of vaccine has greatly modified the usual course and termination of that disease. The real place which this mode of treatment shall take in the therapeutical processes of the future can not now be stated. It must be regarded as still subjudice, with the preponderance of authority in favor of the method. On a candid survey of the whole field, the author is constrained to say, however, that the practical outcome is short of the success which seemed to him warranted by the pretensions put forward by its original promoters.

Authorities referred to:

Bra, Dr. M. La Thérapeutique des Tissues; Compendium des Medications par lea Extraits d' Organs Animaux. Paris, J. Rothschild, 1895, pp. 624.

[To mention the numerous papers and works on the subject would occupy too much space. The work named is the most recent and elaborate on the subject.]