Serum Therapy

SERUM THERAPY. Serum therapy consists in the intro duction into the patient of blood serum containing specific anti bodies, preformed in some other animal, which will (a) neutralise the toxins produced by the corresponding infecting bacteria or (b) destroy the corresponding bacteria themselves—thus estab lishing a condition of "passive" immunity (q.v.).

Action of Microbes.

Disease-producing microbes may be divided into two broad groups (I) those secreting poisonous sub stances or toxins into the surrounding tissues or (2) those multi plying and invading areas far distant from the point at which they gained entry to the body of their host.

Again, speaking generally, natural recovery from a bacterial in fection due to an organism of the first group coincides with the appearance in the blood serum of a neutralising agent known as anti-toxin in adequate amount ; whilst when dealing with microbes of the second class, nature elaborates, also in the serum, a different anti-body—a bacteriolysin or immune body for the purpose of de stroying the invading bacteria. In each instance the resulting anti-body is specific in character—that is to say, it will only act in opposition to the particular toxin in the one case or in the other to the members of that particular species of microbe whose entry into the body provoked its formation—the serum which is the vehicle of the curative substance is termed in this first instance "anti-toxic" and in the second "anti-bacterial." Thus the early and accurate recognition of the bacterium responsible for any infec tion it is proposed to treat determines the selection of the appro priate anti-serum.

Preparation of Anti-serum.

As these sera are nowadays em ployed in considerable quantities it is customary to select a large mammal, such as the horse, for immunisation. After a period of observation during which the freedom of the animal from diseases transmissible to man is established, a series of subcutaneous injec tions is undertaken starting with an artificially attenuated virus or a mixture of toxin and previously obtained anti-toxin as the case may be and gradually increasing the size of the dose and the potency thereof until the animal is able to withstand enormous quantities of highly poisonous material without any ill effects while maintaining perfect physical condition. From time to time small quantities of blood are withdrawn from the animal and the serum tested to ascertain the amount of anti-body that is avail able, and when a suitable stage has been reached the animal is bled to the extent of several pints, the serum carefully separated from the blood corpuscles and passed through a sterile porcelain filter to ensure its freedom from bacteria. Occasionally the serum is

concentrated, some of its unneeded proteins removed and purified.

It is obvious that a correct appreciation of its valency is neces sary for the scientific employment of, any serum in the treatment of disease ; but, unfortunately, bacterial poisons formed by various micro-organisms, and even by different strains of the same species, not only exhibit many variations in toxicity depending upon bi ological factors (not all of which are at present known) but they have, so far, proved incapable of isolation in a state of chemical purity. Consequently, it is only possible in the majority of in stances to effect a comparison by observing the results of their introduction into suitable experimental animals.

Indeed only in the case of diphtheria toxin is there any uni versally accepted standard, for here Ehrlich prepared, many years ago, a standard diphtheria anti-toxin of constant valency which is preserved hermetically sealed in vacuo, by means of which all diphtheria toxins can be graded and the potency of the sera pre pared by their means expressed in anti-toxic units.

In the case of toxins produced by other bacteria, and in the preparation of anti-bacterial sera, the plan usually adopted is to inoculate gradually decreasing doses of the virus into susceptible animals until the smallest quantity that will cause death with cer tainty, and within a specified time, is determined. This is termed the minimal lethal dose (M.L.D.) and forms the basis for the standardisation of the corresponding anti-serum. Varying quanti ties of serum are in turn mixed with a constant dose of virus— usually ioo M.L.D.—and injected into animals until that amount of serum is determined which will effectively neutralise the test dose. This quantity of serum is then regarded as containing one unit of anti-body and the serum which is in process of standardisa tion is stated to contain so many units per cubic centimetre.