Among the marvels of scientific research which have distinguished our century no achievements are more remarkable, nor of greater moment to the welfare of mankind, than those pertaining to the field of biologic, pathologic, and therapeutic investigation. The limits of the present work preclude a detailed treatment of so extensive and complicated a subject; yet a brief summary, elucidating the theory and development of serum-therapy as exemplified in contemporaneous research, should be of interest, as well as benefit, to the student of modern therapeutics.

A glance at the history of therapeutic procedure in the prophylactic treatment of infectious diseases shows that the general principle underlying all later discoveries had been, though crudely, divined at a much earlier period than we are wont to suppose. In view of actual attainment it is natural that the mind should revert to the transcendent services rendered to mankind by Jenner; yet it is known that the ancient Hindus and Persians, as well as the nomad tribes and caravans of farther Asia, practised inoculation of equine virus, or horse-pox - the mammary pustule developed during early lactation in the horse, camel, and cow, and even in woman.

The inoculation of human virus is of immemorial origin, probably coeval with the importation of variola from Asia into Africa by the Saracens. Certain it is that as early as the tenth century the Arabs and Chinese adopted the custom of variolization, the inoculation of small-pox, although the skeptical physicians of the agonsigned the practice as a monoply to women. Of the developments of the treatment for small-pox we refer to special works.

It was reserved for Jenner, however, in 1776, to commence the systematic and exhaustive study of the subject destined to prove inestimably beneficial to mankind. His early experiments were but a repetition of the empirical, yet prophetic, test of the English farmer; and it was not until 1798 that Jenner published his first paper upon the subject, vaccination being transported to America in the following year. Such is the brief, yet eloquent, record of an achievement which experience has proved to be of incalculable benefit to man. To-day there is no question among the more enlightened members of the profession that the operation, properly performed, is an absolute safeguard against the infection of small-pox.

Strange, indeed, is it that a century of comparative quiescence should have elapsed since Jenner pointed the way to the startling accomplishment of the present epoch. Yet not until Pasteur, in 1880, announced to the world the issue of his labors touching the protective inoculation of animals was the broken thread of pathogenic research taken up anew, and the task of solving its mysteries resumed - be it said with more profound acumen and far more complete appliances than ever before.

It is a matter of record how the French savant demonstrated that cultures of the bacilli of chicken-cholera, when thoroughly dried and long exposed to the air, lost their virulence, and that fowls inoculated with the attenuated virus were rendered insensible to the attacks of more energetic micro-organisms. It was, mutatis mutandis, a modification or development of the Jennerian principle: "The history of vaccination constitutes the first step in a long series of labors inspired by the admirable discoveries originating in the genius of Pasteur. The principle is always the same - to diminish the strength of the virus and inject it into the animal which we wish to render immune "(Bernheim).

A striking departure from Pasteur's method by Salmon and Smith, in 1886-87, led indirectly to the latest evolution of inoculative therapy. They showed conclusively that animals may be rendered immune against certain infectious diseases by inoculating them with filtered cultures containing the toxic products of pathogenic micro-organisms entirely free from the living bacteria to which they owe their origin. By this process immunity against the bacillus of hog-cholera was attained in pigeons, the disease being almost invariably fatal to these birds. A little later (1888) Roux, employing similar sterilized cultures, succeeded in protecting susceptible animals against the anthrax bacillus; and more recently (1890) Behring and Kitasato have proved that immunity against the action of the tetanus bacillus may be conferred by the use of toxic products in solution freed from the presence of active germs - in a word, that purely chemical agents sufficed to attain the object hitherto deemed wholly dependent upon the influence of living bacteria. The significance of this discovery could hardly be over-estimated. By it the entire theory of causal phenomena- the protective force in which the immunizing property was supposed to reside - became modified. If not a living organism, but a chemical substance, proved to be the immunizing agent, then resistance to toxic influences must proceed from some source other than bacterial metabolism - some organic force inherent in the inoculated system. To ascertain the nature and operation of this bactericidal power and determine the rationale of acquired immunity now engaged the earnest attention of savants throughout the world. It is the province of the text-book of pathology to discuss the various problems of immunity. In this work the results only of the studies as applied to Therapeutics can be taken up.

Tetanus. - The first proof that tetanus is an infectious disease, of ballicary origin, was furnished by Carle and Cattone, who in 1884 reproduced the symptoms in a rabbit by inoculation of pus taken from a human tetanus wound. The bacilli were found in the adjacent soil, but it was not until 1889 that Kitasato succeeded in isolating pure cultures, proving conclusively the microbic nature of the disease.

The earliest case treated with antitoxin was reported in 1891 by a Bolognese physician, Dr. Gagliardi, the result being very satisfactory.

In December, 1890, Behring and Kitasato demonstrated that the serum of animals rendered immune against tetanus by the injection of iodine trichloride in the blood was capable of neutralizing tetanic poison, whether in the laboratory or in other animals, the property not being possessed by organisms not inoculated. Not only did they succeed in preventing infection, but they recognized in the serum a curative power, as shown in the inoculation and cure of mice. At the same time it was observed by Vaillard that the immunity conferred by the serum was of short duration, lasting only fifteen days.

Kitasato's preventive injection - a mixture of living culture and gradually decreasing doses of iodine trichloride - was perfected by Behring, who successfully applied it to the mouse, rabbit, sheep, and horse. Various results of experimental research ensued, eliciting, among other interesting phenomena, the fact that removal of the spleen renders immunization impossible. In 1891, Vaillard showed that the serum of animals naturally immune is not antitoxic, becoming so only after a powerful dose of tetanic poison, and that the spleen and the fluids of immunized subjects are devoid of antitoxic properties.

The present status of tetanus antitoxin is not settled. It has not fulfilled all that was hoped for it, yet, injection into nerve trunks and within the cerebral substance has in the early stages proved to be of some service. Meltzer has recently suggested magnesium sulphate by intrarachidian injections, and Blake has reported a phenomenally successful result following its use.

Diphtheria. - It is in the treatment of this universal and terrible disease that serum-therapy has achieved its most signal triumphs, the marvels wrought by its influence attracting more and more the attention both of the medical profession and of the laity.

The micro-organism of the malady was described by Klebs in 1883, his investigations being quickly followed by those of Loeffler, who confirmed Klebs' discovery and announced that it was possible not only to insolate, but also to produce, cultures of the microbe.