The therapeutic interest of the subject centers in the application of inoculation to man. The early experiments of Foa and Scabia were without result, neither reaction nor amelioration attending their treatment; but in 1892, Klemperer reported favorably concerning immunization in 40 cases of human pneumonia.

In January, 1893, Lava communicated to the Academy of Medicine in Turin the application of serum-therapy with auspicious results. Ruzzolo also reported successes. Up to the present time, however, it cannot be said that a successful pneumococcus serum has been devised.

Cholera. - The microbe of this terrible disease had been sought since 1848, yet the subject had never been profoundly studied until Koch succeeded in isolating the germ. Being associated with other micro-organisms, the bacillus had remained undetected, being distinguishable, in fact, only in fulminant attacks of the disease, as was noted by Strauss and Roux.

Haffkine has definitely produced results in the immunization against cholera. He has used his serum on a large scale in India, and his results are encouraging.

Septicemia. - The streptococcus of Fehleisen (erysipelatis), which causes erysipelas, was discovered by Nepveu, in France, and Huter, in Germany (1868-80), and has been the subject of careful study by Klemperer and others, in the hope of determining its availability as an immunizing agent. Employing the serum of immunized rabbits, it has been found possible by intravenous injection to cure the disease in mice, the serum proving efficacious only against the disease with which the animal supplying it was inoculated. Subsequent experiments have been attended with varying results, Marmorek, in February, 1895, having succeeded in obtaining a germ of streptococcus so virulent that the hypodermic injection of 1/100000 Cc. was fatal to the rabbit in thirty hours. Inoculation with this microbe or its toxins conferred immunity upon rabbits, which furnished a preventive and curative serum.

Encouraged by previous experimentation, Charrin and Roget now sought to apply the method of serum-therapy in the treatment of puerperal fever. Having satisfied themselves of the curative property of the serum of a mule inoculated with the microbe of erysipelas, collected fifteen days after the eighth inoculation, they injected subcutaneously 8 Cc. of serum in a woman affected with the fever. The report is as follows: "The next day no improvement. A second injection of 8 Cc. Next day condition slightly improved, but still serious. Third injection of 25 Cc. Result, on the following day rapid improvement; decline of fever; general good health; and early establishment of convalescence."

Antistreptococcic serum gives promise of being second only to the diphtheria antitoxin in point of therapeutic value. It has been most successful in erysipelas and puerperal septicemia. Cases of scarlet fever are reported where it has been useful in shortening the duration of the disease and preventing unfortunate complications and sequelae, such as otitis media and other suppurative processes due to streptococci. Aronson has perfected an antistreptococcic serum from which much is hoped. .

The latest reports on antistreptococcic serum are not so encouraging as the earlier ones.

Syphilis. - The pathogenic source of syphilis is still being sought. The most recent work of Schaudinn and Hofmann, corroborated by Flexner, Noguchi, Metschnikoffand others, would seem to show that a spiral organism, Spirochceta pallida, bears some relationship to the disease. Experimental inoculation has succeeded for lower animals, and the way seems to be opening up for a possible serum therapy of syphilis.

Typhoid Fever. - The bacillus of this disease was first detected in the kidneys by Bouchard in 1879. The name was given by Eberth, who studied the germ in 1880-81. The old cultures contain an exceedingly toxic ptomain, besides a soluble substance capable of inoculating animals.

Wright and Semple have devised a method of vaccine immunization against typhoid which promises well. Bokenham has produced a serum, but results are as yet too few to justify therapeutic conclusions.

Reptile Poisons. - It has long been known that certain animals (reptiles) possess natural immunity against their own venom. The poison of the toad having been detected in his blood, the reptile's immunity was at first thought to be due to tolerance, the same condition existing in the salamander and viper.

So far as it affects man, Calmette announces that he has employed serum with success in the treatment of snake-bites, even to the extent of curing them.

Calmette's antivenin has now become perfected and is found a reliable mode of treating cobra-poisoning.

Noguchi has in course of preparation an anticrotalic serum, against rattlesnake-poisoning, which promises well, although not yet perfected.

Carbuncle (Anthrax). - The bacterium of anthrax, of the genus bacillus, has proved a subject of elaborate and interesting experiment, many features of which are of absorbing interest alike to the bacteriologist and the clinician. The animals subjected to inoculation have been chosen with great care, and those supplying the immunizing serum include many species. The general results orotective inoculation may be regarded as useful for sheep, but for man no reliable serum is known.

Rabies. - In January, 1881, Galtier announced that intravenous inoculation of rabid saliva confers immunity upon sheep, confirming his experiments later in the year by injecting the fluid into nine sheep and one goat. Pasteur, Chamberland, Roux, and Thuiller pursued experiments in a similar line, with somewhat negative results.

By passing the virus successively from dogs to monkeys, Pasteur was able to attenuate its virulence, and finally, by transferring the poison from monkeys to rabbits, a serviceable immunizing agent was obtained, still further experiments perfecting the method in view.

Satisfied with his success, Pasteur now turned his attention to the inoculation of man against hydrophobia. The first operation (in 1885) was attended with auspicious results, and from that moment the savant's laboratory was invaded by affected individuals demanding cure. Institutes were founded in various parts of the world, that in Paris being the center of bacteriological study in France. In America the subject has received wide attention, but in many instances the benefits derived from Pasteur's inoculative procedure have been held to be of doubtful importance by intelligent observers.

Pasteur's treatment of hydrophobia is based on the fact that rabic virus may be intensified or attenuated at will. If successive inoculations be made into rabbits with fluid taken either from the dog or the monkey, the virulence may be so increased above that of a street-dog, requiring from twelve to fourteen days for incubation, that after about one hundred inoculations the period of incubation may be reduced to seven or even six days. This, the most powerful virus yet attained, Pasteur termed virus fixe. When protected from light and air this virus retains its strength for a long period. Pasteur further observed that the cords of rabbits which had been dead for some time contained a less virulent poison than those of animals freshly killed, especially when the air was dry and the cord protected from putrefactive influences, the most efficient inoculation being that of an emulsion made from cords exposed to dry air for ten and fourteen days, followed by emulsions of cords exposed for shorter periods.

With regard to the administration of serum, several precautions are of great importance. The absolute cleanliness of the syringe, for example, should be an object of especial care. To this end a glass barrel is preferable, in order that impurities may be readily detected and removed. For packing purposes rubber or asbestos should be employed, and the instrument should be so constructed as to permit cleansing and sterilizing of every part before and after use.

The mode of injection and the amount of dosage (measured in antitoxin units) vary somewhat according to the nature of the disease and the age and susceptibility of the patient. Care should be taken to use only the most reliable preparations.

It has been impossible to present within a necessarily limited space the entire field covered by this profoundly interesting subject. For a multitude of details, embodying a wide range of experimentation, and for many expressions of individual opinion awakened by a consideration of so-absorbing a theme, the student is referred to the extensive bibliography relating to every phase of serum-therapy.

It may be readily imagined what would have been the discussion of Jenner's vaccination had our bacteriological and chemical knowledge and delicate appliances for investigation existed in his day. It is scarcely surprising, therefore, that the renewal of similar studies, after an interval of unprecedented scientific progress, should elicit from all parts of the world a zeal and enthusiasm impossible in any previous epoch, together with a mass of concurrent or dissenting testimony touching new discoveries proportionate to the greatly increased number of competent investigators. Whatever be the limitations of serum-therapy, the consensus of opinion among thoughtful observers is that its importance to mankind and its purpose are deeply rooted in the eternal laws of matter and the methods of great Nature. Its rationale, its mysterious power, and startling phenomena awaken new and greater problems of bacteriological science; yet, though the entire subject, embracing as it does so ample and momentous a field of inquiry, remains sub judice, the character of modern scientific investigation must surely reveal its truth or falsity.