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Thus if a small portion of blood serum of a person suffering from typhoid fever is added to a culture of typhoid-fever germs, the bacteria quickly become clumped together, or agglutinated; but this does not happen in the presence of serum of an individual in health. This test-which bears the name of the French physician, Widal-is a valuable aid in the diagnosis of a suspected case of typhoid fever.

The discovery of one after another of these antidotal chemicals, all evoked in the tissues in response to the onslaught of noxious bacteria, and each serving an important function in the battle against disease, tended naturally to minimize more and more the importance of the white blood corpuscles, whose spectacular activities had at one time been supposed to be all-sufficient.

But now came a series of new observations that brought the leucocyte again to the fore. The observations were made by an English army surgeon, Dr. (now Sir) Almroth Wright, who was investigating that scourge of armies, typhoid fever, and endeavoring to find a means of rendering soldiers in India immune to the disease.

Studying the blood of typhoid patients microscopically, he noted that white blood corpuscles will sometimes ingest the typhoid bacilli very sparingly, at other times with seeming avidity. From this he drew the conclusion that there is a something in the blood, which may be present in less or in greater quantity, which renders the bacilli more susceptible to the attacks of the phagocytes.

To this something he gave the name opsonin, a word coined from a Greek derivative signifying " to make palatable." A long series of investigations convinced Wright and his chief associate, Captain Douglas, that opsonins are developed in the normal organism concomitantly with the development of antitoxines, bactericides, bacteriolysins, and agglutinins in response to the irritation caused by bacterial poisons. Opsonins constitute, in other words, yet another weapon elaborated by the tissues of the body in the fight against disease germs. But they differ from the other chemical agents that we have just been reviewing in that their action is not merely complementary,

VOL. CXXIV.-No. 739.-9

but directly auxiliary, to that of the leucocyte.

There has been some question as to whether the effect of the opsonins is explicable as having made the phagocytes more voracious, or as making the bacteria more susceptible. Metchnikoff and his followers were disposed to take the view that the opsonin stimulates the leucocytes; but the opinion of Wright, which has the balance of authority, is that the direct action of the opsonin is exerted on the bacteria.

Bernard Shaw in a recent play makes a character-whose prototype is obviously Sir Almroth Wright himself-wittily define an opsonin as "what you butter the disease germs with to make your white blood corpuscles eat them"; and this whimsical definition may be accepted as graphically presenting the function of a highly important constituent of the blood serum about which the medical fraternity has been greatly exercised in recent years.

The great importance of the opsonins, from a practical standpoint, depends upon the fact that their relative activity furnishes an index to the resistant power of the patient against a given germ. The test is made in a very tangible way by counting the actual number of bacteria. of a given species that a group of phagocytes in a quantity of blood serum will ingest in a given time. A control," or comparative, test is made with the blood serum of a normal individual. The first fifty leucocytes that come to view in the microscopic field are observed, and the number of bacteria in the body of each (made visible by a differential stain) is counted.

It must be understood that, according to theory, a leucocyte is powerless to ingest a single bacterium unless a certain amount of opsonin is present. As the amount of opsonin increases, up to a certain point, the susceptibility of the bacteria to the predatory attacks of the leucocyte increases also. Moreover, a given opsonin acts only on a single species of bacterium. Leucocytes in a certain sample of blood may therefore be found to possess the power of ingesting, say typhoid bacilli, very readily, while ingesting much more sparingly the tubercule bacilli found in equal abundance in the blood serum about them.

Such a blood would be said to have a high opsonic index for typhoid bacilli; a low opsonic index for tubercule bacilli. Though the opsonins that thus aid the white corpuscles in their attack on bacteria are probably chemically distinct from antitoxines, bacteriolysins, and agglutinins, yet they are produced simultaneously with these other protective bodies, and their presence is held to furnish a fair index to the abundance of these allied bodies. Hence the observation of the opsonic index supplies a highly important means of testing at least approximately the anti-bacterial properties of the blood.

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The theory on which this highly important new method of treatment proceeds is the assumption that the blood and tissues of the human organism contain normally a variable quantity of all the anti-bacterial bodies, and that the tissues will set about manufacturing more of these bodies in response to the influence of an invading host of germs. If the invading germs come in relatively small numbers, or if the response of the tissues of any given individual is peculiarly active and energetic, the invading host is promptly killed off and its poison neutralized by the joint action of the specific antitoxines, bactericides, agglutinins, and opsonins that are instantly engaged against it. So no symptoms of disease develop; and the person whose system has thus repelled invasion by a given germ is said to be "immune" to the disease which that germ would engender in an organism where its attack had been less promptly met.

Similarly a person who has passed through an attack of a germ disease and finally come off victorious carries in his system a residual supply of anti-bacterial bodies, and hence is more or less permanently immune; the fact of such im

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munity to subsequent attacks of measles, scarlet fever, typhoid, etc., being familiar knowledge.

But it is not alone the susceptibility of the individual that determines the result when germs of a disease find entrance into a human organism; much depends also upon the actual number of bacteria that come, and upon the particular strain they represent.

That numbers should count is easily comprehensible; but that individual bacteria of the same species should differ in virulence seems not at first sight so explicable. Yet such is the fact. For example, Dr. Eyre reports experiments on rabbits in which twenty individual pneumococci (the germs of pneumonia) produced death more rapidly than one hundred thousand pneumococci identical in appearance but of another strain. Again the anthrax virus which Pasteur developed owes its efficiency to the "attenuation" of the virulence of the germs through cultivation under peculiar conditions in a test tube; and Pasteur's treatment of rabies assumes the attenuation of the rabies virus through desiccation of a portion of spinal cord (of a rabbit) in which the germs are lodged.

The attenuated virus inoculated in proper quantity and in repeated doses sets up a response in the tissues which is not overwhelming, and the blood is presently saturated with anti-bacterial bodies in sufficient quantity to cope with more virulent strains of the germ introduced in whatever numbers-as from ordinary contagion. In other words, artificial immunity has been induced.

It occurred to Wright that a similar condition of immunity might be induced by inoculating a patient with bacterial germs not "attenuated" in the Pasteurian sense, but actually devitalized by heating. With the dead germs a certain amount of their specific toxine would be introduced; but the number of germs, and hence the quantity of their poison, could be controlled at the will of the operator; and the anti-bacterial response of the organism could be gauged through observation of the opsonic index. Thus the doses could be graded and repeated at proper intervals, until the patient's opsonic index was so high as to indicate the presence of a sufficient quan

tity of anti-bacterial elements in his blood to render him immune to the particular disease in question.

The first disease experimented with was typhoid fever. Wright himself inoculated no fewer than four thousand soldiers in India; and he gratuitously supplied the British government with about four hundred thousand doses of anti- typhoid vaccine for use in the South African war. An individual is rendered immune to typhoid by three inoculations, the first containing 500,000,000, and each succeeding one 1,000,000,000 typhoid bacilli. These numbers may seem alarming. But it should be explained that these incredible hordes of bacilli-comparable in number to the entire human population of the globe-find residence in a few drops of the serum.

We may note that the anti-typhoid inoculation was adopted by the German army, and that more recently it has been adopted for the American army with very gratifying results. But, beyond this, the applications of the new method, its extension to the treatment of developed diseases, and the potentialities that have led to its characterization as the most important of modern therapeutic methods, are matters that fall outside the scope of the present paper. It suffices for the present purpose that the results of the use of this so-called "vaccine therapy" are such as to support very strongly the truth of the theory of immunity upon which its application is founded.

In conclusion we may summarize the findings of modern science as to the real meaning of immunity in some such terms as these: A person is immune to any given disease when his blood serum contains normally, or has had developed in it artificially, a series of specific chemicals which, when called into action by

the intrusion of the disease germs, are able, acting jointly, (1) to neutralize the poison generated by the germs (antitoxines); (2) to kill the germs themselves (bactericides), and to remove them altogether partly by (3) dissolving them (bacteriolysins) and partly by (4) agglutinating and (5) opsoninizing them so that they readily fall prey to the white blood corpuscles that are always present in the blood.

For each specific disease germ, then, there may be at least five antidotes in the system. It follows that the individual who is immune to a score of wellknown germ diseases would have in his blood serum at least a hundred different chemicals whose presence there is meaningless, so far as we know, except as an anticipatory guard against the attack of the disease germs.

These chemicals appear not to interfere in any way with the normal functioning of the body. Indeed, the most thoroughly healthy individual would seem to be one in whose system the most elaborate groups of antidotal bodies have been developed. pare for war" is apparently the motto of the organism. Or, better, let us reflect that in the microbe-haunted world in which we perforce exist the organism is always at war with one host of enemies or another. It is only the large measure of immunity that each of us attains that permits any one to enjoy the modicum of reasonably healthy days with which most of us are blessed.

"In time of peace pre

Our periods of health are not necessarily times when no bacteria assail us, but merely those periods in which the white blood corpuscles--aided by antitoxines, bactericides, bacteriolysins, agglutinins, and opsonins-win their battles so easily and decisively as to attract no notice whatever.

D

The Cock of the Walk

BY MARY E. WILKINS FREEMAN

OWN the road, kicking up the dust, until he marched, soldierwise, in a cloud of it, that rose and grimed his moist face, and added to the heavy, brown powder upon the wayside weeds and flowers, whistling a queer, tuneless thing, which yet contained definite sequences-the whistle of a bird rather than a boy-approached Johnny Trumbull, aged ten, small of his age, but accounted by his mates mighty.

Johnny came of the best and oldest family in the village, but it was in some respects an undesirable family for a boy. In it survived, as fossils survive in ancient nooks and crannies of the earth, old traits of race, unchanged by time and environment. Living in a house lighted by electricity, the mental conception of it was to the Trumbulls as the conception of candles; with telephones at hand, they unconsciously still conceived of messages delivered with the old saying, "Ride, ride," etc., and relays of post-horses. They locked their doors, but still had latch-strings in mind. Johnny's father was a physician, adopting modern methods of surgery and prescription, yet his mind harked back to cupping and calomel, and now and then he swerved aside from his path across the field of the present into the future and plunged headlong, as if for fresh air, into the traditional past, and often with brilliant results.

Johnny's mother was a college grad uate. She was the president of the woman's club. She read papers savoring of such feminine leaps ahead that they were like gymnastics, but she walked homeward with the gait of her greatgrandmother, and inwardly regarded her husband as her lord and master. She minced genteelly, lifting her quitefashionable skirts high above very slender ankles, which were hereditary. Not a woman of her race had ever gone home on thick ankles, and they all had gone home. They had all been at home, even

if abroad-at home in the truest sense. At the club, reading her inflammatory paper, Cora Trumbull's real self remained at home intent upon her mending, her dusting, her house economics. It was something remarkably like her astral body which presided at the club.

As for her unmarried sister Janet, who was older and had graduated from a young ladies' seminary instead of a college, whose early fancy had been guided into the ladylike ways of antimacassars and pincushions and wax flowers under glass shades, she was a straighter proposition. No astral pretensions had Janet. She stayed, body and soul together, in the old ways, and did not even project her shadow out of them. There is seldom room enough for one's shadow in one's earliest way of life, but there was plenty for Janet's. There had been a Janet unmarried in every Trumbull family for generations. That in some subtle fashion accounted for her remaining single. There had also been an unmarried Jonathan Trumbull, and that accounted for Johnny's old bachelor uncle Jonathan. Jonathan was a retired clergyman. He had retired before he had preached long, because of doctrinal doubts, which were hereditary. He had a little, dark study in Johnny's father's house, which was the old Trumbull homestead, and he passed much of his time there, debating within himself that matter of doctrines.

Presently Johnny, assiduously kicking up dust, met his uncle Jonathan, who passed without the slightest notice. Johnny did not mind at all. He was used to it. Presently his own father appeared, driving along in his buggy the bay mare at a steady jog, with the next professional call quite clearly upon her equine mind. And Johnny's father did not see him. Johnny did not mind that, either. He expected nothing different.

Then Johnny saw his mother approach

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Johnny eyed his mother's faded but rather beautiful face, under the rosetrimmed bonnet, with admiration and entire absence of resentment. Then he walked on and kicked up the dust again. He loved to kick up the dust in summer, the fallen leaves in autumn, and the snow in winter. Johnny was not a typical Trumbull. None of them had ever cared for simple amusements like that. Looking back for generations on his father and mother's side (both had been Trumbulls, but very distantly related), none could be discovered who in the least resembled Johnny. No dim blue eye of retrospection and reflection had Johnny; no tendency to tall slenderness which would later bow beneath the greater weight of the soul. Johnny was small, but wiry of build, and looked able to bear any amount of mental development without a lasting bend of his physical shoulders. Johnny had, at the early age of ten, whopped nearly every boy in school, but that was a secret of honor. It was well known in the school that, once the Trumbulls heard of it, Johnny could never whop again. "You fellows know," Johnny had declared once, standing over his prostrate and whimpering foe, "that I don't mind getting whopped at home, but they might send me

away to another school, and then I could never whop any of you fellows."

Johnny Trumbull kicking up the dust, himself dust-covered, his shoes, his little, queerly fitting dun suit, his cropped head, all thickly powdered, loved it. He sniffed in that dust like a grateful incense. He did not stop dust-kicking when he saw his aunt Janet coming, for, as he considered, her old black gown was not worth the sacrifice. It was true that she might see him. She sometimes did, if she were not reading a book as she walked. It had always been a habit with the Janet Trumbulls to read im proving books when they walked abroad. To-day Johnny saw with a quick glance of those sharp, black eyes, so unlike the Trumbulls', that his aunt Janet was reading. He therefore expected her to pass him without recognition, and marched on kicking up the dust. But suddenly as he grew nearer the little, spry figure he was aware of a

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HE LOVED TO KICK UP

THE DUST IN SUMMER

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