That was a dark and stern saying, "Without the shedding of blood there is no remission," and, like all the words of the oracles, of limited application. But it proves true in some unexpected places outside of the realm of theology. Was there something prophetic in the legend that it was only by the sprinkling of the blood of the Paschal Lamb above the doorway that the plague of the firstborn could be stayed? To-day the guinea-pig is our burnt offering against a plague as deadly as any sent into Egypt.

Scarcely more than a decade ago, as the mother sat by the cradle of her firstborn, musing over his future, one moment fearfully reckoning the gauntlet of risks that his tiny life had to run, and the next building rosy air-castles of his happiness and success, there was one shadow that ever fell black and sinister across his tiny horoscope. Certain risks there were which were almost inevitable,—initiation ceremonies into life, mild expiations to be paid to the gods of the modern underworld, the diseases of infancy and of childhood. Most of these could be passed over with little more than a temporary wrinkle to break her smile. They were so trivial, so comparatively harmless: measles, a mere reddening of the eyelids and peppering of the throat, with a headache and purplish rash, dangerous only if neglected; chicken-pox, a child's-play at disease; scarlatina, a little more serious, but still with the chances of twenty to one in favor of recovery; diphtheria—ah! that drove the smile from her face and the blood from her lips. Not quite so common, not so inevitable as a prospect, but, as a possibility, full of terror, once its poison had passed the gates of the body fortress. The fight between the Angel of Life and the Angel of Death was waged on almost equal terms, with none daring to say which would be the victor, and none able to lift a hand with any certainty to aid.

Nor was the doctor in much happier plight. Even when the life at stake was not one of his own loved ones,—though from the deadly contagiousness of the disease it sadly often was (I have known more doctors made childless by diphtheria than by any other disease except tuberculosis),—he faced his cases by the hundred instead of by twos and threes. The feeling of helplessness, the sense of foreboding, with which we faced every case was something appalling. Few of us who have been in practice twenty years or more, or even fifteen, will ever forget the shock of dismay which ran through us whenever a case to which we had been summoned revealed itself to be diphtheria. Of course, there was a fighting chance, and we made the most of it; for in the milder epidemics only ten to twenty per cent of the patients died, and even in the severest a third of them recovered. But what "turned our liver to water"—as the graphic Oriental phrase has it—was the knowledge which, like Banquo's ghost, would not down, that while many cases would recover of themselves, and in many border-line ones our skill would turn the balance in favor of recovery, yet if the disease happened to take a certain sadly familiar, virulent form we could do little more to stay its fatal course than we could to stop an avalanche, and we never knew when a particular epidemic or a particular case would take that turn. "Black" diphtheria was as deadly as the Black Death of the Middle Ages.

The disease which caused all this terror and havoc is of singular character and history. It is not a modern invention or development, as is sometimes believed, for descriptions are on record of so-called "Egyptian ulcer of the throat" in the earliest centuries of our era; and it would appear to have been recognized by both Hippocrates and Galen. Epidemics of it also occurred in the Middle Ages; and, coming to more recent times, one of the many enemies which the Pilgrim Fathers had to fight was a series of epidemics of this "black sore throat," of particularly malignant character, in the seventeenth century. Nevertheless, it does not seem to have become sufficiently common to be distinctly recognized until it was named as a definite disease, and given the title which it now bears, by the celebrated French physician, Bretonneau, about eighty years ago. Since then it has become either more widely recognized or steadily more prevalent, and it is the general opinion of pathologists that the disease, up to some thirty or forty years ago, was steadily increasing, both in frequency and in severity.

So that we have not to deal with a disease which, like the other so-called diseases of childhood, has gradually become milder and milder by a sort of racial vaccination, with survival of the less susceptible, but one which is still full of virulence and of possibilities of future danger.

Unlike the other diseases of childhood, also, one attack confers no positive immunity for the future, although it greatly diminishes the probabilities; and, further, while adults do not readily or frequently catch the disease, yet when they do the results are apt to be exceedingly serious. Indeed, we have practically come to the conclusion that one of the main reasons why adults do not develop diphtheria so frequently as children, is that they are not brought into such close and intimate contact with other children, nor are they in the habit of promptly and indiscriminately hugging and kissing every one who happens to attract their transient affection, and they have outgrown that cheerful spirit of comradeship which leads to the sharing of candy in alternate sucks, and the passing on of slate-pencils, chewing-gum, and other objets d'art from hand to hand, and from mouth to mouth. Statistics show that of nurses employed in diphtheria wards, before the cause or the exact method of contagion was clearly understood, nearly thirty per cent developed the disease; and even with every modern precaution there are few diseases which doctors more frequently catch from their patients than diphtheria. It is a significant fact that the risk of developing diphtheria is greatest precisely at the ages when there is not the slightest scruple about putting everything that may be picked up into the mouth,—namely, from the second to the fifth year,—and diminishes steadily as habits of cleanliness and caution in this regard are developed, even though no immunity may have been gained by a mild or slight attack of the disease. The tendency to discourage and forbid the indiscriminate kissing of children, and the crusade against the uses of the mouth as a pencil-holder, pincushion, and general receptacle for odds and ends, would be thoroughly justified by the risks from diphtheria alone, to say nothing of tuberculosis and other infections.

In addition to being almost the only common disease of childhood which is not mild and becoming milder, diphtheria is unique in another respect, and that is its point of attack. Just as tuberculosis seizes its victims by the lungs, and typhoid fever by the bowels, diphtheria—like the weasel—grips at the throat. Its bacilli, entering through the mouth and gaining a foothold first upon the tonsils, the palate, or back of the throat (pharynx), multiply and spread until they swarm down into the larynx and windpipe, where their millions, swarming in the mesh of fibrin poured out by the outraged blood-vessels, grow into the deadly false membrane which fills the air-tube and slowly strangles its victim to death.

The horrors of a death like that can never fade from the memory of one who has once seen it, and will outweigh the lives of a thousand guinea-pigs. No wonder there was such a widespread and peculiar horror of the disease, as of some ghostly thug or strangler.

But not all of the dread of diphtheria went under its own name. Most of us can still remember when the commonest occupant of the nursery shelf was the bottle of ipecac or soothing-syrup as a specific against croup. The thing that most often kept the mother or nurse of young children awake and listening through the night-watches was the sound of a cough, and the anxious waiting to hear whether the next explosion had a "croupy" or brassy sound. It was, of course, early recognized that there were two kinds of croup, the so-called "spasmodic" and the "membranous," the former comparatively common and correspondingly harmless, the latter one of the deadliest of known diseases. The fear that made the mother's heart leap into her mouth as she heard the ringing croup-cough was lest it might be membranous, or, if spasmodic, might turn into the deadly form later. To-day most young mothers hardly know the name of wine of ipecac or alum, and the coughs of young children awaken little more terror than a similar sound in an adult. Croup has almost ceased to be one of the bogies of the nursery. And why? Because membranous croup has been discovered to be diphtheria, and children will not develop diphtheria unless they have been exposed to the contagion, while, if they should be, we have a remedy against it.

He was a bold man who first ventured to announce this, and for years the battle raged hotly. It was early admitted that certain cases of so-called membranous croup in children occurred after or while other members of the family or household had diphtheria; and for a time the opposing camps used such words as "sporadic" or scattered croup, which was supposed to come of itself, and "epidemic" or contagious croup, which was diphtheria. Now, however, these distinctions are swept away, and boards of health require isolation and quarantine against croup exactly as against any other form of diphtheria.

Cases of fatal croup still occasionally occur which cannot be directly traced to other cases of diphtheria, but the vast majority of them are clearly traceable to infection, usually from some case in another child, which was so mild that it was not recognized as diphtheria until the baby became "croupy" and search was made through the family throats for the bacilli.

For years we were in doubt as to the cause of diphtheria. Half a dozen different theories were advanced, bad sewerage, foul air, overcrowding; but it was not until shortly after the Columbus-like discovery, by Robert Koch, of the new continent of bacteriology, that the germ which caused it was arrested, tried, and found guilty, and our real knowledge of and control over the disease began. This was in 1883, when the bacteriologist Klebs discovered the organism, followed a few months later (in 1884) by LÖffler, who made valuable additions to our knowledge of it; so that it has ever since been known as the Klebs-LÖffler bacillus. This put us upon solid ground, and our progress was both sure and rapid: in ten years our knowledge of the causation, the method of spread, the mode of assault upon the body-fortress, and last, but not least, the cure, stood out clear cut as a die, a model and a prophecy of what may be hoped for in most other contagious diseases.

Great as is the credit to which bacteriologists are entitled for this splendid piece of scientific progress, there was another co-laborer, a silent partner, with them in all this triumph, an unsung hero and martyr of science who deserves his meed of praise—the tiny guinea-pig. He well deserves his niche in the temple of fame; and as other races and ages have worshiped the elephant, the snake, and the sacred cow, so this age should erect its temples to the guinea-pig. From one of the most trifling and unimportant,—kept merely as a pet and curiosity by the small boys of all ages,—he has become, after the horse, the cow, the pig, and the sheep, easily our most useful and important domestic animal. It may be urged that he deserves no credit, since his sacrifice—though of inestimable value—was entirely involuntary on his own part; but this should only make us the more deeply bound to acknowledge our obligation to him.

By a stern necessity of fate, which no one regrets more keenly than the laboratory workers themselves, the guinea-pig has had to be used as a stepping-stone for every inch of this progress. Upon it were conducted every one of the experiments whose results widened our knowledge, until we found that this bacillus and no other would cause diphtheria; that instead of getting, like many other disease-germs, into the blood, it chiefly limited itself to growing and multiplying upon a comparatively small patch of the body-surface, most commonly of the throat; that most of its serious and fatal results upon the body were produced, not by the entrance of the germs themselves into the blood, but by the absorption of the toxins or poisons produced by them on the moist surface of the throat, just as the yeast plant will produce alcohol in grape juice or sweet cider.

Here was a most important clew. It was not necessary to fight the germs themselves in every part of the body, but merely to introduce some ferment or chemical substance which would have the power of neutralizing their poison. Instantly attention was turned in this direction, and it was quickly found that if a guinea-pig were injected with a very small dose of the diphtheria toxin and allowed to recover, he would then be able to throw off a still larger dose, until finally, after a number of weeks, he could be given a dose which would have promptly killed him in the beginning of the experiments, but which he now readily resisted and recovered from. Evidently some substance was produced in his blood which was a natural antidote for the toxin, and a little further search quickly resulted in discovering and filtering out of his body the now famous antitoxin. A dose of this injected into another guinea-pig suffering from diphtheria would promptly save its life.

Could this antitoxin be obtained in sufficient amounts to protect the body of a human being? The guinea-pig was so tiny and the process of antitoxin-forming so slow, that we naturally turned to larger animals as a possible source, and here it was quickly found that not only would the goat and the horse develop this antidote substance very quickly and in large amounts, but that a certain amount of it, or a substance acting as an antitoxin, was present in their blood to begin with. Of the two, the horse was found to give both the stronger antitoxin and the larger amounts of it, so that he is now exclusively used for its production.

After his resisting power had been raised to the highest possible pitch by successive injections of increasing doses of the toxin, and his serum (the watery part of the blood which contains the healing body) had been used hundreds and hundreds of times to save the lives of diphtheria-stricken guinea-pigs, and had been shown over and over again to be not merely magically curative but absolutely harmless, it was tried with fear and trembling upon a gasping, struggling, suffocating child, as a last possible resort to save a life otherwise hopelessly doomed. Who could tell whether the "heal-serum," as the Germans call it, would act in a human being as it had upon all the other animals? In agonies of suspense, vibrating between hope and dread, doctors and parents hung over the couch. What was their delight, within a few hours, to see the muscles of the little one begin to relax, the fatal blueness of its lips to diminish, and its breathing become easier. In a few hours more the color had returned to the ashen face and it was breathing quietly. Then it began to cough and to bring up pieces of the loosened membrane that had been strangling it. Another dose was eagerly injected, and within twenty-four hours the child was sleeping peacefully—out of danger. And the most priceless and marvelous life-saving weapon of the century had been placed in the hand of the physician.

Of course there were many disappointments and failures in the earlier cases. Our first antitoxins were too weak and too variable. We were afraid to use them in sufficient doses. Often their injection would not be consented to until the case had become hopeless. But courage and industry have conquered these difficulties one after another, until now the fact that the prompt and intelligent use of antitoxin will effect a cure of from ninety to ninety-five per cent of all cases of diphtheria is as thoroughly established as any other fact in medicine. The mass of figures from all parts of the world in support of its value has become so overwhelming that it is neither possible nor necessary to specify them in detail. The series of Bayeaux, covering two hundred and thirty thousand cases of diphtheria, chiefly from hospitals and hence of the severest type, showing that the death-rate had been reduced from over fifty-five per cent to below sixteen per cent already, and that this decrease was still continuing, will serve as a fair sample.

Three-quarters of even this sixteen per cent mortality is due to delay in the administration of the antitoxin, as is vividly shown in thousands of cases now on record, classified according to the day of the disease on which the antitoxin was given, of which MacCombie's "Report of the London Asylums Board" is a fair type. Of one hundred and eighty-seven cases treated the first day of the disease, none died; of eleven hundred and eighty-six injected on the second day of the disease, four and a half per cent died; of twelve hundred and thirty-three not treated until the third day of the disease, eleven per cent died; of nine hundred and sixty-three cases escaping treatment until the fourth day, seventeen per cent died; while of twelve hundred and sixty not seen until the fifth day, twenty per cent died. In other words, the chances for cure by the antitoxin are in precise proportion to the earliness with which it is administered, and are over four times as great during the first two days of the disease as they are after the fourth day. One "stick" in time saves five.

This brings us sharply to the fact that the most important factor in the cure of diphtheria, just as in the case of tuberculosis, is early recognition. How can this be secured? Here again the bacteriologist comes to our relief, and we needed his aid badly. The symptoms of a mild case of diphtheria for the first two, or even three, days are very much like those of an ordinary sore throat. As a rule, even the well-known membrane does not appear in sufficient amounts to be recognizable by the naked eye until the middle of the second, or sometimes even of the third, day. By any ordinary means, then, of diagnosis, we would often be in doubt as to whether a case were diphtheria or not, until it was both well advanced and had had time to infect other members of the family. With the help of the laboratory, however, we have a prompt, positive, and simple method of deciding at the very earliest stage. We merely take a sterilized swab of cotton on the end of a wire, rub it gently over the surface of the throat and tonsils, restore it to its glass tube, smearing it over the surface of some solidified blood-serum placed at the bottom of the tube, close the tube and send it to the nearest laboratory. The culture is put into an incubator at body heat, the germs sown upon the surface of the blood-serum grow and multiply, and in twelve hours a positive diagnosis can be made by examining this growth with a microscope. Often, just smearing the mucus swabbed out of the throat over the surface of a glass slide, staining this smear, and putting it under a microscope, will enable us to decide within an hour. These tubes are now provided by all progressive city boards of health, and can be had free of charge at depots scattered all over the city, for use in any doubtful case, within half an hour. Twelve hours later a free report can be had from the public laboratory. If every case of suspicious sore throat in a child were promptly swabbed out, and a smear from the swab examined at a laboratory, it would not be long before diphtheria would be practically exterminated, as smallpox has been by vaccination, and this is what we are working toward and looking forward to.

Our knowledge of the precise cause of diphtheria, the Klebs-LÖffler bacillus, has furnished us not only with the cure, but also with the means of preventing its spread. While under certain circumstances, particularly the presence of moisture and the absence of light, this germ may live and remain virulent for weeks outside of the body, careful study of its behavior under all sorts of conditions has revealed the consoling fact that its vitality outside of the human or some other living animal body is low; so that it is relatively seldom carried from one case to another by articles of clothing, books, or toys, and comparatively seldom even through a third party, except where the latter has come into very close contact with the disease, like a doctor, a nurse, or a mother, or—without disrespect to the preceding—a pet cat or dog.

More than this, the bacillus must chiefly be transmitted in the moist condition and does not float in the air at all, clinging only to such objects as may have become smeared with the mucus from the child's throat, as by being coughed or sneezed upon. As with most of our germ-enemies, sunlight is its deadliest foe, and it will not live more than two or three days exposed to sunshine. So the principal danger against which we must be on our guard is that of direct personal contact, as in kissing, in the use of spoons or cups in common, in the interchange of candy or pencils, or through having the hands or clothing sprayed by a cough or a sneeze.

The bacillus comparatively seldom even gets on the floor or walls of a room where reasonable precautions against coughing and spitting have been taken; but it is, of course, advisable thoroughly to disinfect and sterilize the room of a patient and all its contents with corrosive sublimate and formalin, as a number of cases are on record in which the disease has been carried through books and articles of clothing which had been kept in damp, dark places for several months. The chief method of spread is through unrecognized mild cases of the disease, especially of the nasal form. For this reason boards of health now always insist upon smears being made from the throats and noses of every other child in the family or house where a case of diphtheria is recognized. No small percentages of these are found to be suffering from a mild form of the disease, so slight as to cause them little inconvenience and no interference with their attending school. Unfortunately, a case caught from one of these mild forms may develop into the severest laryngeal type. If a child is running freely at the nose, keep it at home or keep your own child away from it. A profuse nasal discharge is generally infectious, in the case of influenza or other "colds," if not of diphtheria.

This also emphasizes the necessity for a thorough and expert medical inspection of school-children, to prevent these mild cases from spreading disease and death to their fellows. By an intelligent combination of the two methods, home examination of every infected family and strict school inspection, there is little difficulty in stamping out promptly a beginning infection before it has had time to reach the proportions of an epidemic.

One other step makes assurance doubly sure, and that is the prompt injection of all other children and young adults living in the family, where there is a case of diphtheria, with small doses of the antitoxin for preventive purposes. Its value in this respect has been only secondary to its use as a cure. There are now thousands of cases on record of children who had been exposed to diphtheria or were in hospitals where they were in danger of becoming exposed to it, with the delightful result that only a very small per cent of those so protected developed the disease, and of these not a single one died! This protective vaccination, however, cannot be used on a large scale, as in the case of smallpox, for the reason that the period of protection is a comparatively short one, probably not exceeding two or three weeks.

Suppose that, in spite of all our precautions, the disease has gained a foothold in the throat, what will be its course? This will depend, first of all, upon whether the invading germs have lodged in their commonest point of attack, the tonsils, palate, and upper throat, or have penetrated down the air-passages into the larynx or voice-organ. In the former, which is far the commoner case, their presence will cause an irritation of the surface cells which brings out the leucocyte cavalry of the body to the defense, together with squads of the serum or watery fluid of the blood containing fibrin. These, together with the surface-cells, are rapidly coagulated and killed by the deadly toxin; and their remains form a coating upon the surface, which at first is scarcely perceptible, a thin, grayish film, but which in the course of twenty-four to forty-eight hours rapidly thickens to the well-known and dreaded false membrane. Before, however, it has thickened in more than occasional spots or patches, the toxin has begun to penetrate into the blood, and the little patient will complain of headache, feverishness, and backache, often—indeed, usually—before any very marked soreness in the throat is complained of. Roughly speaking, attacks of sore throat, which begin first of all with well-marked soreness and pain in the throat, followed later by headache, backache, and fever, are not very likely to be diphtheria. The bacilli multiply and increase in their deadly mat on the surface of the throat, larger and larger amounts of the poison are poured into the blood, the temperature goes up, the headache increases, the child often begins to vomit, and becomes seriously ill. The glands of the neck, in their efforts to arrest and neutralize the poison, become swollen and sore to the touch, the breath becomes foul from the breaking down of the membrane in the throat, the pulse becomes rapid and weak from the effect of the poison upon the heart, and the dreaded picture of the disease rapidly develops.

This process in from sixty to eighty per cent of cases will continue for from three to seven days, when a check will come and the condition will gradually improve. This is a sign that the defensive tissues of the body have succeeded in rallying their forces against the attack, and have poured out sufficient amounts of their natural antitoxin to neutralize the poisons poured in by the invaders. The membrane begins to break down and peel off the throat, the temperature goes down, the headache disappears, the swelling in the glands of the neck may either subside or go on to suppuration and rupture, but within another week the child is fairly on the way to recovery.

Should the invaders, however, have secured a foothold in the larynx, then the picture is sadly different. The child may have even less headache, temperature, and general sense of illness; but he begins to cough, and the cough has a ringing, brassy sound. Within forty-eight, or even twenty-four, hours he begins to have difficulty in respiration. This rapidly increases as the delicate tissues of the larynx swell under the attack of the poison, and the very membrane which is created in an attempt at defense becomes the body's own undoing by increasing the blocking of the air-passages. The difficulty of breathing becomes greater and greater, until the little victim tosses continually from side to side in one constant, agonizing struggle for breath. After a time, however, the accumulation of carbon dioxide in the blood produces its merciful narcotic effect, and the struggles cease. The breathing becomes shallower and shallower, the lips become first blue, then ashy pale, and the little torch of life goes out with a flicker. This was what we had to expect, in spite of our utmost effort, in from seventy to ninety per cent of these laryngeal cases, before the days of the blessed antitoxin. Now we actually reverse these percentages, prevent the vast majority of cases from developing serious laryngeal symptoms at all, and save from seventy to eighty per cent of those who do.

Our only resource in this form of the disease used to be by mechanical or surgical means, opening the windpipe below the level of the obstruction and inserting a curved silver tube—the so-called tracheotomy operation; or later, and less heroic, by pushing forcibly down into the larynx, and through and past the obstruction at the vocal cords, a small metal tube through which the child could manage to breathe. This was known as intubation. But these were both distressing and painful methods, and, what was far worse, pitifully broken reeds to depend upon. In spite of the utmost skill of our surgeons, from fifty to eighty per cent of cases that were tracheotomized, and from forty to sixty per cent of those that were intubated, died. In many cases they were enabled to breathe, their attacks of suffocation were relieved—but still they died.

This leads us to the most important single fact about the course of the disease, and that is that the chief source of danger is not so much from direct suffocation as from general collapse, and particularly failure of the heart.

This has given us two other data of great importance and value, namely, that while the immediate and greatest peril is over when the membrane has become loosened and the temperature has begun to subside, in both ordinary throat and in laryngeal forms of the disease, the patient is by no means out of danger. While the antitoxins poured out by his body have completely defeated the invading toxins in the open field of the blood, yet almost every tissue of the body is still saturated with these latter and has often been seriously damaged by them before their course was checked. For instance, nearly two-thirds of our diphtheria cases, which are properly examined, will show albumin in the urine, showing that the kidney-cells have been attacked and poisoned by the toxin. This may go on to a fatal attack of uremia; but fortunately, not commonly, far less so than in scarlet fever. The kidneys usually recover completely, but this may take weeks and months. Again, many cases of diphtheria will show a weak and rapid pulse, which will persist for weeks after the patient has apparently recovered; and if the little ones are allowed to sit up too soon, or to indulge in any sudden movements or muscular strains, this weak and rapid pulse will suddenly change into an attack of heart failure and, possibly, fatal collapse. This, again, illustrates the saturation of the poison, as these effects are now known to be due in part to a direct poisoning of the muscle of the heart itself, and later to serious damage done to the nerves controlling the heart, chiefly the pneumo-gastric. Moral: Keep the little patient in bed for at least two weeks or, better, three. He will have to spend a month or more in quarantine, anyway.

Last of all, and by no means least interesting, are the effects which are produced upon the nervous system. One day, while the child is recovering, and is possibly beginning to sit up in bed, a glass of milk is handed to him. The little one drinks it eagerly and attempts to swallow, but suddenly it chokes, half strangles, and back comes the milk, pouring out through the nostrils. Paralysis of the soft palate has occurred from poisoning of the nerves controlling it, caused by direct penetration of the toxin. Sometimes the muscles of the eye become paralyzed and the little one squints, or can no longer see to read.

Fortunately, most of these alarming results go only to a certain degree, and then gradually fade away and disappear; but this may take months or even longer. In a certain number, however, the nerves of respiration, or those controlling the heart-beat, become affected, and the patient dies suddenly from heart failure.

This strange after-effect upon the nervous system, which was first clearly noticed in diphtheria and syphilis, has now been found to occur in lesser degree in a large number of our infectious diseases, so that many of our most serious paralyses and other diseases of the nervous system are now traceable to such causes.

These effects of the diphtheria toxin are also of interest for a somewhat unexpected reason, since it has been claimed that they are effects of the antitoxin, by those who are opposed to its use. Every one of them was well recognized as a possible result of diphtheria long before the antitoxin was discovered, and every one of them can be readily produced by injections of diphtheria bacilli or their toxin into animals.

It is quite possibly true that there are more cases of nerve-poisoning (neuritis) and of paralysis following diphtheria than there were before the use of antitoxin, but that is for the simple and sufficient reason that there are more children left alive to display them! And between a child with a temporary squint and a dead child few mothers would hesitate long in their choice.