Popular Science Monthly/Volume 56/January 1900/The Scavengers of the Body

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THE labors of M. Metchnikoff have made known one of the most curious mechanisms—perhaps the most effective—which Nature employs to protect the organism against the invasion and ravages of microbes. We are only beginning to learn the means which are provided for our defense against the countless swarms of enemies of this class, some of them exceedingly dangerous, among which we have to live and move. In the first rank of these defenses is phagocytosis. The struggle of the organism against its minute assailants is an image of human wars. The cutaneous or mucous integument, continuous over the whole body, constitutes a kind of fortified inclosure which the microbe can not penetrate, except where some breach has been made. On one side of that wall, in the living city, the phagocytes or leucocytes (white cells) form an immense defensive army in a state of continual mobilization, or, as M. Duclaux would say, an innumerable and vigilant police.

These phagocytes or leucocytes are the nomadic elements of our economy. The animal body may be compared to an organized city in which all the living corpuscles, all the cellular elements, are sedentary, each having its place and staying there. Hence the comparison, often made, with the stones of a building, which is not exact, however, because these vital elements grow and increase, enlarging the structure without change of arrangement, while the stones do not. The growth and nutrition of these anatomical elements, it should be added, are carried on exclusively at the expense of liquid matters. Nothing solid can enter them or come out from them. An exception to these two fundamental rules is found in the single case of the leucocytes or white globules of the blood. They have no fixed or determined place in the organism. Besides being carried passively by the flow of the blood in a perpetual circulation along with the red corpuscles, they possess a motion of their own. They can swim in the current that carries them, fix themselves to the walls, and travel in a sort of creeping way, which has been called the amœboid motion.

They are also exceptions to the second law, according to which living cells can dispose only of liquefied matters. All solid bodies that pass within reach of the leucocytes are seized and incorporated by them, provided they are small or inert enough to be enveloped. The nature of the body is of little import. Whatever it may be, it is swallowed and quickly inclosed within the mass of the leucocyte and submitted to the dissolving action of its juices—or, in a way, eaten. Hence the names "phagocyte," or devouring cell, given to the enveloping white globule, and "phagocytosis" to the process. No other element of the organism, or hardly any other, possesses this singular faculty of seizure and swallowing (inglobement).

All the other characteristics of the white globules flow from these two of mobility and phagocytism, the significance of which has been set in a clear light by M. Metchnikoff. These characterstics are the attributes of the most primitive types of animal life. They appertain to cells not yet differentiated, to the unicellular organisms which occupy the first stages of life. They translate the vital energy of elements still independent and isolated, without definite place in the social organization and as yet without special high function, but for that very reason better adapted to the needs of the simplest animality. Their voracity is useful for the preservation of the social organism. By eliminating old, exhausted, diseased cells they rejuvenate the structure and prepare the way for new generations. And when the fecundity of these is exhausted the leucocytes come in to occupy the vacated situations, and conduct the organism thus patched up through a senile degeneracy to natural death.

The leucocytes, white globules, or phagocytes, by virtue of their mobility, are found everywhere—in the blood, in all the organs, and in all parts of the body—but are perhaps most abundant in the blood. The study of them proceeds slowly, and we are still engaged in distinguishing the varieties among them. The most abundant and best known of them—those which answer most closely the description we have given—are those called the polynuclear, neutrophilous leucocytes. They are colored with neutral hues, and have a nucleus like a rolled-up scroll in structure. Other varieties—the eosinophiles, lymphocytes, etc.—are less mobile and have still less marked phagocytic properties.

The roll-call of the phagocytic army would be a long task. The phagocytes are numerous in the sanguineous fluid, but are still six hundred and fifty times less so than the red corpuscles. They are almost as numerous in the lymph and the conjunctival tissue, where, besides occurring in their normal condition, they sport into a variety which appears to have abandoned its migratory habit, for a time at least, and into a giant variety one hundred times larger than the ordinary leucocytes, which M. Ranvier calls clasmatocytes. They are further found in such tissues as the skin and the mucous membrane, where, notwithstanding the cells are so crowded, they make their way into the intestine, and, by a sort of diapedesis (passage through the pores or interstices) called the phenomenon of Stoehr, toward all the free surfaces, whither exterior soluble substances invite them. As they go they destroy the microbes which, advancing in an inverse direction, would invade the organism and provoke an infection of intestinal origin.

The fact that this immense army of phagocytes is always in motion was first clearly recognized by Cohnheim, in 1867. He saw, in inflamed regions, where the vessels are gorged and distended, the white globules thrusting out a prolongation which seemed to pierce the wall, but in reality simply insinuated itself between its elements, and elongating itself, drew its entire body, as it were, through the narrow channel. This emigration, which is produced without making a break, through the pores and interstices of the vascular wall, has been designated diapedesis. It is ordinarily provoked by some foreign body, a pathogenic microbe, for instance, which has introduced itself into the place and spread its irritating secretion or cause of infection there. The phagocytes, attracted from the interior of the vessel, come up and devour the invader. But if they are incapable of dissolving it they bear it away to work their own ruin; they degenerate in their turn, become transformed into globules of pus, and the inflammation results in purulence. The study of the mechanism by means of which the leucocytes traverse the tissues is very interesting.

These remarkable wandering elements are found in all classes of animals, and in all present the same essential characteristics. They are more like free existences than the other cells living in society which compose the bodies of animals, and their history is substantially like that of the naked one-celled organisms. Their various functions and properties are of the highest interest in all departments of physiology. It has been demonstrated, in particular, that the white globules of the blood give rise to the most energetic and most special agencies of living chemistry, to the ferments which determine the coagulation of the blood when drawn from the vessels (coagulating ferment, or thrombosis) and the consumption of sugar (glycolytic ferment), and to numerous diastases. The presence of nuclein in their bodies involves consequences which we are only beginning to perceive.

Behaving like independent beings, the leucocytes or phagocytes perform similar functions with those of the highest animals, feeding, respiring, and reproducing themselves; they move and feel—that is, are impressed by internal excitants. These operations, however, assume with them a character of extreme simplicity. They seem to be the direct result of the physical and chemical properties of the protoplasm that composes them, so that the mysterious side of those vital functions nearly vanishes when we scan them in these their very beginnings. Their respiration is the effect of a sort of affinity between their substance and the vital gas—a chimiotactism directing them toward oxygen. This may be illustrated by forming a microscopic preparation of fresh lymph, imprisoning a few bubbles of air, and sealing it hermetically with paraffin. After two or three hours we can see the leucocytes grouped around the bubbles. When the provision of air is exhausted, several hours afterward, the leucocytes will cease to move and become inert. On inserting a needle, the contact of the air revives them.

The faculty possessed by the leucocytes of seizing solid corpuscles coming in contact with them, inglobing them, and absorbing them, or, as M. Metchnikoff calls it, intracellular digestion or phagocytosis, is easily observed. If we mix fine granulations of carmine or cinnabar, mingled with slightly salted water, with a drop of lymph, we can see the coloring matter penetrating the leucocytary protoplasmic mass, which is soon stuffed with it. The anatomo-pathologists had already observed, in tattooed subjects, white globules charged with grains of charcoal or vermilion. It is legitimate to conclude that some parts of the coloring matter that had been introduced under the epidermis had been taken up by the white globules. This proceeding has been observed in the very act by M. Metchnikoff.

A classic experiment illustrating this operation is now common in our laboratories, and the fact of phagocytosis has come to be regarded as incontestable.

The generality of the phenomenon results from the leucocyte preserving its phagocytic faculty in all its peregrinations, and these peregrinations are unlimited. The tendency of the nomadic elements to push on and insinuate themselves into the finest interstices and the narrowest passages is a rudiment of a tactile sense, to this extent simply a physical phenomenon, which MM. Mascart and Bordet have clearly distinguished. As soon as a leucocyte touches a resisting body it reacts to the contact by applying the largest possible surface to it. It spreads out, becomes thin, stretches itself along, and ceases deforming itself only after it has obtained the maximum of contact. By such mechanism it penetrates objects that offer it any breach and overcomes them. When the foreign body has been disaggregated into fragments, into small enough grains, phagocytosis intervenes and disposes of the remains. In this way the organism sometimes rids itself of splinters of bone that remain in the tissues after a fracture. So, too, the leucocytes, when occasion arises, repair the blunders of surgeons by extracting and absorbing forgotten objects left in wounds, while at other times they act as auxiliaries by destroying things that have been voluntarily abandoned in them, like threads of catgut in buried sutures and drains of decalcified bone.

There are two conditions, under normal circumstances, in which phagocytosis plays a marked part. The first is the case where vital action brings on the destruction of the organs or the tissues, or, to use exact language, their disintegration in a solid form. The wastes of organic activity are usually in liquid form, and, turned into the blood, they are eliminated in that state through the natural emunctories. Sometimes, however, disintegration results in solid wastes, and the phagocytes do the work of carrying them away. This is the case with the red globules of the blood, which, after a longer or shorter career, are deposited in the spleen and break up into débris, some of the parts of which are insoluble in the interstitial liquids. The leucocytes collect around these residues so thickly as sometimes to fuse themselves into a solid mass, a sort of plasmodium or giant cell which digests the débris. At other times, and more rarely the isolated leucocytes are not able to absorb the incorporated matters. They then conduct them to the surface of the intestine and discharge them there. A like phenomenon occurs in the liver. The coloring matter of the blood frequently gives rise to insoluble ferruginous deposits which the leucocytes have to convey to the digestive tube. This occurs when a wound provokes an effusion of blood and a mortification of the red globules or of the neighboring anatomical elements. All of the waste that can not take the liquid form and pass in that condition into the circulatory passages is incorporated within the phagocytes. The mechanism of resorption of bone does not seem different.

The phagocytes perform a similar function in another process which very frequently takes place in various animals that pass through metamorphoses, as in insects whose organs are transformed in changing from one stage of their existence to another, and in tadpoles which lose their tails in becoming frogs; the old parts that disappear are devoured by phagocytes.

Especially in the case of infectious diseases has the protective part performed by the leucocytary phagocytes been brought into full view by M. Metchnikoff. He has shown that the white globules rush to meet the bacterides of inflammation that are introduced through any wound, absorb them, and render them powerless to do harm. In the lymphatic organs—the spleen, the lymphatic ganglions, and the marrow—the white globules are normally accumulated, and there is where the struggle is most active between the bacterides of inflammation which are swarming in the blood and the defensive agents of the organism. The same takes place with the spirilla of recurrent typhus and the microbe of erysipelas.

The leucocytes are capable of adapting themselves to conditions different from those in which they usually live, provided the change is not too abrupt. It may sometimes occur that the poison secreted by a microbe will paralyze and kill the leucocyte, unless care has been taken, by inoculations of virus, at first attenuated and afterward gradually increasing in virulence, to create an immunity in the phagocyte, to make it refractory to the poison and capable of swallowing the toxic bacterium without suffering from it. Explanations have been sought in this property for the virtue of vaccination and the immunity that results from it, but they are evidently only fragmentary, and there are other theories of immunity.

The leucocytes are not always victorious over the microbes, and when these excel in numbers or force it sometimes comes to pass that they are overcome and succumb. Poisoned by the substance they have incorporated, they undergo a fatty degeneration and become globules of pus. Pus is therefore formed of the cadavers of conquered leucocytes. Although that humor ought, for the good of the system, to be rejected, like every other mortified part, it is nevertheless true that the production of it is a beneficent effort, and a salutary reaction of Nature against the morbid agent.

It will be an enduring honor to the name of M. Metchnikoff that he has revealed the importance of the function of phagocytes, and has enriched science with a large number of new truths. A part of this honor will be reflected upon the Pasteur Institute, which has welcomed the eminent biologist for many years, and has intrusted the direction of one of its services to him. The learned Russian, in creating the study of phagocytism, with its causes, mechanism, and consequences, has opened a very extensive field of research to which we have given only a distant and cursory glance.—Translated for the Popular Science Monthly from the Revue des Deux Mondes.