The blood really contains three kinds of anatomical elements: the red globules, the white globules and the microzymian molecular granulations. Anatomically, the blood is constituted by three sorts of figured elements and, by a fourth term, a liquid. Is this the serum, this liquid which is its interglobular and intergranular substance?

The three sorts of anatomical elements are living, insomuch as they are organized and contain microzymas which I have proved to be living by their function as ferments and by their capacity to become vibrioniens by individual evolution, which was a novelty for physiology and even for chemists.

Nevertheless, so far as concern the red globule, since 1846 the statement that it is alive was not a novelty. In fact, in a memoir,1 which merits the more attention that it is never quoted, J. B. Dumas made an observation which must be regarded as of the first importance. It is that to isolate the red globules in their integrity, by mixing the blood with sulphate of soda, a current of air must be introduced; without this they will change, losing their coloring matter which itself also changes. And he said: "The globules of blood act as though they were really living beings, capable of resisting the solvent action of sulphate of soda so long as they are alive, but yielding to this action so soon as they have succumbed to the asphyxiation which affects them by the deprivation of air, and which manifests itself with singular rapidity, either by their change of color or by their rapid solution."  Dumas asserted clearly that the globules breathe; that account must be taken of their membrane in explaining the phenomenon of respiration; and that the breathing of an animal has especially for its object to furnish oxygen to the globules of its blood and to expel "the products into which they convert it." He also remarked that in the discussions and the calculations respecting respiration the blood had always been regarded as a homogeneous liquid, while it was only the serum which possesses this quality. He in no wise disregarded the part taken by the serum in the phenomenon of arterialization, but he insisted on the preponderant part taken in it by the red globules.

1. Dumas, "Recherches sur le sang," C. R.. Vol. XXII, p. 900 (1846).

To understand the blood, one must place oneself in the order of ideas of the memoir of Dumas, but broadened; that illustrious savant did not recognize in it, nor did any one else at that time, other anatomical elements than the globules, but there is another. He saw in the blood only three nitrogenous organic matters: albumen, fibrin and the globules, but there are others.

I will add that, in the serum, he made allowance for the share therein of the phosphates and other mineral matters.

At the moment of a general venesection the blood has been regarded as being that which it is in the vessels while it circulates in them, but as being a mixture of the arterial and venous bloods; and we have seen that at this moment the blood is so thoroughly regarded as being alive that it was regarded as certain that coagulation was its death.

The blood being alive, it is necessary to recognize, in accordance with the doctrine of Bichat, that, as in all the rest of the organism, the only things living in it are the anatomical elements, that is to say, that of the four parts which constitute it, the three kinds of anatomical elements are the only things living in it; the fourth, the serum, or that which will become the serum, the interglobular and intergranular substance, fulfilling with regard to them only one of the conditions of existence.

But as this conclusion conflicts with the prejudices of the schools, it is necessary to know what those prejudices are to combat them, for they are the negations of the doctrine of Bichat and precisely contrary to it. In fact, while it is asserted that the globules of blood, in general the anatomical elements, are only organites, neither plants, nor animals, as M. Pasteur said, that is to say, not living although organised, it was insisted that that which in the blood is still called plasma was living, a liquid whereof all the materials are said to be in a state of perfect solution, that is to say, without any anatomic, figured structure. But it is well to repeat that such was the state of science just as it was before Lavoisier and before Bichat, when the philosophical naturalist, Charles Bonnet, speaking of the organization, called it "the most excellent modification of matter." Even in France a conception more or less analogous to it, that of protoplasm, was preferred to the striking conception of Bichat. But protoplasm or its synonym, blastema, was considered to be organized living matter without structure. Here is one of the most precise descriptions of such matter: "A completely homogenous, amorphous matter without structure can be regarded as organized substance if it is constituted of numerous proximate principles, united molecule to molecule by special combination and reciprocal solution, and however simple may be this organization, it is sufficient to enable one to say that it is alive." Diet, de Med., Littre et Robin, art. Organique (1878).

Van Tieghem said: "Protoplasm is a mixture with water, of a greater or less number of different proximate principles, in the course of continual transformation."

Huxley said: "All protoplasm is similar to protein—all living matter is more or less similar to albumen."

Cauvet said: "Protoplasm is a nitrogenous liquid, more or less flowing, composed of a translucent joining substance and of fatty and albuminoid granulations."

Even Claude Bernard said: "In its simplest condition life, contrary to the idea of Aristotle, is independent of all special form; it resides in a substance defined by its composition and not by its shape; the protoplasm."

Pasteur said: "Living organisms are composed of natural substances such as life elaborates them, the proximate principles of living bodies which possess faculties of transformation which are destroyed by boiling."1

1. C. R., Vol. LXXIII. p. 302. See letter of M. Pasteur to M. Donne. M. Pasteur's manner of thinking was still that of Chevreul [born in 1786. was still alive and active in 1856]— at the time (1810) of the foundation of his chair at the Museum; Chevreul said, speaking of living bodies, that they are organic bodies in contradistinction to inorganic bodies, which we term minerals. Buffon called minerals gross matter, admitting that there was a universally diffused organic matter which he termed organic molecules, but Buffon wrote before the time of Lavoisier. Chevreul spoke of the proximate principles of organic bodies which are the products of life. Pasteur, speaking of the same proximate principles, says that they are natural substances elaborated by life, which have powers of transformation, etc. It may thus be truly said that there was no idea of life as bound to a determined, structural form of living anatomical elements, according to the conception of Bichat. It is thus to be understood how M. Pasteur could class in the same category, as organites, the red globules of the blood and grains of starch. It is true that the amylaceous granule had been regarded as being a vesicle, but Biot and Payen had shown that it was solid throughout its mass, and I have proved, in my researches upon fecula, that it had neither tegument, nor microzymas, being wholly formed of amylaceous matter contaminated with a trace of albuminoid matter.
    In the microzymian theory it is not life which produces or elaborates the proximate principles, but the anatomical elements are constituted into living apparatus by the microzymas, according to the same mechanism by which the fibrinous microzymas cause starch to ferment, and elaborate the numerous proximate principles which I have described as produced in that fermentation.

These quotations are sufficient. Protoplasm is regarded as a pure mixture of proximate principles, that is to say, of materials of a purely chemical order. M. Cauvet and others, M. Frey, for instance, have observed the granulations of the protoplasm, but they were supposed to be pure proximate principles. This mixture was declared by some, as in the course of continual transformation; by M. Pasteur, as endowed with faculties of transformation, but without other proof of what is precisely the point in question, viz., whether such a mixture can spontaneously change, can alter itself, give birth to any living being whatever, be it a cellule or a microzyma. If protoplasm were that which it was thought to be, the conception of Bichat would be purely chimerical.

I have incontestably demonstrated, in contradiction to the theory of protoplasm and against M. Pasteur, that every mixture, artificial or natural, of real proximate principles, with water, is, by itself, in every way unalterable, incapable of giving birth to anything living; in short, as not being in the course of continual transformation and as not possessing any faculty of transformation capable of producing in it any spontaneous alteration. And if in such a mixture, boiling destroys the "faculties of transformation" of some zymas, this latter had not been produced spontaneously, it was the product of a living organism. In short, if the mixture contains some proximate principle which can be altered by oxygenation, by absorbing oxygen from the air, this principle is itself the former product of a living organism through the reaction of a zymas.1  I have given positive proof of all of this while studying the conditions of the spontaneous coagulation of milk, which was said to be a pure mixture of proximate principles. Cow's milk, creosoted by a suitable dose to destroy the influence of the germs of the air and completely protected from all contact with the air, first becomes sour and then coagulates. After which, vibrioniens appear in it. If by filtration, by the process which I have indicated in the case of the blood, both the globules and all the milk microzymas of the creosoted milk are absolutely removed, the limpid liquid which results, containing all the proximate principles of the milk, under the same conditions, does not become sour and consequently neither coagulates nor permits the appearance of the vibrioniens. The "faculties of transformation" then resided in the anatomical element of the milk which had been removed by filtration, and not in the rest of its substance, which maybe called the physiological serum of milk.

1. The zymases are never the products of the spontaneous alteration of an albuminoid matter, but are always the products of the physiological function of a living organism and of an anatomical element in the latter. See the article zymas, "Dictionnaire de la langue francaise." Littre (1869).

The physiological serum of the milk, which has the same composition as blastema or of protoplasm, is then naturally unchangeable and consequently not living.

It is the same with the fourth portion of the blood, which we will call the physiological serum of the latter. And precisely as the anatomical elements of milk are the agents of its spontaneous alteration, because they are living, so the anatomical elements of the blood are, on several accounts, the agents of its spontaneous alteration, as will be proved in the following chapter. But first must be determined the physiological role of this serum, in which are realized the conditions of existence of the anatomical elements, globules and granulations of the blood, while it circulates and after it has been shed.

I understand by "conditions of existence" of an anatomical element (following Bichat's conception), that of the preservation of its physical being at the same time with the integrity of its tegument and that of its content, preserved with its composition unchanged, which it can only be by finding in the medium in which it lives all the materials for its nutrition.

Take, for example, the red globules; we know that in blood, steeped in a certain quantity of water, the soluble contents of its globules are diffused by osmose, the teguments remaining whole; on the other hand, we know that in the same blood, steeped in several times its volume of a saturated solution of sulphate of soda, its globules remain entire, both tegument and content. We can even steep the blood in its own serum, without the globules being altered ; without any trace of the colored content being dissolved.  And it is the same with the molecular granulations as with the globules; so that if in blood, steeped in the solution of sulphate of soda, a small part of their albuminoid atmosphere is temporarily soluble, as we have seen, it is absolutely insoluble in the serum and each granulation remains there whole and independent, the same as each globule, and this constitutes one of the conditions of the circulation.

But to understand the circulation and the reciprocal influence of the vessels and of the elements of their content, a slight diversion into embryology is indispensable.

In studying the development of the fowl to ascertain the role of the microzymas of the vitellus in the formation of the anatomical elements and of the organs, Estor and shown1 that the container and the content of the vascular system are born and developed simultaneously with the aid of the microzymas and the unorganized materials of the vitellus. We have never seen globules in the body of the embryo before the establishment of the circulation; they are formed on the spot. Thus the anatomical elements of the tissues of the vessels and the anatomical elements of the blood contained therein are born at the same time, by the microzymas of the vitellus as builders, in the unorganized intermicrozymian medium of the vitellus. Hence it results that the serum of the embryonal blood comes into existence concurrently with the globules and the granulations, having the non-organized parts of the vitellus for their source. To sum up, container and content are born at the same time, develop at the same time, and at the same time become what they are destined to be in the future.

1. C. R., Vol. LXXV, p. 962 (1872). We were led to undertake this embryological experiment as the consequence of the following experiment of which Estor was a witness: The mother of vinegar formed a microzymas, united among themselves by a hyaline intermicrozymian substance, is a membrane of mucous consistence with which we have compared the false membrane called fibrin; but it is so much vegetable that it is hardly nitrogenized. But in the "mother of vinegar," under the conditions in which one forces its microzymas to live, these become by individual evolution bacteria, or by association manufacturers of cellules. It is the same with the microzymas of beer-yeast, which, in certain media, act as lactic and butyric ferments, undergoing vibrionian evolution; while in others they reproduce the cellule of yeast and the normal alcoholic fermentation." *
The microzymas then can be manufacturers of cellules by grouping themselves together, and being grouped becoming enveloped with a tegument when the conditions of existence of these cellules are united. And it is precisely this which the vitellin microzymas do during embryonic development.
    This new theory of the origin of the cellule does not weaken the axiom of M. Virchow: omnis cellulae cellula.  One cellule may be derived from another cell according to another mode, that is all.
    Consequently, when M. Pasteur said that the globule of the blood is an organite incapable of reproduction because it could not be cultivated like beer-yeast, he was mistaken, not knowing any other mode of reproduction.
For the developments of the theory of the microzymas, manufacturers of cellules, see the following publications: "Conclusions Concerning the Nature of Mother of Vinegar and of Microzymas in General," C. R., Vol. LXVIII, p. 877 (1869); "Researches on the Nature and Origin of Ferments.  Ann. de chemie et de physique," 4th series. Vol. .XXIII. p. 443. And for the theory in its entirely: "Les Microzymas Builders of Cellules." see: "Les Microzymas," etc., M.Chamalet, 60, passage Choiseul, Paris, p 431-463 and p. 948.

The blood ought to be studied not only by itself, but as being to the vessels that which the content of a cellule or of an organ is to its tegument. The tegument of the vascular system consists of the various tissues of the arteries, of the veins and of the capillaries. It must also be borne in mind that the system is directly in relation with the heart, the lungs, the liver, etc., and that the lymphatics (the chyle vessels) communicate directly with it. And as the content of a cellule, of an organ, does not exist without the container, so also the blood does not exist without the vessels which contain it and which make of the whole system an organ in more or less direct relation with every part of the organism.a And it must be observed that if there is any difference between the anatomical constitution of the container of the various regions of the vascular system there is also a difference in their content. Independently of the color there is more oxygen and less carbonic acid in the arterial blood than in the venous. In several regions differences have been observed in the portion of the number of blood globules to that of the leukocytes. Lehmann observed that if the blood obtained from the portal vein gives fibrin by whipping, that of the suprahepatic vein does not furnish any by this means, proving, as we shall see, that the microzymian molecular granulations of the two bloods differ in something, and Denis has already pointed out that the fibrin of the arterial blood is not identical with that of the venous blood, etc.

[This original conception throws a new light upon the purpose and relations of the circulatory system, which I hope to enlarge upon in a future memoir.—Trans.]

Consequently it is physiologically evident that the anatomical elements, conceived as being personally and in individually living from whatever part of an organism they may be taken exist there only because the conditions of their existence are found naturally realized there. It is not otherwise with the blood; the conditions of existence of its anatomical elements are only realized, in each point of the circuit, while it is contained in the vessel and circulating.

It is ordinarily said that the anatomical elements swim in the lymph, the liquor sanguinis or the plasma; those who, with Milne-Edwards, admitted the existence of finely divided fibrin, said that it too floated in the serum. Anatomically, may we continue so to regard the reciprocal relations of the three anatomical elements and of the fourth portion of the blood?  And is it correct to say that at each point of the blood current there are molecular granulations and globules almost in contact with one another? Is it not more correct to say that the fourth part, the serum, is only the intercellular and intergranular substance of these anatomical elements which hinder their immediate contact, a situation analogous to that which is correctly admitted to exist between the anatomical elements of the other tissues? But, if this relation really exists for the blood contained in the vessels, must we not say that the blood not only is not a liquid, but that it is a tissue like that of the content of the spleen, or of the liver, or of the kidney which are more or less flaccid? The softness of the tissue of the content of the vessels is much greater, that is all; we must then say that the blood is a flowing tissue.

The flowing state of the blood tissue is related at the same time to the soft consistence, gelatinous it has been called, and to the elasticity of the globules, whose tegument is incessantly lubricated by the intercellular liquor; to the much softer consistence of the swollen albuminoid atmosphere of the microzymian molecular granulations whose density is nearly equal to that of the serum; to the absolute insolubility of the globules and of the molecular granulations in the intercellular liquor, which again contributes to their individual independence. This general insolubility of the anatomical elements is assured, at every point of the circuit, by the stability and even the origin of the composition of the very complex intercellular liquor, resulting from the nutritive functioning of the anatomical elements of the container and of the content, and at the same time by the matters contributed by the divers organs with which the circulatory system is in relation, and especially with the respiratory apparatus.

At the moment that the blood is shed it may be regarded as being the same flowing tissue that it was in the vessels. Nevertheless, there is already a profound difference, viz., it is not only a mixture of venous and arterial blood, but of the bloods of all the regions, whose anatomical elements are violently placed in new conditions of existence, very different from their physiological conditions.

We shall see how this change in the conditions of exist­ence rapidly determines the manifestation of the phenom­ena of coagulation and then of other alterations of the blood.