As the special properties and activities of any natural body depend on its chemical constitution, and this is, in the long-run, determined by the composition of its molecules, it is a matter of the greatest interest in biology to form as clear and distinct an idea as possible of the nature and properties of the molecules of plasm. Unfortunately, it is only possible to do this approximately, and to a slight extent. As the hypotheses of modern structural chemistry on the molecular formation of complicated organic compounds are often very unsafe, this is bound to be the case in the highest degree as regards the albuminoids and, the most important of all, the living matter or plasm. We have as yet no knowledge of the fundamental features of its very variable chemical structure. The one thing that bio-chemists have told us about it is that the molecule of plasm is very large, and made up of a great number of atoms (over a thousand); and that these are combined in smaller or larger groups, and are in a state of very unstable equilibrium, so that the life process itself causes constant changes in them.

Since the great problem of heredity was forced by Darwin in 1859 into the foreground of general biology, many different hypotheses and theories of it have been framed. All these have in the end to trace it to molecular features in the plasm of the germ-cells; because it is this germ-plasm of the maternal ovum and the paternal sperm-cell that conveys the characteristics of the parents to the child. Hence the great progress that has been made recently in the study of conception and heredity, by means of a number of remarkable observations and experiments, has been of service to our ideas on the molecular structure of the plasm. I have dealt with the chief of these theories in the ninth chapter of my History of Creation, and must refer the reader thereto. In chronological order we have: (1) the pangenesis theory of Darwin (1868), (2) the perigenesis theory of Haeckel (1875), (3) the idioplasm theory of Nägeli (1884), (4) the germ-plasm theory of Weismann (1885), and (5) the mutation-theory of De Bries (1889). None of these attempts, and none of the later theories of heredity, has given us a satisfactory and generally admitted idea of the plasma-structure. We are not even clear as to whether in the last resort life is to be traced to the several molecules, or to groups of molecules, in the plasm. With an eye to this latter difference, we may distinguish the plastidule and micellar theories as two different groups of relevant hypotheses.

In my essay on "The Perigenesis of the Plastidules" (1875) I formulated the hypothesis that in the last instance the plastidules are the vehicles of heredity—that is to say, plasma-molecules which have the property of memory. In this I found support in the ingenious theory of the distinguished physiologist, Ewald Hering, who had declared in 1870 that "memory is a general property of organic matter." I do not see still how heredity can be explained without this assumption! The very word "reproduction," which is common to both processes, expresses the common character of psychic memory (as a function of the brain). By plastidules I understand simple molecules; the homogeneous nature of the plasm in the monera (both chromacea and bacteria and rhizomonera) and the primitive simplicity of their life-functions do not dispose us to think that special groups of molecules are to be distinguished in these cases. Max Verworn has recently (1903) formulated his biogen-hypothesis in the same sense, as a "critical-experimental study of the processes in the living matter." He also takes the active plasma-molecules, which he calls biogens, as the ultimate individual factors of the life-process, and is convinced that in the simplest cases the plasm consists of homogeneous biogen-molecules.

The hypothesis of Nägeli (1884) and Weismann (1885) is totally different from the hypothesis of the plastidules and biogens as simple molecules of the plasm. According to this, the ultimate "vital unities" or individual vehicles of the life-process are not homogeneous plasma-molecules, but groups of molecules, made up of a number of different molecules. Nägeli calls them micella, and assigns them a crystalline structure. He supposes that these micella are combined chainwise into micellar ropes, and that the variety of the many forms and functions of plasm is due to the different configuration and arrangement of these. Weismann says: "Life can only arise by a definite combination of different kinds of molecules, and all living matter must be made up of these groups of molecules. A single molecule cannot live, can neither assimilate nor grow nor reproduce." I do not see the justice of this observation. All the chemical and physiological properties which Weismann afterwards attributes to his hypothetical biophora may be ascribed to a single molecule just as well as to a group of molecules. In the simplest forms of the monera (both the chromacea and the bacteria) the nature of their rudimentary life can be explained on the one supposition just as well as the other. Naturally, this does not exclude a very complicated chemical structure in the large plastidule or biogen as a single molecule. Verworn's biogen-hypothesis seems to me quite satisfactory when it represents the primitive molecule of living matter as really the ultimate factor of life.

The chief process in the evolutionary history of the plasm is its separation into the inner nuclear matter (caryoplasm) and the outer cellular matter (cytoplasm). When both kinds of plasm arose by differentiation from the originally simple plasm of the monera, there also took place the morphological separation of the nucleus (caryon) and cell-body (cytosoma or celleus). As these two chief forms of living matter are chemically different but nearly related, and as they may in certain circumstances (for instance, during indirect cell-division and the partial caryolysis connected therewith) enter into the closest mutual relations, we must suppose that the original severance of the two substances took place gradually and during a long period of time. It was not by a sudden bound or transformation, but by a gradual and progressive formation of the chemical antithesis of caryoplasm and cytoplasm, that the real nucleated cell (cytos) arose from the unnucleated cytode (or primitive cell). Both may correctly be comprised under the general head of plastids (or formative principles), as "ultimate individualities."

I regard as the chief cause of this important differentiation of the plasm the accumulation of hereditary matter—that is to say, of the internal characteristics of the plastids acquired by ancestors and transmitted to their descendants—within the plastids while their outer portion continued to maintain the intercourse with the outer world. In this way the inner nucleus became the organ of heredity and reproduction, and the outer cell-body the organ of adaptation and nutrition. I put forward this hypothesis in 1866 in my General Morphology: "The two functions of heredity and adaptation seem to be not yet distributed between differentiated substances in the unnucleated cytodes, but to inhere in the whole of the homogeneous mass of the plasm; while in the nucleated cell they are divided between the two active constituents of the cell, the inner nucleus taking over the transmission of hereditary characters and the outer plasm undertaking adaptation, or the accommodation to the features of the environment." This hypothesis was afterwards (1873) confirmed by the discoveries of Strasburger, the brothers Hertwig, and others, with regard to cell-cleavage and fertilization; it is particularly supported by the phenomena of caryokinesis(the movement of the nucleus) in sexual generation. Hence we can understand how it is that in the monera (chromacea and bacteria), which propagate by simple cleavage, there is no sexual generation and no nucleus.

The great significance of the nucleus in the life of the cell, as central organ of heredity, and also probably as "the soul of the cell," depends chiefly on the chemical properties of its albuminous matter, the caryoplasm. This one indispensable nuclear element is chemically akin to the cytoplasm of the cell-body, but differs from it in certain respects. The caryoplasm has a greater affinity for many coloring matters (carmine, hæmatoxylin, etc.) than the cytoplasm; and the former coagulates more quickly and firmly than the latter through acids (such as acetic and chromic acid). Hence we need only add a drop of diluted (two per cent.) acetic acid to cells that seem homogeneous to make perfectly clear the separation between the inner nucleus and outer body. As a rule, the firmer nucleus then stands out sharply as a globular or oval particle of plasm; occasionally it has other forms (cylindrical, conical, spiral, or branched). The caryoplasm seems to be originally quite homogeneous and structureless, as we find in many of the protists and many young cells of histona (especially young embryos). But in the great majority of cells the caryoplasm is divided into two or more different substances, the chief of them being chromatin and achromin.

The most common division of the caryoplasm in the cells of the animal and plant body, and the one of chief significance for their vital activity, is that into two chemically different substances, which are usually called chromatin (or nuclein) and achromin (or linin). Chromatin has a greater affinity for coloring (chromos) matter (carmine, hæmatoxylin, etc.), and so this "colorable nuclear matter" is particularly regarded as the vehicle of heredity. The achromin (or achromatin, or linin) is either not at all or less easily colorable, and is akin to the cytoplasm; in direct cell-division it enters into close relations with the latter. Achromin is usually found in the form of slender threads, and hence called "nuclear thread-matter" (linin). Chromatin is generally found in roundish or rod-shaped granules (chromosomata), which exhibit very characteristic changes of form (loop formation, etc.) in indirect cell-division. The chemical, physiological, and morphological difference between chromatin and achromin must not be regarded as an original property of cell nuclei (as is wrongly stated sometimes), but is the outcome of a very early phylogenetic differentiation in the originally homogeneous caryoplasm; and this holds also of two other parts of the nucleus—the nucleolus and centrosoma.

In a good many cells, but by no means universally, we find two other constituents of the nucleus, which owe their rise to a further differentiation of the caryoplasm. The nucleolus is a small globular or oval particle, which may be found singly or in numbers in the nucleus, and behaves somewhat differently towards coloring matter than the closely related chromatin. It has a special affinity for acid aniline colors, gosin, etc. Its substance has, therefore, been distinguished as plastin or paranuclein. The nucleolus is especially found in the tissue-cells of the higher animals and plants as an independent constituent; it is wanting in many of the unicellular protists. The same may be said of the centrosoma, or "central body" of the cell. This is an extremely small granule, on the very limit of visibility, the chemical composition of which is not known very well. We should have paid no attention to this constituent of the cell (distinguished in 1876) if it did not play an important, and perhaps leading, part in indirect cell-division. As the "polar body in the division of the nucleus," the centrosoma exercises a peculiar attraction on the granules distributed in the cytoplasm, which arrange themselves radially about this centre. The centrosomata grow independently and increase by cleavage, like the chromoplasts (chlorophyll particles, etc.). When they have split up, each of the daughter-microsomata acts in turn as a centre of attraction on its half of the cell. However, the great importance which modern cytologists have ascribed to it on this account is discounted by two circumstances. In the first place, we have not succeeded, in spite of all efforts, in discovering a centrosoma in the cells of the higher plants and many of the protists; and, in the second place, a number of recent chemical experiments have succeeded in producing centrosomata artificially (for instance, by the addition of magnesium chloride) in the cytoplasm. Hence many cytologists regard the centrosoma as a secondary product of differentiation in the cell-body, not the nucleus.

Two other parts of the nucleus that we find very often, but by no means universally, in the cells of the animal and plant body are the nuclear membrane (caryotheca) and the nuclear sap (caryolymph). A large number of cells—but not all—have the appearance of vesicles, having a thin skin enclosing a liquid content, the nuclear sap. The achromin then usually forms a frame-work of threads, with chromatin granules in its meshes or knots, within this round vesicle. This very thin nuclear membrane (often only visible as its contour) or caryotheca may be regarded as the result of surface-strain (at the planes of contact of caryoplasm and cytoplasm). The watery and usually clear and transparent nuclear sap (caryolymph) is formed by imbibition of watery fluid (like the frothy structure of the plasm in general). The separation of the nuclear membrane and nuclear sap is not a primary property of the nucleus, but is due to a secondary differentiation in the originally homogeneous caryoplasm.