In his first publication Ehrlich described the granules as products of the metabolism of the cells, deposited within the protoplasm in a solid form, in part to serve as reserve material, in part to be cast off from the cell. On the ground of observations on the liver cells, described in detail in a paper of Frerichs (1883, page 43), Ehrlich gave up this position, though only temporarily. Ehrlich shewed that the liver cells of a rabbit's liver, rich in glycogen, appear in dry preparations as bulky polygonous elements, of a uniform homogeneous brown colour, surrounded by a thin, well-defined yellow membrane. In cells that were not too rich in glycogen, small roundish bodies, clearly of a protoplasmic nature, of a pure yellow, can be seen embedded in the homogeneous cells that are coloured brown with glycogen. "The hyaline cellular ground substance, carrying the glycogen, could not under any circumstances be stained, but the cell-granules above mentioned stained easily with all kinds of dyes. It was further possible to shew by staining that the membrane was chemically different from the granules, since with eosin-aurantia-indulin-glycerine, the membrane stained black, but the granules orange-red."
To these observations Ehrlich added the following conclusion, "that the cells of the liver after food really possess a thin protoplasmic membrane, and a homogeneous glycogen-bearing substance, in which the nucleus and round granules (? functionally active) of protoplasm are embedded.
"On comparing these results with those of more recent investigation of the cells, it is easy to determine the location of the glycogen very accurately. Kupffer has shewn, first for the liver cells—and this is now recognised as generally valid—that their contents do not represent a microscopically single substance. In the 'survival' preparation he found, in addition to the nucleus, two clearly distinct substances: a hyaline ground substance in preponderating amount, and a more scanty, finely granular, fibrillary substance embedded in it. Kupffer calls the first paraplasm, the latter protoplasm. On warming the preparation to about 22° C. manifest though feeble movements appeared in the network. It can hardly be doubted, that of these two substances the granular reticulated one—the protoplasm—is the more important; and it should not be erroneous to suppose that the granulations of the network form the centre of the particular (specific) cell function. In any case, it is desirable to give a special name, such as microsomes (Hanstein) to these forms, which in the liver cells are recognisable as distinct, round or oval granules, colouring yellow with iodine, and easily and deeply staining in other ways."
It was necessary to quote in full from this older paper, to shew that Ehrlich regarded the granules as the special carriers of the cell function so long ago as 1883, a view that Altmann advocated many years later, under the name "theory of bioblasts." Altmann's ever repeated assertion that no one before him had allotted so high an importance to the granules is consequently in disagreement with the facts we have above made sufficiently clear.
The importance Altmann ultimately gave to the granules, which he also calls by the name "Ozonophores" is shewn by his own words (Elementary Organisms, 1st edit., p. 39):
"Our conception of the ozonophores may therefore replace that of the living protoplasm, at least so far as vegetative function is concerned; and may serve us as an explanation of complicated organic processes. Once again, shortly summarising the properties of the ozonophores; as oxygen carriers they can perform reduction and oxydation, and can thus effect the decompositions and syntheses of the body, without losing their own individuality."
In the meantime Ehrlich had made various observations which could not be completely brought into line with his own earlier hypothesis or the far-reaching conclusions of Altmann. Studies in particular on the oxygen requirements of the organism, shewed that the "ozonophores" could certainly not be an important part of the cell. In addition it was found that normally cells occur in which no granules can be recognised by ordinary methods. Finally a pathological observation made untenable the view that the granules are the bearers of the cell function. In a case of pernicious anæmia (cp. Farbenanalytische untersuchungen) Ehrlich found the polynuclear cells of the blood and bone-marrow and their early forms free from all neutrophil granulation. On the grounds of this observation Ehrlich returned to his original assumption that the granules are secretory products of the cells, and defined his standpoint at that time as follows:
"Did the neutrophil granulations really represent the bodies which supply these cells with oxygen, as Altmann supposes, a condition such as we have here brought forward would be impossible, since with the disappearance of the granules death of the cells must follow. But from the point of view of the secretion theory the condition described is easily explainable. Just as under certain conditions fat-cells may completely lose their contents without dying, so the bone-marrow cell, if the blood fails to yield to it the necessary substances, may occasionally be unable to produce more neutrophil granules. And thus it becomes non-granular."
The view, that the granules are special metabolic products of the specific cellular activity, is strongly supported by the great chemical differences between them. Ehrlich made these peculiarities clear for the blood-cells, and found that their granulations differ from one another, not only in their colour reactions, but also in their shape and solubility; so that they must be sharply distinguished.