These two observations can only be interpreted by assuming a loss, in certain terminal stages, on the part of the organism, of its power of forming neutrophil substances. Similar conditions occur in non-leukæmic conditions; for example in a striking case of posthæmorrhagic anæmia described by Ehrlich. It is of great importance to direct attention to these cases, which up to the present have been practically disregarded—for ignorance of their occurrence may easily give rise to gross errors concerning the nature and origin of the mononuclear cells, and to the manufacture of a lienal form of leukæmia.
Finally we have to discuss the important question, how the origin of myelæmic blood is to be explained. According to our conceptions two possibilities come under consideration. Either we have to deal with a passive inflow of bone-marrow elements, or with an active emigration from the bone-marrow into the circulation. This important and difficult question is certainly not fully ripe for discussion. The most weighty objection to be raised against an active emigration of the bone-marrow cells is derived from the behaviour of the white blood corpuscles on the warm microscopic stage. These investigations have been performed by a number of authors of whom may be mentioned Biesiadecki, Neumann, Hayem, Löwit, Mayet, Gilbert, and particularly H. F. Müller on the ground of his summary of this subject. Concerning the behaviour of the forms of cell here involved, all authors are agreed that under no conditions do the lymphocytes shew the smallest spontaneous movement; whilst the polynuclear neutrophil cells always exhibit vigorous contractility. With regard to the forms most characteristic of leukæmic blood the statements are partially contradictory. Some authors deny all spontaneous movement of these cells; but most of them report observations from which it follows that a certain power of spontaneous movement is not to be gainsaid. It will be admitted that in questions of this kind, negative results are weakened by positive data. Thus Jolly recently described similar observations as follows: "C'étaient des changements de forme sur place, lents et peu considérables, formations de bosselures à grands rayons, passage d'une forme arrondie à une forme ovulaire ou bilobée etc. Ces mouvements étaient visibles dans les observations i et iv et appartenaient surtout à des globules de grande taille." It is naturally impossible to decide if these minute movements suffice for a spontaneous locomotion. But one cannot exclude off-hand the supposition that they do. It is indeed supported by a further observation of Jolly on the mononuclear eosinophil cells of the marrow. Hitherto it was taken for established that these cells are completely devoid of spontaneous movement. Jolly however was recently able to examine a specimen from a case of typical leukæmia, in which nearly all the eosinophil cells shewed active movement. He says: "Ces globules granuleux actifs présentaient des mouvements de progression et des changements de forme caractéristiques et rapides; cependant je n'ai pas vu ces globules présenter de pseudopodes effilés; de plus, leurs contours restaient presque toujours assez nettement arrêtés. Ces particularités correspondent exactement à la description, qu'a donnée depuis longtemps Max Schultze des mouvements des cellules granuleuses du sang normal." Examination of dry specimens from the same case shewed, as Jolly expressly mentioned, that the blood contained, as leukæmic blood always does, polynuclear and mononuclear eosinophil cells. In contrast then with all earlier observations, Jolly has demonstrated an active spontaneous movement of the mononuclear eosinophil cells. The amœboid movement of the mononuclear cells is so seldom seen, not because they lack this function, but obviously from defects in the methods of investigation, which as is manifest are rather rough and wholly unsuited for delicate biological processes. There are many instances in the literature of the failures of this method, even in the case of cells with undisputed mobility. Thus Rieder failed to observe any contractility in the majority of polynuclear leucocytes in a case of malignant lymphoma, whereas according to all other observations they possess this property without exception.
We think then we must draw the conclusion that the feeble mobility of the mononuclear cells, both eosinophilous and polynuclear, is only apparent, and is owing to the gross method of investigation. In reality they doubtless have mobility sufficient for emigration.
A further, but much less weighty objection to the view that myelogenic leukæmia is an active leucocytosis is, that pus artificially produced in leukæmic patients has nearly always the histological constitution of normal pus. But from our previous detailed remarks we should only expect a myelæmic constitution of the pus, if the specific morbid agent of leukæmia were present in a concentrated form at the place of inflammation. Just as we saw in pemphigus, Neusser's eosinophilous suppuration occurred only in the specific pemphigus bullæ, but not in the foci of suppuration that were artificially produced. We know that the myelocytes are in no way positively influenced by the chemiotactic stimuli of ordinary infectious agents. On the contrary, it clearly follows from the above-mentioned observations on the transformation of leukæmic blood under the influence of infectious diseases, that the common bacterial poisons act in a negatively chemiotactic sense, both on the eosinophil and on the neutrophil mononuclear cells. Under these circumstances we should indeed expect that artificially produced suppuration in leukæmic patients would have, not a myelæmic, but a polynuclear neutrophil character.
It will be the task of further investigations to examine accurately inflammatory products, e.g. pleuritic exudations, in leukæmic patients, with the object of elucidating the question, whether under special conditions of disease all the leucocytes characteristic for leukæmia may not be able to wander from the blood. Thus in a case of pleurisy in a leukæmic patient, Ehrlich received the impression from the preparations that a "myeloid" emigration had in fact occurred, carrying all the elements in the blood into the exudation. This observation does not prove the point, for numerical estimation of the proportion of white to red blood corpuscles in the exudation was not made. And these estimations are necessary in order to prove indisputably the active emigration of the white blood corpuscles into the exudation, and to exclude their purely mechanical passage, per rhexin, from the blood-stream.
The hypothesis of the active origin of myelæmia is considerably supported by a further train of argument. In leukæmia, besides the myelocytes, the polynuclear leucocytes are also enormously increased, and their active emigration is beyond doubt. And the view, that the mononuclear cells are washed into the blood, excludes that of a single mode of origin of the leukæmic blood condition; and commits us to a highly artificial explanation of its production.
The morphological changes of leukæmic blood under the influence of infectious diseases can only be explained from the standpoint of the emigration theory. For if the white blood corpuscles were mechanically carried out of the bone-marrow as a whole, it is incomprehensible that a bacterial infection should alter this process to a polynuclear leucocytosis. This change of character is easily explained on the other hand, as we have above shewn more in detail, by the assumption that ordinary bacterial poisons act positively chemiotactically only on the polynuclear neutrophil cells, but negatively on the other forms.
We explain the origin of leukæmic blood by the emigration into the blood under the influence of the specific leukæmic agent, not only of the formed polynuclear elements, but also of their mononuclear, eosinophil and neutrophil early stages; and to classify myelogenic leukæmia with the active leucocytoses.