Addendum.
The above was ready for publication in essentially the form here given early in March 1916. Meanwhile Emmet published a detailed description of the aortic cell-clusters in pig embryos (Amer. Jour. Anat., vol. 19, 3, 1916) and announced the publication of a paper "Concerning certain cellular elements in the ccelomic cavities and mesenchyma of mammaRn embryos" (Amer. Jour. Anat., in press for vol. 19). After reading the first of these papers it seemed to me better to note and discuss them in an addendum than to rewrite my article on mongoose hemogenesis and attempt an incorporation of this discussion in the body of a revised paper. A glance at our illus trations shows the essential identity of our observations; and this point is emphasized by a comparison of our descriptions, after allow ance is made for differences in form and degree of development. Our independent observations are in essential agreement, but our inter pretations are wide apart. The embryonic derivation of certain cel lular blood constituents from proliferating and metamorphosing endo thelium seems well established; as is also the origin of leucocyte-like cells (macrophages?) in the serous fluids from the mesothelium of the serous cavities. I incline to view the whole process as a normal hemo genic phenomenon.
Emmel now adheres to a pathologic interpretation, concluding that, while vascular endothelium may not under normal conditions give rise to cellular elements of the blood, "it appears that in both embryo and adult mammals, endothelial tissue ordinarily passive may under certain abnormal conditions, however, assume proliferative activities contributing to the free cellular elements of the circulating blood"; also that "the participation of the mesothelium in the origin of macro phages in the embryonic ccelom is not improbably also a reaction to stimulative conditions arising in part at least through degeneration and disintergration of erythrocytes and other foreign elements escaping into these cavities." Emmel evidently labors under a feeling of compulsion to interpret his findings in harmony with the original angioblast theory, which denies participation of the vascular endothelium in the normal process of the formation of cellular elements of the blood. It may be quite true that abnormal conditions of various sorts, experimental or patho logic, may stimulate the endothelium to proliferative activity, but recognition of this fact does not compel interpretation of all endothelial proliferative activity in terms of abnormal conditions.
That certain abnormal conditions do stimulate endothelium to pro liferation and desquamation and a coincident differentiation proves only that endothelium carries the inherent capacity to thus behave. Similar behavior under early embryonic conditions may be a perfectly normal process. This similarity between a normal embryonic process
and an abnormal later condition may be simply an aspect of a very widespread phenomenon in which a pathologic adult condition is an abnormally reawakened normal embryonic condition, e. g., developing cardiac muscle and hypertrophying cardiac muscle, etc. A leiomyoma arises apparently as the result of a normal differentiation of smooth muscle-cells in an abnormal degree. Tumor cells are generally believed to be biologically of the same nature as normal cells. The cell-clusters above described would, if increased and enlarged to an abnormal de gree, produce a condition comparable to a hemangio-endothelioblastoma.
Emmel's interpretation of the cause of the formation of free meso thelial derivatives appears especially strained. Why may not the mesothefium normally give rise to the cellular elements of the serous fluids as part of its function, by reason of its close genetic relationship to hemogenic mesenchyma and endothelium? At one point Emmel inclines (p. 402) to identify the cells of the cell-clusters of the aorta with macrophages, and he ascribes the cause of their formation to the pres ence of possible toxins produced by the "atrophying" and "degenerat ing" ventral aortic vessels in close association with which some of the cell-clusters are found. This conclusion is based upon a number of fun damental uncertainties. In the mongoose material the cell-clusters consist of typical hemoblasts (mesamceboids) ; this is in agreement with both Maximow's findings for rabbit and Minot's observations on human and rabbit embryos. The endothelial proliferation products of the embryo need therefore not be confused with macrophages. Moreover, Weidenreich derives the macrophages of Metschnikoff from leucocytes, while Evans avers that macrophages and leucocytes have no direct genetic relationship. On the other hand, many hematolo gists derive the leucocytes from the common blood mother-cell, the hemoblast, which may have an endothelial origin. A second uncer tainty involves the manner of the caudal progression of the celiac, the superior mesenteric, and the inferior mesenteric arteries. Evans inclines to explain the process on the basis of an unequal growth between the dorsal and ventral portion of the abdominal aorta, necessi tating thus a less highly differentiated endothelium ventrally. Degen eration of certain ventral vessels probably also occurs; but coincident with this atrophy there may be likewise a new origin of vessels in the formation of progressively lower connections with the main ventral stems; and some of the cell-clusters may be related to the newer vessels, as I believe, rather than to the degenerating vessels, as Emmel believes.