THE CIRCULATION OF THE BONE-MARROW. 31 



entirely devoid of endothelial lining. This earlier view, however, has been quite 

 clearly shown to have been based upon erroneous observations, and the later 

 conceptions, while being divided by two different interpretations, nevertheless 

 agree on the presence of endothelium-lined blood-vessels as the essential basis of 

 the circulation. (2) Langer (1877) was among the first to advance the opinion that 

 the vascular system of the bone-marrow is a closed system lined throughout with a 

 continuous endothelial layer. Bizzozero (1891), a few years later, after more 

 extensive investigations than had hitherto been made, reported as follows: 



"In the marrow of birds one is able to affirm that the venous capillaries are limited 

 by a thin nucleated membrane, consequently they are not the simple hollow spaces in 

 the tissue of the marrow as so many have maintained." 



On the other hand, Bizzozero was not so positive about the circulation in 

 mammals and was rather prone to doubt the completeness everywhere of the vas- 

 cular walls in mammalian marrow. Denys (1887-1888), also drawing his conclu- 

 sions from experiments on the bird, concurred in the observation that the vas- 

 cularization of the marrow is that of a single closed system of vessels lined with 

 endothelium. Again, Van der Stricht (1892) differentiated between avian and mam- 

 malian marrows, in the former observing only closed venous capillaries possessing 

 an endothelial wall throughout their extent, in the latter describing non-continuous 

 vascular walls. Minot (1912) questioned the adequacy of proof for the contention 

 that there are direct openings into the parenchyma from the blood-vessels. Schafer 

 (1912) contented himself with stating that there were two theories, frankly with- 

 holding any opinion in the controversy. 



Finally, Drinker, Drinker, and Lund (1922), in a recent analysis of a very exten- 

 sive series of splendidly controlled injections of marrow, state their belief that the 

 "capillaries conducting blood in the bone-marrow of the mammal in a condition 

 of normal blood formation are closed structures lined throughout with endothelium 

 and not in communication with the marrow parenchyma." (This coincides with 

 my own [1922] observations on mammalian marrow.) They further advance 

 a most interesting explanation of the marrow condition during active hyperplasia. 



"Under conditions of active red-blood-cell formation the extremely delicate walls 

 of these capillaries [venus sinusoids] are grown through by irregularly placed red cells 

 in varying stages of maturity. The capillaries are thus, for a period of varying length, 

 open structures, but the opening presented does not result in flooding the marrow paren- 

 chyma with blood, because of the packing of the immature blood-cells, which is an essen- 

 tial phase in the process of encroachment upon the capillary wall." 



(3) As has been suggested above, the third view is that there is an incomplete 

 endothelial lining to the venus sinuses with openings directly into the parenchyma 

 for the exit of blood plasma and the entrance of mature cells. Weidenreich (1903, 

 1904), in his researches on the marrow as a hemopoietic organ, found that so-called 

 "cell-nests" constitute the blood-forming tissue, that they are appendages of the 

 venous capillaries, and that the endothelium of the latter is deficient in the region 

 of these "cell-nests." Venzlaff (1911) maintained that erythrocytic differentiation 

 takes place within the venous sinuses of avian marrow from lymphocytes that have 

 passed out of the "Leukoblastershaufen" (the "cell-nests" of Weidenreich), in the 



