20 MASS. EXPERIMENT STATION BULLETIN 370 



of malignancy. Foulds (68) and Levine (129) have reviewed the extensive lit- 

 erature on this question and their articles should be consulted for details of this 

 aspect. 



Crank and Furth (27), Rothe Meyer and Engelbreth-Holm (170), Storti and 

 Brotto (183), and Ruffilli (174 d) have demonstrated the agent of fowl leukosis 

 in the blood of recipients immediately after inoculation. Most if not all of the 

 agent disappeared within 24 hours after inoculation, and it was found again in 

 the blood almost simultaneously with the appearance of immature cells. 



Ruflilli (174 d) observed that the whole blood or blood cells were infective for a 

 longer period of time immediately after intravenous inoculation with the leukosis 

 agent than was the blood plasma. This probably was due to simple physical 

 adsorption of the agent to the blood cells. He also found that the bone marrow 

 was infective as early as three hours after intravenous injection of the agent, but 

 infectivity was more readily demonstrable after 24 hours. 



Van den Berghe and d'Ursel (206 a) have indicated that the agent of leukosis, 

 although present in all the blood constituents, may be more concentrated in the 

 immature blood cells than in other fractions of leukotic blood. Their method of 

 study was to use leukotic bloods with different relative amounts of immature 

 cells. The plasma and cells were separated and one portion of the cells was laked 

 by freezing at — 10° C. The plasma was generally found to be the weaker in viru- 

 lence. Laking of the cells had no effect on increasing the activity of the inoculum 

 preparations. 



Ratcliffe and Furth (166) studied the changes in the tissues of fowls killed at 

 various intervals after they had been inoculated with cell-free filtrates, with 

 washed cells, or with whole blood obtained from leukotic birds. The first change 

 observed in chickens receiving cell-free material was a hyperplasia of the erythro- 

 blastic cells in the marrow sinuses, which was followed by the appearance of 

 immature cells in the blood. Chickens inoculated with cell-containing material 

 showed leukemic changes in the blood at a time when the capillary bed of the 

 bone marrow was only partially filled with erythroblasts. Only a slight gran- 

 uloblastic hyperplasia was observed. Three possible explanations of the hyper- 

 plasia were considered: first, irritation of preexisting basophilic erythroblasts; 

 second, stimulation of the reticulo-endothelial cells of the marrow sinusoids; 

 and third, a neoplastic growth of the inoculated cells lodging in the bone marrow. 

 Ratcliffe and Furth favored the first of these theories. No explanation of the 

 manner of development of granuloblastic leukosis was given, although a selective 

 action of the inciting agent of the disease was suggested. Engelbreth-Holm and 

 Rothe Meyer (58) offered an explanation that certain chickens are predisposed to 

 a certain type of the disease and that passage of the agent through these chickens 

 enhances the ability of the agent to produce that specific type of reaction. This 

 idea was substantiated in their Strain Ti which they observed to separate into 

 two branches, one of which was entirely erythroblastic in character, whereas the 

 other was preponderantly granuloblastic. 



Ellermann (42) believed that the granulocytic hematopoiesis was different in 

 granuloblastic leukosis than under normal conditions. Under normal conditions 

 the process proceeds in the following manner: the myelocyte divides to form other 

 myelocytes and some divide to form metamyelocytes and these in turn form the 

 polynuclear cell (heterophil). The pathological development of the granulocytes 

 in granuloblastic leukosis, he believed, began with the much more immature 

 myeloblast which developed into the poikilonuclear cell after passing through 

 the stage of the metamyeloblast. He regarded this poikilonuclear cell as analagous 

 to the leukoblast of Pappenheim. 



