CHAPTER 14 



EXPERIMENTAL INDUCTION OF 

 LYMPHOCYTIC MALIGNANCIES 



STEVEN O. SCHWARTZ 



Our interest in human leukemia compelled the search for a tool to enable 

 the investigation of the etiologic factors responsible for the develeopment 

 of the disease. Because of similarities between lymphatic leukemia in the 

 mouse and human leukemias, we undertook a series of experiments to test 

 these similarities in the two species. We have learned that antigenic similari- 

 ties do exist regarding the white cells and red cells and that the changes in 

 the blood, the marrow, lymph nodes, spleen, liver, lungs, kidneys, and genital 

 organs resemble one another. 



Experiments in which cell-free filtrates were prepared from the brain of 

 leukemic mice soon convinced us that leukemia could be induced by means 

 of a cell-free agent whose characteristics were those of a virus. 



The agent was found to be self-perpetuating in passages through mice. 

 Titration of the agent revealed a progressive fall of activity with almost 

 no ability to induce leukemia in a dilution of 10 \ However, in serial 

 passages through animals of the same species, the cell-free filtrate can be 

 diluted virtually to infinity. In our own experiments the dilutions have 

 been carried out as high as 10~ 44 with excellent retention of leukemia-induc- 

 ing ability. 



One of the intriguing questions in this field is whether leukemia primarily 

 represents a metamorphosis of cells, which would equate it with the car- 

 cinomas, or whether it is primarily a reactive hyperplasia, which later 

 becomes autonomous and irreversible. If leukemia represents a metamor- 

 phosis of cells, one must assume a unicentric origin from a locus where cells 

 have become "malignant," where they multiply, and from which the) 

 metastasize. If, on the other hand, leukemia represents a reactive hyper- 



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