468 BULLETIN OP THE BUREAU OF FISHERIES. 



The results, therefore, from mercury in such high dilution and given intermittently, 

 are less marked than with the high iodine dilutions and the less dilute mercury and 

 arsenic. Nevertheless, as compared with controls, even given in these extremely small 

 quantities, there is an undoubted effect from the mercury. 



Experiment 7 (table xiv) .Arsenic administered in continuous flow, as As 2 O 5 , 

 delivered constantly, drop by drop from floating siphon, making a dilution equivalent 

 to i part of arsenic in 300,000 parts of water. 



Five clinically clean landlocked salmon and five tumored trout were subjected to 

 this treatment. On the fourteenth day of the experiment the following fish were killed 

 and preserved for microscopic examination: One with throat tumor, one with a throat 

 and mouth tumor, and two clinically clean. In addition, two controls, one tumored 

 and one clinically clean, were preserved for comparison. 



At the end of the twenty-second day the experiment was discontinued and the 

 remaining fish preserved. These consisted of three originally clean landlocked salmon 

 and three originally tumored brook trout. Of the latter, there was only one visible 

 tumor left and that greatly reduced in size. In another a red floor was the only visible 

 sign of what was originally a fair sized tumor. (Fig. 109.) In a third there was no 

 macroscopic evidence of the former tumor. 



Microscopically all the thyroids of the fish subjected to treatment showed distinct 

 evidence of regression. This was most marked in the fish in which treatment had been 

 continued for 22 days. The controls, on the other hand, had undergone no regression. 

 The results of microscopic study are briefly outlined in table xiv. 



During the winter of 1910, in order to determine whether the results obtained by the 

 administration of thymol in endemic goiter by McCarrison could be duplicated by the 

 administration of this drug through the medium of the water upon fish with carcinoma 

 of the thyroid, the following experiments were carried out: Thymol at i part to 500,000 

 of water, dissolved by the aid of heat maintained constantly in flowing water for 34 

 days, was without recognizable effect macroscopically or microscopically upon either 

 visible tumors or the early stage. The temperature of the water ranged from 2 to 3 C. 

 A brook trout yearling was killed between the second and third day by thymol at i to 

 200,000, indicating that solution of the thymol in the water was attained. 



Generally speaking, iodine, mercury, and arsenic produce changes in the prolifer- 

 ating thyroid tissue, both in the early and advanced stages of carcinoma of the thyroid, 

 which are scarcely distinguishable from the changes found in spontaneous recovery. 

 In the early stages the change consists in a reversion of the columnar epithelium to the 

 flattened form, return of stainable colloid, disappearance of hyperemia, and the partial 

 disappearance of the most remote extensions of follicles in the outlying tissues. Where 

 regression occurs rapidly in large tumors the first evidences of regression are found in 

 extensive hemorrhages into the substance of the tumor; in some instances extensive 

 areas of the tumor are the seat of hemorrhage. Such hemorrhages are organized by 

 connective tissue. (See fig. 101.) The high columnar epithelium, especially in the 

 peripheral portions of the tumor, are changed to flattened and atrophic cells with 

 greatly diminished protoplasm. The retrograde changes are most marked at the periph- 

 ery, and the entire picture is like that described under spontaneous recovery, except 

 that the process seems to be more rapid and more extensive under treatment with 

 metals. The effect of the metals, particularly mercury, is found as soon as the eighth 



