CARCINOMA OF THE THYROID IN SALMONOID FISHES. 493 



mine whether or not extensive constitutional disturbances can be produced with the 

 agent which we hold responsible for carcinoma of the thyroid in fish will require extensive 

 experiments with young animals carried over a longer period of time than our experi- 

 ments have thus far encompassed. It is quite clear from these experiments that there is 

 a most intimate relation between the experimental production of goiter and the develop- 

 ment of malignant disease of the thyroid in mammals. The infiltration of the capsule 

 in dog 18 is extremely suggestive. Further experiments with older animals carried over 

 a considerable period of time will be necessary before it can be definitely determined 

 whether or not the agent responsible for carcinoma of the thyroid in trout is capable of 

 producing infiltrating, possibly metastasising tumors in mammals. Bircher's experi- 

 ments in producing nodular.struma in rats makes the outlook in this direction promising. 



The first attempts to produce experimental goiter in the lower animals by giving 

 them to drink water from goitrous sources were undertaken by Klebs and H. Bircher 

 (1883?) who, however, did not arrive at successful results. Carle in 1888 and Lustig 

 in 1890 succeeded in producing in both dogs and horses, in regions free from goiter, 

 enlargement of the thyroid as the result of giving them water from goitrous sources 

 over a period of months. The most elaborate and carefully studied experiments are 

 those by E. Bircher, jr., above referred to. Since his observations Rdpin (191 1) and 

 Breitner (191 2) have carried out experiments and confirmed his results especially in 

 rats, dogs, and monkeys, their experiments likewise extending over several months. 



Dieterle, Hirschfeld, and Klinger (1913) have repeated the experiments of Bircher, 

 Wilms, R^pin, and others, and arrive at the following conclusions: That in regions in 

 which goiter is endemic it is possible to produce goiter in rats by giving them copious 

 amounts of water to drink. Their success ranges from 40 to 70 per cent. Second, the 

 nature of the water which is used in a goitrous locality is without significance. The 

 water may be either fresh or boiled, and goiter may be produced with water which at 

 the point of its origin is not a goiter-producing water. Rats in a goiter-free locality 

 in Zurich which were given goiter water from other localities did not at first develop 

 goiter. Later, however, a few positive results were obtained, but it was felt that con- 

 tact infection could not be excluded. Because it is possible to develop goiter in rats 

 in goiter regions with water from goiter-free localities, they conclude that the primary 

 character of the water is not the determining factor in the development of goiter. 

 They point out that in goiter locahties boiling the water does not protect experimental 

 animals against the development of goiter, but that in goiter-free localities boihng the 

 water destroys the goiter-producing character of such water. They conclude that this 

 indicates that the etiologic agent of goiter must be occasionally transmitted through 

 the water. These experiments conform with the work, as yet unpublished, of L,and- 

 steiner, Schlagenhaufer and Wagner, and v. Jauregg, which will show that rats which 

 were given nothing but boiled water from Vienna and kept in a peasant's house in the 

 neighborhood of Rothenthurm in Judenburg, in Steiermark, in which all the inmates 

 of the house were either goitrous or cretinic, developed goiter in a percentage equal to 

 that obtained with rats, using the goitrous water of that locality, whereas attempts to 

 produce goiter in rats in Vienna with the goiter water of Rothenthurm gave only nega- 

 tive results. 



