250 CORTEX 



by Harrop, Swingle, and their collaborators. 264 Adult dogs 

 adrenalectomized in two stages are given a dose of hormone 

 which maintains the non-protein nitrogen at its normal level. 

 When constant conditions are attained, the dosage is progres- 

 sively reduced at 7 to 10 day intervals until the blood non- 

 protein nitrogen rises to a level above 50 mgms. per 100 cc. 

 The potency of the extract is expressed in terms of the dog unit 

 which is defined as the minimum daily kilogram dose necessary 

 for maintaining a dog for a period of 7 to 10 days without loss 

 of body weight and elevation of the non-protein nitrogen level 

 of the blood. 



Although superficial considerations would indicate that this 

 method should prove satisfactory, it suffers in practice from 

 several vital defects. The period of 7 to 10 days, recommended 

 for the maintenance of the animal on a given dose of extract, 

 is entirely too short. Adrenalectomized dogs, maintained on 

 an adequate dose of hormone for some time will often not 

 manifest any signs of insufficiency for 15 to 25 days. This is 

 not unexpected when one considers the survival period after 

 adrenalectomy. Cessation of therapy does not involve any 

 operative trauma or the use of anesthetics and hence the sur- 

 vival period in good health is much longer than it is following 

 adrenalectomy. Consequently, to apply correctly the method 

 of Harrop and his colleagues would involve periods of obser- 

 vation of about a month and necessitate the use of at least 

 several animals to avoid individual variations. For a depend- 

 able assay it would also be necessary to sacrifice the animals at 

 the end of the experiment and prove the absence of accessory 

 tissues or remnants of the adrenals left at operation. To 

 boast that one has used the same animal over a period of years 

 (as has been done) is to display a naive confidence in the 

 operator's infallability, which is undeserved. 



The assay of cortical extracts by the dog method, if accu- 

 rately performed, would involve so much labor, require such 

 an immense amount of extract, and be so long and tedious as 



