Hypophysectomy in Man

Abstract

A CARCINOGENIC COMPOUND MEDS with alcohol.The soft reddish-black waxy extract was sent to our laboratory, where it was fractionally distilled at low pressure, differentially extracted, picrated, and crystal- lized.The whole process required some hundreds of test- tube pilot tests followed by preparation on a larger scale, designed to produce enough material for tests on mice.The two guides used throughout the work were, of course, the fluorescence spectrum and the assay of carcinogenic potency by application to the skin of mice.The various fractions showed a correspondence between the intensity of the Schroeter bands and the carcinogenic potency.By the autumn of 1931 about 7 g. of a yellow crystalline powder melting at 116°had been accumulated, which showed both high carcinogenic potency and powerful fluorescence in the spectral position required.The process by which this compound was tracked down is illustrated by a fine series of photographs of spectra in Hieger's later paper (1937).Without the clue provided by Mayneord's introduction of the fluorescence spectrum the testing for carcinogenic power upon mice of every crystalline fraction which one could isolate from pitch would have been an almost endless task, and even when a pure crystalline carcinogen had been iso- lated there would have been nothing to direct one's attention to the benzanthracene type of molecular structure.The fluorescence spectrum was the single thread that led all through the labyrinth.*Another batch of this crystalline material was fractionated further, in collaboration with C. L. Hewett, who joined the staff in October, 1931, under the direction of J. W. Cook, and several other compounds (2:3-benzcarbazole, chrysene, perylene) were separated from the final fractions of crystals melting at 1600.This product was taken over by Cook for identification.The Identification and Synthesis of 3: 4-Benzpyrene The crystalline material, m.p. 1600, prepared from the distillate of the pitch, was of dubious homogeneity, and by means of a series of fractional crystallizations of the picrates Cook was able to isolate from it two essentially pure crystalline products (m.p. 176°and 187°).Analysis of these two compounds and their picrates showed them to be hydro- carbons uncommonly rich in carbon.Both of them, in fact, appeared to be isomeric with the highly condensed penta- cyclic aromatic hydrocarbon perylene.The major com- ponent (m.p. 176°) showed in high dilution the characteristic fluorescence spectrum discussed above.Consideration of these and other properties led Cook and Hewett to conclude that it might assist identification of these two hydrocarbons to prepare for comparison syn- thetic specimens of the then unknown pentacyclic hydro- carbons isomeric with perylene, 3 : 4-benzpyrene and 1: 2- benzpyrene.This they were able to achieve by methods which, taken in conjunction with one another, established unequivocally the structures of the synthetic products.It was shown by direct comparison that 3:4-benzpyrene was identical with the strongly fluorescing major component of the crystals prepared from the pitch distillate.The synthetic preparation (m.p. 177°) was also highly carcinogenic.The synthetic 1: 2-benzpyrene was identical with the minor com- ponent (m.p. 187°) of the original crystallate.In 1939 the first award of the Anna Fuller Memorial