740 VIII. PROVITAMINS D AND VITAMINS D 



vitamins A and D are present in the non-saponifiable extract. However, 

 because of the fact that the antixerophthalmic action of the non-saponifi- 

 able extract can be destroyed when the product is oxidized, while the anti- 

 rachitic effect is presei-ved under such circumstances, it was first recognized 

 that two distinct fat-soluble vitamins must occur. ^ 



As in the case of sevei'al other vitamins, the disease associated with a 

 dietary vitamin D deficiency was known long before the vitamin itself was 

 recognized. Trousseau,^ in 1873, recommended cod liver oil for the treat- 

 ment of rickets, while Hopkins^' ^ and later Funk^ concluded that rickets was 

 caused by the absence of an "accessory foodstuff" or a vitamin, as it was 

 referred to later by Funk. Mellanby'^' produced rickets in dogs experi- 

 mentally and found that the condition could be cured by animal fats. He 

 believed that the curative factor was "fat-soluble A," or that its distribu- 

 tion was similar to that of the latter vitamin. In 1922, Zucker and his co- 

 workers^ demonstrated for the first time that the antirachitic factor in fish 

 liver oils was concentrated in the non-glyceride portion of the fat, namely, 

 in the unsaponifiable fraction. Recognition of the distribution of vitamin 

 D was greatly aided })y the fact that rickets could be produced experi- 

 mentally in rats. The dietary procedures necessary to elicit rickets had 

 been worked out just before this time by Sherman and Pappenheimer^-'" 

 as Avell as by the brilliant work of McCollum and his associates. ^^~^^ The 

 first phase in the discovery of the chemical nature of vitamin D was termi- 

 nated by the demonstration that it is a vitamin entirel}^ separate from 

 vitamin A, which occurs as a component of the non-saponifiable residue.^ 



1 E. V. McCollum, N. Simmonds, J. E. Beckei-, and P. G. Shiplev, ./. Biol. Chern., 

 53, 253-312 (1922). 



2 A. Trousseau, Lectures on Clinical Medicine, Blakistoii, 1873, Vol. II, p. 734 

 (translated by J. R. Cormack and P. V. Bazire from the 3rd ed., Clinique nddicale de 

 I'Hotel Dieu de Paris, Bailliere, Paris, 1868. 



3 F. G. Hopkins, Analyst, 31, 385-404 (1906). 



* F. G. Hopkins, /. Physiol., U, 425-460 (1912). 



^ C. Funk, Die Vitamine, Wiesbaden, 1914. 



« E. Mellanbv, J. Physiol., 52, liii-liv (1919). 



7 E. Mellanbv, Lancet, 196, I, 407-412 (1919). 



» T. F. Zucker, A. M. Pappenheimer, and M. Barnett, Proc. Soc. Exptl. Biol. Med. 

 19, 167-169 (1922). 



9 H. C. Sherman and A. M. Pappenheimer, Proc. Soc. Exptl. Biol. Med., IS, 193-197 

 (1921). 



"> H. C. Sherman and A. M. Pappenheimer, J. Exptl. Med., 34, 189-198 (1921). 



11 E. V. McCollum, N. Simmonds, H. T. Parsons, P. G. Shipley, and E. A. Park, 

 J. Biol. Chem., 45, 333-341 (1920-1921). 



12 P. G. Shiplev, E. A. Park, E. V. McCollum, N. Simmonds, and II. T. Parsons, 

 J. Biol. Chem., 45, 343-348 (1920-1921). 



13 E. V. McCollum, N. Simmonds, P. G. Sliiplev, and A. E. Paik, J. Biol. Chem., 47, 

 507-527 (1921). 



1* P. G. Shiplev, E. V. McCollum, and N. Simmonds, ./. Biol. Chem., 49, 399-410 

 (1921). 



15 E. V. McCollum, X. Simmonds, P. G. Shipley, and E. A. Park, J. Biol. Chem., 50, 

 5-30, vi (1922). 



