II. CHEMISTRY 133 



indicated in experiments by Mellanby,^ who found that rickets in puppies 

 is a deficiency disease, and that cod Uver oil contains a factor which pre- 

 vents it. In 1922 the vitamin was recognized as a substance distinct from 

 vitamin A by McCollum et al} These workers bubbled air through heated 

 cod liver oil until the antixerophthalmic factor, vitamin A, was destroyed, 

 leaving the antiricketic factor which they later"* termed vitamin D. Zucker 

 etaJ} found that vitamin D appears in the unsaponifiable, or sterol, fraction 

 of cod liver oil, and they suggested that "it may be a sterol related to 

 cholesterol or a cholesterol derivative." 



Proof of the relationship to sterols followed the discovery in 1924 of the 

 antiricketic activation of foods. It was found by Steenbock^ and Hess and 

 Weinstock^ that numerous foods acquire vitamin D activity when exposed 

 to ultraviolet rays. In 1925 further experiments by Hess et al.,^ Steenbock 

 and Black, ^ and Rosenheim and Webster^" demonstrated that in foods it 

 is the sterol content which is activated. Extension of this work led in a 

 few years to the preparation of calciferol, or vitamin D2, in the pure state, 

 and it is noteworthy that this was accomplished before any form of the 

 vitamin had been isolated from natural sources. 



A. THE STEROLS 



The literature of the sterols is voluminous, and the subject complex; 

 only the facts most pertinent to vitamin D will be given here. Bills' review 

 of the physiology of the sterols" will be drawn upon for early material of 

 a biochemical nature. The organic chemistry of vitamin D, particularly in 

 its three-dimensional aspects, has been covered by Lettre and Inhoffen,"^ 



antedates the unrelated classical coinage, rachitis (inflammation of the spine), and 

 is more accurately descriptive of the disease. Hence the terms rickets, ricketic and 

 antiricketic appear preferable to rachitis, rachitic, and antirachitic. 



2 E. Mellanby, Med. Research Council (Brit.) Spec. Rept. Ser. 61, (1921). 



3 E. V. McCollum, N. Simmonds, J. E. Becker, and P. G. Shipley, J. Biol. Chem. 

 53, 293 (1922). 



^ E. V. McCollum, N. Simmonds, J. E. Becker, and P. G. Shipley, J. Biol. Chem. 



65, 97 (1925). 

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



19, 167 (1922). 

 « H. Steenbock, Science 60, 224 (1924); U. S. Pat. 1,680,818 (1928). 

 ^ A. F. Hess and M. Weinstock, J. Biol. Chem. 62, 301 (1924). 

 8 A. F. Hess, M. Weinstock, and F. D. Helman, /. Biol. Chem. 63, 305 (1925). 

 ' H. Steenbock and A. Black, J. Biol. Chem. 64, 263 (1925). 

 •» O. Rosenheim and T. A. Webster, Lancet I, 1025 (1925). 

 " C. E. Bills, Physiol. Revs. 15, 1 (1935). 



"* H. Lettrd and H. H. Inhoffen, Uber Sterine, Gallensauren und verwandte Natur- 

 stoffe. Ferdinand Enke, Stuttgart, 1936. 



