HISTORICAL 



A year later, Woolley et al."^ reported that the chick antidermatitis 

 factor was destroyed by alkali and that j8-alanine could be isolated 

 from the product. They reactivated the acidic portion of the alkali- 

 inactivated concentrate by acetylation, conversion of the product 

 into an acid chloride by treatment with thionyl chloride and reaction 

 with jS-alanine ethyl ester in pyridine solution, followed by hydrolysis 

 with cold sodium hydroxide solution. The substance thus obtained 

 was effective in curing chick dermatitis. 



The authors noted a resemblance between the chick factor and 

 pantothenic acid, a substance that R. J. Williams ® had shown many 

 years before to be one of the components of " bios ", the hypothetical 

 factor essential for the growth of yeast. The name is derived from 

 the Greek meaning " from everywhere ", on account of its widespread 

 occurrence. Its chemical constitution was not known, but R. J. 

 Williams ^ had described a method of preparing a concentrate of 

 pantothenic acid from sheep's liver and had listed some of its pro- 

 perties. Shortly after the publication of the paper by Woolley et at., 

 T. H. Jukes ^^ tested the calcium salt of Williams' pantothenic acid 

 on chicks and found that it was markedly active in curing chick 

 dermatitis when administered in a dose of lo mg. 



Weinstock et al}^ then reported the isolation of ^-alanine from 

 alkali-inactivated pantothenic acid and showed that ^-alanine could 

 replace pantothenic acid for some micro-organisms, though not for 

 others. This strengthened the presimiption that the chick anti- 

 dermatitis factor was identical with pantothenic acid, and further 

 support was given by the fact that a " varnish-like " calcium salt 

 prepared from liver extract ^^ by a procedure similar to that used by 

 Williams in preparing calcium pantothenate gave good growth when 

 fed to rats maintained on a synthetic diet and behaved like panto- 

 thenic acid in stimulating the growth of Streptococcus haemolyticus and 

 the diphtheria bacillus. 



The identity of the liver " filtrate factor " with pantothenic acid 

 was confirmed by Lythgoe et al.,^^ who isolated j3-alanine from the 

 hydrolysate and re-combined it with the lactone half of the molecule. 

 Lythgoe et al. also presented evidence that the " filtrate factor " was 

 not a single entity, but comprised at least three factors : [a) factor a, 

 identical with pantothenic acid ; {h) factor j8 which, unlike factor a, 

 was not extractable from acid solutions by amyl alcohol ; and (c) 

 factor y. 



Similar results were obtained by Black et alM and J. J. Oleson 

 and S. Black,^^ who reported that rats required both pantothenic acid 

 and a factor termed by D. V. Frost and C. A. Elvehjem ^^ the alcohol- 

 ether precipitate factor or factor W, and that these together were not 

 so active as a crude liver extract, which therefore contained at least 



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