INTRODUCTION 



by feeding sulphonaniides to rats, whilst A. D. Welch and L. D. 

 Wright *^ showed that the increase in prothrombin time caused by 

 administration of s alphas uxidine was overcome by feeding a mixture 

 of folic acid and biotin and, to a smaller extent, by giving each 

 factor separately. This result strongly supports the view that the 

 effect of folic acid and biotin is to stimulate bacterial growth in the 

 intestine (page 487) ; the bacteria synthesise vitamin K as well as 

 vitamin B factors. It is the reduction in vitamin K synthesis, of 

 course, that results in the increased prothrombin time. 



Mallory et al.,^^ in view of the similarity in behaviour of an en- 

 zymatic digest of yeast and of a liver extract on the growth and white 

 blood cell counts of sulphasuxidine-treated rats, also favoured the 

 hypothesis that the factor antagonistic to the effects of sulphon- 

 amides in rats was identical with vitamin M. 



Further work confirmed the ability of various forms of folic acid 

 to reverse the effects of sulphonamide treatment, and also indicated 

 that this effect was probably due to stimulation of the growth of 

 intestinal bacteria (page 487). 



From this somewhat lengthy discussion of the biological properties 

 of folic acid, the L. casei factors, the SLR factor, vitamin Be, vitamin 

 M, the anti-sulphonamide factor and xanthopterine, the general con- 

 clusion must be that all these factors are in some way related to one 

 another and, although some may be identical, the differences are suffi- 

 ciently marked in other instances to lead one to believe that they are 

 not all identical. In the ultimate, the only real test of identity is an 

 examination of the chemical properties of the pure substances them- 

 selves. These have recently been made available and the constitution 

 of several of the factors has been determined and some of them have 

 been synthesised. 



The first announcement that the constitution of the L. casei factor 

 had been determined and its synthesis accomplished was made by 

 Angier et al^^ Unfortunately, the note merely reported the synthesis 

 of a compound identical with the L. casei factor of liver, and stated 

 that it stimulated the growth of L. helveticus and 5. faecalis R, and 

 promoted growth and haemoglobin formation in the chick. Not 

 until nearly twelve months later did Angier et al.^"^ disclose the chemical 

 constitution of the L. casei factor and the method of synthesis. The 

 formula assigned to the liver L. casei factor was : 



H2N. N N 



OH 



. -CH2 . NHC y:0 . NH . CH . CHa . CH^ . COOH 



COOH 

 463 



