66o 



NATURE 



[July 22, 1920 



importance in a chemotherapeutic compound, especially 

 if they can be placed in the ortho-position to the 

 element one wishes to incorporate. 



Of greater importance than the group is the mole- 

 cular orientation ; one needs only to mention the 

 effect of introducing an acetyl group to illustrate this 

 point. Compare diorthoaminothiobenzene with its 

 acetyl derivative; the former is practically a specific 

 for metallic poisoning, while the latter is as inert as 

 plain colloidal or sublimed sulphur. Even dipara- 

 aminothiobenzene cannot compare with the ortho- 

 body. The addition of an acetyl group to salicylic 

 acid results in a new analgesic property, while at the 

 same time the undesirable after-effects of salicylates 

 are in some measure eliminated. A similar addition 

 to phenetidin gives us phenacetin with its valuable 

 antipyretic properties. On the other hand, the addition 

 of an acetyl group to parahydroxyphenylethylamine (an 

 active principle of ergot) results in a loss of activity. 

 The introduction of an acetyl group into the choline 

 molecule converts this comparatively inert substance 

 into a powerful heart poison. Highly interesting is 

 the case of aconitine. This intensely poisonous 

 alkaloid is the acetyl derivative -of benzaconine, the 

 lafter substance being relatively non-toxic. Yet the 

 introduction of further acetyl groups into the aconi- 

 tine molecule does not increase, but diminishes, its 

 toxicity. 



Recent Advances in Biochemistry. 



Theoretically, every ingredient of a drug or prepara- 

 tion must have some etfect, though it may be so small 

 as to be inappreciable by any known means ; and 

 some drugs and foods have constituents minute in 

 quantity, and therefore long unknown, of the very 

 highest degree of importance. Indeed, recent advances 

 in biochemistry have proved the existence in drugs 

 and foods of physiologically active substances which 

 give a rational explanation of facts based upon experi- 

 ence and established empirically. 



Fresh in the memories of all of us is the discovery 

 of the cause and cure of beri-beri, constituting one of 

 the romances of medical science. Beri-beri is a 

 disease of a high mortality which ravaged tropical 

 countries and caused much misery. It had long been 

 connected in the minds of the investigators with the 

 rice which formed the staple food of the populations 

 affected by it, but it has only recently been discovered 

 that the disease is caused by the refinements of rice- 

 milling, brought about by the introduction of 

 machinery. It was observed by Eijkmann, the 

 medical officer to a prison in Java, that the poultry 

 of their establishment suffered from symptoms re- 

 markably like those of beri-beri, which was common 

 in his gaol, where the inmates were fed on a rice 

 diet. Investigations showed this observer that the 

 fowls could be quickly cured by adding to their diet 

 the pericarp and embryo of rice removed during the 

 process of milling. 



From this starting point there was established by 

 research a complete correlation between the occurrence 

 of beri-beri and the consumption of steam-milled rice. 

 In districts where rice is polished byhand the disease 

 does not frequently occur, because it rarely happens 

 that the whole of the pericarp and embryo are removed 

 by hand. Fowls fed on polished rice quickly suffered 

 from polyneuritis, and birds almost at the point of 

 death were quickly rescued, it was found, by the 

 administration of a watery extract of rice polishings. 

 Thus was beri-beri found to be caused by the absence 

 from the diet of a substance soluble in water and 

 present in rice polishings. 



This water-soluble constituent belongs to a class 

 of accessory food substances which have been some- 

 what unfortunately named "vitamines." Work on 



NO. 2647, 'V'OL. 105] 



these, vitamines can scarcely be said to have a 

 chemical basis, since all attempts to isolate them 

 have failed. At least three have been recognised : 

 (i) water-soluble B factor, which prevents beri-beri, 

 occurs in the seeds of plants and the eggs of animals, 

 in yeast and liver and grain cereals. 



Scorbutus or scurvy is a disease which in former 

 times caused high mortality. Sailors particularly 

 were subject to attack, this being due to the fact that 

 they were not obtaining another water-soluble vita- 

 mine, (2) the anti-scorbutic factor. The disease yields 

 readily to a diet of potatoes, cabbages, and most fresh 

 fruits. 



Thirdly, there is a fat-soluble vitamine; this is 

 present in cream and butter and beef-fat, and affords , 

 us a rational explanation of our natural preference 

 for real butter over vegetable margarine. Cod-liver 

 oil, which may be regarded aS intermediate between 

 foods and drugs, has long enjoyed a deservedly great 

 reputation as possessing qualities superior to those 

 of other oils. These qualities are due to the fact that 

 good cod-liver oil has a high vitamine content, and is 

 therefore important in the prevention and cure of 

 rickets. On the other hand, vegetable oils, such as 

 linseed, olive, cottonseed, coconut, and palm, contain 

 onlv negligible amounts of this vitamine. 



Biochemistry shows us the importance of other 

 accessory substances besides vitamines. Enzyme 

 action has been shown to be modified or stimulated 

 by the presence of other substances termed co- 

 enzymes. Parallel phenomena have been observed in 

 the digestive processes of mammals in the remarkable 

 activating nature of bodies termed hormones. 



It would be beyond the limits of mv address to go 

 further than these somewhat brief indications that 

 naturally occurring drugs and foods contain substances 

 that long remained unsuspected and still longer un- 

 revealed, but quite enough will have been said to 

 show how unsafe it is to substitute one thing for 

 another. 



Research. 



It is not easy to state concisely what is to be dis- 

 tinguished as pharmaceutical research. All will agree 

 that it means something more than an improvement 

 in processes for the exhibition of drugs in pharma- 

 ceutical preparations. Does it mean problems arising 

 out of the cultivation of drugs not hitherto grown 

 within the Empire, or the intensive cultivation of in- 

 digenous drugs with a view to increased activity, or the 

 chemical investigation of drugs for their active con- 

 stituents; or, again, does it mean research in organic 

 chemistry for the production of new synthetic 

 remedies, or does it mean pharmacological ' experi- 

 ments, or all of these things? I would submit to you 

 the following consideration : We have seen that 

 pharmaceutical preparations of drugs continue to find 

 employment even after the active principles of those 

 drugs have been isolated, and are readily available 

 in a pure state. We have seen that drugs and food- 

 drugs are found to have valuable properties which 

 cannot be stated in definite terms in the present state 

 of our knowledge. Further than this, as our know- 

 ledge of such bodies as vitamines, enzymes, and 

 hormones advances, so increases our respect for the 

 natural source of such bodies — they may be glands or 

 they may be seeds — whether as a food or as a remedial 

 agent. Such mav be the fate of many an "old- 

 fashioned " remedy about which hard words have 

 been used merely because it was not fully understood. 

 Here then, it seems to me, is presented a most fitting 

 subject for pharmaceutical research : to determine 

 and control the conditions of collection and prepara- 

 tion of the parent drug, the process of treatment and 

 manufacture and the conditions of storage, to dis- 



