July 22, 1920] 



NATURE 



659 



Progress in Science and Pharmacy.^ 



By Charles Alexander Hill. 

 'pVVENTY-FOUR years have passed since the 

 •■' British Pharmaceutical Conference met in this 

 great city of Liverpool. On that occasion the late 

 William Martindale in his presidential address dealt 

 with the use in medicine of "active principles" in 

 substitution of the natural, i.e. naturally occurring, 

 drugs. At the same time he described the introduc- 

 tion of synthetic substances into medicine as a 

 novelty. 



To-day it is fitting to reflect upon the changes in 

 pharmacy wrought by progress in science— progress in 

 chernistry and biochemistry, in physics, in physiology, 

 and in the science and practice of medicine; next, to 

 examine the extent to which active principles and 

 synthetics have replaced natural drugs; then tenta- 

 tively to survey the lines upon which future develop- 

 ment may be expected. 



Of the changes that have occurred the increased use 

 of synthetic drugs is the outstanding, though by no 

 means the only, feature. It is noteworthy that im- 

 portant discoveries of new vegetable drugs are prac- 

 tically unknown. The animal kingdom, on the other 

 hand, has furnished us with drugs of the first import- 

 ance; of these the products of the pituitary body, the 

 thyroid gland, and the suprarenal gland afford notable 

 examples. The importance of these discoveries is in 

 nowise diminished if the active principles have been 

 synthesised and can be produced artificially. 



The use of synthetic remedies in medicine is some- 

 times said to date from the introduction of antipyrin 

 in 1884, but chloroform and chloral hydrate had long 

 been known and used, and synthetic salicylic acid 

 was freely used in 1877. Hypnone (acetophenone) 

 followed in 1885 and antifebrin (acetanilide) in 1886. 

 These were succeeded by phenacetin, sulphonal, 

 and trional, and since then there has been a steady 

 flow of new synthetic drugs. 



To-day the world's annual consumption of phen- 

 azone or antipyrin may be roughly estimated at 

 100 tons, of phenacetin at 250 tons, and of medicinal 

 salicylates (sodium salicylate, methyl salicylate, 

 aspirin, and salol) at no less than 2500 tons, and 

 these are a few only out of the multitude of pure 

 chemical substances used in medicine. 



Notwithstanding the remarkable extent to which 

 synthetic drugs have come into use, and despite the 

 increased employment of active principles according 

 as our knowledge of these progresses, the use of the 

 drugs themselves in the form of galenical prepara- 

 tions, whether "standardised" or not, continues to a 

 remarkable, and perhaps significant, extent. Further- 

 more, as we shall see, signs are not wanting of a 

 growing recognition of the truth that many a drug 

 and many a food mav contain valuable properties not 

 readily determined by chemical methods. It may be 

 only^ slowly that the full value of a drug discovered 

 empirically can be stated in scientific terms Para- 

 doxical as it mav seem, the tendency to-dav, with 

 advancing scientific knowledge, is to recoq-nise the 

 failure of the active principle to replace the parent 

 drug. 



When it happens, the replacement of a natural drug 

 by a synthetic substance may be conceived as pro- 

 ceeding ideally in four stages. First, the drug is 

 examined chemically, and from it is isolated a pure 

 substance, frequently an alkaloid or a criucosido, which 

 upon bein.f* subjected to phvsiological tests is found 

 to have an effect similar to' that of the parent drug; 



'1 From the presidential address delivered at the Royal 'Institution 

 Kirerpool, on July 20, at the fifty-seventh annual meeting of the British 

 Pharmaceutical Conference. 



NO. 2647, VOL. 105] 



such a substance is termed the "active principle" of 

 the drug. The second stage is to determine the 

 chemical constitution of the isolated active principle; 

 this, in general, is a matter of extreme difficulty! 

 taxing the resources of our most brilliant organic 

 chemists, which, indeed, is equally true of the third 

 stage, which consists in effecting the synthesis of 

 fhe substance. Once the synthesis has been success- 

 tully accomplished we arrive at the fourth and last 

 stage, which is the manufacture of the substance 

 upon a commercial scale. The case of suprarenal 

 gland and adrenalin affords an illustration. 



It does not follow as a matter of course that if 

 the synthesis of a substance be accomplished the 

 artificial or synthetic article will replace the naturally 

 occurring one. Supposing quinine were to be syn- 

 thesised. It is by no means to be assumed that it 

 would be cheaper to produce it on a large scale in 

 the laboratory than to get Nature to conduct the 

 synthesis, and then to extract the alkaloid from 

 cinchona bark and afterwards purifv it. It has been 

 amply illustrated in the case of cinchona bark that 

 It pays to subsidise Nature and to encourage her to 

 increase her yield. Intensive culture may be a better 

 business proposition than laboratory manufacture. 



Synthetic Drugs. 

 By far the larger number of chemical substances 

 used in medicine are not the active principles of 

 natural drugs. It would l^ad me beyond the confines 

 ot my address to attempt even a cursory survev of 

 what has been accomplished in the limitless field of 

 synthetic drugs, to the enormous consumption of 

 which I have already made reference, or to make 

 more than the barest mention of the fact that syn 

 thetic organic substances are employed as antiseptics 

 anaesthetics, narcotics, hypnotics, and antipyretics! 

 and in the treatment of diseases, notably those of 

 parasitic origin. 



Nor need 1 remind you of the many attempts made 

 by chemico-physiologists to correlate chemical con- 

 stitution and physiological action. Much chemical and 

 physiological work has been done in this fascinating 

 tield of research, and certain generalisations have 

 resulted by deductive reasoning from very numerous 

 data, yet it has to be admitted that really very little 

 is known of this borderland subject. The physical 

 condition of the substance, its solubility, especially 

 Its relative solubiliti.-s in different solvents ("partition 

 coefficient "), its adsorptive power, osmotic properties 

 and other physical properties, have as much to do with 

 its physiological action as has its constitutional 

 formula. 



It may indeed be that the purely chemical action 

 of a drug is destined to play a subordinate rdle in 

 therapy, and that, in the past, the physical action has 

 not been sufficiently considered. 



Chemotherapy shows us clearly that the physio- 

 logical action of a substance is not due to one con- 

 stituent only of that compound, but that it also 

 depends largely upon the molecular orientation of the 

 compound and the ratio of adsorption which exists 

 between it and the protein colloidal particles through 

 which this or that constituent is going to act. Con- 

 sider arsenic, for example. In the treatment of 

 disease plain liquor arsenicalis is not so effective as 

 colloidal arsenic sulphide, nor is the latter so effective 

 as arsenophenylglycine, nor the last so effective as 

 diaminoarsenobenzene. Thev all contain arsenic, but 

 the last, in virtue of its amino-groups, is able to be 

 adsorbed in yery large quantities by the protein col- 

 loidal particles ; consequents, the greatest amount 

 possible of the element gets taken up. So far as can 

 be seen at present, the amino-groups are of great 



