68 



SCIENTIFIC NEWS. 



[July 



20, it 



dicated) suggest this much to future observers, viz. : 

 First of all group your poisons according to their methods 

 of operation, and then see how far the degree of toxicity 

 of the terms of any one group show relationship to the 

 atomic weights of such group. 



But the difficulties of comparison thicken when we 

 consider the physiological action of certain allotropic 

 modifications of the elements. 



Thus compare yellow phosphorus, a body readily in- 

 flammable, soluble in bisulphide of carbon, firing by 

 contact with iodine, with red phosphorus, a body at 

 variance with the yellow variety in the three respects 

 named. Nor is this all. For yellow phosphorus is an 

 active poison, two grains being a certainly toxic dose, 

 whilst red phosphorus is an absolutely inert body. 



Take a second illustration. In its ordinary form 

 oxygen plays the part ot a life sustainer. But oxygen 

 is only a life sustainer in its common form and at ordinary 

 pressure. 



On this latter point I have no time to dwell, save to 

 mention that if an animal be exposed to oxygen at 

 three pressures, the resulting symptoms are not unlike 

 those induced by strychnine, 



There is, however, an allotropic form of oxygen called 

 ozone. The physiological action of ozone was the subject 

 of a communication to the Royal Society of Edinburgh 

 by Dewar and McKendrick (1873). Their experiments 

 were made on both cold and warm-blooded animals, 

 including amongst the latter themselves and their as- 

 sistants. 



The results are remarkable, more particularly when 

 we remember that the air with which they operated, at 

 most only contained 10 per cent, of ozone. 



Placing a large frog in a jar of air, and then ozonising 

 the air, the frog in about half a minute closed its eyes, 

 the respirations fell from 96 to 8 per minute, and the 

 body temperature was lowered 4 or 5° C. The animal 

 recovered in about 8 minutes, when pure air was ad- 

 mitted into the receiver. Death resulted if the animal 

 was exposed for any lengthened period to the action of 

 the ozonised air. 



As regards the action of ozone on warm-blooded 

 animals, Dewar records certain personal experiences, 

 chief amongst which were a tendency to breathe slowly, 

 an enfeebled pulse, and fits of sneezing. 



But now comes the curious part of the story, viz. that 

 at the post-mortem on the animals that died under the 

 influence of ozone, the blood was found to be venous. 

 (The results were similar when pure ozonised oxygen 

 was employed.) It is most remarkable that the post- 

 mortem appearances of death from an intensified oxygen 

 should resemble those of death from carbonic acid. 



I give these illustrations to show why there should be 

 reason to doubt whether the physical or chemical pro- 

 perties of an element can ever suggest either toxic activity 

 or physiological action. 

 2nd. Compounds. 



Is there any relationship between the chemical com- 

 position or constitution of a compound body and its 

 physiological action ? 



The first series of researches on this question was 

 directed to determining whether, in the case of a salt, 

 the acid or the base was, physiologically, the most im- 

 portant ingredient (Blake 1841). 



No doubt most often the active agent of a salt is the 

 base, but this is by no means uniformly the case. Pro- 

 bably the solubility of a compound and the different 



proportions of acid to base in the salt (i.e. whether the 

 compound in question be an acid or a basic salt) are 

 agencies which also help to determine the toxicity of the 

 body and its physiological action. 



A second series of experiments was made by Blake for 

 the purpose of showing that, given a series of isomorphic 

 salts, the intensity of physiological action increased with 

 the molecular weight. He further contended that salts 

 crystallising in different forms had different physiological 

 actions. On this basis he constructed a series of nine 

 groups of salts, each group being characterised by special 

 physiological actions, insisting with much reason that 

 we possess in living matter a reagent (so to speak) 

 capable of aiding us in our investigations into the mole- 

 cular properties of chemical compounds. If from mole- 

 cular constitution you can determine physiological action, 

 probably from physiological action conversely you may 

 determine molecular constitution. 



Another series of experiments in a similar direction 

 were made by Schoff on the Continent, and by Fraser 

 and Crum Brown in this country. 



Of these experiments the most important are those in- 

 dicating how from bodies of vastly different physiological 

 action you may obtain derivatives having similar pro- 

 perties. 



For example, the physiological action of strychnine is 

 primarily exerted on the spinal cord. As a result, con- 

 vulsions occur as a prominent symptom. But if we 

 introduce into the strychnine molecule a methyl group 

 (forming methyl-strychnine), the action of the drug is 

 altered — methyl-strychnine paralysing (strychnine stimu- 

 lating) the motor nerves. 



But here comes a curious fact. If we take morphine, 

 or nicotine, or atropine, or quinine, or veratrine (none of 

 which bodies are comparable in their physiological action 

 to strychnine), and convert them into their methyl- 

 derivatives, the methyl compounds formed (viz. methyl- 

 morphine, methyl-nicotine, etc.) are comparable in their 

 physiological action to methyl-strj'chnine. 



We must admit these experiments to be striking. One 

 treasures any experiment suggestive of the chemical 

 constitution of a body indicating physiological action. 



But again : — The true physiological action of a drug is 

 not so much its general as its selective action, this 

 selective action being largely dependent on the dose 

 administered and the mode of administration. 



For example : Inject into the circulation of a frog a 

 small dose of veratrine, great muscular stiffness results, a 

 large dose similarly administered not producing this 

 effect. And now change the method of administration : 

 Apply the small dose directly to the muscle, you get no 

 symptom ; but apply the large dose directly, and great 

 muscular stiffness results. Here see the modifying 

 influence of dose and of the mode of administration. 



Again, the difficulty of " allotropism " in the case of 

 elements, finds its counterpart in " isomerism " in the 

 case of compounds. Thus cyanogen and paracyanogen 

 are bodies of identical percentage composition, and yet 

 cyanogen is one of the most poisonous of gases, whilst 

 paracyanogen is one of the most inert of solids. 



Or, again, take piperin and morphine. These bodies 

 are of identical percentage and molecular composition. 

 They agree (it is true) in being poisons. But how vastly 

 different their physiological action ! — the one an extreme 

 irritant, the other a powerful narcotic. 



I fear we must admit that, as no a priori reasoning 

 could predict that by combining copper and sulphuric 



