October 27, i ^98] 



NATURE 



617 



is held by several organic chemists. My reason for rejecting it 

 is that it attributes to the " breeding " process (to employ Prof. 

 Pearson's concise, but, as we shall see, not altogether accurate 

 expression) an efficiency which experiment does not justify, I 

 will explain this important point in detail, as those who appeal 

 to the " breeding " process seem to me to do so in a somewhat 

 vague and elastic way. 



This influence of already existing asymmetric molecules, or of 

 asymmetric groups within the molecule, manifests itself in two 

 ways, which I will distinguish as asyuuiietric induction and 

 asytiimetric selection. 



(1) Asymmetric Induction. — If we introduce into an asym- 

 metric molecule a fresh asymmetric carbon atom, or if we 

 render asymmetric a carbon atom which was not previously so, 

 the asymmetry already present will influence the character of 

 the new asymmetry, and of the two possible arrangements of 

 the new asymmetric carbon atom, one will predominate, or may 

 even be the sole form. This influence, however, is entirely 

 ?«/ramolecular ; all attempts to convert asymmetric induction 

 into an ?«/^;-molecular action have failed. Thus various 

 attempts have been made to obtain an optically active substance 

 by allowing a reaction which under symmetric conditions would 

 yield a racemoid mixture, to proceed in a solution containing 

 another optically active substance ; but this dissolved substance 

 was invariably found to be without influence on the course of 

 the reaction, and the resulting product was optically inactive. 

 This influence, therefore, so far as experiment goes, does not 

 extend from molecule to molecule, although within the molecule 

 it is very powerful. 



If the protoplasmic theory of vital synthesis is correct, ac- 

 cording to which the molecules of carbon dioxide and other 

 non-living molecules first combine with the living protoplasm 

 and are afterwards eliminated in the form of asymmetric com- 

 pounds, this asymmetric induction probably determines the 

 asymmetry of the resulting compounds. But even supposing 

 living protoplasm to consist of molecules — ^of which we have no 

 proof— such molecules exercise their peculiar synthetic functions 

 only under the influence of life, and are, therefore, useless as 

 " breeders " for the purposes of Prof. Pearson's argument. Prof. 

 Pearson's twenty non-living asymmetric molecules, formed by 

 the chance play of mechanical forces, would, so far as experiment 

 informs us — although I freely admit that mere negative results 

 are not conclusive — have no more influence on the asymmetry 

 of other molecules formed in their neighbourhood than one toss 

 of a coin has upon another to.ss. 



(2) Asymmetric Selection. — This is of two kinds. The first 

 is that discovered by Pasteur, in which the different degree of 

 affinity of one asymmetric base for two enantiomoi-phous acids 

 (or of one asymmetric acid for two enantiomorphous bases) 

 comes into play, and a separation may be effected, depending on 

 the different solubilities of the resulting salts. But how this 

 process would be available for Prof. Pearson's purpose, one 

 hardly sees. In the most favourable case, his twenty asymmetric 

 molecules would combine with a limited number — twenty, or 

 some simple multiple or sub-multiple of twenty — of molecules 

 from some racemoid mixture that happened to be present, and 

 there would be an end of their action. There is no question of 

 "breeding" here. Their number would not be increased by 

 the process. 



The other kind of asymmetric selection, which is a modifica- 

 tion of that described by Pasteur, was discovered by Kipping 

 and Pope. It depends on the fact that certain asymmetric sub- 

 stances, when in solution, alter in a different degree the solu- 

 bility of two enantiomorphs, without actually, as in the previous 

 case, entering into definite chemical combination with them. In 

 this way a partial separation of enantiomorphs may sometimes 

 be effected. But the applications of the method are very limited. 

 Thus Kipping and. Pope found that whilst, by means of a 

 concentrated solution of glucose, they could effect a partial 

 separation of sodium ammonium dextro- and laevo-tartrates — 

 substances which spontaneously crystallise separately (^i.e. not 

 in racemic combination) at ordinary temperatures — in the case 

 of mandelic acid, which is racemic at ordinary temperatures^ no 

 separation was effected, the tendency to form a solid racemoid 

 overcoming any tendency to separation due to the presence of 

 the glucose. Moreover, this action has never been observed, 

 except with concentrated solutions of the selective substance ; and 

 it is, therefore, quite impossible that Prof. Pearson's twenty 

 molecules — doubtless in a state of unlimited dilution — could in 

 any way influence the solubility of other substances present. 



NO. 15 13, VOL. 58] 



My contention with regard to this "breeding" question, so 

 far as non-living matter is concerned, therefore is : Asymmetric 

 induction "breeds" only within the molecule, and without 

 thereby adding to the number of molecules ; asymmetric selection 

 does not " breed " at all. 



In fact, I do not see what Prof. Pearson is to do with his 

 twenty molecules when he has got them. They will not 

 " breed " in the sense he contemplates. On the other hand, 

 if the process which produced them should go further, so as to 

 yield a sensible quantity of substance, both enantiomorphs must 

 be formed ; and as the chances are equal in favour of the two 

 asymmetric events ; as, moreover, the occurrence of either event 

 does not influence that of the other ; and as the number of 

 molecules in a sensible quantity is very great, Le Bel's ratio, 



Number of occurrences of event I. 

 Number of occurrences of event II. 



will not differ sensibly from unity. 



Several of my critics seem to think that a mere sensible pre- 

 ponderance of one enantiomorph is sufficient. This is not the 

 case unless the minority can be " bred " out of existence ; and 

 I do not think that under symmetrical conditions this is possible. 

 We must bear in mind that, in the case of at least 99 per cent, 

 of those optically active compounds which are products of the 

 living organism, only one enantiomorph is found. It is the total 

 disappearance of the opposite form which we have to explain. 



Prof. Pearson, referring to the hypothesis of the asymmetric 

 carbon atom, says : " Such a geometrical hypothesis cannot give 

 the dynamical explanation of rotatory polarisation required by 

 the physicist." ^ Every chemist, of course, fully recognises 

 this ; and in addressing an audience of chemists, I did not think 

 it necessary to introduce so obvious a qualification of my state- 

 ments. In the present undeveloped state of stereochemistry we 

 are compelled provisionally to treat, as statical, problems which 

 are in reality dynamical. The atoms are considered as being at 

 rest in the positions of equilibrium about which they actually 

 oscillate or revolve. Or, as Van 't Hoff puts it, the problems of 

 stereochemistry are tacitly treated in the form in which they 

 might be conceived to present themselves at the absolute zero of 

 temperature. 



Prof. Fitzgerald makes two suggestions, either of which, he 

 considers, would dispose of my contention that single asymmetric 

 forms cannot arise under chance conditions. In the first of these 

 he supposes a mixture of two enantiomorphs to separate spon- 

 taneously into its right- and left-handed crystalline forms. If 

 life then started from a few such centres, there would probably 

 be a preponderance of one or the other form ; " if it started 

 from a single centre, it must have been either right- or left- 

 handed." 



In reply I would point out that this spontaneous separation of 

 enantiomorphs is confined to crystalline substances ; and I should 

 have thought it fairly obvious that crystalline substances cannot 

 possibly form the organic structural material of living organisms. 

 Can Prof. Fitzgerald imagine crystallised protoplasm ? 



Prof. Fitzgerald's second suggestion is that life "probably 

 started either in the northern or in the southern hemisphere, and 

 in either case the rotation of the sun in the heavens may be a 

 sufficient cause for a right- or left-handed structure in an organism 

 growing under its influence." 



In attributing the origin of the molecular asymmetry of com- 

 pounds produced in the living organism to the apparent diurnal 

 motion of the sun. Prof. Fitzgerald has been anticipated by 

 Pasteur. I had, therefore, carefully considered the question 

 before writing my address. I do not assign any importance to 

 the negative result of the experiment which Pasteur made with 

 the object of detecting such an influence. Indeed, we need not 

 consider Pasteur's experiment at all, inasmuch as nature has 

 been carrying out for us on this very point an experiment of a 

 similar character which has lasted from the first appearance of 

 life on our planet to the present day— and has equally yielded a 

 negative result. For, if this supposed influence were at work, 

 the asymmetric compounds of vegetable origin produced in the 

 northern and southern hemispheres respectively ought to display 



1 Prof. Pearson waives any objections to my reasoning "arising from the 

 fact that it is based on a purely geometrical hypothesis as to the constitution 

 of molecules," &c. But even if Prjf. Pearson feels inclined to put forward 

 these objections, he will find that I p )int out, towards the close of my 

 address, that the reasoning is independent of this hypothesis, and that it 

 holds good equally of the hemihedral crystalline forms of these asymmetric 

 compounds about which there is no hypothesis at all. 



