458 



NATURE 



[September 8, 1898 



hydrates into racemoid lactic acid ; ordinary, or Irevo- rotatory, 

 asparagine is accompanied in plants, as Piutti showed, by a 

 small quantity of its optical isomeride ; and there are other 

 cases. 



These facts might be taken as evidence in favour of Fischer's 

 view that selective consumption is the cause of the phenomenon 

 we are discussing. But I do not think that, in the present 

 state of our knowledge, we can decide between the two views. 

 For that matter both may be correct, each may explain par- 

 ticular cases. What I wish to point out is that Fischer's state- 

 ment that the "miraculous" character of the phenomenon is 

 eliminated by his assumption appears open to question. It is 

 just as much, or as little, miraculous after as before. The pro- 

 duction of a single asymmetric form, and the destruction of one 

 of two opposite asymmetric forms, are problems of precisely the 

 same order of difficulty, and there are only two ways in which 

 either of them has ever been solved : firstly, by the direct action 

 of living matter, and, secondly, by the use of previously existing 

 asymmetric non-racemoid compounds, which are, in the last 

 resort, due to the action of life. Directly, or indirectly, then, 

 life intervenes. 



Doubtless this will appear a very extraordinary statement in 

 view of Jungfleisch's synthesis of racemic acid and its resolution 

 into dextro- and Isevo-tartaric acids by the crystallisation of the 

 sodium ammonium salts. The process does not take place in a 

 living organism ; nor is the aid of life invoked in the shape of a 

 ' micro-organism as in Pasteur's third method of separation. No 

 asymmetric base of vegetable origin is employed as in Pasteur's 

 second method, so that the indirect action of life through its 

 products is also excluded ; sodium and ammonium are sym- 

 metric inorganic radicles, and no substance of one-sided 

 asymmetry is introduced from beginning to end. The process 

 is one of ordinary crystallisation ; the two forms are deposited 

 side by side, the operator afterwards picking out the right and 

 left crystals ant' separating them. The reason why the two 

 tartrates crystallise out and not the racemate, is that at the 

 ordinary temperature of the air at which the crystallisation is 

 conducted they are less soluble than the racemate. At a higher 

 temperature, on the other hand, these solubilities are reversed 

 and the racemate is deposited. The conditions are precisely 

 those which govern the formation or non-formation of ordinary 

 double salts. 



Consequently the overwhelming majority of chemists hold 

 that the foregoing synthesis and separation of optically active 

 compounds have been effected without the intervention of life, 

 either directly or indirectly. Every manual of stereochemistry 

 emphasises this point. 



I have already hinted that I hold a contrary opinion. I have 

 held it for some time, but have not ventured to give public 

 expression to it, except in lecturing to my students. I was 

 deterred chiefly by the impression that I stood alone in my 

 belief. I find, however, that this was a mistaken impression. 

 In a lecture on " Pasteur as the Founder of Stereochemistry," 

 which Prof. Crum Brown delivered before the Franco-Scottish 

 Society in July 1897, and which is published in the Revue 

 fraitfaise (T Adimbourg, he says, referring to the separation of 

 enantiomorphs by crystallisation : — 



" The question has often occurred to me : Do we here get rid 

 of the action of a living organism ? Is not the observation and 

 deliberate choice by which a human being picks out the two 

 kinds of crystals and places each in a vessel by itself the specific 

 act of a living organism of a kind not altogether dissimilar to the 

 selection made by Pemcillium glaucum ? But I do not insist on 

 this, although I think it is not unworthy of consideration." 



It is this question, so precisely posed by Prof. Crum Brown, 

 that I would discuss in detail. I think we shall find that the 

 answer to it will be in the sense which he indicates. The action 

 of life, which has been excluded during the previous stages of 

 the process, is introduced the moment the operator begins to 

 pick out the two enantiomorphs. 



It will doubtless be objected that, if this is the case, there 

 can be no such thing as a synthesis of a naturally occurring 

 organic compound without the intervention of life, inasmuch as 

 the synthetic process is always carried out by a living operator. 



Here, however, we must draw an important distinction. In 

 the great majority of the operations which we carry out in our 

 laboratories — such as solution, fusion, vaporisation, oxidation, 

 reduction and the like — we bring to bear upon matter symmetric 

 forces only— forces of the same order as those involved in the 

 chance motions of the molecules of a liquid or a gas. All such 



NO. T506, VOL. 58] 



processes, therefore, might conceivably take place under purely 

 chance conditions, without the aid of an operator at all. But 

 there is another class of operations, to which Pasteur first drew 

 attention : those into which one-sided asymmetry enters, and 

 which deal either with the production of a single enantiomorph, 

 or with the destruction (or change) of one enantiomorph in a 

 mixture of both, or with the separation of two enantiomorphs 

 from one another. We have already seen that such processts 

 are possible only under one-sided asymmetric influences, which 

 may take the form either of the presence of an already existing 

 enantiomorph, or of the action of a living organism, or of the 

 free choice of an intelligent operator. They cannot conceiv- 

 ably occur through the chance play of symmetric forces. 



We must, therefore, in classifying the actions of the intelligent 

 operator, distinguish between those actions in which his services 

 might conceivably be dispensed with altogether, and those in 

 which his intelligence is the essential factor. To the former 

 class belongs the carrying out of symmetric chemical reactions ; 

 to the latter, the separation of enantiomorphs. 



Take the synthesis of formic acid — a symmetric compound — 

 by the absorption of carbon monoxide by heated caustic alkali. 

 Given a forest fire and such naturally occurring materials as 

 limestone, sodium carbonate, and water, it would not be difficult 

 to imagine a set of conditions under which a chance synthesis of 

 sodium formate from inorganic materials might occur. I do not 

 assert that the conditions would be particularly probable ; still, 

 they would not be inconceivable. But the chance synthesis of 

 the simplest optically active compound from inorganic materials 

 is absolutely inconceivable. So also is the separation of two 

 crystallised enantiomorphs under purely symmetric conditions. 



The picking out of the two enantimorphs is, moreover, to be 

 distinguished from the process of similarly separating the crystals 

 of two different non-enantiomorphous substances, although this 

 distinction is commonly ignored by classing both processes to- 

 gether as mechatiical, in opposition to chemical separations. In 

 the case of the non-enantiomorphs there may be differences of 

 solubility, of specific gravity and the like ; so that other means 

 of separation, involving only the play of symmetric forces, may 

 be resorted to. Such a process may justly be regarded as 

 "mechanical." But the two crystallised enantiomorphs, as we 

 have seen, have the same solubility — at least in symmetric sol- 

 vents ; the same specific gravity ; behave, in fact, in an identical 

 manner towards all symmetric forces ; so that no separation by 

 such means is feasible. It requires the living operator, whose 

 intellect embraces the conception of opposite forms of asym- 

 metry, to separate them. Such a process cannot, by any stretch 

 of language, be termed "mechanical." Conscious selection 

 here produces the same result as the unconscious selection exer- 

 cised by the micro-organism, the enzyme, or the previously 

 existing asymmetric compound. 



I need not point out that if the operator chooses to bring 

 about the separation by an asymmetric solvent, or some other 

 asymmetric means, he is still making use of his conception of 

 asymmetry. He merely effects his end indirectly instead of 

 directly. But in either case he exercises a guiding power which 

 is akin, in its results, to that of the living organism, and is 

 entirely beyond the reach of the symmetric forces of inorganic 

 nature. 



In like manner, it is not of the least consequence, for the 

 purposes of the present argument, whether the micro-organism, 

 with which we have compared the operator, acts directly in 

 fermenting one of two enantiomorphs, or whether it acts in- 

 directly by first preparing an asymmetric enzyme which displays 

 this selective action. The contention, therefore, of E. Fischer, 

 Buchner, and others, that the discovery of enzymes and zymases 

 " has transferred the phenomena of fermentation from biological 

 to purely chemical territory," is true only as regards the imme- 

 diate process, and leaves intact the vitalistic origin of these 

 phenomena. 



We thus arrive at the conclusion that the production of single 

 asymmetric compounds, or their isolation from the mixture of 

 their enantiomorphs, is, as Pasteur firmly held, the perogative 

 of life. Only the living organism with its asymmetric tissues, or 

 the asymmetric products of the living organism, or the living 

 intelligence with its conception of asymmetry, can produce this 

 result. Only asymmetry can beget asymmetry. 



Is the failure to synthesise single asymmetric compounds 

 without the intervention, either direct or indirect, of life, due to 

 a permanent inability, or merely to a temporary disability which 

 the progress of science may remove ? Pasteur took the latter 



