September 8, 1898] 



NATURE 



457 



one molecule of the compound CHjX'V, has an equal chance 

 of affecting the other hydrogen atom in another molecule. If 

 the right-hand hydrogen atom in Fig 3 is replaced by the radicle 

 Z', we obtain the enantiomorph represented in Fig. i ; if the 

 left-hand hydrogen atom, that represented in Fig. 2. The chances 

 in favour of these two events being equal, the ratio, 

 Number of occurrences of event I. 

 Number of occurrences of event II. 



will, ii we are dealing with an infinitely great number of mole- 

 cules, approximate to unity. We therefore obtain a mixture, 

 optically inactive by inter-molecular compensation. 



All cases of the conversion of symmetric into asymmetric 

 compounds may be referred to the same category, no matter 

 whether the chemical process is one of substitution or of 

 addition, or whether the resulting molecule contains one or 

 more asymmetric carbon atoms. Thus, in the reduction of a 

 ketone of the formula X'.CO.Y' to a secondary alcohol of the 

 formula X'. CH(OH).Y' ; in the transformation of an aldehyde 

 by the addition of hydrocyanic acid into a nitrile of an 

 o-hydroxy-acid ; in the oxidation of fumaric acid to racemic 

 acid — cases typifying the various additive processes in which 

 asymmetric groupings are produced — there is one condition com- 

 mon to all : in the symmetric compound, with which we start, 

 there are, in every case, two identical points of attack, 

 equidistant from the plane of symmetry of the molecule, and 

 the result is that the two possible events happen in equal num- 

 ber, so that the mixture of enantiomorphs obtained is optically 

 inactive by compensation. We are, of course, in many cases 

 able afterwards to separate these enantiomorphs by the methods 

 devised by Pasteur, and thus obtain the single optically active 

 compounds ; but we cannot produce them singly as long as we 

 have at our disposal only the symmetric forces which we 

 command in the laboratory. 



Precisely the same state of things prevails when symmetric 

 molecules unite, under the influence of symmetric forces, to 

 build up an asymmetric crjstalline structure. When, for 

 example, sodium chlorate crystallises from its aqueous solution, 

 the number of right-handed crystals is, on the average, as was 

 shown by Kipping and Pope, equal to the number of left-handed 

 crystals. The same fact was proved by Landolt by observing 

 the optical inactivity of the mixture of microscopic right and left 

 crystals obtained by adding alcohol to a concentrated aqueous 

 solution of sodium chlorate. The two possible asymmetric events 

 occur in equal number. 



Non-living, symmetric forces, therefore, acting on symmetric 

 atoms or molecules, cannot produce asymmetry, since the simul- 

 taneous production of two opposite asymmetric halves is 

 equivalent to the production of a symmetric whole, whether the 

 two asymmetric halves be actually united in the same molecule, 

 as in the case of mesotartaric acid, or whether they exist as 

 separate molecules, as in the left and right constituents of racemic 

 acid. In every case, the symmetry of the whole is proved by 

 its optical inactivity. 



The result is entirely different, however, when we allow 

 symmetric forces to act under the influence of already existing 

 asymmetric, non-racemoid compounds. 



Thus if we start with an optically active compound — a com- 

 pound containing one or more asymmetric carbon atoms and 

 non-racemoid — and, by appropriate chemical reactions, render 

 asymmetric some carbon atom in the compound which was not 

 previously so, then it does not follow that the two forms repre- 

 sented by the two possible arrangements of this new asymmetric 

 carbon atom will be produced in equal quantity. The compound 

 with which we start has no plane of symmetry ; and, although 

 there are still the two possible points of attack, one will 

 be more exposed than the other ; in fact, one mode of 

 attack may so predominate that apparently only one asym- 

 metric compound is formed, the other compound, if formed at all, 

 escaping detection by the smallnnss of its amount. A case in point 

 is the conversion of </-mannose by combination with hydrocyanic 

 acid into the nitrile of (/-mannoheptonic acid, studied by Emil 

 Fischer, in which only one nitrile is formed, although there are 

 two ways in which the hydrocyanic acid may attach itself to the 

 aldehyde group of the mannose. On the other hand, the same 

 general reaction, in the union of hydrocyanic acid with ordinary 

 aldehyde CH3.CHO — a symmetric compound — yields the right 

 and left forms of lacto-nitrile CH3.CII(OII).CN in equal 

 •quantity, the two asymmetric events occurring in equal number, 

 and the resulting mixture of compounds being inactive. It is 



NO. 1506, VOL. 58] 



the difference between guidance and no guidance : the asym- 

 metric group present in the mannose guides into a particular 

 path the symmetric forces which bring about the addition of the 

 hydrocyanic acid ; in the case of the symmetric aldehyde the 

 result is left to pure chance. The latter action is like that of 

 tossing a perfectly balanced coin ; in the former the coin is 

 heavily weighted on one side. The saying, ^^ les dis de la 

 Nature sottt pipis" is certainly true of living nature and its 

 products. 



This guiding action displayed by asymmetric compounds may 

 even impart a bias to the crystallisation of those molecularly 

 symmetric substances already referred to, which crystallise in 

 enantiomorphous forms. Thus Kipping and Pope have recently 

 made the interesting observation that the crystals of sodium 

 chlorate which are deposited from an aqueous solution containing 

 200 grams of a^-glucose to the litre consist, on an average, of 

 about 32 per cent, of right-handed to 68 per cent, of left-handed 

 crystals, the asymmetrfc carbohydrate, by its mere presence, 

 favouring the formation of the one asymmetric form of the 

 inorganic salt at the expense of the other. 



These observations possibly afford a clue to the mode of 

 action of the living organism in producing single enantiomorphs. 

 This production of single asymmetric forms may be a result of 

 the asymmetric character of the chemical compounds of which 

 the tissues of plants and animals are built up. The optically 

 active products of the organism — the carbohydrates, the ter- 

 penes, tartaric acid, asparagine, quinine, the serum of the blood, 

 and countless others — have been formed in an asymmetric 

 environment, and their asymmetry is an induced phenomenon. 

 They have been cast, as it were, in an asymmetric mould. 

 According to this view they are a result of the selective pro- 

 duction of one of the two possible enantiomorphous forms. 

 The same would hold good with regard to the organised tissues 

 themselves, developed from inherited asymmetric beginnings in 

 the ovum or the seed, or obtained by fission. The perplexing 

 question of the absolute origin of these asymmetric compounds 

 I will discuss later. , 



Another view has been put forward by Emil Fischer. In his 

 lecture on "Syntheses in the Sugar Group," delivered before 

 the German Chemical Society in 1890, he says : 



" Starting with formaldehyde, chemical synthesis leads, in the 

 first instance, to the optically inactive acrose. In contradis- 

 tinction to this only the active sugars of the af-mannitol series 

 have hitherto been found in plants. 



' ' Are these the only products of assimilation [of carbon 

 dioxide and water] ? Is the preparation of optically active sub- 

 stances a prerogative of the living organism ; is a special cause, 

 a kind of vital force, at work here ? I do not think so, and 

 incline rather to the view that it is only the imperfection of our 

 knowledge which imports into this process the appearance of 

 the miraculous. 



" No fact hitherto known speaks against the view that the 

 plant,, like chemical synthesis, first prepares the inactive sugars ; 

 that it then resolves them into their active constituents, using 

 the members of the af-mannitol series in building up starch, 

 cellulose, inulin, &c., whilst the optical isomerides serve for 

 other purposes at present unknown to us." 



There are, therefore, two opposite processes which would 

 account for the presence of optically active compounds among 

 the substances generated in the living organism, and which we 

 may briefly describe as selective production and selective con- 

 sumption. An instance of artificial selective production is the 

 formation of only one nitrile of ^-mannoheptonic acid already 

 cited. Selective consumption, dissociated, however, from the 

 previous production of the racemoid form, may be illustrated by 

 the fermentation of dextro-tartaric acid in the action, studied by 

 Pasteur and already referred to, of a mould on racemic acid, the 

 Itevo- tartaric acid remaining untouched, and by numerous similar 

 fermentations since discovered. Selective consumption is not 

 restricted to living ferments ; various cases are known of enzymes, 

 or soluble ferments, which can effect the hydrolysis of one 

 glucoside, but not of its enantiomorph. As Emil Fischer, who 

 studied this phenomenon, says : " Enzyme and glucoside must 

 fit each other like key and lock, in order that the one may 

 exercise a chemical action on the other." And a similar selec- 

 tive action, embracing the much more complex phenomenon oi 

 alcoholic fermentation, is displayed by E. Buchner's soluble 

 zymase obtained from yeast cells. 



It is true, moreover, that the organism sometimes produces 

 both enantiomorphs. Thus the lactic ferment converts carbo- 



