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At the moment when Pasteur, entering upon the labours which form the principal subject of this book, abandoned the study of molecular physics and chemistry which had previously occupied him, all his thoughts were directed to the search of means suited to render evident the influence of these causes and these phenomena. At Strasburg he had procured powerful magnets with the view of comparing the actions of their poles, and, if possible, of introducing by their aid, among the forms of crystals, a manifestation of dissymmetry. At Lille, where he was nominated Dean of the Faculty of Sciences in 1854, he had contrived a piece of clockwork intended to keep a plant in continual rotary motion, first in one direction and then in the other. 'All this was gross,' he said to me one day; 'but, further than this, I had proposed, with the view of influencing the vegetation of certain plants, to invert, by means of a heliostat and a reflecting mirror, the motion of the solar rays which should strike them from the birth of their earliest shoots, and in this direction there was more to be hoped for.' He never spoke of these attempts, because he had not had the time to follow them to the issues of which he dreamed; but to this day he remains persuaded that the barrier which exists between the mineral and organic kingdoms--and which is revealed to our eyes by the impossibility of producing, in the reactions of the laboratory, dissymmetric organic substances--can never be crossed until we have succeeded in introducing among these reactions influences of the dissymmetric order. According to Pasteur, success in this direction would give access to a new world of substances, and probably also of organic transformations. As we have succeeded in finding the inverse of right-handed tartaric acid, we may hope to obtain some day all the immediate principles inverse to those now known to us. Who could say what vegetable and animal species would become if it were possible to replace, in the living cells, cellulose, albumen, and their congeners, by their isomers with an inverse action? Certainly the thing is not easy, and Pasteur would be the last person to deceive himself as to the difficulty of the problem. His latest thought on the matter is this:--When the attempt is made to introduce into living species primordial substances, inverse to those now existing, the great difficulty will be to master the tendency (devenir) proper to the species, a tendency which is potential in the germ of each of them. In this germ, it is to be feared, the dissymmetry of the dissymmetric primordial substances which it embraces will always manifest itself. Ah! if spontaneous generation were possible; if we could form from mineral matter a living cell, how much more accessible would the problem become! However this may be, we must seek, by all possible means, to produce molecular dissymmetry by the application of forces which have a dissymmetric action. 'We must,' said Pasteur to me on the day when, starting from the note of Mitscherlich, he passed all these things in review, 'we must invoke the action of solenoid or helix. Entangled at present in labours more than sufficient to absorb whatever of ardour and of force still remains to me, I have no longer time to occupy myself with these questions.' But what great things are to be done in following out this order of ideas, and what a route will be opened to young men possessed of that genius of invention which is evoked so often by persistent work!
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This complete opposition between artificial mineral products and vegetable and animal ones was to Pasteur a truth so well established that he found frequent opportunity of affirming it under decisive circumstances. One day, a very skilful chemist, M. Dessaignes, who later on became one of the correspondents of the Academy of Sciences, announced that he had transformed fumaric and malic acids into aspartic acid. Pasteur, who some time previously had had occasion to study these same acids, had proved that the two first had no molecular dissymmetry--that is to say, they exercised no optic action. In the state of solution they did not turn the plane of polarised light. Aspartic acid, on the contrary, had presented to him molecular dissymmetry, like asparagine itself. If the observation of M. Dessaignes were true, then bodies which were inert in regard to polarised light, and consequently non-dissymmetric, could be transformed in the laboratory into active dissymmetric bodies. The line of demarcation so well established would be broken. Pasteur, whose experience regarding the note of Mitscherlich had shown him how even the most conscientious observers may fail to seize upon fugitive appearances, when unprompted to seek them by a preconceived idea, doubted at once the accuracy of the facts cited by M. Dessaignes. From Strasburg he started for Vendôme, where M. Dessaignes at that time resided. M. Dessaignes immediately gave Pasteur a small quantity of the aspartic acid which he had prepared by means of fumaric and malic acids. Returning to his laboratory, Pasteur immediately recognised that, despite the very close resemblance of the new acid of M. Dessaignes to that derived from asparagine, the former differed from the latter by the complete absence in its case of molecular dissymmetry.
With regard to other facts of the same kind, announced not only in France, but in Italy, and in England--chiefly the pretended formation of grape tartaric acid from succinic acid, artificial and inert, by Perkin and Duppa--Pasteur testified with absolute certainty of judgment to the existence of phenomenal peculiarities proper to these substances, which he had never seen, and which had, on the other hand, been the object of careful study by observers of great talent.
After these verifications and deductions from theoretic views, Pasteur discovered a surprising connection between the prior researches of chemistry and crystallographic physics and the new and entirely unexpected results of physiological chemistry. This connection, like the thread of Ariadne, conducted him to his recent great discoveries in medical biology. M. Chevreul was right when, some years ago, at the Academy of Sciences, he expressed himself thus:--
'It is by first examining in their chronological order the researches of M. Pasteur, and then considering them as a whole, that we are enabled to appreciate the rigour of judgment of that learned man in forming his conclusions, and the perspicacity of a mind which, strong in the truths which it has already discovered, is carried forward to the establishment of new ones.'
III.
Pasteur had thus established that bodies endowed with internal dissymmetry carried this property, in varying degrees, into their compounds or their derivatives. When two of these bodies whose nature has been revealed by the discovery of right-handed and left-handed tartaric acid, where all is chemically identical--and which are only to be distinguished from each other by their inverse crystallographic form, and by their action on polarised light--enter into combination with a substance which is optically and crystallographically inert, the chemical identity ought, under these new conditions, to be preserved. Everything remains optically and crystallographically comparable. The inert element adds nothing to, and takes away nothing from, the dissymmetric faculties of the active one.
To these curious studies Pasteur soon added a new chapter. He reasoned thus:--If into these compounds I introduce a substance possessing in itself the specific properties of dissymmetry, it is evident that this substance, while entering into these combinations, must preserve its own properties. The active substance would, from the moment of its combination, add something to the properties of the molecular group which acts like itself, and subtract something from the properties of the group which acts in the opposite manner. The resultant effect of these actions, sometimes concordant, sometimes antagonistic, would cease to be alike in absolute quantity. And if this be the necessary condition of similitude as to molecular arrangement, this similitude would cease to exist, and with its disappearance would appear all the differences of chemical and physical properties which constitute its outward manifestations.
The facts were found to harmonise with these logical deductions. After having made dissymmetry intervene as a modifier of chemical affinity, he had a strange and manifest proof of the influence of dissymmetry in the phenomena of life.
It had been long known, through the observations of a manufacturer of chemical products in Germany, that the impure tartrate of lime of commerce, if contaminated with organic matters and permitted to remain under water in summer, would ferment and yield various products. Pasteur caused the ordinary right-handed tartrate of ammonia to ferment in the following manner:--He took some very pure crystalline salt and dissolved it, adding at the same time to the liquid some albuminoid matter, about one gramme to 100 grammes of the tartrate. The liquid placed in a warm chamber fermented. During the process of fermentation the liquid mass, previously limpid, became gradually turbid, in consequence of the appearance of a small organism which played the part of ferment. Pasteur applied this mode of fermentation to the paratartrate of ammonia. He saw that this salt also fermented, depositing the same organism. All appeared as if the course of things was the same as in the case of the right-handed tartrate. But Pasteur, having had the idea of following the course of the operation with the aid of the polariscope, soon detected a profound difference between the two fermentations. In the case of the paratartrate, the liquid, at first inert, gradually assumed a sensible power of deviation to the left, which augmented by degrees and attained a maximum. The fermentation was then suspended; there was no longer any of the right-handed acid in the liquid, which, when evaporated and mixed with its own volume of alcohol, immediately furnished a beautiful crystallisation of left-handed tartrate of ammonia.
From that moment a great new fact was established--namely, that the molecular dissymmetry proper to organic matters intervened in a phenomenon of the physiological order, and did so as a modifier of chemical affinity. The kind of dissymmetry proper to the molecular arrangement of the left-handed tartaric acid was, no doubt, the sole cause of the difference between this acid and the right-handed acid, in regard to the fermentation produced by a microscopic fungus. We shall see later on that organised ferments are almost always microscopic vegetables, which embrace in their constitution cellulose, albumen, &c., identical with these same substances taken from the higher class of vegetables and equally dissymmetric. We can thus understand, that for the nutrition of the ferment and the formation of its principles the chemical changes are more easy with one of the two tartaric acids than with the other.
The opposition of the properties of the two tartaric acids, right and left, at the moment when the conditions of life and nutrition of an organised being intervened, showed themselves still more strikingly in a very curious experiment made by Pasteur. He was the first to prove that mildew could live and multiply on a purely mineral soil, composed, for example, of the phosphates of potash, of magnesia, and an ammoniacal salt of an organic acid. For such a development of vegetable life he employed the seed of penicillium glaucum, which is to be found everywhere as common mould, and to which he offered, as its only carbon aliment, paratartaric acid. At the end of a little time the left-handed tartaric acid appeared. Now this left-handed acid could only show itself on the condition that a rigorously equal quantity of the right-handed acid had been decomposed. The carbon of the tartaric acid evidently supplied to the little plant the carbon that was necessary for the formation of its constituents and all their organic accessories. If the microscopic seed of penicillium sown upon this soil was not formed of dissymmetric elements, as is the case with all other vegetable substances, its development, its life, its fructification would accommodate themselves equally well with the left-handed tartaric acid as with the right. The fact that the left-handed tartaric acid is less assimilable than its opposite is due solely and evidently to the dissymmetry of one or other of the primordial substances of the little plant.
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Thus for the first time was introduced into physiological studies and considerations the fact of the influence of the molecular dissymmetry of natural organic products.
Pasteur always speaks with enthusiasm of the grand future reserved for researches which have this influence for their object; for molecular dissymmetry is the only sharp line of demarcation which exists between the chemistry of inorganic and that of organic nature.
FOOTNOTE:
FERMENTATION.
Arrived at this unexpected turn in the road which he had hitherto pursued, Pasteur paused for an instant. Should he commit himself to the course which abruptly opened before him? His scientific instincts urged him to do so, but the prudence and reserve which show themselves to be the basis of his character, whenever he finds himself called upon to make a choice of which the necessity is not absolutely demonstrated, held him back. Was it not wiser to continue in the domain of molecular physics and chemistry? M. Biot counselled his doing so; the route had been made plain, success awaited him at each step, but an incident connected with the University triumphed over his hesitations.
He had just been nominated, at thirty-two years of age, Dean of the Faculté des Sciences at Lille. One of the principal industries of the Département du Nord is the fabrication of alcohol from beetroot and from corn. Pasteur resolved to devote a portion of his lectures to the study of fermentation. He felt that if he could make himself directly useful to his hearers he would thereby excite general sympathy with, and direct attention to the new Faculté. The young man congratulated himself on this idea, and the man of science rejoiced in it still more. He was filled by the reflections suggested to him by the strangeness of the phenomena which he had just encountered in regard to the molecular dissymmetry of the two tartaric acids, in connection with the life of a microscopic organism. He saw new light thrown upon the obscure problem of fermentation. The part so active performed by an infinitely small organism could not, he thought, be an isolated fact. Behind this phenomenon must lie some great general law.
All that has lived must die, and all that is dead must be disintegrated, dissolved or gasified; the elements which are the substratum of life must enter into new cycles of life. If things were otherwise, the matter of organised beings would encumber the surface of the earth, and the law of the perpetuity of life would be compromised by the gradual exhaustion of its materials. One grand phenomenon presides over this vast work, the phenomenon of fermentation. But this is only a word, and it suggests to the mind simply the internal movements which all organised matter manifests spontaneously after death, without the intervention of the hand of man. What is, then, the cause of the processes of fermentation, of putrefaction, and of slow combustion? How is the disappearance of the dead body or of the fallen plant to be accounted for? What is the explanation of the foaming of the must in the vintage cask? of dough, which, abandoned to itself, rises and becomes sour? of milk, which curdles? of blood, which putrefies? of the heap of straw, which becomes manure? of dead leaves and plants embedded in the earth, which transform themselves into soil?
Many different attempts were made to account for this mystery before science was in a condition to approach it. In our age, and at the time when Pasteur was led to the study of the question, one theory held almost undisputed sway. It was a very ancient theory, to which Liebig, in reviving it, had given the weight of his name. 'The ferments,' said Liebig, 'are all nitrogenous substances--albumen, fibrine, caseine; or the liquids which embrace them, milk, blood, urine--in a state of alteration which they undergo in contact with the air.'
The oxygen of the air was, according to this system, the first cause of the molecular breaking up of the nitrogenous substances. The molecular motions are gradually communicated from particle to particle in the interior of the fermentable matter, which is thus resolved into new products.
These theoretic ideas regarding the part played in fermentation by the oxygen of the air were based upon experiments made in the beginning of the century by Gay-Lussac. In examining the process of Appert for the preservation of animal and vegetable substances--a process which consisted in inclosing these substances in hermetically sealed vessels and heating them afterwards to a sufficiently high temperature--Gay-Lussac had seen, for example, the must of the grape, which had been preserved without alteration during a whole year, caused to enter into a state of fermentation by the simple fact of its transference to another vessel--that is to say, by having been brought for an instant into contact with the oxygen of the air. The oxygen of the air appeared, then, to be the primum movens of fermentation.
The illustrious chemists Berzelius and Mitscherlich explained the phenomena of fermentation otherwise. They placed these phenomena in the obscure class known as phenomena of contact. The ferment, in their view, took nothing from, and added nothing to, the fermentable matter. It was an albuminoid substance, endowed with a force to which the name catalytic was given. The ferment in fact acted by its mere presence.
A very curious observation, however, had been made in France by Cagniard-Latour and in Germany by Schwann. Cagniard-Latour, however, was the first to publish this observation, which was destined to become so fruitful. One of the ferments most in use, and known as early as the leavening of dough or the turning of milk, is the deposit formed in beer barrels, which is commonly called yeast. Repeating an observation of the naturalist Leuwenhoeck, Cagniard-Latour saw this yeast, which was composed of cells, multiplying itself by budding, and he proposed to himself the question whether the fermentation of sugar was not connected with this act of cellular vegetation. But as in other fermentations the existence of an organism had not been observed even by the most careful search, the hypothesis of Cagniard-Latour of a possible relation between the organisation of the ferment and the property of being a ferment was abandoned, though not without regret by some physiologists. M. Dumas, for example, recognised that in the budding of the yeast globules there must be some clue to the phenomenon of fermentation. I, however, repeat that as nothing of the kind had been found elsewhere, and as all other fermentations presented the common character of requiring, to put them in train, organic matter in a state of decomposition, the hypothesis of Cagniard-Latour remained a simple incident, instead of having the value of a scientific principle.
Liebig, moreover, carrying general opinion along with him, contended that it is not because of its being organised that yeast is active, but because of its being in contact with air. It is the dead portion of the yeast--that which has lived and is in the course of alteration--which acts upon the sugar.
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