# Popular Science Monthly/Volume 42/November 1892/The Synthesis of Living Beings

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* THE SYNTHESIS OF LIVING BEINGS.
By M. ARMAND SABATIER.
IF it is true that crude or dead matter and living matter are not separated by any impassable gulf, it seems reasonable to think that the resources of our laboratories, of which the power is increasing every day, will be able at some time to prove themselves capable of producing living matter from mineral. I purpose to discuss the legitimacy of this hope, taking into the account the results that have been already obtained, and appreciating the value of the objections that are opposed to it. It has long been supposed that the very complex substances that are the basis of living beings (plants and animals) could not be reproduced in laboratories by the simple combination of the forces which the chemist employs, and which reside in dead matter. "Vital force only," Gerhardt has said, "operates by synthesis and reconstructs the edifice that has been beaten down by chemical forces"; and Pasteur says, "We have not yet realized the production of a dissymmetrical body by the aid of compounds that are not so." These words of two illustrious chemists have met in modern labors a denial which is becoming every day more emphatic. Chemistry has entered upon the road of the synthesis of organic compounds, and has recently made a remarkable step, and has gone beyond a point which had been considered impassable.
Wöhler made the first synthesis in 1828, and obtained urea through the reaction of ammonia on cyanic acid. By taking simple bodies as the point of departure, we have been able to reproduce the carburets of hydrogen and formic acid; from the carburets we have gone up to the alcohols and to all their derivatives. Berthelot produced alcohol by bringing together the gaseous body ethylene and sulphuric acid. The product of this reaction, decomposed by water, furnished alcohol. Wurtz obtained the synthesis of alcohol in another way. He subjected aldehyde to the action of nascent hydrogen, and alcohol was produced by the direct fixation of the hydrogen. As my colleague, M. Oeschner de Coninck, has remarked to me, this synthesis is of particular interest from the biological point of view, with which I am especially occupied; for everything tends to prove that this is the way alcohol is produced in plants. We are then in the presence of a case where the forces of the laboratory follow, for a given end, the same course as the forces of living Nature.
A considerable number of alkaloids of vegetable origin have been obtained directly by synthesis. M. Oeschner de Coninck, ​applying a special process of hydrogenization to the alkaloids of the peridic series, has pointed out a process of synthesis of the volatile vegetable alkaloids. He has obtained an alkaloid presenting the same composition as cicutine, differing from it only in a few physical and chemical properties, but possessing the same toxic action as the alkaloid of the hemlock.
These results, and others, were of a nature to cause hopes to rise; but still the synthesis of the sugars, and of the proteic substances which are the essential basis of protoplasm, seemed to defy the efforts of chemists.
To give an idea of the manner in which these results were regarded only yesterday by the partisans of the special, irreducible character of life, I quote a few lines from a book recently published (1886) by M. Denys Cochin, under the title Evolution et la Vie. After having recognized that modern chemistry entered with Wöhler and Berthelot into the way of synthesis; that it had made the synthesis of urea, formic acid, and ethylic alcohol; that these results had been for a long time regarded as contradictions of the laws of mineral matter and as impossibilities; and that, consequently, science has imitated some of the works of Nature, M. Denys Cochin adds (page 208): "These are arguments of which it would be wrong to exaggerate the weight. It is enough, to show this, to recall roughly the facts on which the discussion bears. Organic matter, vegetable or animal, is formed of very complex substances. The most complex, those which we may regard as the superior products of the synthesis performed by life, are the sugars and the albumens. These superior products are subjected during life to a slow combustion, which is fed by every effort and every expenditure of energy. The complex albumens are split and transformed into simpler albumens; the simplest of all is urea, a product of secretion, the waste of vital combustion; and urea itself splits into water and carbonate of ammonia. Organic matter thus returns to the mineral world. The sugars undergo a series of similar combustions and end by giving carbonic acid and water. . . . Now, the products of which chemistry performs the synthesis are always products of combustion, wastes of living matter, like alcohol, urea, and formic acid. They are never albumens of complex formula, not even sugars, the most perfect products of vital synthesis.
"Is there a line between superior and inferior organic products? Is there a characteristic that permits us to separate between them? Superior organic products are endowed with a curious power. Dissolved in water and traversed by a ray of polarized light, they cause the plane of polarization to turn at a certain angle to the right or the left. There is an unforeseen relation between this power of dissolved bodies and their crystalline ​form. There exist right crystals and left crystals similar to one another as the right hand is to the left, but which can not be laid over one another; the direction of the deviation of polarized light corresponds with the direction of the crystalline form. It must be supposed that, after the solution of a right or left body, its separated molecules are still dissymmetrical. Of like character are the separate steps of a winding stairway; their form tells whether the stairs turned to the right or the left. Now, all superior organic bodies—the albumens, the sugars, dextrin, and cellulose—are what we call active bodies, endowed with the power of turning the plane of polarized light to the right or the left; and never by any artifice of the laboratory has it been possible to prepare directly a right body or a left body. In spite of the synthesis of alcohol urea, and formic acid, we still have a right to say organic matter is not fabricated outside of the living being. The work of life can not be counterfeited. We can not artificially provoke the formation of a cell; we can no more reproduce the materials of which it is made. The substances we have been able to reproduce are only the waste of life returning toward inert matter, and already nearly mineral."
The analysis of these few pages can be summarized by saying that the synthesis of all the products of life, without exception, was long regarded as a contradiction to the laws of mineral matter and as an impossibility. Yet chemistry has performed the synthesis of some products of life—urea, formic acid, ethylic alcohol, etc. But the authors of the challenge do not acknowledge themselves beaten; they have simply drawn back and circumscribed the field of their defeat. "Yes," they say, "we acknowledge that chemistry has been able to perform the synthesis of some products of life; but they are inferior products, refuse. It has still been never able to prepare directly the superior products like albumen and the sugars. We can not counterfeit the work of life."
The reader has been able to view and measure the motion of retreat. We can, with a little kindliness, regard it as having been performed in good order. But we can also, with entire impartiality, see in it the first steps of a backward march which will end in a rout. We can indeed say that the rout has already begun. In fact, the reputed impassable has just been partly passed, and syntheses characterized as impossible have been in large part realized.
The synthesis of the most important of the series of sugars is now an accomplished fact. The researches which have permitted the realization of this immense advance in organic chemistry, and which are the work of M. Fischer and his pupils, have led to a discovery of great importance. In the series of sugars we met ​an optical isomery identical with that of malic and tartaric acids. Sometimes the sugars present a right isomery, a left isomery, and an isomery inactive "by compensation, and a splitting into two sugars, one right and the other left. This is exactly what we have witnessed in right and left tartaric acids, the union of which constitutes paratartaric acid, inactive by compensation. It is not useless to insist upon this resemblance, and to remark that the reactions which have permitted us to effect the synthesis of the principal sugars are of a purely chemical character, and that they demonstrate that the chemist can reproduce substances endowed with the rotatory power and aside from all intervention of life. The sugars, reproduced by synthesis, remain proteic or albuminoid substances. Here, again, the prophets of vital force are found wanting.
M. Grimeux in 1885 had prepared synthetically, by the action of oxychloride of phosphorus upon a mixture of leucine and tyrosine, and further treatment with NH$_3$ (ammonia), an amorphous, colloid substance, offering some of the characteristic reactions of albumen: precipitation on ebullition, the xanthoproteic reaction, the reaction of Millon, and the biuret reaction (soda and sulphate of copper). But M. Schutzenberger has just made a considerable step in the synthesis of those substances. A note in the Comptes rendas of the Institute of January 26, 1891, exposes the results of a successful experiment in the synthesis of a proteic substance presenting all the physical and chemical characteristics of the peptones.
An extended series of researches on the products resulting from the decomposition by hydration of proteic substances, albuminoid or other, under the influence of alkalies (baryta), have led M. Schutzenberger to attempt the synthesis of a proteic substance, starting from the simple terms of its decomposition by hydration. After numerous fruitless attempts he succeeded in forming a nitrogenous compound, which by its characteristics should be placed in the class of proteic substances, by combining, with the elimination of water, the ultimate and crystallizable products arising from the decomposition of albumen and fibrin under the influence of baryta. After a series of operations, of which I do not recite the detail, Schutzenberger obtained an amorphous product, soluble in water, precipitable by alcohol into white, cheesy lumps. The body thus obtained exhibited great characteristic similarities with the peptones. Its physical characteristics, its chemical reactions, and its modifications under the influence of heat, were faithfully like those of proteic substances. A great advance has therefore been made toward synthesis of organic substances, and the future promises still more complete results.
The chemist has then been able to realize the construction of ​most of the complex compounds which appear exclusively reserved for the living organism. These compounds are not merely products of splitting or oxidation, wastes of life, but are also compounds like those which constitute the superior products of life. We should recognize that these products, that this albumen obtained by synthesis, while having the same elementary composition as living albumen and the same physical and chemical characteristics, is nevertheless distinguished from it by a very important point: it does not exhibit the characteristic phenomena of life. It is not capable of performing the part of a leaven, and has not the instability of living albumen. We have for the moment established only one thing: that the chemist is capable of creating, by direct synthesis, the most characteristic compounds and the highest products of life.
Will chemistry ever be able to produce living albumen capable of actively performing the part of a leaven, and endowed with sufficient instability to go through all the modifications that permit the combustions, splittings, and demolitions that lead to disassimilation and excretion? It seems to me that we are permitted to hope for it. But within what limits will this power of the chemist be included? Will he ever be able to make a living being? Will he succeed in making even a simple cell, a grain of starch, a muscular fiber, or any shapely and differentiated element? In order to answer these questions, we must dissipate some confusion and present all the elements of the problem.
To ask the chemist to make directly a differentiated being, or even a muscular fiber, a nervous cell, a grain of starch, is to ask him to do what Nature herself has probably never been able to do, and what it is probably impossible to realize. Can one in good faith exact so much? Is it not enough to ask the chemist to be as powerful as Nature? The question is then reduced to—Will the chemist be able to do what Nature has done? Let us see what Nature has done, looking from the evolutionist's point of view.
If the living form of matter was ever born by virtue of the action of natural forces, the event must have taken place in a medium the conditions of which differed from the existing conditions of our globe; for such formation of natural matter does not seem to be realized among us. Under these special conditions of the medium, living matter must have appeared in the most simple, the most rudimentary condition, for beginnings are always humble and little differentiated. We can conceive nothing of this kind more simple than droplets, more or less minute, of a substance comparable with albumen or protoplasm—that is, a substance fermentable and unstable in sufficient degrees for a current of vital exchanges to be established within it. The droplets ​lived, increased in volume, and multiplied by division, because the vital exchanges could, not be efficacious and properly regulated except on condition that the mass bore a well-determined proportion to the surface. If the mass became too great, the surface would become insufficient, the mass increasing in proportion to the cube of the radius, and the surface in proportion only to the square of the same radius.
The little protoplasmic masses created under special conditions of the medium would continue in that medium as long as it remained the same. But this medium becomes modified, because it ceases to be what it was—a fact clearly established by geology and paleontology—and we may presume that the modifications were made slowly and progressively. The little protoplasmic masses would also modify themselves and adapt themselves to the conditions created around them. The medium being changed, the living being would be changed too; but, the medium changed, the conditions that had permitted the direct formation of living matter, spontaneous or heterogeneous variation, would also have vanished. The new medium would then be such that the little living masses already created would continue to live, adapting themselves to it, but that new living masses could not be directly formed in it.
The first little masses born on the whole surface of the globe, unless the conditions were much more uniform than they are now, became the starting-point of successive generations, which, obeying the law of progress that presides over evolution and subjected to the conditions of the medium, acquired successively differentiations, very slow, but progressive, which determined in the homogeneous mass the appearance of granulations, localizations, limited condensations, partitionings, networks, etc., that made of the homogeneous droplet a more or less complicated organism. Such were the very slow advances, not becoming perceptible till after very long periods and through millions of successive generations. The nucleus of the cell, the muscular fiber, the nervous cell, the grain of starch, the fatty globule, the secretory cell, etc., were not formed by Nature at the first stroke. They are probably the result of work performed during millions of years and through milliards of generations. These milliards of generations of living droplets or living cells have therefore been as many little laboratories, in each of which has been elaborated, perfected, and differentiated the muscular fiber or grain of starch. Each of these little laboratories has brought to this work some share of activity, and each has added something to the differentiation.
Some, for example, have begun by producing more specially contractile particles in the homogeneous protoplasm; others have ​accumulated these particles in particular regions. This concentration is effected very slowly, very progressively. In other ulterior droplets, these regions have progressively delimited themselves; later on, the motions of contraction have gradually oriented themselves to one direction rather than another; still later, this habitual direction of alternate contractions and elongations has determined the formation of the contractile substance into fibrillæ arranged in the same direction, and has achieved the formation of muscular fibers; and so on.
Nature, therefore, has not accomplished the formation of differentiated elements at the first stroke. It has created living matter, simple and homogeneous; and this has been called, through a considerable series of ages and generations, to elaborate the differentiated elements with which we are acquainted. More than Nature can do must not be demanded of the chemist. Those who ask him to create directly the cell and muscular fiber infinitely exceed the absurdity of the persons who would tell the miner, whose business is limited to extracting the mineral, to make an iron-clad vessel with his ordinary tools and methods. He could supply the mineral, but a metallurgist would be needed, with furnaces, retorts, and reagents, to extract the crude metal from it. After him would have to come, to conceive and draw the plans, the founder, men to manipulate the rollers and the hammers, the turners, the polishers, the fitters, and the builders proper, all of whom would contribute in succession and through a long series of days to the preparation, the perfection, and the starting of the various parts of the great vessel; and all this under the eye and direction of the engineer who has conceived the plan and ordered the execution of the work, and provided the means of carrying it into effect.
In like manner an innumerable series of minute workers and minute laboratories have contributed, in conformity with the plan of the Creator, to the differentiation of muscular fiber, of the starch-grain, and of the nervous cell.
What can be expected of the chemist is thus well defined and outlined: it is to create simple living matter—albumen or protoplasm—as Nature has created it. We are authorized to believe that he can do this by the progress that has been recently and rapidly made in organic syntheses.
We have remarked, it is true, that, although the synthesis of albumen has been effected, living albumen, active like that of protoplasm, endowed with a strong leavening power and an instability adapted to vital changes, has not been produced. It is not impossible, as Pfluger believes, that non-living and active albumen are isomers—that is, bodies having the same elementary composition, and differing only in the arrangement of the atoms in the molecule.
​Chemistry has already given proof that it is competent to produce isomeric changes in a considerable number of bodies (as we have seen for hyposulphite of soda); and nothing permits us to certify that, after having produced non-living albumen, it will not ultimately find means to determine in it the isomeric change which will make living albumen of it. It is proper to remark, besides, that life itself produces two isomeric states of albumen: one, the active state in protoplasm; and the other, the passive or inert state in the albumen of the egg, in birds. The latter, which is destined to feed the embryo, may be preserved intact for years, and show itself indifferent to oxygen, which can neither oxidize it nor contribute to its breaking up. It should be remarked, besides, that this albumen, deprived of the leavening power, is a product of secretion of the cells of the oviduct—a fact which comes to the support of the thoughts I have expressed above on the mechanism of excretion.
To create simple living matter the chemist may follow different ways. He may exactly reproduce the conditions of the medium which have favored the appearance of living matter; or, he may find new conditions that will lead to the same result, by producing, for example, the isomeric change of which we have just spoken. The same synthesis may, in fact, be produced in different ways, as has been seen in the case of alcohol. "Will the chemist ever realize either of these conditions? Who can say peremptorily, No? The creation of living matter by chemistry is not, therefore, a priori absolutely impossible.
But, supposing these conditions realized, will the chemist be able to give rise to parcels of living matter which, like the first created at the origin of life on the globe, can become the starting-point for successive generations and for a new evolution in the present conditions of Nature? It seems to me that the answer to this question must be negative—for the reason that the first created parcels lived and were propagated through a long series of ages, among the same conditions as prevailed at their birth; they have since subsisted, notwithstanding the modifications of the medium, because those modifications, slow and taking long spaces of time, have permitted living matter to modify itself slowly and adapt itself to the new conditions. The question, then, amounts to asking, Will the chemist who shall realize, during a sufficient time and within a limited space, the conditions that formerly presided over the formation of living matter, be able to maintain them during sufficient time or to modify them slowly enough for living matter to have to adapt itself and enter into useful and conservative relations with actual Nature? If we consider the time Nature has required to reach this result of adaptation, we may logically conclude that such experiences are utterly outside of the ​conditions permitted to human experience. If, then, man shall some day create living matter, he will be able to observe it during a longer or shorter time; he will be able to study it; but it will be an embryo, the development of which can not be completed, on account of the absence of suitable conditions of the medium.—Translated for The Popular Science Monthly from the Revue Scientifique.