CHAPTER X
SYNTHETIC BIOLOGY
The course of development of every branch of natural science has been the same. It begins by the observation and classification of the objects and phenomena of nature. The next step is to decompose the more complex phenomena in order to determine the physical mechanism underlying them—the science has become analytical. Finally, when the mechanism of a phenomenon is understood, it becomes possible to reproduce it, to repeat it by directing the physical forces which are its cause—the science has now become synthetical.
Modern biology admits that the phenomena of life are physico-chemical in their nature. Although we have not as yet been able to define the exact nature of the physical and chemical processes which underlie all vital phenomena, yet every further discovery confirms our belief that the physical laws of life are identical with those of the mineral world, and modern research tends more and more to prove that life is produced by the same forces and is subject to the same laws that regulate inanimate matter.
The evolution of biology has been the same as that of the other sciences; it has been successively descriptive, analytical, and synthetic. Just as synthetic chemistry began with the artificial formation of the simplest organic products, so biological synthesis must content itself at first with the fabrication of forms resembling those of the lowest organisms. Like other sciences, synthetic biology must proceed from the simpler to the more complex, beginning with the reproduction of the more elementary vital phenomena. Later on we may hope to
unite and associate these, and to observe their development under various external influences.
The synthesis of life, should it ever occur, will not be the sensational discovery which we usually associate with the idea. If we accept the theory of evolution, then the first dawn of the synthesis of life must consist in the production of forms intermediate between the inorganic and the organic world—forms which possess only some of the rudimentary attributes of life, to which other attributes will be slowly added in the course of development by the evolutionary action of the environment.
Long ago, the penetrating genius of Lamarck seized on the idea that a knowledge of life could only be obtained by the comparison of organic with inorganic phenomena. He writes: "If we would acquire a real knowledge of what constitutes life, of what it consists, what are the causes and the laws which give rise to this wonderful phenomenon of nature, and how life can be the source of the multitude of forms presented to us by living organisms, we must before all consider with great attention the differences which exist between inorganic and living bodies; and for this purpose we must compare side by side the essential characters of these two classes of bodies."
Synthetic biology includes morphogeny, physiogeny, and synthetic organic chemistry, which is also a branch of synthetic biology, since it deals with the composition of the constituents of living organisms. Synthetic organic chemistry is already a well-organized science, important by reason of the triumphs which it has already gained. The other two branches of biological synthesis, morphogeny, the synthesis of living forms and structures, and physiogeny, the synthesis of functions, can hardly as yet be said to exist as sciences. They are, however, no less legitimate and no less important than the sister science of synthetic chemistry.
Although morphogeny and physiogeny do not exist as well-organized and recognized sciences, there are already a number of works on the subject by enthusiastic pioneers—independent seekers, who have not feared to abandon the paths of official science to wander in new and hitherto unexplored domains.
The first experiment in physiogeny was the discovery of osmosis by the Abbé Nollet in 1748. He filled a pig's bladder with alcohol, and plunged it into water. He noticed that the bladder gradually increased in volume and became distended, the water penetrating into the interior of the bladder more quickly than the alcohol could escape. This was the first recorded experiment in the physics of nutrition and growth.
In 1866, Moritz Traube of Breslau discovered the osmotic properties of certain chemical precipitates. As I pointed out in the Revue Scientifique of March 1906, Traube made the first artificial cell, and studied the osmotic properties of membranes and their mode of production. This remarkable research should have been the starting-point of synthetic biology. The only result, however, was to give rise to numberless objections, and it soon fell into complete oblivion. "There are," says Traube, "a number of persons quite blind to all progress, who in the presence of a new discovery think only of the objections which may be brought against it." The works of Traube have been collected and published by his son (Gesammelte Abhandlungen von Moritz Traube, 1899).
In 1867 there appeared in England a paper by Dr. E. Montgomery, of St. Thomas's Hospital, On the Formation of so-called Cells in Animal Bodies. This paper, published by Churchill & Sons, is a most interesting contribution and one of great originality. The author says: "There can be no compromise between the tenets of the cell theory and the conclusions arrived at in this paper; the distinction is thorough. Either the units of which an organism is composed owe their origin to some kind or other of procreation, a mysterious act of that mysterious entity life, by which, in addition to their material properties, they become endowed with those peculiar metaphysical powers constituting vitality. Or, on the other hand, the organic units, like the crystalline units of inorganic bodies, form the organism by dint of similar inherent qualities, form in fact a living being possessed of all its inherent properties, as soon as certain chemical compounds are placed under certain physical conditions. If the former opinion be
true, then we must clearly understand that there exists naturally a break in the sequence of evolution, a chasm between the organic and the inorganic world never to be bridged over. If, on the contrary, the latter view be correct, then it strongly argues for a continuity of development, a gradual chemical elaboration, which culminates in those high compounds which, under surrounding influences, manifest those complex changes called vital.
"Surely it is not a matter of indifference or of mere words, if the extreme aim of physiology avowedly be the detection of the different functions dependent on the vital exertions of a variety of ultimate organisms, and the discovery of the specific stimulants which naturally incite these functions into play. Or, on the other hand, if it be understood to consist rather in the careful investigation of the succession of chemical differentiations and their accompanying physical changes, which give rise to the formation of a variety of tissues that are found to possess certain specific properties, to display certain definite actions due to a further flow of chemical and physical modifications."
In 1871 there appeared a memoir by the Dutch savant Harting entitled Recherche de Morphologie synthetique sur la production artificielle de quelques formations calcaires organiques. This memoir, says Professor R. Dubois, had cost Harting more than thirty years of work. "Synthetic morphology is yet only in its infancy, let us hope that in a time equal to that which has already expired since the first artificial production of urea, it will have made a progress equal to that of its older sister, synthetic chemistry."
In the Comptes Rendues of 1882 is the following note by D. Monnier and Karl Vogt:—
"1. Figured forms presenting all the characteristics of organic growth, cells, porous canals, tubes with partition walls, and heterogeneous granules, may be produced artificially in appropriate liquids by the mutual action of two salts which form one or more insoluble salts by double decomposition. One of the component salts should be in solution, while the other salt must be introduced in the solid form.
"2. Such forms of organic elements, cells, tubes, etc., may be produced either in an organic liquid or a semi-organic liquid such as sucrate of lime, or in an absolutely inorganic liquid such as silicate of soda. Thus there can no longer be any question of distinctive forms as characterizing organic bodies in contradistinction to inorganic bodies.
"3. The figured elements of these pseudo-organic forms depend on the nature, the viscosity, and the concentration of the liquids in which they are produced. Certain viscous liquids such as solutions of gum arabic or chloride of zinc do not produce these forms.
"4. The form of these artificial pseudo-organic products is constant, as constant as that of the crystalline forms of mineral salts. This form is so characteristic that it may often serve for the recognition of a minimal proportion of a substance in a mixture. The observation of these forms is a means of analysis as sensitive as that of the spectrum. We may, for example, differentiate in this way the alkaline bicarbonates from the sesqui-carbonates or the carbonates.
"5. The form of these artificial pseudo-organic elements depends principally on the nature of the acid radical of the solid salt. Thus the sulphates and the phosphates generally produce tubes, while the carbonates form cells.
"6. As a rule these pseudo-organic forms are engendered only by substances which are found in the living organism. Thus sucrate of calcium will engender organic forms, whereas sucrate of strontium or barium does not do so. There are, however, some exceptions to this rule, such as the sulphates of copper, cadmium, zinc, and nickel.
"7. These artificial pseudo-organic elements are surrounded by veritable membranes, dializing membranes which allow only liquids to pass through them. These artificial cells have heterogeneous cell-contents, and produce in their interior granulations which are disposed in a regular order. Thus they are both in constitution and in form absolutely similar to the cellular elements which constitute living organisms.
"8. It is probable that the inorganic elements which are present in the natural protoplasm may play an important part
in determining the form which is assumed by the figured elements of the organism."
In 1902, Professor Quinke of Heidelberg, who has consecrated his life with such distinction to the physics of liquids, writes thus of the organogenic power of liquids in a paper published in the Annalen der Physik under the title "Unsichtbare Flüssigkeitschichten": "In 1837, Gustav Rose obtained organic forms by precipitation from inorganic solutions. By precipitating chloride of calcium with the carbonates of ammonium and other alkaline carbonates, he obtained small spheres which grew and were transformed into calcic rhombohedra. He also obtained a flocculent precipitate which later became granular and showed under the microscope forms like the starfish, and discs with undulated borders. At Freiberg, in certain stalactites, Rose also discovered forms consisting of six pyramidal cells around a spherical nucleus.
"In 1839, Link obtained spherical granulations by the precipitation of calcic or plumbic solutions by potash, soda, or carbonic acid. These spherical granulations united after a time to form crystals. Sulphate of iron, ammoniated sulphate of zinc, sulphate of copper precipitated by sulphuretted hydrogen, and saline solutions precipitated by ferrocyanide of potash, all give granular precipitates or discs, of which the granular origin is quite perceptible.
"Runge in 1855 was the first to describe the formation of periodic chemical precipitates. He used blotting paper as the medium in which various chemical substances met by diffusion. In this way he studied the mutual reactions of solutions of ferrocyanide of potash, chloride of iron, and the sulphates of copper, iron, manganese, and zinc. The coloured precipitates appeared at different positions in the paper, and disappeared periodically at greater or longer intervals. The designs formed by these coloured precipitates change with the concentration of the saline solutions, or on the addition of oxalic acid, salts of potash or ammonia, and other substances. These designs are shown in a number of beautiful illustrations which accompany the work. In this
case the capillarity of the paper necessarily exerts a certain influence on the formation of the figures, but in addition to this, Runge admits the intervention of another force hitherto unknown, which he calls 'Bildungstrieb,' the formative impulse, which he considers to be the elementary vital force in the formation of plants and animals.
"In 1867, R. Böttger obtained arborescent forms and ramifications of metallic vegetation by sowing fragments the size of a pea of crystals of the iron chlorides, chloride of cobalt, sulphate of manganese, nitrate and chloride of copper, etc., in an aqueous solution of silicate of sodium of specific gravity 1.18. These forms are due, as I shall show later on, to the surface tension of the oily precipitate; Böttger gives no explanation of the phenomenon.
"To this force, viz. that of surface tension, is also due the cellular forms obtained by Traube in 1866. These were obtained from gelatine and tannin, from acetate of copper or lead, and from nitrate of mercury in an aqueous solution of ferrocyanide of potassium. These cells and precipitated membranes have also been studied by Reinke, F. Cohn, H. de Vries, and myself, who all observed the regression of these membranes, which although colloidal at the beginning of the reaction speedily become friable. This entirely refutes the opinion of Traube as to the constitution of the precipitated membranes. He supposed them to consist of masses of solid substance, with smaller orifices which do not permit the passage of the membranogenous substance, whilst the larger orifices through which it can pass are soon closed by the precipitate, the membrane itself thus growing by a process of intussusception.
"Later on Traube himself considered the precipitated membrane to be a thin, solid gelatinous layer in which the water was mechanically entangled.
"Tamman has also made a number of experiments with solutions of the chlorides and sulphates of the heavy metals, and solutions of phosphates, silicates, ferrocyanides, and other salts. He found that most of these membranes were permeable to the membranogenous solution. According to Tamman, all
precipitated membranes are hydrated substances, and some of them, like the ferrocyanide of copper and the tannate of gelatine are, when first formed, entirely comparable to liquid membranes in all their properties.
"Graham had already obtained colourless jellies by the interaction of concentrated solutions of ferrocyanide of potassium and sulphate of copper. Bütschli also has recently described the microscopic appearance of precipitated membranes produced by ferrocyanide of potassium and acetate or chloride of iron.
"Like Linke and Gustav Rose, Famintzin has obtained spheroidal precipitates by the reciprocal action of concentrated solutions of chloride of calcium and carbonate of potassium. These grow rapidly and suddenly, with concentric layers showing a spherical or flattened nucleus. He also obtained forms resembling sphero-crystals and starch grains.
"Harting, Vogelsang, Hansen, Bütschli, and others have studied the structures which are formed by the reciprocal action of chloride of calcium and the alkaline carbonates. Vogelsang has found small calcareous bodies in the amorphous and globular precipitate formed by chloride of calcium and carbonate of ammonium. He describes spheres attached to one another, vesicles, and muriform structures. The number of these spheroids is increased by the addition of gelatine. Hansen has also studied Harting's method for the formation of sphero-crystals by the action of the alkaline carbonates and phosphates on the salts of calcium in presence of albumen and gelatine. He considers that the latter retard the crystallization and assist the formation of the sphero-crystals.
"I shall show later on that gelatine and albumen essentially modify the precipitate and do not merely act as catalytic substances. The researches of Famintzin, repeated and extended by Bütschli, show that sphero-crystals are produced by the reaction of chloride of calcium on carbonate of potassium without the presence of gelatine or albumen. Bütschli studied the spheroids of carbonate of lime by means of polarized light, and found that the layers were alternately positively and negatively polarized."
Such is the history of morphogenesis as described in 1902 by the authority most qualified for the task, Professor Quinke of Heidelberg.
In 1904, Professor Moritz Benedikt of Vienna treated the whole question in his book, Crystallization and Morphogenesis, of which a French translation appeared in the Maloine Library. This book is full of original and suggestive ideas; it describes the work of Harting, and more especially that of Van Schroën, who considers that crystals like living beings begin as a cell and grow by a process of intussusception. Professor Benedikt has made a complete résumé of the question in an article, "The Origins of the Forms of Life," which appeared in the Revue Scientifique in 1905.
In 1904, Professor Dubois of Lyons presented a report to the Society of Biology on his interesting experiments on mineral cytogenesis. The same year he gave a discourse at the university of Lyons on "The Creation of Living Beings," which has been published by A. Storck of Lyons.
One of the most active of the modern morphogenists is Professor Herrera of Mexico, whose work is illustrated in the Atlas de Plasmogenie by Dr. Jules Félix of Brussels, one of the most enthusiastic disciples of the new science. There is a résumé of Herrera's work in the Memoirs of the Societé Alzate, Mexico.
A bibliography of the works which have appeared on this subject may be found in the book of Professor Rhumbler of Göttingen, Aus dem Lückengebiete zwischen Organischer und Anorganischer Materie, 1906.
In 1907, Dr. Luiz Razetti of Carracas published a magnificent study of the subject under the title Que es la vida.
In 1907, Dr. Martin Kuckuck of St. Petersburg repeated and extended the experiments of R. Dubois, and published his results under the title Archigonia, Generatio Spontanea, Leipzig, Ambrosius Barth.
Butler Burke of Cambridge has also made a series of experiments with radium and barium salts analogous to those of Dubois.
In 1909, Albert and Alexandre Mary of Beauvais published
an interesting study of this question under the title Études expérimentales sur la génération primitive, published by Jules Rousset.
I should mention also among the works of synthetic biology the publications of Professor Otto Lehmann of Karlsruhe, and in particular Flüssige Krystalle und die Theorien des Lebens, Leipzig, Ambrosius Barth.
Professor Ulenhuth of Berlin has published his study on the osmotic growth of iron in alkaline hypochlorites under the title Untersuchungen ueber Antiformin, Berlin, Julius Springer.
Professor Gariel has made a series of researches on osmotic growth which are published in Abraham's Recueil d'expériences de physique.
A. Lecha Marzo of Valladolid published his researches on the growth of aniline colours in the Gaceta Medica Catalana, 1909, under the title Otra nueva flora artificiale.
Dr. Maurice d'Halluin of Lille has also published a volume on osmotic growths under the title, Stéphane Leduc a-t-il créé la vie?
The subjects of the numerous memoirs that I have myself published during the last ten years upon the question are treated anew in the pages of this volume, and a résumé of my researches on osmotic growth has already appeared in the Documents du Progrès, Sept. 1909.
We have thus shown that synthetic morphogenesis has already attracted the attention of a certain number of ardent investigators. Morphogeny has now its methods and its results, and physiogeny is also developing side by side with it, since function is but the result of form. The field of research is opened, and workers alone are needed in order to reap an abundant harvest.