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 {114} 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. {115}
The first experiment in physiogeny was the discovery of osmosis by the Abbe
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 {116} 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. {117}
"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 {118} 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 Fluessigkeitschichten": "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 {119} 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. Boettger 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; Boettger 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 {120} 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.
Buetschli 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, Buetschli, 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 Buetschli, show that sphero-crystals
are produced by the reaction of chloride of calcium on carbonate of
potassium without the presence of gelatine or albumen. Buetschli studied
the spheroids of carbonate of lime by means of polarized light, and found
that the layers were alternately positively and negatively polarized."
{121}
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 Schroen, who considers that crystals like living beings begin
as a cell and grow by a process of intussusception. Professor Benedikt has
made a complete resume 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 Felix of Brussels, one of the most enthusiastic disciples of the new
science. There is a resume of Herrera's work in the _Memoirs of the Societe
Alzate, Mexico_.
A bibliography of the works which have appeared on this subject may be
found in the book of Professor Rhumbler of Goettingen, _Aus dem
Lueckengebiete 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 {122} an
interesting study of this question under the title _Etudes experimentales
sur la generation 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 _Fluessige
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'experiences 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, _Stephane Leduc a-t-il cree 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 resume of my researches on osmotic growth has already
appeared in the _Documents du Progres_, 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.
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