Organic / Inorganic
Synthetic chemistry preceded synthetic biology. It was already an attempt, by freeing itself from vitalism, to return biological chemistry to the world of physics and chemistry. Synthetic biology, today, attempts the same venture. In both cases, however, there remains a "remainder" which is generally not well formalized, and which I did not know how to formalize at the time of writing this short encyclopedia entry (1986). We know today that this remainder is an authentic category of reality, information. Each natural entity thus proceeds from five categories, mass, energy, space, time, and information, which must be articulated together in a rational way. This is the object of the new reflections that are being developed today around the theories of information and their applications in synthetic biology. This reflection goes on during the weekly seminar Stanislas Noria. It prompted the i2Cell conference in february 2018.
Let us start with an older point of view, which highlights the overlap between the world of Arts and that of Sciences:
Before Berthelot, the only goal of chemistry
was to break down things into their simple elements. He was the
first to succeed, by bringing these simple elements together, in
reconstituting things in their normal, natural state. He proved at
the same time the unity of matter, the identity of composition in
the animate, organic things and in the inanimate, inorganic things.
The old scholastic entities by which one thought to account for life
were disappearing. Opium makes one sleep, said Molière's doctors,
because it has a dormitive virtue; organized beings live, said the
ancient chemists, because their elements are kept together by the
vital force. This was to explain a fact by the very word which
qualifies this fact; it was to speak for nothing. Phenomena occur in
living beings which were considered to be very mysterious. The
tissues give rise to products, to very particular things, which were
not found anywhere in inorganic nature and which could not be
produced artificially. It seemed therefore that nature had to remain
indefinitely divided into two kinds of matter: inorganic matter and
organic matter. Undoubtedly, many inorganic elements entered into
the composition of living things; but living things contained or
produced a certain number of elements which seemed to be absolutely
particular to them. The state of affairs was at that point when,
about 1825, Woehler accidentally discovered the synthesis of urea.
Urea is an important material; it is the principal form in which
excess nitrogen is eliminated from the human body. It is contained
in the urine at the rate of twenty-four grams per liter. In 1773,
Rouelle isolated it by treating fresh urine, a process still in use
today. It was not imagined that urea could ever be found in any
other way when Woehler told of his accident. He had found urea, but
he was not looking for it. He was looking for a salt, ammonium
isocyanate, and he found it. But he was astonished to find that this
salt spontaneously transformed itself into urea, which had the same
chemical composition! Synthetic chemistry had just been born, by
chance; we had just found an inorganic thing perfectly identical to
an organic thing, reputedly resistant to any synthesis .
The synthetic method in chemistry is of considerable importance. It is the only one, in fact, which allows one to give an exact account of the composition of things. Analysis is the operation, but synthesis is the proof. We have even managed to synthesize things whose exact composition was unknown. The system could then be characterized as follows, if the two words could be combined: a series of methodical trial and error. One descends into the mystery by the ladder of analysis, and one ascends again by the ladder of synthesis. From a practical point of view, chemical synthesis has allowed the artificial manufacture of plant or animal products, whose extraction was long, difficult and costly.
The opposition between organic and inorganic things is nothing other than the imposition, on common matter, of vitalism. At the end of the eighteenth century, organic things were opposed to their inorganic counterparts only to distinguish inert matter from the matter that, if not living, was at least marked by life: food, excrement and constituents of living matter. This opposition (cultural!) is seldom used today: it is replaced by a similar biological (usually termed 'organic')/inorganic and sometimes psychic/inorganic opposition. The dualism has survived and it is not uncommon to hear people talk about 'living' (or 'organic') products compared to 'dead' (or inorganic) products. We even see some of our contemporaries - probably gifted with a limited cultural scope - saying that butter is alive whereas margarine is not *, just as vanillin extracted from the vanilla bean is opposed to synthetic vanillin.
In fact, it is not necessary to be a dualist to postulate a particular force in the organic world:
"Nature never complicates her means without necessity: if she has
been able to produce all the phenomena of organization, by means of
the laws and forces to which all things are generally subject, she
has done so without doubt, and has not created, to govern one part
of her productions, laws and forces opposed to those she employs to
govern the other part.
It is sufficient to know that the cause which produces the vital force in things where the organization and the state of the parts permit this force to exist and to excite the organic functions, cannot give rise to a similar power in crude or inorganic things, in which the state of the parts cannot permit the acts and effects which we observe in living things."
J.B. de Lamarck, better known as the creator of a theory of the evolution of species, thus poses in 1809 the theme of the difference between organic matter and inorganic matter. Let us note that this way of distinguishing between the two states of matter does not require the existence of a dualism (matter/spirit or matter/life). Lamarck's thought is therefore, despite its animating attitude (the vital force...) quite revolutionary since it allows us to do without a particular principle characteristic of organic matter and thus of life. It is however an isolated attempt, closed on an inadequate finalism, and which has remained without a future. To get rid of dualism, to return to the presocratic way of thinking, supposes that we can find a replacement to this convenient and irrefutable vision (which, of course, does not mean true!: the sentence : "There is a formula in Hebrew that cures all diseases" is irrefutable...) by an adequate representation of the world, from that of inert matter to that of living matter.
Characteristics of inorganic things compared with those of living things
"1. Any raw or inorganic thing has individuality only in its
integral molecule [...]. On the contrary, any living thing has
individuality in its mass and volume [...];
"2. An inorganic thing can have a truly homogeneous mass, and it can also constitute some which are heterogeneous [...]. All the living things, on the contrary, even those which are simplest in organization, are necessarily heterogeneous [...]; "
3. An inorganic thing can constitute either a perfectly dry solid mass, or a liquid mass, or a gaseous fluid. The opposite is true of any living thing [...]. The masses that constitute inorganic things have no form that is particular to the species [...]. Living things, on the other hand, all have, more or less, in their mass, a form that is particular to the species [...].; "
4. The integral molecules of an inorganic thing are all independent of each other [...]. On the contrary, the component molecules of a living thing [...] are [...] dependent on one another because they are all subject to the influences of a cause which animates them and makes them act; because this cause makes them all work together towards a common end [...]; "
5. No inorganic thing needs any movement of its parts in order to preserve itself; on the contrary, as long as its parts remain in rest and inaction, this thing preserves itself without alteration [...]. But as soon as something comes to act on this thing, and to excite movements and changes in its parts, this same thing immediately loses either its form or its consistency [...]; and it even loses its nature or is destroyed (in certain cases). Every thing, on the contrary, which possesses life, is continually, or temporarily, animated by a particular force which unceasingly excites movements in its lower parts which produces, without interruption, changes of state in these parts [...], so that, in it, the movements excited [...] alter and destroy, but repair and renew [...]; "
6. For any inorganic thing, the increase in volume and mass is always accidental and without limits, and this increase is only carried out by juxtaposition (...). The increase, on the contrary, of any living thing is always necessary and limited, and it is only carried out by intus susception, that is to say, by interior penetration, or the introduction into the individual of matters which, after their assimilation, must be added to it and become part of it (...). "
7. No inorganic thing is obliged to nourish itself in order to preserve itself [...]; every living thing, on the contrary [...], cannot preserve life unless it is continually nourished [...]; "
8. Inorganic things [...] are not born, and none of them is ever the product either of a germ or of a bud [...]. All living things, on the contrary, are truly born and are the product either of a germ [...] or of a bud [...]; "
9. Finally, no inorganic thing can die [...]. Every living thing on the contrary, is subject to death [...]. [...]. According to this, what impropriety on the part of those who would like to find a connection and in some way a nuance between certain living things and inorganic things! "
This is how J.B. de Lamarck saw the problem of the inorganic and the living arising in 1809. One will notice his extremely fine description of the properties of life, properties that should be explained, but without having, as he did, recourse to a vital force of which nothing can be said. But the beginning of the XIXth century also saw the birth of the atomic theory and the discovery of the chemical elements, the combination of which produces all inorganic bodies. The question then arises: can chemistry produce organic bodies, assimilated by living beings?
Some of these bodies could be recognized in animal excrement, and urea, discovered by Rouelle in 1773 and crystallized from urine, represented the very type of organic body. In 1828, the German chemist Wöhler succeeded in synthesizing urea from ammonium cyanate, which was considered an inorganic body. By all its properties, synthetic urea is recognized as identical to urea extracted from living beings. It is often thought that Wöhler thus founded organic chemistry, which was gradually stripped of the connotation linking it to life and became nothing more than the chemistry of carbon compounds, and today especially that of petroleum derivatives, which are usually immiscible with water.
From the moment urea was obtained synthetically, a strong current, parallel to the rise of positivist thought, emerged to admit the community of identity of inert matter and living matter. This was, moreover, a resurgence of Lamarck's zoological philosophy where inorganic matter gives rise to living creatures, but within a new paradigm, that of the atomic theory. Several themes will then dominate the birth of biology and its development until today: dualism will reappear in the form of vitalist theories, in which the material support is distinguished from certain essential principles that animate it, and the unifying theories will be divided around concepts related to the inorganic world (analogy with the crystal) or to the organic world (analogy with the mucoid and colloid bodies). Numerous theories and discoveries mark this path.
Fermentation was first explained, before 1840, by Berzélius and Liebig as a catalytic phenomenon that did not allow to distinguish the organic from the inorganic. Then Pasteur, who had observed that the products obtained from living beings have a certain dissymmetry (the crystals of tartaric acid obtained from fermentation are all formed from an optical isomer, giving an oriented crystal, whereas the crystals obtained by chemical means are formed from a racemic and therefore mixed mixture), proposed to eliminate the idea of spontaneous generation. This leads him to infer that living beings are endowed with essential intrinsic properties ** and reintroduces vitalism, which will be constantly taken up until our days, Bergson representing one of the dominant thinkers of this type of paradigm. At the same time, and without resorting to the vitalist demon, many scholars shift the distinction between organic and inorganic to the colloid/crystalloid couple, which takes up themes that have been prevalent since antiquity: living/inert, soft/hard, or moving/static. Fermentation and diastatic activities are the result of colloids, so that the crystallization of ovalbumin in 1890 by Hofmeister obliges to displace the colloid/cristalloid duality which has become irrelevant.
Curiously, we are still close to this time and the crystallization of a new protein is still reported, even if it is not emphasized as much anymore. This is because it is likely that a new duality is being set up. Indeed, it seems that it is particularly unbearable for many human minds to admit the continuity of nature from the inorganic to the organic. The notion of colloid has only recently vanished: until the last war, there was at the Institut de Biologie Physico-Chimique à Paris, first institute founded in Europe for the multidisciplinary study of the phenomena of life, a "Service of colloid chemistry"... This disappearance took place at the time when the essential concept of macromolecule was born. The fundamental difference between the inert and the living lies in the greater complexity of the structures constituting the latter. No difference in nature appears, but on the contrary a very great difference in organization. Like small molecules, macromolecules are crystallizable and consequently the colloid/crystalloid duality does not bring anything directly relevant. However, this topic underlines that some of the physico-chemical aspects of macromolecules can differ significantly from those of small molecules.
From the inorganic to the organic: the origin of life
Let us first note that, contrary to what is often asserted, it is not at all obvious that life is improbable, at least in environments similar to the Earth. To be convinced of this, we can observe that the choice of possible parameters is very limited but fundamentally generative. Indeed, the atoms that form the molecules of life are not random: to make stable and complex edifices requires a good chemical reactivity, a large enough abundance, a great molecular stability. This immediately rules out the heaviest atoms, since it is the external orbitals that fuse to form molecules. The peeling off of the internal electronic layers makes most of the macromolecular edifices formed by atoms with many internal layers very unstable, and only hydrogen, boron, carbon, nitrogen, oxygen and fluorine remain as fundamental atoms for the synthesis of complex, stable and diversified macromolecules. Lithium and beryllium form ions. It is then the abundance of these elements that will determine their presence in macromolecules: lithium, beryllium and boron are very rare in the universe, it is not surprising that they are not found as major constituents of life. Fluorine combined with carbon gives very stable molecules, probably too stable to allow a metabolism at temperatures where water is liquid: it does not appear either as a major constituent. Finally, it is appropriate to mention one of the most recently highlighted aspects where osmosis seems, concretely, to play the role of a process underlying the functioning of living beings: the chemosmotic mechanisms responsible, thanks to a displacement of protons, for the synthesis of the chemical energy used by living beings.
This is a model phenomenon, described by the English chemist P. Mitchell, and for which he was awarded a Nobel Prize. It is known, in fact, that more than 95% of the energy used by plants and animals comes from a metabolism called oxidative phosphorylation, which takes place in specialized organelles, essentially made up of membrane structures, the mitochondria. It is known, in all cases, that this is a complex mechanism involving electron transport, during which some molecules are oxidized, while, in parallel, the transformation:
ADP + phosphate ——> ATP
where ATP is the universal donor of chemical energy. This major problem of biology, studied for more than half a century, and never solved, was remarkably formulated by Mitchell in 1961, who had the merit of noticing how the geometrical arrangement of molecules within living systems lent itself to the setting up of a remarkable coupling between the mechanisms of cellular respiration or photosynthesis, and the phosphorylation leading to ATP. His idea was that there must exist in parallel with the transformation of chemical energy or light energy into chemical energy a particular translocation of an appropriate molecular support, a process in which the membrane must play a leading role, its structure allowing the separation, the compartmentalization of energy in space. His idea, which seems valid (although it has not been explicitly proven) is that it is a chemiosmotic phenomenon involving active transport of protons (H+), so that water can freely cross the membrane but the concentration of protons (the pH) is unequal on both sides of it. This osmotic theory is based on the following four postulates:
a/ The enzyme responsible for the synthesis of ATP is a membrane protein, whose reversible catalytic activity is sensitive to the chemiosmotic gradient of protons, allowing a phosphorylation according to a fixed quantitative ratio protons/phosphate.
b/ The respiratory or photosynthetic chains are made up of membrane proteins whose activity is sensitive to the chemosmotic gradient of protons, according to a defined ratio of transferred protons/electrons. Their tendency to translocate protons from one side of the membrane to the other is in the same direction as the hydrolytic activity of the membrane ATPase.
c/ There are specific transport systems in the membrane, depending on the proton concentration, which allow osmotic equilibrium and the transport of metabolites.
d/ All these systems are inserted in a closed membrane which has the property of being (freely) permeable to water, but of presenting a strong osmotic barrier to the permeability of various molecules or ions in solution, in particular protons and OH– ions.
This hypothesis has the merit of giving a homogeneous picture of the cell functioning and of introducing a particular hierarchy in the set of activities of a cell by privileging the membrane which can thus coordinate a large number of processes. It is clear in particular - and Mitchell insists on this point - that the concepts related to osmosis will have to be refined and better understood if we want to progress, in particular the geometrical notions associated with this process, bringing into play concrete molecular structures, initially present, will have to be deepened. Thus, under an aspect quite different from what one could have imagined at the beginning of the XXth century, the study of osmosis and the formulation of the concepts associated with it will be at the center of the concerns of those who want to produce adequate models of life.
** Pasteur's attitude is particularly clear when he talks about fermentations, in a long dispute with Claude Bernard, who reduced them to banal chemical reactions whereas Pasteur implied the necessity of a living principle for them to take place.