Asservir la nature?... Etrange expression. Pour y parvenir, Philokratos, il faut d'abord la respecter, l'écouter, lui obéir. C‘est ce que j'essaie de faire, maladroitement. Vois cette toupie. Je puis la lancer, non l'asservir; ce n'est pas à moi qu'elle obéit, mais à une loi (...}, une loi que j‘ignore encore (**)

Le Puits de  Syène (1962)
Jacques MONOD

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Order and necessity

This text was given as a lecture in honour of Jacques Monod on the tenth anniversary of his death in 1986. It has been slightly modified to improve its readability (the transcription of oral presentations is always very clumsy).  The original was published in 1987:

A Danchin
Order and Necessity
In "From enzyme adaptation to natural philosophy: heritage from J Monod" (E Quagliariello, G Bernardi, A Ullmann, Eds) Elsevier Sciences Publishers. (1987) pp 187-196 (Symposium "J Monod and molecular biology, Yesterday and Today". Trani. Italy: 13-15 dec 1986)

Because this lecture was a tribute to Monod's contribution to science, it focused on his views, without discussing the work of others who contributed to his achievements. In particular, because Monod was implicitly a Platonist/Pythagorean (with his emphasis on the importance of the beauty of things), he thought that symmetry should be introduced into the concept of allostery. In fact, it was an additional feature that was absent from Jean-Pierre Changeux's original work on the enzyme threonine deaminase, where the first hypothesis of the binding of a regulatory molecule to the enzyme that could be located at a different site from the binding site of the catalytic substrate was presented (hence the word allostery coined by Monod in the introduction to the lecture where Changeux's work was presented). Symmetry is not an essential element of the concept of allostery.

Jacques Monod has been celebrated not only for his well-known and still relevant scientific contribution, but also for his reflection on the status of life. In a world dominated by the rise of radical empiricism and operational controls, his contribution is both original and of primary importance. His premature death is therefore all the more regrettable. Not only is there much to say about Science as we practice it, but it seems necessary to bring our questions to the forefront. The industrial revolution disconnected Science from Philosophy, in order to avoid questions that could be raised against production and profit. It was therefore important for a scientist from an emerging (and major!) discipline to question the nature of the processes underlying the creation of the corresponding knowledge. In what follows, I will try to place Jacques Monod's thinking in the highly evolving context of concept production in biology. And what will help me is the fact that Jacques Monod's thinking was precisely undergoing a steady evolution of its own. For those who knew him well, what I am about to say will probably appear either as a truism or as a misunderstanding (depending on their sympathy for Monod's personality). For me, he was a young mind, almost adolescent, I would be tempted to say, with the corresponding qualities and defects. This means enthusiasm, ingenuity, deep intuition, dogmatism and versatility. It also means that his thinking is a stage, not a final thought: each stage is carefully built on foundations temporarily accepted as definitive, but destined to be questioned. Thus, the issues I will develop below should be understood as a tribute, not a criticism. Indeed, what could be more desirable for a scientist than a permanent questioning of the very foundations of his knowledge?

I. A philosophy of adaptation: telenonomy

Biology, because it puts Man into question, from its origins to the rules that have allowed emergence of consciousness, is the priviledged target of a finalistic approach, that permits, using implicit postulates, to avoid a large number of ethical problems as well as eschatological prospects without gods. Jacques Monod‘s position in this debate is, in a sense, "premolecular“: he remains highly sensitive to the meaning of things, and this is the reason for a concept he presents as essential to his thinking, the concept of teleonomy. For the theme that is at the heart of his quest is adaptation, and its origin, a theme that was central to his finest scientific discoveries. But adaptation implies a goal, and indeed, the most aggressive among the adversaries of molecular biology in general, and of Monod in particular, would recurrently give examples of adaptation as impossible to explain without asking for an explicit finality. One finds in the word "teleonomy" two superimposed concepts, that of a law, a reason (a nomos) and, precisely, that of a finality, an intention, a goal. We have here a remarkable revival of Aristotle's entelechy, understood as a necessity, by a scientist well known for his "reductionism"! Now, it seems to me, and this was the occasion for a very stormy (but fascinating) discussion with Jacques Monod, that this residuum of finalism is not only useless but noxious, and due to an erroneous interpretation of the concept of chance. Thus, for me, this concept is but a step in the progression of  Monod's thought towards a vision of Life as a pure and bare consequence of the complete absence of will or desire in the birth of living organisms. This would have certainly led to the deep feeling of complete solitude that Jacques Monod appeared to both loathe and like, and for which he created, quite unnecessarily, his own vision of chance.

Indeed Monod has certainly evolved in his own vision of life, starting, as almost everyone does, from a purely "instructive" attitude (meant to answer to the implicit question: why?) to a very "selective" view (meant to answer, in most cases, to the mechanistic question: how?). Whereas he wrote in 1949: "L'hypothèse essentielle, pour expliquer l'accroissement « autocatalytique » de l'activité enzymatique, c'est de supposer que les rencontres « efficaces » entre amorces spécifiques et « matériaux de construction » non spécifiques, seraient favorisées par la présence de molécules du même type déjà formées. En d'autres termes, la probabilité de formation d'une structure active donnée serait d'autant plus élevée que cette structure serait déjà representée à un plus grand nombre d'exemplaires. L'effet du substrat serait de stabiliser les structures déjà formées, et de favoriser ainsi la naissance de nouvelles structures semblables. On voit facilement comment, même si l'effet primaire était assez petit, il pourrait se traduire (par suite de la compétition entre les différents types de molécules pour les matériaux non specifiques) par un accroissement relatif considérable."1, which is a remarkable foreshadowing of the "selective stabilisation" hypothesis* underlying his theory of allostery, one finds in the text written in 1961 together with F. Jacob, where the term "allosteric inhibition" was first proposed, clear traces of a purely "instructive" approach ("Studies of the structure of the two (allosteric and catalytic) sites and of their interaction, using analogues of the substrate and inhibitor, might conceivably lead to interpretations in terms of the "induced-fit" theory of Koshland (1959)"), in a very "selective" background ("This brings up another issue which must be mentioned at this point, although it was not discussed during the conference, evidently because it is implicitly considered as settled. A few years ago, the question was often debated whether any further (non-genetic] structural information needed to be furnished, or might conceivably be used in some cases, at the stage of tertiary folding in protein synthesis. Such a "finishing touch" has been considered as one of the possible mechanisms which might account for the effect of antigen in antibody synthesis (Pauling, 1940) and of inducer in enzymatic adaptation (Monod and Cohn, 1952). In the latter case, no evidence against this possibility has accumulated (cf. Monod, 1956, Jacob and Monod, 1961) and proof has been obtained that inducer action is completely unrelated to the structure of the binding site of the induced enzyme (Perrin et al., 1960). In the meantime, speculations on the origin of antibodies reverted from "instructive" to purely "selective" theories (Burnet, 1959 ; Lederberg, 1959))2. The "induced-fit" process was rejected by him a few years later, on the ground that it was clearly "instructive"3.

Perhaps should I make clearer these concepts. "Instructive" theories postulate the existence of a causal agent, exterior to the system, that directs its evolution. A deeper analysis permits us to distinguish two levels in an instructive theory4: the approach that I shall term "animist" (which is typically represented by the evolutionist theory of JB de Lamarck) supposes the existence of a motor that can be interiorised and can drive the system's evolution; the model that I shall term "attractive", more recent in biology (but quite similar to Pythagorean or Platonist models) supposes that there exists, in essence, forms that are able to act as "attractors" and thus shape material systems. "Selective" theories, on the opposite, leave to contingent interactions the only driving force that makes living systems evolve5. Here, once again, it seems possible to separate between two types of models. The "preformist" model assumes (as does the attractive model, inside the system) the existence of preexisting stable forms, that are not visible at the start, then progressively actualized through selective interactions with the environment. Finally, the "generative" model refuses – in spite of the hypothesis of a local determinism – to predict specific structures, but postulates that the very existence of living systems (contingent a priori but necessary a posteriori) implied, as soon as the first organized systems existed (due to contingent interactions), a further evolution generated by the interactions (necessary, because everything is in movement) of the system with its environment. During this evolution only stable structures can persist long enough to constitute a living system: this is the work of selection, purely passive, and the result is constant production of emergent structures. In the instructive model one postulates the existence of both preexisting external forms and a mover that is able to have them imprinted on the system under study: the attitude that follows tends to abandon such vitalistic constraints. A simple way out is to postulate that innate structures preexist: they are present inside rather than outside the system. This is what Jacques Monod does, as one can see for instance in his insistence on the role of symmetry in the theory of allosteric inhibition. The preformist selective theory is still slightly impregnated with some instructivism: a living system will be perceived as having a goal, as reflected in the word "teleonomy". The problem is then to find what are the innate structures, as well as to describe a process permitting to actualize them. One remarks here that such a solution of the problem posed by the existence of living systems leads to a major question: if form is inside the system, can it have the global properties of the whole? The answer must be negative, and this leads Monod, in order to keep to the founding postulates, to reject the "holistic" explanation as non pertinent. This is why his writings look so "reductionist", as emphasized by his adversaries. But one has to replace the holistic interpretation by a new one: in the most modern approaches, that would certainly have been chosen by Jacques Monod, had he lived longer, there is no goal, there exists only the consequence of contingent interference of independent causal series, due to necessity of laws that must be identified. A living system is the result of a structure and a process: the structure possesses features of a memory, and the process uses the structure as a pattern to build the organism. One will separate, according to the generally accepted terms, between a genetic program, and an actualization of the program. The result is, in evolution, of a progressive alteration of the program, after modification of the hereditary memory, and during ontogeny, of every living system's identity, as a function of the environment in which it develops. Thus, perturbations in the environment will be, after a kind of "sifting", integrated to the individual, which, accordingly, will behave as an image of the world. One should no longer speak of adaptation but of adequation instead.

Perturbations are necessary simply because the underlying physico-chemical processes must have some variability. What the program prescribes are rules for the average unfolding of an average organization in an average environment. This has a specific consequence: the actual number of molecules specified by a given gene is often small (this is true in particular of molecules involved in regulation, and also, because of amplification at the level of translation, of the number of mRNA molecules); therefore, the corresponding behaviour of individual cells is submitted to Poissonian statistics; thus, even if one assumes that the program is reproduced with rigorous accuracy, in a constant environment, the progeny of a starting cell must vary, quite significantly. This means that there exists always some cellular individuality. As a consequence a given program can have various actualizations, even in a given environment, and it is not possible to predict whether it will be adapted. What the external medium does is simply to stabilize selectively all that is not completely incompatible with it. Because of the variations in expression of a given program – actualized in individuals – it becomes difficult to tell whether a given variation (a mutation in a broad sense) is positive, neutral or deleterious, for this would be meaningful only in a specific environment, depending on the number of individuals considered... Thus, processes controlled by selective stabilization, without breaking the constraints imposed by the laws of physics and chemistry, explain some of the rules which produce living systems, without asking for an unnecessary finalism. It should be emphasized here that whereas these processes are deterministic, this by no means implies that their consequences are foreseable!

With respect to this scheme, which I think self-consistent, Jacques Monod‘s thought represents a crucial step, the passage from a macroscopic level to the microscopic world. But this passage could not be operated without difficulties, and it is quite understandable that his thought was still penetrated, in spite of his denial, with a finalistic flavour. He certainly had well-known precedents: Darwin himself did not escape this snag, and when Spencer formulates his theory as "selection of the fittest" one is compelled to discover the existence of an internal finalism (who is able to tell what is the fittest?) inside a selective approach. This is also the reason for the concept of teleonomy that postulates a kind of prescience of adaptation. Also, in a more subtle way, Jacques Monod introduces another "motor", "attractive" this time (as did Pythagore or Thom), when he calls for a general constraint of symmetry.

I now come to a crucial point in my argument. Trying to substantiate his thought with the authority of two millenaries, Jacques Monod, being confident in his memory, wrote as an epigraph for his famous book, a sentence attributed to Democritus. What remains from the presocratic philosophers is not much, so that it is rather easy to find out all what remains from Democritus: when looking into the few hundred thoughts left by this author I failed to find the corresponding sentence. Where does this reminiscence come from? Looking into the collection of pre-Socratic philosophical remains I found a sentence, from a man who might have been a master of Democritus, Leucippus, in which an epigraph, very similar yet absolutely contradictory to that of Monod features:

Oὐδὲν χρῆμα μάτην γίνεται ἀλλα πάντα ἐκ λόγου τε καὶ ὑπ᾽ ἀνάγκης 6

Nothing comes to be at random, but all things for a reason and of necessity (translation WCK Guthrie7)

Certainly, Logos cannot be interpreted as chance!  But this reflects a typically Greek thought, of an archetypal scientific nature. Thus, one should get rid of chance, or, at least discuss its form, which I shall do in what follows. Curiously, I think this will stay in the line that Monod initiated, in spite of the disputable use of the words he made.

II. The secrets of Life

In an unpublished theatre play, Le puits de Syène, Monod stages the fight between Science and all obscurantisms (including the quest for power or glory), in hellenistic Egypt. And the hero to which he identifies, Epistemos, says for instance : "Asservir la nature?... Etrange expression. Pour y parvenir, Philokratos, il faut d'abord la respecter, l'écouter, lui obéir. C‘est ce que j'essaie de faire, maladroitement. Vois cette toupie. Je puis la lancer, non l'asservir; ce n'est pas à moi qu'elle obéit, mais à une loi [...], une loi que j‘ignore encore" **(Jacques Monod, Le puits de Syène, unpublished). This is a view of science that owes nothing to chance!, and I shall try to show below how much looking for Laws can bring to Biology.

Greek thinkers did not use the concept of chance as we do today (following a most popular interpretation of quantum mechanics), as meaning "indeterminism". They had for this concept two words: τυχη (which one is still in use) and αὐτόματον, which express that things are contingent, that the movement of atoms is eternal and without necessary external first cause. Greek chance is contingency, precisely what Jacques Monod describes in his book when Dr Dupont is hit by the hammer falling from the hand of M. Dubois: this is also the case when Monod, using a word borrowed from André Gide, speaks of a "gratuitous" inducer. This kind of chance is not indeterministic, but corresponds to unpredictable interference of causal series. Contingency gives varied environments as space for the evolution of living systems: this is the basis for a (passive!) sieving that leads to phylogenesis. This is where appears a fundamental facet of Jacques Monod's thought, his extension of the role of selection at the molecular level. The theory of allosteric inhibition, still often misunderstood, is a paragon of the role of selection in a mechanical process that operates not during a million years of evolution, but immediately, in present day living organisms.

There, was an example of a biological law, of a "secret of life", as Jacques Monod once said8. This is for me a hint that he was on the way of Leucippus sentence: what counts for the origin of the living is the existence of laws, specific to life, superimposed on the ordinary physico-chemical world. Such laws, conceptually extremely deep and abstract, are not initially geometrical (as is symmetry, for instance) as are the laws of physics or chemistry. What are they? It is possible, bearing in mind that these are not the only laws of life, to enumerate a few. The one which seems to me the most important, by far, and which would ask for a description much longer than this text, is the law of coding9. This law tells how it is possible for a material system to act both as a template, allowing construction of objects chemically and structurally different from itself, and a substrate for the action of the latter objects. This law has been operating at least twice: by founding the genetic code, and by being at the root of language. Other examples are being discovered: one can think that forms of what is a hierarchy play a major role in living organisms autonomy (it may have a geometrical dimension, permitting the separation of inside and outside); also, and to the contrary, it seems to me that acentered systems, endowed of global properties may have a major role in the differentiation of organisms (they may be operating in the formation of the immune network). To these laws are associated geometrical structures: the tree to the former, the helix (or the circle when the geometrical constraint is two-dimensional), to the latter. Finally there is a law, reflected in the process of "genetic takeover" as described by Cairns-Smith that may be central to metabolic processes, and which is associated to the geometrical structure of the rope, made of hundreds of small fibers, building a macroscopic structure10.

III. Ethics and materialism: the postulate of objectivity

Jacques Monod's main purpose when he wrote his book was both epistemological and ethical, as he answered during an interview a few years later: "J'ai tout de même abordé le plus redoutable de tous les problèmes: les rapports entre l'éthique et la connaissance. Cette question m'a toujours profondément tourmenté (...) et (...) je ne vous cache pas qu'il n'y a pas à sortir du dilemme que j'ai posé, on y est complètement enfermé. Ce dilemme est le suivant si je reviens au postulat d'objectivité. Si l‘on accepte cet axiome, qui se révèle très efficace, comme la science moderne le prouve, pour construire la connaissance, on admet aussi que l'univers est sans objet et objectif. (...) . Tout le problème est de savoir s'il est possible de construire un système, et là je me place uniquement du point de vue de la logique, où il n'y aurait plus cette imperméabilité totale entre l'éthique et la connaissance objective, celle reconnue comme telle, celle qui ne viole pas le postulat d'objectivité. (...) Ce que j'ai voulu proposer est ceci: dans un monde où les systèmes d'éthique traditionnelle sont ruinés, dans la mesure où personne n'y croit, pas même ceux qui y adhèrent encore, le seul système éthique acceptable et qui pourrait ne pas être en contradiction avec la construction d'une connaissance et d'une technologie scientifiques, est un système de valeurs franchement et ouvertement existentiel, se fondant sur le postulat initial que l'on sait être un postulat mais que l'on a choisi pour tel. C'est la définition de ce que j'ai appelé « l'éthique de la connaissance »"11.

Thus, at the heart of his thought one finds the postulate of objectivity. Postulate, therefore metaphysical, from which every scientist places his own quest in the sociocultural context of his time, and which allows him to approach the subject by objectiving reality. Curiously, this function led Monod to perceive the position of Man in the Universe as unique, and subject to an irremediable solitude, interpreted as the sign of an utter originality, prooving that life is the result of pure chance, without any determinism. This is why he marvelled at the strange features of living organisms, features that he reduced to aesthetical "universals": what is true for E. coli must be true for the elephant2. In turn these universals must impose their rule, and genetical constraints are absolute: the pathway for innovation is restricted, and one may fear that Man could evolve towards decline, because of the progresses of medicine12... One is therefore far from the revolutionary biology of recent years, during which genomes appeared as "fluid", while many universals have been questioned!

In Jacques Monod's words living organisms are defined by the fact that they go after a goal, and a major part of his argument is to define the conditions required for building materially such goals. This is the reason for proposing the interaction of chance, perceived as essential, and necessity. Chance is the motor that permits constitution of a goal, and this is related to the familiar, but to my mind erroneous, interpretation of the second law of thermodynamics, suggesting that every material system would spontaneously evolve towards disorder. Is it really necessary? And can't one go without both chance and goals?

It seems to me that a reappraisal of the second law of thermodynamics, looking for an interpretation more consistent with the physical laws underlying material living systems, can solve the problem. Entropy and disorder: if one needs two words for a single concept, this suggests that ideology is present at least in one among the two. Thermodynamics was created at the start of the industrial era, it was meant to be the science of work. Work represents the usable form of energy, which implies that there exists a corrupt form, and a process a completely improbable creation: the necessity for evolving leads to a statistical mechanics standpoint, the philosophy of work was shifted towards a philosophy of order. A social analogy was immediately apparent (and still is nowadays where one can find (sic) thermodynamic models of economy or all kinds of social phenomena!) and it was parallel to a reflection on mankind's degeneration, starting during the XIXth century (see Gobineau for instance) and pursued in well known circumstances during the XXth. The analogy between entropy and disorder is therefore far from being harmless, because of the cultural connotations it conveys. Thus, Life would be a permanent strife against corruption (genetical in particular) and the "struggle for life" would correspond to a struggle against an increase of entropy... In fact, entropy is but one of the measures of the tendency, for a material system, to evolve {towards equilibrium); it reflects the aptitude for exploration of all accessible energy states (including space) for all components of the system. Such exploration can lead to orderly or disorderly structures (but always more stable than the original state, i.e. more probable). In the case of living systems evolution, which depends on entropy increase, leads to exploration of a large number of potentialities, including those that are, as stated above, structured according to the abstract laws which are specific of life (coding for instance). Some among such systems {i.e. material sets constituted of a structure and a dynamic organization) are locally (in time and space) stable; they derive from selective constraints (selective stabilization) and make living systems as observed. Finally, the inescapable increase of entropy forces evolution as soon as environmental conditions are changed (which is inevitable because living systems are growing systems). This is reflected both in the structure of phylogeny: it is a tree structure, and in the very small number of material objects that are at the basis of life. We are, as a matter of fact, very for from chance.

Contrary to what is usually thought, indeed, the actual number of molecular species derived from living organisms is very limited, as compared to what would be produced by chance combination: there are certainly less than 1015 different protein types; this looks large but is nothing when compared to the random possibilities for a protein of 100 amino acids (20100). Phylogenic linkage still reduces the choice inside related families, which implies that the proteins present in a species have specific features (not yet unraveled!). In particular one can think that there exists a system for scavenging erroneously translated proteins (this will also scavenge foreign proteins): the "self" proteins would be protected simply because they have coevolved with the scavenging system. This would imply that each species possesses a "protein landscape" specific to it, thus adding to the constraints.

Rather than universals (apart from the abstract biological laws), as Jacques Monod expected, we shall be confronted to entire families of related objects and discover constraints at the level of RNA, proteins and DNA. We are still very near to the origin of life. It becomes therefore vain to see life as a completely improbable creation: the necessity for evolving leads to a systematic exploration of reality, everywhere in the Universe. Only the specific way is unique, as well as individual systems: it becomes even more fascinating to try understand the underlying laws.


1. Monod J (1949)
The critical hypothesis to explain the "autocatalytic" enhancement of enzyme activity is to assume that the "productive" meetings between specific reaction primers and non-specific "building blocks", would be favored by the presence of already formed molecules of same type. In other words, the probability of formation of a particular active structure would be much higher if this structure would have been present in a greater number of copies. The effect of the substrate would be to stabilize the structures already formed, and thus promote the birth of new similar structures. One can easily see how, even if the primary effect was quite small, it may result (due to competition between different types of molecules for the non-specific building blocks) by a significant relative enhancement.
In: Unités biologiques douées de continuité génétique. CNRS, Paris pp 181-199
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2. Monod J & Jacob F (1961) Cold Spring Harb Symp Quant Biol 26:389-399 back to text

3. Monod J, Wyman J & Changeux JP (1965) J Mol Biol 12:38-113 back to text

4. Danchin A (1979) Rev Quest Sci 150:151-164 back to text

5. Danchin A (1979) Rev Quest Sci 150:323-337 back to text

6. Diels H (1901) Die Fragmente der Vorsokratiker. Weidmannsche Buchhandlung back to text

7. Guthrie WKC (1962 repr. 1978) A history of Greek philosophy. Cambridge University Press, Cambridge back to text

8. Ullmann A (1979) In: Lwoff A & Ullmann A (eds) Origins of molecular biology. Academic Press, New Iork pp 165-170 back to text

9. Danchin A (1983) L'oeuf et la poule. Fayard, Paris back to text

10. Cairns-Smith (1983) Genetic takeover. Cambridge University Press, Cambridge back to text

11. Monod J (1977)
I nevertheless approached the most formidable of all problems: the relationship between ethics and knowledge. This question has always deeply troubled me (...) and (...) I will not deny that we cannot get out of the dilemma that I have posed, we are completely locked up in it. This dilemma is the following, as I go back to the postulate of objectivity. If one accepts this axiom, which is very effective, as proven by modern science, to build knowledge, one also admits that the universe is without purpose and of objective nature. (...). The problem is whether it is possible to build a system, and here I place myself only from the point of view of logic, where there would no longer be that total impermeability between ethics and objective knowledge, that recognized as such, which does not violate the postulate of objectivity. (...) What I want to propose is this: in a world where the traditional ethical systems are ruined, since nobody believes in them, not even those who still adhere to them, the only ethical system that would be acceptable and would not be in contradiction with the construction of a scientific and technological knowledge, is a system of values frankly and openly existential, based on the initial assumption that we know to be an assumption but that one has chosen as such. This is the definition of what I called " the ethics of knowledge". Prospective et Santé 1:11-22 back to text

12. Monod (1970) Le hasard et la nécessité. Le Seuil, Paris back to text


* The role of selective stabilisation was further developed, in a model of learning and memory in the nervous system of animals by Jean-Pierre Changeux, Philippe Courrège and myself.

JP Changeux, P Courrège, A Danchin
Proc Natl Acad Sci U S A (1973) 70: 2974-2978 pubmed pnas


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** Enslaving nature? ... Strange statement. To achieve this feat, Philokratos, one must first show respect to nature, listen to it, obey to it. This is what I am trying to do in my awkward way. See this spinning top. I can spin it, not enslave it, it did not obey to me, but to a law (...}, a law that I do not know yet. back to text