Reflections on the Nature of Molecular Mechanisms

Introduction

Imagine yourself in a biological laboratory. In front of you is a test tube with a set of instructions on how to determine its contents. You perform the instructions and everything seems to accord with what was predicted by them. What just happened? Do you understand what happened? Surely not. What would it take for you to understand what just happened? A common response would be, that you should be able to explain the procedure by invoking a number of chemical mechanisms which supposedly explain why each instruction is what it is; had one been different the procedure would probably not have worked.

Now imagine yourself in the same laboratory, with the same test tube, but this time with no instructions, but only the understanding of various chemical mechanisms. If the test you are supposed to perform was simple you would certainly manage to perform it successfully. However, when more complex tests are demanded of you, you have to involve a whole host of experimental techniques, for most of which there exist only discrete instructions on how to use them. You, as an experimental biologist, are not concerned with all the details of their mechanical and chemical implementation and simply trust that they sufficiently conform to standards expected from the instructions. We often suppose that, if we had the time, we could have carefully studied and understood every aspect of the experimental techniques we use in terms of objective and clearly structured mechanisms. However, what would happen if we bracketed this presupposition?

The work of French philosopher and physician Georges Canguilhem (1904-1995) provides a surprisingly relevant answer to this question. His texts on philosophy of biology are full of diverse ideas and approaches. Nevertheless, one of his central aims was to provide a consistent critique of mechanical explanation of biological phenomena. He insists, that a conviction of ‘mechanisms all the way down’ described above stems from a misguided approach to the metaphysics of living phenomena. Throughout his work, Canguilhem provides a number of examples from biology and medicine, but unfortunately, he did not keep pace with the development of molecular sciences. The latter are what interest us the most in the present essay. After presenting Canguilhem’s historical critique of mechanical explanation, we proceed with the presentation of his idea of biological originality, which provides an excellent starting point for the presuppositionless approach to mechanical explanation. Next, we try to define the concept of molecular mechanism, which we divide in thick and thin variants. In the end we apply this understanding to the current state of biological research and show that advancements in molecular biology – especially with respect to the central dogma of molecular biology and protein moonlighting – support Canguilhem’s critique of naive mechanical explanation. 

Mechanistic description of nature

In his essay Machine and organism Georges Canguilhem explicates his critique of the mechanical theory of nature as a way of explaining the organic world (Canguilhem 2008, 75). Mechanical explanations of biological phenomena were historically applied to more obviously mechanical parts of the living body (e.g., blood vessels as hydraulic tubes, muscles as cords, teeth as pliers) (ibid., 78). During the 20th century with the advancement of biomolecular sciences, mechanical approach, also borrowing from mechanisms of organic chemistry, became the primary tool for the investigation of cellular and subcellular levels (Kohler 1975, 314). Thus, the mechanical conception became progressively more abstract, hardly being comparable to what was traditionally understood as a mechanical process.

However, Canguilhem raises an important concern regarding all kinds of mechanical explanations. His critique starts with a historical investigation of the unidirectional relation between a machine, whence the mechanical explanation is supposed to take its cue, and the (part of an) organism, which is to be explained with reference to it. Taking the machine either as a given or as a result of careful mathematical construction, most philosophers and mechanical biologists conceptualized the machine as “theorems solidified and displayed in concreto” (ibid., 76). Even though this view might seem like a reasonable explanation of the relationship between theoretical knowledge and its application, Canguilhem takes the precedence of theory over technique to be a crucial mistake influencing the mechanist biological paradigm (ibid.). We will follow Canguilhem in turning the explanatory direction and try to explain how we could understand machines as originary biological phenomena (ibid., 95). But to fully understand what this might mean and how it can be applied to the concept of molecular mechanisms, we have to cover some basic historical turning points.

What is a mechanism?

One might ask, why should machines and mechanisms both be considered when talking about mechanical explanations of living beings? In an influential text dealing with mechanisms in neuroscience and molecular biology, Machamer, Darden and Craver, mention machines only twice – once in a historical context (Machamer, Darden and Craver 2000, 15) and once when discussing algorithmic interpretation of mechanisms (ibid., 17). Accordingly, perhaps the notions of machine and mechanism can be considered independently. However, Machamer, Darden and Craver are a perfect example for what Canguilhem tries to undermine, as it seems that in their writing mechanism is nothing more than a theorem that “can be instantiated in biological wet-ware or represented in the hardware of a machine”. (ibid.) After a careful reading of their definition of the concept of mechanism, the independence of a theoretical model over a practical machine is more than apparent: 

“Mechanisms are entities and activities organized such that they are productive of regular changes from start or set-up to finish or termination conditions.” (ibid., 3)

In contrast to their treatment of the relationship between machine and mechanism as two seemingly independent concepts, Canguilhem strives for a more nuanced and historically informed conceptualisation. In fact, his definition presents a deep connection between them:

“We may define a machine as an artificial construct, a work of man, whose essential function depends on mechanisms. A mechanism is a configuration of solids in motion such that the motion does not abolish the configuration. The mechanism is thus an assemblage of deformable parts, with periodic restoration of the relations between them.” (Canguilhem 2008, 76f)

Seen from Canguilhem’s point of view, a mechanism is merely a physical part of a machine, which it constitutes. He continues:

“The assemblage consists in a system of connections with a determined degree of freedom: for example, a pendulum and a cam valve each have one degree of freedom; a threaded screw has two. The material realization of these degrees of freedom consists in guides – that is, in limitations on the movements of solids in contact. In any machine, movement is thus a function of the assemblage, and mechanism is a function of configuration.” (ibid., 77)

In the second part of his definition especially, we can clearly see the stark difference between the two definitions of mechanism. While the former one is entirely theoretical, merely a rule for constructing mechanical explanations, the latter one intimately connects the concepts of mechanism and machine. Furthermore, the latter considers both the mechanism and the machine from a material standpoint, where practical implementation is more important than theoretical consistency or descriptive adequacy. This difference between theoretical understanding of what a mechanism is and a practical manifestation of it, should be kept in mind as it forms the backbone of our understanding of Canguilhem’s critique of mechanical explanation. In the next chapter we will try to show that thinking about machines in a more practical way can solve an important problem – the problem of the invention of machines. 

Living Organism as a Machine

Ever since the birth of philosophy in ancient Greece mechanical analogies between animals and machines existed, which “presuppose[d] man-made devices, in which an automatic mechanism [was] linked to a source of energy whose motor effects continue[d] well after the human or animal effort they release[d] had ceased.” (Canguilhem 2008, 79f): be it Aristotle’s comparison of organs to parts of war-machines, Plato’s definition of the movement of vertebrae via an analogy of pivots, or Descartes’ interest in automatons (ibid., 80). Canguilhem accordingly summarizes that “we may therefore say that, so long as a living human or animal ‘sticks’ to the machine, the explanation of the organism by way of the machine cannot be born.” (ibid.) However, we would miss an important historical inflection point, if we did not stress the role of Descartes’ invention of the concept of animal-machine. It was a result of an advance in mechanisation, by which more machines were invented, which enabled extended propagation of movement and activity devoid of human interaction (ibid.). This encouraged Descartes to try and create a biology that would consider all living beings as machines, thus trying to do away with a naive, more anthropomorphic way of explaining living phenomena. By considering an explanation via mechanisms as more fundamental, rational and scientific than an explanation via purposiveness of particular parts of a living being, he inspired a style of thought that is often calledmechanistic biology.[1]Though Descartes’ biology seems to do away with most of what we might perceive as an ancient remainder of Aristotle’s biology, Canguilhem thoroughly shows that the situation is not as … Continue reading

In brief, the mechanism is supposed to explain how the machine manages to imitate the living being, which in turn explains the functioning of the living being itself. However, the machine can only imitate what has already been given in the living world: “The Cartesian God […] works to equal the living itself. The model for the living machine is the living itself.“ (ibid.) Accordingly, the mere possibility of constructing a machine that would perfectly imitate a living being serves as the proof of their equivalence. Using this presupposition as a starting point, Descartes does indeed try to remove teleology from the living world, by introducing the concept of mechanism and the notion of the animal-machine, but he manages to do this only in appearance. Surely, the use of machines and mechanisms in explaining the living world can be somewhat divorced from the human construction and the use of machines in the first place. However, the practical relationship between the machine and the living being can only be suppressed and not completely removed. It is in fact of immense importance for the understanding of mechanisms, as it elucidates, how a mechanism’s explanatory power is clearly manifest to the extent that it seems to be the most convincing explanation possible.  Only because we use mechanisms in everyday life are we able to perceive the purpose they are supposed to provide in an explanation. Precisely because machines themselves are tied to our experience of them, Descartes has to invoke God, who steps in and acts as the supreme transcendental constructor, who manages to pass through an infinity of mechanisms producing a living being, infinitely more complex than a simple machine (like a clock) yet still mechanical in its essence (ibid., 85). This step seems to lift mechanistic biology above all already invented machines and tries to support the claim that living beings are built of, as of yet, mostly undiscovered mechanisms. Nevertheless, Descartes’ argument fails precisely because it seems that without a transcendental constructor, hiding mechanisms all around the organic world, the supposed equality of machines and organisms appears frivolous.

If we take machines as a given – in case of organic mechanism by God himself – we may say that mechanical explanation makes the representation of biological knowledge more objective by removing from it a naively intuitive comprehension of biological function, replacing it with an objective mechanism. However, this only works until we ask ourselves about the wider (practical) context in which everyday machines exist. This context gives the machine’s mechanisms meaning and manifests their purpose, which is eventually clear enough to replace naïve teleological explanation. Considering this, we must agree that machines do not exist merely for themselves, but rather serve certain functions demanded by us humans. Accordingly, Canguilhem writes that “machines can be considered organs of the human species” (ibid., 87) Thus “to explain organs or organisms through mechanical models is to explain the organ using the organ” (ibid.). Taking machines and mechanisms as the starting point of biology is thus hopelessly circular. So let us try to invert the relationship – let us try to understand mechanisms from an organic point of view.

Machine as Biological Originality

In order to reverse the relationship between the mechanical and the organic, Canguilhem claims that we can understand a novel machine and its mechanism only as long as we understand the purpose it was built to serve. “It is thus necessary to see the machine functioning so as then to appear to deduce the function from the structure.” (ibid., 88) Furthermore, as long as we take machines and mechanisms as something that is already granted, we can explain desired (biological) problems with them; if they are not granted, however, the process of invention of a new machine or a mechanism turns out to be extremely hard to rationally explain or predict (ibid., 87). This fact is of utmost importance, as the invention and subsequent construction of a machine is something that is foreign to the machine itself and thus the preservation of its functioning (and purpose) rests upon constant external supervision so as not to collapse; even in cases, where machines are regulated by other machines, the regulating machine is imposed on the regulated by us (ibid.).

On the contrary, the human body and all living things have the ability to self-construct, self-renew, self-conserve, self-regulate and self-repair (ibid., 88). Moreover, a single organ can serve more than one function in the body. For example, we rarely see bones as anything more than a support structure, which is an obvious function due to their rigidness and stability. However, bone marrow is a crucial component of our immune system and the main hematopoietic organ. This “polyvalence of organs” (ibid.) is essential for the distinction between organic and mechanical, the latter of which is characterised by the utter lack of it. A machine, by which an organ is supposed to be explained, has a clear purpose as it is “rigid, univocal [and – above all -] univalent” (ibid., 89). This is achieved by the practice of standardisation, which simplifies models and replacement parts in order to grant a more rational and ordered understanding of the causes within machines. “Any part is equivalent to any other with the same purpose” (ibid., 88) The more a part or a machine is standardized, the clearer its purpose is; this leads to the purpose being almost completely manifest, thus appearing to explain the purpose of an organ or a living being simply and efficiently by substituting for it. Yet, organs and living beings are not rigid and their purpose is not manifest but are pluripotent and their purposes are latent and diverse (ibid., 89). The aforementioned substitution is thus an oversimplification rather than an explanation. 

“It can easily be said that there is more purpose in the machine than in the organism, because the purpose of the machine is rigid, univocal, and univalent. A machine cannot replace another machine [with a different purpose]. The more limited the purpose, the more the margin of tolerance is reduced, and the more hardened and pronounced the purpose appears to be. In the organism, by contrast, one observes – and this again is too well known to be insisted upon – a vicariousness of functions, a polyvalence of organs. Doubtless, this vicariousness of functions and polyvalence of organs are not absolute, but they are so much greater than in the machine that there can really be no comparison.” (ibid., 89)  

Let us look at an example of how a new biochemical mechanism is described. In his book Exprimentalsysteme und epistemische Dinge Hans-Jörg Rheinberger (2001) explores the history of scientific research on the process of protein synthesis. His understanding starts with a brief description of the context in which the question of protein synthesis first became obviously relevant – cancer research. His aim is to show how an experimental system, first developed in the medical context of cancer research, later transformed into a system in which the fundamental questions of molecular biology could be investigated (ibid., 36). Accordingly, the birth of the first cell-free system for studying protein synthesis resulted less from detailed research employing biochemical research techniques, than from a practical approach, which Rheinberger dubs “Techno-Opportunism” (ibid., 38). Zamecnik expresses his research attitude in one of his articles thusly:

“At our present primitive state of knowledge of the chemical factors involved in carcinogenesis, it may be premature, however, to consider a single avenue of biochemical study as being the most promising one. It may be more practical to take advantage of whatever new opportunities become available, in the hope that a definite clue turned up in any corner of the field may lead to a connection with the hereditary properties of the cell.” (Zamecnik 1950, 660) 

We want to emphasise (as is apparent from Zamecnik’s quote), that at no point theoretical understanding of the process was what guided the research – the researchers most of the time wanted to create a stable and predictable procedure, whose repetitions would be variable but consistent. Hence, we can harken back to Canguilhem, who insists that even though we think it impossible to build mechanisms and machines without a scientific explanation, historically speaking the logical consistency of mechanism was abstracted away after their physical implementation – a machine – was developed and stable:

“The logical anteriority, at any given moment, of a knowledge of physics [or (bio)chemistry] to the construction of [biological] machines cannot and must not allow us to forget the absolute chronological and biological anteriority of the construction of [biological] machines to the knowledge of physics [or (bio)chemistry].” (ibid., 92)

Moreover, the incentive to develop new experimental procedures, which we might later try to abstract into mechanisms, is the most fundamental moment for understanding the development of new techniques and machines. In the case of protein synthesis it was the subjective understanding of what it means to have cancer, that was progressively abstracted from first being a predictor for the difference in the rate of protein synthesis to being a special case of dysfunction of the process of protein synthesis. That is what Canguilhem means when he says that machines are themselves best understood as biological originalities. He simply stresses the fact that a living being always tries to overcome challenges encountered in itself or its environment by inventing and employing machines; not through theoretical problem solving, but practical trial and error. The subjective reaction of the living being to an obstacle is that which encourages it to overcome it; hence biological originality and consequently all technique (also bio-medical machines) is subjective in its origin, but objective in its implementation:

“If there is any objective sign of this universal subjective reaction […] to vital depreciation in disease, it is precisely the existence, coextensive in space and time with humanity, of medicine as a more or less scientific technique for healing diseases.” (Canguilhem, 132)

Retro futurism. Lab 1950s

What Is a Molecular Mechanism?

Notwithstanding the complex subjective-objective character of biological originality, how might we theoretically describe a fully abstracted, merely objective molecular mechanism? Mechanisms are considered crucial components of chemistry and science at large, because they can characterize specific chemical compounds and help us make predictions about chemical reactions under controlled laboratory conditions. For example, isn organic chemistry in order to be able to synthesise an organic compound one has to abstract a specific chemical reaction, i.e., break it into well-determined standardized steps. Consequently, one scan determine a unique procedure that makes the reproducibility and control over the process of synthesis and its subsequent mechanistic explanation possible. According to Goodwin (2012) there are two notions of chemical mechanisms. The first is the thick notion, where one visualises the progress of a specific reaction as a continuous stream of events, and the thin one, where one tries to represent the dynamics of a reaction as a discrete set of steps (ibid., 310). The latter, being discontinuous, is often highly idealized and abstract, but dominates the world of chemistry and chemical research still until present day. The reason for this, is that determining the thick representation of a mechanism is often very strenuous or mostly impossible to satisfy. Moreover, the extra information beside the notion and structural determination of stable reactive intermediates and transition states is often unnecessary and does not provide any additional explanation that is relevant.

The crucial component of determining the thin mechanism is breaking the problem into smaller standardized steps. These then allow us to determine the “bottlenecks” of the reaction, which are normally situated at so-called rate determining steps of an otherwise continuous reaction, at which the reaction is of a considerably slower rate and thus easier to detect. The structure and stability of the intermediates at these rate determining steps enables us to explain the observable features of the chemical reaction. The stability of intermediates highly influences where alternative paths are or are not possible, as stable intermediates have more potentialities for divergent reaction paths than unstable ones. Similarly, as in Canguilhem’s essay, this standardization of parts – here an ordered set of reaction intermediates and transition states – allows us to reuse them to predict novel reactions, keeping in mind the limited potentialities of these standardized parts. This is often used to create and/or optimize synthesis of new compounds in organic chemistry (Goodwin 2012, 322). However, the role of mechanistic explanation in organic chemistry serves as a tool of inquiry, contrary to biology where it often serves as an explanatory goal (ibid., 325).

That is why the thick notion of a mechanism is the ideal to which mechanistic biology strives. Merely stating a set of abstract intermediates found in a thin explanation, would miss the highly interconnected nature of biological processes in vivo. Doing this would amount to making an organism a mere standardized part of an experimental machine. Though this is exactly the role many model organisms play, it can hardly be said to be the ideal of biological understanding. To cherry-pick organisms, which we can easily understand, is to fail to understand anything but how we managed to change them to biological machines, serving our practical and research purposes. In all other organisms, where a thick explanation would be more welcome, one would have to pass through an infinity of steps – quite like the Cartesian god passes through infinity – in order to create animal-machines. Contrary to the cartesian goal of an infinitely complex thick mechanism, in organic chemistry the thick notion of mechanism “plays a more abstract, conceptual role because it fits naturally into the theoretical models [i.e. thin explanations] that chemists use to represent chemical transformations” (Goodwin 2012, 312). It is therefore often used as a mathematical representation of a chemical transformation, explaining transformations of standardized entities found in the thin version of the mechanism; it is definitely not the goal itself.

It would seem that rationalization by standardization in organic chemistry is sufficient in order to grasp the meaning of a specific chemical reaction. This is what happens in highly standardized experimental setups, where the reaction and its context are closely controlled. By this, the mechanism is abstractly separated from its material manifestation (in the experimental machine) and idealized into a term by which it becomes a standardized experimental technique. Accordingly, Canguilhem insists that this kind of “rationalization of techniques makes one forget the irrational origin of machines” (ibit., 95). Once again, we have taken the (bio)chemical technology of manufacturing reactions in the laboratory as simply given, thereby forgetting that all the technology had a practical and concrete origin.

Invoking Kant’s discussion of practical nature of art, Canguilhem equates the process of invention (as opposed to application) to artistic creation (Canguilhem 2008, 93). Contrary to theoretical knowledge of an already constituted idealized mechanism, the invention of a new mechanism requires the practical knowhow of solving a concrete problem. For Caguilhem, the invention of steam engine is more a solution to the problem of draining mines than it is a theoretical application of thermodynamics (Canguilhem 2008, 95). Following Rheinberger, who we introduced above, one might say that a similar relationship exists between cancer, protein synthesis and molecular biology. And while organic chemistry is very successful in its research and thin representations of mechanisms might suffice, they have often proven to be problematic, when considering biochemical reactions in vivo – concrete problems of unstandardized biological individuals. These happen between much larger molecules, with many more potentialities, and on a much larger scale.

The Central Dogma

To continue our discussion of the history of molecular biology, let us consider the so-called central dogma of molecular biology. In 1957 Crick held a lecture, as part of a symposium on the Biological Replication of Macromolecules at the University College London. The lecture was originally entitled “Protein synthesis” but dealt also with other aspects central to molecular biology. It was the first time the central dogma was conceptualized. The concept proposed the possible flow and directionalities of information between the molecules of nuclelic acids and proteins in living organisms. The highly criticized central dogma of molecular biology known as a simple two step information transfer DNA → RNA → protein was later popularized by Watson’s textbook Molecular Biology of the Gene (1965), which oversimplified Crick’s original idea (Cobb 2017, Crick 1970).

However, we can learn something by inspecting the experiments and findings that overthrew this oversimplified idea of sequential information that we understand today as the central dogma of molecular biology (DNA → RNA → protein).

The discovery of reverse transcriptase in 1970, an enzyme crucial for replication of RNA through a DNA intermediate of retroviruses, provided proof of the possibility of DNA synthesis from an RNA template, thus enabling the reverse flow of information from RNA to DNA (Temin 1970). Another example was characterization of prions as proteinacious infectious particles which were the cause of several neurodegenerative diseases. In 1982 Stanley B. Prusiner proved for the first time that the agent causing this pathogenesis was a protein particle causing structural deformation of host prion proteins and formation of structured aggregates only via its tertiary structure, without the presence of any nucleic acid, which was usually associated with infectivity, thus making an example how protein-protein flow of information is also possible (Prusiner 1998,1982). This was another example of how the central dogma of molecular biology was incompetent in predicting this interaction possibility. There are also other examples such as protein folding which is assisted with specialized proteins called chaperones, the splicing of precursor mRNA and mRNA editing to its mature form, chromatin modifications and the role of small interfering RNAs (Morange 2009). If we looked further, we would be bound to find many more instances in which the central dogma of molecular biology would be insufficient to provide a relevant explanation. 

To summarize, the concept that was first formulated in the 1950s as such presented a very “thin” mechanism that could only be applied to the standardized experimental conditions of that era. The extreme advancement of new technologies and major improvements of existing ones enabled much more thorough examination of living mechanisms, thus enabling to explicate much more of the pluripotency of living mechanisms that was not possible at the time the concept of molecular dogma was formed. 

Functional Polyvalence of Moonlighting Proteins

It is quite fascinating looking back at the history of development of sequencing technologies that now represent the central tool of many biological sciences but were only invented about 45 years ago (Shendure 2017). After the conclusion of the Human genome project in 2000 a  big explosion of genome sequences became available  due to development of next-generation sequencing and later third generation sequencing technologies. Sequencing became affordable and several genomes and other types of sequences became accessible (Giani 2020). Thus, it seemed that function and purpose of different proteins encoded by DNA could be extracted by studying merely nucleic acid sequences.

However, with development of such research the idea of one gene – one protein – one function has become too trivial as an increasing number of proteins have been found to facilitate more than one function. Hence, we arrive at the so-called concept of moonlighting proteins (Jeffrey 1999).

The term moonlighting is usually associated with having an extra (usually night) job and is in the context of proteins associated with proteins having multiple independent functions, which are dependent on their cellular or developmental context (Singh 2020). These are however not proteins which are the result of gene fusions, homologous but not identical proteins or splice variants. Both or multiple functions have to be present at the same domain and the inactivation of one of the functions should not have an influence over another(Huberts 2010, Jeffrey 1999).  The phenomenon of protein moonlighting is mostly associated with changes in cellular localization, oligomeric state, the cellular concentration of a ligand, substrate, cofactor, or product (Jeffrey 1999). It has been documented both in eukaryotic and prokaryotic organisms (Huberts 2010).

There are several examples of proteins that “moonlight” which are compiled into databases such as Moonprot (http://www.moonlightingproteins.org/), MultitaskProtDB-II (http://wallace.uab.es/multitaskII/), and MoonDB (http://moondb.hb.univ-amu.fr/) . 

Many of the additional functions of moonlighting proteins have been implicated in pathogenesis, cell division and apoptotic signalling. For example, many moonlighting proteins have been connected with virulence of bacteria and fungal pathogenesis. These are primarily housekeeping proteins or proteins which are ubiquitous, but are by an “unknown” mechanism secreted outside the cell, where they can play an important role in the invasion of the host organism (Singh 2020). Additionally, several soluble enzymes moonlight as structural proteins in the lens of the eye, for example heat shock proteins (proteins involved in protein folding, i.e., chaperones) of Drosophila have been found upon sequence comparison to closely resemble α-crystallin of vertebrate eye lens. Interestingly enough, experimental elaboration of functional equivalence derived from sequence comparison later showed, that isolated mammalian α-crystallin could in vitro perform the so-called original chaperone function of protein folding (the function normally associated with heat shock proteins). Though, this might seem as a proof of the close connection between protein function and their amino acid sequence/structure, the fact that the function was rationally transposed from heat shock proteins to mammalian α-crystallin speaks more in favour of the notion of manifest functionality of mechanisms developed by Canguilhem. Many other examples of secondary functions involve DNA or RNA binding to regulate transcription or translation (Jeffery 2003). 

Perhaps the most famous example of protein moonlighting is Glyceraldehide-3-phosphate dehydrogenase (GAPDH), which is primarily known to catalyse the 6th step in glycolysis, the process of glucose breakdown by which the cell harnesses energy. GAPDH – aside from its glycolytic function – has been implicated in apoptosis, iron transport, membrane fusion, transcriptional regulation, vesicle transport from the endoplasmic reticulum to the Golgi apparatus, and cellular response to hostile environmental changes, such as hypoxia and oxidative stress (Singh 2020).

Protein moonlighting points to our lacking scientific process and the awareness of multitude of additional functions a single protein can perform. Taken seriously, it could contribute to discovering additional unbiased paths to better characterize or approach the multitude of interactions that are natural to the information network of proteins in organisms (Singh 2020). Moreover, the concept of multifunctionality is very applicable in systems biology and diverse omics disciplines that rely on the advancement of sequencing technologies and (computational) information analysis tools. 

Conclusion

Canguilhem would most definitely have a lot to say about the current approach to studying the organic world. Since his thought is somewhat outdated for today’s life sciences, we have tried to update it for a modern scientific audience. We have done so, by introducing the concepts of thin and thick mechanisms, for which we tried to show how they connect to important factors in Canguilhem’s understanding of mechanical biology. As one of us is a biochemist, we strongly suspect that the contemporary scientific climate is in fact favourable to Canguilhem’s critique of mechanical explanation. The epistemic accessibility of organic phenomena is not dependent on the underlying metaphysical reality of organisms, but rather our ability to critically invent and apply mechanisms by which we interact with them. The presented critique of mechanical explanation is not a push to abolish such practices, but rather a suggestion to remedy their occasional intellectual arrogance.

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References

References
1 Though Descartes’ biology seems to do away with most of what we might perceive as an ancient remainder of Aristotle’s biology, Canguilhem thoroughly shows that the situation is not as simple. In fact, Canguilhem insists that in “the theory of the animal machine, which has generally been seen as a rupture with the Aristotelian conception of causality, […] all the types of causality invoked by Aristotle are found, though not in the same place and not simultaneously.” (ibid., 85) Following a quote from Descartes’ Treatise on Man, he points out that Descartes’ theory of animal machine needs a builder (a God) that acts as an efficient cause by which the machine-animal comes to be: “I assume their body to be but a statue, an earthen machine formed intentionally by God.” (Descartes quoted in ibid., 84) Formal cause is that which God tries to emulate, in the case of the quote at hand a man: “formed intentionally by God to be as much as possible like us.” (ibid.) While the final cause is what is to be imitated by the animal-machine, i.e. behaviour.