Synthetic biology and its alternatives. Descartes,Kant and the idea of engineering biological machines

The engineering-based approach of synthetic biology is characterized by an assumption that ‘engineering by design’ enables the construction of ‘living machines’. These ‘machines’, as biological machines, are expected to display certain properties of life, such as adapting to changing environments and acting in a situated way. This paper proposes that a tension exists between the expectations placed on biological artefacts and the notion of producing such systems by means of engineering; this tension makes it seem implausible that biological systems, especially those with properties characteristic of living beings, can in fact be produced using the specific methods of engineering. We do not claim that engineering techniques have nothing to contribute to the biotechnological construction of biological artefacts. However, drawing on Descartes’s and Kant’s thinking on the relationship between the organism and the machine, we show that it is considerably more plausible to assume that distinctively biological artefacts emerge within a paradigm different from the paradigm of the Cartesian machine that underlies the engineering approach. We close by calling for increased attention to be paid to approaches within molecular biology and chemistry that rest on conceptions different from those of synthetic biology’s engineering paradigm.     

Barbieri’s Organic Codes Enable Error Correction of Genomes

Barbieri introduced and developed the concept of organic codes. The most basic of them is the genetic code, a set of correspondence rules between otherwise unrelated sequences: strings of nucleotides on the one hand, polypeptidic chains on the other hand. Barbieri noticed that it implies ‘coding by convention’ as arbitrary as the semantic relations a language establishes between words and outer objects. Moreover, the major transitions in life evolution originated in new organic codes similarly involving conventional rules. Independently, dealing with heredity as communication over time and relying on information theory, we asserted that the conservation of genomes over the ages demands that error-correcting codes make them resilient to casual errors. Moreover, the better conservation of very old parts of the genome demands that they result from combining successively established nested codes such that the older an information, the more numerous component codes protect it. Barbieri’s concept of organic code and that of genomic error-correcting code may seem unrelated. We show however that organic codes actually entail error-correcting properties. Error-correcting, in general, results from constraints being imposed on a set of sequences. Mathematical equalities are conveniently used in communication engineering for expressing constraints but error correction only needs that constraints exist. Biological sequences are similarly endowed with error-correcting ability by physical-chemical or linguistic constraints, thus defining ‘soft codes’. These constraints are moreover presumably efficient for correcting errors. Insofar as biological sequences are subjected to constraints, organic codes necessarily involve soft codes, and their successive onset results in the nested structure we hypothesized. Organic codes are generated and maintained by means of molecular ‘semantic feedback loops’. Each of these loops involves genes which code for proteins, the enzymatic action of which controls a function needed for the protein assembly. Taken together, thus, they control the assembly of their own structure as instructed by the genome and, once closed, these loops ensure their own conservation. However, the semantic feedback loops do not prevent the genome lengthening. It increases both the redundancy of the genome (as an error-correcting code) and the information quantity it bears, thus improving the genome reliability and the specificity of the enzymes, which enables further evolution.     

‘Steps’ to Agency: Gregory Bateson,Perception, and Biosemantics

Gregory Bateson was welcomed into Biosemiotics as one of its precursors along with C. S. Peirce and Jacob von Uexküll He certainly endorsed Peirce pragmatic concern with learning as an essential characteristic of mammalian life, and also endorsed von Uexküll’s notion that the fundamental unit of animate existence is organism plus econiche. But he was at odds both with the subjectivism and with the cognitivism that connects Peirce to von Uexküll. Bateson rests his case on information theory which, he believes replaces many metaphysical notions that were the background to Peirce and von Uexküll’s approaches to ‘meaning.’ His idea of cybernetic ‘feedback’ in information circuits or networks yields a new understanding of recursiveness. Yet biofeedback in mammalian interaction had to be wrestled away from technical cybernetics and its thermodynamic rules about information, for the latter payed no attention to ‘meaning’ (“Bioentropy” section). Of the contrasts between Peirce and Bateson, the most significant is that Bateson regards ‘difference’ as primary to perception, while Peirce is concerned with continuity as primary from perception to cognition. This contrast is at the heart of Bateson’s Korzybski Lecture (see “On the Title of ‘Steps’” section), and shows how ‘difference’ in Learning develops orders and levels (see “Memory and Learning” section) leading to different categories of learning. With regard to perception, Bateson argues that the processes of perception do not bind perception to conscious awareness in any exclusive sense. Further, patterns of perception are not bounded by the skin for they include all external pathways along which information can travel. This recursive activity develops ‘agency’ (“Perception and Consciousness” section). We are ourselves interact with living mental ‘things’ but interactions with animate ‘creatura,’ is not the same as the objective interactions we purse in measuring inanimate material ‘things’ (pleroma) (“How Bioentropy Informs Bateson’s Notions of Pleroma and Creatura ” section). The grasping of context in communicative interaction, for example, is unique to creatura (“Context in Recursive Communication” section). Recognition of ‘difference’ occurs through communicative interactions and is meta-physical (without dimension). The pattern of interaction is the ‘thing,’ and ostensive aspects of communication are contextual, inclusive of all ‘external’ aspects vital for interpretation of ‘signals’ between initiators and responders to messages. Towards the end of his life, Bateson’s concerns with non-human conditions of ‘meaning’ and ‘mind’ in nature, resulted in his dropping several of the Peirce’s conditions of semiosis, as he looks at ‘meaning’ without language. He rests his method the propositional order of Peirce’s abduction rather than the latter’s full array of abduction, induction and deduction. Bateson is supported by the Biosemantics of Ruth Millikan, this paper will argue, who also believes that the derivation of meaning in animals through natural signs requires the stripping away of any ‘meaning rationalism’ (“Meaning Rationalism” section). Together they provide joint conclusions about as sign use in the ecosystems of creatura (“Conclusion” section).     

Meaning in Nature: Organic Manufacture?

The paper examines Marcello Barbieri’s (2007) Introduction to Biosemiotics. Highlighting debate within the biosemiotic community, it focuses on what the volume offers to those who explain human intellect in relation to what Turing called our ‘physical powers.’ In scrutinising the basis of world-modelling, parallels and contrasts are drawn with other work on embodied-embedded cognition. Models dominate biology. Is this a qualitative fact or does it point to biomechanisms? In evaluating the 18 contributions, it is suggested that the answers will shape the field. First, they will decide if biochemistry and explanatory reduction can be synergised by biosemantics. Second, they will show if our intellectual powers arise from biology. Does thinking use—not a language faculty—but what Marko? and colleagues call semiosis by the living? Resolution of such issues, it is suggested, can change how we view cognition. Above all, if the biomechanists win the day, cultural models can be regarded as extending natural meaning. On such a view, biomechanisms prompt us to act and perceive as we model our own natural models. This fits Craik’s vision: intellect gives us the alphanumerical ‘symbols’ that allow thoughts to have objective validity. For the biomechanist, this is explained—not by brains alone—but, rather, by acting under the constraints of historically extended sensoria.     

Experimental history and Herman Boerhaave’s chemistry of plants

In the early eighteenth century, chemistry became the main academic locus where, in Francis Bacon’s words, Experimenta lucifera were performed alongside Experimenta fructifera and where natural philosophy was coupled with natural history and ‘experimental history’ in the Baconian and Boyleian sense of an inventory and exploration of the extant operations of the arts and crafts. The Dutch social and political system and the institutional setting of the university of Leiden endorsed this empiricist, utilitarian orientation toward the sciences, which was forcefully propagated by one of the university’s most famous representatives in the first half of the eighteenth century, the professor of medicine, botany and chemistry Herman Boerhaave. Recent historical investigations on Boerhaave’s chemistry have provided important insights into Boerhaave’s religious background, his theoretical and philosophical goals, and his pedagogical agenda. But comparatively little attention has been paid to the chemical experiments presented in Boerhaave’s famous chemical textbook, the Elementa chemiae, and to the question of how these experiments relate not only to experimental philosophy but also to experimental history and natural history, and to contemporary utilitarianism. I argue in this essay that Boerhaave shared a strong commitment to Baconian utilitarianism and empiricism with many other European chemists around the middle of the eighteenth century, in particular to what Bacon designated ‘experimental history’ and I will provide evidence for this claim through a careful analysis of Boerhaave’s plant-chemical experiments presented in the Elementa chemiae.     

Where Did Information Go? Reflections on the Logical Status of Information in a Cybernetic and Semiotic Perspective

This article explores the usefulness of interdisciplinarity as method of enquiry by proposing an investigation of the concept of information in the light of semiotics. This is because, as Kull, Deacon, Emmeche, Hoffmeyer and Stjernfelt state, information is an implicitly semiotic term (Biological Theory 4(2):167–173, 2009: 169), but the logical relation between semiosis and information has not been sufficiently clarified yet. Across the history of cybernetics, the concept of information undergoes an uneven development; that is, information is an ‘objective’ entity in first order cybernetics, and becomes a ‘subjective’ entity in second order cybernetics. This contradiction relegates the status of information to that of a ‘true’ or ‘false’ formal logic problem. The present study proposes that a solution to this contradiction can be found in Deely’s reconfiguration of Peirce’s ‘object’ (as found in his triadic model of semiosis) into ‘thing’ and ‘object’ (Deely 1981). This ontology allows one to argue that information is neither ‘true’ nor ‘false’, and to suggest that, when considered in light of its workability, information can be both true and false, and as such it constitutes an organism’s purely objective reality (Deely 2009b). It is stated that in the process of building such a reality, information is ‘motivated’ by environmental, physiological, emotional (including past feelings and expectations) constraints which are, in turn, framed by observership. Information is therefore found in the irreducible cybersemiotic process that links at once all these conditions and that is simultaneously constrained by them. The integration of cybernetics’ and semiotics’ understanding of information shows that history is the analytical principle that grants scientific rigour to interdisciplinary investigations. As such, in any attempt to clarify its epistemological stance (e.g. the semiotic aspect of information), it is argued that biosemiotics does not need only to acknowledge semiotics (as it does), but also cybernetics in its interdisciplinary heritage.     

Bioelementology as an interdisciplinary integrative approach in life sciences: Terminology,classification, perspectives

The article presents the proposed concept of bioelements and the basic postulates of bioelementology for assessing and discussing them in the scientific community. It is known that chemical elements exist in the organism not by themselves, but in certain species having close interaction with other components. Such units are proposed to be called bioelements: the elementary functioning units of living matter, which are biologically active complexes of chemical elements as atoms, ions or nanoparticles with organic compounds of exogenous or biogenous origin. The scientific discipline that studies bioelements, is proposed to be called bioelementology. This discipline could lay the foundation for the integration of bioorganic chemistry, bioinorganic chemistry, biophysics, molecular biology and other parts of life sciences.     

“My appointment received the sanction of the Admiralty”: Why Charles Darwin really was the naturalist on HMS Beagle

For decades historians of science and science writers in general have maintained that Charles Darwin was not the ‘naturalist’ or ‘official naturalist’ during the 1831–1836 surveying voyage of HMS Beagle but instead Captain Robert FitzRoy’s ‘companion’, ‘gentleman companion’ or ‘dining companion’. That is, Darwin was primarily the captain’s social companion and only secondarily and unofficially naturalist. Instead, it is usually maintained, the ship’s surgeon Robert McCormick was the official naturalist because this was the default or official practice at the time. Although these views have been repeated in countless accounts of Darwin’s life, this essay aims to show that they are incorrect.     

Cells as irreducible wholes: the failure of mechanism and the possibility of an organicist revival

According to vitalism, living organisms differ from machines and all other inanimate objects by being endowed with an indwelling immaterial directive agency, ‘vital force,’ or entelechy. While support for vitalism fell away in the late nineteenth century many biologists in the early twentieth century embraced a non vitalist philosophy variously termed organicism/holism/emergentism which aimed at replacing the actions of an immaterial spirit with what was seen as an equivalent but perfectly natural agency—the emergent autonomous activity of the whole organism. Organicists hold that organisms unlike machines are ‘more than the sum of their parts’ and predict that the vital properties of living things can never be explained in terms of mechanical analogies and that the reductionist agenda is doomed to failure. Here we review the current status of the mechanist and organicist conceptions of life particularly as they apply to the cell. We argue that despite the advances in biological knowledge over the past six decades since the molecular biological revolution, especially in the fields of genetics and cell biology the unique properties of living cells have still not been simulated in mechanical systems nor yielded to reductionist—analytical explanations. And we conclude that despite the dominance of the mechanistic–reductionist paradigm through most of the past century the possibility of a twentyfirst century organicist revival cannot be easily discounted.     

A Short History of Biosemiotics

Biosemiotics is the synthesis of biology and semiotics, and its main purpose is to show that semiosis is a fundamental component of life, i.e., that signs and meaning exist in all living systems. This idea started circulating in the 1960s and was proposed independently from enquires taking place at both ends of the Scala Naturae. At the molecular end it was expressed by Howard Pattee’s analysis of the genetic code, whereas at the human end it took the form of Thomas Sebeok’s investigation into the biological roots of culture. Other proposals appeared in the years that followed and gave origin to different theoretical frameworks, or different schools, of biosemiotics. They are: (1) the physical biosemiotics of Howard Pattee and its extension in Darwinian biosemiotics by Howard Pattee and by Terrence Deacon, (2) the zoosemiotics proposed by Thomas Sebeok and its extension in sign biosemiotics developed by Thomas Sebeok and by Jesper Hoffmeyer, (3) the code biosemiotics of Marcello Barbieri and (4) the hermeneutic biosemiotics of Anton Marko?. The differences that exist between the schools are a consequence of their different models of semiosis, but that is only the tip of the iceberg. In reality they go much deeper and concern the very nature of the new discipline. Is biosemiotics only a new way of looking at the known facts of biology or does it predict new facts? Does biosemiotics consist of testable hypotheses? Does it add anything to the history of life and to our understanding of evolution? These are the major issues of the young discipline, and the purpose of the present paper is to illustrate them by describing the origin and the historical development of its main schools.     

A day of systems and synthetic biology for non‐experts

From understanding ageing to the creation of artificial membrane‐bounded ‘organisms’, systems biology and synthetic biology are seen as the latest revolutions in the life sciences. They certainly represent a major change of gear, but paradigm shifts? This is open to debate, to say the least. For scientists they open up exciting ways of studying living systems, of formulating the ‘laws of life’, and the relationship between the origin of life, evolution and artificial biological systems. However, the ethical and societal considerations are probably indistinguishable from those of human genetics and genetically modified organisms. There are some tangible developments just around the corner for society, and as ever, our ability to understand the consequences of, and manage, our own progress lags far behind our technological abilities. Furthermore our educational systems are doing a bad job of preparing the next generation of scientists and non‐scientists.     

Spencerism and the Causal Theory of Reference

Spencer’s heritage, while almost a forgotten chapter in the history of biology, lives on in psychology and the philosophy of mind. I particularly discuss externalist views of meaning, on which meaning crucially depends on a notion of reference, and ask whether reference should be thought of as cause or effect. Is the meaning of a word explained by what it refers to, or should we say that what we use a word to refer to is explained by what concept it expresses? I argue for the latter view, which I call ‘Darwinian’, and against the former, ‘Spencerian’ one, assuming conceptual structures in humans to be an instance of adaptive structures, and adaptive relations to an environment to be the effect rather than the cause of evolutionary novelties. I conclude with the deficiency – both empirically and methodologically – of a functionalist study of human concepts and the languages they are embedded in, as it would be undertaken in a paradigm that identifies meaning with reference or that gives reference an explanatory role to play for what concepts we have.     

From computational quantum chemistry to computational biology: experiments and computations are (full) partners

Computations are being integrated into biological research at an increasingly fast pace. This has not only changed the way in which biological information is managed; it has also changed the way in which experiments are planned in order to obtain information from nature. Can experiments and computations be full partners? Computational chemistry has expanded over the years, proceeding from computations of a hydrogen molecule toward the challenging goal of systems biology, which attempts to handle the entire living cell. Applying theories from ab initio quantum mechanics to simplified models, the virtual worlds explored by computations provide replicas of real-world phenomena. At the same time, the virtual worlds can affect our perception of the real world. Computational biology targets a world of complex organization, for which a unified theory is unlikely to exist. A computational biology model, even if it has a clear physical or chemical basis, may not reduce to physics and chemistry. At the molecular level, computational biology and experimental biology have already been partners, mutually benefiting from each other. For the perception to become reality, computation and experiment should be united as full partners in biological research.     

Commentary: oxidative stress reconsidered

All definitions of the terms ‘oxidative stress’ and ‘antioxidants’ implicate that oxidants are just damaging. However, there is increasing evidence that reactive oxygen species (ROS) are not only toxic but that we need them for healthy life. This change in paradigm has been discussed at the third international symposium on ‘Nutrition, oxygen biology and medicine—micronutrients, exercise, energy and aging disorders’, of the Society for Free Radical Research France and the Oxygen Club of California on April 8–10, 2009 in Paris. The beneficial effect of a low to moderate concentration of oxidants produced during exercise was taken as most discussed example. In this case, ROS are required for normal force production in skeletal muscle, for the development of training-induced adaptation in endurance performance, as well as for the induction of endogenous defense systems. Taking antioxidants during training prevents adaptation. Although substantial progress on the understanding of the physiological functions of ROS was communicated at the meeting, it remained obvious that a lot of work is needed to fully understand the conditions and individual situations under which ROS are beneficial or detrimental.     

Pattern Cladistics and the ‘Realism–Antirealism Debate’ in the Philosophy of Biology

Despite the amount of work that has been produced on the subject over the years, the ‘transformation of cladistics’ is still a misunderstood episode in the history of comparative biology. Here, I analyze two outstanding, highly contrasting historiographic accounts on the matter, under the perspective of an influential dichotomy in the philosophy of science: the opposition between Scientific Realism and Empiricism. Placing special emphasis on the notion of ‘causal grounding’ of morphological characters (sensu Olivier Rieppel) in modern developmental biology’s (mechanistic) theories, I arrive at the conclusion that a ‘new transformation of cladistics’ is philosophically plausible. This ‘reformed’ understanding of ‘pattern cladistics’ entails retaining the interpretation of cladograms as ‘schemes of synapomorphies’, but in association to construing cladogram nodes as ‘developmental-genetic taxic homologies’, instead of ‘standard Darwinian ancestors’. The reinterpretation of pattern cladistics presented here additionally proposes to take Bas Van Fraassen’s ‘constructive empiricism’ as a philosophical stance that could properly support such analysis of developmental-genetic data for systematic purposes. The latter suggestion is justified through a reappraisal of previous ideas developed by prominent pattern cladists (mainly, Colin Patterson), which concerned a scientifically efficient ‘observable/non-observable distinction’ linked to the conceptual pair ‘ontogeny and phylogeny’. Finally, I argue that a robust articulation of Antirealist alternatives in systematics may provide a rational basis for its disciplinary separation from evolutionary biology, as well as for a critical reconsideration of the proper role of certain Scientific Realist positions, currently popular in comparative biology.     

Reflexions sur l'usage,en biologie,de la theorie de l'information

For living beings, information is as fundamental as matter or energy. In this paper we show: a) inadequacies of quantitative theories of information, b) how a qualitative analysis leads to a classification of information systems and to a modelling of intercellular communication. From a quantitative point of view, the application in biology of information theories borrowed from communication techniques proved to be disappointing. These theories ignore deliberately the significance of messages, and do not give any definition of information. They refer to quantities, based upon arbitrarily defined probabilistic events. Probability is subjective. The receiver of the message needs to have ‘meta-knowledge’ of the events. The quantity of information depends on language, coding, and arbitrary definition of disorder. The suggested objectivity is fallacious. In common language, the word ‘information’ is synonymous with knowledge of order. Following common sense a message (letters, coded signals, etc.) is information just in case it is interpretable, i.e.if it fits to a previously acquired meaning (the words of an available language, etc.). The consequence is that calculation of quantities in the sense of Shannon can be used for transmissions, but it is itself meaningless (has no significance). In linguistics and semantics, information is composed of a ‘signifier’, a physical medium (letters, coded signals, etc.), and a ‘signified’ or significance. The nature of information is complex. The laws of linguistics and semantics are valid not only at the human, organismic level, but also at the cellular and molecular level. The physiology of sensations gives us many examples for application of a concept of information An electromagnetic wave of 0,7% give us the sensation of a red colour. Sensations have no physical reality. They are purely subjective. At the cellular level communication operates by means of chemical messengers (first messengers), which generally do not penetrate the plasmic membrane. Specific captors operate as transductors: external factors are converted into secondary messengers (cyclic AMP, Ca ion, etc.). Sometimes, electric signals (like depolarization waves) may also play a part in the intercellular communication. Such processes are characterized by changes in a sequence of different molecules carried by a physical signal. What is transmitted is themeaning of the message (significance) which can be memorized by the cell, providing a possible following use. At the molecular level one can find also the processes of linguistic nature. We know that the significance of a word is changed with changing the order of letters (ADD→DAD, etc.). In the same way bases C and U are coding for serine (UCC), leucine (CUC) or proline (CCU). Here, amino-acids express the significance. In spite of the fact that this key-lock mechanism may explain many reactions, the examples prove that other elements are necessary for understanding the information. The living cell is the receiver. The message actualizes only previously learned and memorized significances or actions (trigger effect). Significance is not an emergent property of the shape of the message. It depends on the receiver and the transmitter. A word can have more than one meaning. Similarly, a messenger can order different physiological responses: muscular tension, hormonal secretion, etc.. Thus a chemical messenger is a signal which is identified and interpreted by the receiver, depending upon specific languages and previous learning. These views are in harmony with immunological and Jerne's theory (of idiotypical net). The above mentioned considerations led the author to propose thetheory of data transfer, which takes into account significance. In this theory the quantity of information is the product of the probabilistic recognition of message and the value of significance as determined by its semantic level. (See: Acta biotheoretica vol. 41 No 1/2 June 1993.) The complex nature of information asks to propose a qualitative classification with respect to thematerial support and thesignificance.

1. The material support may be linear in time (sequential reading, ADN translation)-The material support may be referred to non-temporally (drawings, logos, holograms) (Reading is instantaneous)-The material support may be in circulation, or in stock.
2. The significance may be local (tissues, organs) or general (organisms). Asignificance may be a command to be executed (imperative, conditional order) or knowledge to bememorized. The purpose of significance may be a coding for space (for morphology) or for time (ontogeny, ageing).

Conclusion: Information cannot any longer be regarded as an object. Its nature is complex, at all levels of a living being. At the molecular level to memorize an information by modification of a molecule is comparable with writing words on a diary. The key-lock process does not suppress the question of the interpretation, i.e. relations existing between the shape of a microscopic element as a molecule, and its macroscopic effect, as an antenna or a leg. There are still many unclear points in these relations, e.g. the sweet taste of molecules of tomatine and monelline. The abstract nature of significance which at the human level is concerned to mental processes, is not only a philosophical problem. In fact, there is a hypothesis based on quantum mechanics which allows to consider a physical nature of significance. In any case, the important conclusion is that significance in bio-information must be considered in relation to the message-receiver. The receiver must no longer be considered a passive one. The qualitative classification of information will allow an understanding of circulation of information in organisms and between cells.     

The definitions of information and meaning two possible boundaries between physics and biology.

The standard approach to the definition of the physical quantities has not produced satisfactory results with the concepts of information and meaning. In the case of information we have at least two unrelated definitions, while in the case of meaning we have no definition at all. Here it is shown that both information and meaning can be defined by operative procedures, but it is also pointed out that we need to recognize them as a new type of natural entities. They are not quantities (neither fundamental nor derived) because they cannot be measured, and they are not qualities because are not subjective features. Here it is proposed to call them nominable entities, i.e., entities which can be specified only by naming their components in their natural order. If the genetic code is not a linguistic metaphor but a reality, we must conclude that information and meaning are real natural entities, and now we must also conclude that they are not equivalent to the quantities and qualities of our present theoretical framework. This gives us two options. One is to extend the definition of physics and say that the list of its fundamental entities must include information and meaning. The other is to say that physics is the science of quantities only, and in this case information and meaning become the exclusive province of biology. The boundary between physics and biology, in short, is a matter of convention, but the existence of information and meaning is not. We can decide to study them in the framework of an extended physics or in a purely biological framework, but we cannot avoid studying them for what they are, i.e., as fundamental components of the fabric of Nature.