This paper attempts to pose a question about the nature of "biological information" at its most basic level, seen from the perspectives of science, biosemiotics, and general semiotics. What has been called the central dogma of molecular biology is the idea that the genetic information flows only in one direction, from the genome to the biochemical activities in the cell. However, while this seems to presuppose a specific referential concept of information of some kind (or perhaps only a primitive one specifying sequences of chemical monomers). Such a concept does not seem to be well defined in molecular biology, and there are reasons to ask if there is any concept of 'semantic' information at this level of biology - or any clear concept of information at all. This 'Sarkar challenge' will be contrasted with the more visionary views of biosemiotics about the nature of information, communication and semiosis in living systems. Are we facing incompatible world views or just different paradigms?
Published (except the abstract) in 1999 in Semiotica 127 (1/4): 273-293. [special issue: Biosemiotica. See the contents here]
The core idea of this communication is crude and simple, namely to ask: How can we be sure that there are any `intrinsic' signs or any information in a basic living system such as a cell, as claimed by biosemioticians?
From the very start, I have to formulate a disclaimer about the name referred to in the title, that is to say, that it is my honest guess that the eminent philosopher of biology Sahotra Sarkar would not have imagined to be placed in the context of semiotics representing an antagonistic point of view on what I here construe as a foundational idea in biosemiotics. Sarkar has written on a semiotic question in relation to biology, though only implicitly, but in the article referred to here, he has not committed himself to any strong views about biosemiotics. My purpose is not to invent antagonisms between widely different kinds of scholarship; it is to disclose a fundamental question about the relationship between the conceptual fields of, first, biosemiotics (as we know the tradition from the writings of Thomas A. Sebeok, Jesper Hoffmeyer, Thure von Uexküll and others) and second, the very `normal science' of biology as a general paradigmatic understanding of living beings, their evolution, development, and basic nature as organized physical systems, including the `spontaneous' semiotics of the scientists within biology (in this context especially molecular biology and cell biology), and third and too briefly, a very fascinating way of conceiving everything from a fundamental `pansemiotic' perspective, as reflected in the writings of C.S. Peirce, and recently revitalised in a contemporary philosophical context by Floyd Merrell in his book Signs Grow: Semiosis and Life Processes. In order to emphasize that one faces different distinct options with respect to the foundations of biosemiotics, the work of Sarkar (and of Merrell) are just used as points of departure, though the works of others could have been used as well.
My question can, in all its preparatory simplicity, be formulated: If living nature is first and foremost characterized by its semiotic character, so that the very key to any understanding, scientific or philosophical, of life is semiosis, sign-action and sign-interpretation, rather than molecular reactions, as in the reductionist explanations of `the molecular machinery of life', must we then, as semioticians or even biosemioticians, postulate that biologists in a sense have already been doing semiotics -- although in a more superficial, unreflected, metaphorical way, or perhaps on an intuitive or subconscious level -- because otherwise it is difficult to understand the fact that we do seem to have witnessed an immense progress in knowledge of the basic biological processes during this century. If it is true that life is basically semiotic (as Hoffmeyer, Sebeok, von Uexküll and others claim), and it is also true that for instance molecular biology has revealed basic facts about life, could it be that the scientists within molecular biology have been talking semiotics all their life? This hypothesis -- that we may call "the Jourdain hypothesis", after Monsieur Jourdain in Molière's Le Bourgeois Gentilhomme, who suddenly realized that he has been talking prose for forty years without knowing it -- states that scientists spontaneously have invented a semiotic vocabulary, yet without realizing so, simply by studying life (living cells and their semiosic biochemistry) at the molecular and cellular level. Of course there might be alternative hypotheses implying other ways of understanding the complex relationship between life itself, sign processes, biology as the study of life, semiotics as the study of sign processes, and the study of science from the perspective of philosophy, sociology, semiotics, history, etc.
Another way to ask this question is to say: Have semiotic concepts any necessary explanatory role in biology, or could they have? If yes, how come? What examples could we give? And if not, does this represent a major challenge to biosemiotics as an alternative theoretical frame for a rational understanding of living organisms? If one cannot from an old-fashioned positivist or physicalist point of view see any legitimate use of or need for semiotic concepts in the attempt to explain life's most basic mechanisms, could biosemiotics then be saved so to speak, by certain extra-scientific considerations, such as the need for a more comprehensive view of the world than what physics and chemistry (interpreted in a physicalist or an instrumentalist way) can provide? Or can we in fact point to certain fractures, paradigmatic anomalies and unsolved riddles within the fields of molecular, developmental and evolutionary biology that are of such a complex and austere character that even the most optimistic hopes for hard-nosed reductionist explanations is doomed to fail?
As someone who will like to see the biosemiotic research programme flourish, but feels uncertain about its precise epistemological nature with respect to biology, I find it important to face such challenges, i.e., to see how far we can go in positing biosemiotics as an alternative research programme that may complement or eventually, in the future, even displace the molecular paradigm. But we should also be prepared to be forced to take more moderate positions, viz. suggesting biosemiotic concepts as a tool box that in certain domains of biology may help to organize our knowledge better, pose more interesting questions, and make alternative testable hypothesis, even though it may not take the role of an alternative paradigm. Being willing to take this adventure, we should face the possibility of severe criticism from the traditional domains of biology that has enjoyed a tremendous success in understanding for instance the basic mechanisms of heredity and metabolism, seemingly without any kind of use of semiotics or semiotics-based models.
Molecular biology seen as quasi-semiotics
However, one may still argue that even though molecular biology is reductionist in its rhetoric as well as in its methods, it is still not a branch of physics, it is rather an autonomous science with certain notions that are peculiar seen from a physicalist point of view; notions that only can be understood as quasi-semiotic, though they are not usually realized as being so. Information or `biological information' may be such a concept. If so, we have at least one crucial case for a biological term with a paradigmatic well-defined meaning within the heart of the `reductionist' paradigm of molecular biology, a term that is accepted by the majority of scientists in that field, yet a term that at a very fundamental level stands in need for being specified and explicated, although the existing theories of physics, chemistry and biology has not been able to supply a satisfying theoretical frame for this explication. That information is a quasi-semiotic concept is simply to say that when used by molecular biologists, it is not used as an explicit semiotic term; the meaning of `information' in the paradigm of molecular biology seems to be understood (usually as sequence specification and sequence conservation through DNA-duplication) without the help of semiotic theory. This fact, however, leaves open a vista for the biosemioticians, namely to transform this notion from being an implicit, quasi-theoretical and quasi-semiotic one in molecular biology to be a full and central category of biosemiotics, and furthermore to search in general semiotics for conceptual resources that might be used to answer other unresolved questions of molecular biology, such as the question about the origin of this information.
In my own approach to biosemiotics I have been sympathetic to this move, that is, to acknowledge that molecular biology really provides, to some extent, reductionist explanations for biologic phenomena, and yet to emphasize that this paradigm does not really explain the emergence of biological information in purely physico-chemical terms, because `information' is simply not a chemical or a physical concept, and because the biological information referred to here really functions for the living organism as a crucial tool -- a sine qua non for the maintenance of the very organismic system (because this system cannot rely only on the self-organizing properties of chemical processes far from thermodynamic equilibrium) -- so this information has to have its `meaning' (in the functional, not propositional sense of the word) defined relative to the level of properties of the organism, even if the organism is just a single free living cell (Emmeche 1990, 1991, 1998). So on this first stage, I am willing to grant some plausibility to the argument that what reductionist molecular biology has revealed about biological life -- by elucidating the structure of DNA (1953), cracking the genetic code (in the early 1960s), and mapping out some of the mechanisms of gene expression and regulation in simple and complex organisms (in the past 35 years) -- is that life basically is structured `like a language' (compare Jakobson 1973), that is, as a semiotic system, even though it takes biosemiotics really to explicate the very nature and specificity of the genetic code (as a code) and to explain why `language' after all is not so good a metaphor (Emmeche and Hoffmeyer 1991), and to see the code-duality of life as a basic kind of semiotic system sui generis (Hoffmeyer and Emmeche 1991).
The Jourdain hypothesis could be substantiated by exploring the concepts of molecular biology that deal with information transfer, signalling, and communication between molecules and cells. The underlying (biosemiotic) idea would be that these concepts keeps reappearing in molecular biology not just because of their metaphorical qualities which make them convenient devices for exposition of existing knowledge and for creating new conjectures, but because the very subject matter of molecular biology is communication and sign interpretation within and between cells. This is what the tradition of biosemiotics has claimed about the findings of cell and molecular biology, biochemistry and immunology. Thus, the genetic code must be seen as an obvious instance of a semiotic system -- indeed it is "but one of several endosemiotic systems" (Sebeok 1991: 154) -- and in general, one can argue that molecules carry out semiosis in living systems and that "the biological function of a molecule is, in general, not wholly determined by its chemical structure" (Kawade 1996: 210). Life can be seen as having differentiated certain molecules and conferred biological significance on them, which is "exactly a form of semiosis, being concerned with creation of meaning out of the physical world of molecules" (ibid.). The immune system may also be open to a semiotic description as suggested by Sercarz et al. (1988) and also studied by the biochemist Kilstrup (1997), who developed his own `sign link' notation as an elegant description of general biochemical pathways; a notation that emphasizes the fact that all biochemical regulation is concentration dependent and follows the law of mass action. In a classic paper Thomkins (1975) conceived of `a metabolic code' in which a specific intracellular symbol (i.e., an effector molecule such as cyclic AMP which accumulates when a cell is exposed to a particular environment) represents a unique state of the environment, and this symbol has a `domain' defined as all the metabolic processes controlled by the symbol. Stjernfelt (1992) analysed the interactions of macromolecules in the cell as an instance of `categorical perception' as a primitive concept in biology -- "of course deprived of any psychologism in the noun `perception'" (ibid. p. 441) -- which is topological in the sense that it erect classes (of biochemical processes) and in the sense that it relies on the topological features of the molecules classified; Stjernfelt envisaged a natural and continuous history of semiosis, "ranging from the most simple categorical perception based on morphological, steric features of matter to more and more complex types of signs, and in the same movement to more and more complex types of subjectivity -- that is, functional capacity in the system interpreting the categorically perceived units" (ibid., p.444). Such a natural history of signification has been developed further in the comprehensive biosemiotics of Hoffmeyer (1996) -- with more emphasis on the apparent leaps in the continuum with the emergence of new coding systems. Finally, one may see the pansemiotic approach of Merrell (1996) as one further step in this reflexive movement, i.e., not so much as an attempt to develop a biosemiotics (as a semiotics of life) as a vision of seeing the ubiquitous sign-action in the universe as a living process, and in this manner to describe signs as agents striving to fulfilment by way of other signs.
However, a certain suspicion -- in fact, `the Sarkar challenge' in a preliminary form -- may enter here, namely that it is only from the perspective of semiotics that these terms may appear as interesting indices for the existence of semiosis in any profound and intrinsic sense in the subject matter of that science, and that something much more mundane is going on. One could claim (as I think many molecular biologists would tend to do) that these quasi-semiotic terms are just used in a metaphoric sense or simply as short-hand descriptions of a more precise physical-chemical way of describing the interactions in the cell which -- from the molecular point of view -- does not involve any sorts of intentional actions or purposive conduct. Take again the important notion of `molecular recognition'; should this notion really imply the same sense of `recognition' as recognition as a semiotic act that presupposes the existence of memory, representations, categorization and other processes that are normally conceived as belonging to the cognitive level (recognition as a kind of cognition)? This is not what the molecular biologists are implying. `Molecular recognition' refers simply to a special form of physical contact between large macromolecules (e.g., an enzyme and its substrate, or a piece of DNA and a piece of a regulatory DNA-binding protein), where the weak (non-covalent) chemical bondings that easily form between any two biomolecules are of relatively high stability because some of the molecules accidentally fits together like lock and key. The random physical process of diffusion is the first step to molecular recognition; thermal motions bring all kinds of molecules together and then pull them apart. When the surfaces of two molecules match well, enough weak bonds (and hydrophobic interactions which are not bonds strictly speaking) can form between their surfaces to temporarily withstand the thermal motions that tend to break them apart. Thus, it is the physical requirements for matching that account for the specificity (the lock and key feature) of biological recognition on the molecular level, such as occurs between an enzyme that can only catalyse a very specific part of the whole metabolism due to its `recognition' or ability to fit physically to just one or a few species of molecules.
Other processes in the cell, that seem to have a more informational, cybernetic, semiotic (or even cybersemiotic) nature, such as the activation or inhibition of DNA transcription of a gene, are also crucially dependent on this molecular mechanism. To understand on the molecular level how some genes in certain cell types are turned on, while they remain silent in other cell types (`silent' means `not expressed', i.e., the protein about which the gene contains sequence information is not synthesized), one has to study in physical details the regulation of the genes in question. Structural genes (coding for proteins) are often regulated by the products (DNA-binding proteins) of regulator genes, and this regulation is mediated by molecular recognition. To give an example, we can observe what Molecular Biology of the Cell, a paradigmatic textbook in that field, explains about this form of regulation. According to Alberts et al (1994, p. 408),
"Molecular recognition in biology generally relies on an exact fit between the surfaces of two molecules, and the study of gene regulatory proteins has provided some of the clearest examples of this principle. A gene regulatory protein recognizes a specific DNA sequence because the surface of the protein is extensively complementary to the special surface features of the double helix in that region. In most cases the protein makes a large number of contacts with the DNA, involving hydrogen bonds, ionic bonds, and hydrophobic interactions. Although each individual contact is weak, the 20 or so contacts that are typically formed at the protein-DNA interface add together to ensure that the interaction is both highly specific and very strong (Figure 9-9). In fact, DNA-protein interactions are among the tightest and most specific molecular interactions known in biology."
It is evident from this passage that there are no intentional ascriptions involved in talking about molecular recognition, the recognition term seems to be simply shorthand for a longer expression describing the establishment of hydrogen and other weak bonds between partly complementary surfaces of two molecules. The insinuation of the Jourdain hypothesis, that molecular biologists imagine (even subconsciously) that some kind of interpretative process is on work here, seems to be far-fetched.
However, a reply to this objection could be that a pure physical or chemical description of the molecular recognition process is in no way incompatible with the human interpretation of this process as an intrinsic semiotic one, a process that has an intrinsic functional meaning for the organism, an instance of biosemiosis, even though what is focused on here is just a single node in the whole semiotic web of the cell's cybernetic and thus purposive and informational processes, such as the crucial feed-back processes involved in regulation of gene expression by the action of DNA-binding proteins. The biosemiotician -- who would have a much broader view of what constitutes a semiotic process than a cognitivist (for whom semiosis is constituted by mental representations of some kind, e.g., as understood within functionalism in the philosophy of mind) -- would still have to explain the precise nature of the molecular interactions as having to do with signs, `standing-for' (representational) relations, and interpretations. The semiotic nature of the process of molecular recognition could be an emergent feature of the molecular mechanisms of its parts -- biosemiosis could be a supervenient property on the physics and chemistry of the living cell. It would take a separate article to explore this suggestion; I will only mention that the concept of emergence of new unpredictable entities or properties on higher levels of organization has a long history in natural philosophy and biology (Fernandez et al. 1991; Blitz 1992; Beckermann et al. 1992; Emmeche et al. 1997), and that attempts to specify how such properties are physically grounded -- though they cannot be reduced to physics -- have found philosophical expression in the concept of supervenience (e.g., Kim 1993), according to which one set of properties (let's say a set of semiotic relations) are supervenient on a second set (the base set, e.g., physical relations) when they are so related that there could not be a difference in the first (supervening) without there being a difference in the second (base) set though there could be a difference in the second with no difference in the first.
We are now prepared for the more fundamental Sarkar challenge. First, I will present Sahotra Sarkar's main point so far as possible in its own right, though with a few comments of my own, and second, I will transpose its implications from the context of the history of molecular biology to be a challenge to the foundations of biosemiotics.
Sarkar's critique of informational terms in molecular biology
We have seen that terms with informational (and semiotic) connotations are in use in molecular biology, though opinions may divide between biologists and biosemioticians on what the bearings of this fact really is. But certainly most biologists would admit that information -- in some sense of the word -- is involved in the subject matter of their science. What sense of information, then, does the biologists' notion of biological information really have? And is this sense acceptable?
Francis Crick (who with James D. Watson proposed the double helix model of DNA in 1953) was probable the first to make explicit what is now taken as current notion of information in molecular biology, a notion that along with other informational notions in biology has been questioned for various reasons several times (e.g., Apter & Wolpert 1965, Stuart 1985a, 1985b, Oyama 1985), recently by Sarkar (1996).
A very famous claim, that really started as nothing more than a bold hypothesis when it was proposed by Crick in September 1957 at the `Symposium for the Society of Experimental Biology', was by himself called `The Central Dogma' (Crick 1958, for historical details see Judson 1979). This hypothesis defined the difference between two kinds of biological specificity (the specificity of each DNA sequence for its complementary strand and the specificity of the relation between DNA and protein) in terms of information:
"The Central Dogma. This states that once `information' has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or on amino acid residues in the protein." (Crick 1958: 153; italics in the original).
This sense of information -- sequential information about the components (nucleic acid residues and amino acids) of DNA and protein, the translational relations of which are specified in a genetic code -- is what biologists hold to be roughly equal to `genetic information' and to be fundamental to biology as a physical science. In making the distinction between the functions of deoxyribonucleic acids (DNA) and proteins, the central dogma can also be seen as a restatement of the reasons why environment-dependent features acquired by an organisms during its life (but not from its genes) could not be inherited by its offspring. It is a remarkable general claim, as it says nothing about what the machinery of transfer is made off, nothing about errors, nothing about particular control mechanisms, and it was intended to apply only to full fledged cells and organisms, not to events related to primordial cells at the origin of life and the code (cf. Crick 1970).
Sarkar's critique of the use of information in molecular biology covers several significantly different notions of information: the sequence notion of information in the central dogma just mentioned; cybernetic notions of information as feed-back in the context of the operon model of gene regulation; and notions derived from various attempts to apply mathematical information theory in biology. As the first of these notions is the most important, we shall focus on this.
Sarkar observes that it is nearly universally accepted among biologists that (i) hereditary information resides in the DNA, (ii) that this information is transferred from DNA to RNA through the process of transcription and from RNA to protein through the process of translation, and (iii) never from protein to DNA (as stated in the central dogma). His main thesis is that these three `precepts' are at best misleading, and, more likely, simply vacuous in the sense that they do not perform any significantly explanatory or predictive role at all:
"The reason for this is that there is no clear technical notion of "information" in molecular biology. It is little more than a metaphor that masquerades as a theoretical concept, and (...) leads to a misleading picture of the nature of possible explanations in molecular biology". (Sarkar 1996: 187f).
Sarkar maintains that had information, contrarily to what he thinks, managed to play a significantly explanatory role, then it would have provided a striking example of non-reductionist explanation in biology. He gives two criteria for counting as a "significant explanation", namely first, that the explanatory factors must help codify a body of knowledge so that it may be viewed as conforming to some general pattern, and second, that it must answer new important questions, which is, of course historically context-dependent, the "questions that were important to molecular biology in the 1950s are not those that are important now" (ibid., p.188). Sarkar's position on the role of this `sequence' or `genetic code' concept of information is nuanced, or complicated. His claim is not exactly that the informational notions from the very start was misleading; he states (p. 189) that "the explicit introduction and systematic use of that concept [information, C.E.] was the most important part of the reconceptualization involved in the emergence of molecular biology as a conceptual enterprise" that was distinct from its immediate ancestors such as biochemistry.
However, it was introduced in an attempt to navigate in a "terminological morass" (p.191) of that time. Sarkar notes that the term information was already used by Watson and Crick in their second 1953 paper on the structure of DNA, but first defined explicitly by Crick (1958) as the two kinds of biological specificity, as noted above. Sarkar gives a detailed exposition of the research in the late fifties and early sixties that led to the cracking of the genetic code, i.e. the establishment of the well known code table of the 64 codons of DNA that includes the start and stop codons and the base triplets standing for the 20 amino acids (the code proved to be degenerate). He emphasizes that the code was not cracked by formal considerations deriving from constraints on the efficiency of information transmission or other information-based reasoning. The code was cracked as a step-wise experimental denouement (the first codon was deciphered in 1961 using a cell-free system and RNA sequences; by 1966 the entire code was established). Sarkar asks rhetorically "what does the use of a concept of a code carrying information still do?" (ibid. p. 199) and answers:
"At the very most, it provides a succinct look-up table on the basis of which one can predict the sequence of the polypeptide chain that would be determined by a particular DNA chain provided at least five conditions, discovered since 1966, are fulfilled. Unfortunately, if prediction is the goal, these conditions are quite debilitating" (Sarkar 1996: 199).
Without going into technical details, these conditions according to Sarkar are: 1. that the code is universal, i.e., the same in all organisms (which is not universally true); 2. that the transcription initiation points are known (frameshift mutations are seen as a problem here); 3. that we know the intron/exon boundaries (which we for the present do not know on the basis of DNA sequence information alone); 4. that we similarly know about the precise coding/non-coding boundaries on the genome (which we do not precisely, cf. the vague notion of `junk-DNA'); 5. that `mRNA-editing' is no problem (which it is indeed in some organisms). So these conditions are not generally met, and Sarkar concludes that the code, or the `information' contained in it, is of little predictive value in novel contexts (p. 201). The code says nothing about the dynamics, the temporal progress of gene expression.
The upshot of the critique is, that `information' and `code' are in a sense unnecessary terms in contemporary biology, and that (as I read Sarkar) molecular biology would always in its whole history have been better off, if it had not adventured into the informational analogies, and that at least one example, the search by Crick and others in the late 1950s for a `comma-free code' proved to be misleading because it was only motivated (or motivated too much) by informational considerations, that is, explanatory factors were searched for that had no "physical warrants" (thus this part of the research programme was according to Sarkar non-physicalist, and therefore it failed, ibid., p.213, 217). By implication, the type of explanation that is characteristic of (successful) molecular biology is a "physicalist reductionist explanation" (p. 217). So Sarkar can recommend the biologists (at least as "a rather striking possibility") that they should "abandon the notions of codes and information altogether and pursue a thoroughly physicalist reductionist account of the interactions between DNA, RNA and protein" (p.218).
The Sarkar challenge - can `biosemiosis' explain life?
Now, what has all this -- a philosopher's post hoc critique of some failures in the history of biological research -- to do with biosemiotics? I think it is rather obvious. If Sarkar is right about information, it is not just a terminological problem for molecular biology that the scientists in this field use inadequate terms that give some wrong associations (and as he would add, a wrong picture of the nature of explanation). Even though Sarkar agues about reduction only at the epistemological level without drawing ontological implications of his analysis, it is hard to escape the conclusion that if his analysis is right, the consequence is not just that the conceptual framework of molecular biology should be modified, but the very idea that a living cell somehow contains, process, and transmit information (intrinsic information, not information conceptually projected by observers) must be rejected. In other words, if the Jourdain hypothesis fails, then this would constitute a serious challenge to biosemiotics.
This attempt to relate the possible implications of Sarkar's critique to biosemiotics may seem dubious, but can be justified exactly because many biosemioticians have used the informational terminology in molecular biology to claim something like the Jourdain hypothesis, including the promise that biosemiotics -- supported by the framework of general semiotics, especially the `heavy' tradition of C.S. Peirce -- may, in the future, provide a more secure and clarified ground for all this information talk. The shape of this clarification may look like this, put very briefly: `Information' is (even in the context of mathematical information theory, but also in the context of The Central Dogma) "a difference that makes a difference" (Bateson 1972) -- remember that one single point mutation, one single amino acid change, may be crucial, vital or lethal -- but semiotically, this is to say that it is something that makes a difference about something to somebody in some respect or capacity. Making a difference can be analysed in terms of the mechanics or physics of the process, as throwing a little gravel into a clockwork makes enough differences to the machinery that it cannot function. However, at the level of the simple physical movement of wheels and gears, we don't need the concept of function, which is only interesting from the perspective of the functioning of the whole, its dynamic stability. Similarly, the substitution of one single amino acid residue can be described as a single chemical reaction with certain chemical effects on the properties of the protein in question, but to see the good or bad consequences for the organism, we need the concept of function. Function, however, is connected to `the biological meaning' of the DNA sequence that specified the primary amino acid sequence that characterised the protein. On this level of biosemiosis, it is hard to escape the fact that the semiotic concepts are tightly connected to the functional concepts. Semiosis is normally functional. Thus, this sketch for a clarification of the informational terminology in molecular biology proposes that the concept of `biological information' in the sequential form is an irreducible semiotic concept, and at the same time, an irreducible functional concept. What remains, then (the task of a later paper), is to clarify the deeper conceptual relation between biological functionality and biosemiosis on this basic level. But to restate the justification for the relevance of Sarkar's critique: It is relevant, because if Sarkar is right, the Jourdain hypothesis is wrong, and then maybe biosemiotics is also wrong, and if Sarkar is wrong, the Jourdain hypothesis may seem to be vindicated, and is still valid as a motivation for biosemiotic research.
Is the analysis of Sarkar wrong, then? I think it is very important to distinguish its historical material and exposition, which is very detailed, from its philosophical agenda, which is highly disputable. One can pose a lot of questions that the work of Sarkar referred to here raises but does not answer: 1. What role does a broad conceptual framework -- whether we wish to call it a paradigm, a specific scientific style or mode of reasoning, or a special way of seeing the subject matter of a discipline -- play in an experimental, empirical, science such as molecular biology? 2. Could it be that even the most declared reductionists (such as Crick himself) in fact deploys more holistic concepts when it seems to be fruitful from simple pragmatic considerations? 3. Is present day molecular biology `reductionist' in Sarkar's own terms? 4. Would strict abandonment of informational terminology prove to be a theoretical advance in contemporary molecular biology? 5. To what extent is all scientific terms of a metaphorical nature, laden with allusions to other fields of knowledge? 6. How are the meaning of scientific concepts constituted?
An obvious criticism against Sarkar is that his criteria for the significance of explanation makes him blind to the importance of a central relatively stable core (cf. Lakatos 1970), a backbone-like role of well established concepts of a field, even though these concepts are not explicitly in the forefront when new hypothesis are stated or a theory is attempted to be expanded. The fact that information in the sense of the central dogma does not answer new important questions in molecular biology (even though this can be disputed) does not logically imply that `it is little more than a metaphor' or that its explanatory role is lost. The notion still plays a skeleton role in the framework of the field -- we have never faced another scientific revolution that completely changed the basic ideas about the genetic basis of protein metabolism as established by the first golden age of molecular biology in the fifties and sixties. Thus, the claim of Sarkar (ibid., p. 189) that "explanations in contemporary biology which invoke `information' fail to meet these criteria" (i.e., comprehensive codification of a body of knowledge and the answering of new questions) hinges upon what one really means with explanation, the role of individual concepts and general established ideas in a given instance of explanation. What role does the old concept of a `quantum of energy' play in a contemporary explanation of laser cooling or Bose-Einstein condensation? Hardly a big suspicious role seen in isolation, but still, it forms a basic part of the whole conceptual and theoretical framework of that field. Sarkar even admits that "loss of significance of a pattern of explanation is not always a function of age" and that for instance "Darwinian explanations are often significant even today" (ibid. p. 188). If so, and if these presuppose concepts that also can be accused of having a somewhat metaphorical status (such as natural selection, that by Darwin was invented in part by an analogy to artificial selection in animal breeding), why should not the basic structural relationship between DNA, mRNA and proteins still not have an explanatory role somehow within the same contemporary paradigm of molecular biology?
Seen from the perspective of biology, it is hard to escape the feeling that the genetic code somehow essentially is really a good example of a phenomenon in which `memory', `information', and transfer and use of that information is involved (as emphasized by biologists, linguists and even mathematicians such as von Neumann). This does not mean that there are no problems in specifying the exact nature of `reference' or the genetic code's aspect of being `symbols' (not in the cognitivist sense, but in a general semiotic sense). In semiotics, the sign is allowed to `stand for' or refer to its object in a variety of ways that demand strict analysis.
It is important to note that Sarkar nowhere states that the genetic code, or its information, explains nothing! Of course, there is a lot to be said about the conditions (gene regulation) for the transcription and translation of the genetic information to make proteins out of single amino acids, but beside the necessity of revealing these conditions, we still have to know the genetic code. Given the right conditions (such as the identification of a reading frame, of intron/exon boundaries, etc.) one can still predict the amino acid sequence! Sarkar claims that this "is not a particularly revealing explanation" (p. 201), and in this he is right, but the reason he is right is not that there is no informational specification (in the sense defined by Crick 1958) of amino acid sequence in proteins by DNA; the reason is that we of course today know this fact, that is, that given these and these conditions, the DNA contains sequence information about proteins. Sarkar can hardly blame anybody that new discoveries can only be made once, and once made, they can either be falsified (that is the empirical facts must be reinterpreted), or recasted within a quite new frame of understanding, or simply integrated into a current, sound, normal, expanding research programme. Matured and integrated knowledge need not become irrelevant or obsolete.
What then, have we leaned from the Sarkar challenge to biosemiotics? I think that we should take scepticism about the nature of explanations referring to ill-defined terms very seriously. I do think that the most important scepticism -- taken from a purely biological (or natural science) point of view -- regarding `information' in molecular biology is not so much the very existence of a code of some kind; the code may easily be seen as merely a regularity in certain biochemical reactions given by the evolution of the cellular machinery that embodies the dynamics of code-interpretation (to let the biosemiotic language creep in). It is more important, as a molecular biologist to be sceptic against the idea that information (taken as a sequence of bases in DNA) somehow `refer' to something. Because, as chemists, we have never encountered molecules with any cognitive referential capacities. It is only to us, as chemists, that a molecule refer to our knowledge of this and similar molecules. But here enters point that prompt us to go beyond the pure reductionist chemical view: Living beings are historical beings. Their structure bear traces (signs!) of the past, just as their genetic make up confer upon them certain dispositions of future possibility, that is, abstract or general (the category of thirdness) if-then conditions, such as "if I (as a cell) encounters an increased concentration gradient of molecules of lactose, then certain genes will be activated that allows me to feed upon this food source". We can give very reductionist, or better, detailed molecular accounts of each step in the chain of causal interactions that allow this metaphorical expression of the genetically determined dispositions of the E.coli cell to be approximately true. But the details should be embedded in a larger structure, just as a molecule of DNA is embedded in a larger organismic structure, the structure of a cell. At this point the emergent character of the endosemiotic and exosemiotic (sugar-cell interaction) processes is comprehended.
We could ask: What is really the nature of `biological information' at its most basic level? We may not find any single description to reveal the ontological essence of this information, because one can claim that the genetic code, almost (with minor variations) universally shared by all living organisms, is a complex phenomenon in the sense of descriptive complexity, i.e., it requires several non-equivalent descriptions. Three such descriptions are:
(A) The biological description, according to which the genetic code is a special, tRNA-mediated relationship between (i) DNA bases and (ii) amino acids, or more precisely between (i) each one of the 64 possible specific base triplets (codons) in protein-coding regions of DNA (in a reading frame provided by the start codon, the promoter sequence and other regulatory initiation sequences) and (ii) each one of the 20 different amino acids that forms the building blocks of the protein to be synthesized. This code is fully describable at the molecular level as it is materialised in the whole protein synthesis machinery of the cell (DNA, mRNA, tRNA, ribosomes, and a bunch of specific enzymes that catalyze the necessary reactions), although pure chemical descriptions must be supplied with the functional notions of biology, which is why a kind of teleological or final causation seems to play a role in the general description of the whole process. The origin of this ingenious design-character of the code-mediated protein synthesis (and its `proximate', i.e., efficient, formal and material causes) must itself be explained by the `ultimate' causes of the emergence and evolution of living cells with this form of information-controlled metabolism. Therefore, even the pure biological aspect of the genetic code cannot be explained by one single explanation, it requires evolutionary as well as functional accounts (to use Mayr's distinction with respect to biological causation, cf. Mayr 1961).
(B) The biosemiotic description, which in many ways parallels the biological one, but completely changes the focus from the detailed molecular `mechanics' of the biochemistry of life to the evolutionary sign- or information-based properties of the process, which is understood not primarily as a physical process in an isolated cell, but as sign-interpretation in the perspective of the species in its ecosystem. Biosemiotically, the genetic code is an instance of code-duality (as the system of human language, though essentially different from language) between a digital and an analogic mode of existence (of messages of some kind); the digital mode of a species creates a space of semiotic freedom for exploration of other combinations of the pieces of `memorised' experiences with the environment in the evolutionary history of the species. The origin of such a code is, as in biology, explained through a cumulative process of steps from the formation of inside-outside asymmetries (closed surfaces), through proto-communication, to real code-duality and the special kind of future-directedness (or intentionality) of life seen in the `semiotic looping' of organism and environment into each other through the activity of their interfaces (Hoffmeyer 1996, 1998).
(C) The pansemiotic description of the genetic code may not by necessity differ from the biosemiotic, thus being critical about too easy `text'-metaphors for the DNA code, and emphasizing a dynamic and non-determinist view of the genotype-phenotype relation (Merrell 1996, as inspired by the interactionist view of Lewontin et al. 1984). An important thing to note about pansemiotics as an approach to biological phenomena is that these are not necessarily seen as signs emergent from a non-semiotic level, because semiosis is universally present on all levels. So we get the (to my opinion highly disputable) thesis that the semiotic character of the genetic code is based on fundamental molecular semiosis, such as seen in for instance molecular recognition. Ultimately, all physical interactions are of a triadic nature (though some are degenerate triadic relations). I will not dwell upon this idea here.
The point that life is a complex phenomenon makes it amenable to investigations from various approaches. Applying a concerted set of approaches is possibly necessary to attack some of the unsolved riddles in biology, such as the origin of life (and with it, the genetic code), the origin of the eukaryotic cell and the early evolution of multicellular organisms, where reductionist explanations given entirely on the molecular level seem to fail. As the semiotic nature of these processes could be an emergent feature of molecular interactions structures in organisms, biosemiotics could help to explain the supervenient nature of life. This will have relevance to the field between physics and biology called complex adaptive systems, that attempts to understand self-organization and the emergence of higher levels. Important insights from molecular biology about the role of biological information for the possibility of complex self-organization need to be integrated with both thermodynamic and computational approaches to living systems and with biosemiotic foundational research. Important for such an analysis will be a study of the interplay of causal and semiotic aspects of the emergence of complex systems, that is, a study of dynamic, functional, and semiotic causation.
I am very grateful to Sahotra Sarkar, Lucia Santaella, Anne Gammelgaard, Erika Nietzert and Jesper Hoffmeyer for comments and criticism.
 One could make an antirealist counter against the formulation of this hypothetical condition and suggest a weaker condition, namely that it is true that biosemiotics claims that life can be described from a semiotic point of view, but not necessarily true that life "an sich" is or is not semiotic, i.e., to transform the ontological claim to an epistemological one. However, in the writings of what in this paper is identified with biosemiotics (e.g., Sebeok, Hoffmeyer, Jakob and Thure von Uexküll) a basic metaphysical thesis is that living Nature is intrinsically semiotic, there are signs in living nature not simply as an effect of being imputed by us, the observers. This semiotic realism is fundamental to biosemiotics, and it is in no way identical with `naive realism', as it acknowledges that our theories stand in no simple relation to nature, our knowledge is no simple `mirror of nature'. Semiotic realism, as an ontological claim is thus fully compatible with either a critical realism or a more `relaxed' pragmatism concerning the epistemological level.
 I guess we all believe at least a certain amount of what the scientists tell us about DNA and genes and proteins, in this sense we take it to be true they have some reality. This claim about what we believe is not my attempt to sneak in some version of genetic determinism. Nor am I imputing scientific realism (in the sense of traditional philosophy of science) upon our basic confidence in most of genetics and molecular biology (as sciences, not as ideologies); my claim may simply be reformulated to say that that laymen do share with scientists what Arthur Fine have called the core position or "the natural ontological attitude", that is, one accepts established scientific theories (or bodies of knowledge, as it is controversial if molecular biology has much theory in the strict sense) and take the results of scientific investigations for true in the same sense as we trust our senses, on the whole, with regard to the existence and features of everyday objects. (What distinguish realists from various branches of antirealism, then, is what philosophical interpretation one eventually prefers to add to the core). See Fine 1984.
 Such a transformation of concepts from one paradigm (e.g., molecular biology) to another paradigm (e.g., biosemiotics; or the other way round) is hardly possible without a change of meaning. The relation between these two conceptual structures remains to be investigated. Rather than being a competing scientific paradigm, a more likely interpretation of biosemiotics is that it constitutes a part of a whole new theoretical and philosophical footing (not to say foundation) of biology.
 As a molecular system the genetic code has a lot of interesting chemical and biochemical properties that might be studied as such, abstracting from its functional and semiotic properties. This is a general semiotic point: The sign, apart from its relational triadic semiotic properties, may also be studied in its non-semiotic physical aspects. Compare Johansen 1993.
 terminologically, it might have been more appropriate, instead of "biosemiotics", to call the attempts to describe biological processes and entities in semiotic terms "semiobiology" (cf. Kawade, this volume), thus preserving the term biosemiotics for Merrell's programme of looking at semiosis as a living process. The problem with the term semiobiology, however, is that it makes the field seem to be a special parcel of biology, while it is rather an alternative kind of biology, or , in another interpretation of biosemiotics, an alternative foundational philosophy of biology.
 perhaps I should add here that this is neither what Stjernfelt (cited above) nor other biosemioticians would imply, because we acknowledge the existence of crucial differences in complexity of the semiotic process when we deal with e.g., recognition and memory in molecules, cells, brains and societies.
 I will only mention here that the terminological explication of the term (sequential) information in Crick 1958 (as a term for biological specificity) is not coincident with the introduction of the very concept. First, as emphasized by Crick (interviewed in Judson 1979, see also Crick 1970), these ideas were around by at least molecular biologists in the late 1950s. Second, as mentioned by Sarkar, the idea of a `code script' dates back at least to the influential lectures by Erwin Schrödinger in 1943, published in his famous little book (Schrödinger 1944). Third, the very idea of genetic determination or inheritance as some kind of information transfer -- even without the term information -- dates longer back in the history of biology. Thus Ernst Mayr writes that "The coded `genetic program,' modified from generation to generation and incorporating historical information, became a familiar and powerful concept. A history of the antecedents of this concept as not yet been written. Hering (1879) and Semon's (1904) concept of the mneme, although originally introduced to bolster the idea of an inheritance of acquired characters, is definitely in this tradition. Even closer is His's comparison (1901) of the activity of the germ plasm as messages, the consequences of which can be far more complex than the simple message. Nevertheless, the concept of the genetic program as an unmoved mover (Delbrück 1971) was so novel that nobody had come even close to it prior to the 1940s." (Mayr 1982: 824). John Maynard Smith mentions the German biologist August Weismann, writing in the end of the 19th century, as "one of the first people to see that what matters in heredity is a flow not of matter or energy but of information." (Maynard Smith 1986: 10).
 that is, sequential information, as explicitly stated by Crick 1970. In that article, he emphasizes the negative character of the central dogma (saying that certain kinds of possible transfer of sequence information, those from proteins, did not exists) as distinct from the positive "sequence hypothesis", also of the 1958 paper, saying that overall transfer of sequence nformation from nucleic acids to proteins did exist.
 which may explain a part of its fame as a molecular grounding of neo-Darwinism against any sort of Lamarckism. However, as Sarkar notes, the inheritance of acquired characters is a complex separate issue, and should not be conflated with the specific question of direction of transfer of sequence information between DNA and protein.
 Judson (1979:336) compares the central dogma to to Einstein's e=mc2 in deserving the same kind of general currency.
 One may sense here the philosopher's preference for not just specific kinds of actual working ways of making explanations in science, but also for a specific picture of explanation that these may allude to. A possible general critique of Sarkar's approach is to say that the premise of the critique is a certain preferred preconception of the nature of explanations, and not empirical cases of actual misleadnings (in contemporary biology) of some of the unlucky terms. However, that would not be quite fair, as Sarkar has a case, namely an early mistaken idea of Crick and co-workers from the mid-fifties (related to the attempts to break the genetic code, and inspired by Gammow) about the nature of a `comma-free code'; this idea was not motivated or justified by experimental work, but only by formal or abstract considerations of information coding economy. These early attempts "to play the game of solving the coding problem formally" (Sarkar 1996: p.191) proved to be mistaken. However, Sarkar has no cases of failures in contemporary molecular biology due to the concept of information.
 Even though Sarkar (personal communication) emphasizes that he carefully avoid saying that the informational interlude was a mistake in any sense.
 this summery of Sarkar's critique abbreviates perhaps too much of the technical details about the specific notion of "physicalist reductionst explanation" that Sarkar thinks is characteristic of molecular biology. However, there is in this part of his claims a deep problem , because it is not evident that, given that an explanatory factor in an explanation has a physical warrants (i.e., is obtained formally or informally from physical theory or is recognized as mechanisms from physical experiments, Sarkar 1996: 213), how this property of `physicalism' should contribute to the explanation as being reductionist. This part of Sarkar's analysis should be contrasted (more in detail than possible here) with the one given by Harold Kincaid (1990) in which he argues against the idea that advances in molecular biology should support the claim the biology is reducible to chemistry. Kincaid's arguments is based on (1) the multiple realizability of the predicates of molecular biology (which may not hit Sarkar's different notion of reductionism); (2) their realization is context-sensitive; and (3) that explanations in molecular biology often presuppose biological facts rather than eliminates them.
 One could ask "Why should a critique against informational concepts be necessarily also a critique against semiotics?" (cf. Lucia Santaella: "Life: Information processing or Semiosis? Comments on Claus Emmeche's paper on Sarkar's Challenge to Biosemiotics"; presented at the "Seminar for advanced studies in Communication and Semiotics: Biosemiotics and Cognitive Semiotics" in Sao Paolo, August 19-21, 1998). I do not think the failure of informational terminology to work as a coherent theory of molecular biology implies a failure of biosemiotics as such, and I agree that "If informational concepts are quasi-semiotic concepts, a critique against them might be a motivation for the development of more scientific concepts, that is, of fully semiotic concepts" (L. Santaella, ibid.). I am thankful to Lucia Santaella for these comments, and I hope to give a more detailed answer in a subsequent paper.
 Bateson comes out as a full blown semiotician, and the same does Crick the reductionist when re-interpreted through the glasses of Peirce. One, two, three, we have a triadic relation of representation! No mystery!
 I am aware that it is controversial to speak simply of "the" concept of function, and that a whole tradition in the philosophy of biology has been disputing about a precise definition of functions and teleological explanations (cf. Emmeche 1990; an entry to recent literature is Schaffner 1993). The notion of biological functionality must be explained before an analysis of its relation to biosemiosis. In this paper I will simply allude to the intuitive sense of function as some part or process of an organized system that plays a specific role in the system and eventually contributes to maintain the system. Any account of the notion of function in the science of biology should be able to distinguish between the research process of identifying `the true' function of a part (e.g., of the heart) and the research process of identifying a causal history (e.g., evolution by natural selection and ontogenetic development) of the part or process that realizes a given function. The true function can be discovered before the full causal history is known. Thus, it is plausible that the notion of function may be explained without reference to the theory of evolution. The theory of evolution may presuppose functional notions.
 Let me also just mention that only one of the two alternatives to the notion of sequence information that Sarkar mention is purely physicalist (to return to the old notion of biological specificity and develop it further), the other is a suggestion of elaborating a new informational account broader than the sequence notion, and along the lines of S.A. Shapiro. The interpretation of this possibility may prove to have much biosemiotic interest, and may be a subject for a later paper.
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