A Brief History of Code Biology

by Marcello Barbieri

In 1909 Wilhelm Johannsen proposed that the molecules that carry hereditary information are different from those that are responsible for the structure of the cell and in order to distinguish those two categories he called them genotype and phenotype (Johannsen 1909).

At the beginning this dualism was rejected because it was thought that proteins account for both heredity and metabolism, but in the 1950s it became clear that genes and proteins have fundamentally different functions and the genotype-phenotype duality became universally accepted. On top of that, the computer gave an immediate legitimacy to that duality because the distinction between software and hardware is equivalent to the distinction between genotype and phenotype and the cell has been described ever since as a biological computer made of biological software and biological hardware.

The problem with this model is that a computer does not generate its own codes – it receives them from a human operator, i.e. from an external agent – whereas the genetic code is generated inside the cell from an internal agent. This is why in 1981 I proposed that the cell is not a duality of genotype and phenotype but a trinity of genotype, phenotype and ribotype, where the ribotype is the ribonucleoprotein system of the cell that makes proteins according to the rules of the genetic code (Barbieri 1981).

The ribotype is usually regarded as an intermediary between genotype and phenotype but the crucial point is that it is the ribotype that defines the genes and that fabricates the proteins. This is the third party that makes of every living cell a trinity of genotype, phenotype and ribotype. The genotype is the seat of heredity, the phenotype is the seat of metabolism and the ribotype is the seat of the genetic code.

The semantic theory of evolution

After the publication of the ribotype theory I went back to an historical fact that I could not understand: the fact that the genetic code appeared on Earth at the origin of life and no other code arrived until the codes of culture, almost four billion years later. To me this was incomprehensible because I could not see why the mechanism that gave origin to the genetic code stopped working for billions of years and came back again in human culture. At that time this conclusion seemed inevitable but in reality there was an argument that was suggesting otherwise.

The mechanisms of evolution have been one of the most controversial issues in biology and the great debate about them culminated, in the 1930s and 40s, in the Modern Synthesis, the view of life according to which natural selection is the sole mechanism of evolution. But where does natural selection come from?

We know that the copying of the genes is the elementary act that leads to heredity, but when the process of copying is repeated indefinitely another phenomenon comes into being. Copying mistakes become inevitable and in a world of limited resources not all changes can survive and a process of selection is bound to take place. Molecular copying, in other words, leads to heredity, and the indefinite repetition of molecular copying in a world of limited resources leads to natural selection. This is how natural selection came into being. Molecular copying started it and molecular copying has perpetuated it ever since. Which means that natural selection would be the sole mechanism of evolution if molecular copying were the sole fundamental mechanism of life.

The discovery of the genetic code, however, has proved that there are two molecular mechanisms at the basis of life, the copying of the genes and the coding of proteins. Life, in other words, is not based on copying alone. It is based on copying and coding, and this implies that evolution took place by two distinct mechanisms. More precisely, the existence of copying and coding at the molecular level implies that there are two distinct types of evolutionary change: evolution by natural selection, based on copying, and evolution by natural conventions, based on coding.

This idea was published in ‘The Semantic Theory of Evolution’ (Barbieri 1985) a book which explicitly proposed that natural conventions appeared throughout the whole history of life and not just at the beginning and at the end of it. At that time there was no evidence in favor of this conclusion but eventually the discoveries of new codes started appearing and a few years later I could describe some of them in ‘The Organic Codes’ (Barbieri 2003).

A book review

In March 2001 I sent to Thomas Sebeok a draft of ‘The Organic Codes’, and a few weeks later he invited me to review a special issue of Semiotica that was dedicated to the coming of age of Biosemiotics and to celebrating Jakob von Uexküll as the chief architect of that new discipline (Kull 2001). I accepted and I acknowledged that the two main points of the special issue – the making of Biosemiotics and the recovery of Jakob von Uexküll from oblivion – came out with clarity and force, and were a success.

There was however a third point that I did not agree with. It was the idea that Biosemiotics was the crowning achievement of the idealistic tradition that goes back to Goethe, Schelling, Saint-Hilaire, von Baer and Driesch, a ‘vitalistic’ approach that has been the historical antagonist of the ‘mechanistic’ approach of Galileo, Newton, Lamarck, Darwin and Mendel. I fully agreed with the project of introducing meaning in biology, but I argued that vitalism was not the right approach.

I sent my review to Sebeok in August 2001 saying that I had not been able to write an impartial report and therefore that I would not be surprised if he turned it down. To my surprise, however, Sebeok accepted it and to me that meant that in principle he was not against the mechanistic approach. His implicit message, in my opinion, was that vitalism is not compulsory in Biosemiotics. A mechanistic approach to meaning cannot be ruled out, and people who are proposing it should be listened to. Sebeok died a few months later, on December 21, 2001, and that implicit message was probably his last contribution to Biosemiotics. Personally, I took it as an invitation to join the biosemiotic community and I decided to give it a try.

The decisive change came in 2004, at the fourth Gathering in Biosemiotics organized by Anton Markoš in Prague. Jesper Hoffmeyer, Claus Emmeche, Kalevi Kull, Anton Markoš and myself decided that what was uniting us – the introduction of meaning in biology – was more important than our divisions, and we should make that visible. Up until then, I had been referring to the study of biological meaning as Semantic Biology, whereas Markoš had been calling it Biohermeneuthics, but we accepted to give up our favourite names and to adopt the term Biosemiotics that Sebeok had been campaigning for with so much passion and vigour. I also proposed to start a new journal and a few years later I became the founder and first editor-in-chief of the Springer journal Biosemiotics.

My hope was to gradually turn Biosemiotics into an increasingly scientific field but there was an obstacle on the way: most biosemioticians were supporting the idea that all living beings, including single cells, are capable of interpreting the world.

Interpretation at the cellular level

Free-living single cells (bacteria and protozoa) make up the great majority of the living world, and countless studies have shown that they have a context-dependent behaviour in the sense that they can react in different ways to different environmental conditions. Thomas Sebeok argued that a context-dependent behaviour comes from an interpretation of the environment and concluded from this that all living systems, from bacteria to animals, have the ability to interpret the world. In reality, the behaviour of bacteria and protozoa is accounted far more naturally by the combination of two or more organic codes. A context- dependent behaviour means a context-dependent expression of genes, and this is obtained simply by associating a signal transduction code to the genetic code. It takes only two context-free codes, in other words, to produce a context-dependent behaviour.

The experimental results, in short, tell us that coding and decoding is all that goes on at the cellular level, and yet the biosemioticians were claiming that interpretation does take place at that level because decoding can be regarded as a form of interpretation. There are many examples of this trick in the literature, and these are two of them.

(a) In the paper “What Does It Take to Produce Interpretation?”, Søren Brier and Cliff Joslyn (2013) proposed to solve the problem in this way: “…we can identify interpretation in general as any process which encounters a sign and takes it for its meaning in virtue of some code … Thus a ribosome is an interpreter. And the right amino acid is its interpretation of some codon.”

(b) In the paper “Anticipatory Functions, Digital-Analog forms and Biosemiotics”, Argyris Arnellos, Luis Emilio Bruni, Charbel Niño El-Hani and John Collier (2012) claimed that signal transduction is a process of interpretation because “… receptors act as interpreting systems”.

The conclusion was that interpretation does take place in the cell because we can define it in terms of processes that are present at the cellular level.

The birth of Code Biology

As editor-in-chief of Biosemiotics I was committed to publish contributions from all schools of Biosemiotics, including those which claimed that ribosomes interpret the messenger-RNAs. The codons of a messenger-RNA are recognized by the complementary anticodons of the transfer-RNAs and saying that a ribosome is interpreting a messenger RNA is like saying that a key is interpreting a lock in order to open a door.

I realized that my editorial commitment was becoming incompatible with a scientific approach and the sole solution therefore was for me to resign from the journal. That decision however was pre-emptied by an unexpected event: at the 2012 Gathering in Biosemiotics that took place in Tartu I was expelled from the governing board of the biosemiotic society with a public vote of the general assembly.

That put an end to my project to turn Biosemiotics into a scientific field and I went back to my previous field but with a difference. The term Semantic Biology was replaced by Code Biology because it is primarily codes that give us the experimental proof that meaning exists in living systems.

This is why at the end of 2012 I resigned as editor-in-chief of Biosemiotics and together with a few colleagues founded the International Society of Code Biology. We also decided to leave no doubt about the scientific nature of our project and to this end we explicitly wrote in the constitution of the new society that “Code Biology is the study of all codes of life with the standard methods of science”.

Code Biology, in conclusion, started in 1985 with the name of Semantic Biology and the publication of its major ideas, but was officially established with its present name in 2012, when the International Society of Code Biology was founded.


Arnellos A, Bruni LE, El-Hani CN and Collier J (2012) Anticipatory Functions, Digital-Analog forms and Biosemiotics. Biosemiotics, 5, 331-367.

Barbieri M (1981) The Ribotype Theory on the Origin of Life. Journal of Theoretical Biology, 91, 545-601.

Barbieri M (1985) The Semantic Theory of Evolution. Harwood Academic Publishers, London & New York. Reissued in 2020 in the Routledge Library Editions, https://doi.org/10.1201/9780429290039.

Barbieri M (2003) The Organic Codes. An Introduction to Semantic Biology. Cambridge University Press, Cambridge, UK.

Brier S and Joslyn C (2013) What Does It Take to Produce Interpretation? Informational, Peircean and Code-Semiotic Views on Biosemiotics. Biosemiotics, 6, 143-159.

Johannsen W (1909) Elemente der exacten Erblichkeitslehre. Gustav Fischer, Jena.

Kull K (ed) (2001) Jakob von Uexküll: A Paradigm for Biology and Semiotics. Semiotica, 134 (1/4), Mouton de Gruyter, Berlin.