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Biosemiotics is the idea that life is based on semiosis, i.e., on signs and codes. This idea has been strongly suggested by the discovery of the genetic code, but so far it has made little impact in the scientific world and is largely regarded as a philosophy rather than a science. The main reason for this is that modern biology assumes that signs and meanings do not exist at the molecular level, and that the genetic code was not followed by any other organic code for almost four billion years, which implies that it was an utterly isolated exception in the history of life. These ideas have effectively ruled out the existence of semiosis in the organic world, and yet there are experimental facts against all of them. If we look at the evidence of life without the preconditions of the present paradigm, we discover that semiosis is there, in every single cell, and that it has been there since the very beginning. This is what biosemiotics is really about. It is not a philosophy. It is a new scientific paradigm that is rigorously based on experimental facts. Biosemiotics claims that the genetic code (1) is a real code and (2) has been the first of a long series of organic codes that have shaped the history of life on our planet. The reality of the genetic code and the existence of other organic codes imply that life is based on two fundamental processes--copying and coding--and this in turn implies that evolution took place by two distinct mechanisms, i.e., by natural selection (based on copying) and by natural conventions (based on coding). It also implies that the copying of genes works on individual molecules, whereas the coding of proteins operates on collections of molecules, which means that different mechanisms of evolution exist at different levels of organization. This review intends to underline the scientific nature of biosemiotics, and to this purpose, it aims to prove (1) that the cell is a real semiotic system, (2) that the genetic code is a real code, (3) that evolution took place by natural selection and by natural conventions, and (4) that it was natural conventions, i.e., organic codes, that gave origin to the great novelties of macroevolution. Biological semiosis, in other words, is a scientific reality because the codes of life are experimental realities. The time has come, therefore, to acknowledge this fact of life, even if that means abandoning the present theoretical framework in favor of a more general one where biology and semiotics finally come together and become biosemiotics.
Biosemiotics: a new understanding of life
Marcello Barbieri
Received: 19 September 2007 / Revised: 16 February 2008 / Accepted: 19 February 2008
Springer-Verlag 2008
Abstract Biosemiotics is the idea that life is based on
semiosis, i.e., on signs and codes. This idea has been
strongly suggested by the discovery of the genetic code, but
so far it has made little impact in the scientific world and is
largely regarded as a philosophy rather than a science. The
main reason for this is that modern biology assum es that
signs and meanings do not exist at the molecular level, and
that the genetic code was not followed by any other organic
code for almost four billion years, which implies that it was
an utterly isolated exception in the history of life. These
ideas have effectively ruled out the existence of semiosis in
the organic world, and yet there are experimental facts
against all of them. If we look at the evidence of life
without the preconditions of the present paradigm, we
discover that semiosis is there, in every single cell, and that
it has been there since the very beginning. This is what
biosemiotics is really about. It is not a philosophy. It is a
new scientific paradigm that is rigorously based on
experimental facts. Biosemiotics claims that the ge netic
code (1) is a real code and (2) has been the first of a long
series of organic codes that have shaped the history of life
on our planet. The reality of the genetic code and the
existence of other organic codes imply that life is based on
two fundamental processescopying and coding and this
in turn implies that evolution took place by two distinct
mechanisms, i.e., by natural selection (based on copying)
and by natural conventions (based on coding). It also
implies that the copying of genes works on individual
molecules, whereas the coding of proteins operates on
collections of molecules, which means that different
mechanisms of evolution exist at different levels of
organization. This review intends to underline the scientific
nature of biosemiotics, and to this purpose, it aims to prove
(1) that the cell is a real semiotic system, (2) that the genetic
code is a real code, (3) that evolution took place by natural
selection and by natural conventions, and (4) that it was
natural conventions, i.e., organic codes, that gave origin to
the great novelties of macroevolution. Biological semiosis,
in other words, is a scientific reality because the codes of
life are experimental realities. The time has come, therefore,
to acknowledge this fact of life, even if that means
abandoning the present theoretical framework in favor of
a more general one where biology and semiotics finally
come together and become biosemiotics.
Keywords Biosemiotics
Semiotics is the study of signs , and biosemiotics can be
defined, therefore, as the study of signs in living systems.
This is the literal definition of the discipline, a version that
can be referred to as sign-based biosemiotics because it is
explicitly based on the concept of sign. Biosemiotics,
however, can also be defined as the study of codes in
living systems, a version that is referred to as code-based
biosemiotics. There have been historical disputes between
the two versions but, as we w ill see, they are not
incompatible, and both share the idea that every living
creature is a semiotic system, i.e., that semiosis (the
production of signs) is fundamental to life. The evidence
for this conclusion comes primarily from the genetic code,
DOI 10.1007/s00114-008-0368-x
M. Barbieri (*)
Dipartimento di Morfologia ed Embriologia,
Via Fossato di Mortara 64,
44100 Ferrara, Italy
but modern biology has never accepted it. The discovery of
the genetic code has been universally recognized as one of
the greatest scientific breakthroughs of all times but not as
proof that semiosis exists at the molecular level. Modern
biology has not acceptedlet us repeat thisthat the
existence of the genetic code implies that every cell is a
semiotic system. And this is no accident. The rejection of
the semiotic nature of life has been, and continues to be,
extremely widespread because it is the logical consequence
of at least three concepts that lie at the very heart of modern
1. The first is the model that describes the cell as a duality
of genotype and phenotype, i.e., as a biological
computer where genes provide the software and
proteins the hardware. The crucial point is that a
computer ha s codes but is not a semiotic system
because its codes come from a codemaker, which is
outside it. This makes it legitimate to say that cells too
can have a code without being semiotic systems. All we
need, for that conclusion, is the idea that the genetic
code was assembled by natural selection, i.e., by a
codemaker that is outside the cell just as the human
mind is outside the computer.
2. The second basic concept is physicalism, the doctrine
that everything in life, including signs and codes, is
ultimately reducible to physical quantities. This implies
that the genetic code is not a real code but a linguistic
expression that biologists have adopted simply because
it was intuitively appealing. Deep down, according to
this view, the geneti c code is but a metaphor because all
its features must be completely accounted for by
physical quantities.
3. The third basic concept of modern biology is the belief
that every biological novelty has been brought into
existence by natural selection. The codes, be they
organic or mental, are outstanding phenomena, but as
long as they are not a mechanism of evolution, they do
not account for anything fundamentally new. This
conclusion is reinforced by the fact that the genetic
code appeared at the origin of life, whereas the codes of
culture arrived almost four billion years later. They came
into being respectively at the beginning and at the end of
lifes history and are considered, therefore, as utterly
exceptional phenomena, not as ordinary biological
The genotypephenotype model, physicalism, and natural
selection are the three pillars of modern biology, and they are
totally alien to the idea that semiosis is fundamental to life.
This idea, therefore, can become part of biology only if we
prove that all the above concepts can be replaced by more
general ones. That is what biosemiotics is really about. It is
about a new biological paradigm that gives us (1) a new
model of the cell, (2) a real alternative to physicalism, and
(3) a new mechanism of evolution. These are the great
novelties of biosemiotics, and this review is dedicated almost
exclusively to illustrating them. More precisely, Part 1 is
dedicated to the semiotic structure of the cell, Part 2 to the
nature of information and meaning, Part 3 to the organic
codes, and Part 4 to the mechanisms of evolution, whereas
Part 5 will give a brief overview of the present state of
Part 1: the semiotic structure of the cell
The code model of semiosis
Semiotics is usually referred to as the study of signs (from
the Greek semeion = sign), but this definition is too
restrictive because signs are always associated with other
entities. A sign, to start with, is always linked to a meaning.
As living beings, we have a built-in drive to make sense of
the world, to give meanings to things, and when we give a
meaning to something, that something becomes a sign for
us. Sign and meaning, in other words, cannot be taken apart
because they are the two sides of the same coin. Semiotics,
therefore, is not just the study of signs; it is the study of
signs and meanings together. The result is that a system of
signs, i.e., a semiotic system, is always made of at least two
distinct worlds: a world of entities that we call signs and a
world of entities that represent their meanings.
The link between sign and meaning, in turn, calls
attention to a third entity, i.e., to their relationship. A sign
is a sign only when it stands for something that is other than
itself, and this otherness implies at least some degree of
independence. It means that there is no deterministic
relationsh ip between sign and meaning. Different lan-
guages, for example, give different names to the same
object precisely because there is no necessary connection
between names and objects. A semiotic system, therefore, is
not any combination of two disti nct worlds. It is a
combination of two worlds between which there is no
necessary link, and this has an extraordinary consequence.
It implies that a bridge between the two worlds can be
established only by convent ional rules, i.e., by the rules of a
code. This is what qualifies the semi otic systems, what
makes them different from everything else: a semiotic
system is a system made of two independent worlds that are
connected by the conventional rules of a code. A semiotic
system, in conclusion, is necessarily made of at least three
distinct entities: signs , meanings, and code.
Here, at last, we have a definition where it is stated
explicitly that a code is an essential component of a
semiotic system. It is the rules of a code that create a
correspondence between signs and meanings, and we can
say, therefore, that an act of semiosis is always an act of
coding, i.e., it is always a convention. More precisely, we
can say that an elementary act of semiosis is a triad of sign,
meaning, and convention, whereas a semiotic system is a
whole set of signs and meanings that are linked together by
all the various conventions that make up a code.
Signs, meanings, and conventions, however, do not
come into existence of their own. There is always an
agent that produces them, and that agent can be referred to
as a codemaker because it is always an act of coding that
gives origin to semiosis. In the case of culture, for example,
the codemaker is the human mind since it is the mind that
produces the mental objects that we call signs and mean-
ings and the conventions that link them together. We come
in this way to a general conclusion that can be referred to as
the code model of semiosis: a semiotic system is a triad of
signs, meanings and code that are all produced by the same
agent, i.e., by the same codemaker.
This conclusion is highly relevant to biology because it
tells us precisely what we need to prove in order to show
that the cell is a semiotic system. We need to prove that in
every living cell there are four distinct entities: signs,
meanings, code and codemaker.
The molecules of life
Modern biology is based on three extraordinary experi-
mental facts: (1) the discovery that most biological
structures and functions are ultimately due to proteins, (2)
the discovery that the hereditary instructions for making
proteins are carried by strings of nucleotides called genes,
and (3) the discovery that genes are translated into proteins
by a universal set of rules, which has become known as the
genetic code.
These discoveries have confirmed that genes and
proteins are the key molecules of life but have also revealed
something totally unexpected about them. They have
shown t hat g ene s and proteins d iffer from all other
molecules not only because of their size, shape, or chemical
composition but primarily because they are produced in a
totally different way. In the inorganic world, the structure of
molecules is determined by the bonds that exist between
their atoms, i.e., by internal factors. In living systems,
instead, genes are built by molecular machines which
physically stick their nucleotides together following the
order of a template which is external to the growing
molecule. In a similar way, proteins are made by molecular
machines which bind amino acids in the order prescribed
by an external template of nucleotides.
Genes and proteins, in short, are assembled by molecular
robots on the basis of outside instructio ns. They are
manufactured molecules, as different from ordinary mole-
cules as artificial objects are from natural ones. Indeed, if
we accept the commonsense view that molecules are
natural when their structure is determined from within and
artificial when it is determined from without, then genes and
proteins can truly be referred to as artificial molecules, as
artifacts made by molecular machines. This in turn implies
that all biological objects are artifacts, and we arrive at the
general conclusion that life is artifact-making.
The discovery that genes and proteins are manufactured
molecules has direct implications for the origin of life
because it tells us that primitive molecular machines came
into existence long before the origin of the first cells. The
simplest molecular machines we can think of are molecules
that could join other molecules together by chemical bonds,
and for this reason we may call them bondmakers. Some
could form bonds between amino acids, some between
nucleotides, others between sugars, and so on. It has been
shown, for example, that short pieces of ribosomal RNA
have the ability to form peptide bonds, so it is possible that
the first bondmakers were RNA molecules of small or
medium-size molecular weights. Among the various types
of bondmakers, furthermore, some developed the ability to
join nucleotides t ogether in the order provided by a
template. Those bondmakers started mak ing copies of
nucleic acids, so we can call them copymakers.
In the history of life, molecular copying came into being
when the first copymakers appeared on the primitive Earth
and started copying nucleic acids. This implies that natural
nucleic acids had already been formed by spontaneous
reactions on our planet, but that was no guarantee of
evolution. Only the copying of genes could ensure their
survival and have long-term effects, so it was really the
arrival of copymaking that set in motion the extraordinary
chain of processes that we call evolution. The first Major
Transition o f the history of life (Maynard Smith and
Szathmáry 1995) is generally descri bed as the origin of
genes, but it seems more accurate to say that it was the
origin of molecular copying, or the origin of copymakers,
the first molecular machines that started multiplying nucleic
acids by making copies of them.
The genetic code
Proteins are the key building blocks of all living structures,
as well as the engines of countless reactions that go on
within those structures. For all their extraordinary versatility,
however, there is one thing they cannot do. Unlike genes,
they cannot be their own templates. It is simply not possible
to make proteins by copying other proteins. The transition
from natural to manufactured molecules, therefore, was
relatively simple for genes but much more complex for
proteins. Manufactured genes could be made simply by
copying natural genes, and all that was required to that
purpose w ere molecules which had a polymerase-like
activity. Manufactured proteins, instead, could not be made
by copying, and yet the information to make them had to
come from molecules that can be copied because only those
molecules can be inherited. The information for manufactur-
ing proteins, therefore, had to come from genes, so it was
necessary to bring together a carrier of genetic information (a
messenger RNA), a peptide-bondmaker (a piece of ribosom-
al RNA), and molecules that could carry both nucleotides
and amino acids (the transfer RNAs). The first protein-
makers, in short, had to bring together three different types
of molecules (messenger, ribosomal, and transfer RNAs),
and were, therefore, much more complex than copymakers.
The outstanding feature of the prote in-makers, however,
was not the number of components. It was the ability to
ensure a s pecific correspondence between genes and
proteins, because without it there would be no biological
speci ficity, and without specificity there would be no
heredity and no reproduction. Life, as we know it, simply
would not exist without a specific correspondence between
genes and proteins.
Such a correspondence would be automatically ensured
if the bridge between genes and proteins could have been
determined by stereochemistry, as one of the earliest
models suggested, but that is not what happens in Nature.
The bridge is always provided by molecules of transfer
RNA, first called adaptors, that have two recognition sites:
one for a group of three nucleotides (a codon) and another
for an amino acid. In this case, a specific correspondence
could still be guaranteed automatically if one recognition
site could determine the other, but again that is not what
happens. The two recognition sites of the adaptors are
physically separated in space and are chemically indepen-
dent. There simply is no necessary link between codons and
amino acids, and a specific correspondence between them
can only be the result of conventional rules. Only a real
code, in short, could guarantee biological specificity, and
this means that in no way the genetic code can be dismissed
as a linguistic metaphor.
Protein synthesis arose, therefore, from the parallel
evolutions of the translation apparatus and of the genetic
code, and the final machine was a code-and-template-
dependent-protein-maker or, more simply, a codemaker.
The second Major Transition of the history of life is
generally described as the origin of proteins, but it would
be more accurate to say that it was the origin of
codemaking, or the origin of codemakers, the first
molecular machines that discovered molecular coding and
started populating the Earth with codified proteins.
The cell as a trinity
The idea that life is based on genes and proteins is often
expressed by saying that every living system is a duality of
genotype and phenotype. This model was proposed by
Wilhelm Johannsen in 1909, but was accepted only in the
1940s and 1950s when molecular biology discovered that
genes are chemically different from proteins and, above all,
when it became clear that genes carry linear infor mation,
whereas proteins function by their three-dimensional
structures. The genotypephenotype duality is, therefore, a
dichotomy that divides not only two different biological
functions (heredity and met abolism) but also two different
natural entities (information and energy). It is the simplest
and most general way of defining a living system and has
become the foundational paradigm of modern biology, the
scheme that transformed the energy-based biology of the
19th century into the information-based biology of the 20th.
In the 1950s and 1960s, however, the study of protein
synthesis revealed that genes and proteins are not formed
spontaneously in the cell but are manufactured by a system
of molecular machines based on RNAs. In 1981, the
components of this manufacturing system were called
ribosoids, and the syst em itself was given the collective
name of ribotype (Barbieri 1981, 1985). The cell was
described in this way as a structure made of genes, proteins,
and ribosoids, i.e., as a trinity of genotype, phenotype, and
This model is based on the conclusion that the ribotype
had a historical priority over genotype and phenotype.
Spontaneous genes and spontaneous proteins did appear on
the primitive Earth but could not give origin to cells
because they did not have biological specificity. They gave
origin to copymakers and codemakers, and it was these
molecular machines made of ribosoids that evolved into the
first cells.
The RNAs and the proteins that appeared spontaneously
on the primitive Earth produced a wide variety of ribosoids,
some of which were synthetizing ribosoids, whereas others
were ribogenes, and others were riboproteins (or ribo-
zymes). The systems produced by the combination of all
these mol ecules, therefore, had a ribotype, a ribogenotype,
and a ribophenotype. Eventually, evolution replaced the
ribogenes with genes and the riboproteins with proteins, but
the synthetizing ribosoids of the ribotype have never been
replaced. This shows not only that the ribotype is a distinct
category of the cell but also that it is a category without
which the cell simply cannot exist.
The ribosoids of the ribotype are the oldest phylogenetic
molecules that exist on Earth (Woese
2000), and they
firmly remain at the heart of every living cell. Genes,
proteins, and ribosoids are all manufactured molecules, but
only ribosoids can be also makers of those molecules. This
concept can perhaps be illustrated by comparing the cell to
a city where proteins are the objects, genes are the
instructions, and ribosoids are the maker s of both objects
and instructions, i.e., the inhabitants of the city.
It is an experiment al fact, at any rate, that every cell
contains a system of RNAs and ribonucleoproteins that
makes proteins according to the rules of a code, and that
system ca n be described, therefore, as a code -and-
template-dependent-protein-maker or more simply as a
codemaker. That 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 codemaker of
the cell, the seat of the genetic code.
The defining feature of signs and meanings
A semiotic system is made of signs, meanings, code, and
codemaker, and we know that there is a genetic code in
protein synthesis. We also know that proteins are made by a
system of ribonucleoproteins that is the physical seat of the
genetic code and functions, therefore, as the codemaker of
the cell. This tells us that every living cell does have a
genetic code and a codemaker. But what about the other
two entities? Can we say that there are also signs and
meanings at the molecular level? Can these entities exist in
the cell? In order to answer this question, let us examine
first the traditional signs and meanings of culture and see if
they have a qualifying feature that can be extended to the
molecular level.
The signs and meanings that we are familiar with are
often the mental representations of objects or events of the
physical world. A sign, for example, can be a spoken word,
and its meaning can be a mental image. The mental image
of an object is normally evoked by different words in
different languages, and this clearly shows that mental
sounds and mental images are separable. When they are
separated, however, they no longer function as signs and
meanings. To a non-English speaker, for example, a word
like twitch may have no linguistic meaning, and in this
case, it would be just a sound not a sign. There is no
contradiction, therefore, in saying that signs and meaning
are distinct mental objects, and that they cannot be taken
apart because when they are taken apart, they simply stop
functioning as signs and meanings.
This makes us understand an extremely important
feature of semiosis. It tells us that a mental sign, or a
mental meaning, is never an intrinsic property of a mental
object. It is something that the mind can give to a mental
object and that the mind can take away from it.
To this conclusion, one could object that terms like
mental signs and mental objects are a clear case of
mentalism, and that this is no longer the received view,
today. The important point, however, is that the conclusion
remains valid even if we accept that the sounds and images
of our perceptions are just the results of neuron firings, and
that the mind is but a product of the brain. Even in this
case, the link between the neuron firings that produce the
signs and the meanings of any language is based on the
rules of a code and are totally dependent upon the agent of
that code, i.e., upon the codemaker of the system.
Signs and meanings simply do not exist without a
codemaker and outside a codem aking process. The code-
maker is the agent of semiosis, wher eas signs and meanings
are its instruments. We conclude, therefore, that signs and
meanings are totally dependent on codemaking, i.e., they
are codemaker-dependent entities. This is the qualifying
feature that we were looking for because it is completely
general and can be applied to all systems. We can say,
therefore, that signs and meanings exist at the molecular
level, and in particular, in protein synthesis, only if we
prove that in prote in synthesis t here are co demaker-
dependent entities.
The sequences of genes and proteins
All biochemistry textbooks tell us that there is a genetic
code in protein synthesis, but none of them mentions the
existence of signs and meanings. At first sight, in fact, these
entities do not seem to exist at the molecular level. The
translation apparatus can be regarded as a codemaker
because it is the seat of the code that creates a correspon-
dence between genes and proteins, but these molecules
appear to have only objective chemical properties, not the
codemaker-dependent properties that define signs and
meanings. A messenger RNA, for example, appears to be
a unique and objective sequence of molecules, but let us
take a closer look.
A messenger RNA is certainly a unique and objective
chain of nucleo tides, but in no way is it a unique sequence
of codons because different codemakers could scan it in
different ways. If the nucleotides were scanned two-by-two,
for example, the sequence of codons would be totally
different. The same chain of nucleotides, in other words,
can give origin to many sequences of codons, and it is
always the codemaker that determines the sequenc e because
it is the codem aker that defines the codons. A linear
sequence of codons, in short, does not exist without a
codemaker and outside a codemaking process. It is totally
dependent on codemaking and is, therefore, a codemaker-
dependent entity, which is precisely what a sign is.
In the same way, the linear sequence of amino acids that
is produced by the translation apparatus is also a code-
maker-dependent entity because only a codemaker can
produce it. Any spontaneous assembly of amino acids
would not make linear chains, and above all, it would not
arrange the amino acids in a specific order. Specific linear
sequences of amino acids can be produced only by
codemakers, but different codemakers would arrange the
amino acids in different ways, which shows that the
sequence of a protein is only one of the many possible
meanings that could be given to a string of nucleotides.
The sequence of a gene and the sequence of a protein, in
conclusion, are not objective properties of those molecules.
They are codemaker-dependent properties because they do
not exist without a codemaking process and because they
would b e different if the codemaker had a different
structure. The sequences of gen es and proteins, in short,
have precisely the characteristics that define signs and
meanings. They are codemaker-dependent entities made of
organic molecules and are, therefore, organic signs and
organic meanings. All we need to keep in mind is that signs
and meanings are mental entities when the codemaker is
the mind, but they are organic entities when the codemaker
is an organic system (Barbieri 2003a).
We reach in this way the conclusion that every living cell
contains all four components of semiosis (signs, meanings,
code and codemaker) and is, therefore, a real semiotic system.
Two types of signs
Signs have been divided since antiquity into two great
classes that are traditionally represented by symbols and
symptoms. Augustine (389 AD) called them signa data and
signa naturalia, a distinction that continues to these days
under the terms of conventional signs and natural signs
(Deely 2006; Favareau 2007). The conventional signs are
those where there is no physical relationship between
signifiers and meanings, and a connection between them
can be established only by arbitrary rules, i.e., by
conventions. Words, for example, are signs (because they
stand for the named entities) and are conventional signs
because they are not determined by the characteristics of
the named entities. In the same way, there is no necessary
connection between symbols and the entities that they stand
for (between a flag and a country, for example).
In natural signs, by contrast, a physical link is always
present between signifier and signified. Typical examples
are the symptoms that doctors use to diagnose illness es
(spots on the skin, a fever, a swollen area, etc.), as well as a
variety of cues (smoke as sign of fire, odors as signs of
food, footprints as signs of organisms, etc.). In all these
cases, there is a physical relationship between the visible
signs and the invisible entities that they point to, and yet the
relationship is underdetermined, so much so that it takes a
process of learning and an act of interpretation to establish
it. The diagnosis of an illness from symptoms, for example,
is always an interpretive exercise, and even simple
associations, such as those between clouds and rain, depend
upon processes of learning and memory.
At the molecular level, we have seen that in protein
synthesis, a sequence of nucleotides is used as a sign by a
codemaker to produce a sequence of amino acids according
to the rules of the genetic code. In that case, there is no
necessary connection between the components of the two
molecules and the codons of nucleotides are used, therefore,
as conventional organic signs, i.e., as organic symbols.
A sequence of nucleotides, however, can also be used by
a copymaker to produce a complementary copy of itself,
and in that case, the relationship between the two sequences
is no longer established by adaptors but by direct physical
interactions between complementary regions. These inter-
actions, however, occur between very small regions of the
molecules, and that means that the first sequence provides
only a limited number of physical determinants for the
second. The first sequence, in other words, does have a
physical relationship with the second, but such relationship
is undetermined and represents, therefore, only a cue, i.e.,
a natural organic sign, for the second.
We conclude that the distinction between natural and
conventional signs exists also at the molecular level and
represents in fact a divide between two very different types
of molecular processes. Sequences of nucleotides are used
as natural signs in molecular copying and as conventional
signs in molecular coding . The transcription of genes, in
other words, is based on natural organic signs , whereas the
translation of genes into proteins is based on conventional
organic signs.
In both cases, a sequence of nucleotides provides
for the assembly of a second sequence, but
the meaning of that information is determined by the
molecular machine that actually perfor ms the assembly.
Organic information and organic meaning, in short, are not
intrinsic properties of the molecules that carry them, and
this raises a new problem. What kind of entities are they?
Part 2: the nature of information and meaning
The claim of physicalism
In 1953,WatsonandCrickproposedthatthelinear
sequence of nucleotides represents the information carried
by a gene. A few years later, the mechanism of protein
synthesis was discovered, and it was found that the
sequence of nucleotides in genes determines the sequence
of amino acids in proteins with a process that amounts to a
transfer of linear information from genes to proteins. In
both types of molecules, therefore, biological information
was identified with, and defined by, the specific sequence
of their subunits.
The concept of biol ogical information threw a complete-
ly new light on the century-old mystery of inheritance
(heredity is the transmission of information) and quickly
transformed the whole of biology from an energy-based
into an information-based scien ce. It must be underlined,
however, that biological information, or biological speci-
ficity (as some prefer to call it), cannot be measured and
cannot, therefore, be regarded as a physical quantity. So,
what is it? A similar problem arises with the genetic code.
The rules of a code cannot be measured and a code,
therefore, cannot be a combination of physical quantities.
So what is it?
According to an influential school of thought, biological
information and the genetic code are simply metaphors. They
are linguistic constructions that we use in order to avoid long
periphrases when we talk about living systems, but no more
than that. They are like those computer programs that allow us
to write our instructions in English, thus saving us the trouble
to write them with the binary digits of the machine language.
Ultimately, however, there are only binary digits in the
machine language of the computer, and in the same way it is
argued that there are only physical quantities at the most
fundamental level of Nature.
This conclusion, known as physicalism,orthe physicalist
thesis, has been proposed in various ways by a number of
scientists and philosophers (Chargaff 1963;Sarkar1996,
2000; Mahner and Bunge 1997; Griffith and Knight 1998;
Griffith 2001;Boniolo2003). It is probably one of the most
deeply dividing issues of modern science. Many biologists
are convinced that biological information and the genetic
code are real and fundamental components of life, but
physicalists insist that they are real only in a very superficial
sense, and that there is nothing fundamental about them
because they must be reducible, in principle, to physical
It has to be pointed out that the physicalist thesis could be
true. In fact it would be rigorously true if genes and proteins
were made by spontaneous assemblies because these
processes are fully described by physical quantities. The
point, however, is precisely that genes and proteins are not
spontaneous molecules. They are molecular artifacts because
they are manufactured by molecular machines, and this gives
us a real alternative to the physicalist thesis. More precisely,
we can prove that physicalism is wrong if we show that it is
valid only for spontaneous objects, i.e., if we show that there
is a fundamental difference between spontaneous objects and
artifacts. To this purpose, we need to go back to our question
about biological information and the genetic code.
Information is notoriously a difficult issue, and often
biologists tend to identify it with genetic sequences, which
are in fact only a particular type of information. A proper
introduction to this field is undoubtedly called for, and the
reader can find it in qualified publications such as those by
Yockey (2005), Battail (2006), and Forsdyke (2006), in
addition of course to the classic papers by Shannon (1948).
Here, however, we are interested precisely in that particular
type of information that is expressed by sequences and in
those particular relationships that are the rules of the genetic
code. Given that these entities cannot be measured, what
exactly are they?
Organic information
In genes and proteins, as we have seen, biological (or
organi c) information has b een defined as the specific
sequence of their subuni ts. This definition, however, is
not entirely satisfactory because it gives the impression that
information is a static property, something that molecules
have simply because they have a sequence. In reality, there
are countless molecules which have a sequence but only in
a few cases this becomes information. That happens only
when copymakers use it as a guideline for copying. Even
copymakers, however, do not account, by themselves, for
information. Copymakers can stick subunits together and
produce sequences, but without a template, they would
produce only random sequences, not specific ones.
Sequences alone or copymakers alone, in other words,
have nothing to do with information. It is only when a
sequence provides a guideline to a copymaker that it
becomes information for it. It is only an act of copying, in
other wor ds, that brings organic information into existence.
This tells us that organic information is not just the
specific sequence of a molecule but the specific sequence
produced by a copying process. This definition underlines
the fact that organic information is not a thing or a property but
the result of a process. It is, more precisely, an operative
definition because information is defined by the process that
brings it into existence. We realize in this way that organic
information is as real as the copying process that generates it,
but we still do not know what kind of entity it is. How does it
fit into our description of Nature?
According to a long tradition, natural entities are divided
into quantities and qualities. Quantities can be measured
and are objective, whereas qualities are subjective and
cannot be measured. In the case of organic information,
however, this scheme breaks down. Organic information is
not a quantity because a specific sequence cannot be
measured. But it is not a quality either because linear
specificity is a feature that we find in organic molecules,
and is, therefore, an objective feature of the world not a
subjective one.
A scheme based on quantities and qualities alone, in short,
is not enough to describe the world. In addition to quantities
(objective and measurable) and qualities (subjective and not-
measurable), we must recognize the existence in Nature of a
third type of entities (objective but not-measurable). Infor-
mation is one of them, and we can also give it a suitable
name. Since we can describe it only by naming its sequence,
we can say that organic information is a nominable entity or
that it belongs to the class of the nominable entities of Nature
(Barbieri 2003b; 2004).
We conclude that organic information is a new type of
natural entity, but we also conclude that it belongs to the
same class of objective entities that contains all physical
quantities. Therefore, it has the same scientific status as a
physical quantity. This, however, raises a new problem
because there are two distinct classes of physical quantities:
a small group of fundamental quantities (space, time, mass,
charge, and temperature) and a much larger group of
derived quantities. That distinction applies to all objective
entities, so we need to understand whether organic
information belongs to the first or to the second group.
Luckily, t his problem has a straightforward solution
because the sequences of genes and proteins have two very
special characteristics. One is that a change in a single
component of a biological sequence may produce a sequence
which has entirely new properties. This means that although
a biological sequence can be said to have components,itis
at the same time a single indivisible whole. The second
outstanding feature is that from the knowledge of n elements
of a biological sequence we cannot predict the element (n+1).
This is equivalent to saying that a specific sequence cannot
be described by anything simpler than itself,soitcannotbea
derived entity.
We conclude that organic information has the same
scientific status as the physical quantities because it is an
objective and reproducible entity. But we also conclude that it
does not have the status of a derived physical quantity because
it cannot be expressed by anything simpler than itself. This
means that organic information has the same scientific status
as the fundamental physical quantities, i.e., that it is a
fundamental (or irreducible) entity of Nature (a similar
conclusion was also described in Küppers 1990 and 1992).
Organic meaning
A code is a set of rules, which establish a correspondence
between the objects of two independent worlds. The Morse
code, for example, is a correspondence between groups of
dots and dashes with the letters of the alphabet, and in the
same way, the genetic code is a correspondence between
groups of nucleotides and amino acids. Let us notice now
that establishing a correspondence between, say, object 1
and object 2, is equivalent to saying that object 2 is the
meaning of object 1. In the Morse code, for example, the
rule that dotdash corresponds to letter A, is equivalent
to saying that letter A is the meaning of dotdash. In the
code of the English language, the mental object of the
sound apple is associated to the mental object of the fruit
apple, and this is equivalent to saying that that fruit is the
meaning of that sound.
By the same token, the rule of the genetic code that a
group of three nucleotides (a codon) corresponds to an
amino acid is equivalent to saying that that amino acid is
the organic meaning of that codon. Anywhere there is a
code, be it in the mental or in the organic world, there is
meaning. We can say, therefore, that meaning is an entity
which is related to another entity by a code, and that
organic meaning exists whenever an organic code exists
(Barbieri 2003a).
The existence of meaning in the organic world may seem
strange, at first, but in reality, it is no more strange than the
existence of a code because they are the two sides of the
same coin. To say that a code establishes a correspondence
between two entities is equivalent to saying that one entity
is the meaning of the other, so we cannot have codes
without meaning or meaning without codes. All we need to
keep in mind, onc e again, is that meaning is a mental entity
when the code is between mental objects, but it is an
organic entity when the code is between organic molecules.
Modern biology has readily accepted the concept of
information but has caref ully avo ide d the conce pt of
meaning, and yet, organic information and organic meaning
are both the result of natural processes. Just as it is an act of
copying that creates organic information, so it is an act of
coding that creates organic meaning. Copying and coding
are the processes; copymakers and codemakers are their
agents; organic information and organic meaning are their
results. But the parallel goes even further. We have seen
that organic information cannot be measured, and the same
is true for organic meaning. We have seen that organic
information is an objective entity because it is defined by
the same sequence for any number of observers, and that is
also true for organic meaning, which is defined by coding
rules that are the same for all observers. Finally, we have
seen that organic information is an irreducible entity
because it cannot be described by anything simpler than
its sequence, and the same is true for organic meaning,
which cannot be defined by anything simpler than its
coding rules.
Organic information and organic meaning, in short,
belong to the same class of entities because they have the
same general characteristics: They both are objective-but-
not-measurable entit ies, they both are irreducible, or
fundamental, entities of Nature, and since we can describe
them only by naming their components, they both are
nominable entities (Barbieri 2003b, 2004). Finally, let us
underline that they are the twin pillars of life because
organic information comes from the copying process that
produces genes, while organic meaning comes from the
coding process that generates proteins.
Operative definitions
Physical quantities have three fundamental properties: (1)
they are objective, (2) they are reproducible, and (3) they
are defined by operative procedures. This last property is
particularly important because it has provided the solution
to one of the most controversial issues of physics. The
controversy was about the theoretical possibility that the
entity which is measured may not be the same entity which
has been defined. This led to the idea that there should be
no difference between what is measured and what is
defined, i.e., to the concept of operative (or operational)
definition: a physical quantity is defined by the operations
that are carried out in order to measure it.
It was this operational approach that solved the defini-
tion problem in physics, and it is worth noticing that we can
easily generalize it. Rather than saying that a natural entity
is defined by the operations that measure it, we can say that
a natural entity is defin ed by the operations that evaluate it
in an objective and reproducible way. The advantage of this
generalized formulation is that it applies to all objective
entities, so it can be used not only in physics but in biology
as well. To this purpose, we only need to notice that a
measurement is an objective and reproducible description
of a physical quantity, just as the naming of a specific
sequence is an objective and reproducible description of
organic information, and just as the naming of a coded
entity is an objective and reproducible description of
organic meaning.
Whereas the physical quantities are evaluated by
measuring, sequences and codes are evaluated by naming
their components, but in both cases the entities in question
are defined by the operations that evaluate them, and this is
the essence of the operative approach. We may add that
organic information and organic meaning can also be
defined by the processes of copying and coding that bring
them into existence, and that too amoun ts to an operative
definition (Barbieri 2003b, 2004 ).
We conclude that organic information and organic
meaning can be defined by generalized operative proce-
dures that are as reliable as the operative procedures of
physics. This means that the definitions of information and
meaning should no longer be at the mercy of endless
debates on terminology as they have been in the past. The
operative definitions are scientific tools which are justified
by their own prescriptions, so there is no point in asking
whether they are right or wrong. All we can ask of them is
whether they contribute or not to our description and to our
understanding of Nature.
At this point, we can summarize all the above arguments
with the following concepts:
1. The sequence used by a copymaker during a copying
process is organic information.
2. The sequence used by a codemaker during a coding
process is an organic sign.
3. The sequence produced by a c odemaker during a
coding process is an organic meaning.
4. Organic information, organic signs, and organic mean-
ings are neither quantities nor qualities. They are a new
kind of natural entities, which are referred to as
nominable entities.
5. Organic information, organic signs, and organic mean-
ings have th e same scientific status as physical
quantities because they are objective and reproducible
entities that can be defined by operative procedures.
6. Organic information, organic signs, and organic mean-
ings have the same scientific status as fundamental
physical quantities because they cannot be reduced to,
or derived from, simpler entities.
The unexpected properties o f artifacts
Sequences, codes, signs and meanings exist only in a world
of artifacts because they are brought into existence by
copying and coding, the very processes that give origin to
artifacts. But can we really say that a set of artifacts is a
world? Are there regularit ies and laws in such a world in
addition to those of physics and chemistry? In order to find
this out, let us start from the special case of those particular
human artifacts that we call numbers.
There is little doubt that numbers arose by co unting, and
that counting was favored by natural selection because it
had practical advantages. The process of counting, how-
ever, produces exclusively natural numbers, but then we
have discovered prime numbers, rational and irrational
numbers, real and imaginary numbe rs, and an endless
stream of mathematical theorems. All these additional
entities were not produced by counting, and this is why
some mathematicians s ay that n atural numbers were
invented by man but that all other rules of mathematics
could only be discovered, as if they had an existence of
their own. In practice, this is equivalent to saying that the
world of mathematics was generated by the genetic rule of
counting, and then it developed into an increasingly
complex world full of additional or epigenetic properties.
A world of artifacts, in short, may not be completely
described by the coding rules that generate the artifacts. It
may well have unexpected rules of its own, rules that we
may call epigenetic because they were not present at the
beginning and appeared only during a process of explora-
tion and development.
Can we extend this conclusion to other artifacts? Today,
something similar seems to exist also in the world of
language, where it has been discovered that children learn
to speak by using only a limited number of inputs from the
environment. According to Chomsky (1975), this suggests
the existence of a universal grammar, a mechanism that has
the ability to retrieve the countless rules of any particular
language from a limited sample of them. It is as if the brain
of a child explores the world of language and discovers
an unlimited number of new rules simply by applying the
basic algorithm of the univer sal grammar.
A parallel conclusion appears to be valid also in the world
of proteins. There is a universal mechanism in every cell that
produces linear polypeptides from linear sequences of genes,
but then the polypeptides fold up into three-dimensional
proteins whose forms and behaviors are not written in the
genes, and living cells appear to engage in a veritable
exploration of the potentialities of the protein world.
Mathematics, language, and proteins are very different
sets of artifacts, but deep down, there is something in
common between them. They all have (1) a genetic
algorithm that starts producing the objects of a potentially
unlimited new world of artifacts (numbers, words, or
proteins) and (2) an explorator y procedure that brings into
existence additional or epigenetic properties of the new
world that were not present at the beginning. We conclude,
therefore, that many types of artifacts have unexpected
properties which can be discovered only by a process of
exploration, and in those cases we can truly say that we are
in the presence of new explorable worlds. We also conclude
that a complete description of a world of artifacts requires
new fundamental entities in addition to physical quantities,
and that is tantamount to saying that the claim of physi-
calism does not apply to the living world.
Schrödingers prophecy
In 1944, Erwin Schrödinger wrote What is Life?, a little
book that inspired generations of scientists and became a
landmark in the history of molecular biology. There were
two seminal ideas in that book: one was that the genetic
material is like an aperiodic crystal, the other was that the
chromosomes contain a code-script for the entire organism.
The metaphor of the aperiodic crystal was used by
Schrödinger to convey the idea that the atoms of the genetic
material must be arranged in a unique pattern in every
individual organism, an idea that later was referred to as
biological specificity. The metaphor of the code-script was
used to express the concept that there must be a miniature
code in the hereditary substance, a code that Schrödinger
compared to a Morse code with many characters, and that
was supposed to carry the h ighly complicated plan of
development of the entire organism. That was the very
first time that the word code was associ ated to a biological
structure and was given a biological function.
The existence of specificity and a code at the heart of life
led Schrödinger to a third seminal conclusion, an idea that
he expressed in the form of a prophecy: Living matter,
while not eluding the laws of physics as estab lished up to
date, is likely to involve hitherto unknown other laws of
physics, which, however, once they have been revealed,
will form just an integral part of this science as the former.
Schrödinger regarded this prophecy as his greatest contri-
bution to biology, indeed, he wrote that it was my only
motive for writing this book, and yet that is the one idea
that even according to his strongest supporters did not stand
up to scrutiny. Some 30 years later, Gunther Stent gave up
the struggle and concluded that No
other laws of physics
turned up along the way (Stent and Calendar 1978).
Instead, the making and breaking of hydrogen bonds seems
to be all there is to understanding the workings of the
hereditary substance.
Schrödingers prophecy seems to have been shipwrecked
in a sea of hydrogen bonds, but in reality that is true only in a
very superficial sense. The essence of the prophecy was about
the existence of something fundamentally new, and that turned
out to be true. As we have seen, life is based on organic
information and organic meaning, and these are indeed new
fundamental entities of Nature. Schrödinger invoked the
existence of new laws rather than of new entities, but that
was only a minor imperfection and should not have been
allowed to obscure the substance of the prophecy.
There is, however, one thing that Schrödinger might not
have appreciated in the answer that here has been given to
the question What is Life?. Together with many other
physicists, he believed that scientific truths must have
beauty, and the answer Life is artifact-making might not
be elegant enough to meet his criterion of truth. Luckily,
there is a simple way out of this impasse because the word
artifact-making maintains its meaning even when we drop
all its letters but the first three. In this way, the statement that
Life is artifact-making becomes Life is art, and that is a
conclusion that even Schrödinger might have approved of.
Part 3: the organic codes
The fingerprints of the organic codes
Codes and conventions are the basis of all cultural
phenomena and from time immemorial have divided the
world of culture from the world of nature. The rules of
grammar, the laws of government, the precepts of religion,
the value of money, the cooking recipes, the fairy tales and
the rules of chess are all human conventions that are
profoundly different from the laws of physics and chemis-
try, and this has led to the conclusion that there is an
unbridgeable gap between nature and culture. Nature is
governed by objective immutable laws, whereas culture is
produced by the mutable conventions of the human mind.
In this century-old framework, the discovery of the
genetic code in the early 1960s came as a bolt from the
blue, but strangely enough it did not bring down the barrier
between nature and culture. On the contrary, various
protective belts were quickly built around the old divide
with arguments that effectively emptied the discovery of the
genetic code of all its revolutionary potential. The first
protective belt was the argument that the genetic code is
fundamentally a metaphor because it must be reducible, in
principle, to physical quantities. The second protective belt
was the idea that the genetic code has been an extraordinary
exception, something that happened at the origin of life and
was never followed by anything similar ever since.
But are we sure that the genetic code is the only organic
code of the living world? Luckily, this is a problem that we can
deal with, because if other organic codes exist we should be
able to discover them by the standard experimental procedures
of science, just as we have discovered the genetic code.
The first step, in this enterprise, is to underline the
difference t hat exis ts between copy ing and coding, a
difference that is particularly evident in transcription and
translation. In transcription, an RNA sequence is assembled
from the linear information of a DNA sequence, and in this
case a normal biological catalyst (an RNA polymerase) is
sufficient because each elementary step requires a single
recognition process. In translation, instead, two indepen-
dent recognition processes must be performed at each step,
and the system that performs the reactions (the ribosome)
needs special molecules, first called adaptors and then
transfer RNAs, in order to associate codons to amino acids
according to the rules of the genetic code. Without a code,
in fact, a codon could be associated to different amino acids
and biologi cal specificity, the most precious of life s
properties, would be lost.
These concepts can easily be generalized. We are used to
think that biochemical processes are all catalyzed reactions,
but in reality we should sharply distinguish between
catalyzed and codified reactions. Catalyzed reactions are
processes (like transcription) that require only one recogni-
tion process at each step, whereas codified reactions require
(like translation) two independent recognition processes at
each step and a set of coding rules. The catalyzed reactions,
in other words, require catalysts, whereas the codified
reactions require adapto rs, i.e., catalysts plus a code.
Any organic code is a set of rules that establish a
correspondence between two independent worlds, and this
necessarily requires molecular structures that act like
adaptors, i.e., that perform two independent recognition
processes. The adaptors are required because the two worlds
would no longer be independent if there were a necessary
link between them, and a set of rules is required in order to
guarantee the specificity of the correspondence. In any
organic code, in short, we should find three major features:
1. A correspondence between tw o independent worlds.
2. A system of molecular adaptors.
3. A set of rules that guarantee biological specificity.
We conclude that the adaptors are the key molecules of
the organic codes. They are the molecular fingerprints of
the codes, and their presence in a b iological process is a
sure sign that that process is based on a code. This gives us
an objective criterion for the search of organic codes, and
their existence in Nature becomes, therefore, first and
foremost, an experimental problem.
The splicing codes
One of the greatest surprises of molecular biology was the
discovery that the primary transcripts of the genes are often
transformed into messenger RNAs by removing some RNA
pieces (called introns) and by joining together the remain-
ing pieces (the exons). The result is a true assembly because
exons are assembled into messengers, and we need,
therefore, to find out if it is a catalyzed assembly (like
transcription) or a codified assembly (like trans lation). In
the first case, the cutting-and-sealing operations, collective-
ly kn own as splicing, would require only a catalyst
(comparable to a RNA-polymerase), whereas in the second
case they would need a catalyst and a set of ada ptors
(comparable to ribosome and tRNAs).
This suggests immediately that splicing is a codified
process because it is implemented by structures that are
very much comparable to those of protein synthesis. The
splicing bodies, known as spliceosomes, are huge molecular
machines like ribosomes and employ small molecular
structures, known as snRNAs or snurps, whic h are like
tRNAs. The similarity, however, goes much deeper than
that because the snRNAs have properties that fully qualify
them as adaptors. They bring together, in a single molecule,
two independent recognition processes, one for the begin-
ning and one for the end of each intron, thus creating a
specific correspondence between the world of the primary
transcripts and the world of messengers.
The two recognition steps are independent not only
because there is a physical distance between them but
above all because the first step could be associated with
different types of the second one, as demonstrated by the
cases of alternative splicing. The choice of the beginning
and of the end of an intron, furthermore, is the operation
that actually defines the introns and gives them a meaning.
Without a complete set of such o perations, primary
transcripts could be transformed arbitrarily into messenger
RNAs, and there would be no biological specificity
In RNA splicing, in conclusion, we find the three basic
characteristics of all codes: (1) a correspondence between
two independent worlds, (2) the presence of molecular
adaptors, and (3) a set of rules that guarantee biological
specificity. We conclude, therefore, that t he processing of
RNA transcripts into messengers is truly a codified
process based on adaptors and takes place with rules that
can rightly be given the name of splicing codes (Barbieri
1998, 2003a).
The signal transduction codes
Living cells react to a wide variety of physical and chemical
stimuli from the environment, and in general their reactions
consist in the expression of specific genes. We need, therefore,
to understand how the environment interacts with the genes,
and the turning point, in this field, came from the discovery
that the external signals (known as first messengers)never
reach the genes. They are invariably transformed into a
different world of internal signals (called second messengers)
and only these, or their derivatives, reach the genes. In most
cases, the molecules of the external signals do not even enter
the cell and are captured by specific receptors of the cell
membrane, but even those that do enter (some hormones)
must interact with intracellular receptors in order to influence
the genes (Sutherland 1972).
The transfer of information from environment to genes
takes place, therefore, in two distinct steps: one from first to
second messengers, which is called signal transduction,
and a second path from second messengers to genes, which
is known as signal integration. The surprising thing about
signal transduction is that there are hundreds of first
messengers (hormones, growth factors, neurotransmitters,
etc.), whereas the known second messengers are only of
four types (cyclic AMP or GMP, calcium ions, inositol
trisphosphate, and diacylglycerol; Alberts et al. 1994).
First and second messengers, in other words, belong to
two very different worlds, and this suggests immediately
that signal transduction may be based on organic codes.
This is reinforced by the discovery that there is no
necessary connect ion between first and second messengers
because it has been proved that the same first messengers
can activate different types of second messengers, and that
different first messengers can act on the same type of
second messengers. The only plausible explanation of these
data is that signal transduction is based on organic codes,
but of course we would also like a direc t proof.
The signature of an organic code, as we have seen, is the
presence of adaptors and the molecules of signal transduc-
tion do have the defining characteristics of the adaptors.
The transduction system consists of at least three types of
molecules: a receptor for the first messengers, an amplifier
for the second messengers, and a mediator in between
(Berridge 1985). The system performs two independent
recognition processes, one for the first and the other for the
second messenger, and the two steps are connected by the
bridge of the mediator. The connection, however, could be
implemented in countless different ways since any first
messenger can be coupled with any second messenger, and
this makes it imperative to have a code in order to
guarantee biological specificity.
In signal transduction, in short, we find all the three
characteristics of the codes: (1) a correspondence between two
independent worlds, (2) a system of adaptors that give
meanings to molecular structures, and (3) a collective set of
rules that guarantee biological specificity. The effects that
external signals have on cells, in conclusion, do not depend on
the energy or the information that they carry, but on the
meaning that cells give them with rules that we can rightly
refer to as signal transduction codes (Barbieri 1998, 2003a).
The cytoskeleton codes
A cytoskeleton is absolutely essential for typical eukaryotic
processes such as phagocytosis, mitosis, meiosis, ameboid
movement, organelle assembly, and three-dimensional orga-
nization of the cell, i.e., for all those features that make
eukaryotic cells so radically different from bacteria. The actual
cytoskeleton, in reality, is an integrated system of three
different cytoskeletons made of filaments (microfilaments,
microtubules,andintermediate filaments), each of which
gives a specific contribution to the three-dimensional form of
the cell and to its mobility.
The driving force of the cytoskeleton is a very unusual
mechanism that biologists have decided to call dynamic
instability. The cytoskeletal filaments
especially micro-
tubules and microfilamentsare in a state of continuous
flux where monomers are added to one end and taken away
at the other, and the filament is growing or shortening
according to which end is having the fastest run. But what
is really most surprising is that all this requires lots of
energy, which means that the cell is investing enormous
amounts of energy not in building structures but in making
them unstable!
In order to understand the logic of dynamic instability,
we need to keep in mind that cytoskeletal fil aments are
unstable only when their ends are not attached to special
molecules that have the ability to anchor them. Every
microtubule, for example, starts from an organizing center
(the centrosome), and the extremity which is attached to
this structure is perfectly stable, whereas the other extremity
can grow longer or shorter and becomes stable only when it
encounters an anchoring molecule in the cytoplasm. If such
an anchor is not found, the whole microtubule is rapidly
dismantled and another is launched in another direction,
thus allowing the cytoskeleton to explore all cytoplasms
space in a short time.
Dynamic instability, in other words, is a mechanism that
allows the cytoskeleton to build structures with an
exploratory strategy, and the power of this strategy can be
evaluated by considering how many different forms it can
give rise to. The answer is astonishing: the number of
different structures that cytoskeletons can create is poten-
tially unlimited. It is the anchoring molecules (that
strangely enough biologists call accessory proteins) that
ultimately determine the three-dimensional forms of the
cells and the movements that they can perform, and there
could be endless varieties of anchoring molecules. The best
proof of this enormous versatility is the fact that the
cytoskeleton was invented by unicellular eukaryotes but
was later exploited by metazoa to build completely new
structures such as the axons of neurons, the myofibrils of
muscles, the mobile mouths of macrophages, the tentacles
of killer lymphocytes, and countless other specializations.
Dynamic instability, in conclusion, is a means of creating
an endless stream of cell types with only one common
structure and with the choice of a few anchoring molecules.
But this is possible only because there is no necessary
relationship between the components of the cytoskeleton
and the cellular structures that the cytoskeleton is working
on. The anchoring molecules (or accessory proteins) are
true adapto rs that perform two independent recognition
processes: microtubules on one side and different cellular
structures on the other side. The resulting correspondence is
based, therefore, on arbitrary rules, o n true natural
conventions that we can refer to as the cytoskeleton codes
(Barbieri 2003a).
The compartment codes
Eukaryotic cells not only produce molecules of countless
different types but manage to deliver them to different
destinations with astonishing precision, and this gives us
the problem of understanding how they manage to cope
with such an immensely intricate traffic. The first step in
the solution of this mystery came with the discovery that
the Golgi apparatus is involved not only in the biochemical
modification of many molecules but also in the choice of
their geographical destination. But the truly remarkable
thing is that all this is achieved with an extremely simple
mechanism. More precisely, the Golgi apparatus delivers
countless molecules to their destinations with only three
types of vesicles. One type has labels for the transport of
proteins outside the cell and another for their delivery to the
cell interior, whereas the vesicles of the third type carry no
destination label and are programmed, by default, to reach
the plasma membrane. The solution is extraordinarily
efficient. With a single mechanism and only two types of
labels, the cell delivers a great amount of proteins to their
destinations and also manages to continually renew its
plasma membrane.
The Golgi apparatus, however, is a transit place only for
a fraction of the cell proteins. The synthesis of all
eukaryotic proteins begins in the soluble part of the
cytoplasm (the cytosol) together with that of a signal that
specifies their geographical destination. The piece of
the amino acid chain that emerges first from the ribosome
(the so-called peptide leader) can contain a sequence that
the cell interprets as an export signal to the endoplasmic
reticulum. If such a signal is present, the ribosome binds
itself to the reticulum and delivers the protein into its
lumen. If not, the synthesis continues on free ribosomes,
and the proteins are shed into the cytosol. Of these ,
however, only a fraction rema ins there because the amino
acid chain can carry, in its interior, one or more signals,
which specify other destinations such as the nucleus, the
mitochondria, and other cell compartments. Proteins, in
conclusion, carry with them the signals of their geograph-
ical destination, and even the absence of such signals has a
meaning because it implies that the protein is destined to
remain in the cytosol.
The crucial point is that there is no necessary correspon-
dence between protein signals and geographical destina-
tions. The export-to-the-nucleus signals, for example, could
have been used for other compartments or could have been
totally different. They and all the other geographical signals
are purely conventional labels, like the names that we give
to streets, to cities, to airports, and to holiday resorts. The
existence of eukaryotic compartments , in other words, is
based on natural conventions, and to their rules of
correspondence, we can legitimately give the name of
compartment codes (Barbieri 2003a).
A world of codes
In the 1980s and 1990s, Edward Trifonov started a life-long
campaign in favor of the idea that the nucleotide sequences
of the genomes carry several messages simultaneously and
not just the message revealed by the classic triplet code. He
concluded that there are many overlapping codes in the
genome and gave them the collective name of sequence
codes. That conclusion rests upon Trifonovs definition that
a code is any sequence pattern that can have a biological
function or codes are messages carried by sequences or
a code is any pattern in a sequence which corresponds to
one or another specific biological function (Trifonov 1989
1996, 1999).
The plurality of codes described by Trifonov is a result
of his particular definition but is not necessarily limited by
that, and may well be compatible with other approaches.
The splicing code, for example, is a code not only
according to his criterion but also according to the operative
definition that a code is a set of rules of correspondence
implemented by adaptors. This suggests that Trifonov s
conclusion may have a general validity, and at least some of
his sequence codes could well be true organic codes. For
the time being, however, let us acknowledge the fact that
according to Trifonovs definition, there are at least eight
sequence codes in the genomes of living creatures, in
addition to the classic triplet code (Trifonov 1996): (1) the
transcription codes, (2) the gene splicing code, (3) the
translation pausing code, (4) the DNA structure code,or
DNA shape code,(5)thechromatin code,(6)the
translation framing code, (7) the modulation code, and (8)
the genome segmentation code.
Other authors have adopted different definitions of code,
but this is hardly surprising because biologists are used to
employing concepts without waiting for their precise
definition (there are still many definitions of species, for
example, but that does not prevent biologists from using the
word species in all cases). What reall y matters is that the
experimental evidence suggests the existence of a wide
variety of organic codes in Nature whatever is the criterion
used for defining them. More precisely, the existence of the
following has been reported:
1. The Adhesive Code (Readies and Takeichi 1996;
Shapiro and Colman 1999)
2. The Sugar Code (Gabius 2000; Gabiu s et al. 2002)
3. The Histone Code (Strahl and Allis 2000; Turner
2000, 2002; Gamble and Freedman 2002)
4. The Neural Tran scri pt iona l Cod es (Jessell 2000;
Flames et al. 2007)
5. A Regulatory Code in mammalian organogenesis
(Scully and Rosenfeld 2002)
6. A Code of Post Translational Modifications (Khidekel
and Hsieh-Wilson 2004)
7. A Neural Code for written words (Dehaene et al. 2005)
8. A Nuclear Receptors Combinatorial Code (Perissi and
Rosenfeld 2005)
9. A Transcription Factors Code (Tootle and Rebay 2005)
10. An Acetylation Code (Knights et al. 2006)
11. An
Estrogen Receptor Code (Leader et al. 2006)
12. The Metabolic Codes (Bruni 2007)
13. The RNA Codes (Faria 2007)
14. The Error-Correcting Codes (Battail 2007; Gonzalez
15. The Modular Code of the Cytoskeleton (Gimona 2008)
16. A Lipid-based Code in nuclear signaling (Maraldi 2008)
17. The Immune Self Code (Neuman 2008)
18. The Signal Transduction Codes (Faria 2008)
19. The Codes of Language (Cowley 2008)
20. The Musical Code (Reybrouck 2008)
These discoveries have largely been seen as proof of the
extreme complexity of life, which they certainly are, but
they are also much more than that. They may look like
those increasingly complex epicycles that people had to
invent in order to keep the Ptolemaic syst em up, but in
reality they raise fundamental questions and point to a new
Copernican framework for biology. We have already seen
that the existence of the genetic code proves that the cell is
a semiotic system, and in the following sections, we will
see that the existence of many other organic codes brings to
light a new mechanism of evolution.
Part 4: the mechanisms of evolution
Molecular change and evolutionary change
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 1940s, in the Modern
Synthesis, the theoretical framework where natural selec-
tion is regarded as virtually the sole mechanism of
evolutionary change.
Natural selection is due to chance variations in the
transmission of hereditary characters and is based, there-
fore, on the mechanism of molecular copying because the
copying of a gene is the elementary act that leads to
heredity. When a process of copying is repeated indefinite-
ly, however, another p henomenon comes into being.
Copying mistakes become inevitable, and in a world of
limited resources not all changes can be implemented,
which means that a process of selection is bound to take
place. Molecular copying, in short, leads to heredity, and
the indefinite repetition of molecular copying in a world of
limited resources leads to natural selection. That is how
natural selection came into existence. Molecular copying
started it and molecular copying has perpetuated it ever
since. This means that natural selection would be the sole
mechanism of evolution if molecular copying were the sole
basic mechanism of life.
As a matter of fact, this could have happened. If living
systems could have been made entirely of RNA enzymes
and RNA genes, only the copying of RNA molecules
would have been necessary, and natural selec tion could
indeed have been the sole mechanism of evolution. But that
is not what happened. Long before the origin of the first
cells, proteins were being made on the primitive Earth, and
proteins, unlike genes, could not be made by copying.
The discovery of the genetic code has proved that there
are two distinct molecular mechanisms at the basis of life,
transcription and translation, or copying and coding. The
discovery of other organic codes, furthermore, allows us to
generalize this conclusion because it proves that coding is
not limited to protein synthesis. Copying and coding, in
other words, are distinct molecular mechanisms, and this
suggests that they give origin to two distinct mechanisms of
evolution because an evolutionary mechanism is but the
long-term result of a molecular mechanism. More precisely,
copying leads, in the long run, to natural selection and
coding to natural conventions. In order to accept this
conclusion, however, we must prove that the two mecha-
nisms are truly different, i.e., that coding cannot be reduced
to copying. That is, therefore, our challenge. We can prove
that natural conventions are a distinct mechanism of
evolution only if we prove that copying and coding are
two fundamentally different mechanisms of molecular
Copying and coding
Copying and coding are both capable of bringing novelties
into the world, but they do it in very different ways. By its
very nature, the copying mechanism produces either exact
copies or slightly different versions of the copied molecules.
This means that natural selection produces new objects only
by modifying previous ones, i.e., by making objects that are
only relatively different from their predecessors. Natural
selection, in short, creates relative novelties, not absolute
In the case of coding, the situation is totally different. The
rules of a code are not dictated by physical necessity, and this
means that a new code can establish relationships that have
never existed before in the Universe. The objects that are
assembled by the rules of a new code can have no relationship
whatsoever to previous objects. Natural conventions, in short,
create absolute novelties, not relative ones.
A second difference between the two mechanisms is that
copying operates on individual molecules, whereas coding
involves a collective set of rules . The difference between
natural selection and natural conventions, in other words, is
the difference that exists between individual change and
collective change. An example of this difference can be
seen in any language whose evolution is due to variations
that take place not only at the level of the individual words
but also at the level of the collecti ve rules of grammar.
A third difference between copying and coding is that
they involve two different entities. A variation in the
copying of a gene changes the linear sequence, i.e., the
information of that gene. A variation in a coding rule,
instead, ch ange s the meaning of th at rule. The g reat
difference that exists between copying and coding, and,
therefore, between natural selection and natural conven-
tions, comes from the difference that exists between
information and meaning.
There are, in conclusion, three major differences be-
tween copying and coding: (1) copying modifies existing
objects whereas coding brings new objects into existence,
(2) copying acts on individual objects whereas coding acts
on collective rules, and (3) copying is about biological
information whereas coding is about biological meaning.
Copying and coding, in short, are profoundly different
mechanisms of molecular change, and this tells us that
natural selection and natural conventions are two distinct
mechanisms of evolutionary change.
Different mechanisms at different levels
The idea that natural selection can work at different levels
of organization (genes, organisms, species) has been at the
center of countless debates in evolutionary biology. Less
attention has been given to the alternative possi bility that at
different levels of organization there may be at work
different mechanisms of evolution. There is, however, at
least one case that gives us a clear example of this
alternative. It is the origin of mitochondria in the precursors
of the eukaryotic cells.
For a long time, it has been assumed that mitochondria
came into being by gradual evolution from within the cell,
but then it was found out that they originated by the
incorporation of whole cells into other cells by endo sym-
biosis. Those two types of cell had been in existence for
millions of years before the symbiosis event, and all their
components had been copied at each generation and had
been subject to evolution by natural selection. Their coming
together in symbiosis, however, was a process that took
place at the cellular level. It was the cells acting as whole
systems that gave origin to endosymbiosis. Their compo-
nents had to be compatible with endosymbiosis, but in no
way had been selected for that purpose. Endosymbiosis, in
short, is a mechanism that exists only at the cellular level,
not at the molecular level, and represents, therefore, a
distinct mechanism of evolution.
In the case of the organic codes, the situation is
somewhat intermediate between the molecular and the
cellular level. The genetic code, for example, is at the
same time a supramolecular system and a subcel lular one.
All its molecular components must be inherited and copied
individually, and yet a code is necessarily a collective
entity. The important point is that coding, like endosymbi-
osis, does not exist at the molecular level. Coding belongs
to the supramolecular level just as endosymbiosis belongs
to the cellular level. There is no doubt that copying is
absolutely necessary for coding, but the cruci al point is that
it is not sufficient for it because copying is a molecular
mechanism w hereas coding is a supramolecular one.
Coding cannot be reduced to copying because they are
fundamentally different mechanisms of molecular change
that operate at different levels of organization. We
conclude, therefore, that evolution was not produced only
by natural selection but by natural selection and by natural
conventions (Barbieri 1985, 2003a), which in no way is a
belittlement of natural selection. It is only an extension of it.
Codes and macroevolution
The role of the organic codes in the history of life can be
appreciated by underlining that their origins are closely
associated with the great events of macroevolution. Any
time that a new organic code came into being, something
totally new appeared in Nature, something that had never
existed before.
The origin of the genetic code, for example, made it
possible to produce proteins with specific sequences and to
pass them on indefinitely to other systems. That gave origin
to biological speci ficity and to heredity, the most funda-
mental of lifes properties. The origin of the genetic code, in
short, was also the origin of protein-based life, i.e., of life-
Similar considerations apply to the other organic codes.
The signal transductio n codes, for example, allowed
primitive systems to produce their own signals and,
therefore, to separate their internal space from the outside
environment. That was a precondition for the origin of
individuality, and in particular for the origin of the cell.
Another great innovation was brought about by the
codes of splicing because the appearance of a complete set
of splicing rules brought something unprecedented into
being. Splicing requires a separation in time between
transcription and translation and that was a precondition
for their separation in space, i.e., for the origin of the
nucleus. The defining feature of the eukaryotes, in other
words, was made possible by the origin of the splicing
Many other eukaryotic innovations were brought into
existence by other organic codes. The cytoskeleton codes,
for example, allowed the c ells to build their own scaffold-
ings, to change their own shapes, and to perform their own
movements. The origin of embryos was also associated
with organic codes because typical embryonic processes
like cell determination, cell adhesion, cell migration, and
cell death have all the qualifying characteristics of codified
phenomena (Barbieri 1998, 2003a).
In the case of embryonic development, furthermore, we
have entirely new codes before us. The correspondence is
no longer between two types of molecules, like genes and
proteins or first and second messengers, but between
molecules and cell-states. The determination of the body
axes, for example, is obtained by a link between molecules
and cell memory. The body axes are the same in all
triploblastic animals, but their molecular determinants are
of countless different types, which shows that there is no
necessary link between molecules and cell states. This
means that the link between molecular determinants and
cell states can only be realized by codes that we can refer to
as body pattern codes.
The major events in the history of life, in short, went
hand in hand with the appearance of new organic codes,
from the first cells all the way up to multicellular life, and
this suggests a very deep link between codes and evolution.
It suggests that the great events of macroevolution were
made possible by the appearance of new organic codes.
The contribution of the codes
The history of life has been punctuated by the appear-
ance of ne w organic codes, and it has been deeply shaped
by their characteristics. Five of them are particularly
1. Discontinuity. The evolution of the individual rules of a
code can take an extremely long time, but the origin
of a new code corresponds to the appearance of a
complete set of rules and that is a sudden event. The
great evolutionary novelties produced by a new code,
therefore, appeared suddenly in the history of life. This
is a new explanation of the discontinuities that
paleontology has documented, and shows that natural
selection and natural conventions had complementary
roles. Natural conventions account for the discontinu-
ities of the history of life, whereas natural selection
explains the gradual transformations that took place in
2. Invariance. The genetic code appeared at the beginning
of the history of life and has remained substantially the
same ever since. The same apply to the deep codes that
define prokaryotes and eukaryotes. Once in existence,
they have not been changed despite the fact that all the
molecular components of a code must be inherited and
are subject, therefore, to the chance variations of the
copying mechanism and to the long-term results of that
mechanism, i.e., to natural selection and to neutral drift.
The fact that the deep organic codes have been
conserved for billion of years suggests that their
conservation is the top priority in all living systems.
Everything else can be changed except the rules of the
basic codes of life. While morphological structures did
rise and fall countless times, the deep organic codes
have never been removed. This tells us that they truly
are the fundamentals of life, the invariants that persist
while everything else is changing.
3. Additivity. A new organic code has never abolished
previous codes. The genetic code has not been removed
by the signal transduction codes, and neither of them
has been supplanted by the splicing codes. A new code
has always been added to the previous ones, which
shows that new codes do not ori ginate b y the
transformation of previous codes. Once in existence,
organic codes do not tend to change, and the origi n of a
new code is always the origin of an entirely new set of
4. Stability. The genetic code is presen t in all living
creatures, but the other organic codes appeared in
increasingly smaller groups. The greater the number of
codes, the smaller the number of speci es, which possess
them. This shows that living systems coexist whatever
is the number of their codes. Eukaryotes d id not
remove proka ryotes, and metazoa did not remove
unicellular eukaryotes. Every organic code, in short,
represents a stable form of life.
5. Complexity. The addition of new organic codes to a
living system can rightly be regarded as an increase of
complexity of that system. The structural complexity
of some organisms did diminish in time, as many cases
of simplification clearly show, but the complexity of the
codes has never been lowered. Even the animals which
lost or reduced the greatest number of parts, in order to
lead a parasitic life, have conserved all the fundamental
codes of animal life. The number of organic codes is,
therefore, a new measure of biological complexity, and
probably it is more fundamental than all the other
parameters which have been proposed so far.
The contribution of natural selection
Life is essentially a manufacturing activity based on the
molecular mechanisms of copying and coding. This
conclusion may appear to give importance only to internal
factors, as if the environment had almost no role to play, but
that is far from being the case. The concept that life is
artifact-making gives at least three major roles to the
To start with, it is the environment that provides the
building blocks for the manufacturing activity of the living
systems. All components of life come from the environment
and eventually go back to it, which means that any living
system is totally dependent o n its surrounding world.
The second point is that it is the environment that
decides whether the structures manufactured by copying
and coding are viable or not. Copying and coding have the
potential to create an unlimited number of artifact s, but not
all of them actually work in the real world. Copying and
coding propose, but in the end it is the environment that
disposes of their products.
The third point is that the environment is not only the
place where living systems exist. It is also the place that
living systems tend to become adapted to. We have learned
from Darwin that in a world of limited resources, not all
organisms can survive, and a process of selection is bound
to take place. The survival can be a matter of luck, but in
general it is the degree of adaptation to the environment
that gives the best chances of success, and this means that
organisms tend to become more and more adapted to their
The process of adaptation allows organisms to become
increasingly capable to cope with the surrounding world,
and, therefore, to reduce the distance that separates them
from reality. Natural selection can be regarded, therefore, as
a process that allows organisms to incorporate increasing
amounts of reality into their constitution, even if the gap
between internal and external reality can never be abolished.
François Jacob has expressed this concept with admira-
ble clarity: If the image that a bird gets of the insects it
needs to feed its progeny does not reflect at least some
aspects of reality, there are no more progeny. If the
representation that a monkey builds of the branch it wants
to leap to has nothing to do with reality, then there is no
more monkey. And if this did not apply to ourselves, we
would not be here to discuss this point (Jacob 1982).
Common Descent
Darwins greatest contribution to Biology was probably the
theory of Common Descent, the idea that all the organic
beings which have ever lived on this Earth may be descended
from some one primordial form (Darwin 1859). In fact,
when Dobzhansky (1973) wrote that Nothing in biology
makes sense except in the light of evolution, it was
Common Descent that he had in mind. The idea that all
creatures of the present are linked to all creatures of the past
is indeed the greatest unifying theme in biology, the concept
that we use as an Ariadnes thread to reconstruct the history
of life.
Common Descent, however, is compatible with different
mechanisms of evolution, and in order to find out the truth
about it we need to know the actual mechanisms that gave
origin to biological objects in the course of time. How did
novelties appear in the hist ory of life? Did new objects arise
by natural selection alone or by natural selection and by
natural conventions?
If evolution took place only by natural selection, we
would have to conclude that nothing similar to the genetic
code appeared again in the four billion years of lifes
history. But we know that many other organic codes exist in
life, and this means that there have been many other origins
because any new organic code gives origin to unprecedented
structures. We have, therefore, two very different versions of
Common Descent before us. Evolution by natural selection
alone implies Common Descent with a Single Origin,
whereas evolution by natural selection and by natural
conventions leads to Common Descent with Multiple Origins
(this is not the old theory that cells originated many times
because the multiple origins are referred to codes not to
The idea that natural conventions bring absolute novel-
ties into existence is equivalent to saying that life has not
lost its creative powe r in the course of time. The origin of
embryos, the origin of the mind, or the origin of language,
for example, do not seem to be less of a novelty than the
origin of the cell. The theory of Common Descent with
Multiple Origins makes us realize that absolute novelties
appeared not only at the beginning but throughout the entire
history of life. And that is not a belittlement of Darwins
theory of Common Descent. It is only an extension of it.
Part 5: biosemiotics today
Code-based biosemiotics
The discovery of the genetic code took place between 1961
and 1966 (Nirenberg and Matthaei 1961; Speyer et al.
1963; Nirenberg et al. 1966; Khor ana et al. 1966) and
inspired an approac h to semiotics that can be referred to as
code-based biosemiotics because it assumes that coding is
the defining feature of semiosis.
The manifesto of this approach was written by George and
Muriel Beadle in 1966 with a single simple sentence: the
deciphering of the genetic code has revealed our possession of
a language much older than hieroglyphics, a language as old as
life itself, a language that is the most living language of all
even if its letters are invisible and its words are buried in the
cells of our bodies (Beadle and Beadle 1966).
In 1974, Marcel Florkin coined the term biosemiotics
for the study of this molecular language and gave the names
biosemes and biosyntagms to the basic units of molecular
semiosis. He emphasized, however, that meaning does not
exist at the molecular level and claimed that the genetic
code is a correspondence between structures and functions,
not between signs and meanings: A bioseme carries no
bedeutung,nomeaning, because its signifier is a
molecular structure and its signified is a biological
function (Florkin 1974). The idea that semiosis can exist
without meaning may seem paradoxical, today, and yet
Florkins conclusion was entirely logical because it was the
consequence of two basic concepts of modern biology.
One is the idea that the cell is a duality of genotype and
phenotype, i.e., a biological computer made of genetic
software and protein hardware. The crucial point is that a
computer contains codes but is not a semiotic system
because its codes come from a codemaker, which is outside
the system. The second basic concept is the idea that all
biological novelties are generated by natural selection, i.e.,
by an agent, which is outside the cell just as the human
mind is outside the computer. But if the cell is a biological
computer assembled by natural selection, it is perfectly
legitimate to say that it is not a semiotic system, and this
justifies Florkins statement that there is no real meani ng in
it. Ultimately, that leads to the physicalist thesis that there is
no real code either at the molec ular level, and that
molecular semiosis is merely an illusion.
The computer model of the cell, in short , keeps semiosis
out of the cell, and this is why the first true model of
molecular semiosis was the idea that every cell is a trinity
of genotype, phenotype, and ribotype, i.e., the idea that the
cell contains an internal codemaker (Barbieri 1981, 1985).
This was complemented by the idea that coding is not
reducible to copying, and, therefore, that natural selection
(based on copying) and natural conventions (based on
coding) are two distinct mechanisms of evolution (Barbieri
1985, 2003a).
Another important contribution to code-based biosemiotics
came from the discovery of an increasing number of organic
codes. That development started with the unveiling of the
sequence codes by Trifonov (1987, 1989, 1996, 1999)and
has grown slowly but steadily ever since (Barbieri 2008).
The code based approach to biosemiotics, in short, is a
road that started with the recognition of semiosis at the
molecular level and worked its way up by extending the
concepts of code and meaning to the higher levels of
biological organization. At about the same time, however,
there was also another road to biosemiotics that was being
developed. A road that went exactly the other way round,
i.e., that started at the higher levels and worked its way
down towards the lower ones.
Sign-based biosemiotics
The idea that animals have feelings, psychologies, and even
minds has been entertained in various ways throughout the
centuries, but for a long time it has been taken almost for
granted that only man is a semiotic animal, i.e., that only
man makes us e of signs. This idea was explicitly
challenged for the first time only in 1963, when Thomas
Sebeok suggested that animal communication is also based
on signs and proposed the term zoosemiotics for the new
science of animal semiosis (Sebeok 1963, 1972).
That proposal set Sebeok out on a long search for
evidence of semiosis in the vario us fields of the life
sciences, and eventually the hunt paid off. The first decisive
clue came from reading, in 1976, the original German
edition of Theoretische Biolog ie by von Uexküll (1928).
That book convinced Sebeok that von Uexküll had already
provided abundant evidence of semiosis in the animal
world and had been in fact the unintentional founding
father of zoosemiotics. The next crucial development was
the extension of semiosis beyond the animal world, a
generalization that took place in various stages.
In 1981, Martin Krampen argued that plants engage in
vegetable semiosis (phytosemiotics), and in 1988,Sorin
Sonea proposed that semiosis goes on even in the bacterial
world. Still in 1988, Giorgio Prodi suggested that a primitive
form of semiosis exists also in molecules and cells and gave
it the name of protosemiosis or natural semiosis (Prodi
1988). The word zoosemiotics became increasingly inad-
equate, and in 1991 Sebeok replaced it with biosemiotics, a
term proposed by Stepanov in 1971, but which had appeared
for the first time in 1962 when Friedrich Rothschild used it
to illustrate a new approach to psychology (Kull 1999).
Sebeoks greatest contribution, however, was probably
the silent revolution that he brought about in semiotics
itself. Up to the 1960s, semiotics was a deeply divided
field, virtually on the edge of anarchy, because it was still
split into two major schools, one founded by the Swiss
linguist Ferdinand de Saussure (18571913) and the other
by the A merican philosopher Charles Sanders Peirce
(18391914). The main difference between them is that
Saussure defined the sign as a dual entity, a combination of
signifier and signified (de Saussure 1916), whereas Peirce
insisted that it is a triadic relationship between a representa-
men,anobject, and an interpretant (Peirce 19311958).
According to Peirce, any act of semiosis cannot involve less
than three parties because there must necessarily be a
process of interpretation between sign and meaning.
Sebeoks silent revolution effectively disposed of Saussure
and put Peirce squarely at the center of semiosis. The most
authoritative treatise of semiotics, published in four
volumes between 1997 and 2003 by Roland Posner, Klaus
Robering, and Thomas Sebeok, makes it clear that by the
1990s, semiotics had become a largely unitary field, and
that semiosis was defined in unmistakably Peircean terms:
We stipulate that the following is a necessary and
sufficient condition for something to be a semiosis: A
interprets B as representing C. In this relational
characterization of semiosi s, A is the Interpretant, B
is some object, property, relation, event, or state of
affairs, and C is the meaning that A assigns to B.
(Posner et al. 1997).
By the 1990s, in short, the Peirce approach to semiotics
had become almost universally accepted, and it was taken
virtually for granted that the extension of semiosis first to
the animal world and then to the entire living world was
nothing but the extension of Peirce semiosis to life. Sebeok
expressed this concept in no uncertain terms by declaring
that: there can be no semiosis without interpretability
(Sebeok 2001).
The identification of semiosis with Peirce semiosis was
also accepted by Jesper Hoffmeyer in Signs of Meaning in
the Universe (1996), the book where he wrote his manifesto
and condensed it in the statement that the basic unit of life is
the sign, not the molecule. There was, therefore, a genuine
continuity from Sebeok to Hoffmeyer, and their biosemiotics
can rightly be referred to as sign-based biosemiotics,or
more precisely, as interpretation-based biosemiotics.
The role of interpretation
In code-based biosemiotics, semiosis is defined by coding
not by interpretation. This is because the rules of the
genetic code have been virtually the same in all living
systems and in all environments ever since the origin of
life, which clearly shows that they do not depend on
interpretation. In sign-based biosemiotics, instead, interpre-
tation is a defining feature of semiosis, and there is,
therefore, a sharp difference between the two approaches.
But is this difference insurmountable? Could we not say,
for example, that the codemaker of the cell is also an
? Why should we not generalize the concept of
interpretation and say that any act of coding is also an act of
In principle, of course, we could, but there is a caveat. If
we generalize the concept of interpretation in order to
include coding, why do we not go the whole way and
generalize it even further? Why do we not say, following
Taborsky (1999, 2002), for example, that any function
is an act of interpretation, whereby the function f
interprets x as representing y? In this way, all physical
laws expressed by functions like f(x)=y would be processes
of interpretation and, therefore, acts of semiosis.
This point is important because Peirce himself embraced
this view and concluded that semiosis exists everywhere in
the Universe. We realize in this way that if we extend the
concept of interpretation, we end up with a pansemiotic
view not a biosemiotic one. If we want to keep the
biosemiotic idea that semiosis exists only in life, therefore,
we must also keep the traditional concept of interpretation,
and in this case, we can no longer apply the Peirce model to
the cell. This does not mean, of course, that the Peirce
model is wrong. It means that it is valid only for those
living systems that are capable of interpretation in the
traditional sense of the word, i.e., for organisms that have a
nervous system.
It is likely that the behavior of the first animals was
almost entirely determined by genes, but the number of
hard-wired responses could not grow indefinitely, and
animals started resorting to processes of learning in order
to increase their behavioral repertoire. Learning how to
respond to a signal, on the other hand, means learning how
to interpret that signal, and this amounts to the construction
of a behavioral code whose rules are context-dependent.At
the same time, learning requires a memory where the results
of experience are accumulated, and this means that
interpretation is also a memory-dependent process. A
process of interpretation, in short, is a new type of semiosis
that is profoundly different from organic semiosis because
it is dependent on learning, mem ory and context.
Systems capable of interpretation, in turn, evolved in
many different ways and eventually a third type of semiosis
appeared, a semiosis that was based on symbolic codes
shared by all members of a community, i.e., on language
(Deacon 1997). The evolution of semiosis was character-
ized, therefore, by three great innovations: (1) the origin of
organic semiosis (the semiotic threshold), (2) the origin of
inte rpreta tion (the hermeneutic threshold), and (3) the
origin of language (the symbolic threshold). It was a
process that started at the origin of life with context-free
codes and produced codes that were more and more
context-dependent. Today, our cultural codes are so heavily
dependent on context that we can hardly imagine semiosis
without interpretation, and yet they are distinct processes,
and we need to keep them apart if we want to understand
the origin and the evolution of life.
Five schools and a minimal unit y
In addition to code- and to sign-based biosemiotics, there
are at least three other schools that have recognized the
existence of semiosis in organic life. One is the school
founded by Gregory Bateson who described evolution as a
cosmic process of learning (Hoffmeyer 2008). Another
school is the approach developed within physics by
Howard Pattee who proposed, since the 1960s, that there
must have been an epistemic cut at the origin of life (Pattee
1969, 1972, 2001). The third school was inspired by the
philosophy of hermeneutics and was developed in particu-
lar by Anton Markoš (2002) who argued that biology can
catch the essentials of life only by embracing the approach
of the humanities.
There is no space, in this brief review, for these additional
themes of biosemiotics, and the interested readers are invited
to consult the literature and the historical accounts (Favareau
2007). What is important, here, is to underline not only the
existence of different schools of biosemiotics but also the
fact that a few small steps towards unification have already
been taken.
The first came in 2004 at the fourth Gathering in
Biosemiotics organized by Anton Markoš in Prague. Jesper
Hoffmeyer, Claus Emmeche, Kalevi Kull, Anton Markoš,
and Marcello Barbieri met in a pub and decided that what
was uniting themthe introduction of meaning in biology
was far more important than their divisions. Up until then,
Barbieri had referred to the science of biological semiosis
as semantic biology,orbiosemantics, whereas Markoš had
been calling it biohermeneuthics, but they accepted to give
up their favorite names and to adopt the term biosemiotics
that Thomas Sebeok had been campaigning for with so
much passion and vigor. That is when biosemiotics really
came of age. It happened when people decided to work
together not because they had the same ideas but because
they accepted to put their differences aside in the interest of
a greater goal.
Today, the differences still exist, but there is also a
minimal unity in the field because there are two basic
principles, or postulates, that are accepted by virtually all
1. The first postulate is the idea that semiosis is unique to
life, i.e., that a real divide exists between life and
inanimate matter. This sharply differentiates biosemiotics
from pansemiotics, the doctrine that accepts the
existence of semiosis even in the physical world.
2. The second postulate is the idea that semiosis and
meaning are natural entities. This sharply divides
biosemiotics from the doctrine of
intelligent design
and from all other doctrines that maintain that the
origin of life on Earth was necessarily the product of a
supernatural agency.
Today, in conclusion, biosemiotics is not yet a unified
field from an academic point of view, but it is nonetheless a
field that provides a new paradigm for biology. Almost
everything remains to be written, but the important point is
that the main signposts of the new framework are already in
The major conclusion of this review is that biological
semiosis is a reality because semiosis is based on codes,
and organic codes are experimental realities. An equivalent
formulation is that all living creatures are semiotic systems
because organic codes exist in all of them. This conclusion
is based on a variety of arguments that here have been
divided, for convenience, into five parts.
1. In Part 1, we have seen that the cell can be described as
a trinity of genotype, phenotype, and ribotype because
it is made of three distinct types of informational
molecules that have three distinct biological roles.
Genotype and phenotype are, respectively, the seats of