Immunity and Ecology
Gilles NadeauVie aquatique
• Our marvellous computing tools and chaos
mathematics enable us to create images that
evoke well the unity of the living in its interiority,
its complexity, its plasticity and temporality.
Feedback loops, interaction and inscriptions
networks, where memory entanglement seems to
be appearing in the virtual field. That’s why I
choose to present to you, in parallel to this
exposé, the fractal art of Gilles Nadeau, one of the
best in his discipline.
• This faculty of memory must have preceded the
living beings on planet Earth, as Yves Couder, a
complex system’s physicist, recently received at
l’Académie des Sciences de France, declares:
“We are currently studying an oil drop surfing on
the waves it creates in a vibrating oil bath. These
waves contain in their structure a memory of their
preceding trajectory. Our fascination for this
system comes from their specific auto-
organisational regimes, almost biological, where
the information coded in the past contributes in
determining the present.”
• “In a same way, the appearing of the Fibonacci
number in vegetal spirals has a deep link with
Gaz incandescent Gilles Nadeau
Le tourbillon de la vie
• In the nineteenth century, the great physiologist Claude
Bernard introduced the concept of “milieu intérieur”
which is equivalent, in a certain way, to an “inner
ecology”. In the twentieth century, genetics and
molecular biology have revealed to us always more
numerous and unexpected actors of life. It seems that
even in the cell’s nucleus, viruses have been recruited or
domesticated to become collaborators of the cell. With
Lynn Margulis, we will see endosymbiosis becoming a
decisive factor of evolution in all eucaryotes. The story of
this very uncommon scientist will allow us to reflect
upon the frontiers and the links between strictly scientific
research and philosophy of biology. Then, inspiring
ourselves from the works of Philippe J. Sansonetti and
Jules Hoffman, we will see that man himself is an
eucaryote-procaryote hybrid. We will turn ourselves
toward symbiosis in the vegetal kingdom, like those
existential relations between trees and fungus and finally,
will regard men nature relations. At all scales, we are
looking at molecular, cellular, tissular, etc., dialogues.
These are messages and signalling pathways and we’ll be
talking about biosemiotics, a neglected branch of
ethology. At all scales also, we will see how much we’ve
been blurred by the “all genetic” approach. Oiseaux de nuit Gilles Nadeau
• By sequencing the genome, geneticists have cut
the branch on which they sat: population genetics.
And as biology had placed population genetics at
the center of its interpretation, the whole thing
crumbles. It would be more accurate, maybe, to
talk about a conceptual Titanic, reputably
unsinkable, slowly drowning in the ocean, after
crashing into an iceberg: epigenetics.
• What’s left of the “classical genetics” ? 2% of the
genome, the famous genetic code, which finally
looks like a keyboard on which life plays.
• Here are a few phrases taken from the course
program presentation “Analyse des génomes”
2013-2014 at l’Institut Pasteur:
• “But if it is so difficult to define genes models, we
have to remember that finally each genome is only
a snapshot taken from a process of permanent
• If, the more we learn about genes, the less we
know what they are, may be is it that, in reality,
they don’t exist. At least, not as a molecular object
we could precisely define.”
Embrangle (lumière diffuse) Gilles Nadeau
The magnitude of our ignorance
• The more recent studies concerning viruses showed that
there are between 10 billion and 1000 billion virus
We know 10, 000 of them. (Didier Raoult, L’Autre en
nous 2013) Are we going to continue giving them names?
• Around 10 billions viruses are detectable in one litre of
ocean water, and sometimes more in clear water, that
which can allow 10 23 bacterial infections per second
(Hendrix 2003). This lets us imagine the number of gene
transfers happening at every second in all aquatic milieus.
• There are between 100,000 and 1 million protein
“species” in our body. 900 000 unknowns.
• RNA, at first supposed to be a unidirectional messenger,
becomes multiform and multi-featured ; it is often RNA
who decides! We have discovered thousands of RNA
variants, small and long. They sometimes act like an
enzyme, which is a protein, and sometimes have two
strands, like DNA. They are changing roles and costumes.
The concept of the gene has been dissolved and the
codons are often degenerated or homonyms. There are
many exceptions to the rule, the code. The traditional
genetic model now looks completely simplistic. Nature
and culture, innate and acquired seem to be inextricably
intertwined and all those processes are inside us, like an
organic memory from the past.
• Only 2% of the genome encodes proteins, our ancient
definition of a gene. More than 45% of our genome comes
from a retroviral origin.
Spirit of Buddharot Gilles Nadeau
Plasticity of life, even in the nucleus
• Darwin had already underlined the unity of the
living, but the unity we are now discovering is
much more profound, engaging numerous actors
evolving in networks unexpectedly complex. It is
doubled with a plasticity that classical genetics
excluded by principle. One is overcome by
vertigo in front of such complexity.
• Modern biology has reached a dead end, facing
the comeback of the two heresies that it had
thought to be completely eliminated, Lamarckism
• Organisms do participate in their evolutive
transformation. They are not simply acted on like
things. They are real actors changing their
environment, not only submitting to chance and
Without denying the role of contingency, I will
propose the idea that there is in the living an
interiority which corresponds more or less with
Spinoza’s “conatus”, Nietzsche’s “will for
power”, “ Husserl’s “intention”, or Bergson’s
“vital impulse” .
• All these philosophers have in common the
notion of “desire”. Life is desire. Gilles Nadeauperroquet
Classical genetics and selfish DNA
• At the beginning of the twentieth century, we rediscovered the work of Gregor Mendel who, by studying heredity in the
green peas, had been the founding father of genetics. Biologists were still largely Lamarckians and could hardly believe that
the Darwinian natural selection was sufficient to comprehend the evolution of species.
• It is August Weissman who separated completely the innate from the acquired, the interior from the exterior, the future
from the past, cutting the tails of mice on many generations. The siblings were born with long and normal tails and this
became the proof that Lamarck was wrong. Weissman demonstrated that mutilations were not transmitted!
• Fifty years later, Francis Crick imposes the central dogma of genetics. In the living cell, information goes one way only: from
the nucleus toward the outside.
DNA > RNA > proteins.
• It’s Francis Crick himself that baptises this the “central dogma”. This is a monologue, a closing of the nucleus that allows the
saving of a mechanistic theory of life.
• Genes are the particles of heredity.
Spirale marchante Gilles Nadeau
New generation sequencing
• 50 years later, the new generation sequencing
(NGS) enabled scientists to analyse the
transcriptome and the epigenome, which means
the way DNA is being read in the living cell. It’s
only then that they realized that cellular
differentiation is an epigenetic phenomenon.
• 2% of the DNA encodes protein. In the 98% left
over once called “junk DNA”, we now know that
45% of it transcribes in reverse sense in association
with a family of enzymes present everywhere in
the living, reverse transcriptases.
• It has now been demonstrated that the
retrotransposons LINE-1 (Long Interspersed
Nuclear Elements) play a key role in the human
genome. Utilising reverse transcriptase, these
jumping genes are violating the central dogma of
genetics. They are roughly 30 times more
numerous than the “real genes” (coding for
proteins) in the genome. They are ATGC like the
rest. We generally consider them as retroviruses
that had invaded the genome.
Le dinausore disparu Gilles Nadeau
Proteins > RNA > DNA ?
• Retrotransposition is a common
mechanism in all eucaryotes. It has
largely contributed in evolution
and genome plasticity. LINE-1
retrotransposons represent more
than 17% of the human genome. It
is the only mobile and
autonomous active element and is
responsible for the amplification
of non autonomous
retrotransposons like Alu
sequences and retropseudogenes.
Thus, through evolution, LINE-1
has contributed in forming almost
a third of our genome mass.”
Génomique, génétique, bioinformatique et biologie systémique (Blanc SVSE 6)
2012 : projet RETROGENO Agence nationale de recherche Fr.
Slope embrangle Gilles Nadeau
A different interpretation
• Patrick Forterre presented recently a theory
regarding the origin of DNA from an RNA world. It
is important to recognize that the origin of life
and in particular the genetic code is still very
mysterious. Meanwhile, it appears more and
more clearly that RNA preceded DNA in the
evolution of life.
• “It is currently admitted today that competitive or
symbiotic interactions between viruses and cells
represent the principal motor of biological
evolution. (Forterre et Prangishvili, 2013; Koonin et Dolja,
• RNA viruses (retroviruses) produce complex
molecules and some are able to repair their RNA.
Viruses can create new proteins. There are new
genes in the viruses and that was unexpected.
Viruses create novelty.
• In this interpretation, viruses didn’t only invade
genome, they co-created it. nuit étoilée Gilles Nadeau
Yamanaka, the come back of
• Mr Yamanaka, the 2012 Nobel prize in biology, amazed
the scientific community by producing the first IPS
(Induced Pluripotent Stem cells). Using only 4
transcription factors, he succeeded in bringing back an
adult cell to its stem cell pluripotency. This was
• The interaction cascade that he initiates must be very
complex and operates in multilevel networks, but he
succeeds in inducing it without understanding all the
wheels of the machine. The important is the message:
in this case, 4 transcription factors.
• Mr Yamanaka started his research from 24
transcription factors (proteins) that he had “spotted”
while studying embryonic stem cells.
• He tried all sorts of combinations to finally find that
with only 4 proteins, and using a virus as Trojan horse,
we could reprogram a cell. This opens the way to
therapy and some leukemia are now being cured using
• Other ways are possible. One must find the right
cocktail. Small RNAs and C vitamins can improve the
effiiciency of the process.
• “And thus the wonderful truth became manifest that a
single cell may contain within its microscopic compass the
sum total of the heritage of the species” EB Wilson 1900.
Reflets dans l’eau Gilles Nadeau
Cellular memory, epigenetics
• We are witnessing, in the cell’s interiority, molecular
dialogues largely more complex than what we
expected. (We were expecting monologues, reflexes).
During the embryonic development, the pluripotent
stem cell interprets the genome regarding temporal and
spatial signals from its milieu. Therefore , we could
consider the black matter of the genome , the trash
DNA, as a memory, a recipe book or a repertoire of past
evolution. There are feedback loops everywhere.
• This hypothesis calls back a forgotten tradition in
biology: organic memory. Théodule Ribot, Ewald
Hering, Ernst Haeckel and Francis Darwin participated
in the elaboration of it. Almost a century ago, in 1918,
Richard Semon committed suicide when his
Lamarckian theory of organic memory was ruined by
the apparent triumph of August Weissman genetic
theory. Richard Semon had created the concept of
“mneme” and biological engrams.
• Some recent experiences using DNA to stock
information have demonstrated the gigantic capacities
of the double strand genome as memory stocking space.
Oeuf décoratif Gilles Nadeau
Lynn Margulis, the symbiosis
• Lynn Margulis will be recognized as a
great biologist of her time. Against
most of her contemporaries, she
criticized the genetic theory, and made
lots of powerful enemies. She looked
in old papers and resuscitated
discredited theories. (Merezhkovsky)
• Her journey demonstrates that an
isolated researcher, open to something
else than “nouveauté” in this case
genetics, and equipped with a different
philosophy, can achieve extraordinary
results. She had to demonstrate lots of
courage and tenacity to have her point
of view accepted and finally teach to
young students as it is today. Coquille de pierre Gilles Nadeau
• We can think that she went too far, but one
cannot deny that the chloroplast symbiosis
among vegetal and the mitochondrial
symbiosis among both plants and animals
constitute fundamental steps in the
evolution of species. We are discovering
more and more animals utilising
chloroplasts. (bioluminescent bacteria).
• Considering the “Gaïa” theory that she
developed with James Lovelock, we can
also think that she went too far. However, it
is true that the atmosphere and the
temperature of our planet were deeply
modified by the living beings. We’re
thinking upside down in pretending that life
only reacts to its environment. It is life
itself that first changed the environment and
its regulation. Here, once again, there are
dialogues and feedback loops.
Loupe Gilles Nadeau
Symbiosis in the symbiosis
• In the last twenty years, the number of discoveries
revealing the importance of symbiosis in the living
• Every eucaryote that we know has, or had
mitochondria. Genes are transferred from the
mitochondria to the cell nucleus. The mitochondria
looses some autonomy, but receives proteins in
An eucaryote incorporates another eucaryote. Lots
of secondary endosymbiosis and tertiary , loss of
secondary and further reacquisition. Endosymbiosis
with bacteria, fungus, and protists. Leguminous
symbiosis with rhizobium which allows nitrogen
fixation, essential for the plant metabolism.
• Around sub-oceanic volcanos, an incredible
diversity of organisms are utilising chemo-
synthesis. It’s another biochemistry. Mussels, clams
and worms authorizing bacterial infections in some
parts of their bodies.
• We observe a reduction in genome size of the
symbiote. (bacteria). Evolution often goes from the
complex to less complex. Toward the simple. Two spheres for Keith Gilles Nadeau
• Greenflies, ants, bees,
integrating different type
bacteria that fulfill their
shortages in vitamins and
• When the insect changes his
diet, a new shortage brings up
a new symbiosis. There is
mutual recognition of
partners and those symbiosis
are intimately linked to
• Take note that different
symbiotes and different
symbionts are using the same
signalling pathways to
produce different proteins. Tête de tyrannausore Gilles Nadeau
• Recent discoveries concerning the microbiome, the immune
system and the genetic and epigenetic interactions between
the gut flora and physiology made our understanding of
biology much more complicated.
• The innate immune system can recognize around 100
enemies. It already exists among the simplest organisms.
Just like for the genetic code, we know nothing about its
origin. It is required for the starting of the induced immune
system. Until recently, we didn’t even know that bacteria
and archaea had an adaptative immune system: CRISPR, a
far more precise gene editing tool than anything we did
• The acquired or induced immune system can recognize
millions, may be billions of microbial structures.
• Its adaptation capacities seems infinite. The unfolded
mucous intestinal membrane (epithelium) would cover a
tennis court. What an interface! What a playing ground for
billions of bacteria and viruses. The capacity to discriminate
between a pathogen and a commensal in order to respect the
microbiome and to destroy pathogens could be seen as an
essential motor of the immune system evolution.
• Looking at it from a co-evolutive perspective, the
microbiome and the pathogens have forged the immune
system and in return, the immune system sculpts the
microbiome and eliminates the pathogens.
The epithelium, a fertile ground
• Axenic mice (without microbiome) seem
unable to efficiently extract calories from
foods. They are also very nervous. The gut
microbiome does influence the mood, the
behaviour and even the brain development.
• Natural delivery and breastfeeding are very
important. During the first year of life, some
bacteria will form a “niche” leading to the
expression of enzymes which themselves will
create a favourable environment for other
microbes. The microbiome must be
• Fecal transplantations have proven their
efficacy and represent a shortcut in treating
digestive system dysfunctions.
• We must adopt a larger look on immunity
than the old Koch and Pasteur point of view.
Biological reality is more a matter of internal
ecology and balanced microbe population.
We should replace the notion of pathogen by
the concept of dysbiosis (unbalanced
microbiome, not necessarily pathogen).
Petit bonhomme vert Gilles Nadeau
Mycorhizes, evolution by
• It is a symbiosis between a blue
algae and a fungus (mushroom)
that created lichens, inaugural
flora of terrestrial environments.
• “Almost all living plants are
prospering using the mycorhizian
symbiosis. An ancient and happy
relation dating from more than
400 million years. A real motor of
André Fortin (Découvrir Le magazine de l’ACFAS mars 2014).
Roches magnétiques Gilles Nadeau
• We just saw how much symbiosis played a
major role in evolution. At the basis of
photosynthesis in vegetal and of respiration
in animals, it is still a symbiosis that allowed
living beings to emerge from water, and to
create the placenta in mammalians.
• Endosymbiosis theory has been rejected for
a long time. Why? It contradicts gradual
evolution and shortcuts vertical heredity,
being the source of horizontal gene transfers.
• These gene transfers happen far more
frequently than previously thought.
“Symbiotic associations are the rule, not the
exception. Every development is a co-
development. All organisms are mixed,
heterogeneous, non pure. It’s unity in the
Thomas Pradeu, (development, information and causation) dec.
6 2013 Collège de France.
Does biological sympathy exist?
Bois sculpté Gilles Nadeau
The logic of the living: a language?
• For more than a century now, biology has been inspired by
physical science, aspiring to the same status as physics. Many
thinkers are now proposing that the genetic system’s
complexity could be more easily understood as a natural
language. Actually, genes resemble words, sequence evokes
the phrases and the code is like syntax and/or grammar. In
language, every laws have exceptions. Language is alive. It is a
historical, contingent, plastic and creative construction. A
“bricolage” . Just like living things had to improvise to create
new proteins to face the unpredictable reality, we need new
concepts and words to enrich our thinking, and this process
doesn’t seem to be limited. Even the meaning of words
changes through the centuries. But also regarding their
position in the phrase and, in many languages, a small accent
can mean very much. Natural language possesses that fluidity
and plasticity characterizing the living. It largely outworks
mathematical language in terms of fluidity, specially the verbs,
real time and action words.
• The word “sense” (in French) has three different meanings.
Perception, orientation, and meaning. Even the simplest
organisms perceive and orientate themselves to survive and
reproduce. Even in its small world (umwelt) and without being
conscious of the meanings and concepts, it lives them,
embodies and incarnates them.
• There is a neglected branch of ethology: biosemiotics.
• Perception is signification, without any words or concepts. Plantes tropicales Gilles Nadeau
Charles Peirce, Jacob von Uexküel
Inspired from Charles Peirce triad (the sign, the
interpret, the object), biosemiotics was developed
in the works of Jacob von Uexküel. At the opposite of
Watson and Skinner’s behaviourism (reflexes), Von
Uexküel proposed an ethology where each organism
interprets the world according to its needs, forging
the world itself in many manners. Even though Von
Uexküel inspired many thinkers such as Heidegger,
Deleuze, Merleau-Ponty, Canguilhem and many
others, his school of thought was in minority. Richard
Dawkins is an ethologist.
Joseph Hoffmeyer writes: “Cells, like organisms, are
historical entities wearing in their cytoskeleton and
their DNA traces from the past, going back at more
than 3 billion years. They are perpetually measuring
actual situation by comparing it to their ancestral
background and make choices based on such
Thus, we could say that the sign, instead of the
molecule, is the basic unity to study life.”
Yin-Yang Gilles Nadeau
• Just as humanity is facing
a major ecological
challenge, how can we
succeed, equipped with
an almost “fixist” theory,
and a philosophy affirming
that conscience and free
will are pure illusions?
(Daniel Dennett). We are
now at a crossroads. After
more than a century of
Mendelian genetics, we
still haven’t found life,
which has brought many
philosophers to declare it
does not exist!
Pleine lune Gilles Nadeau
Chaotic phoenix Gilles Nadeau
As for the idea that the living body might be treated by some superhuman calculator in the
same mathematical way as our solar system, this has gradually arisen from a metaphysic which
has taken a more precise form since the physical discoveries of Galileo, but which, as we shall
show, was always the natural metaphysic of the human mind. Its apparent clearness, our
impatient desire to find it true, the enthusiasm with which so many excellent minds accept it
whithout proof, all the seductions, in short, that it exercises on our thought, should put us on
our guard against it. » (Henri Bergson, L’Évolution créatrice, p.20)
• “But Bergson’s warning was not taken
seriously by the biologists, too much
occupied at pushing the “living” in the
frame of their contemporary physics.
Outside the closed circle of real
philosophers, Bergson’s theses were
deformed, even ridiculed. The “élan
vital” he was talking about was
confused with a simplistic vitalism.
• This misunderstanding is quite salutary,
because it permits in one shot to
discredit every argument he presented.
Bergson was however showing a
prudence that was lacking in his
Without a doubt, Bergson argues, “the
vital principle doesn’t explain much: at
least, it has the advantage of keeping a
signboard on our ignorance, while
mechanism invites us to forget it.”
Gérard Nissim Amzallag, L’Homme végétal, pour une
autonomie du vivant, éd. Albin Michel, 2003 pp.321-329).
Vincent Gilles Nadeau