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Presentation entitled: Symbiosis, Coevolution, Immunity and Ecology. Fractal art exhibition, Philosophy of biology, Epigenetics.

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  1. 1. Symbiosis, Coevolution, Immunity and Ecology Gilles NadeauVie aquatique Interpreting life Gilles St-Pierre
  2. 2. Fractal images • 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 quasi-crystals.” Gaz incandescent Gilles Nadeau
  3. 3. 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
  4. 4. Paradigm shift? • 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 changes. • 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
  5. 5. The magnitude of our ignorance • The more recent studies concerning viruses showed that there are between 10 billion and 1000 billion virus species. 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. (Yves Chupeau) • 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
  6. 6. 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 and vitalism. • 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 genes. 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
  7. 7. 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
  8. 8. 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
  9. 9. 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
  10. 10. 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, 2013, ) • 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
  11. 11. Yamanaka, the come back of embryology • 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 considered impossible. • 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 these techniques. • 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
  12. 12. 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
  13. 13. 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
  14. 14. Symbiosis, endosymbiosis • 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
  15. 15. Symbiosis in the symbiosis • In the last twenty years, the number of discoveries revealing the importance of symbiosis in the living beings exploded. • 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 return. 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
  16. 16. Symbiosis avalanche • Greenflies, ants, bees, integrating different type bacteria that fulfill their shortages in vitamins and amino acids. • 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 immunity. • Take note that different symbiotes and different symbionts are using the same signalling pathways to produce different proteins. Tête de tyrannausore Gilles Nadeau
  17. 17. Immunity, microbiome, supersymbiosis • 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 before. • 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. loupe s Gilles Nadeau
  18. 18. 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 constructed. • 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
  19. 19. Mycorhizes, evolution by cooperation • 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 evolution. André Fortin (Découvrir Le magazine de l’ACFAS mars 2014). Roches magnétiques Gilles Nadeau
  20. 20. Biosemiotics • 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 plurality.” Thomas Pradeu, (development, information and causation) dec. 6 2013 Collège de France. Does biological sympathy exist? Bois sculpté Gilles Nadeau
  21. 21. 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
  22. 22. 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 interpretations. Thus, we could say that the sign, instead of the molecule, is the basic unity to study life.” (Hoffmeyer, 1996) Yin-Yang Gilles Nadeau
  23. 23. Ecology • 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 scientists and philosophers to declare it does not exist! Pleine lune Gilles Nadeau
  24. 24. Bergson 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)
  25. 25. Memory • “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 protagonists. 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.” (E.C.p 42) Gérard Nissim Amzallag, L’Homme végétal, pour une autonomie du vivant, éd. Albin Michel, 2003 pp.321-329). Vincent Gilles Nadeau
  26. 26. Lived time “Wherever anything lives, there is, open somewhere, a register in which time is being inscribed.” E.C., p.20 gilstpierre@videotron.ca Tous droits réservés©