From Renoir to Epigenomics. How we are using the marks on cells’ DNA to study autoimmunity

Luncheon of the boating party
Luncheon of the boating party is an oil on canvas painting by Pierre-Auguste Renoir. It was painted in 1881 and is now at The Phillips Collection in Washington, DC. Image obtained from flickr (CC BY license).

Simple answers to complex questionsAuthorship: Eddie Cano-Gámez.

Autoimmunity from Bosch to Renoir

The painting is called Luncheon of the Boating Party. In it a group of friends are having lunch. At one end of the table a young woman gesticulates while talking to her little dog. There is another woman drinking from a glass and yet another one stares into space, caught in her own thoughts. It is a fine summer afternoon and somehow, despite the immobility of the characters, one can hear the distinctive clattering of glasses and ice cubes. When Pierre-Auguste Renoir painted this scene in 1881, his abilities as an artist were no doubt at their best: he was to become one of the most iconic exponents of French impressionism. Back then, few would’ve thought that only 10 years later Renoir’s arms would be wrapped in bandages and that a personal assistant would need to hand him his paint brushes. Renoir, as many others before and after, became a victim of a condition poorly understood at the time: rheumatoid arthritis.

Renoir is not the only example of arthritis in art or in history. The Portrait of a Youth painted by Sandro Botticelli as early as 1480 could in fact depict a man with juvenile arthritis. And it is possible that even earlier Hieronymus Bosch picked arthritic individuals as some of the subjects for his Procession of the Cripples. Bosch lived 300 years before Renoir, and Renoir 150 years before us. Yet, despite the medical advances of our times, there is still no cure for rheumatoid arthritis. The medications that exist focus only on making quality of life better. Why is this the case? Is finding a cure for rheumatoid arthritis really such a difficult task? And if so, where does the difficulty come from? To understand this, we need to plunge into the depths of autoimmune disease.

portrait of a young man
Portrait of a young man by Sandro Botticelli (1483). Now at the National Gallery of Art (Washington, DC). Image obtained from flickr (CC BY license)

Rheumatoid arthritis is only one of tens of conditions classified as autoimmune diseases. Some others include multiple sclerosis (a brain condition), inflammatory bowel disease (an autoinflammatory condition of the intestines) and lupus (an incredibly complex condition, famously popularised by the TV series House MD). If taken as a group, these diseases affect between 3% and 10% of the population. But, perhaps counterintuitively, it is not the joints, the brain or the intestines which are directly affected in these diseases, but rather something less obvious. What all of these disorders share is a faulty immune system. Under normal circumstances, the immune system attacks pathogens which try to infect us. In autoimmune disease, however, it destroys healthy organs like the brain or the components of the joints. Why this happens has been an outstanding question in the field of immunology for decades and different hypotheses have been proposed to explain it. Perhaps the most widely known is the idea that some bacteria have evolved to “look like humans”. If we zoom into these pathogens very closely (at the level of individual molecules on their surface), these bacteria would look incredibly similar to human tissues. This can confuse the immune system, which can not tell them apart from our own organs. This explanation, called molecular mimicry, appears in several textbooks. But molecular mimicry cannot explain every disease. Sometimes there is something else which triggers autoimmunity: it could be something we ate (like gluten in individuals predisposed to celiac disease) or something we were exposed to. Sometimes there is no evident cause at all. Perhaps the most sincere thing to say would be that we do not really understand.

Setting the scene

There is, however, one  very curious fact about autoimmune diseases which could help us understand them: these conditions tend to cluster in families. In such families, it is common to find several members who all suffer from arthritis, or who show different types of immune disease. This intriguing fact immediately suggests that there must be something that predisposes people to diseases, something passed from generation to generation, something hidden in the letters of human DNA. But what exactly is this something? This is the very question which has fuelled the last 15 years of research.

To answer this, geneticists devised a simple approach. They first set out to find all possible individuals suffering from autoimmune disease and recruited as many Renoirs and Portraits of young men as possible. Once recruited, geneticists took cells from these individuals and read their DNA. The idea was straightforward: to compare their DNA with that of healthy people. In this way, whichever sections of the DNA predisposed people to, say, arthritis could be identified. And indeed, they were found. Thanks to these studies (called genome-wide association studies or GWAS) today we have mapped hundreds of differences between healthy and sick individuals. Most of these come in the form of tiny changes to the sequence of DNA (often no bigger than a single letter). We call these genetic variants. The next step was, in principle, extremely simple: to study those genetic variants and find out what exactly they were doing. But there was a problem: this task turned out to be extremely difficult.

To fully understand what makes this a difficult problem, we have to explore human DNA in more detail. For the purpose of this blog, let’s imagine DNA not as a molecule, but as a book. In fact, let’s imagine DNA isn’t simply any book, but a copy of The Bald Soprano, the absurdist play by Eugène Ionesco (La cantatrice chauve in the original French). Let us read the first lines of The Bald Soprano:


THE CHARACTERS: Mr. Smith, Mrs. Smith, Mr. Martin, Mrs. Martin, Mary, The Maid, The Fire Chief.

SCENE: A middle-class English interior, with English armchairs. An English evening. Mr. Smith, an Englishman, seated in his English armchair and wearing English slippers, is smoking his English pipe and reading an English newspaper, near an English fire. He is wearing English spectacles and a small gray English mustache. Beside him, in another English armchair, Mrs. Smith, an Englishwoman, is darning some English socks. A long moment of English silence. The English clock strikes 17 English strokes.

MRS. SMITH : There, it’s nine o’clock. We’ve drunk the soup, and eaten the fish and chips, and the English salad. The children have drunk English water. We’ve eaten well this evening. That’s because we live in the suburbs of London and because our name is Smith.

MR. SMITH: [continues to read, clicks his tongue.]

Let’s now stop for a moment and analyse our imaginary DNA fragment. The opening begins: “The characters: Mr. Smith, Mrs. Smith…” It is perfectly clear that nobody is meant to read this sentence aloud. Then why did Ionesco wrote it? This line tells the producer of the play how many characters she should hire. The second line is even more puzzling: “Scene: A middle-class English interior, with English arm-chairs…” Again, it is obvious that nobody need recite this aloud (though it does makes a funny reading). It is an indication for the people in charge of designing the costumes and props which will appear on stage. It isn’t until the third paragraph that we find something which ought to be read: “Mrs Smith: There, it’s nine o’clock…“. But even here, the line opens with two words (Mrs Smith) which should not be read aloud: they are meant to indicate who will be in charge of reading the line. Obviously, The Bald Soprano is not meant to be read but to be performed on stage. It is its performing nature which begs for this long list of indications to set the scene, the characters and even the tone of voice.

Photograph from a representation of The Bald Soprano (1968). Image obtained from Wikimedia Commons.

DNA is no different: it is also meant to be performed (though, in this case, not by actresses but by cells). In fact, only 2% of human DNA is directly readable in the way “There, it’s nine o’clock” is. We call this DNA coding and it contains genes. The remaining 98%  (which people used to call junk DNA) is not meant to be read. It is non-coding, and it does not contain genes. Some of it is structural (i.e. it acts like scaffolding in chromosomes), while some of it contains long lists of indications that specify which cell should read each gene, under which circumstances, and at which level. We call this DNA regulatory. Because these indications are not written in standard “genetic code”, we are as of today, unable to decipher them (perhaps not surprisingly, since we are not the performers which were originally meant to read them).

Now we are in a position to understand why it is so difficult to understand autoimmune disease. The vast majority of genetic variants linked to arthritis or other autoimmunities are in non-coding DNA. Since we cannot read non-coding DNA, we do not know what these sections mean. For example: which cell is using this DNA? (which in the Ionesco analogy would mean which actress is reading these lines?). It is difficult to know, since the immune system is formed of tons of different cells (T cells, B cells, macrophages, dendritic cells, neutrophils and a long list of other creatures) and the possibilities are endless. Moreover, we do not know what the function of this non-coding DNA is at all. Does it regulate the level of gene expression (equivalent to how loudly or quietly a line should be read) or does it regulate the context in which genes are active (equivalent to the moment of the play in which a line is read)? Once we answer these questions for one genetic variant, we will need to do it again and again for the hundreds of variants linked to disease. Hence the complexity of the problem. How could we ever hope to find a cure for arthritis if we can’t understand any of this information?

In a recently published study, we proposed an alternative approach. Let’s go back to the Ionesco example. If human DNA really was a copy of The Bald Soprano, and if it were to be performed, what would happen? Perhaps the actress interpreting Mrs Smith would have her own copy of the play. Not only that: she would need to learn it by heart, which means she would flip the pages over and over again, folding the corners of the most difficult paragraphs and highlighting her favourite passages. DNA is no different. Each cell has its own copy, and this copy is covered with the marks and highlights that the cell has added to read it more easily. We call this collection of marks the epigenome, and the field dedicated to study them epigenetics. What if we could read the copies of The Bald Soprano owned by different cells and compare their personal marks? Perhaps that could help us read the non-coding genome.

Notes in book margins
Epigenetic marks might act like footnotes and marks in books, rapidly indicating where a passage is located and how to read it. This example captures the thoughts of a reader of Shakespeare’s Hamlet. Image obtained from flickr (CC BY license)

Break a leg!

And that is how we set out to prepare our performance. We first recruited our actresses, our cells. To do so, we obtained T cells and monocytes from a handful of healthy people (we focused on T cells and monocytes because a large body of research suggests they hold the key to autoimmunity). Next we asked them to play their respective roles: in the lab, we tricked these cells into believing that they were seeing a pathogen or some other type of immune threat. Once cells reacted, we recorded their behaviour by looking at the marks they added to their copies of the DNA. We focused on one particular mark, a type of chemical modification which works as a bookmark, physically separating the sections of DNA which are frequently read or used.

Finally, we cross compared the notes of different performers. We asked which lines were highlighted by each cell, zooming specifically into the DNA sections linked to , say, arthritis. We wanted to understand which cells were constantly using these sections of the DNA. Could any of them be reading an abnormally high number of “arthritis” passages? This is equivalent to finding out which actress is playing the villain of a play by only looking at the highlights on her copy. Each cell was assigned a score according to how likely it was to be “the villain”. In more scientific terms, these are measurements of how often a cell reads or uses the DNA regions associated with disease (a measurement we call enrichment). We did this using genetic variants linked to different autoimmune diseases.

Our observations confirmed our suspicions: we found that T cells are extremely important in autoimmunity. But not just any T cells. Our evidence points to memory T cells in particular (a more experienced type of T cell) . It is very likely that something is going wrong in the T cells of people with autoimmune diseases. But not only that: because we read their DNA at different points in time, we also have a pretty good idea of when T cells start malfunctioning. This seems to happen very early (perhaps only a few hours) after they start responding to a threat. T cells fail to do their job, so to speak, during the first act of the play. Perhaps here, like in classic Greek tragedies, all the events which slowly unfold and come to haunt us in the final scene have their origin at the very beginning of the first act (think for example of the oracle in Oedipus Rex).

But what does this mean to people suffering from autoimmunities? Can this information be used in any way to cure future Renoirs? The answer is perhaps, but definitely not immediately. Our work gives one clear message: that we should be studying in more detail what T cells do when they start responding. Which part of this process is defective in autoimmunity? And how can we correct it? The solution to this problem lies very far ahead, but we are slowly moving towards it.

Eddie is a PhD student in genetics at the Wellcome Sanger Institute and The University of Cambridge. For any concerns, suggestions or comments regarding this blog, please contact the author at

Facing the unknown: how genetics (almost) led me to absurdism


“To imagine that you know, to populate the unknown with projections, is very different from knowing that you don’t…”

-Rebecca Solnit, A Field Guide to Getting Lost


I am terrified by the certainty of the unknown. I’ve always been. The entirety of my life has been a battle with the uncertain; a fruitless attempt to grasp the meaning, to hold of some stable object in this chaos: a cliff, a rock, a table… to hold of it and to never let go. I find it so hard to make decisions. Will the path I take when walking home affect my fate and that of everyone around me, for instance? Am I choosing one among several different opposite worlds every time I take a step and choose one direction over the other? Will sharing or not my umbrella with this man cause him to fall in the hands of a murderer, as it did to the characters in Oscar de la Borbolla’s Wittgenstein’s Umbrella? Will the teaspoon of sugar in my teacup irreparably alter the structure of the cosmos? After all, is it not known since Edward Lorenz that the flap of a butterfly’s wings in Brazil can set off a tornado in Texas? And how could one embrace determinism at all after reading on chaos theory? There is stochasticity. There is random variation. We stand in the eye of a storm.

Lorenz Attractor

The reasons why I find decision making hard have nothing to do with the act of choosing and everything to do with the unknown. Or, as Kierkegaard put it, with the fact that life can only be understood backwards, but must be lived forwards. How marvellous would it be to ponder all possibilities thoroughly before walking out of bed! Then I would have no trouble deciding, because I would know. Sometimes I think this is the very reason I decided to study genomics and not any other branch of science. It is the ultimate cause of my fascination with high throughput data. Statistics is my philosophy to dealing with the unknown, the undetermined. How to know if this is better than that, for example? Through statistics this is simple: either you repeat the decision millions of times in a  computer and see the differences (permutations) or use a model that describes uncertainty and estimate how likely each outcome is (statistical distributions). Statistics is also my immaterial cell (as in Louis Bourgeois’s cells): the place I have to hide from the constant waves of vastness, information, expectations…

One of Louise Bourgeois’s Cells at Guggenheim Museum, Bilbao

Biologists create hypotheses. Artists paint rags in blue. Social scientists contrast theories. And while all these theories and hypotheses and paintings are equally likely to explain the unknown, that very same fact renders them useless. When you really think about it, were the homunculus or the ether not valid scientific theories once? Were they not taken as fact? Or, as Rebecca Solnit puts it when talking about cartography, people continued to seek places that had been made up out of imagination and desire. How can one then decide which theory to believe in? Statistics opposes to this school of thought by directly dealing with stochasticity and hence is like a lighthouse traversing the thick fog, the endless emptiness in the seas of knowledge. Is this not so? So I thought. I was convinced of it. It helped me sleep at night. I stopped dreaming of snakes, picturing snakes feeding of my ignorance and fear. And this worked surprisingly well until a rather common autumn afternoon of 2017 when I sat at my desk to read an article on statistical genetics. The title was “An expanded view of complex traits: from polygenic to omnigenic“.  I read it from top to bottom. I cant even recall blinking. I could hear a storm in the distance. Suicidal teacups propelled from shelves to floor and shattered in pieces. The earth vibrated. I looked under the bed and saw a snake, meters and meters of snake. But I could not chase it out. I felt as one sometimes feels when trying to listen to Ligeti. And that feeling stayed with me ever since…


Geneticists like performing association. Which sections of our genome influence how tall we are? And which influence our skin colour? The method is called genome-wide association. Despite its complexity, the idea is very simple: if we compare the DNA of a large group of people with different heights, can we find statistically significant differences? And where in the genome are these differences located? The method in fact seems to work very well, as there now exists an endless catalogue of associations for all sorts of things: interesting aspects of human biology such as height, coronary artery disease, body mass index, immune diseases, schizophrenia, but also more obscure metrics as liking or disliking marmite or being “intelligent” (don’t get me started on this one…). It is not that we geneticists are determinists (though some might be). On the contrary, we fully acknowledge the role of the environment in all of these aspects and realise that some of the genetic effects might be small, but we are still able to find them. Each one of those associations exists. There is no doubt about it. They have a statistical reality and, I believe, they will eventually have a material reality too once we manage to find out just how this DNA section makes us taller or smaller. The same happened with genes, which were for decades a statistical concept (see Mendel or Hunt Morgan or Fisher) before acquiring materiality with the elucidation of the DNA structure.

Screen Shot 2018-01-27 at 14.07.26
List of genome-wide association studies performed since the early 2000s. (Visscher et al., 2017)

There is, however, a rather annoying fact in this type of association: height, immune diseases or schizophrenia are all complex traits. This means they are not caused by one or two genes, but rather by what now geneticists estimate to be thousands of segments in the genome acting together. And how can this be? How can more than 1000 little associations shape my propensity to, say, diabetes? The general belief is that most of these thousands of associated regions work in synergy in a handful of cells within our body, that they are, in other words, affecting the same functions. In his book Being mortal (an account of ageing and death), Atul Gawande compares ageing with the slow obsolescence of a complex machine: complex systems -power plants, say- have to survive and function despite having thousands of critical components. Engineers therefore design these machines with multiple layers of redundancy: with backup systems, and backup systems for the backup systems. The backups may not be as efficient, but allow the machine to keep going even as damage accumulates. Gavrilov argues that’s exactly how human beings appear to work. Perhaps complex diseases work like this too: each of these associated regions might somehow damage the function of one tiny component in the marvellous cell machinery (perhaps in a very specific context), and it is only from the accumulation of all damage that disease emerges. The quest then is (and by quest I mean my personal quest otherwise called PhD) to find out which components these are, and where and when they disfunction. So as you see it is all very data driven. It is as certain as it gets. Is it not? Yes. I have moved to the lighthouse, and through the window I see light beat darkness.

And yet, as I read Jonathan Pritchard‘s article that autumn afternoon I stumbled into this chain of arguments: there are thousands of genomic regions associated with disease, and we expect to find more and more in the close future. Thus, there might very possibly be tens of thousands of associations. Collectively, they even seem to locate to random places in the DNA. However, we only really have about 20,000 genes. This means that every single gene can influence, to some extent, our propensity to disease. Coming back to Gawande’s allegory, damage in every single component of the machine contributes to its obsolescence. Doesn’t matter if it is only a colourful piece of plastic with no apparent function: if it breaks, the function of the machine will be somehow modified. Or, the way it was phrased in the article: we conclude there is an extremely large number of causal variants with tiny effect sizes spread widely across the genome […]. More generally, the heritability of complex diseases is spread broadly, implying that a substantial fraction of all genes contribute to […] disease.

But Boyle et al. venture even further and propose a rather dark theory of why this is such… We know related genes are connected in huge networks, so that one gene can affect the behaviour of other genes with similar functions. For example if the proteins they encode are physically together, altering one will alter the other. Similarly, there is mutual dependence if you need the presence of one gene to express the other one. There are endless imaginable scenarios. But what Boyle et al. propose still terrifies me: that every gene is somehow connected to every other gene in a gigantic network, a network impossible to grasp by the human mind (very much like the human connectome). In this scenario, altering one individual gene will affect (either mildly or strongly) the behaviour of all others (so long, dreams of targeted genetic engineering!). Thus, even if a gene is unrelated to a particular disease, it will surely affect another gene which is related (just because they are connected). Research in network theory finds that most real-world networks tend to be highly interconnected; this is referred to as the ‘‘small world’’ property of networks -they say- If this is the case […] then any gene that is expressed […] is likely to be just a few steps from one or more core genes. Consequently, any variant […] is likely to have non-zero effects. That night I could not sleep. I dreamt of corridors with endless doors and saw myself lost in a house where all rooms looked exactly the same.

Figure form Boyle et al., 2017 explaining how all genes might interact in a network, contributing to disease

According to the six degrees of separation theory, we are never farther than 6 steps from any other living creature. Take the human example: how far am I from Pope Francis? In fact, I know a woman whose grandfather met the Pope last week, so I am only 3 steps away from him. In theory, it is extremely unlikely this sum will ever exceed 6. Pritchard’s article made me think of this fact. Cellular networks, social networks, the connectome, the six degrees of separation… All paths lead to the same conclusions: to a complex spider, to a monster with a thousand heads we are unable to fight, to the unconceivable… But there also exists a beautiful side to this: it means that any death, any disappearance, any act of violence we commit could have a repercussion in everybody else. It means our actions impact every single living creature, and it urges us to act respectfully. I believe this to be beautiful.

In any case, the path of statistics, with its apparently deceiving certainty, seems to have led me back to the unknown, to the wild. I am back at square zero. They say life is like a game of Hopscotch, but where is the last square? And are we able to access it?

Six degrees of separation. Graphical representation.


For months I pondered how to write this down, how to convey this ocean of contradicting ideas and feelings. Over the winter I flew back home to spend the holidays with my family. There, I found an interesting 1948 book: The Tunnel, by Argentine writer Ernesto Sabato. It was a Christmas present from my sister. The Tunnel is absurdist literature (e.g. Albert Camus et al.), and it also has a good deal to do with facing uncertainty. It tells the story of a crime: the crime of a man who murdered a woman. As we make our way through to the end, we discover this man’s anguish is caused by uncertainty too (in this case, the impossibility to know if the woman loves him only).  To face the unknown, he ponders each possibility in his mind and weights it based on what he perceives of her: ragged pieces of conversation, memories of her voice inflections, time discrepancies… His conclusions would eventually lead him to madness. Madness and anguish stem from the unknown.

Should I too embrace the absurd, I asked myself. Because while I calculate P values and hide behind thousands of permutations run in a computer cluster, Sabato’s characters embrace the fog. They decide to face the impossibility of knowing. I pondered it, but I could not. There must be a way out. We have to keep seeking meaning. But perhaps I too have been looking for places made up out of imagination. Perhaps, as Solnit suggests, I should recognise this fact and ask the people in charge of the Kyoto Encyclopaedia of Genes and Genomes or STRING or all those other databases on biological networks to add a tiny label: TERRA INCOGNITA… The terra incognita spaces on maps say that knowledge too is an island surrounded by oceans of the unknown, but whether we are on land or water is another story.

Silence as impossibility. A field guide to finding oceans in seashells

Nature_HD_Wallpapers_www.laba.wsWhat do we really hear in the insides of a seashell?

Building bridges between arts and science   |    Eddie CG

We were born from boiling water. Millions of years ago we inhabited the deep. Tiny micelles of dust, we coalesced in the surface of a spring. Looking back to our origins thus means looking back to the sea, diving into that vast darkness to recover something lost. The song of the ocean carries our story, a narrative hidden in the sounds of roaring waves. And where are we to find that song if not in the insides of a seashell?

Anybody can listen. All we need to do is to hold a shell against our ears. In fact, the seashell is not even necessary: our hands curled around our ears will do just fine. Then, miraculously, we hear the waves, the currents. But what exactly is this sound? Where does it come from? And what does it mean?

To approach these questions we need to ask ourselves something first: is silence possible? Does it exist? I anticipate most of us will immediately answer “yes, silence does exist”, because we are used to the notion of it. Silence is when a teacher asks you to keep quiet, when music stops, or when something alive dies and everything else stays respectfully still. Is this not so? But let us think about this a little more, can we truly stop listening to every single sound? Can we stay in complete silence? As we will soon see silence, if real, might actually sound incredibly similar to the ocean trapped inside a shell.

Sound, and hence everything we are capable of hearing, stems from the physical vibration of an object. Think about the air: it is transparent, but this does not mean it is empty. On the contrary, air is composed of millions of particles which bounce back and forth, colliding against each other like marbles inside a box. Air is a thiner version of the sea, invisible to our eyes but perceptible to, say, our skin. Particles in the air move fast, sometimes faster in fact than a bullet escaping from a shotgun, and most of the times they end up crashing against the surface of some object before bouncing back to space. The strength of these collisions is perceived as atmospheric pressure: we can feel it rest over our shoulders, we let it inflate our lungs like paper bags. It is pressure which pushes air inside our noses and thus, it is this imminent violence of colliding objects which keeps us alive.

But I was saying that sound stems from the vibration of an object. Somewhere, a string or a metallic rod or a muscle moves back and forth and, in doing so, imprints its movement to the surrounding air. Like a toddler who plays and as a result moves the colourful balls inside a ball pit, particles in the air are projected in the direction of the vibration: first forward, and then receding backwards. Upon vibration, air moves back and forth as a spring, and this movement generates a pressure wave. Sound is itself a pressure wave. Sound is the clear indication that somewhere something is moving.

So what happens when we listen to the sounds of a shell? Shells are round, hollow objects. They only have one opening. Such tiny caves! Objects with these shape (baubles, bottles, vases…), formally called Helmholtz resonators, all produce aquatic sounds when held against our ears. The reason behind this is that Helmholtz resonators amplify sounds which were originally too quiet to be perceived, too faint. This phenomenon occurs because these hollow objects are not actually empty, but rather filled with air. And so when sound waves (pressure waves) move the molecules in the opening of the resonator to move, air is pushed towards the insides of the cavity, going back to its original position when the oscillation recedes. This generates a pressure wave inside the shell (the resonator) and, if the waves inside and outside the cavity vibrate at the same speed, resonance is triggered. The original imperceptible sound is then amplified: it emerges from the guts of the cave, it becomes audible. Consequently, a seashell filters the sounds it receives and amplifies a selection of them: it amplifies every sound whose frequency is equal to the natural frequency of the shell (or, to be precise, to the frequency of any of its harmonic sounds).

What this means is that oceanic sounds inside seashells are not actually born within the shell, but rather outside it. They had been there all along, floating around us like whispers, like secret words of love. Only by traversing the shell, however, can they be heard. But then, where does the sound of the ocean come from? Are we surrounded by invisible seas? In fact, some of them belong to currents of air in movement, rivers of air. But some others have a fascinating history. These are the sounds of our own existence.

American composer John Cage was obsessed with the idea of silence. In his book For the birds he recalls a time he was invited to Harvard to test an anechoic chamber, a sound proof room whose walls are designed to absorb all sounds, creating absolute silence. The structure of anechoic chambers is fascinating. Floor, walls and ceiling are covered with a perpetual repetition of regularly spaced pointy shapes. When sound waves reach these shapes they are fragmented in ever smaller parts, tiny remnants of what once existed. Moreover, walls in the chamber are also covered entirely with a soft, porous material capable of absorbing the remaining movement. Inside such chambers, pressure waves are exhausted and sound gets lost, never capable of finding its way back to the human ear. It vanishes. It disappears. Anechoic chambers are the  opposite of seashells: they represent an inverted Helmholtz resonator, a black hole of sound which swallows everything that exists. Thus the term anechoic, deprived from any echo.

When John Cage visited Harvard he intended to step into a black whole. He wanted to face silence, emptiness. Never would he imagine he was about to find the exact opposite. As narrated in his book, inside the Chamber John Cage witnessed disappearance. Sounds got lost. Everything stopped. But as time went by, he came cross a series of persistent sounds. Vibrations capable of resisting even the anechoic walls. Complete silence was never reached. What could these sounds be? Where did they come from? What did they mean? They had to be born closely, otherwise the walls would trap them. Surprisingly, what John Cage heard was the ocean.
To be completely clear, this is not what For the birds says: I added those last words. But it does not make any difference. What Cage heard were the sounds of his own existence: the sound of blood as it flowed turbulently throughout his arteries, indeed a very similar sound to that of a river (and are we not conscious rivers?); valves in his heart opening and closing, like banging doors; the gutural sounds of his throat as fluids moved up and down; air flowing into his lungs in a faint whistle… Our body has its own collection of sounds. Existing means vibrating, moving, sounding. The sounds John Cage heard inside that chamber are the same sounds we can hear amplified when holding a seashell against our ears. It was as if he had moved into the deepest sections of a gigantic shell, washed by the sound waves of life. Eager to show this to the world, John Cage created 4′ 33”, a composition for piano containing no more than 4 minutes and 33 seconds of silence. For four endless minutes, the audience could turn to themselves. They could listen their own music.
johncage-433John Cage (1912 – 1992), American musician and composer.


In fact, at least for the human observer, silence is an impossibility. It exists somewhere for sure; perhaps in the farthest realms of outer space or in synthetic patches of vacuum. But no human being will ever find it, because life relies on lungs that breathe, hearts that pump, bowels that digest. And each of these processes makes a sound. We only reach silence with dead. To be quiet is to die.

So how to listen to the insides of a seashell? It is simple. Hold it against your ear, close your eyes and let the waves bathe your soul. It is not the ocean you are hearing: it is you, it is your very own existence. But perhaps it is the ocean too. Were we not born from boiling water? Millions of years ago we inhabited the deep. It should come as no surprise we still carry the sound of roaring waves washing ashore. We are memories, recollections. We carry the voices of our aquatic past.