The words that are the most important are those that you never said, those written in the language that has existed for more than two hundred thousand years, long before any known human alphabet. You find them in the blank spaces between the lines of any good novel, they are that pain that is left once the last page is over.
They are the ones that Michael Ventris could never decipher: the very devotion and the dreaming love he spent on a tongue spelled a long time ago by mouths closed by soil that has become rock.
You find them in the definition of the constant of Euler, that number that tells the story of the attempt at drawing a curve, that is never close enough, like we can never say exactly what we meant or reach what we wanted. That number that best describes, better than any novel, the hopes without a sound when you are young and sick and your recovery is not going to happen, or even worse, it will happen when it won’t matter anymore. The desires desired between four walls.
I had never seen the ocean, I was afraid of what I would have found. And you know what I discovered? My observations have shown that all those words that you were never able to say, those that chase you like a vice, a bad habit that you can’t quit, they find their way out to the ocean, like migrant snakes, or rivers. Then, only here, all mixed up, they encounter the courage to release their load of anger, fear, love. But one over the other, in all the languages we have invented, they lose any hope of being understood and become a crowd that rapes its rage against the cliffs, without relief, over and over. And yet, this giant beast, this monument to all the mistakes we have made, at the end becomes only a dog that licks your feet on the shore, still afraid, powerless.
I have collected a long list of words like those and you’ll never know them because they are hidden within the pages of the books you see closed in one of my drawings. And after all the dancing of graphite on the candid lake of paper, all the formulae cherished with the point of my pencil, what I really have been trying to say, what I meant was
The world must be wonderful, beyond the muffled atmosphere of these rooms and the obstinate curtain of encephalopathy; now that Autumn is still a harmless chrysalis, an apparently unlikely threat, while the industriousness of men swarms again, in search of untouched paths.
The Autumn of intellectual and material adventures, of encounters and discoveries, remains an unfulfilled promise, which I nevertheless do not give up on cultivating. Because I don’t know if Ulysses kissed his stony Ithaca during this season, but I like to think so.
I am perpetually mocked by the indiscreet rotation of the wall clock, which turns on the spot; while Rilke’s panther remains trapped in my chest.
When I got sick, about 20 years ago, for the first time I started thinking about diseases and loss of health. And I remember coming to the conclusion of how fortunate I was, from a physical standpoint. Not of how fortunate I had been in the past (that was obvious), when I could conquer mountains, running on rocks with my 15 Kg bike on the shoulders; no, of how fortunate I was in that very moment, while confined at home, mostly lying horizontally. I was fortunate, I could still move my hands, I had still all my body, even if I couldn’t use it in the outside world, even if most of the usual activities of a 20 years old man were far beyond reaching, I realized how fortunate I was. And after 20 years I still say that, as for the physical functioning, I am a very lucky man. There are even some years, during the core of the summer, in which I can run for some minutes in the sun. I am blessed.
I am aware that this might offend some patients, but I think that those who have ME/CFS in the vast majority of cases are fortunate too, from a physical standpoint. Yes, it is annoying to need help from others for so many things, but with assistance and some arrangements, you can go on with a productive life… unless you have cognitive impairment.
Actually, I never felt fortunate concerning my cognitive functioning. That has been a true tragedy, I have lost my entire life because of the cognitive damage, by any means because of the limitations of my body. I would have had a meaningful life (according to any standard) even with physical limitations way worse than mine if I had had a functioning brain. But I lost it when I was 20 before I could get the best from it and that is the only real tragedy.
As an example of what I am saying, consider a person like Stephen Hawking: he has been a prolific scientist, he had a stellar career (literally), he shaped our culture with his books for the general public, he was a father of three, and so forth. And yet for most of his life, while he was doing all these things, his physical functioning was way worse than the one of the average ME/CFS patient (worse even of a very severe patient, probably). For many years he could use only the muscles of the head. That’s it. Think about that. Was he missing or invisible? Definitely not!
Was he a disabled man? Yes, technically speaking he was, but in fact, he has never really been disabled, if we judge from his accomplishments. He once said that the disease somehow even helped him in his work, because he could concentrate better on his quantum-relativistic equations¹.
So what I am saying is that if we consider the physical functioning in ME/CFS, it is a negligible problem in most of the cases. The only thing that matters is the impairment in cognition (in the cases in which it is present), especially if it starts at a young age (consider that after you reach your thirties there is very little chance that your brain will give a significant contribution to humanity, even if you are perfectly healthy, so it is not a big loss if you get sick after that age). That is disastrous and there is no wheelchair you can use for it. For all the other symptoms you can find a way to adjust, just as Hawking did in a far worse situation.
This might be one of the reasons for the bad reputation of ME/CFS: there isn’t awareness about cognitive issues, no one talk about them (and in some cases, they are in fact not present at all). But I am pretty sure that the real source of disability in these patients, the lack of productivity, is due to their cognitive problems (when present). Also because in a world like ours, you can work even without using most of your muscles. It is not impossible, I would say it is the rule for a big chunk of the population.
The following one is an interview with Norwegian neurologist Kristian Sommerfelt, in which he points out some analogous considerations. He has done some research on ME/CFS with the group of Fluge and Mella, including the well-known study on pyruvate dehydrogenase. From the subtitles of the video (minute 3:38):
“This [the cognitive problem] is a very typical ME symptom and some of what I believe causes the main limitation. I don’t think the main limitation is that they’re becoming fatigued and exhausted by moving around, walking, running, or having to sit still. If it were just that, I think many ME-patients could have had a much better life. But the problem is that just actively using the mind leads to problems with exactly that, using the mind. It comes to a stop, or slow down, depending on how ill they are.”
¹ It seems that Stephen Hawking had a very unusual presentation of Amyotrophic Lateral Sclerosis (ALS): one half of those with this disease die within 30 months from the first symptom; moreover one out of two ALS patients has a form of cognitive impairment which in some cases can be diagnosed as frontotemporal dementia [R]. So, Stephen Hawking was somehow lucky, in his tragedy, and he doesn’t represent the average ALS patient. I mentioned his case as an example of a person with very severe physical impairment and no apparent cognitive decline, not as an example of the average ALS patient.
The following video is meant to be a presentation of both the blog and of myself. As I started improving again, some days ago, I decided to record this monologue, so that there could be a video memory of my struggle.
This winter I have spent almost three months in South America, to see if I would have improved during the austral summer, as I usually improve during the Italian summer; and in fact, I did improve. When I came back to Italy (in March) I had a relapse, though. For the last three months, I have been mostly horizontal, without reading or thinking for most of the time.
Now I am climbing the mountain again: I started my rehabilitation reading novels some days ago, then I switched to simple calculations and now I have written my first small code since March. And when I will reach the cognitive level I had about 20 years ago just before I got sick, I will lose everything for months (or years) and I will have to wait without thinking much (despite my best efforts) until I can start all over again…
One of my short-lived summer improvements (2013). During all these years, as soon as I started feeling better, I opened my books, even before taking a shower and having my hair cut. Happy as a child for most of the time, but also profoundly saddened for the time lost, especially at the beginning of the improvement, when I could realize how much time had passed from the previous positive phase.
Each time I had to start exactly from where I had left many months or even years before (the longest gap has been 5 years without studying). I had to do a cognitive rehabilitation each time, learn again how to read properly, how to do math, how to discipline my thoughts, how to code. It is a hard process each time. And then, a few weeks after, when I recovered enough to function mentally, I relapsed again.
I am pretty sure that only this complete, obsessive devotion to studying has saved me from very bad cognitive disability.
Before getting sick, coding and math had taught me how to think. Then, when I became ill, each equation I wrote, each drawing and code, all those efforts made to bring my soul back from wherever it was, they kept me alive for all these years.
“I can’t say if it is titanic patience or endless desperation. What are they waiting for? Have they given up waiting? Which is the present they are immersed in?”
Italo Calvino, Palomar
For most ME/CFS patients (about two thirds), the disease has an oscillating course, with some periods of improvements followed by worsening of symptoms. Some of them can even experience recoveries, only to find themselves trapped again, weeks or months later (Stoothoff J et al. 2017), (Chu L. et al. 2019). Some anecdotes suggest that there might be a correlation with seasons, with improvements in summer, but there are no systematic surveys on that, to my knowledge.
As for me, in the last 20 years of pitiful combat with this monster, I experienced some substantial short-lived improvements, mainly during the core of summer. At the very beginning of the disease, I also recovered for one whole year. It was the year 2001, I was 21 and that year has been the only period of normality in my whole adult life. I spent these 12 months studying desperately and what I am as a person is mainly due to what I learned back then. I had already been very sick for about two years and when I recovered, it was as if I were born again. It was a second chance and I was determined to do all right from day one. I decided what was really important to me and I devoted myself to my goal: learning quantitative methods to use in engineering and – one day – in biology.
When darkness caught me again, I was, among other things, reviewing all the main theorems of calculus (particularly those about differential equations) with my new skills and I remember thinking that I was becoming good at developing my own proofs. I had become good at thinking and so, I reasoned, I could finally start my life! But in a few weeks, my mind faded away, and there was nothing I could do to keep a grip to all my beloved notes and books. They became mute and closed as monolithic gravestones. I remember clearly that along with this severe and abrupt cognitive decline, I developed also orthostatic intolerance, even though I hadn’t a name for it back then. But I couldn’t keep sitting, and I didn’t know why. I was forced to lay as if the gravitational acceleration had suddenly increased. My brain had changed to a lifeless stone, and so did my body.
From that very moment, my only thought has been how could I go back to my books and my calculations. And this still is my first thought, when I wake up in the morning. After almost 20 years.
I have experienced some short improvements in these years, during which I had to learn again how to study, how to do calculations, how to code. I never went back to what I was, though. And my brain is ageing, of course, as anyone else’s brain does. But in these short periods of miraculous come back I experience a rare sense of joy (along with anger and fear). Something that you can experience only if you have been facing death.
I was born and I died dozens of times in the last 20 years, and this gives me the perception that, in fact, I cannot die: I feel as if I were immortal and I had lived for a thousand years while at the same time still being in my twenties, since I have no experience of life.
In fact, I lived only when I crossed these short bridges from one abyss to the following one.
During last summer, I’ve pursued a lot of things. I delivered a speech in Turin, after the screening of the documentary Unrest, about the OMF-funded research on the use of the measure of blood impedance as a possible biomarker for ME/CFS (video, blog post, fig. 1, fig. 2).
Then I flew to London to attend the Invest in ME conference, the annual scientific meeting that gathers researchers from all over the world who shared their latest work about ME/CFS. There I met Linda Tannenbaum, the CEO of the Open Medicine Foundation, whom I had the pleasure to encounter for the first time about a year before in Italy, and I introduced myself to Ronald Davis (fig. 3), the world-famous geneticists turned ME-researcher because of his son’s illness. I presented to him some possible conclusions that can be driven from the experimental results of his study on the electrical impedance of the blood of ME/CFS patients, with the use of an electrical model for the blood sample (R, paragraph 6).
In London, I was able to visit the National Gallery and while I was passing by all these artistic treasures without being able to really absorb them, to get an enduring impression that I could bring with me forever, I decided to sit down and to copy one of these masterpieces (I can’t draw for most of the time, and when I improve for a few weeks in summer, I usually have to carefully choose where to put my energies). I sat probably beside one of the least important portraits collected in the museum (Portrait of a young man, Andrea del Sarto, figure below) and I started copying it with a pen. When I finished, the museum was closing, so that I missed all the works by Van Gogh, among many other things.
We were at the beginning of June, I was experiencing my summer improvement, a sort of substantial mitigation of my illness that happens every other summer, on average. But because of these travels, I elicited a two-month worsening of symptoms, during which I had to stop again any mental and physical activity: I just lay down and waited. At the beginning of August, I started thinking and functioning again and I almost immediately decided to quit what was my current project (a 600-page handbook of statistics that I commenced in 2017) and I started studying mathematical modelling of enzymatic reactions (figures 4 and 5).
I knew that these reactions were described by ordinary differential equations and that I could solve them numerically with the methods that I studied just before I got sick, about 18 years ago. I was interested in the metabolic trap theory by Robert Phair, an OMF-funded researcher. So I downloaded a chapter of one of the most known books of biochemistry and a thesis by a Turkish mathematician on metabolic pathways simulation and I started my journey, working on the floor (I have orthostatic intolerance even when I get better in Summer, so I can’t use a desk, figure 6). I ended up learning the rudiments of this kind of analysis, also thanks to a book by Herbert Sauro and to some suggestions by dr. Phair himself! Some of the notes I wrote in August are collected here.
At the beginning of September, I was absorbed by the problem of how to study the behaviour of the steady states of tryptophan metabolism in serotoninergic neurons of midbrain as the parameters of the system change. This kind of analysis is called bifurcation theory and I literally fell in love with it… In figure 6 you can also see a drawing: I was drawing a picture I have been thinking about for the last 20 years. It is a long story, suffice it to say that in 1999, just before my mind faded away for 18 months, I started studying the anatomy of a man who carries a heavy weight on his back (see below). That was my first attempt to communicate what was happening to me, to describe my disease.
Only recently I considered to not represent the weight, which is a more appropriate solution since this is a mysterious disease with no known cause, and I made a draft (the one in figure 2) that I then used as a starting point for the drawing below. I finished this new drawing at the beginning of September, in a motel room of San José, in California, just in time for donating it to Ronald Davis (figures below) when I moved to the US to attend the third Community Symposium at Stanford (see here). In California, many surprising things happened: I met again Linda Tannenbaum and Ronald Davis, and yes, I encountered also Robert Phair! But this is another story…
In the following pictures, you can see how the drawing evolved. Notably, the figure in the centre changed his face and some part of his anatomy. The three figures are meant to be a representation of the same figure from three different points of view. It is more like a project for a sculpture, a monument that is much deserved by these patients.
At Stanford, I had the chance to be face to face with one of my preferred sculptures ever: The Thinker, by Rodin, in both its version: the model moulded first, on the top of The Gates of Hell, and the big one (crafted later), now considered the iconic symbol of Philosophy, but likely originally meant to be a metaphor for creative thinking (I say that because the original sculpture included in The Gates of Hell is a representation of the Italian poet Dante Alighieri, depicted in the act of imagining his poem).
At the end of September, my mind started fading away again. I knew that would have happened, even though I had an irrational hope that this year would have been different. At that point, I was in Italy and I asked some friends to help me organize a trip to the southern hemisphere, in order to live another summer. It required more time than I would have hoped. I am going to leave from Italy only tomorrow. My goal: Argentina. I have been able to do something, at a highly reduced speed, in October, though. I have developed a model for solar radiation at sea level, in function of the day of the year, of the latitude, and of the distance from the Sun (I have considered the actual elliptic orbit of our planet). The main problem has been the modelling of absorption and of diffusion of radiant energy from our star by the atmosphere, but I solved it. Part of these notes are here, but I want to self-publish the end product, so I keep the rest to myself. In that period, I was also able to find the exact solution of the improper integral known as the Stefan-Boltzmann law, something I tried to do in the summer of 2008, in vain, in one of my recovery-like periods. In figure 6 you can see one of the results of my model for solar radiation: the monochromatic emissive power at sea level in function of the day of the year, for the city of Buenos Aires.
My intention was to use that model to choose the perfect place where to move in order to have environmental conditions that closely resemble the ones that we have in Rome from June to September (the period in which my improvements happen). I also wanted to quantitatively study the effect of both infrared radiation and ultraviolet radiation on my biology. There are several interesting observations that can be made, but we will discuss these subjects another time, also because I had to quit this analysis given my cognitive deterioration. The video below is a byproduct of the geometric analysis that I had to pursue in order to build my model for solar radiation at sea level.
Dawn and dusk at a latitude of 42 degrees north, during three years of the silent rolling of the Earth on its silken ellipse. Three years of adventures, suffering, joy and death.
So, by November my mind was completely gone and my physical condition (namely orthostatic intolerance and fatigue) had worsened a lot. This year I have been able to try amphetamines: I had to go from Rome to Switzerland to buy them (they are restricted drugs that can’t be sold in Italy and can’t be shipped to Italy either). One night I felt good enough to take a train to Milan and then to take another transport to the drug store. And back. I managed to do the travel but I pushed my body too far and I had to spend the following month in bed, 22 hours a day, with an even worse mental deterioration. It is like having a brain injury. Amphetamines have been useless in my case, despite two studies on their potential beneficial effect in ME/CFS.
Right now, I am collecting all the books and the papers that I need with me in Argentina (figure above), in case I will improve enough to study again. But what am I going to work on?
I want to finish my model of solar radiation, with some notes on the effect of infrared radiation, ultraviolet radiation and length of the day on the immune system. There is a mathematical model published recently that links the length of the day to the power of the innate immune system, and I want to write a code that calculates the relative activity of the innate immunity in function of latitude and day of the year. I would like to self- publish it as a booklet.
I want to finish my handbook of statistics.
I need to correct a paper submitted for publication (it has been accepted, but some corrections have been required).
I want to deepen my understanding of the bifurcation theory for metabolic pathways and to continue studying tryptophan metabolism with this new knowledge.
I want to complete my work on autoantibodies in ME/CFS (see this blog post) and to submit it to a journal. I have been working on that for a while, inventing new methods for the quantitive study of autoimmunity by molecular mimicry.
Should I improve again in Argentina, several avenues can be followed in order to understand the reason why summer causes this amelioration in my own case. I have many ideas and I’ll hopefully write about that in the future. Of course, I also want to read all the new research papers I have missed in the last months. I will bring with me my handbook of anatomy for artists because I hope to be able to draw again, and I won’t miss this opportunity to leave some other handcrafted images behind me for posterity, that can’t care less, obviously! I would really like to finish the drawing below because I feel that in this draft I have found a truly elegant (and mechanically correct) solution for the hip joint of a female robot.
Now I am useless, my mind doesn’t work and I am housebound. I can’t read, I can’t draw, I can’t do calculations, I can’t do coding, I can’t cook… This has been the quality of my life for most of the last 20 years. This is a huge waste: I would have used these years to perform beautiful and useful calculations and to pursue art. I would really make people understand how tragic this disease is in its cognitive symptoms, what we lose because of it. This is, in fact, the reason behind this blog post: I wanted to give an idea of what I can do when I feel better, and of what I would have done if there had been a cure.
I have lost most of my adult life, but I will never accept to waste a day without fighting back.
In these long years, I have not been able to draw for most of the time, but even in the worst moments, my mind elaborated images that I could then put on paper as soon as I would have been able to. Now I can’t even think of these images, which tells me that something new has occurred to my mind. I have been drawing and thinking of images since I was four. Then, when I was a young adult, I found that these images could be translated into mathematical ideas, which opened another world for me. I don’t know whether the disease has taken completely over or if this is part of the process of ageing, but it is very hard to accept.