A leap of faith

A leap of faith

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).

Figure 1. Group photo after the screening of Unrest in Turin, Italy, with the organizer of the event (Caterina Zingale, second from the right) and representatives of two Italian ME/CFS associations.
Figure 2. Question time after the screening of Unrest. On the screen, a drawing of mine.

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).

Figure 3. Talking to Ron Davis about a possible explanation for the increase in electrical impedance in the blood of ME/CFS patients in London, during the last Invest in ME conference (blog post).

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).

Figure 4. The plot of the reversible Michaelis-Menten equation for ribulose-phosphate 3-epimerase. The intersection of the surface with the plane is the state of equilibrium of the reaction (the rate of production of X5P is the same as the rate of its transformation into Ru5P) (R).
Figure 5. The plot of the concentrations of S, P, ES and E for the transformation of L-tryptophan into N-formylkynurenine by IDO-2. This is a semianalytical solution that I found using the approximation of the Lambert function. I also pursued numerical solutions, of course (R).

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.

Figure 6. In August I was studying mathematical modelling of metabolic pathways, sitting on the floor: because of my orthostatic intolerance, I can’t sit for long, especially when I need to think. You can see the book by Sauro opened in the foreground, the thesis by a Turkish mathematician (red cover), and the handbook of Octave (blue/red cover).

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 of communicating what was happening to me, of describing 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…

resilience 2


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.

emissive power.png
Figure 7. The monochromatic emissive power of the sun at noon, at sea level, at a latitude of -32° N, in function of the wavelength and of the day of the year. Note that the vertical axis is expressed in W on microns multiplied by square meters.

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.

WhatsApp Image 2020-01-05 at 19.04.31(1).jpeg

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?

  1. 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.
  2. I want to finish my handbook of statistics.
  3. I need to correct a paper submitted for publication (it has been accepted, but some corrections have been required).
  4. I want to deepen my understanding of the bifurcation theory for metabolic pathways and to continue studying tryptophan metabolism with this new knowledge.
  5. 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.QR-A_000026

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.

Ronald Davis at Columbia University

Ronald Davis at Columbia University

All the following studies have been made mainly thanks to private funding. Please, consider a donation to the Open Medicine Foundation, in order to speed up the research. See this page for how to donate to OMF.

OMF Scientific Advisory Board Director Ronald W. Davis, PhD, has just delivered a speech about ME/CFS at the Albert Einstein College of Medicine at Columbia University in New York. In what follows you find several screenshots that I have collected during the lecture, accompanied by a very short description. I imagine that a video will be soon made available but in the meantime let’s take a look at these slides.


Indoleproprionate is reduced in ME/CFS patients. This molecule is not produced by our own metabolism, it comes from a bacterium of the gut (Clostridium sporogenes) which is low in patients. It has a neuroprotectant effect. Indoleproprionate is currently used in some clinical trials for other diseases and it might be available in the next future as a drug.

Hydroxyproline is high and this is believed to indicate collagen degradation. Ron Davis talked about the case of a ME/CFS patient who turned out to have a problem in the craniocervical junction which was fixed by surgery. Is there a link between high hydroxyproline and abnormalities of the joints (the neck among them) that some patients seem to have?


The increase in electrical impedance in blood samples (as measured by the so-called Nanoneedle device) only happens when cells from ME/CFS patients are incubated with plasma from patients. When these same cells (white blood cells) are incubated with plasma from healthy donors, the impedance is normal. For an introduction to this experiment, click here. The published work is here.


The Nanoneedle study has been extended with 20 more patients and 20 more controls.  This device can be used for drug screening, other than for diagnosis.


The peptide called Copaxone, now used in Multiple Sclerosis, seems to work in reducing the impedance in the nanoneedle device (click on the images to enlarge). Suramin also has some effect (on the right). It doesn’t seem as good as Copaxone though, to me…

SS-31 is an experimental drug for the mitochondrial membrane. It does work when used in the nanoneedle device! (click on the images to enlarge).

Nailbed capillaroscopy could be a new instrument for ME/CFS diagnosis. Inexpensive and already in use in hospitals.


No new or known pathogen has been found in patients, so far. This project is still in progress. It is updated as new technologies for pathogen hunting become available.


All the severe patients have at least one defective copy of the IDO2 gene. The same applies to 46 additional ME/CFS patients that have been recently tested for this gene. This is a common genetic problem in the general population, but it is ubiquitous in these patients. And a statistically significant difference is thus present between ME/CFS patients and healthy controls. This discovery has lead to the development of the metabolic trap hypothesis, which has been recently published (here). For an introduction, read this blog post of mine. They are planning to test the metabolic trap hypothesis in vivo using cellular cultures!


Patients have high mercury (maybe from fish in their diet) and low selenium in hair. Low selenium can reduce the conversion of T4 to T3 in the liver. Low T3 might be a cause of fatigue. High uranium was also detected!


All these studies have been made mainly thanks to private funding. Please, consider a donation to the Open Medicine Foundation, in order to speed up the research. See this page for how to donate to OMF.



Historia magistra vitae?

Historia magistra vitae?

What is happening with the CCI-hypothesis in the ME/CFS community closely resembles what happened in Italy (mainly, but not only) with the CCVI-hypothesis of Multiple Sclerosis (MS). There was this new avenue, completely unexpected and very fascinating (to me, at least), that linked MS to a defect in the venous system of the neck, named Chronic cerebrospinal venous insufficiency (CCVI) by the Italian researcher Paolo Zamboni [1]. Several MS patients underwent surgery to correct one or more veins of the neck and described themselves as cured of MS thanks to this surgery. Among them also a prominent patient advocate, Pavarotti’s wife, who gave enormous publicity to this kind of technique [2].

The diagnosis of CCVI was somehow subjective, and only CCVI-literate doctors could do it properly. The same applied for the surgery. Several surgeons in private practice started doing the surgery on MS patients, earning a lot of money in a very short period of time.

Does this seem familiar?

After a decade and several well-designed studies, no correlation between CCVI and MS has been demonstrated [3], [4].

I am not saying that there is no correlation between CCI and ME/CFS. We don’t know yet. I personally find interesting these new hypotheses about the effect of abnormal mechanical strains on the functioning of the brainstem and the possible link to ME/CFS-like symptoms and I am trying to study this new field (see this blog-post), among all the other hypotheses about the aetiology of ME/CFS.

What I would like to point out with this post is that it is perfectly possible that several patients improve with this kind of surgery even in the absence of any link between CCI and ME/CFS. This is a weird (and fascinating) phenomenon that we have already seen in other diseases. It always has the same pattern: a somehow subjective diagnosis that only a few physicians can do, a surgery or a drug that many physicians are warning against, a huge amount of patients who say that they have recovered after the intervention.

C’è del marcio a Bologna?

C’è del marcio a Bologna?

I disabili possono costituire una fonte di reddito cospicua per chi lavora nell’ambito della assistenza a queste persone. Per le disabilità riconosciute, infatti, il sistema sanitario offre (giustamente) dispositivi costosi e personale con le più varie mansioni. Ma in molti casi appalta questo genere di servizi.

Come funziona un appalto? Si redige un capitolato di gara, che elenca i requisiti che i candidati devono possedere per poter partecipare alla gara. Questo capitolato viene reso pubblico solo al momento del bando. Il vincitore sarà l’ente che, tra i candidati, meglio soddisfa i requisiti del capitolato di gara.

Un anno fa, dopo una indagine di vari mesi, la Guardia di Finanza di Bologna ha iscritto nel registro degli indagati quattro dipendenti Ausl e due rappresentanti della Associazione Italiana Assistenza Spastici (AIAS Bologna) con l’accusa di aver truccato un appalto. Infatti il file del capitolato di gara sarebbe stato corretto più volte – prima ancora del bando – dai rappresentanti di AIAS Bologna, in modo da cucirsi addosso il concorso e assicurarsi la vittoria [1], [2].

Si parla di due milioni e 130 mila euro circa, in tre anni, con possibile rinnovo per altri tre anni. Si tratta della gara per il Centro Regionale Ausili (che include anche il Centro Ausili Tecnologici) e per il Centro Adattamento Ambiente Domestico. La gara è stata sospesa [3], [4].

Dopo ulteriori accertamenti, il procedimento contro uno dei dipendenti Ausl è stato archiviato, ma per il resto l’indagine è ancora in piedi, che io sappia [5].

Io stesso sono il beneficiario dei servizi di una di queste aziende appaltatrici, che assistono le persone con disabilità. E non potrei fare a meno di questi servizi, non sopravviverei.

Proprio per questo mi infastidisce non poco venire a sapere di tali illeciti (presunti, fino a che il procedimento giudiziario non termina il suo corso). E perché sono spiacevoli e pericolosi questi illeciti? Perché in fondo suggeriscono che le disabilità più remunerative sono quelle a cui si presta più attenzione e a cui si offrono più servizi.

Lettera aperta all’Osservatorio Malattie Rare

Non sarebbe necessario scrivere una nota all’articolo pubblicato dall’Osservatorio Malattie Rare (O.ma.r.) sulla malattia di Lyme alcuni giorni fa [1], in cui si liquidano i possibili esiti cronici della patologia in parola come non esistenti o riconducibili ad altre patologie, “non ultime le patologie psichiatriche”. Non sarebbe necessario, ho scritto, perché coloro che si occupano professionalmente della malattia di Lyme, nonché i pazienti, sono consapevoli che in realtà le possibili sequele della infezione acuta da Borrelia burgdorferi sono ben documentate in letteratura e costituiscono un problema di enorme portata su cui si concentra oggi molta ricerca, spesso di alto profilo [2].

E allora perché questa preterizione? Perché un articolo divulgativo pubblicato da O.ma.r. ha notevole risonanza e – se incompleto o impreciso – rischia di alimentare false credenze tra i neofiti. L’articolo in questione è encomiabile nel divulgare nozioni preziose sulla fase acuta della malattia e nel mettere in guardia contro test e trattamenti non provati, ma è del tutto fuorviante nella parte dedicata alle sequele croniche (penultimo paragrafo).

La malattia di Lyme risponde alle attuali cure antibiotiche nel 90% dei casi. Questo significa che un decimo di coloro che ogni anno, in estate, contrae la malattia per il morso di un vettore (principalmente l’Ixodes ricinus in Europa) andrà incontro a una condizione cronica (cioè con durata superiore ai sei mesi) e debilitante, nota in seno alla comunità scientifica con il nome di post-treatment Lyme disease syndrome, PTLDS [3], [4]. Il nome scelto (che si potrebbe tradurre come Sindrome della malattia di Lyme dopo trattamento) sta a indicare che i pazienti sperimenteranno sintomi, nonostante i trattamenti della fase acuta.

La causa della PTLDS è al momento non nota. Alcuni studi supportano l’ipotesi che ci sia una disfunzione immunitaria in questi pazienti. Due studi hanno dimostrato la presenza di anticorpi contro il sistema nervoso centrale nella metà dei pazienti PTLDS [5], [6], solo per citare i più recenti. Per approfondimenti su questo argomento si legga qui e qui. La ricerca in questo campo continua [7].

Altri gruppi hanno dimostrato la persistenza del patogeno – dopo trattamento – sia nel modello animale della malattia di Lyme [8], [9], [10], che negli esseri umani [11], [12]. Presso la Columbia University è stata avviata una raccolta di tessuti provenienti da individui deceduti, che abbiano avuto una ben documentata infezione da Borrelia burgdorferi (link) proprio per indagare ulteriormente questo aspetto.

Numerosi sforzi e investimenti sono stati profusi recentemente nella ricerca di nuovi agenti antimicrobici per questa infezione, nella speranza di scongiurare le sequele croniche, da parte della Università di Stanford [13], [14], della Università Johns Hopkins [15], [16], [17], della Università Northeastern [18].

Nell’articolo di O.ma.r si legge che la sindrome in questione – chiamata impropriamente post-Lyme dall’autore – è caratterizzata da “sintomi soggettivi – e dunque non quantificabili – quali affaticabilità e difficoltà a concentrarsi”. A questo proposito è quasi superfluo ricordare che molti sintomi sono soggettivi, finché l’ingegneria non ci offre uno specifico strumento di misura: si pensi alla risonanza magnetica nella sclerosi multipla o all’elettroencefalogramma nella epilessia. In secondo luogo, questi sintomi sono solo in parte soggettivi, infatti i pazienti PTLDS presentano alterazioni quantificabili nel sistema immunitario [5], [6], nella espressione genica [19], nel metabolismo [20], etc.

Per quanto riguarda il riferimento all’ambito psichiatrico, vale la pena fare delle considerazioni. E’ senz’altro vero che le principali patologie psichiatriche (i disturbi dell’umore da un lato e le psicosi dall’altro) contemplano gli episodi infettivi come fattore di rischio [21], [22], tuttavia la PTLDS semplicemente non si sovrappone alle patologie psichiatriche, né nella presentazione clinica, né nella epidemiologia, per questo è una categoria nosografica a sé stante (vedi qui). Per fare un esempio concreto: negare l’evidenza, come sembra fare questo articolo, è una delle possibili manifestazioni della schizofrenia paranoide [23], ma né questo tipo di sintomi né altri sintomi patognomonici per malattie psichiatriche sono menzionati nella definizione di caso della PTLDS [4].

Paolo Maccallini


  1. Orzes, E. (2019, Nov. 7). Malattia di Lyme, attenzione alle false credenze. O.ma.r. (link)
  2. Instutute of Medicine (2011, Apr. 20). Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes – Workshop Report. Cap. 7 (link).
  3. Centers for Disease Control and Prevention. Post-Treatment Lyme Disease Syndrome. (link).
  4. Aucott, J., Crowder, L., & Kortte, K. (2013). Development of a foundation for a case definition of post-treatment Lyme disease syndrome. Int J Infect Dis, 17(6), p. e443-e449. (link).
  5. Chandra A, Wormser GP, Klempner MS, et al. Anti-neural antibody reactivity in patients with a history of Lyme borreliosis and persistent symptoms. Brain Behav Immun 2010;24:1018–24 (link).

  6. Jacek E, Fallon BA, Chandra A, Crow MK, Wormser GP, Alaedini A. Increased IFNalpha activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits. J Neuroimmunol 2013;255:85–91 (link).

  7. Maccallini, P; Bonin, S; Trevisan, G. Autoimmunity against a glycolytic enzyme as a possible cause for persistent symptoms in Lyme disease. Med Hypotheses. 2018 Jan. (link).
  8. Hodzic E, Feng S, Holden K, Freet KJ, Barthold SW. Persistence of Borrelia burgdorferi following antibiotic treatment in mice. Antimicrob Agents Chemother. 2008 May; 52(5) (link).

  9. Yrjänäinen H, Hytönen J, Hartiala P, Oksi J, Viljanen MK. Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment. APMIS. 2010 Sep 1;118(9) (link).
  10. Embers, M et al. Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS One. 2012; 7(1). (link).

  11. Marques, A. et al. Xenodiagnosis to detect Borrelia burgdorferi infection: a first-in-human study. Clin Infect Dis. 2014 Apr; 58(7):937-45 (link).
  12. Sapi, E. et al.The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease. Antibiotics 2019, 8(4), 183. (link).
  13. Wagh D, Pothineni VR, Inayathullah M, Liu S, Kim KM, Rajadas J. Borreliacidal activity of Borrelia metal transporter A (BmtA) binding small molecules by manganese transport inhibition. Drug Des Devel Ther. 2015 Feb 11;9:805-16. (link).
  14. Venkata Raveendra Pothineni et al. Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening. Drug Des Devel Ther. 2016; 10: 1307–1322. (link).
  15. Feng J, Wang T, Shi W, Zhang S, Sullivan D, Auwaerter PG, Zhang Y. Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library. Emerg Microbes Infect. 2014 Jul; 3 (7). (link).
  16. Jie Feng, Megan Weitner, Wanliang Shi, Shuo Zhang, David Sullivan, and Ying Zhang. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library. Antibiotics (Basel). 2015 Sep; 4(3): 397–410. (link).
  17. Feng J, Auwaerter PG, Zhang Y. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One. 2015 Mar 25;10(3). (link).
  18. Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells. Antimicrob Agents Chemother. 2015 Aug;59(8):4616-24. (link).
  19. Jerome Bouquet et al. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease. mBio. 2016 Jan-Feb; 7(1). (link).
  20. Fallon BA et al. Regional cerebral blood flow and metabolic rate in persistent Lyme encephalopathy. Arch Gen Psychiatry. 2009 May;66(5):554-63. (link).
  21. Benros ME et al. Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry. 2013 Aug;70(8): 812-20. (link).
  22. Benros ME et al. Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. Am J Psychiatry. 2011 Dec;168(12). (link).
  23. Rajiv Tandon et al. Definition and description of schizophrenia in the DSM-5. Schizophrenia Research, Volume 150, Issue 1, October 2013, Pages 3-10. (link).






Nelle grotte francesi di una località chiamata Lascaux degli uomini dipinsero il mondo che li circondava, più di diecimila anni fa. E’ tutto ancora lì, come lo hanno lasciato.



Lo immagino su una roccia

seduto con il mento in un palmo

per cento e più dei secoli

della nostra storia


Immagino che si sia commosso

il Tempo per una volta

nelle stanze intime della terra

ha fermato i giorni a quel giorno

che l’ultimo dei pittori

lasciò un disegno

e portò via i suoi colori


Sono ancora lì i cervi megaceri

non si sono estinti i mammut

in quelle grotte

un fiume perduto si è conservato

ecco,  lo attraversa un gruppo di renne

per sempre

e l’altra sponda non arriva mai


Immaginate che mi sia commosso

seduto con il mento in un palmo

sulla riva di quel fiume

il mondo non si è perduto


La terra ha chiuso da tempo le gole

di quelle genti

ed è diventata pietra

eppure ho visto l’ultimo dei pittori

guardare il suo lavoro

seduto con il mento in un palmo

è ancora lì

e diecimila anni fa

non ha portato via i suoi colori



Lettera al Ministro della Salute

Nei giorni scorsi mi è stato chiesto di scrivere un breve discorso da pronunciare davanti al ministro Giulia Grillo, in una delle tante occasioni in cui la aristocrazia contemporanea concede la voce alle istanze degli elettori. Non ho mai considerato i politici degli interlocutori interessanti, per due ordini di ragioni, collegate fra loro: la prima è che non li ritengo artefici della storia, la seconda è che, in media e con qualche proverbiale eccezione a suffragio della regola, si tratta di persone mediocri.

Del resto una persona in gamba di certo non si dedica alla politica, non ne avrebbe il tempo né la motivazione. Immaginate se Fancis Crick, anziché prendere d’assalto la struttura del DNA a colpi di funzioni di Bessel, si fosse dedicato alla amministrazione delle piccolezze pubbliche: che perdita, che delitto contro l’umanità! Euclide, che da solo ha prodotto il volume che è secondo per diffusione solo alla Bibbia (che però vanta decine di autori tra evangelisti e profeti, oltre il Creatore dell’Universo), ci avrebbe lasciati orfani della spina dorsale della nostra formazione se, anziché donarsi alla matematica, si fosse fatto traviare dall’agone politico. Se Newton si fosse perso in dibattiti sulla cosa pubblica, la prima equazione differenziale della storia avrebbe dovuto attendere forse decenni, ma non sarebbe mai stata così bella. I ministri passano senza lasciare traccia, le persone grandi – magari travestite da miserabili (si pensi a Van Gogh o a Srinivasa Ramanujan) – cambiano il mondo per sempre e sempre per il meglio.

Insomma, gli individui di talento non devono occuparsi di politica, è umiliante. E altrettanto umiliante è, a mio avviso, cercare di interloquire con gli amministratori della polis. Ciò nonostante, poiché mi è stata fatta questa richiesta accorata, ho scritto quanto segue, controvoglia e consapevole di aver compiuto un passo ulteriore nel mio personale cammino verso l’inferno.


Illustre Ministro e gentili convenuti,

attraverso queste poche righe apprenderete della esistenza di una patologia a cui è associato un livello di disabilità non inferiore a quello della sclerosi multipla, dell’artrite reumatoide o dell’insufficienza renale [1] e la cui prevalenza nella popolazione generale è superiore a quella della sclerosi multipla [2]. Di questa malattia non avete probabilmente mai sentito parlare ma è possibile che ciascuno di voi abbia conosciuto almeno una volta nella vita una persona che ne è afflitta: un’amica, o il figlio di un collega; individui produttivi fino a un certo momento della loro esistenza, poi inspiegabilmente scomparsi dalla scuola o dal lavoro, per un male che non riescono a chiamare per nome.

Si stima che 240 mila italiani ne soffrano, circa lo 0.4% della popolazione [3]. Di questi, l’80% non è in grado di svolgere una attività lavorativa [4] e il 25% è costretto in casa o a letto dalla severità dei sintomi [5]. Il loro funzionamento fisico e mentale sarà compromesso per sempre – solo il 5% dei pazienti guarisce [6] – e la loro vita sarà ridotta in molti casi a una sopravvivenza improduttiva.

Riuscite a ricordare la vostra peggiore influenza? Una fatica prepotente vi costringe a letto, la mente diventa incapace di formulare pensieri, è necessaria assistenza anche per piccoli gesti quotidiani. Ecco, in prima approssimazione è possibile affermare che le persone affette da questa condizione sperimentino quel tipo di compromissione tutti i giorni, dal momento dell’esordio della patologia. E la caratteristica dei pazienti, il sintomo patognomonico della condizione, è che qualunque tentativo di evadere dalla cattività fisica e mentale peggiora i sintomi. Ogni sforzo, anche il più triviale, acuisce la patologia. L’età media di insorgenza della malattia è 33 anni, ma sono documentati casi di esordio a meno di 10 anni di vita e a più di 70 [7]. E naturalmente, più precoce è l’esordio e maggiori sono i danni nella vita del paziente: i ragazzi perderanno l’istruzione, lo sport, gli amici e il futuro; gli adulti dovranno rinunciare al lavoro e alla famiglia.

Chiunque di voi o dei vostri congiunti può sviluppare la malattia domani. In quel caso malaugurato, al termine di un percorso annoso tra vari ospedali e specialisti, dopo aver speso i risparmi in cerca di una risposta, scoprireste che nessuna cura potrà restituirvi la salute. Non conta quanto talentuosi foste prima, quante risorse avete a disposizione, non conta la vostra posizione sociale: la vita sarà rovinata per sempre.

Tutti coloro che professionalmente si occupano di questi pazienti, dai ricercatori ai medici, si riferiscono alla patologia con la sigla ME/CFS, un nome con una lunga storia, troppo lunga da raccontare qui.

Non spetta a me parlare delle anomalie immunitarie, metaboliche e neurologiche documentate in questi pazienti negli ultimi 30 anni, ma fornirò al Ministro, e a chiunque sia interessato, la documentazione scientifica raccolta sin qui sulla ME/CFS, tra cui in particolare una revisione della letteratura ad opera della prestigiosa National Academy of Medicine, la quale nel 2015 ha definito la ME/CFS “una malattia multisistemica, seria, cronica che limita drammaticamente la vita di chi ne è colpito” (7).

Ad oggi non è possibile salvare queste persone, ma c’è una comorbidità che le affligge su cui si può e si deve intervenire: la cronica mancanza di fondi per la ricerca e di assistenza sanitaria ed economica. C’è bisogno di ambulatori dedicati, di consapevolezza diffusa e di ricercatori che indirizzino i loro sforzi verso questo problema. In Italia abbiamo tutta la tecnologia e le competenze scientifiche per giocare un ruolo di primo piano nella corsa alla ricerca di una cura, ricerca che attualmente vede impegnati alcuni gruppi sparsi nel pianeta, con risorse umane ed economiche tragicamente troppo modeste. Con una sua decisione, Ministro, si può cambiare il corso di queste vite lasciate fino ad oggi sole ad affrontare lo iato muto della loro esistenza.

Paolo Maccallini


  1. Falk Hvidberg, M, et al. The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS). PLoS One. . 6 Jul 2015, Vol. 10, 7.
  2. Jason, LA, et al. Differentiating Multiple Sclerosis from Myalgic Encephalomyelitis and Chronic Fatigue Syndrome. Insights Biomed. 12 Jun 2018, Vol. 2, 11.
  3. Jason, LA, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med. 11 Oct 1999, Vol. 159, 18, p. 2129-37.
  4. Klimas, N e Patarca-Montero, R. Disability and Chronic Fatigue Syndrome: Clinical, legal, and patient perspectives. Binghamton : Routledge, 1998. p. 124.
  5. Pendergrast, T, et al. Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome. Chronic Illn. Dec 2016, Vol. 12, 4, p. 292-307.
  6. Cairns, R e Hotopf, M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond). . Jan 2005, Vol. 55, 1, p. 20-31.
  7. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Institute of Medicine. Washington (DC) : National Academies Press (US), 2015.