Italian Pioneers in Cardionephrology: how some fundamental Italian cardiorenal researches have passed into oblivion

Abstract

A historical research was made on papers published by Italian scientists on cardiorenal diseases. The investigated period is between the beginning of the 20th century and the entry of Italy into the Second World War, 1940. 34 papers dealing with the relationship between the kidney and the cardiovascular system were retrieved. All but two articles were published in Italian medical periodicals. The topics covered are varied and range from cardiotoxicity of substances in uremia to the role of renal disease in vascular damage. Some articles are forerunners of later pathophysiological concepts and research technologies. These concern early atherosclerotic vascular damage and the presence of dialyzable cardiotoxic substances in renal insufficiency. Unfortunately, these highly innovative researches have had little diffusion and have fallen into oblivion in Italy and abroad. In conclusion, our research shows that in the first half of the 20th century in Italy there was a lively interest in cardio-renal diseases and that some researchers had produced precursor results of what was confirmed many years later.

Keywords: cardionephrology, cardiorenal studies, Italian scholars, history of nephrology

Introduction

Thanks to the Mario Timio’s series of congresses in Assisi, dedicated to Cardionephrology, this branch of Nephrology has experienced growing success in Italy and in the world since 1987 [1]. Although the term Cardionephrology apparently was coined in 1991, studies on the relationship between kidney disease and the heart have a much longer history [24]. An attempt to define cardiorenal disease was made in 1914 in Philadelphia by the renowned clinician Alfred Stengel (1868-1939). According to this eminent clinician “the term comprises cases of combined cardiovascular and renal disease without such manifest predominance of either as to justify a prompt determination of the one element as primary and important and the other as secondary and unimportant” [5]. This term was also used in death certificates in USA [4]. Among the early studies on cardiorenal syndromes, the best known are those performed in UK, France and USA [3, 4].

In Italy in the first half of the 20th century such definition was not diffused, although the relationship between heart and kidney was the object of several studies. The heart involvement in uremia, in acute and chronic glomerulonephritis and the early atherosclerotic changes associated with chronic renal failure were the topics most frequently dealt with. To our knowledge, these studies remained almost as unknown abroad as at home. Only belatedly through the references of the paper on “The pathogenesis of renal cardiopathy” from the Pisa group published in 1957 some early Italian work on cardiorenal disease has come to light [6].

To what extent the lack of acknowledgment and of citations of early Italian studies in the cardiorenal field can be justified can only be established from a retrospective survey of the early research carried out in this field. We have therefore undertaken this study with the aim of retrieving Italian papers dealing with cardiorenal disease, published in the first half of the 20th century. We subsequently analyzed the retrieved studies and compared them with contemporary international researches.

 

Material and Methods

We searched the medical bibliographic databases for articles that dealt with kidney pathophysiology and disease written by Italian authors, published between the year 1900 and 1940, entry of Italy into the Second World War. Then many Italian doctors were drafted into the army and stopped their normal activities. Moreover, the war was a turning point for medical research worldwide since because of it changed completely [7]. Therefore, we chose 1940 as the end limit for our research. Among the papers we have therefore selected those that dealt with the relationship between the kidney and the cardiovascular system. The articles in this selection were analyzed for the purposes of this research.

 

Results

We retrieved 638 papers of Italian authors published in the period 1900-1940. Among these, 34 (5.4%) dealt with the relationship between the kidney and the cardiovascular system. All but two papers were published in Italian journals. The main topics dealt with are shown in chronological order in Table1.

Year Subject Bibl Ref #
1911 Urea concentrations and heart function 8
1914 Heart Hypertrophy in unilateral kidney disease 9
1924 Lipid metabolism in GN and uremia 10
1924 CV changes in different kidney diseases 11
1930 Heart failure and the kidney 12
1935 Heart involvement in acute GN 13
1936 Vascular lesions in chronic GN 14
1939 Electrocardiographic changes in Uremia 15
1940  Atherosclerosis, myocardium changes and heart failure in chronic GN 15
Table 1: Cardiorenal topics in Italian researches (1900-1940). GN: Glomerulonephritis. CV: Cardiovascular.

Representative papers are listed in the references [8-16]. In Figure1 is shown the cover of the oldest cardiorenal Italian paper we were able to retrieve, published in a French journal. Almost all authors were from internal medicine institutes. Only one was a surgeon [17].

Cover of one of the oldest cardiorenal Italian papers published in a French journal.
Figure 1: Cover of one of the oldest cardiorenal Italian papers published in a French journal. The subject is the effect of urea on the heart, one of the hottest topics of the period.

 

Characteristics of researches

Most were clinical studies. Others were clinico-pathological [9, 14, 16]. Only two were based on experiments made in lab with animals [15, 17]. Blood pressure measurement, electrocardiogram, x-ray and blood chemistry were the clinical investigation tools employed. Since early researches much emphasis was placed on the role played by urea or other toxic substances produced by kidney disease on the heart [8, 18]. Later papers generally dealt with single nephropathies in their relationship with heart diseases. An attempt was also made to list individual types of renal diseases with their association with cardiovascular complications [19].
Several papers aimed at discriminating the effects of hypertension on the cardiovascular system from those produced directly by kidney disease [9,13]. The cardiovascular complications investigated were heart hypertrophy and failure, arrhythmias and electrocardiographic changes, macrovascular and microvascular changes. In none of the retrieved papers pericarditis was a subject of research. Generally, the authors published only one paper on cardiorenal disease. Only one researcher published several papers on this subject, in the period from 1935 to 1940, Fernando Marcolongo (1905-1969) from Turin [13, 16, 20-22].

 

Discussion

We found that from the beginning of the 20th century to the war, Italian researchers published a fair amount of papers dealing with cardiorenal diseases [18]. The results of some of these studies have maintained their value over time and have proved to be the forerunners of research lines that are still current today. Table 2 summarizes the results of two papers that we believe are the most relevant in this respect.

Year Research Bibl Ref#
1939 Study of the effect of serum from uremic patients on guinea pig heart. Dialysis of serum removed its toxic effect on myocardium. First demonstration of dialyzable heart toxic substances in uremia. 14
1940 Demonstration that early coronary atherosclerosis in chronic glomerulonephritis is independent of hypertension and other general risk factors. Clinical and pathological study. 15
Table 2: Outstanding cardiorenal Italian researches (1900-1940).

Generally, the different themes dealt with in the articles we retrieved do not differ from those of contemporary international medical literature, except for pericarditis. This uremic complication, although dealt with in the Italian textbooks of the time, is not present in the articles we have found. Uremic pericarditis, on one hand, was the object of several researches carried out in the US during the same period [23, 24]. On the other hand, it should be emphasized the particular interest shown by some Italian authors towards vascular lesions, which today we would define as atherosclerotic, associated with chronic nephropathies. In some of the papers, the hypothesis that atherosclerotic lesions are a direct consequence of nephropathy is put forward [14].

The most significant and original research on the relationship between vascular lesions and chronic nephropathies is the one carried out by Marcolongo [16]. This study was based on pathological observations, during a period of several years, and the respective clinical characteristics of 44 cases of chronic glomerulonephritis. The conclusions of the study are original and differ from what was generally believed not only in Italy but also in the US at the time and years later [25, 26]. In fact, against common thought, this research suggests a direct role played by nephropathy in the pathogenesis of coronary atherosclerotic lesions. In particular, this research, carried out on young subjects, indicates a particular role of nephropathy in the interrelation between coronary artery disease, hypertension and heart failure. In the sample population studied the other well-known risk factors for atherosclerosis were absent. The short duration of arterial hypertension, resulting from the young age and the short time of the disease, ruled out its role in the pathogenesis of the coronary lesions. Therefore, nephropathy was indicated as the key element in favoring the early development of coronary damage.

This, to our knowledge, is the first study identifying a specific role of the kidney in the development of vascular damage. Unfortunately, the well-known studies made in the US, dealing with the same matter, published many years later do not mention this innovative research published in Italy at the time of the start of the Second World War [27, 28]. The only recognition of this innovative research came many years later in the seminal article on renal heart disease from the Pisa group [6]. We attribute the Italian language of the medical periodical and the date of publication, coinciding with Italy’s entry into World War II, among the causes of the scarce recognition obtained by this innovative research.

Another research that deserves a particular mention is an animal testing carried out in Genoa [15]. The experiment consisted in studying the effects of the serum of uremic patients, its dialysate or its ultrafiltrate on the heart of guinea pigs. The authors found that the injection of dialyzed sera from the uremic patients did not induce any cardiac changes in the guinea pig. Conversely, the dialysate and the ultrafiltrate of the uremic serum induced a myocardial toxicity which manifested itself with various alterations of the electrocardiogram. To rule out a possible interference of hypertensive substances the experiment was repeated with the serum of a hypertensive subject without uremia. In this case the injection of the ultrafiltrate did not induce any myocardial change. The authors conclude that they demonstrated for the first time that uremic serum contains myocardiotoxic substances. Most interestingly their experiment shows that these substances are removable with ultrafiltration or dialysis. This research introduces for the first time in the scientific world the possible removal of cardiotoxic uremic substances with dialysis. Surprisingly, this discovery was ignored in subsequent years even in well-documented texts such as Cameron’s on the history of dialysis or in other more recent historical reviews on cardionephrology [29, 4]. We ascribe to the use of the Italian language and to the time of publication, simultaneous to the war declaration, the cause of this outstanding research going unnoticed.
As far as the author is concerned, it is worth underlining that most of the authors of these early researches have subsequently played an important role in Italian internal medicine before and after the Second World War. Some of them such as Nicola Pende (1880-1970) and Luigi Condorelli (1899-1985) obtained chairs at the most prestigious Italian universities and founded illustrious schools of internal medicine and cardiology. The same observation was previously made for early scholars of nephrology [30, 31]. Marcolongo became professor of internal medicine and was among the founders of the Italian Society of Nephrology [32].

Our investigation of early cardiorenal studies in Italy allows us some brief considerations. The first is that the problem of the complex pathological relationships between kidney and heart was well present in the scholars of the time. Therefore, many researches were conducted on the subject. Some of these, even in the light of subsequent scientific advances, appear to be forerunners of new knowledge. Unfortunately, for a whole series of circumstances related to the troubled period and the use of Italian in the publication, these results were not sufficiently widespread in the scientific community. Consequently, the value of these researches did not obtain the deserved recognition and went soon into oblivion. Other similar forgetfulnesses have been reported recently in the nephrology field [33]. We, therefore, hope with our research that we have drawn historical attention to these forgotten studies.

 

Acknowledgments

We are grateful to Mrs. Susanna Mattioli of the Biomedical Library of the University of Perugia for her invaluable help in retrieving the historical papers.

 

Bibliography

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Interview with Vito Cagli: his life as a nephrologist and more

Abstract

This interview describes the numerous and important contributions that Vito Cagli, who was born in Ancona in 1926, has given to the Italian Nephrology and to other fields of Medicine. These contributions, that are very poorly known today, were produced especially in the years in which Cagli worked as deputy director of the Centre for the Investigation and Treatment of Hypertension and Renal Diseases at Policlinico Hospital Umberto I in Rome. This interview also describes the early phase of Italian Nephrology before the introduction in our country of renal biopsy and of hemodialysis.

Keywords: History of Nephrology, History of Italian Nephrology, History of arterial hypertension

Sorry, this entry is only available in Italian.

Introduzione

Questa intervista è nata da un suggerimento del collega e amico Attilio Losito ed è stata fatta dalla co-autrice Bianca Gualandi il 9 marzo scorso a Roma, nella casa dell’intervistato. Essa racconta la storia di vita nefrologica, e non solo, di Vito Cagli, nato ad Ancona nel 1926.

Laureatosi in Medicina presso l’Università di Roma nel 1950, Cagli si è specializzato in Medicina Interna nel 1956, e in Igiene e Tecnica Ospedaliera nel 1966. Dal 1961 al 1966 ha prestato la sua opera come assistente medico nel reparto di Medicina Interna dell’Ospedale San Giovanni di Roma. Successivamente, per molti anni, è stato vice-direttore del Centro per lo Studio e la Cura dell’Ipertensione Arteriosa e delle Malattie Renali del Policlinico Umberto I di Roma, e dal 1993 al 1999 ha diretto il Centro di Dialisi di una Casa di Cura romana. 

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Interview to Attilio Losito: my half-century life as a nephrologist in Perugia

Abstract

In this interview Attilio Losito tells us about his first nephrological experiences gained in the late sixties of the past century in the Institute of Patologia Medica in Perugia directed by Giovanni Gigli, and his subsequent experiences, which also included a period at Guy’s Hospital in London. The interview also describes the important contributions that the school of Perugia produced in the field of nephrology and its main protagonists. This nephrological life story highlights: the role that internal medicine, with its multidisciplinary approach, had in the development of nephrology in its beginnings; the importance of cooperation with foreign institutions; the contributions that specialised research laboratories attached to renal units have given to the improvement of the diagnosis and to the understanding of the pathogenesis of nephropathies.

Keywords: history of nephrology, history of Italian nephrology, history of Italian internal medicine

Sorry, this entry is only available in Italian.

Introduzione

di Giovanni B. Fogazzi

In questa intervista Attilio Losito racconta la sua storia di vita nefrologica iniziata alla fine degli anni sessanta del secolo scorso nell’Istituto di Patologia Medica di Perugia, diretto da Giovanni Gigli, e protrattasi per circa cinquanta anni. L’intervista descrive anche le figure principali che operarono nella scuola nefrologica di Perugia e i suoi importanti contributi in diversi settori della nostra specialità, dalla introduzione di nuove tecniche dialitiche all’uso di metodiche innovative per lo studio della patologia renale e della patogenesi delle nefropatie, alla nascita della cardionefrologia. Questi contributi furono favoriti da diversi fattori: che ai suoi albori la nefrologia di Perugia fosse parte della medicina interna, ciò che che ha favorito un approccio multidisciplinare al paziente nefropatico, che nel corso degli anni è andato via via scomparendo, in Italia e non solo; la collaborazione con centri clinici e di ricerca stranieri, tra cui il Guy’s Hospital di Londra, di cui Attilio Losito ha frequentato sia la nefrologia sia diversi laboratori; la possibilità di disporre di un laboratorio di ricerca clinica annesso alla nefrologia di Perugia. Su quest’ultimo aspetto mi permetto di affermare, con il pieno sostegno di Attilio Losito, che la progressiva scomparsa di questi piccoli e specializzati laboratori, a causa di una reclamata necessità di centralizzazione dei laboratori clinici, ha avuto un impatto negativo sulla ricerca nefrologica nel nostro Paese, con svantaggio anche per i nostri pazienti nefropatici.

 

Perché hai deciso di fare il medico? E perché hai deciso di dedicarti alla nefrologia?

Ambedue i miei genitori erano medici così come molti dei loro amici. Durante gli ultimi anni di liceo, ascoltando le loro conversazioni, rimasi colpito dalle prospettive che in quegli anni si aprivano per la medicina grazie alle nuove scoperte. Fu quindi una naturale conseguenza iscrivermi a medicina. La prima materia clinica che incontrai fu la Patologia Medica il cui docente, come vedremo, era uno dei primi cultori della Nefrologia in Italia. Le sue lezioni sul rene e gli altri argomenti erano affascinanti e questo mi spinse a far domanda di internato in quell’Istituto.

 

Come è nata la nefrologia a Perugia?

A Perugia la nefrologia è nata sotto l’impulso di Giovanni Gigli (1913-1991), che era stato chiamato alla cattedra di Patologia Medica dell’Università nel 1961.

La sua chiamata rientrava nel vasto progetto di sviluppo della facoltà promosso dal rettore Giuseppe Ermini (1900-1981), che aveva scelto la politica di attirare a Perugia giovani cattedratici con l’ambizione di successivi trasferimenti a sedi più prestigiose. Così in quegli anni passarono per Perugia, e vi crearono la loro scuola, Paride Stefanini (1904-1981), Adamo Grilli (1907-1989), Roberto Burgio (1919-2014), Paolo Larizza (1912-2000) ed altri luminari che in seguito lasciarono la loro impronta sulla medicina italiana.

Gigli, che era già noto in Italia per i suoi studi nefrologici svolti a Pisa sotto l’egida di Gabriele Monasterio (1903-1972), rientrava tra queste figure, e fu il primo clinico con cui io, studente, venni in contatto. Come era di norma a quei tempi, portò con sé un gruppo di giovani allievi [1,2], che furono poi i miei docenti.

Nell’Istituto di Patologia Medica, che comprendeva circa 70 letti, si ricoveravano pazienti con tutte le patologie internistiche, ma il nome di Gigli attirava soprattutto pazienti nefropatici da gran parte del centro-Italia, così che una buona parte delle degenze erano di tipo nefrologico. All’inizio, non c’era uno staff specificamente preposto a questi pazienti e quasi sempre era il direttore che sopraintendeva alla loro cura. Quando nel 1966 fui ammesso come studente interno, la terapia dell’insufficienza renale cronica era basata principalmente sulla già famosa “dieta di Pisa”, messa a punto da Sergio Giovannetti (1924-2000) e Quirino Maggiore (1932-2017) [3].

In quell’istituto preparai la mia tesi di laurea sulle alterazioni dell’equilibrio idro-elettrolitico ed acido-base.

L’istituto comprendeva anche diversi laboratori, uno per le analisi cliniche di routine e gli altri dedicati ai vari filoni di ricerca (compreso un centro di fisiopatologia respiratoria del CNR diretto da Carlo Augusto Sorbini) all’interno dei quali i giovani medici erano tenuti a svolgere delle attività. A me furono affidate, per i pazienti della mia corsia, l’esecuzione dell’esame emocromocitometrico e l’esame delle urine e, per tutti i richiedenti interni ed esterni, la misurazione dell’osmolarità plasmatica ed urinaria e della calcemia. Queste incombenze, ancorché modeste, aprivano la strada ad un approccio scientifico alle varie problematiche cliniche.

 

Come ebbe inizio la dialisi?

Nel 1967 la locale Cassa di Risparmio donò all’Istituto, su richiesta di Gigli, un rene artificiale tipo Kiil, che fu destinato al trattamento dell’insufficienza renale acuta. All’inizio le sedute dialitiche si svolgevano sotto la direzione diretta di Gigli (che aveva maturato esperienze con il rene artificiale dapprima in Svezia, a Lund, e poi a Pisa) e dell’aiuto Giulio Muiesan (1928-1989). In seguito, visto il successo dei trattamenti eseguiti, fu acquistato un secondo rene artificiale con lo scopo di creare una sezione specifica e iniziare il trattamento dei pazienti con insufficienza renale cronica. Questo tipo di attività non attraeva gli assistenti più anziani, che preferivano seguire il filone cardiologico o pneumologico, e l’incarico venne perciò affidato al giovane Umberto Buoncristiani (1939-2016), sotto la supervisione di Gigli.

Nel 1968, grazie anche alla presenza nella Clinica Chirurgica di un buon angiochirurgo che garantiva la qualità degli accessi vascolari, l’attività dialitica per l’insufficienza renale cronica potè decollare. Si rese subito necessario affiancare qualcuno a Buoncristiani per garantire la continuità assistenziale e venni indicato io, che ero il più giovane tra i volontari. I miei compiti erano di tipo ancillare: preparare le soluzioni dialitiche, controllare con il refrattometro ottico – che allora svolgeva le funzioni del conducimetro – la concentrazione dei soluti totali nel bagno di dialisi, e sovraintendere alla preparazione dei dializzatori. Buoncristiani e io ci alternavamo nei turni di guardia, che comprendevano anche quelli dell’intero Istituto. Le urgenze dialitiche più frequenti erano le occlusioni degli shunt artero-venosi, gli edemi polmonari e le iperpotassiemie, che erano di difficile gestione, dati i lunghi tempi di preparazione del dializzatore Kiil.

L’anno seguente, con l’aumento del numero dei pazienti, l’Ospedale decise di assumere stabilmente il personale medico dedicato alla dialisi e, dopo Buoncristiani, fummo assunti io e Mario Timio, che si era associato a noi. Il nostro servizio di dialisi era l’unico in un’area geografica molto vasta e rapidamente le richieste superarono le possibilità di trattamento. In questa situazione Buoncristiani ritenne che la dialisi peritoneale, che fino ad allora veniva utilizzata solo per i pazienti acuti, fosse un’alternativa praticabile e vi si dedicò con determinazione, anche contro lo scetticismo molto diffuso a livello nazionale [4]. Nel frattempo, il servizio di emodialisi era stato potenziato sino a disporre di 10 postazioni dialitiche ed erano stati assunti altri due colleghi della Patologia Medica, Loris Lorusso e Carmen Carobi (1941-2017). Grazie a questo incremento di risorse umane e materiali, e grazie alla dialisi peritoneale, riuscimmo a rispondere alle esigenze assistenziali.

Nel frattempo, nel 1968, quando le scuole di specializzazione di nefrologia ancora non esistevano, su consiglio di Gigli mi iscrissi alla scuola di medicina interna dell’università di Pisa, diretta da Gabriele Monasterio, nella quale lo studio delle malattie renali occupava un posto di rilievo. Poi, nel 1972, quando furono aperte le prime scuole di nefrologia, mi iscrissi alla scuola di Bologna, per la grande esperienza maturata in quella sede nella biopsia renale.

 

Quali erano le figure di riferimento nell’Istituto diretto da Gigli?

Il servizio di dialisi era parte dell’Istituto di Patologia Medica e di conseguenza lo sparuto gruppetto dei dializzatori poteva fruire del laboratorio interno e del supporto clinico dei colleghi più anziani, che avevano maturato le loro prime esperienze nella Clinica Medica di Pisa, sviluppando diverse competenze specifiche (Figura 1). Alcuni tra questi si dedicavano a tematiche molto affini alla nefrologia.

Il gruppo di Giovanni Gigli i
Fig. 1: Il gruppo di Giovanni Gigli in occasione del primo congresso di Cardionefrologia ad Assisi nel 1987

Camillo Valori (1932-2007), che poi divenne patologo medico a Terni, si era specializzato al Hammersmith Hospital di Londra nel campo del sistema nervoso simpatico e Timio si associò subito a lui per le ricerche in questo settore [5].

Vittorio Grassi (1934-2016) ci supportava nel disimpegno nei disordini più complessi dell’equilibrio idro-elettrolitico ed acido-base e nei primi rudimenti di statistica medica appresi alla scuola di Giulio Maccacaro (1924-1977) [6].

Giulio Muiesan, che era l’aiuto-primario, spiccava su tutti per le sue grandi capacità cliniche e carisma. I giovani medici si ispiravano a lui per il suo metodo clinico sfrondato dai molti orpelli ancora presenti nella medicina italiana, che aveva appreso nelle sue lunghe permanenze in ospedali anglosassoni. Copriva con queste sue caratteristiche le complessità delle varie problematiche internistiche che si presentavano nella nuova attività dialitica. Muiesan era anche interessato alla nefrologia e alla ricerca nefrologica. Infatti, aveva apposto la sua firma il 28 Aprile del 1957 a Parma all’assemblea di fondazione della Società Italiana di Nefrologia, ed era stato il trait d’union tra Monasterio e Jean Oliver (1889-1976) a New York per lo studio sulla glicosuria renale [7]. Grazie a Muiesan si era sviluppata anche una collaborazione con Stanley Peart (1922-2019) del Saint Mary’s Hospital di Londra, che per primo purificò l’angiotensina e ne individuò la struttura [8]. Mediante questa collaborazione Muiesan e Vincenzo Renzini, giovane ricercatore e uno dei fondatori del gruppo dell’ipertensione (1938-2005), produssero ricerche sul sistema renina angiotensina e sui rapporti tra ipertensione e sistema nervoso autonomo [9]. In questo contesto si sviluppò anche una collaborazione con Glenn Lubash della Cornell University, uno dei pionieri della emodialisi [10]. Presso di lui, trasferitosi a Baltimora, lavorò per più di un anno nel 1970-71 Carlo Alicandri (1940-2007), sempre in campo nefrologico. Nell’Istituto si era così creata un’atmosfera internazionale stimolante per tutti noi, arricchita dalle visite di figure nefrologiche di grande rilievo come il britannico Oliver Wrong (1925-2012), uno dei padri della nefrologia inglese [11]. Personalmente, ricordo ancora quando mi trovai ad accompagnare al laboratorio delle catecolamine Vincent DeQuattro (1933-2001), noto ipertensiologo della University of California, Los Angeles (UCLA). A tutto questo va aggiunto che diversi colleghi avevano fatto un’esperienza almeno semestrale nei maggiori ospedali londinesi.

Le ricerche sul sistema adrenergico in particolare ebbero una notevole risonanza nazionale ed internazionale [12]. Infatti, nel corso degli anni, diversi colleghi da centri nefrologici italiani e stranieri vennero a Perugia per apprendere da Valori e Renzini. In particolare, si sviluppò un notevole interesse sulle relazioni esistenti tra sistema cardiocircolatorio e rene, inizialmente studiate da Gigli e Muiesan a Pisa [13,14]. Questo fu il filone che seguì con perseveranza Mario Timio, che oggi viene considerato il fondatore della cardionefrologia [15].

Grazie a Muiesan si andò allargando sempre più anche lo spazio dedicato all’ipertensione arteriosa, e questo fatto portò alla nascita, a Perugia nel 1974, del Gruppo di Studio Italiano dell’Ipertensione Arteriosa. Nel 1983, questo si trasformò in Società Italiana dell’Ipertensione Arteriosa, di cui Muiesan divenne il secondo presidente, quando già si era trasferito a Brescia dove fondò la sua scuola. Nei primi incontri sull’ipertensione, tenutisi localmente, fummo coinvolti anche noi del gruppo della dialisi insieme a studiosi di tutta Italia (Figure 2 e 3).

Programma della Sezione sull’ipertensione arteriosa
Fig. 2: Trevi 1975. Programma della Sezione sull’ipertensione arteriosa del corso pratico di aggiornamento “Dibattiti in Cardiologia”. In basso a destra il titolo della relazione tenuta da Attilio Losito
Attilio Losito giovane relatore
Fig. 3: Trevi 1975. Attilio Losito giovane relatore nella Sezione sull’ipertensione arteriosa del corso pratico di aggiornamento “Dibattiti in Cardiologia”

Pertanto, se da un lato la presenza di professionalità diverse all’interno dell’istituto diluiva il ruolo di ciascuna di esse, dall’altro questa forniva un ventaglio di conoscenze che arricchivano ogni singola specialità. Ogni problema clinico, cardiologico, ematologico, pneumologico, trovava la risposta all’interno della clinica. Nella situazione attuale questo non è più possibile ma allora si verificava regolarmente nei grandi istituti internistici, con grande beneficio della completezza delle conoscenze. Di questo se ne giovò particolarmente la nascente attività dialitica, che in quella fase pionieristica presentava quasi sempre problematiche multidisciplinari.

 

Quali furono gli sviluppi successivi?

Nel campo della dialisi Buoncristiani proseguiva il suo impegno ed i suoi studi su nuovi sviluppi della dialisi peritoneale anche con apparecchi automatici di sua invenzione. In pochi anni si era affermato come leader italiano in questa tecnica dialitica [16].

Per quanto riguarda la diagnostica nefrologica, nel 1973 io introdussi la biopsia renale la cui tecnica avevo appreso da Vittorio Bonomini a Bologna, dove frequentavo la scuola specializzazione in Nefrologia. Il mio interesse per la biopsia renale era stato in parte guidato da Giorgio Menghini (1916-1988), caro amico di famiglia, che aveva introdotto una nuova tecnica di biopsia epatica che lo aveva reso famoso nel mondo [17]. Grazie a lui a Perugia arrivarono molti colleghi interessati ad apprendere tale metodica, e tra questi vi fu anche Bonomini, che voleva adattare l’ago Menghini, poco traumatico, alla biopsia renale.

Per i primi anni le biopsie vennero processate da noi nel nostro laboratorio, che era fornito di tutta l’attrezzattura necessaria per l’esame istologico e in immunofluorescenza. Quest’ultima la eseguivamo anche per gli altri centri della regione che cominciarono a loro volta a fare le biopsie. In seguito ci affidammo all’anatomo-patologo Emilio Bucciarelli, che aveva approfondito le sue conoscenze a Birmingham presso il laboratorio di Douglas Brewer (1919-2016), un’autorità nel campo della istopatologia renale. Con Bucciarelli si stabilì un’amichevole e fruttuosa collaborazione che produsse buoni risultati [18].

Nel corso degli anni, più volte Gigli aveva sostenuto che, una volta avviato il programma dialitico, si dovesse avviare un programma per lo studio dell’immunologia delle glomerulopatie, che nell’istituto non era coperto da nessuno. Per questo motivo mi aveva suggerito di recarmi presso un centro di Chicago, con cui lui aveva sviluppato una collaborazione. In previsione di questo programma avevo vinto una borsa di studio del Ministero della Pubblica Istruzione e, nel 1971, ottenuto il diploma americano dell’Educational Commission for Foreign Medical Graduates (ECFMG). Tuttavia, nel 1972 tale programma si arrestò per l’imprevisto trasferimento di Gigli a Pisa in sostituzione di Monasterio.

Alcuni anni dopo, la necessità di un salto qualitativo sull’argomento proposto da Gigli si ripresentò. Per studiare l’immunologia delle glomerulonefriti mi orientai verso la Renal Unit del Guy’s Hospital di Londra, diretta da Stewart Cameron, che era allora un centro di riferimento internazionale per lo studio delle glomerulopatie. Partii per Londra nel Febbraio 1976 e vi rimasi fino all’Aprile 1977 grazie ad una borsa di studio del British Council. Nella Renal Unit, oltre a Cameron, vi erano altre due figure di spicco: Chisholm Ogg e Gwyn Williams (Figura 4). Cameron era famoso per la qualità delle sue lezioni, gli interventi e le discussioni sui casi clinici. Piaceva agli studenti e attraeva colleghi da tutto il mondo, la sua cultura era enciclopedica e non limitata alla sola medicina. Ogg era il clinico per eccellenza: nell’approccio ai problemi clinici impersonava il pragmatismo britannico, scegliendo sempre la via diretta. Williams, cui ero stato affidato, era conosciuto per gli studi del sistema sul complemento nelle glomerulonefriti effettuati all’Hammersmith Hospital e si applicava alla ricerca con grande rigore scientifico. Con lui approfondimmo l’interazione tra farmaci immunosoppressivi e funzione leucocitaria [19].

Il gruppo della renal unit del Guy's hospital
Fig. 4: Il gruppo della renal unit del Guy’s hospital. In prima fila, da destra Gwyn Williams e Stewart Cameron; primo da sinistra Chisholm Ogg

Il Guy’s Hospital era un centro di eccellenza in vari settori della medicina e io cercai di approfittarne appieno. Infatti, collaborammo con l’immunologo Thomas Lehner, che al Guy’s aveva creato un centro di riferimento mondiale per la malattia di Behçet, sviluppando una ricerca sull’immunità umorale in questa malattia [20]. Il genetista Matteo Adinolfi (1929-2020) della Pediatric Research Unit, mi permise di approfondire alcuni aspetti tecnici che mi furono utili in seguito nelle ricerche di genetica clinica. In seguito Adinolfi mi mise in contatto con i genetisti del St George’s Hospital con cui sviluppai una proficua collaborazione [21]. Inoltre, dai colleghi del dipartimento di medicina interna, appresi il metodo di determinazione degli anticorpi anti-DNA basato sull’immunofluorescenza indiretta su Crithidia Luciliae, della quale mi diedero un inoculo che avevano ottenuto dalla Croce Rossa olandese. Rientrato a Perugia, introdussi questo test in Italia, dimostrandone la affidabilità e la riproducibilità [22], e distribuii culture di Crithidia Luciliae a colleghi di diverse parti di Italia. Con questo semplice metodo la determinazione degli anticorpi anti-DNA divenne alla portata di molti centri, sostituendo così la metodica basata su test radioimmunologici, che poteva essere utilizzata solo in pochissimi istituti di ricerca. Un altro aspetto interessante del mio soggiorno londinese fu la frequentazione con i colleghi italiani che si specializzavano in varie branche della medicina. Quasi tutti in seguito ottennero in Italia o in Inghilterra posizioni di prestigio. Londra allora offriva moltissimo anche dal punto di vista sociale. Durante il mio soggiorno londinese la Regina Elisabetta visitò i nostri laboratori. Qui mostrò interesse per vari esperimenti, compresi quelli invasivi (Figura 5). Ebbi anche occasione di incontrare Donna Vittoria Leone in visita all’Ospedale Italiano, centro di incontro di quasi tutti i medici italiani a Londra (Figura 6).

Pass nominale per “A. Lossito”
Fig. 5: Pass nominale per “A. Lossito” (sic) al 17° e 18° piano del Guy’s hospital durante la visita della Regina Elisabetta II
Visita di Donna Vittoria Leone
Fig. 6: Visita di Donna Vittoria Leone (moglie dell’allora Presidente della Repubblica Giovanni Leone) all’Ospedale Italiano di Londra. Attilio Losito primo da sinistra, indicato dalla freccia. Da: La Voce degli Italiani. Quindicinale degli Italiani in Gran Bretagna 1976; 29(5):2 

Come mettesti a frutto queste esperienze al tuo rientro in Italia?

Al mio rientro a Perugia il nostro servizio di dialisi si staccò dalla Patologia Medica e divenne autonomo in una nuova e più grande sede. Oltre all’aumento delle postazioni dialitiche ottenemmo 16 letti di degenza ed un laboratorio dedicato. Lo staff si arricchì dei validissimi colleghi Massimo Cozzari, Loretta Pittavini, Pino Quintaliani e Ivano Zampi. Potemmo così sviluppare al meglio le potenzialità del settore dialitico e nefrologico.

Nel campo della dialisi peritoneale Buoncristiani ideò e collaudò il suo pratico sistema di connessione per la CAPD (continuous ambulatory peritoneal dialysis) [23]. Questa tecnica impiegò un po’ di tempo per ottenere i meritati riconoscimenti ma alla fine li ottenne. Infatti, in un articolo del 2010, Dimitrios Oreopulos (1936-2012), la massima figura mondiale nel campo della dialisi peritoneale, affermava che “il sistema Y di Perugia ha ridotto l’incidenza delle peritoniti e oggi tutti i nefrologi sono d’accordo con i principi di questo sistema” [24]. Colleghi di tutta Italia frequentarono il nostro reparto per apprenderne la tecnica.

La creazione ex novo di un laboratorio dedicato alle esigenze nefrologiche fu molto impegnativa ma per noi fu un grande successo. Peraltro ci consentì di fornire risposte tempestive ai quesiti clinici urgenti e di allestire tecniche nuove e all’avanguardia per i tempi. Elettroliti e osmolarità erano a disposizione per le emergenze. Per l’esame delle biopsie renali, oltre a disporre di esame istologico e in immunofluorescenza, avevamo introdotto la metodica dell’immunoperossidasi. Ai fini di ricerca potevamo studiare la funzione leucocitaria, determinare le frazioni e l’attivazione del complemento, eseguire gel-filtrazione ed eseguire esami spettrofotometrici. La disponibilità di una camera fredda, una centrifuga refrigerata ed il grande lavoro di Zampi, ci consentirono di studiare le crioglobuline e di separare la componente C1q dal plasma per un suo successivo utilizzo [25]. Infatti, grazie a questo, potemmo misurare gli immuno-complessi circolanti con un metodo originale, in fase solida, di nostra ideazione basato sul C1q [26]. All’epoca, i complessi immuni circolanti erano un argomento “caldo” ed attualissimo [27]. Noi non ci fermammo alla loro semplice determinazione ma cercammo di individuarne le azioni flogogene [28]. Nel campo dell’immunopatologia renale, con uno studio abbastanza complesso di micro-eluizione, dimostrammo per primi il meccanismo immunologico della glomerulonefrite della lue congenita [29].

Grazie alla determinazione degli anticorpi anti-DNA, centralizzata nel nostro laboratorio, avevamo accesso a tutti i casi di LES ricoverati nel Policlinico. Questa larga base di pazienti ci consentì di effettuare diverse ricerche su questa malattia. In particolare studiammo il ruolo svolto dai complessi immuni circolanti e la funzione leucocitaria [30,31]. Sviluppammo anche, in questo settore dell’immunologia clinica, collaborazioni con ematologi e infettivologi che, allargando l’orizzonte degli interessi, portarono a risultati interessanti [32,33]. Grazie ad alcune tecniche da noi sviluppate potemmo anche effettuare diversi studi sulla biocompatibilità delle membrane dialitiche [34]. Per questi studi fummo tra i pochi italiani invitati ad un simposio sulla biocompatibilià ad Amsterdam, dove Buoncristiani presentò il suo sistema di dialisi (Figura 7). Gli studi sulla fluorescenza leucocitaria suscitarono interesse tra gli immunologi, e per questo io fui invitato a mostrare la nostra tecnica da Gianfranco Bottazzo (1946-2017) al Middlesex Hospital di Londra, dove lavorava. Localmente, il ruolo di questa attività di immunologia clinica ci venne riconosciuto quando mi venne affidato il corso di “tecniche immunologiche” per la specializzazione in igiene.

Amsterdam 1983. Programma del congresso sulla biocompatibilità in dialisi
Fig. 7: Amsterdam 1983. Programma del congresso sulla biocompatibilità in dialisi, con la relazione di Attilio Losito programmata dalle 14.45 alle 15.05

 

Quale fu il corso dell’attività del centro dopo queste importanti innovazioni?

Buoncristiani proseguì con grande impegno l’affinamento delle tecniche di dialisi peritoneale da lui ideate [35,36]. Inoltre all’inizio degli anni ’80 cominciò a studiare e sperimentare una metodica per l’emodialisi quotidiana che diversi anni dopo avrebbe applicato sistematicamente (Figura 8) [37].

Umberto Buoncristiani
Fig. 8: Umberto Buoncristiani. Dialisi quotidiana: un sensibile progresso… Da: Dialisi Oggi, n.d., pp. 7-11

Nell’altro settore, quello cardionefrologico, Timio portò a termine gli studi sul sistema adrenergico e sui rapporti tra apparato cardiocircolatorio e rene [38,39,40].

In quegli anni iniziò la frammentazione del gruppo originale. Nel 1983 avevo istituito il centro di dialisi dell’Ospedale di Marsciano (PG), dove rimasi come consulente responsabile sino al 2000. Timio si era trasferito a Foligno, dove istituì un servizio di dialisi autonomo e dopo pochi anni avviò ad Assisi la serie dei suoi congressi di Cardionefrologia che funsero da base per la creazione di questa branca specialistica in Italia (Figura 9). A Perugia si completò l’Ospedale Silvestrini, dove venne trasferito il servizio di nefrologia e dialisi. Qui si svilupparono ancor più le tecniche dialitiche innovative sotto l’impulso di Buoncristiani e prese corpo il programma di trapianto renale. Al Policlinico rimase un’unità operativa di nefrologia e dialisi di ridotte dimensioni, senza laboratorio, di cui nel 1990 mi fu affidata la responsabilità (Figura 10). Rivolsi così di nuovo i miei interessi all’ipertensione arteriosa in collaborazione con i colleghi degli altri Istituti Clinici [41].

Assisi 1987. Annuncio del primo convegno di Cardionefrologia
Fig. 9: Assisi 1987. Annuncio del primo convegno di Cardionefrologia
Il team dell’'unità di nefrologia e dialisi di Perugia nel 2008
Fig. 10: Il team dell’’unità di nefrologia e dialisi di Perugia nel 2008

La fase “storico-pioneristica” della nefrologia perugina era conclusa. Tuttavia, l’approccio metodologico originale, partito 50 anni prima con Gigli e trasmesso di collega in collega sino all’attuale gruppo nefrologico diretto da Riccardo Fagugli, è rimasto ed è ancora presente oggi. 

 

Bibliografia

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  32. Velardi A, Spinozzi F, Rambotti P, Tabilio A, Losito A, Zampi I, Cernetti C, Martelli MF, Grignani F, Davis S. The in vivo effect of thymic factor (thymostimulin) administration on circulating immune complexes and serum lysozyme levels in untreated Hodgkin’s disease patients. J Clin Oncol 1983; 1:117-25.
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  34. Losito A, Buoncristiani U, Cecchini C. Abnormal leucocyte locomotion induced by haemodialysis membranes. A clue to dialysis leucopenia. J Clin Lab Immunol 1983; 10:87-90.
  35. Di Paolo N, Buoncristiani U. Automatic peritoneal dialysis. Nephron 1983; 35:248-52.
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  37. Buoncristiani U. Fifteen years of clinical experience with daily haemodialysis. Nephrol Dial Transplant 1998; 12:148-51.
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  39. Timio M, Martini F, Venanzi S, Ronconi M, Lippi G, Pippi C. La funzione ventricolare sinistra nei pazienti in trattamento dialitico peritoneale. G Ital Cardiol 1984; 14:570-6.
  40. Timio M, Ronconi M, Venanzi S, Lazzaroni P, Lori G. Effect of biofiltration on cardiac arrhythmias. Int J Artif Organs 1986; 9(S3):129-32.
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My life as a nephrologist with a passion for renal pathology

Abstract

This article retraces the nephrological life of Giovanni Barbiano di Belgiojoso, which started in the late 1960s. Since the beginning renal pathology was his main interest and he was among the pioneers who introduced in Italy the use of immunofluorescence technique in the examination of renal biopsies. Over the years Barbiano di Belgiojoso has carried out, often in cooperation with other nephrological groups, many clinico-pathological studies on a wide spectrum of glomerular diseases. He also played a key role in the foundation and in the activities of the “Group of Renal Immunopathology” of the Italian Society of Nephrology.

Keywords: history of nephrology, history of Italian nephrology, history of renal pathology

Sorry, this entry is only available in Italian.

Introduzione di Giovanni B. Fogazzi

Il presente scritto racconta la vita nefrologica di Giovanni Barbiano di Belgiojoso a partire dalla fine degli anni Sessanta del secolo scorso, incominciata nella Divisione di Nefrologia dell’ospedale Niguarda di Milano diretta da Luigi Minetti. Fin dall’inizio il suo interesse si è rivolto principalmente allo studio della patologia renale e delle sue implicazioni cliniche. Ciò lo ha portato ad essere tra i primi nel nostro Paese ad applicare e diffondere la tecnica dell’immunofluorescenza nell’esame delle biopsie renali (che aveva appreso da Jean Berger a Parigi) e a condurre studi clinico-patologici su un’ampia gamma di nefropatie, in stretta collaborazione con gli altri gruppi nefrologici milanesi e non solo. La seconda fase della vita nefrologica di Barbiano di Belgiojoso si è svolta, a partire dal 1984, all’ospedale Luigi Sacco di Milano, dove ha diretto fino al pensionamento, in qualità di primario, la Divisione di Nefrologia e Dialisi, senza mai interrompere la sua attività di ricerca clinica sulle patologie glomerulari. Tra i suoi meriti va ricordato anche il ruolo che ha avuto nella fondazione e nelle attività del Gruppo di Immunopatologia Renale della Società Italiana di Nefrologia.

 

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A life devoted to nephrology

Abstract

This paper by Mauro Sasdelli describes the dawn and the development of nephrology first in Bologna, where Sasdelli studied in the nineteen-sixties, and later in Arezzo; the author tells us of the dedication, the enthusiasm, the hard work of all involved, but also of their conflicts and banter. The paper describes the important contributions to nephrology made by prominent personalities such as Domenico Campanacci, Vittorio Bonomini and Pietro Zucchelli, not only at a local level but also more broadly. Finally, text and images of this “personal history” can also be read as the integration of an article published on this same journal in 2016, “The dawn of Nephrology and Dialysis in Bologna with Vittorio Bonomini and Pietro Zucchelli” (Giornale Italiano di Nefrologia, vol. 33, n. 4).

 

Keywords: history of nephrology, history of Italian nephrology, history of the Italian Society of Nephrology

Sorry, this entry is only available in Italian.

Introduzione

di Giovanni B. Fogazzi

Questo articolo, scritto da Mauro Sasdelli, descrive la nascita e lo sviluppo della nefrologia a Bologna (a partire dai primi anni ‘60 del secolo scorso) e poi ad Arezzo, così come sono stati vissuti in prima persona dall’autore, con grande dedizione, entusiasmo e molto lavoro, ma anche – come il lettore noterà – con spirito critico e allegria. Dallo scritto emerge inoltre l’importante contributo che forti personalità quali Domenico Campanacci, Vittorio Bonomini e Pietro Zucchelli diedero alla nostra specialità, non solo a livello locale. Infine, mi piace ricordare che questa “storia personale” va ad integrarsi, come testo e iconografia, con l’articolo pubblicato su questo stesso giornale nel 2016, “L’alba della Nefrologia e Dialisi a Bologna con Vittorio Bonomini e Pietro Zucchelli” (Giornale Italiano di Nefrologia, vol. 33, n. 4) [1]. 

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Avvocato Gerardo Marotta (Naples April 26, 1927 – January 25, 2017): in memoriam

Abstract

This paper summarizes life and works of Avvocato Gerardo Marotta (1927-2017), Founder and President of the Italian Institute for Philosophical Studies from 1975 until his death. He obtained cum laude the Degree in Law discussing a thesis on “The Concept of State in Classical German Philosophy and Hegelian Left”. He was a follower of the Italian Institute for Historical Studies founded by the Philosopher Benedetto Croce. He was a fellow of the Gramsci Group of Naples and a founder of the Association New Culture. He and his young colleagues were very appreciated by the leaders of the Communist Party, however they could not be regimented and were expelled in 1954. Later Marotta was for 20 years a successful lawyer with great expertise in Administrative Law. Finally, he created  the Italian Institute of Philosophical Studies and drove it to international appreciation. The list of Marotta’s Honors is impressive. He collected more than 300,000 books and journals devoted to Philosophy and History which will finally be utilized in a specific library funded by the Campania Region. He is known as the last Jacobin (as per his own definition), has been defined L’Homme des Lumières by Jacques Derrida. He supported Nephrology for a series of programs of vast culture, such as: i. the birth of the International Association for the History of Nephrology (1993), ii. the Appeal for Clinical Research (1997), iii. Survival is not Enough (2007 to present) and iiii. the International Conference on the Human Capital of Age (2016).

Key words: Gerardo Marotta, Italian Institute for Philosophical Studies, History of Nephrology, Appeal for Clinical Research, Survival is Not Enough, The Human Capital of Age

Introduction

On January 25 2017 Avvocato Gerardo Marotta (Figure 1), Gold Medal for the Meritorious of Culture, died in Naples at the age of almost 90 years. He was the Founder and President of the Italian Institute for Philosophical Studies, an institution which cares for Philosophy in Europe and beyond and is Gold Medal of the European Parliament.

We honor him for founding the Italian Institute for Philosophical Studies and for the many achievements which will be presented below, as well as for his interest and support to various nephrological initiatives, namely: i. the birth of the International Association for the History of Nephrology (1993), ii. the Appeal for Clinical Research (1997), iii. Survival is not Enough (2007 to present) and iiii. the International Conference on the Human Capital of Age (2016).

 

Gerardo Marotta: his life

Gerardo Marotta, the last descendant of the Dukes of Sicily, was born in Naples on April 26, 1927. He studied Law at the University Federico II and obtained the Laurea cum laude with a thesis on the “Concept of State in Classical German Philosophy and the Hegelian Left”.

He nurtured his interests in law and philosophy, as well as in history, literature and all the arts. He was among the young scientists who were fostered at the Italian Institute for Historical Studies founded by Benedetto Croce at the Study Group Antonio Gramsci. He was the founder and the soul of the Association New Culture, which in the years 1946-1953 organized conferences and seminars to give cultural grounds to the rebirth of Italy following the catastrophe of World War II. To those events many illustrious personalities (artists, literates, philosophers, scientists and jurists) gave their support and voice. Among them were Antonio Banfi, Ranuccio Bianchi Bandinelli, Roberto Pane, Natalino Sapegno, Vasco Pratolini, Domenico Rea, Luigi Incoronato, Vittorio Viviani, Nicolas Guillen, Dario Puccini and other poets and writers. In those days Marotta promoted exhibitions of painters and sculptors, including a great show of Renato Guttuso and one of Augusto Perez and a series of conferences on Music and Arts started with a conference of Massimo Mila on “Music and arts” at the Conservatorium of Naples.

He married in 1960 Emilia Mancuso, a talented bright lady, very learned in modern art. She was the sister of Sara Mancuso Caccioppoli, the wife of the great mathematician Renato Caccioppoli (1904-1959), the nephew of Maria Bakunin, (1873-1960) the daughter of Mikhail Bakunin. So, two extraordinary citizens of Naples had many reasons to meet and to discuss. Emilia and Gerardo had three children: Valeria, Massimiliano and Barbara who survive them. Massimiliano revived the Società di Studi Politici founded by Benedetto Croce, and he still directs it. Emilia Mancuso Marotta died in 2006. After the death of Gerardo Marotta, Massimiliano was elected President of the Italian Institute for Philosophical Studies.

At the beginning of the Fifties, Gerardo Marotta was instrumental in organizing the Seminar for Juristic Studies (started by Vezio Crisafulli), the Seminar for Biological Studies (established by Giuseppe Montalenti), the Seminar for Architecture (created by Luigi Piccinato), the Seminar for Historical Studies Antonio Gramsci directed by Guido Piegari, Nino Cortese, Domenico De Marco and Giuseppe Palomba. There were also seminars on the Neapolitan Revolution in 1799, the Italian Resurgence and The Southern Question, the Years of Giolitti and on various problems of history and historiography.

The activity of the Gramsci Group and of the Association New Culture was very much appreciated by some of the leading people of the Italian Communist Party. However the young intellectuals were difficult to regiment. The conflict was inevitable and in 1954 the group was expelled from the party. There are responsibilities for this, the main characters have great names. Books have been written on that event.

At this point Marotta devoted himself to the profession. He organized a law firm of lawyers experts in administrative law with many talents for “eminent domain”. They were successful. The office was busy of clients. They made money, which Marotta utilized to start and grow his library of more than 300,000 books on philosophy, and history, including journals of philosophy.

On May 27 1975 at the National Academy of Lincei (Lynx Academy) in Rome, Gerardo Marotta, Enrico Cerulli (President of the National Academy of Lincei), Elena Croce, Pietro Piovani and Giovanni Pugliese Carratelli founded the Italian Institute for Philosophical Studies (IISF, its Italian abbreviation). In the constitution Gerardo Marotta was nominated the Life-President.

Gerardo Marotta in starting the Italian Institute for Philosophical Studies made reference to his experience in the Association New Culture. He gave all personal resources to the new institution and in a few years turned it into a prestigious international Center for Research.

On March 31 1980 Gerardo Marotta, rejuvenating the spirit of the old Neapolitan Academies and of the Neapolitan Enlightenment, established the School for Higher Studies in Naples. In 1981 Marotta founded the Journal “Nouvelles de la République des Lettres”. Directors were Paul Dibon and Tullio Gregory. Among the promoters were: J. F. Battail, G. Costa, G. Erikson, L. Firpo, E. Garin, H. Gouhier, R. Hahn, A. Jammes, P. O. Kristeller, J.C. Margolin, H.J. Martin, P. Raab, J. B. Trap, R. Töllner, I. R. Willison.

Strong links of scientific collaboration were established with the Universities of Padua, Turin, Genoa, Urbino, the National Academy of Lincei, The National Institute for Renaissance, the Academy of Science in Turin, and at international level with the Ecole Pratique des Hautes Etudes in Paris, the Warburg Institute of London, the CERN in Geneva, the Universities of Hamburg, Tübingen, Sorbonne in Paris, Berlin, Vienna, Valladolid, with the Landau Institute in Moscow, and many other foreign institutions. This conferred prestige to the Italian Institute for Philosophical Studies, which received international recognition on June 22 1993 during the Séance of the European Parliament. There a delegation of IISF, composed of philosophers and scientists from every part of the world, presented The Appeal for Philosophy and the Appeal for Humanistic Research. They were co-signed by Hans-George Gadamer (1900-2002), ​Ilya Prigogine (1917-2003), Paul Ricoeur (1913-2005), and Paul Oskar Kristeller (1905-1999). The appeals were adopted by the European Parliament. In that occasion after the speech of President Egon Klepsch, Prof. Antonio la Pergola, Emeritus President of the Italian Constitutional Court, gave a talk to illustrate the activity of the Institute from which we quote:

“The double appeal of the Italian Institute for Philosophical Studies is linked to the roots of the common European Conscience. Our Parliament is asked to meet the needs of the civil society. This is an authoritative message from the world of culture. We cannot neglect it. The Italian Institute for Philosophical Studies understands the reasons why the new generation, the future directing class needs to be educated to a creative thinking, to philosophy, to capacity of judgment. Thus we take the responsibility to promote a rebirth of Humanism which might bring new life in every branch of science and to drive growth. Man turns into imago Dei (God’s image), to the sense of universe, when he discovers the perennial value of his liberty and dignity, of his right to govern life and to impress, as in the happy days of our history, the mark of his work on history. The Italian Institute for Philosophical Studies has given the first impulse to the mobilization of men of culture to revisit Humanism. It is a program of broad breathing. Its realization will occur through school, and is under the care of the public opinion, to the value deserved by great proposal which needs to grow even here in Strasbourg and in the other European Institutions. The appeals add to the notion of Europe which starts to unify in areas different from market and economy. The Italian Institute for Philosophical Studies re-fired in the city a focal of the interest to the spreading of the thought, to reflection on topics which are central and cannot be escaped. This activity receives support and admiration of all countries, it is at the service of a Weltanschauung which is also wisdom of politics… For this, as President of the Commission for Culture, I express appreciation for the initiative of the Neapolitan Institute. Its Appeal traces a main route based on a more mature Europeism”.

 

Gerardo Marotta: Honors

  • Dr Honoris Causa in Philosophy at the University of Bielefeld, Germany (February 8, 1988).
  • Dr Honoris Causa in Philosophy at the Erasmus University in Rotterdam, The Netherlands (November 8, 1988).
  • Dr Honoris Causa in Education at the University of Urbino, Italy (November 1988).
  • Diploma of Honor of the European Parliament for his activity in favor of European Culture (1994).
  • Prize of Illustrious Neapolitans from the Prix Naples Foundation (December 3, 1994).
  • Silver Bowl of Friendship from the Cultural Centre St. Vincent “for his role in promoting in Southern Italy the broadest cultural initiative of the Country: that consists in the creation in Italy and in the Whole South of the summer schools and the Courses for Advanced Training” (December 3, 1994).
  • The Italian Institute for Philosophical Studies was awarded the Prix International pour la paix Jacques Muhlethaler for the activity in favor of peace between individuals and people, at the University of Rome, Italy (May 18, 1995).
  • Dr Honoris Causa in Philosophy at the University of Paris III Sorbonne Nouvelle (June 24, 1996).
  • Dr Honoris Causa in Architecture at the Seconda Università degli Studi di Napoli (July 10, 1997).
  • Prize Artigiani della Pace (Turin, June 10, 1997).
  • Premio Capo Circeo from Vereinigung für Deutsch-Italienische Freundschaft (Capo Circeo, December 11, 1997).
  • Prix Mecenate dell’Associazione Amici della Scala di Milano “for the foundation of the Italian Institute for Philosophical Studies, School for Higher Studies in Naples, for his work and the resources granted in envisaging and directing its national and international work for Research, Teaching, Exhibitions and Publications and for his generous activity in promoting and producing culture, since his young age” (October 23, 1999).
  • International Prix “Naples Inclusive City” from the International Association of Catholic Apostolate, for “his noble tireless activity guided by exemplary wisdom in support of the culture which belongs to the historic patrimony of the City of Naples” (December 20, 1999).
  • Medal Peter the Great from The Russian Academy of Natural Sciences (February 23, 2000).
  • Prix “Universum” for exceptional merits in the field of philosophy (October 15, 2000).
  • Dr Honoris Causa in Philosophy at the University of Pavia (October 25, 2000).
  • Dr Honoris Causa in Philosophy at the University of Bucarest (October 26, 2000).
  • Prix Gold Lemon (March 2001).
  • Die Goethe Medaille (March 23, 2001).
  • Mediterranean Award “Culture”, Fondazione Mediterraneo (January 2002).
  • Chevalier de la Légion d’Honneur of French Republic (June 2003).
  • Honorary Member of the Institute for Philosophy of the Russian Academy of Sciences (Moscow, September 2010).

 

A message of Hans-George Gadamer and others

The messages of the greater philosopher of today, Hans George Gadamer (Figure 2), accompany the activity of the Institute throughout the world, and the great messages to the European Parliament of our delegation in the years 1991 and in 1993, attest the prestige of the Institution on which Gadamer expressed his opinion:

“I am happy to affirm the great Heredity of this city is now in good hands. It is a merit of the Italian Institute to have started this initiative. In fact, the restart of philosophy promoted by the Italian Institute for Philosophical Studies is known worldwide. It will honor the great Neapolitan tradition if it will be capable to keep living the heredity and the great European Thought and to build upon these premises new forms of thought and life. This allows us to think that Europe will be capable to survive the menace of our times. I do hope that the Institute will represent a model for Europe in order to avoid the bureaucratization of the Studies. Without initiatives of this kind, culture is lost since the bureaucratization of the studies, which is the fellow companion of the industry of our times, turns culture into stones and works against creativity as well as against human relationships”.

The scientists of the Massachusetts Institute of Technology have declared that the “Italian Institute for Philosophical studies is a unique institution not only for its service to culture but also for keeping high the flag of philosophy in a world obsessed by materialism and trivial interests. The initiative of the Italian Institute has taken for philosophy contributes to the survival to what is dear to us of the world of thought and culture. We share the willingness of the Italian Institute for Philosophical Studies to create a new cadre of investigators capable to take on their shoulders the cultural heritage of the great European philosophical tradition which is nowadays under pressure from many sites”.

sB. Smith, Professor at The Warburg Institute in London, in a paper discussed the international role of the Institute and included it among the most important centers of the present cultural Europe along with the Warburg Institute and the Institut pour la Recherche et l’Histoire des Textes of Paris. Paul Oskar Kristeller underlined the importance of the Italian Institute for Philosophical Studies for the world culture and remarked that the School for Higher Studies in Naples founded by Avvocato Gerardo Marotta has, with its peculiar characteristics, a place for itself in the tendency in Europe and USA to organize centers for research devoted not only to natural sciences and mathematics, but also to philosophical, historical and philological sciences, as it happened with the Institute for Advanced Studies of Princeton, the Mellon Foundation, the Scuola Normale Superiore of Pisa. He felicitated the Italian Institute for Philosophical Studies for the capability to emerge as a significant institution for the world contemporary culture, for its huge number of fellows and for focusing its activity on fields neglected by other universities and institutions. In fact, it covers history of philosophy and the history of ideas from the antiquity to present.

 

Paul Dibon on the Institute

Paul Dibon (1915-1995) of the École Pratique des Hautes Études in Paris commented: “In the course of my long academic career I had the honor and the privilege to teach for many years in many countries and to cumulate a series of different and fertile experiences. I can affirm that the meetings I had on the history of ideas in the 17th century at the School for Higher Studies in April will remain as an original, promising experience. It confirms the confidence already expressed on the future of this Neapolitan Institution, at the time of the Opening Ceremony in the Hall Giovambattista Vico, in May 1980 [… ] in the course of the sessions at the Higher School another comparison was possible. It concerned the fellows who originating in various fields were attracted by common intellectual interests. I have had personal talks with some of them, who, coming from northern regions, discovered in Naples a specificity of its daily life as well as of its rich cultural tradition”.

Théodore F. Geraets, Dean of the Faculty of Literature and Philosophy at the University of Ottawa, has written in the issue no. 4 (1981) of the Annali della Pubblica Istruzione, “the importance of the initiative started in Naples by Avvocato Marotta is inimitable and with difficulty could be understood in its entireness”. Henri Gouhier, Academician of France, in 1986 dedicated to Avvocato Gerardo Marotta the book on Blaise Pascal. Karl Heinz Ilting (1925-1984) dedicated to Marotta the edition of the Unpublished Berlinese Works of Hegel on Philosophy of Religion by writing “To Gerardo Marotta and to the Hegelians of Naples”. Vittorio Hösle dedicated to Gerardo Marotta his volume Verità e storia.

The Institute now is the centre of a dense network with the most important centers of research like the Warburg Institute in London and the École Pratique des Hautes Études, the Hegel Archive in Bochum, and many European and American Universities. The seminars of the Institute, many of them are organized abroad, attract researchers from Italy and from abroad.

The international recognition stimulates the efforts of the Institute to renovate modern culture and the rebirth of civil life in Naples and in Southern Italy.

 

A word of Reinhart Koselleck

“What characterizes the Italian Institute for Philosophical Studies founded by Gerardo Marotta is not only the reference to a tradition which from Vico to Croce is linked to the genius loci, but its capacity to irradiate its impulses in all fields of knowledge and towards the other countries of the world. I do not know of any other scientific institution capable to impress a so deep mark in the culture of the whole Europe as it happened with the Italian Institute for Philosophical Studies”. With these words, on February 6, 1988 Reinhart Koselleck (1923-2006) gave the reasons of the Laurea Honoris Causa the University of Bielefeld conferred to Gerardo Marotta to consecrate the European and International meaning of the Institute he has founded, directed and animated.

 

Laurea Honoris Causa at the Erasmus University in Rotterdam and at the University of Bielefeld

In the same year another Laurea honoris Causa in Philosophy was conferred to Gerardo Marotta at the Erasmus University in Rotterdam in a solemn ceremony with motivations identical to those of the illustrious German historian:

“In the person of Gerardo Marotta, the Universities of Bielefeld and Rotterdam have honored a scientific institution and a center of high culture which emerged and attracted the interest of the world for its intense and prestigious activity, his personal work, his passion for the Institute that he envisaged, and realized with personal energy and resources”.

In the Laudatio we read:

“Avvocato Gerardo Marotta – as motivated by Hans George Gadamer – is a meritorious and noteworthy personality I know. I am unable to indicate another professional of the law of the same value in his efforts towards a true culture and for philosophy. He has devoted to it great personal efforts and with a marvelous energy has created the Italian Institute for Philosophical Studies which is worthy of the great name of Benedetto Croce [ …] I, myself, for more than 10 years have taken part to these efforts and I can say that I have not found in any other part of the world a group of participants informed and active like that I meet at the Institute in Naples”. “Avvocato Gerardo Marotta is the soul although a very confident man. It is evident that he is driven by the love for the country and for the public good. And I have had the possibility to appreciate that this attitude is shared by many intellectuals and young people. The antique tradition which goes back to Vico survives […]. Without any doubt Gerardo Marotta is a great promoter of philosophical and scientific studies”.

The recognition for the Institute was not only international but also national. In 1988 Gerardo Marotta received the gold medal from the President of the Italian Republic for his cultural merits.

In 1988, the President of the Council of Ministers conferred the Prize for Culture to the Italian Institute for Philosophical Studies.

 

The Silver Cup of Friendship from the Cultural Centre Saint Vincent

On December 3, 1994 the Cultural Centre Saint Vincent conferred to Avvocato Gerardo Marotta the Silver Cup of Friendship with the following motivation:

“In agreement with the Autonomous Region of Valle d’Aosta and the National Order of Journalists, in occasion of the Information Day which took place at Saint Vincent on December 3-4 1994, has conferred to Avvocato Gerardo Marotta, President of the Italian Institute for Philosophical Studies of Naples, the Golden Cup of Friendship for the organization in Southern Italy the broadest and most relevant cultural initiative promoted in Italy in recent years. Tens of seminars have been organized in small towns once centers of attraction for philosophy to which have given their contribution authoritative scientists. The goal was to wake the cultural and historical memory of a thought that gave to Southern Italy a peculiar identity, a memory which can represent a powerful lever for its civil rebirth. Of this relaunch, Avvocato Gerardo Marotta is the most qualified and passionate protagonist”.

 

The Capo Circeo Prize

On December 13 1997 the Vereinigung für Deutsche-Italienish Freundschaft conferred to Avvocato Gerardo Marotta the Prize Capo Circeo with the following motivation:

“The undersigned mayors of Southern Municipalities in association with those of Abruzzo, Naples, Bergamo declare solidarity to the Italian Institute for Philosophical Studies: “His great polyhedral personality, enriched by a charge of civil passion, which early in his life let him participate in many social and political battles, has now reached a universal meaning, having used all his energy and economical resources to the foundation and development of the Italian Institute for Philosophical Studies, which has now reached levels of world excellence. We cannot forget his efforts to publish the Hegelian texts in their original form, as world premiere, and his priority as patron in helping so many teachers and fellows who with passion were with him. The activities of the Italian Institute for Philosophical Studies have represented the industrial flywheel for new publishing houses from Naples to Milan, thus contributing to the diffusion of science and culture. Together with Gerardo Marotta the Prize Capo Circeo was also attributed to the Philosopher Hans George Gadamer, the German Minister for Interior Affairs M. Kanther, the State Secretary for economy of the Government of Bavaria H.G. Spitzner, the State Minister for Foreign Affairs W. Hoyer, and the Germanist Carlo Volpi”.

In previous editions the Prize Capo Circeo was granted to The Chancellor Helmut Kohl, to the Politologist Sir Ralf Dahrendorf, Ernst Jünger, Augusto Del Noce, Renzo de Felice, the Historian Jeans Petersen, Joachim Fest, Ernst Nolte, W. Sawallish, Claudio Abbado, G.G. Gensher, the Minister for Foreign Affairs Klaus Kinkel, Alfred Herrhausen President of the Deutsch Bank, F.J. Strauss President of Bavaria, The Mayor of Berlin Eberhard Diepgen, the Germanist Marino Freschi, Angelo Bolaffi, and the German Archeologist Bernard Andreae.

 

Honorary Citizenships 1993-1996

Many municipalities in Southern Italy – among which are Agropoli, Bomba, Brienza, Castelnuovo Cilento, Cesa, Diamante, Gioi Cilento, Melfi, San Sebastiano al Vesuvio, Somma Vesuviana, Vatolla-Perdifumo, have bestowed to Gerardo Marotta the Honorary Citizenship for his cultural and civil effort which inspired him to give birth to hundreds of courses of Higher Formation, meetings, historical and didactic exhibitions, in every place in Southern Italy to wake up the historical memory and the hectic-civil conscience.

Two hundred Mayors and Municipalities in Southern Italy addressed the President of the Italian Republic on occasion of the first centenary of the death of Silvio Spaventa (1893) an appeal where we can also read:

“The undersigned Mayors of the Municipalities of Southern Italy, in association with those of Abruzzo, Naples and Bergamo declare their solidarity to the Italian Institute for Philosophical Studies in order to continue the work to keep alive the historical memory in Southern Italy and to reaffirm that the unity of the Italian People and the unity of the State are indispensable for the building of the United States of Europe, since the European conscience of the state must deepen the roots in the conscience of the state of each country (… ). Mr. President of the Republic, we are proud that the appeal for Philosophy and humanistic research of the Italian Institute for Philosophical Studies departed from Naples to the European Parliament and to the United Nation Organization, and that Naples and Southern Italy have received full recognition from the highest international institutions”.

On June 22 1993 in the European Parliament a delegation of the Scientific Committee of the Italian Institute for Philosophical Studies was received by the President of European Parliament Hon. Professor Egon Alfred Klepsch and by the President of the Cultural Commission of the European Parliament.

 

Historical and Didactic Exhibitions in the municipalities of Southern Italy in the years 1982-1997

In the document of the Mayors of Southern Italy we read:

“It is an indisputable merit of the Italian Institute for Philosophical Studies to have rejuvenated with new and appropriate studies, with tens and tens of historical and didactical exhibitions, through seminars and meetings on the “Neapolitan Republic of 1799”, Gaetano Filangieri, the state according to reason, Francesco De Sanctis, documents for an intellectual biography, The Hegelians of Naples, The Building of the United States, Silvio Spaventa politician and statist of the unified Italy. This occurred with the support of the patriotism of reason, and the awareness that in Southern Italy exist great values and enlightening traditions of the National Resurgence and of the United States”.

Hundreds of municipalities hosted the historical and didactic exhibitions. The long list includes: Acri, Afragola, Agropoli, Altamura, Agnone, Ariano Irpino, Atripalda, Avella, Avellino, Avigliano, Barano d’Ischia, Brienza, Campobasso, Camposano, Castellaneta, Diamante, Eboli, Ercolano, Fasano, Foggia, Forio d’Ischia, Frattamaggiore, Grumo Nevano, Ischia Ponte, Isernia, Lagopesole, Laureana Cilento, Lauro, Manduria, Massa Lubrense, Matera, Mattinata, Nocera Inferiore, Nola, Ortodonico, Pescocostanzo, Pignola, Pomigliano d’Arco, Ponticelli, Portici, Procida, Salerno, San Gennaro Vesuviano, San Giorgio a Cremano, Sarno, Sava, Scafati, Somma Vesuviana, Sorrento, Soveria Mannelli, Taranto, Terranova di Pollino, Torre del Greco, Trani, Tricarico, Vairano Scalo, Vatolla, Vico Equense.

Many Italian and European cities hosted historical and didactical exhibitions on philosophical traditions of Southern Italy: Turin, Bergamo, Rome, Venice, Paris, Lille, Kassel, Trier, Bielefeld, Geneva and Strasbourg.

In 1997 The Italian Institute for Philosophical Studies awarded 1250 scholarships, organized 1350 seminars, conferred 442 research scholarships, and published 135 books.

 

Schools and Institutions for Higher Learning of the Italian Institute for Philosophical Studies in Italy and abroad

  1. Schools for Higher Learning in 543 municipalities of Southern Italy where the Institute organized thousands of seminars and contributed to the institution and development of 237 libraries;
  2. The International Institute of Higher Scientific Studies founded in 1980 at Palazzo Serra di Cassano that organized congresses at CERN in Geneva and throughout Europe and in its permanent headquarters in Vietri sul Mare;
  3. Schools for Higher Learning in Biology and Cybernetics directed by Cloe Taddei Ferretti with the participation of many scientists and the publication of a volume with preface of the Nobel Prize Ilya Prigogine. The book contained many favorable opinions of scientists belonging to the international community as it is evident in the monograph Le Scuole Internazionali di Biofisica e Biocibernetica dell’Istituto Italiano per gli Studi Filosofici/The International Schools for Biophysics and Biocybernetics of the Italian Institute for Philosophical Studies;
  4. The Annual Schools for Higher Learning in collaboration with the Warburg Institute in London supported by the Italian Institute for Philosophical Studies with annual scholarships for meritorious students and investigators;
  5. The School of Heidelberg founded in the year 2000, launched by Hans-George Gadamer, and organized directly by the Italian Institute for Philosophical Studies. This school represents Italian culture and is indispensable for cultural collaboration between different countries;
  6. Schools for Higher Learning with the Program Diffiety School in the Municipality of Santo Stefano del Sole. Subsequently the Institute founded, in collaboration with the same Municipality, the International Foundation Tullio Levi-Civita. Professor Alexandre Vinogradov, a Member of the Academy of Science in Moscow and Professor at the University of Salerno, was nominated Director. The International Institute Tullio Levi-Civita hosts investigators from all over the world. Its academic year is celebrated annually in Naples at Palazzo Serra di Cassano. The courses take place in various locations in Southern Italy with the participation of professors and investigators from various continents.

 

The Assize of the City of Naples and Southern Italy

At the beginning of the nineties of last century Antonio Iannello, Secretary of Italia Nostra, Alda Croce, President of the Library Benedetto Croce, and Gerardo Marotta, created the “Assise della Città di Napoli e del Mezzogiorno d’Italia”. It was a public assembly which met every Saturday morning and debated cultural, political, economical problems of the Neapolitan area under the presidency of Aldo Masullo, Professor of Moral Philosophy. Among the topics discussed over the years were the “rebuilding after the quake of November 23, 1980”, “Water as public good“ (against its privatization), the “depollution of the Gulf of Naples after the closure of the still mill”.

 

The Library of the Italian Institute for Philosophical Studies

Marotta assembled a library of Philosophy, including journals and manuscripts of classical German Philosophy and from the Hegelians from Naples. The books, more than 300.000, are currently stored in various depositories. After Marotta’s death interest has grown to build a library for them not far from the Institute financed by the Government of Regione Campania. The library was the long-lasting problem for Avvocato Marotta, till his death. He was promised a lot but at the end no one helped.

 

Who was Gerardo Marotta?

This question was nicely answered recently by Francesco Barbagallo, Emeritus Professor of Contemporary History at the University Federico II of Naples. He gave the inaugural address for the Academic Year 2017-2018 of the Italian Institute for Philosophical Studies. The address was entitled “Gerardo Marotta. A European Patriot” (1).

Barbagallo writes:

“Azeglio Ciampi, President of the Italian Republic during a visit to the Italian Institute for Philosophical Studies on September 9, 1999 said <we all shall applaud to his learned madness, provident madness, in the sense that his passion, the enthusiasm he used in furthering life of this Institute. Behind his passion there is the pride to claim all that Naples means for the history of Europe, the history of Italy, Naples that in its culture finds the roots of its strength and of its future>” (2).

Barbagallo also recounted that “Marotta organized in Saint Petersburg an international conference on L’Homme des Lumières. Thus, on the occasion of the awarding of a Laurea Honoris Causa at the University Paris III- Sorbonne-Nouvelle in 1996 Jacques Derrida said <I think that he is L’Homme des Lumières. Should someone ask me abruptly which is the model for l’homme des Lumières 1996 I might not find a better identification>” (3).

On commenting the foundation of the Institute, Barbagallo gives the word to Antonio Gargano who was with Marotta since the beginning and helped him until his death for forty years (1). Gargano says:

The foundation of the Institute was born by a consideration shared with Husserl of a “crisis of European Humankind” […] The spiritual image of Europe entails a perspective which is valid for the whole humankind however one must come back and revive her which is to revive the great philosophical schools. This ambition presided the birth of the Italian Institute for Philosophical Studies”.

The concluding lines of Barbagallo are about the nomination of Marotta as Senator for life: “It remains incomprehensible the failure to appoint him as senator for life, [Marotta] the Italian who would have deserved it more” (1).

 

Gerardo Marotta and his interest in Nephrology

The Origins of the International Association for the History of Nephrology

Marotta was an honorary member of the International Association for the History of Nephrology (IAHN). He was the main actor in organizing the first International Meeting on History of Nephrology which was organized in Naples and Montecassino in 1993 (see the website of IAHN at iahn.info). The American Journal of Nephrology in 1994 reported (5) On the Future of the History of Nephrology. The conference on the History of Nephrology was held in Naples on 28-30 October 1993 under the sponsorship of the Seconda Università di Napoli, Baylor College of Medicine and the Italian Institute for Philosophical Studies. These Institutions were represented by Domenico Mancino, W. T. Butler, and Gerardo Marotta, respectively (5).

Marotta was pleased of the honorary membership awarded to him at the closing of the fourth Congress in Montecassino organized by Luigi Iorio.

 

The Appeal for Clinical Research

On September 15-17 1997 an International Conference on Human Clinical research: Ethics and economics was held in Naples, at the Palazzo Serra di Cassano. It was supported by the Italian Institute for Philosophical Studies and co-chaired by Natale G De Santo and Garabed Eknoyan. That Conference promoted the Appeal for Clinical Research (6-8).

The Appeal reads (7):

“Health care has improved markedly over the past five decades, in large measure because of advance made in patient-directed clinical research. The study of the whole human being which has proceeded extremely fruitfully heretofore, is now threatened by its own success by the advent of technological developments from studies in molecular biology. The profound shift over the past decades from patient-oriented clinical research to research at the cellular and molecular level has not only created new ethic and religious dilemmas, but just as importantly has caused a shift of financial support to the more expedient studies at cellular level. As a result, the study of the whole human being is languishing at a time that this kind of research is absolutely essential in furthering human health and transferring laboratory strategy to the clinical arena.

While the new technologies can be relied upon to provide basic solutions, patient-oriented clinical research is essential – now more than in the past – in order to translate the advances in molecular biology into the practical and functional terms applicable to the whole human physiology and metabolism to attain a better understanding of human biology, to improve the cure of human illnesses, and to deliver a better health to all mankind. It is fair to say that if both modes of research-molecular and clinical-are to prosper in the future, as they must, the patient-oriented research must receive stronger institutional and governmental support to do research and to provide answers to the ethical and moral problems raised by advancing frontiers of cellular research.

We appeal to all concerned and responsible public, private and governmental authorities to lend their support to this initiative”.

The Appeal was signed by Gerardo Marotta, Lawrence K Altmann, E. H. Ahrens, Donald Seldin, Garabed Eknoyan, Natale G De Santo, Anita Aperia, Ruth Ellen Bulger, Curtis Meinert, Ruth Faden, Lewis Wolpert, Dietrich von Engelhardt, Gȕnther Stock, Mario Condorelli, Klaus Hierholzer, Miroslav Mydlik, Antonio Spagnuolo, Goffredo Sciaudone, Kiyoshi Kurokawa, Giovambattista Capasso, Massimo Cirillo, Domenico Mancino, Dimitri Nenov, Boleslaw Rutkowski, L.W. Henderson, and Walter Hörl +5,000.

 

Survival is Not Enough

Survival Is Not Enough is the annual international event of the Italian Institute for Philosophical Studies and the Second University of Naples. It started in 2007 in Naples, following a suggestion of Rosa Maria De Santo to Professor Antonio Gargano, General Secretary of the Italian Institute for Philosophical Studies (IISF). The event was approved in January 2007 at the Meeting of the Scientific Committee of the Institute and has been organized annually from 2007 to present around the “World Kidney Day”. The aim is to discuss the needs of patients with chronic kidney disease (8, 9) and the possibility to ameliorate the quality of a machine-dependent life. The events are held in different sites with an identical format. Renal patients and their associations, philosophers, economists, nephrologists, renal transplant surgeons, expert in bioethics, and health care managers, teachers and principals of primary and secondary schools, university students are invited to discuss the possibility to grant the best cures and care to patients treated with dialysis, a technique that provides a “Life with many losses and various dependencies”. Losses include even the possibility of selecting foods and beverages, playing sports, undertaking a demanding job, having a refreshing sleep, properly expressing one’s own feelings, fulfilling the responsibilities toward the family, having an orgasm and menstruations. Dependencies are linked to the place one lives, physicians, dialysis staff, dialysis machines, dialysis shift, and dialysis calendar (10). Marotta maximally supported this event which according to him “linked philosophy with real life and confronts with the sufferer and the state organizations supporting good health in chronic disease”. He was there for the opening ceremony of that event which was co-chaired by Natale G De Santo, Giuseppe Remuzzi, Guido Bellinghieri.

Survival Is Not Enough has the ultimate aim to promote prevention and organ donation as the most reasonable and economically sound action for such global disaster. The presence of philosophers, as third parties, aims to give tutorial help to the needs of the sufferers who are no longer under the patronage of physicians who are now told by managers what, how much, and for how long they can prescribe to patients. Since 2008, Survival Is Not Enough has been extended also to the University of Foggia and later to the University of Bari by Loreto Gesualdo, to the University of Messina by Guido Bellinghieri and Vincenzo Savica (11), to Athens by Athanasios A. Diamandopoulos, to the University of Gaziantep by Ayse Balat, to the Pavol Jozef Šafárik University in Košice by Miroslav Mydlik and Katka Derzsiova.

From 2009 onward the event has been organized in many cities on the shores of the Mediterranean Sea including Naples, Bari, Benevento, Brindisi, Caserta, Catania, Palermo, Rende, Rome, Salerno, Trieste, Athens, Gaziantep, Patra, Koper, Tunis, Sfax, as well as in Central-Eastern Europe (Gdansk, Košice, Bucharest, Varna), and in Turkey at the University of Gaziantep and Istanbul, under the leadership of Ayse Balat. Leading nephrologists and managers with international reputation, as well as teachers, principals and primary, secondary schools and university students have participated in such events (12).

 

Outcomes

Various quests have arisen for (i). a new cadre of managers capable of keeping health accounts in balance without cutting expenditure but by reducing waste of resources; (ii). the promotion of prevention as the only measure capable of reducing costs in the long run; (iii). the promotion of clinical research by turning biomedical discoveries into treatments and cures; (iiii). the need of a 4P Medicine (predictive, personalized, preventive and participatory), as suggested by Leroy Hood, the founder of the Institute for System Biology in Seattle, WA; (v). the promotion of organ donation, being kidney transplantation the safest, cheapest procedure, and associated with the longest survival and best quality of life of the patients; (vi). the awareness of the risks connected with the emerging of the Medico-industrial Complex as discussed by Arnold S. Relman in New England Journal of Medicine in 1980; (vii). health systems based on patient’s needs. Aiming “to do different things and to do things differently, by putting the patient in the centre of the system and by wearing patient’s shoes”, as stressed by Fiona Godlee in the British Medical Journal in 2009.

 

Publications

Papers related to Survival Is Not Enough have been published in the Journal of Nephrology (9), Giornale Italiano di Nefrologia (11, 13), Seminars in Nephrology (10), the American Journal of Kidney Disease (14), the Journal of Renal Nutrition (15), and the Italian Journal of Public Health (16). Likewise, they have also appeared as selected annual proceedings (12 – 14) in the series “i testimoni del tempo / witnesses of the times”, a philosophical series published in Naples by Metis and the Italian Institute for Philosophical Studies. It was founded and directed by the late Aniello Montano (1941-2015), Professor of Moral Philosophy at the University of Salerno, who published elegant monographs of appealing printing, size and binding.

 

Some presentations

Invited presentations were discussed at the 2nd Meeting of the International Federation of Kidney Foundation in Curitiba (Brazil) in 2007, the Celebration of the 50th Birthday of the Medical Faculty of the Šafárik University in Košice (Slovakia) in May 2009, the 2011 Nagoya Congress of the Society for Uremic Toxins, the 2012 Congress of the Tunisian Society of Nephrology in Sfax, the 2012 Congress of the Algerian Society of Nephrology in Algiers, at the 2015 Congress for Hippocratic Medicine in Athens, the 2016 Congress of the Hellenic College of Nephrology, in Portaria, and at the 2016 Congress of the Mediterranean Society of Nephrology in Cappadocia (Turkey).

 

The battle for organ donation

Following the advice of Professor Francesco Paolo Casavola, President Emeritus of the Constitutional Court and President of the National Committee of Bioethics in Italy, and of Gerardo Marotta, Survival is Not Enough has focused on finding a rational approach to prevent the opposition to organ donation after death, as well as on developing familial decisions in order to register in donors’ list while alive. A family decision might help in respecting the will to donate if and when death might supervene. We do now think that young people registering for organ donation should discuss the decision with the family, so that if donation becomes a possibility, everyone knows what to do. Thus, students are asked to campaign in their family for modernity and make the will for organ donation a family decision, since no one lives alone, and at the end the body of the deceased, after organ removal, is given back to the family. Since transplantation represents modernity, we suggest that its related laws should be reviewed frequently in order to benefit from all the advantages emerging from modernity.

Because transplantation saves lives, it costs less in comparison with other therapies, is innovative and provides excellent results, nephrologists should tell the patients, from the very beginning, that transplantation is the best option. Thus teaching organ donation to students of primary, middle and high schools is the cornerstone on which the program is built (12). The Italian Association of Organ Donors (AIDO) operating in the Campania Region and Survival Is Not Enough have joined forces and now diplomas are assigned to families of donors. The last time Marotta was present in Caserta was in 2014 (Figure 3). In that occasion he addressed more than six hundred students of the Lyceum Manzoni and explained them their triple duty (“to study a lot, to study a lot, to study a lot”). The last time Marotta was present in Naples was in March 2016 (Figure 4).

 

The Human Capital of Age

On September 15-16 2016 took place in Naples an International Conference promoted by The University of Naples Federico II, The Second University of Naples, The Italian Institute for Philosophical Studies and Organized by ARFACId. This was the last international Event to which Gerardo Marotta participated. Marotta did not have the time to see the proceedings Il Capitale Umano dell’età: La saggezza della vita (The human capital of age: the wisdom of life) with a preface of Professor Giuseppe Galasso (25) and The Human Capital of Age (2, 27). However he was pleased to learn about its main outcome represented by the founding of the European Association for Professors Emeriti.

 

Final comments on Gerardo Marotta: the Man and his Action

Nuccio Ordine, Professor of Italian Literature at the University of Calabria at Rende, Italy, on the death of Gerardo Marotta, wrote a significant comment on the Man and on his Action (28).

“Europe of Culture lost its fiercest “Avvocato”/(Lawyer). Gerardo Marotta, fighting with all of his strength for more than fifty years, protected teaching, scientific research and any form of culture capable of educating the younger generation in human solidarity and love for the common good. For decades in the amphitheatres of the Sorbonne, or in the halls of the École des Hautes Études en Sciences Sociales in Paris, at the Warburg Library in London, in the corridors of the Institute for Advanced Studies at Princeton, at Die Freie Universität in Berlin and in the various offices of Italian Cultural Institutes, it was enough to mention “the Avvocato” to think immediately about the Italian Institute for Philosophical Studies and of Gerardo Marotta its president”. “The Institute, from the very “beginning“, was structured as an “active” school open to the “new alliance” between natural and human sciences“ (28).

Giuseppe Galasso, Emeritus Professor of Contemporary History at the University Federico II in Naples, and Member of the Academy of Lincei in Rome, on the death of Gerardo Marotta wrote about “The Constructive Utopia of Marotta” (29). “There were utopia and dreams in his personality. They preceded that in the thought and in the action of Gerardo Marotta, who died last Tuesday at the age of 89 years, impressions and appearances induced to believe in it, but there was no utopia, there were no dreams as a way to escape from reality, or impotence to cope with it. It was just the contrary. There were strong and concrete pushes to work constructively in the reality using acute judgment and practical wisdom. His dream, his utopia, were in seeing the Republic of Plato realized and triumphant on the dregs of Romulus, just to use the words of Gianbattista Vico (1668-1744), much loved by Marotta, as all the other great exponents of the Neapolitan Thought from Giordano Bruno (1548-1600) to Tommaso Campanella (1568-1639) and to Benedetto Croce (1866-1952). Marotta saw that the Republic was exemplified in the short season of 1799. For him, the subsequent ferocious Bourbon repressions decapitated the flowers of the highest spirits of Naples, thus causing a decadence from which the Neapolitan bourgeoisie and its culture were unable to get out” (29).

 

ACKNOWLEDGEMENTS

Heartfelt thanks are due to Emanuela Appetiti, CEO of the Institute for the Preservation of Medical Tradition, Washington DC, USA, for accurate revision and editing of this manuscript.

We thank Malcolm E. Phillips, Retired Nephrologist and Medical Director of Charing Cross and Hammersmith Hospitals Trust London, United Kingdom, for many relevant suggestions.

 

References

  1. Barbagallo F. Gerardo Marotta, patriota europeo di Napoli. – Prolusione per l’anno Accademico 2017-2018, Naples, November 27, 2017.
  2. Saluto del Presidente della Repubblica Carlo Azeglio Ciampi, in Per Gerardo Marotta, a cura di C. Piga, M. Isacchini e A. Ciccarelli, Arte Tipografica, Naples 1999, p. XVII.
  3. Derrida J. Per Gerardo Marotta: dare e ricevere ragioneivi, p. 108.
  4. Gargano A. L’Europa nella crisi del mondo contemporaneo. In L’attività internazionale dell’Istituto Italiano per gli Studi Filosofici, IISF, Naples 2003, p. 28.
  5. Eknoyan G, De Santo NG, Massry S.G. On the Future of History of Nephrology. Am J Nephrol 1994; 14; 255-256.
  6. De Santo NG, Eknoyan G, Capasso G, Marotta P. Human Clinical research: Ethics and Economics. Istituto Italiano per gli Studi Filosofici, Naples, 1996.
  7. De Santo NG, and Eknoyan G. Human Clinical research: Present Disorders and Future Promises. In Human Clinical Research: Ethics and Economics, ibidem, pp. 21-40.
  8. Eknoyan G, De Santo NG. A brief History of Human Clinical Research. Ibidem, pp. 41-54.
  9. De Santo NG, De Santo RM, Perna AF, Bellinghieri G, Cirillo M. Survival Is Not Enough – Quality of life in CKD. J Nephrol 2008; 21 (S13): 1-166.
  10. Fabrazzo M, De Santo RM. Depression in Chronic Disease. Seminars in Nephrology 2006; 26: 56-60.
  11. De Santo NG, Gesualdo L, Procaccini DA, Bellinghieri D, Savica V, Perna A, Santoro D, Cirillo M (Eds). Sopravvivere non basta. Costruire una sanità che parta dalle esigenze dei malati. G. Italiano di Nefrologia 2008: 25 (6): 628-753.
  12. De Rosa G. Organ donation: a tool to teach solidarity in elementary school children. In De Santo NG, Balat A, Gesualdo L et al (Eds), I testimoni del tempo / witnesses of the times no. 28, Naples, Metis, 013:59-66.
  13. De Santo NG, Scarabelli A, Citterio F, De Santo LS, De Rosa G. The Italian places of Nicholas Green 20 years after his assassination. G. Italiano di Nefrologia 2014; 31(3): 1-12.
  14. Green R, De Rosa G, Scarabelli A, De Santo LS, Citterio F, De Santo NG. The murder of Nicholas Green: Organ Donation 20 Years Later. Am J Kidney Dis 2014; 64 (4): A17-9.
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  17. De Santo NG, De Santo RM, Perna A, Anastasio P, Bilancio G, Pollastro RM, Cirillo M (Eds). Sopravvivere non è abbastanza. Qualità della vita nella malattia renale cronica. Una nuova generazione di economisti della salute. I testimoni del tempo / witnesses of the times no. 19;2007:1-50. Naples, Metis, 2007.
  18. De Santo NG, De Santo RM, Perna A, Anastasio P, Pollastro RM, Di Leo VA, Bilancio G, Cirillo M (Eds). Sopravvivere non basta. Migliorare la qualità della vita. I testimoni del tempo / witnesses of the times no. 20. Naples, Metis 2008.
  19. De Santo NG, Perna A, Bilancio G, De Santo RM, Di Leo VA, Cirillo M (Eds). Sopravvivere non basta. Dare qualità alla vita degli ammalati. I testimoni del tempo / witnesses of the times no. 20. Naples, Metis 2008: 1-39.
  20. De Santo NG, De Santo RM, Perna A. Grimaldi R, Cirillo M (Eds). Sopravvivere non basta. Ricerca clinica e prevenzione elementi fondanti di una sanità giusta con i bisogni dei malati e dai conti in ordine. i testimoni del tempo / witnesses of the times no. 23-24. Naples, Metis 2010: 1-62.
  21. De Santo NG, Bellinghieri G, Balat A, Pisot R, Nenov D, Fortunato G, Appetiti E, De Santo RM, Montano A, Savica V, El Matri A, Venditti G, Diamandopoulos A, and Marotta G (Eds). Survival Is Not Enough. i testimoni del tempo / witnesses of the times no. 27, Naples, Metis 2012.
  22. De Santo NG, Gesualdo L, Rutkowski B, Balat A, Pisot R, Vlakakos D, El Matri A, Nenov D, Mydlik M, Bellinghieri G, Derzsiova K, Diamandopoulos AA, Appetiti E, Savica V, Venditti G, Cirillo M, De Santo RM, Marotta G, and Montano A (Eds). The needs of CKD patients – Survival Is Not Enough 2013. I testimoni del tempo / witnesses of the times no. 28. Naples, Metis 2013: 1-163.
  23. De Santo NG, Balat A, Gesualdo L, De Rosa G, Mydlik M, Vernaglione L, Bellinghieri G, Savica V, Vairo A, Sannicandro D, Cirillo M, Vlachakos D, Musacchio R, Pisot R, Derzsiova K, Nenov D, Venditti G, Castaldi G, De Santo RM, Diamandopoulos A, (Eds). Survival Is Not Enough: Organ Donation a Family Decision. I testimoni del tempo / witnesses of the times no. 29. Italian Institute for Philosophical Studies, Naples 2014:1-152.
  24. De Santo NG, Citterio F, Balat A, Gesualdo L, Diamandopoulos A, Vernaglione L, Bellinghieri G, Mydlík M, Vairo A, Nenov D, Green R, Savica V, Derzsiová K, Demircioğlu Kılıç B, Eustratiadis G, Venditti V, De Santo RM, Appetiti E, De Rosa G. Survival Is Not Enough 10: Prevention and Organ Donation: One and the Same Path. I testimoni del tempo no.30. Italian Institute for Philosophical Studies, Naples 2016.
  25. De Santo NG, Santini L and Bonavita V (a cura di). Il capitale Umano dell’Età. Prefazione di Giuseppe Galasso. Guida Editori, Naples 2017.
  26. Bonavita V, Chieffi G, Cokkinos DA, De Santo NG, Eknoyan G, Erich J, Fine L, Galasso G, Geronikoulo S, Mannemann J, Nwaneri N, Santini L. The Human Capital of Age. Istituto Italiano per gli Studi Filosofici. I testimoni del tempo. No. 31. Naples, Metis, 2017.
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  29. Galasso G. L’utopia costruttiva di Marotta. Il Corriere della Sera. Milan, January 27, 2017.

Aphorisms related to nephrological subjects in Rhazes’ Kitāb al-Murshid aw al-Fuṣūl (The Guide Book or The Book of Aphorisms)

Abstract

We present the aphorisms related to nephrology in The Guide Book or The Book of Aphorisms (Kitāb al-Murshid aw al-Fuūl) by Rhazes (865-925 AD), based on the edited version of the book by the noted historian of Islamic Medicine A. Z. Iskandar published in 1961. We briefly discuss the aphorisms related to nephrology presented in the Guide Book under the titles of “diuresis”, “the urine”, “discharge of excretions of the kidneys”, “discharge of excretions of the bladder”. The aphorisms contain basic and general physiological and pathological information on diuresis and urine based on traditional humoral principles. They do not address any specific diseases.

Keywords: Rhazes, Medieval medicine, The Guide Book, The Book of Aphorisms, History of Nephrology

Introduction

Abū Bakr Muḥammad ibn Zakariyyā al-Rāzī (865–925 AD), also known as Rhazes in the Western world, was an eminent physician and philosopher during the golden age of the Islamic world in medieval times. He compiled over 200 works on various chemical, philosophical, ethical subjects, with over half of them on medicine (1). The founding father of the history of science, George Sarton (1884-1956), says that “Rhazes was the greatest physician of Islam and the Middle Ages” (2). His originality, clinical acumen and observational aptitudes are best known for his most celebrated works, the Liber Continens (Kitāb al-Ḥāwī fī al-Ṭibb), Liber ad Almansorem (Kitāb al-Manṣūrī fī al-Ṭibb), and De Variolis et Morbilis (Kitāb al-Jadarī wa al-Ḥaṣba) (2). Less well known is his Kitāb al-Murshid aw al-Fuūl (3), which means The Guide Book or The Book of Aphorisms (4). Written late in his career this is a relatively short general treatise based on his earlier observations and meant as an introduction of basic principles for students of medicine (4). Although Salomon Negri (1665-1727), a teacher of Oriental Languages in Early Modern Europe, mentions this book as Liber directionis et vocatur Liber sectionum in his Latin translation of Ibn Abī Uṣaybiʿa’s ʿUyūn al-Anbāʾ fī Ṭabaqāt al-Aṭibbāʾ (5), actually The Guide Book was never translated into Latin (4). Although it appears to have continued to be used in learning medicine as mentioned by Maimonides (1135-1204) as one of the books he read for his medical education after settling in Fustat in Egypt following his exile from Cordoba in 1148 (6).

In brief, in the prologue of The Guide Book, Rhazes criticizes Hippocrates’ Aphorisms and states that he wrote this book as a gateway to the art of medicine and to show a way to learners:

Abū Bakr Muḥammad ibn Zakariyyā al-Rāzī, God bless his glorious soul, said [the following]: What made me angry is the confusion and lack of order, the obscurity and remissness of the whole or most of the comprehensive art of Hippocrates’ Aphorisms, and his advice on the easiness to memorize aphorisms and attach them to people motivated me to present the comprehensive art of medicine and its phrases through aphorism. I managed to do that by explaining, representing, and leaving out overstatements and details that lead into obscurity. Where contradiction exists, it necessitates investigation and further scrutiny to this gateway to the art and a way for learners. God guides to the right (3, p 17).

 

Materials and Methods

The edited version of Rhazes’ The Guide Book or The Book of Aphorisms by the noted historian of Islamic Medicine, Dr. Albert Zakī Iskandar was studied (3). The edited text was arranged by Iskandar using the copies of Kitāb al-Murshid aw al-Fuṣūl in the İstanbul Süleymaniye Manuscript Library, Ayāṣōfyā, Nr. 3724, and in Dār al-Kutub al-Miṣriyya, Tibb Talʿat, Nr. 594 (3). This is a relatively short book of 377 aphorisms. Table 1 shows the sections of this book (3). Aphorisms related to nephrological subjects in The Guide Book by Rhazes are translated from Arabic into English and briefly discussed in this study.

 

Results

As shown in Table 1, the first title of aphorisms related to nephrological subjects regards diuresis. The first aphorism under diuresis states that diuresis is one of the strongest bodily discharges necessary to protect health:

Aphorisms on diuresis

#149 Diuresis is one of the strongest discharges that are needed in many conditions; the ancients preserved health through diuresis (3, p 55).

 

The second aphorism mentions the benefits of diuresis and lists diseases for which diuresis is beneficial:

#150 Diuresis expels excretions of the second and third digestion; it is beneficial for aches of the joints and back. It desiccates the body, and he [the patient] is cleared from dropsy and many humid diseases. However, violence in and permanence of can result in demise of the patient due to emaciation and fatal collapse and can cause ulcers in the urinary bladder and the penis. It provokes thirst: those affected by this illness always drink water and have white watery urine (3, p 55).

 

The third aphorism lists diuretic drugs:

#151 Diuretic drugs: Seed of Celery and aniseed, …, and seeds of watermelons/melons and the flesh of watermelons/melons. Furthermore, many aromatic spices, seasonings, and oxymels have a moderate diuretic effect. However, cantharides, musk, stavesacre, and māhīzahraj [herbals that poison fish] are bad; these should not be used, except in case of need and provide improvement, if harm has not taken place (3, p 55).

 

The second heading of aphorisms is related to urine. The first aphorism under this heading states that urine reflects the condition of blood:

Aphorisms on urine

#192 Urine reflects the condition of blood; therefore, it is separated on what we will mention, if God will (3, p 68).

 

The second aphorism explains the formation of urine:

#193 When water and food arrive at the stomach, it [the stomach] comprises them and grinds them, until it becomes something like thick water of barley, which physicians call chyle. Then, the chyle is passed to the duodenum and jejunum. Blood vessels, called “the lacteals”, grow from inside the liver to the bottom of the stomach and to the intestines. They absorb the chyle like the absorption of substances from the earth by tree roots, until the chyle is placed in the blood vessels, located in the flesh of the liver, where it changes into blood. While cooking and transforming [of the chyle], foam, which is yellow bile, and dreg, which is black bile, are generated in it [the liver] just as it is generated in other juices that are cooked. Then, the gall bladder attracts this foam, while the spleen attracts the dreg and the kidneys attract the residual thin water, which is in them. Thereafter, the blood is purified and is good for the flesh covering the body. Hence, the urine reflects the condition of blood, which is short in cooking amount or excessive (3, p 69).

 

The third aphorism states that urine, which reflects the condition of blood, also indicates the condition of the kidney, bladder, and urinary tract. The color and consistency of urine indicate the cooking amount of blood:

#194 Urine, which indicates the condition of blood, can reflect many conditions of the kidney and urinary bladder because it is the place where the urine passes and because urine is only separated from blood after being cooked with it. Urine indicates the cooking amount of blood with its color and consistency. Thus, if the amount of cooking was less, it [the urine] will be thin and white, if it [the amount of cooking] was excessive, it [the urine] will be thick and red, and if it [the amount of cooking] was moderate, it [the urine] will be yellow and moderate in thinness and thickness. If the heat in the liver is exceeded highly, it [the urine] will be black and intensely thick, similar to how it exists in fatal acute diseases (3, pp 69-70).

 

The fourth aphorism addresses uroscopy. Urine should be left to rest a while before the sediment is examined:

#195 Likewise, whatever turbidity and thickness in water and other fluids descend and settle, when it has sat for a while, also conditions the urine. Therefore, anyone who wants to examine urine should leave it to rest for hours and then inspect it (3, p 70).

 

The fifth aphorism asserts that urine should be obtained after the person has slept for a long time and before drinking:

#196 Urine should be collected after the patient awakes from a very long sleep and before he drinks something. This is because if it is taken after he drinks something, the condition of urine will be corrupted (3, p 70).

 

The sixth aphorism explains the conditions in which urine darkens:

#197 Urine becomes darker, unless the person eats and drinks. Therefore, errors in the coloring [of the urine] should be considered. For example, when urine collection is delayed from the morning to noon, the patient has not yet eaten or drunk anything; hence, urine becomes strongly colored compared to the one collected in the morning. It should not be decided on predominance of heat that accounts for the amount of that dye, since nothing of it had been dyed for that period [of dietary abstinence], urine becomes darker, unless the person drinks. It [dyeing] Is only indicative of the amount of cooking in the liver, which exists shortly after the completion of digestion and not after a long period (3, pp 70-71).

 

The seventh aphorism clarifies how the vessel, the matula, should be and for how long urine should be left for before the inspection of the urine sediment:

#198 One interested in examining the condition of sediments should collect urine in a big white and round vessel and leave it for three to ten hours to stand for whatever should settle in it (3, p 71).

 

The eighth aphorism asserts that frequent urination is no indication of the condition of cooking:

#199 Urine that comes out quickly and successively like in illness called “passing urine by driblets [dysuria]” is not a matter of the cooking; therefore, such kind of water does not dry in the liver when the cooking is completed, but comes out quickly. Thus, we find someone with “diabetes” urinating this kind of water because he passes water shortly after drinking (3, pp 71).

 

The ninth aphorism mentions that things (gravel?) in the urine of people having difficulty in passing their urine are only generated in the kidney, bladder, and urinary tract:

#200 We find exquisite things in the urine of those who have difficulty in passing urine and passing urine in driblets, which were generated only in the kidney, urinary bladder, and urinary tract and not in the liver when it is cooked (3, p 71).

 

The 10th aphorism reports that sediments settle at the bottom of the vessel when the cooking has been complete. Sediments that float or remain suspended in the urine reflect the condition of the cooking:

#201 When the ripeness is complete, sediments settle at the bottom of vessel, and when it [the ripeness] was intermediate, they were [the sediments were] suspended, and when it [the ripeness] was at the beginning, they [the sediments] floated (3, p 71).

 

The 11th aphorism clarifies that bright white sediments are the best indicators of a complete cooking:

#202 The bright white sediment is praiseworthy and indicative of complete ripeness because cooking power is complete; the white suspended [sediment] is about half of the ripeness; the white cloud is of beginning matter being excreted in the urine, because torrential [sediment] only suspends and floats and that of a complete cooking does not exist in it (3, pp 71-72).

 

The 12th aphorism states that all sediments that are not white are bad, but that the black ones are the worst:

#203 All sediments different from the white colored ones are bad; therefore, they indicate an excess cooking, but black ones are the worst. Thus, things that are cooked do not turn black, but they do when burned by strong heat (3, p 72).

 

The 13th aphorism explains conditions of black sediments:

#204 The matter of black sediments can be in contrast to that of white [ones]; therefore, the sediment is evil, while the floating sediment is less evil, and the suspended one is evil in the middle because the sediment indicates the completeness of cooking by ripening or combustion; the suspended [sediment indicates that the ripening is] in the middle, and the cloud [indicates that it is] at the beginning (3, p 72).

 

The 14th aphorism mentions that sand, stone, fleshy strands, hair, plates and bran present in urine do not indicate the condition of blood:

#205 Sand, stone, strands of flesh, hair, plates, and bran exist in urine. None of these sediments indicate a [pre-]existing condition in the blood because they only occur in urine after its separation from the liver (3, p 72).

 

The 15th aphorism provides Tabence books on urine, in case it is required:

#206 If you understood the essence that I explained, comprehending partial matters was easy and does not necessitate looking at [other] sources. There is a special book on urine. In this [book], we guided [the reader] to what we collected in al-Jami’ al-Kabīr, and there is no agreement, [one should refer] to Kitāb al-Maġnīs [Book of Magnus], and Kitāb al-Iṣṭafan [Book of Stephan], Kitāb al-Arsīlūs [Book of Archelaus] and what the “excellent” Galen mentioned in Kitāb al-Buḥrān [περὶ χρίσεων/De Crisibus]. The best is to continue investigating; there is no single book but it is acquaintance with these books that it is learned from what is inside. This is not only true for this section but also true for other sections (3, pp 72-73).

 

There are two aphorisms regarding discharges of excretions of the kidney and bladder:

Discharge of excretions of the kidney

#302 Excretions of the kidney are discharged with diuretics. Their temperaments are altered by mixing them with warming or cooling drugs, or by bandaging the lumbar region while the patient lies down on where he is warmed by them, or by what is administered as clyster (3, pp 98-99).

Discharge of excretions of the bladder

#303 Excretions of the bladder are discharged with diuretics. If the temperament is altered and ulcers develop they are healed up by mixing drugs that cure wounds— different from diuretic drugs— which are used to coat the pubic area that is then  bandaged with it, and they are injected into the urethra (3, p 99).

 

An aphorism under the title of bad signs informs that bad urine is bad in all diseases:

Bad signs

#351 Badness of urine is bad in all diseases. Its goodness in all diseases is not an indication of recovery from that disease but an indication of fevers and diseases of the liver and urinary tract (3, p 115).

 

Discussion and Conclusion

Rhazes systematically arranged the aphorisms related to nephrological subjects in The Guide Book or The Book of Aphorisms. He informed the reader of the importance and benefits of diuresis and diuretic drugs in the first group of aphorisms.

He explains how urine is formed and what the consistency and color of the urine indicates. Furthermore, he emphasizes how urine should be examined and how the color and consistency of urine, its sediments, and other contents have to be interpreted in the second group of aphorisms.

The basic and general physiological and pathological information on urine and diuresis is based on humoral paradigm. He does not refer to any specific disease subjects. When chapter 19 “On urine and kinds of sediment and colors and consistency of urine” in Liber Continens was examined (7), it became evident that the information provided on urine in The Guide Book is an abbreviated introduction to medicine presented in his Liber Continens.

One of the basic sources for the section on urine in Liber Continens is Galen’s Kitāb al-Buḥrān (περὶ χρίσεων/De Crisibus) (7) that also mentioned as a reference by Rhazes in his aphorism. The Book of Magnus, the Book of Stephan, and the Book of Archelaus are also part of his sources in Liber Continens (7). In addition, Rhazes cites many other authors and their books in Liber Continens, including Hippocrates, Galen, Rufus of Ephesus, Stephanus of Athens, Magnus of Emessa, Aaron of Alexandria, Paul of Aegina, Masīḥ al-Dimashqī, Ayyūb al-Ruhāwī al-Abrash, ʿAlī al-Ṭabarī, Ibn Sarābiyūn, Ḥunayn, al-Yahūdī, and Phythagoras al-Iskandarānī (7).

The fourth discourse titled “On the nature of the science of medicine and grades of physicians” of Four Discourses (Chahār Maqāla) by Niẕāmī-i-ʿArūḍī-i-Samarqandī contains a list of the syllabuses on medical education in the Islamic world of the 12th century reveals that Kitāb al-Murshid aw al-Fuṣūl by Rhazes was considered as one of the reference books alongside with Hippocrates’ Aphorisms (Fuṣūl), Ḥunayn b. Isḥāq’s Questions (Masāʾil), and Nīlī’s Commentary (8).

 

Acknowledgement

Preparation for publication of this article is partly supported by Turkish Neurosurgical Society.

 

References

  1. Sadi LM  (1996) The millenium of ar-Razi (Rhazes) (850-932 A. D.?). In: Islamic Medicine Volume 25, Muḥammad Ibn Zakarīyā al-Rāzī (d. 313-925) Text and Studies II, Collected and Reprinted by Fuat Sezgin in collaboration with Mazen Amawi, Carl Ehrig-Eggert, Eckhard Neubauer, Institute for the History of Arabic-Islamic Science at the Johann Wolfgang Goethe University, Frankfurt Am Main, pp 252-262.
  2. Sarton G (1953) Introduction to the History of Science, Reprinted, Volume I. From Homer to Omar Khayyam. The Williams & Wilkins Company, Baltimore, p 609.
  3. Iskandar AZ (1961) Kitāb al-Murshid aw al-Fuṣūl maʿa Nuṣūṣi Ṭıbbiyyati Muḫtārati li-Abī Bakr Muḥammad b. Zakariyyā al-Rāzī. Majallatu Maʿhad al-Maḫṭūṭāt al-ʿArabiyya 7: 1-125.
  4. Diamandopoulos A, Goudas P (2013) The Hippocratic aphorisms of nephrological interest under the light of current clinical knowledge. Ελληνιϰή Νεφϱολογία 25: 99-108.
  5. Ranking GSA (1996) The life and works of Rhazes (Abū Bakr Muḥammad bin Zakarīya ar-Rāzī). In: Islamic Medicine Volume 25, Muḥammad Ibn Zakariyā al-Rāzī (d. 313-925) Text and Studies II, Collected and Reprinted by Fuat Sezgin in collaboration with Mazen Amawi, Carl Ehrig-Eggert, Eckhard Neubauer, Institute for the History of Arabic-Islamic Science at the Johann Wolfgang Goethe University, Frankfurt Am Main, pp 73-104.
  6. Bortz JE (2011) “The medical books I have read so far”. A research into the books read by Maimonides (1138-1204) for his medical education. eä 3: 1-11.
  7. Abū Bakr Muḥammad ibn Zakariyyā al-Rāzī (2000). Al-Ḥāwī fī al-Tibb. Vol. VI. Dar al-Kotob al-Ilmiyah, Beirut, pp 2729-2823.
  8. Nidhámí-i-‘Arúḍí-i-Samarqandí (1900) The Chahár Maqála (“Four Discourses”). Translated into English by Edward G. Browne. Reprinted from the Journal of the Royal Asiatic Society, July and October, 1899. Luzac & Co., London, pp 109-110.

Nils Alwall- a personal appreciation

Abstract

I first met Nils in 1964 at the founding of the EDTA (sic) in Amsterdam. I was 29, he was 60. Later I worked with him, now retired from clinical work, on committees over the next couple of decades. During this time he assumed Presidency of both the EDTA and the ISN; he was one of the major founders of Nephrology, as well as a pioneer of and major contributor to electrolyte balance, haemodialysis, ultrafiltration and related techniques. He had introduced renal biopsy in 1944, but remained silent on this subject until after Claus Brun published his work 8 years later. Nils studied arteriovenous shunts for repeated dialysis during the 1940s, but was blocked by the red rubber and glass tubing – all that was then available. I was immediately impressed by the quiet modesty of this most original man; but despite this he achieved international fame in Europe, although was never well known in the United States. His Festschrift in 1985 in Nephron amply demonstrated his status. His “rival”Pim Kolff (1911-2009) was in contrast slightly younger, outlived Nils by 20 years, and was a fine communicator and great extrovert. Nils was a physiologist and pharmacologist until 36 years old, only then becoming a clinician. Strangely Nils had performed the first haemodialysis at my alma mater, Guy’s Hospital London, in 1948 on a visit, 15 years before we established a renal unit there. Characteristically, he never told me about this event, and I only discovered the story after his death.

Keywords: Nils Alwall, History of haemodialysis, history of nephrology

Introduction

I am grateful to Dr Håkon Westling (1, 2) for some of the following details of Nils’ early life, about which he never spoke, at least with me. Nils Andersson was born into a rather poor farming family in 1904, in an undeveloped area of Kristianstad in NE Skåne in the far SW of Sweden. His elder brother took over the family farm, but Nils – who was early on a bright scholar – matriculated and was able to go to university in nearby Lund in 1923 when only 17 years age, but only with continued financial help from an uncle, who remains a shadowy figure. Nils was a brilliant student in his undergraduate career, attaining the highest marks in almost all subjects. To begin with, he studied classics – Latin and Greek – and only later decided to read medicine during his first year in Lund, becoming an unpaid physiology research assistant in 1926. This had the advantage of providing him with somewhere to live, as well as a small laboratory and office.

Three years later in 1929 he moved from physiology to pharmacology, and graduated MD in 1932. He played an active part in student organizations, social and intellectual. He became close to the historian Lauritz Weibull and spent much time in the latter’s house. Despite his quiet exterior, Westling describes the young Alwall (he changed his name from Andersson in 1927, because “there were too many Anderssons”, but perhaps also as a break from his background and childhood) as a “pusher”, a tough customer who would fight for what he wanted (Figure 1). His politics were radical and he was concerned about the physician’s role in society. He believed strongly in education as a motor for change and better health, and gave public lectures regularly in Southern Sweden for more than 20 years.

 

Early research

In his physiological studies he worked for Professor Torsten Thunberg on intermediary metabolism. Then in 1932 he changed to pharmacology headed by Gunnar Ahlgren again on intermediary metabolism, studying dinitrophenols and thyroxine, showing that they acted similarly and synergistically. He publicly defended his PhD thesis in 1935, in the manner of the time. Sitting in the room that September afternoon was Nobel Prize-winner August Krogh, a friend of Thunberg’s whose work Nils much admired, who was to receive an honorary degree during the same session. Krogh’s work and thinking on capillary fluid exchange were an important influence on Nils’ thinking, and led him eventually into ultrafiltration and then dialysis.

In 1935-6 he spent a year in Pécs in Hungary working at pharmacology. Around this point he made a momentous decision to start clinical work. What led to this change of direction we do not know, but he started work with Sven Ingar in the Medical clinic in Lund. Meanwhile the second world war soon swept through Europe, and although Sweden remained neutral, he did military service as a doctor, being sent to Germany to study the effects of the wide use of amphetamines and other stimulants in Hitler’s forces – a subject which has re-surfaced recently*.

About this time, in 1941, he began to study fluid exchange, and to forward this work, designed an ultrafiltration apparatus for use in rabbits (Figure 2). A well-known story, which parallels Kolff’s use of material from a downed German plane to make his dialyser, is that Alwall used the new plastic Plexiglass© employed in the cockpit of an American aircraft forced to land in Sweden. He did some experiments on nephrectomised animals which could be maintained in a state of overload, and realised his ultrafilter could also remove potentially toxic solutes. Thus his work on the “artificial kidney”began – but as a secondary output from work on ultrafiltration.

He was particularly interested in accumulation of fluid in the lungs, and studied this in detail radiographically in his rabbits, some of which had been nephrectomised. He was influenced in this thinking by Krogh’s work on fluid exchange in capillaries. At first he used a flat-plate dialyser for his rabbits (Figure 2), but he was aware of the work of haematologist William Thalhimer (1884-1961) in New York, who had used cellophane sausage tubing to dialyse dogs, and managed to obtain some of this despite the restrictions of war, and built the first model of a static coil type of dialyser (Figure 3). All this was in complete ignorance that Thalhimer’s ex-collaborator, cardiac surgeon Gordon Murray (1894-1976) in Canada, would go on to build a couple of years later a similar static coil dialyser – but without any ability to control ultrafiltration. The unique feature of Alwall’s dialyser was that it had an outside glass container as well as the metal inner support for the tubing wound on it helically, which allowed the controlled ultrafiltration he sought, unlike Kolff’s rotating drum machine (of which Alwall was equally oblivious) one of whose major disadvantages was wild uncontrolled swings in the volume of body water during dialysis. Alwall pioneered the view of water as major toxin in uraemic patients. He attended the first international meeting on The kidney organized by the Renal Association of the UK in London in 1953, and described his work on in vivo ultrafiltration, and precipitated a vivid and wide-ranging discussion. In this conference dialysis was not mentioned anywhere in the programme! – and Kolff did not attend.

During the mid-1940s Alwall slowly developed his coil machine with the idea of treating renal failure in humans (3), but unlike Kolff – who never asked if he could dialyse patients, had no lab and no animal experiments – he was restrained from trying it in a human subject until June 1946, when : “…we were finally allowed to perform our first treatment in a moribund patient….As an associate professor I depended on the permission of the director of our medical department, who feared the new method. The general opinion was adverse”.

Altogether 8 patients with various types of chronic irreversible uraemia were dialysed in 1946-7 (4), but not surprisingly they achieved little long-term benefit – although temporarily they mostly felt much better for a while. However the second patient, treated in 1947 (case no 702 in ref 10, Fig 1.7 Chapter 1) had severe anuric acute glomerulonephritis, was dialyzed once – and survived. The first patient treated with dialysis for acute renal failure from mercuric chloride suicidal poisoning was fitter and also survived, but local physicians’ opinions were heavily against this form of “active”treatment, and the (to us now expected) persistent mortality of around 50-60% even in “reversible”forms of acute renal insufficiency which emerged led to a term in Sweden to describe a patient who was “Alwallized”– that is, dialysed and who then – died. Although an article in the Lancet in 1948 (5) helped greatly to disseminate knowledge of his work, the general opinion from 1945-50 was that dialysis added nothing to conservative treatment with fluid restriction and anti-catabolic nutrition (6).

This was a bleak time for him. His work, although intellectually satisfying, published and clinically useful, was however not generally accepted, he had little money despite being in his 30s, and promotion eluded him: despite having been acting professor for two years following the death of his supervisor, in 1948 he applied but failed to obtain a Professorship in medicine following Ingar’s death. Only in 1957 did he finally obtain a personal chair in Lund, in renal diseases, as his international reputation had been established. His unit in Lund, which started dialysis in June 1946, still exists and is the longest-serving dialysis unit in the world after 71 years. Ironically, not being appointed to a general medical position and finally being able to specialise saved him from the burdens of departmental responsibility, which might have allowed him no time to work and sterilized his intellect.

 

Alwall introduces needle aspiration renal biopsy

Before we consider his work in dialysis in greater detail, we must mention also his work on renal biopsy in 1944, still during WW2. By this time needle liver biopsy was well-established, and some practitioners had already obtained samples of kidney by accident. But Alwall was the first to set out deliberately to study renal tissue. He performed renal biopsies on 12 patients without incident and success in obtaining useful tissue in 10; two patients showed amyloidosis, the others – mostly with minor proteinuria or haematuria – showed tissue within normal limits judged by the technology of the day. In the unfortunate 13th patient the left kidney could not be seen on the X-ray plate but Alwall proceeded with biopsy of the right kidney obtaining inadequate tissue: the patient bled, went into shock and became anuric, despite a renal decapsulation (a technique in favour at that time) and died. Alwall published these results (7) (Figure 4) only after the Danes Claus Brun (1915-2015) and his mentor Bjarne Iversen (1889 – 1966) had written their paper on successful renal biopsy in 1951. This death must have been well-known locally, and may in part explain some of the hostility later to his promotion.

1947 was an important year as Nils made first written contact with Pim Kolff, who sent him some valuable Visking cellophane tubing, and his unit dialysed 11 patients from all over Sweden with a few from the rest of Scandinavia, on 21 occasions. Most had exacerbations of chronic disease. He talked in Copenhagen and at the Scandinavian Congress of Surgery, and in May 1948 finally met Kolff, who had been invited to meetings in Stockholm and Lund.

The arteriovenous shunt and developments in dialysis machinery

Problems with access led him to research the idea of an arteriovenous shunt, which he wrote about in 1948-9 (8). Even though these rubber and glass shunts (Figure 5) failed eventually in both rabbits and humans, a number allowed repeated dialysis (9), and it is often forgotten that by the 1950s he was able to dialyse a number of patients for 6 months or more. In 1963 (10) he wrote “these procedures – arteriovenous shunt and filling of closed tubings with heparin…- were also used in the treatments of patients … the present writer later abandoned the use of arteriovenous shunt or any other form of permanent cannulation, because of local infection and the difficulty of avoiding blood-clotting…”

For the first time Nils was able to obtain grants for his work, but even more important was collaboration with two commercial companies to build his dialyser – the Trelleborgs vulcanite company, and the Avesta steel works. He built machines using both materials (Figure 6), but by 1950 was working entirely in steel, which had the big disadvantage that the large apparatus with its double layer of metal was very heavy and difficult to lift. The detailed evolution of his machine is summarised by Carl Kjellstrand and his colleagues (12).

 

The wider world

Nevertheless there was wide interest is using his machine. Franz Volhard (1872 -1950), having survived Hitler’s Germany despite his prolonged opposition to Nazi politics, wrote asking if Alwall could loan him a machine, but at that point Alwall could not oblige. This is interesting because Volhard had opposed the use of dialysis when Georg Haas (1886-1971) used it in the 1920s in Germany (6). Alwall and Volhard met in Munich in Germany in 1949, but further collaboration with Volhard was terminated when the latter died in a car crash in 1950. But during the 1950s Nils’ machine was used in about 50 units worldwide, including first Copenhagen and Cracow (Dr Hanicki), to which he donated machines, Haifa in Israel, Newcastle in the UK, in Australia, Israel, Cuba, Australia and even the United States, where TS Danowski used it for dialysis in children in that year, and George Jernstedt of Pittsburgh collaborated to make a commercial model together with the Westinghouse company, which however did not sell in competition with newer, easier-to-use models such as the Kolff-Watschinger twin-coil disposable dialyser from Baxter Inc. Many others in central and Eastern Europe used the Alwall dialyser in the 1950s. Alwall was particularly concerned with development in of Nephrology in the then Communist bloc, and collaborated with Dutz and Klinkmann in Germany, with others in Russia, and in the (then) Czechoslovakia.

During the 1940s and 1950s Alwall collaborated mostly with surgeons who were more receptive to the idea of an artificial “kidney”than their physician colleagues. During 1947-9, 35 patients were dialysed 56 times in Lund, but elsewhere both in the USA and the UK, so-called “conservative”treatment for acute renal injury, including volume restriction and high energy diets to decrease catabolism, became more popular. This could tide patients over in relatively non-catabolic situations which included the majority of acute renal injury in that period, as a result of abortion, mismatched transfusions and haemoglobinuria, mercury poisoning and sulphonamide crystalluria in younger, previously-fit patients (6). Opinion swung against haemodialysis for a decade; in addition many surgeons and urologists used peritoneal dialysis, which had developed in parallel. For example, no haemodialysis at all was done in the United Kingdom from 1949 to 1957.

But Alwall never gave up and went on treating the rapidly increasing number of patients referred to Lund, still the only unit doing dialysis in Sweden. He worked hard to ensure that this situation did not persist, but beginning with a second unit in the North of the country in 1958, within a few years there were 17 dialysis units in the country of 7.5 million inhabitants. The struggles that he endured and overcame during the 1950s are detailed in his own account (13), and in the biography by Carl Kjellstrand and colleagues (12). By the end of the decade he had a bigger unit to head, recognition of the specialty, more staff and a personal chair – but after what a huge struggle! It took an Act of the Swedish national parliament to achieve the final steps.

By the end of the 1950s an amazing 1000 patients had been dialysed in Lund, mostly for acute renal failure, but some also knowingly or with undiscovered chronic renal insufficiency, and Alwall thought it time to summarise his experience. His book of 1963 Therapeutic and diagnostic problems in severe renal failure, (10) (Figure 7) although little known or read today, is one of the landmark publications in Nephrology. An amazing amount of data are presented, most in the form of graphs of data from individual patients, each drawn by Alwall himself and autographed. It is meticulous, but difficult to read and extract broad data from. It does however contain for the historian of dialysis an amazing bibliography of over 95% of all papers published until then on the subject of the artificial kidney – nearly 1400.

Medical advances in the field of acute renal failure and dialysis were many in the 1950s, but two require mention: in 1955 Nils described contrast-induced acute renal failure (14), and began in the early 1950s to explore the role of dialysis in the treatment of patients with overdoses of various medicines, beginning with barbiturates (15).

 

Long-term dialysis and its consequences

As is well known, in 1960 Scribner had his colleague Wayne Quinton make an arteriovenous shunt from the new electrical insulator material PTFE (Teflon©). Quinton rapidly added silicone rubber to the design, and by two important meetings later in the year (the ASAIO and the first meeting of the ISN), three patients had been using these shunts for regular dialysis for a numbers of months. In Evian at the ISN meeting, just 12 people formed the audience for Scribner’s epic paper; one of them was Nils Alwall, to whom Scribner gave some material to make a shunt.

At the end of his 1963 book (10), Alwall presented depressing data on his early attempts to use the arteriovenous shunt to treat end-stage renal failure. All 10 patients had died quite early after starting long-term dialysis. This surprise was part of an experience noted worldwide, and many wondered what “magic”Scribner and his colleagues concealed. Nils thus quietly went off to Seattle to work for some months himself there, to learn on site how to do long-term dialysis – and found that meticulous attention to detail, the use of pumpless dialysis with long sessions (6-8h) and meticulous control of weight, salt and water intake and blood pressure were the main components of the “magic”(6). He returned and re-started a now successful programme of long-term dialysis in Lund in 1964.

Only at this point when he had done so much, did I meet Nils Alwall. It was at the founding meeting of the EDTA (or ERA as it later became) – in Amsterdam, in 1964. Nils was 58, and I half his age, having worked in what became Nephrology for only three years. By chance, I have a photograph of our meeting (Figure 8), when pictures of the audience were taken during a session by Willem Drukker, one of three founders of the Association. I was in awe of this quiet, modest man who had done so much. From then, however I met him regularly through the Councils of the ISN and the EDTA-ERA during the following fifteen years, when his political achievements gradually took over from his innovation in dialysis.

 

Sweden, Europe and the world

With long-term dialysis looming as a treatment for a large number of individuals in irreversible renal failure, in all developed countries, a heated debate ensued as to what to do. Alwall played a central role in this debate not only in Sweden, but world-wide. In 1965 as he had drawn the attention of the government to the problem repeatedly, he was asked to prepare a report, which was finally accepted but only after a long struggle: 7 dialysis units in the regions of Sweden each serving a million inhabitants, were planned and executed with expansion of transplant facilities in parallel. At that time the huge size of the problem was not apparent: even Scribner pictured just a few thousands per year in the whole USA entering end-stage renal failure. And everyone forgot the patients would accumulate with successful long-term outcomes, unless transplantation could meet demand –which it still fails to do. But Alwall had done his homework better – and proposed that eventually 70 people per million per year would need treatment in Sweden, a figure close to the actual Swedish data today. Many other countries, especially the United States, showed a much greater proportion of the population requiring treatment, for reasons that remain under discussion. Had governments with central health systems realised that this 0.1% of the population with renal failure would consume more than 1% of the total health budget, their response in Sweden and the UK might have been very different. In the UK, a similar plan had been suggested by another giant of early Nephrology, Hugh de Wardener, and accepted for 35 units, but after a promising start ran aground 5 years later when costs became apparent and hepatitis ravaged the nascent hospitals.

His experience of organization and leadership in Sweden made Nils an obvious candidate for the Presidency of the ISN, on whose council he had served since it was formed in 1960, and from 1975 to 1978 he served in this high office. During this time a new constitution was designed and accepted, the finances put on a more secure footing, and a Society organization set up. He had been also President of the European Dialysis and Transplant Association in 1971 – an annual rotation with the meeting, which was held in Stockholm that year, but he served as president the following year.

 

New dialysers

Having forged his work-horse machine for dialysis in acute renal failure, Nils in the 1960s turned his attention to regular long-term dialysis. A disposable dialyzer for placement in a machine was already in use in many units for acute dialysis (the Kolff-Watschinger twin coil), and this suggested that disposable rather than re-buildable dialysers for regular long-term dialysis would be needed. After a short flirtation with coil models, he designed a flat-plate dialyser mimicking the Kiil mode, together with Holger Crafoord of Tetrapak, who founded Gambro AB as a company to manufacture this dialysis machinery. This disposable dialyser (Figure 9) came out in 1967; it was heavy with a metal clamping frame, but did the job. By 1970 it had been completely redesigned in plastic as the Gambro Lundia dialyser (Figure 9) and its successors, and were widely-used for long-term dialysis, until capillary hollow-fibre dialysers took over in the 1990s. Gambro became one of the largest manufacturers of dialysis machinery in the world.

In 1971 at the age of 65 Nils retired as university rules required, but remained active. He worked hard as President of the ISN from 1975 to 1978, and as at that time the President did much of the work of later delegated to the Secretary General, this occupied much of his attention. At that time there was no permanent office with only a couple of paid staff in the Treasurer’s office, and things were run on a very cheap basis with the President and Secretary General (John Moorhead) again doing most of the work themselves (16).

During this decade also he became interested in the problem of urinary tract infections, especially in women, and he published a number of papers on the epidemiology, diagnosis and management of this problem. In the 1980s he published a series of papers in Dialysis and Transplantation giving a detailed history of his work concentrating on events in Sweden, and later Europe and the world (13).

In 1985, the journal Nephron devoted a number to a valediction of Nils Alwall. The dedication was written by his pupil Carl Kjellstrand (14), who had worked with Nils in Lund in the early 1960s, and was a co-author of part of his giant book of 1963 (10). The same year he was invited to lecture by the International Society for Artificial Organs, and the text of this talk summarising the development and impact of the artificial kidney was published in its journal in 1986 (11) – posthumously; Nils had died, aged 81, earlier in that year. He had left behind him an enormous legacy, which Carl described more fully in his biography of Nils in the book he edited in 2012 (12).

Numbers of people have commented how Nils’ legacy has to some extent been forgotten – or never appreciated, notably Kjellstrand (12, 17), Klinkmann (18), Shaldon (19) – and the present author (6). One problem from the beginning was that Alwall remained one step behind Kolff in the design, production and use of his clinical artificial kidney (dialyzer). Also, he never promoted the treatment as vigorously as Kolff. The two were opposite poles: Kolff visibly energetic, outgoing, travelling, talking, making and giving his machines on a scale Alwall could never match. Most important of all, Kolff was invited by Isidore Snapper, also Dutch, to go to New York shortly after WW2. His talks were heard by the pioneering Boston group, and his kidney updated and modernized by them as the Kolff-Brigham dialyzer, and then employed in the battle casualties in the Korean war which gave enormous publicity and momentum to the treatment, and swung opinion against conservative treatment in traumatised and postoperative patients (6). Finally Kolff took Irvine Page’s invitation to immigrate to Cleveland, Ohio, and he never returned to Europe.

In contrast, Alwall had little or no profile in the United States, and still has not today. The great majority of his papers were published in Scandinavian journals little read in the Anglo-Saxon speaking world – or in France, where Nephrology was blossoming in Toulouse, Lyons and Paris in the 1950s. I can find no mention of any visit to the United States in the 1950s or even the 1960s, although he travelled extensively within Europe and went to Egypt in 1956. Only in 1978, because of the ISN, did he go to North America, to Montreal. Until then, no-one invited him with expenses, and he writes he lacked the means to travel to (for example) to the annual ASAIO conferences in the 1950s and 1960s. He did have visitors to Lund from the USA however – including Stefan Rosenak in 1952 (another forgotten pioneer (6)) and Scribner in 1958 whilst the latter was working in London. Scribner visited again in 1960. Finally, his disposable dialyser came a decade after Bruno Watschinger and Kolff’s massively popular twin coil, manufactured commercially by Baxter’s. As an example, in the United Kingdom only the Newcastle Unit led by David Kerr used Alwall’s machine, then quietly abandoned it for static coil dialysis. At root was Alwall’s quiet, meticulous careful and modest personality. In short, he did not “sell”himself. The steely determination remained hidden.

I will finish on a personal note. In 1948, Nils was asked by a Dr Adler to come to London to dialyse a patient in my own hospital, Guy’s Hospital. The patient had polycystic kidneys and dialysis relieved much of his symptoms. An account of this episode was published (20), but it was 14 years before we at Guy’s took up dialysis for acute renal failure. I was still at school when this early dialysis occurred and characteristically, Nils never told me about it, and I discovered the story only some years after his death in 1986, when doing research for my book on the history of dialysis (6).

 

 

*Footnote : Here I am quoting Dr Westling – Alwall himself wrote in 1980 “from the beginning of World War II until 1949 I had no opportunity to go abroad”. Perhaps he wished to conceal this episode.

 

References

  1. Westling H. Konstgjord Njure. En Bok om Nils Alwall. Stockholm, Atlantis, 2000.
  2. Westling. Personal communications, 2001-2.
  3. Alwall N. On the artificial kidney I. Apparatus for dialysis of the blood in vivo. Acta Med Scand 1947; 128: 317-325.
  4. Alwall N, Norviit L. On the artificial kidney II. The effectivity of the apparatus. Acta Med Scand 1947 (196 suppl) 250-258.
  5. Alwall N, Norviit L, Steins M. Clinical extracorporeal dialysis of blood with artificial kidney. Lancet 1948; i: 60-62.
  6. Cameron JS. The first practical haemodialysis machines: Kolff, Murray and Alwall In: A history of the treatment of renal failure by dialysis. Oxford, Oxford University Press, Chapter 8, pp 87-91.
  7. Alwall N. Aspiration biopsy of the kidney. Including i.a. a case of amyloidosis diagnosed through aspiration biopsy of the kidney in 1944 and investigated at autopsy in 1950. Acta Med Scand 1952; 143: 431-435.
  8. Alwall N, Bergsten BW, Gedda P, Norviit L, Steins AM. On the artificial kidney IV. The technique of animal experiments. Acta Med Scand 1949; 132: 392-411.
  9. Alwall N, Norviit L, Steins AM. On the artificial kidney VII. Clinical experiences of dialytic treatment of uraemia. Acta Med Scand 1949; 132: 587-601.
  10. Alwall N. Therapeutic and diagnostic problems in severe renal failure. Copenhagen, Munksgaard, 1963. p. 30.
  11. Alwall N. Historical perspective on the development of artificial kidney. Artif Organs 1986; 10: 86-99.
  1. Kjellstrand C, Lindergård B, Odar-Cederlof I. Nils Alwall, the first complete artificial kidney and the development of acute and chronic dialysis. In: Ing T, Rahman MA, Kjellstrand CM (Eds) Dialysis. History development and promise. World Scientific, New Jersey etc. 2012 pp 77-88.
  2. Alwall N. On the organization of treatment with the artificial kidney and clinical nephrology in the 1940s and flowing decades. A contribution to the history of medicine. Dialysis Transplant 1980; 9: Part I The nineteen forties: 307-311, Part II The turn of the decade 1949/1950: 475-508, Part III The nineteen fifties 559-569, Part IV The nineteen sixties the first Part 669-713, V the nineteen sixties, second part, and the nineteen seventies 752-758,771.
  3. Alwall N, Erlanson P, Tornborg A. The clinical course of renal failure occurring after intravenous urography and/or retrograde pyelography; casuistics of 11 cases (including 7 deaths) ; on indications for and risks involved in the use of contrast media, including some remarks on the risk of aspiration biopsy of the kidney. Acta Med Scand 1955; 152: 163-173.
  4. Alwall N, Lunderqvist A. On the artificial kidney XXV. Dialytic treatment of severe barbiturate poisoning in two patients. Acta Med Scand 1955; 143: 299-306.
  5. Robinson R, Richet G. International Society of Nephrology. A forty year history. Kidney Int 2001; 59: suppl 79, S-1 – S-100.
  6. Kjellstrand C. (Ed). Dedication to Nils Alwall. Nephron 1985; 39: 71-72.
  7. Klinkmann H. Historical overview of renal failure therapy – a homage to Nils Alwall. Contr Nephrol 1990; 78: 1023.
  8. Shaldon S. Alwall’s often forgotten contribution to haemodialysis. Semin Dial 2006: 260.
  9. Windschauer H. Artificial kidney at Guy’s. Guys Hosp Gaz 1948; 62: 155-157.