During the first quarter of this century and until the eve of the Second World War, the influence of German medical culture was prevalent in Italy, as far as Pathology, Pharmacology and Clinical Science were concerned. I was studying Fahr, Loehlein, on renal pathology, together with Vohlard. But, this matter was included in the unitary field of Internal Medicine, when I had to fulfill my clinical experience. Therefore, I was involved in other types of research, such as Carbohydrate Metabolism, treatment of Diabetes, Liver disease, Clinical Electrocardiography, Hematology, etc., in different periods of time.
The constant observation of patients, in spite of the environmental restrictions of the Second World [War] period, led my first studies on renal pathology, starting from a renal involvement of systemic polyarteritis nodosa. The subsequent widening of this experience allowed me to investigate deeply on vascular nephropathies with secondary hypertension, with related glomerular lesions and malignant nephrosclerosis. Besides, I devoted myself to clinical investigations on renal failure with an accelerated and irreversible course, such as in pregnancy pre-eclamptic toxemia, infections and shock, through studies on another form of vascular pathology of the kidneys, which I defined as acute thrombotic angiopathy with bilateral cortical necrosis, further included in the pathogenesis of intravascular coagulation.
My experience on other cases of acute renal failure was later extended to the histopathogenesis of a glomerulonephritis now defined as rapidly progressive, which I analyzed at that time especially in the glomerular capsule and its exudative, proliferative and fibrinoid necrotic processes: in this way, I was able to trace a form indicated as capsular acute glomerulonephritis. On the other hand, my interests on systemic vasculitis included, towards the end of the '40s, the first observations in Italy on temporal arteritis, and the pathology of the renal glomeruli in lupus erythematosus. In the latter case I described a syndrome, which at first I called malignant erythematovisceritis, and I included in my studies on systemic connective tissue diseases, compared with the international contributions on their clinical, immunological and therapeutic aspects. These examples enlightened me about nephrology, with all the subsequent developments, not only of the morphological aspects, but also for the larger field of functional manifestations.
BEGINNING OF RENAL PHYSIOLOGY
Before the Second World War, physiology in Italy, although promoted by outstanding personalities, was not specifically directed towards the kidney, and most clinicians did not take into much consideration single functions, but only global evaluations already investigated by Vohlard on urine concentration and dilution, or limited to the urea-clearance, disregarding the importance of the glomerular filtration rate although Rehberg's achievements on the creatinine clearance for measuring this function dated back to 1926.
Only at the beginning of the post-war period I was able to take advantage of Addis's, Ellis's, and other contributions on glomerulonephritis. But particularly Homer Smith's fundamental work, known at the beginning of the '50s, was a crucial turning point for the knowledge and measurement of circulatory, secretory and excretory functions of different segments of the nephron, in an original alliance between physiology and clinical medicine that led to important progress for all nephrological studies. Further on, my personal experience was also directed to functional disorders such as renal diabetes.
As far as the renal blood circulation is concerned, I cannot forget to mention the research dating before the '50s on the intrarenal blood flow redistribution and the cortical ischemia, and the discussion on the experimental so-called "Trueta shunt" towards the medulla, linked with the acute renal failure in the pathophysiology of shock. Starting from a different methodology, further advances were more acceptable with Oliver's investigations on nephron dissection and on the localizations of toxic and ischemic lesions in different tubular segments. I quote only this field of research for my studies on symmetrical cortical necrosis and for the experimental investigations I performed with my collaborators on tissue biochemical enzymatic changes and in particular of the kidney during the shock of crush syndrome.
INVESTIGATIONS OF FUNCTION OF DIFFERENT TUBULAR SEGMENTS.
I used to follow the measurement of osmolar clearance, free-water clearance, sodium and water reabsorption, osmotic diuresis and solute-free diuresis, studying many classes of diuretics, beginning in the early '50s with acetazolamide, later the first thiazides, furosemide and other new agents. The effects on water and electrolytes reabsorption of different nephron segments were investigated, from the proximal to the loop and the distal tubule. In this way the diuretic drugs and some hormonal interferences (spirolactones, aldosterone, ADH), were considered not only for their therapeutic effects, but also for the possibility of using them as tools of research on tubular ion exchange.
In later years, I was attracted by the physiological research on tubular reabsorption and on hemodynamic functions at glomerular level, performed by micropuncture techniques on experimental animal. This was possible through the work done by my co-worker Vittorio Andreucci in Dallas, at the Department of Donald Seldin and Floyd Rector, at the beginning of the '70s, and continued in Parma, for the first time in Italy, with original contributions.
BEGINNING OF ITALIAN SOCIETY OF NEPHROLOGY AND ISN.
In the second half of the '50s, the first National Societies of Nephrology were created in England and in France. When in 1957 I promoted in Parma the foundation of the Italian Society of Nephrology, the nephrological studies initiated their major development, and grew progressively throughout Italy during the 40 years that followed, with important contribution not only at a national, but also at an international level.
At the beginning of the '60s, the International Society of Nephrology was also created, thanks to the initiative of Jean Hamburger. At that time, the first International Congress took place in Evian (France) together with the first executive committee of the society, where I took part as representative of Italy together with Gabriele Monasterio. During the following 15 years of my participation in the Committee, the science of nephrology had been developing as a new discipline, whose roots were in Internal Medicine, while new advances in pathophysiology of renal diseases also involved many biological functions related to the homeostasis of the whole organism.
BEGINNING A CHRONIC DIALYSIS PROGRAMME
After the early experience with hemodialysis in acute renal failure, dating from the second half of the '50s, I realized that a new era was opened by chronic dialysis with the Scribner-Quinton shunt and the Altervovenus (AV) fisutla of Cimino-Brescia. Two of my co-workers, Vincenzo Ferioli since 1965 and Vincenzo Cambi since 1969, respectively spent two years fellowship in Lyon (with Jules Traeger) and Seattle (with Belding Scribner) to improve the experience on dialysis techniques and modalities of treatment. In Italy, the first application of chronic dialysis treatment was exceedingly difficult, because hospitals were not prepared, and administrators were diffident toward a life-saving therapy that was carried on only in a few pioneering centers.
In the '60s, my group in Parma had to work for haemodialysis in hard conditions, because of the crowding of patients coming from different parts of Italy where hospitals were not ready with new technology. But, adopting peritoneal dialysis, as it was already performed in Seattle with the silastic catheter created by Henry Tenckoff, we were able to treat a greater number of patients, and this alternative treatment was to be later particularly developed by Giuseppe La Greca. In fact, after the thirty years, marked by incredible efforts, but also rich of new discoveries, the technique of continuous ambulatory peritoneal dialysis and the general achievements of nephrology, made it possible, in the '70s, to re-organize many dialysis centers.
TENSIONS BETWEEN THE SCIENCE AND THE BUSINESS OF NEPHROLOGY
In the second half of the '60s and in the following decade, research, that was carried on with purely scientific purposes, clashed with the experience of chronic dialysis. We thought that the new discipline of nephrology could become the sole dominion of new professional figures: the dialysis operators, whose technical ability was precious, but without aiming at scientific research. Economic interests appeared, and created further confusion, while a prevalence of the poor facilities and financial resources could be diverted to technical demands. The problem was not limited to Italy, and discussions were going on in Europe, so that we, for the moment felt, the risk that medical science and technique, nephrology and dialysis, could part their ways.
Since my participation in the European Dialysis Transplant Association, in the second half of the '60s and later with my involvement in the Council, I was aware of the importance of joining dialysis and transplants activities with renal physiology and clinical nephrology. Just on the occasion of the annual EDTA Congress, which I presided over in Florence in 1972, for the first time in Italy, these intentions were confirmed, but became official only in 1982 under the Presidency of Vittorio Andreucci. Finally the new Constitution, voted in 1996, was entitled to the "European Renal Association", preceding the classical EDTA wording, harder to indicate the crucial significance of an historical evolution.
It is well know that this treatment is strictly associated to the problem of diet, to which Italian nephrologists (Carmelo Giordano from Neaples, Gabriele Monasterio, Sergio Giovannette, and Wuirino Maggiore from Pisa, Giuseppe Maschio from Padua, Guarnieri from Trieste, and others have given the first original contributions.
Now I'd like to mention the investigation of Giovanni Garini and other members of the Parma department, on the slowing effect of low protein diet on the progression of chronic renal failure. Under these conditions a preservation of nutritional status, serum protein levels and nitrogen balance has been demonstrated, together with improvement of endocrine and metabolic disturbances, and correction of several aminoacid contents of muscular tissue. Above all, the importance of the compliance of the patients has been stressed, such as it is realized with various and acceptable diet preparations when minimal vegetable protein content is supplemented with amino acids. One may add that these effects are conditioned by preceding nutritional status, age of the patients, level of renal failure, duration of treatment. Therefore, the alimentary components should be adaptable to different clinical influences, such as variations of protein requirement or utilization, caused by uremic derangement, catabolic episodes, infectious complications.
In a different condition (Nephrotic Syndrome) the same group of Garini showed that a protection of renal function could be maintained with higher protein content, providing that ACE-inhibition is associated to improve renal circulation. As far as other possible mechanisms of diet are concerned, I could quote the hypothesis of a stimulation of protein synthesis from intestinal ammonia liberated from urea substrate of the enlarged nitrogen uremic pool. This anabolic process was previously demonstrated, outside of uraemia, only in malnourished children and in growing rats. But one had to know whether, in chronic uraemia, ammonia liberated from intestinal urea degradation to portal circulation would be reabsorbed with urea at a greater extent, while it is known that urea cannot be directly utilized for resynthesis.
The research I carried on with my co-workers on experimental rats, under chronic uremic conditions from subtotal nephrectomy, showed an increase of portal urea without any significant increase of protal ammonia in comparison to normal; whereas in acute uraemia brought about by bilateral uretheral ligation a significant increase of portal ammonia was evident, being equal the blood level of urea in all experimental conditions. These data are in accordance with a relationship between chronic uraemia in inhibition of ammonia reabsorption for the gut, so that its utilization for protein synthesis would not become possible. Our data agree with those of Tizianell and De Ferrari from Genoa, on the lack of any increase of portal ammonia and amino acids in man with chronic renal failure.
In addition, we could show in chronic uremic rats a significant resumption of ammonia reabsorption under aldosterone inhibition with potassium canreonate. In fact hormonal factors, such as an aldosterone excess among other metabolic disturbances of chronic uraemia, could rule out an anabolic effect of low protein diet. But I cannot now go into the details of facts and hypothesis involved in this long story.
Co-operation between bioengineering and clinical experience became more and more active in the mid-sixties. Since that time I could follow the research initiated by Scribner and Babb, through the participation of Vincenzo Cambi in the Seattle team. One aimed at identifying the metabolic products accumulated in the course of uremic syndrome and partially removed by dialysis, and particular importance was given to substances of middle molecular weight, instead of limiting uremic toxicity to urea, potassium, phosphorus, and acid metabolites. This hypothesis originated the so-called "square meter hour hypothesis" and later the "middle molecule hypothesis". In fact it was observed that peripheral neuropathy was less frequent in peritoneal dialyzed patients, probably because of a better removal of uremic toxins of middle molecular weight from the greater surface area and permeability of peritoneal membrane.
New technical devices were prepared changing flow of blood and dialysate flow in extracorporeal circuit, increasing surface area and permeability of dialysis membranes and time of treatment, modifying composition and ultrafiltration of dialysis fluid. Considering my participation to the new events, I mention the "short dialysis" successfully developed by Vincenzo Cambi and the research which I initiated with Paolo Dall'Aglio and later with Carlo Buzio and other co-workers on the isolation of middle molecules from uremic blood. Our purpose was the identification of solutes responsible of the uremic toxicity, which could be removed by dialysis treatment. Further on, the investigation performed in the same department by Giorgio Savazzi on peripheral nerve conduction velocity gave significant contribution to testing uremic toxicity and related influence of dialysis treatment.
Now, I have to confess that the current results hint at the retention of many substances, each one non specific nor limited to a particular molecular weight. Their pathophysiological effects may be variable with the long lasting of uraemia and its treatment. But all the mechanisms of uremic toxicity are not yet completely understood, while effects of biocompatibility of dialysis membranes, including cytokines and oxygen radicals are under investigation.
THE INTERDISCIPLINES APPROACH - FAMOUS NAMES
Long survival by dialysis treatment removed the initial fear of a technical overwhelming, because it caused new discoveries and experience in the field of chronic renal failure and internal medicine. Nephrology became a subspecialty with very strict relation with all disciplines in the medical field.
At the very beginning of my official appointment, there were no problems because the nephrological activity was included in a Medical Clinic comprehensive of all branches of Internal Medicine. The clinical experience with different patients enabled me to study renal circulatory insufficiency during heart failure, and particularly the pathogenesis of Epato-Renal Syndrome concerning circulatory and tubular functions and various responsiveness to diuretic and other means of treatment. Other studies included Analgesic Nephropathy epiodemiology, clinical and morphological aspects of Pyelonephritis and therapeutic research on urinary infection and renal stones, Toxic Nephropathies from non-steroidal anti-inflammatory drugs (NSAID) and antibiotics. Further on, I would like to quote immunochemical studies carried on by Rosario Maiorca and Lionello Scarpioni, on serum and urinary proteins, for diagnosis of different kinds of proteinuria and aspects of monoclonal gammopathies.
As far as glomerular nephropathies are concerned, my work has been developing with increasing practice of renal biopsies and related immunohistological research. In fact, I chose to organize together three main subspecialties which seemed to me at most inter-related: Nephrology Clinical Immunology and Medical Genetics. For the histopathology, I am indebted to the early assistance of Giorgio Olivetti from the Institute of Pathology of Parma University, and more recently to my co-worker Landino Allegri and his studies on autoimmune glomerual pathology.
And I cannot forget to express my appreciation to the essential contribution to the clinical and histological research of Stewart Cameron; to whom I am very indebted, Robert Heptistall, Madame Habib, Priscilla Kincaid Smith, and Italian nephrologists, such as Giuseppe D'Amico, Luigi Minetti, Claudio Ponticelli and their groups in Milan, and many other well known very distinguished colleagues.
Genetics is now in Parma proceeding under the responsibility of Mario Savi dedicated to molecular basis in relationship to histocompatibility for kidney transplantation and to ???? . A further enlargement of the department has included, with Innocente Franchini, the discipline of Preventive Medicine.
As an example of the interactive work, I tried to keep in the Institute of Medical Clinic of Parma, I presented an invited lecture at the National Congress of the Italian Society of Internal Medicine with my main ad first co-worker Alberico Borghetti, for an extensive report of our experience on the physiopathological and clinical aspects of renal failure. And this work included the participation of 16 members of the same Institute. And here I quote those collaborators already mentioned in this interview and elsewhere, Almerico Novarini for an excellent contribution and Giorgio Cocconi for the study of hemostasis.
FRIENDS AND INFLUENCES
These are overwhelming memories. People and events surrounding the course of my long experience in the field of nephrology. Besides people and facts I have already mentioned, I cannot forget some other friends of mine I met outside Italy, such as John Merrill, for his original and pivotal contribution to the conservative management and dialysis therapy of renal failure, Gabriel Richet, from the great school of Jean Hamburger, Paul Michielsen and important expert from Lovanium in kidney transplantation, Niells Alwall from Stockholm, the pioneer of the artificial kidney since the '40s, Jan Brod who organized an early congress of the International Society in Prague, but had to leave his country in 1970, due to the political events.
And several more people, such as Dr. Valek, who remained in Prague; Hans Sarre, the heir of Franz Vohlard, Thadeusz Orlowsky and Szigmund Hanicki, two generous Poles; Hugh De Wardener from London who went deep into new aspects of renal physiology, Arthur Kennedy from Glasgow, the first EDTA President in 1972-75 period, after the new constitution we had prepared in Barcelona with Emilio Rotelar and all the Council members; I remember Bruno Watschinger, from Austria, who gave a substantial contribution to the beginning of the hemodialysis therapy, J. Bergstrom from Stockholm, who investigated uremic toxicity, and many more friends whose names I have not here have the time to list as I would like: they increased my scientific and human experience.
Now I would like also to remember some international meetings I had opportunity to promote periodically, for several years, through personal contacts. First of all, every year for a long time eminent colleagues came to Parma from the main European and American centers, to discuss about the main current topics of Nephrology. As a second example, an annual triangular meeting was organized, during ten years, in Lyon, Bern, and Parma, respectively by Jules Traeger, Francois Reuby and myself, in turn, in order to present the personal experience and that of our medical staff: individual opinions could be directly compared and current research freely discussed.
CHANGES IN SOCIETY REFLECTED IN ??? RENAL DISEASES.
My recent comments concerned epidemiology of glomerulonephritis. In fact, social and economic status, crowded dwelling houses and poor hygenic conditions result in diffusion of infections. On the other hand, antimicrobial therapy has changed the course of several forms of glomerulonephritis that were considered as irreversible. Dramatic effects appeared for cases of lomerulonephtitis classified as primary ones from clinical point of view, but eventually included in a secondary pathology on the basis of etiologic investigation (tumor, infection and so on).
Consequently, new means of prevention and therapy have been achieved. In addition, the role of toxic factors related to industrial pollution should be investigated. Furthermore, we have followed the effects of immunosuppressive therapy causing a complete reversal of the prognosis of some autoimmune renal diseases. The lowering incidence of post-streptococcal glomerulonephritis, mainly remarkable in our countries, was compared with its persistence in the less developed world, possibly related to a nephritogenic streptococcal strain carrying an endocellular antigen which Lange called "endostreptosin". We tested it through chromatographic identification and its specific antibody response. Any case, the progress in the epidemiological investigation for many types of glomerulonephritis is mandatory, by considering different strata of population in geographic areas.
CLINICAL CAUSE OF GLOMERULONEPHRITIS.
I have been particularly interested in this subject, and now I would like to stress my concern about asymptomatic patients, presenting with mild and isolated urinary abnormalities. Under these circumstances it was difficult to verify if the real tendency pointed toward a healing or to a progressive worsening. Therefore, an extensive research was planned and carried out on the renal patients of the department for many years, regularly measuring total protein excretion and albuminuria after immunoelectrophoretic detection, even at minimal quantitative levels, as persisting from the beginning or after an acute nephritic syndrome (poststreptococcal, etc.). We showed that pathological isolated albuminuria in ortho and clinostatism or only in clinostatism was related to glomerular mesangial lesions, even with normal levels of total proteinuria. Normalization of albuminuria resulted as a more suitable index rather than total proteinuria for the assessment of recovery.
This outcome was confirmed after a long follow up or by normal histologyn and negative immunofluorescence. On the other hand, persistent pathological albuminuria was followed by pathological values of total proteinuria after a variable period of time, in cases of worsening evolution of the nephropathy. This method revealing subclincal glomerular damage allows identification of patients who need a follow up, even if renal biopsy is not repeated. Parallel investigation on total proteinuria and albuminuria on normal individual was carried out by Carlo Buzio and other co-workers of mine, in relationship to distribution of normal dates, and protein load circadian rhythm.
A further extension of these studies has been more recently continued by Buzio, Borghetti and other members of the department on hypertensive patients under high protein diet with normal GFR but reduced renal reserve. One could show that calcium channel blockers, but not ACE inhibitors, raised GFR, PRF and protein excretion by acting on glomerular selectivity and tubular reabsorption. Beside, differential excretion of single fractions of proteins and their quantitative inter-relations were measured and compared with the degree of glomerular tubular lesions in several renal diseases.
It is well known that cadaveric transplantation depends on a strict collaboration with intensive care units in finding and preparing available organs. No transplantation is possible if this collaboration is deficient, even if surgical and nephrological facilities are effective. Perhaps an inadequate involvement of intensive care units to this activity still persists in some parts of Italy, and causes a low kidney procurement, so that several people must address their request to the transplant centers which are active in different territories of our country.
An other problem is dealing with consent from the donor's relatives. The possibility of a refusal depends on cultural levels and local traditions. However, these difficulties may cease if the matter is brought to an adequate attention of public opinion and people are correctly informed, in order to avoid any misunderstanding about the identification of brain death as the death of the individual as a whole. A real education should clarity the groundlessness of certain opinions, coming from some bioethicians and philosophers, who question the definition of cerebral death.
According to this opinion, some still agree with transplant, though thinking organ donation anticipates death, which they assume would only correspond to cardiac arrest. Therefore, donation would be a lethal intervention, a particular case of active euthanasia. Against these baffling opinions it is important to confirm the validity of the concept of brain death that corresponds to the real death, even if some isolated vegetative and neuriendocrine activities occasionally persist, in patients who are only apparently alive under artificial cardiopulmonary assistance.
Moreover, somebody insinuates the suspicion that the short number of transplantations in some regions depends on the potential interference of this treatment on the business related to dialysis therapy. However, I think that this hypothesis does not seem to be acceptable, because the number of patients who are nowadays eligible for kidney transplantation is too small to significantly affect the size of increasing dialysis population. The problem of living donor transplantation is too big to be discussed here. I can say that comparing my opinion with those of philosophers, biologists and ethicists, I do not expect nowadays the social response to this demand to go over the current level. However, new hopes about psycho-social feelings should evolve towards this extraordinary opening of human solidarity. This is my hope, at least.
GREATEST ??? AND SATISFACTIONS.
I am aware of my limits, about the goals I could not reach, and the opportunities I missed. I do not like to talk about degrees of satisfaction, because I do not want to judge the credit I can take from my results. However, the regret for what I could not bring to an end could be cancelled if members of my department, students, pupils, or patients will consider as valid the lines I have suggested. The great number of co-workers of mine that had the opportunity to reach a key position in Nephrology units of Universities and Hospitals throughout this Country helps me to hope for a continuity of advancing progress, and it is enough to justify my job.
PREDICTIONS OF THE FUTURE OF NEPHROLOGY.
In the field of renal physiopathology, the progress of current studies on gene expression of vasoactive hormones such as Angiotensin and Endoltelin will allow to know better the effects of vasoconstiction and also of hyperplasia and hypertrophy of mesangium, on glomerular permeability, protein excretion and sclerosis, with the participation of mediators of inflammation, citokines and autacoids.
With regard to transplantation, the improvement of immunology and the possibility to induce the tolerance of genetical unrelated organs without the help of immunosuppressive therapy, are realistic goals, even if they are limited by the small numbers of living or cadaveric donors. A possible solution could be offered by xenotransplantation, if the new transgenic science can offer real possibilities to control the rejection. In any case, one has to face the unexplored field of hybridism and chimera, at the edge of genetic identity of the human being, and the possible danger of still ignored infections.
Gene engineering will probably allow to implant Erithropoyethin gene into endothelium or muscle cells, near the vascular access of dialysis patients; this will probably solve definitely the problem of anaemia. On the other hand, since calcium sensing receptor proteins of parathyroid glands have been already cloned, the corresponding genes will probably be utilized to restore the calcium sensitivity and correct hypercalcemia in some forms of secondary hyperparathyroidism. Other attempts to utilize gene engineering will consider the possibility to introduce normal genes in order to substitute the lacking ones in renal polycystosis and other associated hereditary kidney diseases. Further on, therapeutic molecular modulation of genes involved in the synthesis of factors related to expansion of mesangium could be studied in order to slow the progression of glomerulonephritis.
Cell therapy will probably be introduced in assembling an artificial kidney, more effective than current dialysis machines, by spreading out endothelial cells on artificial filtering membranes; cells, previously isolated and cultured in vitro, will be engineered to produce anticoagulant factors and mesangial substances. At the same time, isolated and cultured epithelial cells will be implanted into hollow fiber devices, after the introduction of genes coding for specific funcions of water and solute transport, but I cannot go further. In conclusion, the way towards new conquests leads to two different targets, both important but in contrast with each other: that is the increase of expectancy or of quality of life. According to an utopic aspiration both targets could be combined, but in practice they are conflicting, and a selective parting between these two medical interventions is often unavoidable.
In the years to come, probably sooner than it can be predicted, the question will arise about the limits of the currently increasing role of artificial means, biotechnology and transgenic science, not only for radical treatments, but also for potential changes affecting the debated definition of life. New duties and responsibilities are emerging at the horizon, and they have to be shared with the whole social context, getting over the limits of scientific research. In this scene, interdisciplinary resources should allow a comprehensive solution of an old but still impending problem, once opposing nature against culture, and today the spontaneity of life against the intervention of science and technology.
LATEST WORK - POST RETIREMENT
My studies on glomerulonephritis could not possibly cease all of a sudden, and I also examined new metabolic aspects of diabetic nephropathy, and related diet therapy, in comparison with early achievements which I made at the beginning of my career. Today the field of bioethics has caught my main interests. I believe that after a long time of full immersion in the empirical investigation of facts, it is time of addressing the cognitive functions to find out the criteria which are involving the fundamental choices.
For some years I just considered the search for significant values as an important duty, in order to justify the lines of action. Therefore I have adopted an epistemological approach to the modern issues of science, also including the impressive explosion of interest about bioethics and medical humanities. I have considered the concept of life and death in the current evolution of biology and medicine, and the ethics of transplantation in relationship to criteria of brain death and the meaning of artificial cardiorespiratory assistance. In this connection a critical approach to the development of biotechnology seems to me as necessary to reevaluate ethical principles. I feel that traditional rules of objective rationality and acceptance of a transcendence are at a confrontation with the claims for subjective autonomy of human being. I now attend to debates on medical care at the end of life, and on voluntary euthanasia proposed as aberrant, physician suicide.
Moreover, I have studied the new and worrying phenomenon of voluntary dialysis withdrawing or withholding, with relation to decision autonomy of the patient, physicians duties and liberty of conscience. Finally, I entered the problem of allocation of scarce medical resources, which is deeply involving the whole society. In the field of Nephrology, this choice was distressful in the past, when the shortage of dialysis machines could not meet all the increasing needs. Today this problem has been solved in Western industrial countries, but not yet in the greatest part of world population, where even elementary resources for basic means of sustenance get out of hands. Furthermore, the response to the demand for transplantation is far from adequate, everywhere. History is continuously moving and we have to face an unpredictable evolution. As for me, I will try to go on my way, as long as I can.