Milestones in European Thyroidology (MET)
Nino Salvatore (1932-1997)
Gaetano Salvatore ("Nino" for his many friends worldwide) was born in Naples on 28 July 1932. He graduated in Medicine from the University of Naples, after studying at the Institute of General Pathology directed by Professor Luigi Califano. From 1956 to 1958 he worked at the Collège de France in Paris under the supervision of Professor Jean Roche, one of the discoverers of triiodothyronine. It was at the Collège de France that he developed his passion for the thyroid gland - a passion that he passed on to his many pupils and that led Naples to become a focal point in the field of endocrinology research.
Upon his return to Naples in 1959-60, he organized a small research team composed by young medical students who were at that time working toward their M.D. degree. These students soon became contagiously affected by Nino's enthusiasm for research and they rapidly learned the techniques he had brought back from Paris. Following in the footsteps of his mentor Professor Califano who had received training at the Naples Zoological Station, Nino Salvatore transferred part of his laboratories to this marine biology Institute, which was one of the most important research institutions at that time in Europe, certainly the most important in Naples. Nino continued his collaboration with Jean Roche while at the Zoological Station, and made important contributions to the comparative pathophysiology of thyroid gland.
In fact, he demonstrated the existence of thyroid hormones in lower species of Chordates, namely the cephalochordate amphioxus, and in the urochordates Ciona intestinalis and Clavelina laepadiformis. In both cephalochordates and urochordates, hormonal biosynthesis takes place in iodoproteins that have the same function as thyroid iodoproteins in vertebrates, but their structure is different and they are not localized in either thyroid follicles (a morphological structure not present in these species) or in the "endostyle", a subpharyngeal glandular sac, which is the ancestral structure of thyroid follicles in higher species. In C. intestinalis these proteins occur in the tunica. Within a very short time Nino and his young collaborators demonstrated the existence of thyroid function in the lowest vertebrate class, i.e., the cyclostomata. In particular, in Petromyzon planeri (lamprey) larva (ammocoetes) the iodide concentration mechanism is present and thyroid hormones are produced in the endostyle. In the adult Petromyzon planeri, after metamorphosis, thyroid follicles can be found spread along the intestinal duct in which a protein very similar to thyroglobulin is found.
During the same period, Nino Salvatore's group demonstrated that thyroid function does not exist below the phylum of Chordates and that iodinated tyrosines are indeed found in the scleroproteins of Gorgonids, such as Euricella verrucosa, however, these proteins serve only a structural function and are not related to the thyroid iodoproteins of higher organisms. In 1961 Nino Salvatore returned to France, this time to Prof. Yves Derrien's laboratory in Marseille, where he refined various biochemical techniques and began to study the structure of thyroid iodoproteins. From April 1962 to January 1964 he worked in the renowned laboratory led by Ed Rall and Jacob Robbins at the Clinical Endocrinology Branch of the National Institutes of Health in Bethesda, USA. This was a very fruitful time for Nino. In collaboration with his wife Marisa, Hans Cahnmann and Jack Robbins he devised a new method for the purification and isolation of thyroid iodoproteins and, subsequently, in studies to which I also collaborated, he described and characterized a new thyroid iodoprotein rich in iodine and thyroid hormones, namely 27S thyroglobulin. On his return to Naples, Nino continued to generate ideas and initiatives. Apart from being involved in the organization activities of the Institute of General Pathology, he continued to lead his research group, which had grown considerably, he developed an intensive program of international exchanges, and many foreign investigators spent time in the Naples laboratory. He continued visiting laboratories in the United States and in Europe to improve technologies, to start new collaborations and to circulate new ideas. As an almost unique example for the Italian university biomedical environment of the time, Nino returned to Bethesda as a Full Professor of General Pathology for long intervals between 1972 and 1974. He went to France in 1975 and to the Catholic University of Louvain in Belgium in 1976. Finally, in 1977, he received the greatest recognition from the US government to foreign researchers, the Fogarty Scholarship in Residence. This Scholarship entails a 12-month stay at the National Institutes of Health in Bethesda with complete freedom to carry out research in the topic of one's choice. Throughout this period of travel and the Fogarty Fellowship, Nino did not abandon active research but continued his work on the biosynthesis and structure of thyroid iodoproteins. He proceeded with these studies until his death. His last publication on the molecular mechanism underlying the synthesis of thyroid hormones (T3 and T4) in the large thyroglobulin molecule appeared posthumously in the Journal of Biological Chemistry in 1997.
Between 1965 and 1971 Nino worked with his collaborators on various research lines related to thyroid iodoproteins. This was possible because his young collaborators had spent long periods of training in foreign laboratories, thus continuing the tradition started by Prof. Califano. This network of exchanges, together with collaborations established with foreign laboratories, brought outstanding expertise and skills to the new Institute of General Pathology, which in 1982 became the Department of Cellular and Molecular Biology and Pathology "L. Califano", of which Nino was the founder, located at the new Medical School, of which Nino was also one of the founders and to which he moved in 1972.
From 1972 to 1992 Nino Salvatore was head of the Centre of Experimental Endocrinology and Oncology of the National Research Council (CNR), which has always been strictly linked to the Department. The main scientific contributions of the Department and of the CNR Centre in this period came from his group, which, with great foresight, he helped to mature as researchers. Even at this stage Nino Salvatore continued to make tremendous contributions to science. And he realized the importance of bringing together the expertise acquired abroad by his collaborators on issues different from the ones faced by him 20 years before. He greatly encouraged the choice of a common biological system on which the various experiences acquired by his former collaborators could converge. This system was obviously the thyroid, and most of Nino's former pupils chose this system, each with their own competence and expertise. Other research lines, not correlated with the thyroid gland, flourished as well at the Department. Nino Salvatore had the great merit of promoting the union of all these different expertise and of having encouraged the union between cellular and molecular biology, which produced important results in terms of both technology and ideas.
In this period, the various research groups working at the Department of Cellular and Molecular Biology and Pathology in Naples made important discoveries related to the physiology and pathology of the thyroid, and in such diverse fields as genetics, immunology and oncology. Among the research activities developed in this period, I would like to mention, as regards thyroid research, the studies related to the production of a system of rat thyroid cells which carry in vitro all the differentiated functions proper of the thyroid gland, the FRT-L system, which has been used by thyroid researchers worldwide, the neoplastic transformation of these cells with viral and cellular oncogenes, the isolation and characterization of the rat thyroglobulin gene and of its promoter, the studies on thyroglobulin gene structure and of hormonal biosynthesis.
Nino Salvatore's interest in the thyroid gland went beyond basic research studies. He also encouraged the applicability of thyroid studies to important social medical issues, such as the endemic goiter, which is widespread in many Italian regions, especially in the South, and to the early diagnosis of another major thyroid disease, congenital hypothyroidism.
Thus far I have focused on the scientific activity of Gaetano Salvatore, but his merits and influence go far beyond. Nino seized every opportunity possible to think about something new. So he used his position as NIH Fogarty Scholar to set-up an exchange program with the support of the Italian Ministry of University and Research (MUR). This program lasted from 1981 to 1997 and under this scheme many young and not so young Italian researchers trained at NIH and NIH researchers came to Italy. The impact of this program on biological research in Italy as a whole cannot be overestimated. From 1981 to 1997, Nino served as Dean of the Medical School of Naples Federico II University, and was one of the main promoters of the new Italian regulations on medical studies. From 1987 to 1997 he returned to his first love, the Naples Zoological Station, now known as the Stazione Zoologica "Anton Dohrn", of which he became President, and helped to bring about its renewal. He chaired the CNR Committee for Biotechnology from 1994 to 1997; in this framework he promoted two biotechnology projects in Italy. He was a member of the European Commission's Advisory Committee for Medical Training and contributed to the harmonization, at a European level, of the Specialization Schools of Medical Faculties. Nino was national member of the Accademia dei Lincei, and President of the European Thyroid Association, of which he was one of the founders and promoters.
I think what struck people about Nino was his enthusiasm for life as a whole. He was a music lover, and was particularly knowledgeable about Baroque music. As President of the Stazione Zoologica he founded a chamber music group that still performs baroque music at the Stazione. He was an enthusiast of electronic equipment, and he has left a valuable collection of computer chess games. Nino liked good food, and, on occasions, took over the kitchen creating the same confusion in the kitchen as in the laboratory when he decided to work with his own hands. He was a volcano, and he has left a void in Italian research and culture that will be difficult to fill.
1. Roche J., Lissitzky S., Michel R., Sur la triiothyronine, produit intermédiaire de la transformation de la diiodothyronine en thyroxine. C. R. Acad. Sci., Paris, 1952 (25 Fév.), 234 : 997-998.
2. Gross J., Pitt-Rivers R., The indentification of 3,5,3'-L-triiodothyronine in human plasma. The Lancet 1952 (March 1) i : 439-441.
3. Roche J., Lissitzky S., Michel R., Sur la présence de la triodothyronine dans la thyroglobuline. C.R.Acad. Sci., Paris, 1952 (10 mars), 234 : 1228-1230.