Milestones in European Thyroidology (MET)
Jean Roche (1901-1992)
Jean Roche was born in Sorgues (Vaucluse, France) in 1901. His father was a country physician in the south of France. Jean Roche graduated as medical doctor from the University of Montpellier (France) and first stayed in Montpellier. He worked in the laboratory of Prof. Eugène Derrien and Prof. Edouard Hédon who had described at the end of the 19th century, the secretory role of the pancreatic islets of Langerhans. A few years later, Jean Roche moved to Strasbourg as Chef de travaux in the Department of Biological Chemistry (1925-30). During that period, he travelled abroad, visited and stayed in different renowned research centres in England and Germany. He worked in S. Sörensen's laboratory at the Carlsberg Institute in Copenhagen and with Sir W. Hardy in Cambridge. He then moved to Lyon for a short period of time before being appointed in 1931 as Professor of Biological Chemistry at the Medical School of Marseille (France) where he stayed for 17 years. There he held important teaching responsibilities and with the cooperation of Prof. Yves Derrien, he developed and stimulated research in biochemistry. The school of Biochemistry of Marseille quickly grew up and acquired an international reputation. During the same period, Roche obtained his PhD degree in Sciences and graduated in pharmacy.
Roche was interested in proteins, particularly the respiratory proteins. He investigated the different normal and pathological hemoglobins and other oxygen-carrier proteins in vertebrates and invertebrates. He determined the molecular weight of these proteins by osmometry and ultracentrifugation. He published on the heterogeneity and on different characteristics of these proteins, at a time when chromatography and electrophoresis were not yet existent.
The reputation of Roche rapidly grew among the French universities and the scientific circles. In 1938, he was appointed to the board of the Conseil Supérieur de la Recherche Scientifique (France) which later on, led to the setting up of the Centre National de la recherche Scientifique (CNRS). After World War II, he became a member of the Board of Directors of the CNRS.
In 1947, he was appointed as Head of the Laboratoire de Biochimie générale et comparée at the Collège de France in Paris. The Collège de France is a top institution dedicated to teaching and research. Jean Roche remained in charge of his department until the time of his retirement in 1972. Roche also assumed the direction of the marine laboratory of Concarneau (France) where biochemical studies were performed on different marine species and have contributed to the evolutive classification of different species.
From the 1950's on, the research studies in Roche's department progressively became oriented in thyroid biochemistry. With his coworkers and particularly Raymond Michel, Serge Lissitzky and Jacques Nunez, Roche characterized the iodoaminoacids present in the thyroglobulin molecule, mainly by radiochromatography. In 1952, Roche together with Raymond Michel and Serge Lissitzky identified, the 3,5,3'-triiodothyronine molecule (T3) in the rat thyroid hydrolysates. The same year, Gross and Pitt-Rivers at Mill Hill (London) reported on the presence of T3 in the human plasma and demonstrated the antigoitrogenic activity of T3. Gross and Pitt-Rivers quickly abandonned the hypothesis according to which T3 resulted from the deiodination of T4. Roche and coworkers and Leloup and Lachiver in Paris as Querido, Schut and Terpstra in Leiden strengthened the hypothesis of a coupling mechanism of the iodotyrosines leading to thyroxine and triiodothyronine as it was later on confirmed.
Retrospectively, it is interesting to point out how sometimes, the international recognition of a significant scientific discovery like T3 , partly depends on the political or linguistic environment. In the case of T3, no doubt that Roche, Michel and Lissitky as well as Pitt-Rivers and Gross have been the "mother and fathers" of T3 although their approaches had been different. Indeed in Paris, the approach had esssentially been biochemical, mainly in vitro or in thyroid animals while the aims of the research in London had been more physiological, focused on the identification of an unknown spot observed on the radiochromatography of human blood after in vivo radioiodine (131I) administration, previously observed in Montreal by Leblond and Gross (1-3). In the general scientific atmosphere of the 1950's, it is to be remembered that communication between scientists was uneasy at the international level. A latin country like France was only publishing in french journals. In Germany, English was not frequently spoken, partly as a consequence of World War II. In international meetings, there were significant problems to have German-, French-, Italian- and English-speaking people communicating between themselves. Most of the scientists were just reading and quoting their national literature. Thus as an example, one started speaking of Graves disease in the English literature while the same clinical disturbance was described as Basedow disease in Germany and France. The same has been true for T3. The birth of European scientific societies definitely helped to break down these frontiers. The European Thyroid Association - Association Européenne de Recherches sur la Glande Thyroïde born in 1967 undoubtedly contributed to solve the cultural gap between clinicians and scientists.
The hepatic metabolism of T4 and T3 leading to the glycuronoconjugation of the iodothyronines was investigated in Roche's laboratory by Closon, Tata and Varrone while with Salvatore and Covelli, Roche was studying the action of T3 on the respiratory mechanisms of carcinomatous cells and on Escherichia coli. Contributions to the understanding of iodine metabolism and thyroid biochemistry in various animal species were actively published. Many foreign researchers visited or worked in Roche's laboratory.
This period of time was very exciting in thyroid research not only because of the identification of the different iodinated compounds present in the thyroid gland but also because of the understanding of the role of the thyroglobulin molecule in the biosynthesis of the thyroid hormones and of the importance of all the intra-thyroidal enzymatic machinery leading to thyroid hormones secretion. As a tracer of thyroid metabolism, radioiodine (131I) was an extraordinary physiological tool. Biochemistry, analytical chemistry and physico-chemistry, electron microscopy were rapidly developing. Thyroglobulin appeared not only as a system of storage of the thyroid hormones but as an important step in the synthesis of T4 and T3 through the iodination of the tyrosyl residues and the coupling reactions. Another field rapidly expanding in Roche's laboratory was related to the understanding of the peripheral metabolism of the thyroid hormones as extensively studied by Jacques Nunez and Claude Jacquemin.
Roche was a member of the French Académie des Sciences. He was honoured by many universities and 15 foreign universities awarded him the title of " Doctor Honoris causa" for his work.
In 1961, he was appointed as Rector of the University of Paris. In 1968, with diplomacy and courage he faced the French students left-wing upheaval in Paris which quickly developed into a national political and social movement aiming to shake up the "old society". Those among the senior members of the ETA who attended the ETA Marseille meeting in 1968 remember the agitated atmosphere of the general assembly ! Later on, Roche was appointed as French General Delegate for international University Relationships. In 1994, an important research institute oriented to the biology of cellular interactions was created at the faculty of Medicine in Marseille and was named as Institut Jean Roche in his memory. The network of this institute actually includes some 130 research and teaching staff and 30 post-doctoral researchers.
Aside from the teacher and the researcher, everyone remembers Jean Roche's personality. He was an open-minded person, always taking the time to listen to people taking advice from his experience. His ability to act diplomatically helped to solve or to save many delicate situations. Jean Roche was a member of the boards of several research organizations or foundations such as the Institut Curie (Paris), the Foundation Louis de Broglie (Paris) or the italian CNR among others. He most actively supported many research centres and their researchers as well. During his life, Jean Roche personally helped many of his co-workers to settle and to develop their research laboratory in their own university. He was very generous and had the art of keeping many links with all his co-workers, helping the young people to find their way and always supporting and stimulating new research developments. Jean Roche was not only a scientist. He had a broad culture, especially in history and literature. It was always enjoyable to spend time with him exchanging ideas or memories.
When the International Thyroid Conference was organized in Rome in 1965, Jean Roche was a member of the Scientific Program Committee. It is during this meeting that at the initiative of Christian Beckers, an informal lunch meeting was held to discuss how to stimulate and to support thyroid research in Europe. A clear-cut project had indeed progressively emerged. Some "young Turks" were back from the U.S. after several years of research or clinical training and had settleld down in Europe. They had enjoyed the meetings of the North-American scientific societies like the American Thyroid Association and the Endocrine Society. The time was coming to create a European thyroid association responsible for organizing an annual thyroid meeting and to stimulate scientific exchanges between the European thyroid centres. Jean Roche became President of the newly born European Thyroid Association - Association Européenne de Recherches sur la Glande Thyroïde. During his office (1967-1971), Jean Roche guided the first steps of the ETA, actively supporting the organization of the meetings, stimulating the participation of young researchers and handling with diplomacy all the European linguistic problems and the unavoidable tensions between centres. Rosalind Pitt-Rivers succeeded Jean Roche as President in 1971 and kept the same policy, giving to the ETA the best chances to grow and to expand. The ETA has certainly to be indebted to Jean Roche and Rosalind Pitt-Rivers as well as to many others to have made from the ETA an "enjoyable party " !
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.