Milestones in European Thyroidology (MET)
Serge Lissitzky (1919-1986)
Serge Lissitzky was 67 years old when he died in 1986. He was born in 1919 in Bourg-en-Bresse (France). His life has been largely devoted to medical biology and biochemistry, to teaching and to research and above all, to thyroid research.
After brilliant high-school studies and one year spent at the University of Sciences in Paris, he joined the French Navy Medical School in Bordeaux just a few months before the beginning of World War II. After the defeat and the invasion of France by the German army in 1940, the Navy Medical School moved to Montpellier under the Vichy administration. In 1943 when the Germans invaded Vichy (France), the school was disbanded and he escaped through Spain to join the Free French Forces in Northern Africa. Incorporated as a medical officer in the French First Army, he participated in the Allies' landing in Provence (1944) and in the campaign in Germany (1945). After the armistice, he served in Vietnam before returning to France in 1946. During all these events, he was twice confronted with heavy fighting during the Rhine and Danube battles and once in Vietnam where from the banks of the Red river near Haïphong, the Chinese army unexpectedly fired at the warship on which he was on duty. His medical and strategic skills to organize the assistance for wounded soldiers during these tragic events were rewarded by several military citations (War Cross and Légion d'Honneur). The acquaintances made among the military doctors remained among his closest friends.
He responsibly performed his military duties but the vocation of Serge Lissitzky was to get involved in biological chemistry. Indeed in the pre-war period, he succeeded passing several scientific degrees at the University of Paris and got his PhD in 1952(1). Serge Lissitzky quickly orientated himself to research in 1949 after joining Prof. J. Roche at the "Laboratoire de Biochimie Générale et Comparée " in the Collège de France in Paris. In cooperation with Jean Roche and Raymond Michel, he investigated iodine metabolism in the thyroid gland with new developing techniques, particularly radiochromatography with radioiodine 131I as a tracer.
An intensive work yielded several breakthroughs in thyroid biochemistry, namely (a) the discovery of a thyroid iodotyrosine-desiodase and the development of the concept of iodine re-cycling within the thyroid gland(2), (b) the discovery of l-triodothyronine at the same time as Jack Gross and Rosalind Pitt-Rivers in London(3,4) and © the demonstration that thyroxine and triiodothyronine were part of the thyroglobulin molecule and were secreted after the proteolysis of thyroglobulin(5). In 1953 and after 3 years spent in Roche's laboratory, Serge Lissitzky moved to Algiers and worked as a physician at the Maillot military hospital and taught as Professor at the University. It is important to mention that during the same period he developed a new field of research with Dr F Miranda, succeeding in the isolation and the characterization of scorpion toxins which became of the highest importance for neurobiological studies(6,7).
The milestones of Lissitzky's future work were thus planted in his mind when he moved to the Medical School of the University of Marseille in 1954 after being nominated there as Professor of Biochemistry. In 1960, he became Head of the Department of Biochemistry. He rapidly expanded his research in thyroid hormone metabolism, mainly the deiodination of iodothyronines by the peripheral tissues. This work was done in connection with Rosalind Pitt-Rivers and Jamshed Tata in London, John Stanbury and Sidney Ingbar in the US, Jacques Nunez in Roche's laboratory and in association for a time with Aldo Pinchera (Pisa).
In 1962, the emergence of new separation techniques led him to return to studies on thyroglobulin in order to gain a better knowledge of the formation and the production of thyroid hormones. This became a life-long pursuit for him and in the continuity of the laboratory of biochemistry in Marseille where thyroglobulin had been previously purified by Yves Derrien, Raymond Michel and Jean Roche in 1948. The research studies progressively shifted from the biological chemistry of iodocompounds to the cellular and molecular biochemistry of an integrated endocrine gland: the thyroid gland.
Lissitzky headed a research unit in his laboratory entitled "Physiopathologie de la fonction thyroïdienne", rapidly supported by the CNRS and INSERM. Several teams of researchers including P. Carayon, Y. Malthiery, J. Mauchamp , M. Rolland, J. Ruf and J. Torresani were therein involved in the purification, the biochemical and immunological characterisation of thyroglobulin, the setting of in vitro organomimetic cellular models for the study of the thyroid function and of the thyrotropin receptor and its transduction pathways, the study of thyroid hormone action and the molecular cloning of thyroglobulin.
At the time, thyroglobulin was the hub of many networks he established in France and farther. Several senior scientists came to his laboratory for some months and became his friends such as Salvatore, Greif, Greer, Becarevic, Gorbman, Burrow and DeGroot. There were also connections with the Clinical Endocrinology Branch at the National Institutes of Health (Bethesda, US), with some European groups as the Naples group with Nino Salvatore and Roberto Di Lauro, the Brussels group with Jacques Dumont and Gilbert Vassart and the Amsterdam group with Jan de Viljder. Serge Lissitzky was also concerned to bring new insights into different thyroid pathologies as in congenital goiters resulting from an impaired thyroglobulin synthesis, in Graves disease, in autoimmune thyroid diseases or in thyroid cancers for which early developments of in situ hybridization were used to show a correlation between differentiation and thyroglobulin gene transcription.
While remaining very much involved in thyroid research, Serge Lissitzky's laboratory continued to pursue the work initiated in Algiers, aiming at the isolation and characterization of the neurotoxins present in the venom of the Androctonus australis Hector scorpion. The effect of the venom on the Na+ and K+ ion channels was demonstrated. In the late '70s, F. Miranda and H. Rochat expanded this research and developed an important research unit devoted to the study of animal toxins.
In 1970, Serge Lissitzky opened a new unit in charge of the measurement of proteic hormones, essentially by radioimmunological procedures in his department. Serum hormonal levels were measured for patients. At the same time, monoclonal antibodies of thyroglobulin and thyroperoxidase were produced. Endocrinological studies were also performed on the hormonal regulation of the normal and adenomatous pituitary.
All these studies resulted in over 300 publications. They led him to participate in numerous national and international scientific societies. Lissitzky chaired the French Societé de Chimie Biologique and Société d'Endocrinologie. He was elected a member of the French Académie de Médecine and was awarded by the Académie of Sciences. He also belonged to several international societies such as the British Biochemical Society, the European Molecular Organization (EMBO), the American Thyroid Association (ATA) and of course to the European Thyroid Association (ETA) of which he has been a founding member and an Executive Committee member. Lissitzky welcomed the second ETA meeting in Marseille in 1968. He was awarded the ETA Ames prize in 1983 and lectured on "Thyroglobulin entering into Molecular Biology" (8) . He acceded to the position of honorary member of the ETA joining Ros Pitt-Rivers, Jean Roche and Jack Gross, all involved as himself in T3 discovery.
During his life, Serge Lissizky has been an envisioned scientist guided by a bright and creative intelligence associated to a deep scientific curiosity and a communicative enthusiasm, all of which gave him a great charisma. His attractive character and his renown allowed his department to rapidly expand and split in many research groups. His personality was very convivial and playful, enjoying life with humour. In the laboratory, he was a hard worker and his authority, sometimes coloured by a military taint, was respected because he was as rigorous for himself as for the others. Despite his numerous administrative tasks and responsibilities, he remained unpretentious and available to everyone for thought-provoking discussions and "think-tank" meetings.
1. Lissitzky S.F., "Biochimie des acides aminés iodés marqués par I131 dans le corps thyroïde", PhD thesis submitted at the Faculté des Sciences de l'Université de Paris (1952).
2. Roche J., Michel O., Michel R., Gorbman A., Lissitzky S. The enzymatic dehalogenation of halogenated tyrosine derivatives by the thyroid gland and its physiological role. II. Biochim Biophys Acta. 1953, (Dec.12)4:570-6
3. 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.
4. Gross J., Pitt-Rivers R., The indentification of 3,5,3'-L-triiodothyronine in human plasma. The Lancet 1952 (March 1) i : 439-441.
5. 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.
6. Miranda F., Lissitzky S., Purification of the toxin of scorpion venom (Androctonus australis L.). Biochem Biophys Acta, 1958, 30 : 217-218.
7. Miranda F., Lissitzky S., Scorpamins : the toxic proteins from scorpion venom. Nature (London), 1961,190 : 443-444.
8. Lissitzky S., Ames-Miles Prize lecture of the European Thyroid Association (1983), "Thyroglobulin entering into Molecular Biology". Europ. J. Clin. Invest. 1983, 7 : 65-76